Davis, CA, United States
Davis, CA, United States

The University of California, Davis , is a public research university located in Davis, California, just west of Sacramento. It encompasses 5,300 acres of land, making it the second largest UC campus in terms of land ownership, after UC Merced. UC Davis also has the third-largest enrollment in the UC System after UCLA and UC Berkeley.The 2015 U.S. News & World Report college rankings named UC Davis as the 9th best public university, 38th nationally, and 4th of the UC schools, following UC Berkeley, UCLA, and UC San Diego. UC Davis is one of 62 members in the Association of American Universities.The Carnegie Foundation classifies UC Davis as a comprehensive doctoral research university with a medical program, and very high research activity. UC Davis faculty includes 23 members of the National Academy of science, 25 members of the American Academy of Arts and science, 17 members of the American Law Institute, 14 members of the Institute of Medicine, and 14 members of the National Academy of Engineering. Among other honors, university faculty, alumni, and researchers have won the Nobel Peace Prize, Presidential Medal of Freedom, Pulitzer Prize, MacArthur Fellowship, National Medal of Science, and Presidential Early Career Award in Science and Engineering.The university has expanded over the past century to include graduate and professional programs in medicine , law, veterinary medicine, education, nursing, and business management, in addition to 90 research programs offered by UC Davis Graduate Studies. UC Davis' School of Veterinary Medicine is the largest in the United States and is ranked second in the nation.The UC Davis Aggies athletic teams compete in the NCAA Division I level, primarily in the Big West Conference as well as the Big Sky Conference and the Mountain Pacific Sports Federation. In its first year of full Division I status, 11 UC Davis teams qualified for NCAA post-season competition. Wikipedia.


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Kim S.H.,University of California at Davis
Journal of Arthroplasty | Year: 2010

Two objectives of this study were (i) to estimate the number of primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) performed on morbidly obese people in the United States, and (ii) to estimate the economic impact of morbid obesity on hospital resource use. In 2006, approximately 2.9% (6713 cases) of primary THA and 4.2% (20 964 cases) of primary TKA recipients were diagnosed as morbidly obese. Despite the controversy associated with increased infection risk and failure rate, a large number of morbidly obese people seem to consider that the benefits outweigh the risks. When sex, age, race, and primary payer were held constant, the hospital resource consumption for unilateral primary THA and TKA was 9% ($1432) and 7% ($1025) higher among morbidly obese patients than among nonobese patients, respectively. © Elsevier Inc.


Cowgill E.,University of California at Davis
Bulletin of the Geological Society of America | Year: 2010

The Pamir salient defi nes the western end of the Himalayan-Tibetan orogen and has overthrust the Tarim-Tajik basin to the north by ~300 km along a late Cenozoic, south-dipping intracontinental subduction zone. Field mapping, structural measurements, and analysis of mesoscale structures along a 32-km-long reach of the Yarkand River document the tectonic evolution of the east fl ank of this salient, between the North Pamir to the west and the Western Kunlun Shan to the east. The study area is cut by a set of four, north-northwest-striking, steeply dipping brittle faults. Microstructures and asymmetric outcrop-to map-scale folds indicate right slip along these faults. Between these structures, fault-bounded panels of Phanerozoic strata are deformed by en echelon folds with axes that trend more westerly than the adjacent faults, consistent with dextral transpression. The fault system described here extends for ~350 km along the eastern fl ank of the Pamir salient. Transpressional right slip along this set of faults, here called the Kashgar-Yecheng transfer system, appears to have accommodated late Cenozoic separation of the North Pamir from the Western Kunlun Shan during south-directed intracontinental subduction beneath the leading edge of the Pamir salient. Correlation of major faults suggests total slip along the Kashgar-Yecheng transfer system is likely on the order of ~280 km. This offset estimate implies long-term slip rates of 7-15 mm/a along the Kashgar-Yecheng transfer system when combined with previous sedimentologic, stratigraphic, and thermochronologic data that indicate deformation along the east fl ank of the Pamir started between the late Eocene and early Miocene. These results imply that the fi rst-order structures on the western and eastern fl anks of the Pamir are asymmetric: previous work has shown that deformation in the west was accommodated by anticlockwise vertical axis rotation of the Pamir over the eastern margin of the Tajik basin. This rotation is generally interpreted to refl ect n orthwest-directed radial thrusting, in contrast to the transpressional right-slip transfer faulting on the east side reported here. © 2009 Geological Society of America.


Rapson D.,University of California at Davis
Journal of Environmental Economics and Management | Year: 2014

I estimate a dynamic structural model of demand for air conditioners, the most energy-intensive home appliance in the US. The model explores the links between demand for durable goods and expected changes in key attributes: energy efficiency and price. I incorporate expectations explicitly as a feature of the choice setting, and use parameter estimates from the model to calculate durable good demand elasticities with respect to energy efficiency, electricity price, and price of the durable itself. These estimates fill a large gap in the literature, and also shed light on consumer behavior in this setting. Results indicate that consumers are forward-looking and value the stream of future savings derived from energy efficiency. © 2014 Elsevier Inc.


Doyle J.A.,University of California at Davis
Annual Review of Earth and Planetary Sciences | Year: 2012

Molecular data on relationships within angiosperms confirm the view that their increasing morphological diversity through the Cretaceous reflected their evolutionary radiation. Despite the early appearance of aquatics and groups with simple flowers, the record is consistent with inferences from molecular trees that the first angiosperms were woody plants with pinnately veined leaves, multiparted flowers, uniovulate ascidiate carpels, and columellar monosulcate pollen. Molecular data appear to refute the hypothesis based on morphology that angiosperms and Gnetales are closest living relatives. Morphological analyses of living and fossil seed plants that assume molecular relationships identify glossopterids, Bennettitales, and Caytonia as angiosperm relatives; these results are consistent with proposed homologies between the cupule of glossopterids and Caytonia and the angiosperm bitegmic ovule. Jurassic molecular dates for the angiosperms may be reconciled with the fossil record if the first angiosperms were restricted to wet forest understory habitats and did not radiate until the Cretaceous. © 2012 by Annual Reviews. All rights reserved.


Whitehead A.,University of California at Davis
Journal of Experimental Biology | Year: 2012

Organisms that live in variable environments must adjust their physiology to compensate for environmental change. Modern functional genomics technologies offer global top-down discovery-based tools for identifying and exploring the mechanistic basis by which organisms respond physiologically to a detected change in the environment. Given that populations and species from different niches may exhibit different acclimation abilities, comparative genomic approaches may offer more nuanced understanding of acclimation responses, and provide insight into the mechanistic and genomic basis of variable acclimation. The physiological genomics literature is large and growing, as is the comparative evolutionary genomics literature. Yet, expansion of physiological genomics experiments to exploit taxonomic variation remains relatively undeveloped. Here, recent advances in the emerging field of comparative physiological genomics are considered, including examples of plants, bees and fish, and opportunities for further development are outlined particularly in the context of climate change research. Elements of robust experimental design are discussed with emphasis on the phylogenetic comparative approach. Understanding how acclimation ability is partitioned among populations and species in nature, and knowledge of the relevant genes and mechanisms, will be important for characterizing and predicting the ecological and evolutionary consequences of human-accelerated environmental change. © 2012. Published by The Company of Biologists Ltd.


Invernizzi P.,IRCCS Instituto Clinico Humanitas | Invernizzi P.,University of California at Davis
Hepatology | Year: 2011

Primary biliary cirrhosis (PBC) is an autoimmune biliary disease characterized by injury of small and medium size bile ducts, eventually leading to liver cirrhosis and death. Although the causes remain enigmatic, recent evidence has strengthened the importance of genetic factors in determining the susceptibility to the disease. Besides the strong heritability suggested by familial occurrence and monozygotic twins concordance, for decades there has not been a clear association with specific genes, with the only exception of a low risk conferred by a class II human leukocyte antigen (HLA) variant, the DRB1*08 allele, at least in some populations. The picture has become more complete when strong protective associations between PBC and the HLA DRB1*11 and DRB1*13 alleles were found in Italian and UK series. However, HLA genes have begun again to attract interest thanks to recent genome-wide association studies (GWAS), which clearly demonstrated that the major components of the genetic architecture of PBC are within the HLA region. As expected in a genetically complex disease, GWAS also identified several novel non-HLA variants, but it is worth noting that all of them are in immuno-related genes. In this review, the paradigmatic tale of what, and how, we learned about HLA genes in PBC will be retraced with particular focus on how GWAS are enabling a rewriting the story of PBC pathogenesis. These recent discoveries will not only drive functional studies but will also hold the promise of developing novel disease-specific treatments. © 2011 American Association for the Study of Liver Diseases.


Cappa C.D.,University of California at Davis
Atmospheric Measurement Techniques | Year: 2010

Aerosol thermodenuders provide a measure of particle volatility. The information provided by a thermodenuder is fundamentally related to the kinetics of evaporation and condensation within the device. Here, a time-dependent, multi-component model of particle and gas-phase mass transfer in a thermodenuder is described. This model empirically accounts for the temperature profile along the length of a typical thermodenuder and distinguishes between the influence of the heating section and of the adsorbent denuder section. It is shown that "semi-volatile" aerosol is particularly sensitive to the inclusion of an adsorbent denuder in the model. As expected, the mass loss from evaporation of particles as they pass through the thermodenuder is directly related to the compound vapor pressure, although the assumptions regarding the enthalpy of vaporization are shown to also have a large influence on the overall calculated mass thermograms. The model has been validated by comparison with previously measured mass thermograms for single-component aerosols and is shown to provide reasonable semi-quantitative agreement. The model that has been developed here can be used to provide quantitative understanding of aerosol volatility measurements of single and multi-component aerosol made using thermodenuders that include adsorbent denuder sections. © Author(s) 2010.


Coats R.,University of California at Davis
Climatic Change | Year: 2010

The purpose of this study was to quantify the decadal-scale time trends in air temperature, precipitation phase and intensity, spring snowmelt timing, and lake temperature in the Tahoe basin, and to relate the trends to large-scale regional climatic trends in the western USA. Temperature data for six long-term weather stations in the Tahoe region were analyzed for trends in annual and monthly means of maximum and minimum daily temperature. Precipitation data at Tahoe City were analyzed for trends in phase (rain versus snow), decadal standard deviation, and intensity of rainfall. Daily streamflow data for nine gaging stations in and around the Tahoe basin were examined for trends in snowmelt timing, by two methods, and an existing record for the temperature of Lake Tahoe was updated. The results for the Tahoe basin, which contrast somewhat with the surrounding region, indicate strong upward trends in air temperature, a shift from snow to rain, a shift in snowmelt timing to earlier dates, increased rainfall intensity, increased interannual variability, and continued increase in the temperature of Lake Tahoe. Two hypotheses are suggested that may explain why the basin could be warming faster than surrounding regions. Continued warming in the Tahoe basin has important implications for efforts to manage biodiversity and maintain clarity of the lake. © 2010 The Author(s).


Navrotsky A.,University of California at Davis
Journal of Materials Chemistry | Year: 2010

Oxides based on the fluorite structure are important as electrolytes in solid oxide fuel cells, thermal barrier coatings, gate dielectrics, catalysts, and nuclear materials. Though the parent fluorite structure is simple, the substitution of trivalent for tetravalent cations, coupled with the presence of charge-balancing oxygen vacancies, leads to a wealth of short-range and long-range ordered structures and complex thermodynamic properties. The location of vacancies and the nature of clusters affect the energetics of mixing in rare earth doped zirconia, hafnia, ceria, urania, and thoria, with systematic trends in energetics as a function of cation radius. High temperature oxide melt solution calorimetry has provided direct measurement of formation enthalpies of these refractory materials. Surface and interfacial energies have also been measured in yttria stabilized zirconia (YSZ) nanomaterials. Other ionic conductors having perovskite, apatite, and mellilite structures are discussed briefly. © 2010 The Royal Society of Chemistry.


Saxton M.J.,University of California at Davis
Biophysical Journal | Year: 2010

Lateral diffusion in the plasma membrane is obstructed by proteins bound to the cytoskeleton. The most important parameter describing obstructed diffusion is the percolation threshold. The thresholds are well known for point tracers, but for tracers of nonzero radius, the threshold depends on the excluded area, not just the obstacle concentration. Here thresholds are obtained for circular obstacles on the continuum. Random obstacle configurations are generated by Brownian dynamics or Monte Carlo methods, the obstacles are immobilized, and the percolation threshold is obtained by solving a bond percolation problem on the Voronoi diagram of the obstacles. The percolation threshold is expressed as the diameter of the largest tracer that can cross a set of immobile obstacles at a prescribed number density. For random overlapping obstacles, the results agree with the known analytical solution quantitatively. When the obstacles are soft disks with a 1/r 12 repulsion, the percolating diameter is ∼20% lower than for overlapping obstacles. A percolation model predicts that the threshold is highly sensitive to the tracer radius. To our knowledge, such a strong dependence has so far not been reported for the plasma membrane, suggesting that percolation is not the factor controlling lateral diffusion. A definitive experiment is proposed. © 2010 by the Biophysical Society.


Farouki R.T.,University of California at Davis
Computer Aided Geometric Design | Year: 2012

One hundred years after the introduction of the Bernstein polynomial basis, we survey the historical development and current state of theory, algorithms, and applications associated with this remarkable method of representing polynomials over finite domains. Originally introduced by Sergei Natanovich Bernstein to facilitate a constructive proof of the Weierstrass approximation theorem, the leisurely convergence rate of Bernstein polynomial approximations to continuous functions caused them to languish in obscurity, pending the advent of digital computers. With the desire to exploit the power of computers for geometric design applications, however, the Bernstein form began to enjoy widespread use as a versatile means of intuitively constructing and manipulating geometric shapes, spurring further development of basic theory, simple and efficient recursive algorithms, recognition of its excellent numerical stability properties, and an increasing diversification of its repertoire of applications. This survey provides a brief historical perspective on the evolution of the Bernstein polynomial basis, and a synopsis of the current state of associated algorithms and applications. © 2012 Elsevier B.V. All rights reserved.


Law C.Y.,University of California at Davis | Pham A.-V.,University of California at Davis
Digest of Technical Papers - IEEE International Solid-State Circuits Conference | Year: 2010

In wireless communications, high demand for superb video and audio quality increases the required transfer data rate. The unlicensed 7GHz bandwidth at V-band in North America has been drawing a lot of attention by companies and research institutions. Research topics done using CMOS fabrication, which appears to be a more appealing process due to its high level of integration, have been demonstrated to be a viable semiconductor for gigabit wireless at 60GHz [1]. According to the Federal Communications Commission (FCC) regulations, the maximum radiation power for 60GHz systems can reach up to 40dBm [2]. However, due to device limitations such as low maximum operating frequencies and low breakdown voltage, very few power amplifier (PA) designs using CMOS processes with high output power have been reported. To date, medium- to high-power amplifiers in this frequency range are normally implemented using III-V semiconductor fabrication processes. ©2010 IEEE.


A pro-thrombotic, pro-inflammatory diet can play a causative role in atherosclerotic-cardiovascular diseases. Dietary intervention studies provide insight into their pathophysiological manifestations and opportunities for prevention and management. We previously showed in an acute-meal setting that a beverage containing polyphenolic- and antioxidant-rich strawberry (Fragaria) vs placebo attenuated postprandial (fed-state) increases in biomarkers of oxidative and inflammatory stress, and insulin concentrations, induced by a high carbohydrate/fat (HCF) meal. In the present study, we aimed to extend our findings and investigate hypotheses related to the effects of chronic/6-week (wk) strawberry consumption on HCF meal-induced increases in glucose, insulin, and indicators of inflammation and hemostasis.Methods: In a crossover design, 14 women and 10 men (mean age, BMI: 50.9±15 years, 29.2±2.3 kg/m(2), respectively), were randomized to a 6-wk strawberry or placebo beverage followed by an HCF meal with assessments for 6-hours (h) postprandially. HCF meal responses after 6-wk strawberry beverage showed significantly attenuated postprandial PAI-1 concentrations compared to the placebo (p =0.002); the difference was most notable at 6 h. The IL-1 β response was attenuated with strawberry compared to the placebo (p =0.05). IL-6 attenuation was apparent but non-significant; IL-6 rose significantly from baseline to 6 h after the HCF meal following a placebo (p ≤0.01), although it remained relatively flat following the strawberry beverage from fasting to 6 h. No significant treatment-related differences were apparent for platelet aggregation, hsCRP, TNF-α, insulin, or glucose. These data are the first to suggest that regular consumption of strawberry, a polyphenolic- and antioxidant-rich fruit, may provide protection from HCF meal-induced increases in fibrinolytic and inflammatory factors in at-risk men and women.


Oakes L.M.,University of California at Davis
Journal of Cognition and Development | Year: 2010

Habituation of looking time has become the standard method for studying cognitive processes in infancy. This method has a long history and derives from the study of memory and habituation itself. Often, however, it is not clear how researchers make decisions about how to implement habituation as a tool to study processes such as categorization, object representation, and memory. This article describes the challenges for implementing this tool and describes a set of best practices for its use to study perception and cognition in infancy. © 2010 Taylor & Francis Group, LLC.


Isman M.B.,University of British Columbia | Grieneisen M.L.,University of California at Davis | Grieneisen M.L.,Wenzhou University
Trends in Plant Science | Year: 2014

Our analysis of >20. 000 papers on botanical insecticides from 1980 to 2012, indicates major growth in the number of papers published annually (61 in 1980 to 1207 in 2012), and their proportion among all papers on insecticides (1.43% in 1980 to 21.38% in 2012). However, only one-third of 197 random articles among the 1086 papers on botanical insecticides published in 2011 included any chemical data or characterization; and only a quarter of them included positive controls. Therefore, a substantial portion of recently published studies has design flaws that limit reproducibility and comparisons with other and/or future studies. In our opinion, much of the scientific literature on this subject is of limited use in the progress toward commercialization or advancement of knowledge, given the resources expended. © 2013 Elsevier Ltd.


Lagattuta K.H.,University of California at Davis
Child Development Perspectives | Year: 2014

Remembering the past can shape current emotions and behaviors as well as bias anticipations of the future. This awareness that mental states and emotions cohere across time-sometimes called mental time travel-is a fundamental component of social cognition critical for assessing risk, making decisions, and understanding others. In this article, I highlight early competencies and development in young children's reasoning about connections among life history, mind, and emotion. I focus primarily on children's knowledge about emotions and decisions caused by being reminded about the past and thinking about the future. Findings reveal surprising insights in children as young as 3-4 years of age, age-related changes through middle childhood into adulthood, and individual differences that have implications for mental health. © 2014 The Society for Research in Child Development.


Lonnerdal B.,University of California at Davis
Journal of Pediatrics | Year: 2010

Human milk contains a multitude of bioactive proteins, with very diverse functions. Some of these proteins are involved in the synthesis and expression of milk, but the majority appears to have evolved to provide physiological activities in the breast-fed infant. These activities are exerted by a wide variety of mechanisms and have largely been unraveled by in vitro studies. To be active in the gastrointestinal tract, these proteins must be able to resist proteolytic degradation, at least for some time. We have evaluated the human milk proteins lactoferrin, haptocorrin, α1-antitrypsin, and transforming growth factor -β in an in vitro digestion model, mimicking the conditions of the infant gastrointestinal milieu. These bioactive proteins are resistant against proteolysis and can remain intact or as larger fragments through passage of the gastrointestinal tract. In vitro digestibility assays can be helpful to assess which human milk proteins can resist proteolysis and to what extent. © 2010 Mosby, Inc. All rights reserved.


Kopp A.,University of California at Davis
Trends in Genetics | Year: 2012

Most animals are sexually dimorphic, but different taxa have different sex-specific traits. Despite major differences in the genetic control of sexual development among animal lineages, the doublesex/mab-3 related (Dmrt) family of transcription factors has been shown to be involved in sex-specific differentiation in all animals that have been studied. In recent years the functions of Dmrt genes have been characterized in many animal groups, opening the way to a broad comparative perspective. This review focuses on the similarities and differences in the functions of Dmrt genes across the animal kingdom. I highlight a number of common themes in the sexual development of different taxa, discuss how Dmrt genes have acquired new roles during animal evolution, and show how they have contributed to the origin of novel sex-specific traits. © 2012 Elsevier Ltd.


Hsu P.Y.,University of California at Davis | Harmer S.L.,University of California at Davis
Trends in Plant Science | Year: 2014

Circadian clocks integrate environmental signals with internal cues to coordinate diverse physiological outputs so that they occur at the most appropriate season or time of day. Recent studies using systems approaches, primarily in Arabidopsis, have expanded our understanding of the molecular regulation of the central circadian oscillator and its connections to input and output pathways. Similar approaches have also begun to reveal the importance of the clock for key agricultural traits in crop species. In this review, we discuss recent developments in the field, including a new understanding of the molecular architecture underlying the plant clock; mechanistic links between clock components and input and output pathways; and our growing understanding of the importance of clock genes for agronomically important traits. © 2013 Elsevier Ltd.


The compliance of the human trabecular meshwork (HTM) has been shown to dramatically stiffen in glaucomatous patients. The purpose of this study was to determine the impact of substratum stiffness and latrunculin-B (Lat-B) on the expression and activity of the mechanotransducers, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ), in primary HTM cells as the cells start to recover from Lat-B treatment. Primary human trabecular meshwork (HTM) cells were cultured on hydrogels possessing stiffness values mimicking those found in normal (5 kPa) and glaucomatous meshworks (75 kPa), or tissue culture polystyrene (TCP; >1 GPa). Cells were treated with 2.0 μM Lat-B in DMSO or DMSO alone. RT-PCR was used to determine the impact of substratum stiffness and/or Lat-B treatment on the expression of YAP, TAZ, 14-3-3σ, plasminogen activator inhibitor-1 (PAI-1), and connective tissue growth factor (CTGF). Immunoblotting was used to determine the expression of YAP and TAZ as well as the phosphorylation status of YAP. Immunofluorescence was used to determine YAP protein localization. YAP and TAZ mRNA expression were upregulated on the 75 kPa hydrogels in comparison to the 5 kPa hydrogels and TCP. Treatment with Lat-B resulted in a rapid and dramatic downregulation of YAP and TAZ on the 75 kPa hydrogels. On hydrogels, Lat-B treatment increased the phosphorylation of YAP at S127, while decreasing it on TCP. Similarly, Lat-B treatment resulted in markedly decreased nuclear localization of YAP on the hydrogels but elevated nuclear localization on TCP. Lat-B treatment of HTM cells on the 75 kPa hydrogels also increased 14-3-3σ mRNA, a protein important in YAP/TAZ degradation. In addition, Lat-B treatment decreased CTGF and PAI-1 mRNA on the 75 kPa hydrogels. In conclusion, substratum stiffness alters YAP/TAZ expression and YAP localization in primary HTM cells which then may modulate the expression of extracellular matrix proteins important in glaucoma. During the recovery period after Lat-B treatment, gene expression changes are more dramatic on substrates with stiffness similar to glaucomatous meshwork. Use of these hydrogels may more accurately reflect the alterations occurring in HTM cells in glaucoma after treatment with this drug. Copyright © 2013 Elsevier Ltd. All rights reserved.


Quantum chemical calculations on the transformation of the bisabolyl cation into an array of sesquiterpenes (iso-γ-bisabolene, trichodiene, cuprenene, laurene, isochamigrene, chamigrene, chamipinene, sesquithujene, sesquisabinene, microbiotene, dunniene, cumacrene, isobazzanene, bazzanene, barbatene, widdradiene, and thujopsene) are described. The bisabolyl cation is the hub of a complicated web of carbocations involved in the construction of diverse and complex molecular architectures present in a large number of Nature's sesquiterpenoids. The results of quantum chemical calculations on the multitude of rearrangements described herein provide reasonable answers to several persistent mechanistic questions in the world of terpene biosynthesis and also provide examples of general reactivity principles for terpene-forming (and other) carbocation rearrangements. © 2014 American Chemical Society.


Perkins T.A.,University of California at Davis
The American naturalist | Year: 2012

Both exotic and native species have been shown to evolve in response to invasions, yet the impacts of rapidly evolving interactions between novel species pairs have been largely ignored in studies of invasive species spread. Here, I use a mathematical model of an interacting invasive predator and its native prey to determine when and how evolutionary lability in one or both species might impact the dynamics of the invader's spatial advance. The model shows that evolutionarily labile invaders continually evolve better adapted phenotypes along the moving invasion front, offering an explanation for accelerating spread and spatial phenotype clines following invasion. I then analytically derive a formula to estimate the relative change in spread rate due to evolution. Using parameter estimates from the literature, this formula shows that moderate heritabilities and selection strengths are sufficient to account for changes in spread rates observed in historical and ongoing invasions. Evolutionarily labile native species can slow invader spread when genes flow from native populations with exposure to the invader into native populations ahead of the invasion front. This outcome is more likely in systems with highly diffuse native dispersal, net directional movement of natives toward the invasion front, or human inoculation of uninvaded native populations.


Ronald P.C.,University of California at Davis
PLoS biology | Year: 2014

Over the last 300 years, plant science research has provided important knowledge and technologies for advancing the sustainability of agriculture. In this Essay, I describe how basic research advances have been translated into crop improvement, explore some lessons learned, and discuss the potential for current and future contribution of plant genetic improvement technologies to continue to enhance food security and agricultural sustainability.


Myers T.W.,University of California at Davis | Berben L.A.,University of California at Davis
Journal of the American Chemical Society | Year: 2011

Hydrogen abstraction by aluminum(III)-oxo intermediates via reaction pathways reminiscent of late transition metal chemistry has been observed. Oxidation of M+[(IP2-)2Al]- (IP = iminopyridine, M = Na, Bu4N) yielded [Na(THF)(DME)][(IP -)(IP2-)Al(OH)] (3) or [(IP-) 2Al(OH)] (4), via O-atom transfer and subsequent C-H activation or proton abstraction, respectively. © 2011 American Chemical Society.


Zhao J.,University of California at Davis | Osterloh F.E.,University of California at Davis
Journal of Physical Chemistry Letters | Year: 2014

Photochemical charge generation, separation, and transport at nanocrystal interfaces are central to photoelectrochemical water splitting, a pathway to hydrogen from solar energy. Here, we use surface photovoltage spectroscopy to probe these processes in nanocrystal films of HCa2Nb 3O10, a proven photocatalyst. Charge injection from the nanoparticles into the gold support can be observed, as well as oxidation and reduction of methanol and oxygen adsorbates on the nanosheet films. The measured photovoltage depends on the illumination intensity and substrate material, and it varies with illumination time and with film thickness. The proposed model predicts that the photovoltage is limited by the built-in potential of the nanosheet-metal junction, that is, the difference of Fermi energies in the two materials. The ability to measure and understand these light-induced charge separation processes in easy-to-fabricate films will promote the development of nanocrystal applications in photoelectrochemical cells, photovoltaics, and photocatalysts. © 2014 American Chemical Society.


Rannala B.,University of California at Davis
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

Bayesian inference of species divergence times is an unusual statistical problem, because the divergence time parameters are not identifiable unless both fossil calibrations and sequence data are available. Commonly used marginal priors on divergence times derived from fossil calibrations may conflict with node order on the phylogenetic tree causing a change in the prior on divergence times for a particular topology. Care should be taken to avoid confusing this effect with changes due to informative sequence data. This effect is illustrated with examples. A topology-consistent prior that preserves the marginal priors is defined and examples are constructed. Conflicts between fossil calibrations and relative branch lengths (based on sequence data) can cause estimates of divergence times that are grossly incorrect, yet have a narrow posterior distribution. An example of this effect is given; it is recommended that overly narrow posterior distributions of divergence times should be carefully scrutinized. This article is part of the themed issue ‘Dating species divergences using rocks and clocks’. © 2016 The Author(s) Published by the Royal Society. All rights reserved.


Bassil E.,University of California at Davis | Blumwald E.,University of California at Davis
Current Opinion in Plant Biology | Year: 2014

The biochemical characterization of cation/H+ exchange has been known since 1985 [1], yet only recently have we begun to understand the contribution of individual exchangers to ion homeostasis in plants. One particularly important class of exchangers is the NHX-type that is associated with Na+ transport and therefore salinity tolerance. New evidence suggests that under normal growth conditions NHXs are critical regulators of K+ and pH homeostasis and have important roles, depending on their cellular localization, in the generation of turgor as well as in vesicular trafficking. Recent advances highlight novel and exciting functions of intracellular NHXs in growth and development, stress adaptation and osmotic adjustment. Here, we elaborate on new and emerging cellular and physiological functions of this group of H+-coupled cation exchangers. © 2014.


Hong Y.J.,University of California at Davis | Tantillo D.J.,University of California at Davis
Chemical Society Reviews | Year: 2014

Biosynthetic production of cyclobutanes leads to many complex natural products. Recently, theoretical work employing quantum chemical calculations has shed light on many of the details of cyclobutane-formation, in particular, for terpene natural products. Specific insights and general principles derived from these theoretical studies are described herein. This journal is © the Partner Organisations 2014.


Shih W.,University of California at Davis | Yamada S.,University of California at Davis
Journal of Cell Science | Year: 2012

Cancer cells that originate from epithelial tissues typically lose epithelial specific cell-cell junctions, but these transformed cells are not devoid of cell-cell adhesion proteins. Using hepatocyte-growth-factor-treated MDCK cells that underwent a complete epithelial-tomesenchymal transition, we analyzed cell-cell adhesion between these highly invasive transformed epithelial cells in a threedimensional (3D) collagen matrix. In a 3D matrix, these transformed cells formed elongated multicellular chains, and migrated faster and more persistently than single cells in isolation. In addition, the cell clusters were enriched with stress-fiber-like actin bundles that provided contractile forces. N-cadherin-knockdown cells failed to form cell-cell junctions or migrate, and the expression of the Ncadherin cytoplasmic or extracellular domain partially rescued the knockdown phenotype. By contrast, the expression of N-cadherin-α-catenin chimera rescued the knockdown phenotype, but individual cells within the cell clusters were less mobile. Together, our findings suggest that a dynamic N-cadherin and actin linkage is required for efficient 3D collective migration. © 2012.


DeMaster D.M.,University of California at Davis | Ghetti S.,University of California at Davis
Cortex | Year: 2013

Episodic memory, or the ability to form and retrieve conscious memories about specific past events, improves during childhood. Previous adult neuroimaging results indicate a central role of the hippocampus in episodic retrieval, but it is not clear whether the contribution of the hippocampus changes during development. Traditionally, developmental improvements in episodic retrieval have been thought to depend on strategic processes mediated by the prefrontal cortex (PFC), a region that is considered to have a protracted course of development relative to the hippocampus. The primary goal of the present study was to test the hypothesis that the development of episodic retrieval is also associated with changes in hippocampal function. Children ages 8- to 11-years-old and adults ages 18-25 (N = 41) encoded black and white line drawings surrounded by either a green or red border. Functional magnetic resonance imaging (fMRI) data were acquired while participants attempted to recall which colour was originally paired with each drawing. Correct recall of item-colour pairings indicated successful episodic retrieval. Activity in the anterior hippocampus, but not in the posterior hippocampus, was associated with episodic retrieval in adults, whereas activity in the posterior, but not in the anterior hippocampus, was associated with episodic retrieval in children. Developmental differences were also found in regions in anterior lateral PFC and posterior parietal cortex. Overall, these results support the view that the development of episodic memory is supported by functional changes in the hippocampus as well as in other critical cortical regions. © 2012 Elsevier Ltd.


Chedin F.,University of California at Davis
Progress in Molecular Biology and Translational Science | Year: 2011

The deposition of DNA methylation at promoters of transposons, X-linked genes, imprinted genes, and other lineage-specific genes is clearly associated with long-term transcriptional silencing. Thus, DNA methylation represents a key layer of epigenetic information in mammals that is required for embryonic development, germline differentiation, and, as shown more recently, for the function and maturation of neuronal tissues. The DNMT3A, DNMT3B, and DNMT3L proteins are primarily responsible for the establishment of genomic DNA methylation patterns and, as such, play an important role in human developmental, reproductive, and mental health. Progress in our understanding of this important protein family has been rapid in recent years and has been accompanied by stunning developments in the analysis of the human DNA methylome in multiple cell types. This review focuses on recent developments in the characterization of the DNMT3 family of DNA methyltransferases at the biochemical, structural, and functional levels. Interconnections between the DNA-based and histone-based layers of epigenetic information are particularly highlighted, as it is now clear that de novo methylation occurs chiefly in the context of nucleosomal templates. © 2011 Elsevier Inc.


Rogawski M.A.,University of California at Davis
Epilepsy Currents | Year: 2011

In the 1990s there was intense interest in ionotropic glutamate receptors as therapeutic targets for diverse neurological disorders, including epilepsy. NMDA receptors were thought to play a key role in the generation of seizures, leading to clinical studies of NMDA receptor blocking drugs in epilepsy. Disappointing results dampened enthusiasm for ionotropic glutamate receptors as a therapeutic target. Eventually it became appreciated that another type of ionotropic glutamate receptor, the AMPA receptor, is actually the predominant mediator of excitatory neurotransmission in the central nervous system and moreover that AMPA receptors are critical to the generation and spread of epileptic activity. As drugs became available that selectively target AMPA receptors, it was possible to demonstrate that AMPA receptor antagonists have powerful antiseizure activity in in vitro and in vivo models. A decade later, promising clinical studies with AMPA receptor antagonists, including the potent noncompetitive antagonist perampanel, are once again focusing attention on AMPA receptors as a drug target for epilepsy therapy. © American Epilepsy Society.


Baar K.,University of California at Davis
Sports Medicine | Year: 2014

Maximizing metabolic stress at a given level of mechanical stress can improve the adaptive response to endurance training, decrease injury, and potentially improve performance. Calcium and metabolic stress, in the form of heat, decreases in the adenosine triphosphate/ adenosine diphosphate ratio, glycogen depletion, caloric restriction, and oxidative stress, are the primary determinants of the adaptation to training. These stressors increase the activity and amount of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a), a protein that can directly induce the primary adaptive responses to endurance exercise: mitochondrial biogenesis, angiogenesis, and increases in fat oxidation. The activity of PGC-1a is regulated by its charge (phosphorylation and acetylation), whereas its transcription is regulated by proteins that bind to myocyte enhancing factor 2, enhancer box, and cyclic adenosine monophosphate response element sites within the PGC-1a promoter. This brief review will describe what is known about the control of PGC-1a by these metabolic stressors. As the duration of calcium release and the amount of metabolic stress, and therefore the activation of PGC-1a, can be directly modulated by training and nutrition, a simple strategy can be generated to maximize the adaptive response to endurance training. © The Author(s) 2014.


Hoffman M.D.,University of California at Davis
International journal of sports physiology and performance | Year: 2014

PURPOSE: To examine pacing among the most successful runners in the 161-km Western States Endurance Run (WSER) to determine if variations in segmental speed relate to performance, ambient temperature, and calendar year.METHODS: Segmental speed and coefficient of variation (CV) in speed were analyzed for 10 race segments of 24 races from 1985 through 2013.RESULTS: Segmental speeds did not differ between the eventual winners and lead runners and only differed between the 1st and 2nd finishers in the 2nd half of the race. Mean CV in speed was lower (P < .01) for the winners (12%) than for the other top-5 finishers (14-15%). CV in speed was related (r = .80, P = .006) to finish time for the fastest 10 finish times at the WSER. Multiple linear-regression analysis revealed mean CV in speed for the top-5 runners to be related to maximum ambient temperature (coefficient =.14, P < .05) and calendar year (coefficient = -.086, P = .034).CONCLUSIONS: Mountain trail running is characterized by wide variations in speed, but the fastest times are achieved when speed fluctuations are limited. This is generally accomplished by the winners remaining relatively close behind the lead runners before taking the lead in the middle half of the race, and then avoiding slowing as much as the other top runners in the latter race stages. Variations in speed increase with high ambient temperatures, and the small decrease in segmental speed variability among top runners across the nearly 30 y of this study suggests that the best runners have improved at pacing this race.


Leal W.S.,University of California at Davis
Annual Review of Entomology | Year: 2013

Our knowledge of the molecular basis of odorant reception in insects has grown exponentially over the past decade. Odorant receptors (ORs) from moths, fruit flies, mosquitoes, and the honey bees have been deorphanized, odorant-degrading enzymes (ODEs) have been isolated, and the functions of odorant-binding proteins (OBPs) have been unveiled. OBPs contribute to the sensitivity of the olfactory system by transporting odorants through the sensillar lymph, but there are competing hypotheses on how they act at the end of the journey. A few ODEs that have been demonstrated to degrade odorants rapidly may act in signal inactivation alone or in combination with other molecular traps. Although ORs in Drosophila melanogaster respond to multiple odorants and seem to work in combinatorial code involving both periphery and antennal lobes, reception of sex pheromones by moth ORs suggests that their labeled lines rely heavily on selectivity at the periphery. © 2013 by Annual Reviews. All rights reserved.


Bokulich N.A.,University of California at Davis | Bamforth C.W.,University of California at Davis
Microbiology and Molecular Biology Reviews | Year: 2013

Brewing beer involves microbial activity at every stage, from raw material production and malting to stability in the package. Most of these activities are desirable, as beer is the result of a traditional food fermentation, but others represent threats to the quality of the final product and must be controlled actively through careful management, the daily task of maltsters and brewers globally. This review collates current knowledge relevant to the biology of brewing yeast, fermentation management, and the microbial ecology of beer and brewing. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Lo E.,University of California at Davis | Deane S.,University of California at Davis
Autoimmunity Reviews | Year: 2014

Immune thrombocytopenia, or ITP, has been recognized as a clinical entity for centuries, and the importance of humoral mechanisms in the pathophysiology of ITP has been recognized for decades. Despite the long history of the syndrome, progress in understanding its epidemiology and management has been hindered by inconsistencies in nomenclature and classification schema together with the inherent heterogeneity in characteristics of global populations and ITP-associated disorders. In the past decade, great strides have been made in devising a common language for caregivers and investigators alike through standardization definitions and outcome measures, while new tools have become available for management of its clinical manifestations. In 2009, an International Working Group presented proposed standards for definitions, classification criteria, and outcome measures. The American Society of Hematology adopted these standards in 2011, including them in that body's guideline for immune thrombocytopenia. Despite the progress made so far, 20th century interventions such as corticosteroids and IVIg remain the mainstay of therapy. However, advances in treatment have led to the introduction of targeted therapies for select patients with chronic disease. In this paper, we review aspects of the epidemiology and pathophysiology of ITP and discuss the recent changes in guidelines for nomenclature, diagnosis, and treatment. © 2014.


Fannjiang A.C.,University of California at Davis
Inverse Problems | Year: 2010

Inverse scattering from discrete targets with the single-input-multiple- output (SIMO), multiple-input-single-output (MISO) or multiple-input-multiple- output (MIMO) measurements is analyzed by compressed sensing theory with and without the Born approximation. High-frequency analysis of (probabilistic) recoverability by the L1-based minimization/regularization principles is presented. In the absence of noise, it is shown that the L1-based solution can recover exactly the target of sparsity up to the dimension of the data either with the MIMO measurement for the Born scattering or with the SIMO/MISO measurement for the exact scattering. The stability with respect to noisy data is proved for weak or widely separated scatterers. Reciprocity between the SIMO and MISO measurements is analyzed. Finally a coherence bound (and the resulting recoverability) is proved for diffraction tomography with high-frequency, few-view and limited-angle SIMO/MISO measurements. © 2010 IOP Publishing Ltd.


Yang Z.,CAS Institute of Zoology | Yang Z.,University College London | Rannala B.,CAS Institute of Zoology | Rannala B.,University of California at Davis
Nature Reviews Genetics | Year: 2012

Phylogenies are important for addressing various biological questions such as relationships among species or genes, the origin and spread of viral infection and the demographic changes and migration patterns of species. The advancement of sequencing technologies has taken phylogenetic analysis to a new height. Phylogenies have permeated nearly every branch of biology, and the plethora of phylogenetic methods and software packages that are now available may seem daunting to an experimental biologist. Here, we review the major methods of phylogenetic analysis, including parsimony, distance, likelihood and Bayesian methods. We discuss their strengths and weaknesses and provide guidance for their use. © 2012 Macmillan Publishers Limited. All rights reserved.


Tucker R.P.,University of California at Davis
Journal of Experimental Zoology Part B: Molecular and Developmental Evolution | Year: 2013

Horizontal gene transfer (HGT), also known as lateral gene transfer, results in the rapid acquisition of genes from another organism. HGT has long been known to be a driving force in speciation in prokaryotes, and there is evidence for HGT from symbiotic and infectious bacteria to metazoans, as well as from protists to bacteria. Recently, it has become clear that as many as a 1,000 genes in the genome of the choanoflagellate Monosiga brevicollis may have been acquired by HGT. Interestingly, these genes reportedly come from algae, bacteria, and other choanoflagellate prey. Some of these genes appear to have allowed an ancestral choanoflagellate to exploit nutrient-poor environments and were not passed on to metazoan descendents. However, some of these genes are also found in animal genomes, suggesting that HGT into a common ancestor of choanozoans and animals may have contributed to metazoan evolution. © 2012 Wiley Periodicals, Inc.


Borchers A.T.,University of California at Davis | Gershwin M.E.,University of California at Davis
Autoimmunity Reviews | Year: 2014

Complex regional pain syndrome (CRPS) is a term used to describe a variety of disorders characterized by spontaneous or stimulus-induced pain that is disproportional to the inciting event and accompanied by a myriad of autonomic and motor disturbances in highly variable combinations. There are no standards which can be applied to the diagnosis and would fulfill definitions of evidence-based medicine. Indeed, there are almost as many diagnostic criteria as there are names to this disorder. The umbrella term CRPS has been subdivided into type I and type II. CRPS I is intended to encompass reflex sympathetic dystrophy and similar disorders without a nerve injury; while CRPS II occurs after damage to a peripheral nerve. There are numerous etiological pathophysiological events that have been incriminated in development of CRPS, including inflammation, autoimmune responses, abnormal cytokine production, sympathetic-sensory disorders, altered blood flow and central cortical reorganization. However, the number of studies that have included appropriate controls and have sufficient numbers of patients to allow statistical analysis with appropriate power calculations is vanishingly small. This has led to over-diagnosis and often excessive pharmacotherapy and even unnecessary surgical interventions. In this review we provide a detailed critical overview of not only the history of CRPS, but also the epidemiology, the clinical features, the pathophysiological studies, the proposed criteria, the therapy and, in particular, an emphasis that future research should apply more rigorous standards to allow a better understanding of CRPS, i.e. what it is, if it is, and when it is. © 2013 Elsevier B.V.


Aim: In this study, I examined the relative contributions of geography and ecology to species diversification within the genus Nerita, a prominent clade of marine snails that is widely distributed across the tropics and intertidal habitats. Specifically, I tested whether geographical patterns of speciation correspond primarily to allopatric or sympatric models, and whether habitat transitions have played a major role in species diversification. Location: Indo-West Pacific, eastern Pacific, Atlantic, tropical marine intertidal. Methods: I used a previously reconstructed molecular phylogeny of Nerita as a framework to assess the relative importance of geographical and ecological factors in species diversification. To evaluate whether recently diverged clades exhibit patterns consistent with allopatric or sympatric speciation, I mapped the geo-graphical distribution of each species onto the species-level phylogeny, and examined the relationship between range overlap and time since divergence using age-range correlation analyses. To determine the relative contribution of habitat transitions to divergence, I traced shifts in intertidal substrate affinity and vertical zonation across the phylogeny using parsimony, and implemented randomization tests to evaluate the resulting patterns of ecological change. Results: Within the majority of Nerita clades examined, age-range correlation analysis yielded a low intercept and a positive slope, similar to that expected under allopatric speciation. Approximately 75% of sister species pairs have maintained allopatric distributions; whereas more distantly related sister taxa often exhibited complete or nearly complete geographical overlap. In contrast, only 19% of sister species occupy distinct habitats. For both substrate and zonation, habitat transitions failed to concentrate towards either the tips or the root of the phylogeny. Instead, habitat shifts have occurred throughout the history of Nerita, with a general transition from the lower and mid-littoral towards the upper and supra-littoral zones, and multiple independent shifts from hard (rock) to softer substrates (mangrove, mud and sand). Main conclusions: Both geography and ecology appear to have influenced diversification in Nerita, but to different extents. Geography seems to play a principal role, with allopatric speciation driving the majority of Nerita divergences. Habitat transitions appear insignificant in shaping the early and recent history of speciation, and promoting successive diversification in Nerita; however, shifts may have been important for respective divergences (i.e. those that correspond to the transitions) and enhancing diversity throughout the clade. © 2010 Blackwell Publishing Ltd.


Urayama S.,University of California at Davis
World Journal of Gastroenterology | Year: 2015

Pancreatic ductal adenocarcinoma (PDAC) is the fourth and fifth leading cause of cancer death for each gender in developed countries. With lack of effective treatment and screening scheme available for the general population, the mortality rate is expected to increase over the next several decades in contrast to the other major malignancies such as lung, breast, prostate and colorectal cancers. Endoscopic ultrasound, with its highest level of detection capacity of smaller pancreatic lesions, is the commonly employed and preferred clinical imaging-based PDAC detection method. Various molecular biomarkers have been investigated for characterization of the disease, but none are shown to be useful or validated for clinical utilization for early detection. As seen from studies of a small subset of familial or genetically high-risk PDAC groups, the higher yield and utility of imaging-based screening methods are demonstrated for these groups. Multiple recent studies on the unique cancer metabolism including PDAC, demonstrate the potential for utility of the metabolites as the discriminant markers for this disease. In order to generate an early PDAC detection screening strategy available for a wider population, we propose to expand the population of higher risk PDAC group with combination clinical and metabolomics parameters. © The Author(s) 2015.


Goshima G.,Nagoya University | Scholey J.M.,University of California at Davis
Annual Review of Cell and Developmental Biology | Year: 2010

The mitotic spindle accurately segregates genetic instructions by moving chromosomes to spindle poles (anaphase A) and separating the poles (anaphase B) so that, in general, the chromosomes and poles are positioned near the centers of the nascent daughter cell products of each cell division. Because the size of different types of dividing cells, and thus the spacing of their daughter cell centers, can vary significantly, the length of the metaphase or postanaphase B spindle often scales with cell size. However, significant exceptions to this scaling rule occur, revealing the existence of cell size-independent, spindle-associated mechanisms of spindle length control. The control of spindle length reflects the action of mitotic force-generating mechanisms, and its study may illuminate general principles by which cells regulate the size of internal structures. Here we review molecules and mechanisms that control spindle length, how these mechanisms are deployed in different systems, and some quantitative models that describe the control of spindle length. Copyright © 2010 by Annual Reviews. All rights reserved.


Xu L.,University of California at Davis | Li S.,National University of Singapore | Stohr B.A.,University of California at San Francisco
Annual Review of Pathology: Mechanisms of Disease | Year: 2013

Telomere biology plays a critical and complex role in the initiation and progression of cancer. Although telomere dysfunction resulting from replicative attrition constrains tumor growth by engaging DNA-damage signaling pathways, it can also promote tumorigenesis by causing oncogenic chromosomal rearrangements. Expression of the telomerase enzyme enables telomere-length homeostasis and allows tumor cells to escape the antiproliferative barrier posed by short telomeres. Telomeres and telomerase also function independently of one another. Recent work has suggested that telomerase promotes cell growth through pathways unrelated to telomere maintenance, and a subset of tumors elongate telomeres through telomerase-independent mechanisms. In an effort to exploit the integral link between telomere biology and cancer growth, investigators have developed several telomerase-based therapeutic strategies, which are currently in clinical trials. Here, we broadly review the state of the field with a particular focus on recent developments of interest. © 2013 by Annual Reviews. All rights reserved.


Yang Y.,University of California at Davis
Decision Support Systems | Year: 2010

In this paper, we propose a simple, yet powerful approach to profile users' web browsing behavior for the purpose of user identification. The importance of being able to identify users can be significant given a wide variety of applications in electronic commerce, such as product recommendation, personalized advertising, etc. We create user profiles capturing the strength of users' behavioral patterns, which can be used to identify users. Our experiments indicate that these profiles can be more accurate at identifying users than decision trees when sufficient web activities are observed, and can achieve higher efficiency than Support Vector Machines. The comparisons demonstrate that profile-based methods for user identification provide a viable and simple alternative to this problem. © 2010 Elsevier B.V. All rights reserved.


Bodine S.C.,University of California at Davis
International Journal of Biochemistry and Cell Biology | Year: 2013

Loss of skeletal muscle mass occurs frequently in clinical settings in response to joint immobilization and bed rest, and is induced by a combination of unloading and inactivity. Disuse-induced atrophy will likely affect every person in his or her lifetime, and can be debilitating especially in the elderly. Currently there are no good therapies to treat disuse-induced muscle atrophy, in part, due to a lack of understanding of the cellular and molecular mechanisms responsible for the induction and maintenance of muscle atrophy. Our current understanding of disuse atrophy comes from the investigation of a variety of models (joint immobilization, hindlimb unloading, bed rest, spinal cord injury) in both animals and humans. Under conditions of unloading, it is widely accepted that there is a decrease in protein synthesis, however, the role of protein degradation, especially in humans, is debated. This review will examine the current understanding of the molecular and cellular mechanisms regulating muscle loss under disuse conditions, discussing the similarities and areas of dispute between the animal and human literature. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. © 2013 Elsevier Ltd. All rights reserved.


Marshall D.J.,University of Queensland | Morgan S.G.,University of California at Davis
Current Biology | Year: 2011

Naturalists and scientists have been captivated by the diversity of marine larval forms since they were discovered following the advent of the microscope. Because they often bear little resemblance to adults, larvae were identified initially as new life forms, classified into different groups based on the similarity of their body plans and given new names that are still with us today. The radically different body plans and lifestyles of marine larvae and adults have led most investigators historically to study the two phases of complex life cycles in isolation. More recently, important ecological insights have sprung from taking a holistic view of marine life cycles. Meanwhile, the evolutionary (phenotypic and genetic) links among life-history phases remain less appreciated. In this review, our objective is to evaluate the evolutionary links within marine life cycles, and explore their ecological and evolutionary consequences. We provide a brief overview of marine life histories, discuss the phenotypic and genetic links between the two phases of the life cycle and pose challenges to advance our understanding of the evolutionary constraints acting on marine life histories. © 2011 Elsevier Ltd. All rights reserved.


Hell J.W.,University of California at Davis
Science Signaling | Year: 2010

When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric Gs protein-adenylyl cyclase-adenosine 3′,5′-monophosphate-protein kinase A (PKA) signaling cascade. One of the main PKA targets implicated in this response is the L-type Ca2+ channel CaV1.2, which mediates Ca2+ influx into cardiomyocytes. Because of its central function in regulating heartbeat, and because the underlying molecular mechanism has remained elusive, understanding the regulation of CaV1.2 has been considered the holy grail for the field of channel regulation. New evidence from the quest to solve the mystery of CaV1.2 regulation has revealed that reproducible reconstitution of this regulation in heterologous cells requires a perfect balance of the ratio of CaV1.2 to A-kinase anchor proteins (AKAPs). Proteolytic processing of the cytosolic C terminus of the central, pore-forming α11.2 subunit of CaV1.2 contributed to its regulation by PKA, and Ser 1700 in the C terminus of the α11.2 subunit emerged as the relevant PKA phosphorylation site.


Ralph P.,University of California at Davis | Ralph P.,University of Southern California | Coop G.,University of California at Davis
PLoS Biology | Year: 2013

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2-12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world. © 2013 Ralph, Coop.


MacLean K.A.,University of California at Davis
Psychological science : a journal of the American Psychological Society / APS | Year: 2010

The ability to focus one's attention underlies success in many everyday tasks, but voluntary attention cannot be sustained for extended periods of time. In the laboratory, sustained-attention failure is manifest as a decline in perceptual sensitivity with increasing time on task, known as the vigilance decrement. We investigated improvements in sustained attention with training (approximately 5 hr/day for 3 months), which consisted of meditation practice that involved sustained selective attention on a chosen stimulus (e.g., the participant's breath). Participants were randomly assigned either to receive training first (n = 30) or to serve as waiting-list controls and receive training second (n = 30). Training produced improvements in visual discrimination that were linked to increases in perceptual sensitivity and improved vigilance during sustained visual attention. Consistent with the resource model of vigilance, these results suggest that perceptual improvements can reduce the resource demand imposed by target discrimination and thus make it easier to sustain voluntary attention.


Forget A.L.,University of California at Davis | Kowalczykowski S.C.,University of California at Davis
Trends in Cell Biology | Year: 2010

The Rad51 protein is essential for DNA repair by homologous recombination. After DNA damage, Rad51 localizes to nuclear foci that represent sites of DNA repair in vivo. In vitro, Rad51 self-assembles on single- or double-stranded DNA to form a nucleoprotein filament. Recently, the merging of innovative single-molecule techniques with ensemble methods has provided unique insights into the dynamic nature of this filament and its cellular function. The assembly and disassembly of Rad51 nucleoprotein filaments is seen to be regulated by recombination accessory proteins. In this regard, the BRC repeats of the BRCA2 protein were shown to modulate the DNA binding selectivity of Rad51. Furthermore, single-molecule studies explained the need for a DNA translocase, Rad54 protein, in the disassembly of Rad51 double-stranded DNA filaments. © 2010 Elsevier Ltd.


Roll-Mecak A.,Cell Biology and Biophysics Unit | McNally F.J.,University of California at Davis
Current Opinion in Cell Biology | Year: 2010

In 1993, an enzyme with an ATP-dependent microtubule-severing activity was purified from sea urchin eggs and named katanin, after the Japanese word for sword. Now we know that katanin, spastin, and fidgetin form a family of closely related microtubule-severing enzymes that is widely distributed in eukaryotes ranging from Tetrahymena and Chlamydomonas to humans. Here we review the diverse in vivo functions of these proteins and the recent significant advances in deciphering the biophysical mechanism of microtubule severing. © 2009 Elsevier Ltd.


Chen L.,University of California at Davis
Journal of the American Heart Association | Year: 2012

Mitochondrial fusion protein mutations are a cause of inherited neuropathies such as Charcot-Marie-Tooth disease and dominant optic atrophy. Previously we reported that the fusion protein optic atrophy 1 (OPA1) is decreased in heart failure. We investigated cardiac function, mitochondrial function, and mtDNA stability in a mouse model of the disease with OPA1 mutation. The homozygous mutation is embryonic lethal. Heterozygous OPA(+/-) mice exhibit reduced mtDNA copy number and decreased expression of nuclear antioxidant genes at 3 to 4 months. Although initial cardiac function was normal, at 12 months the OPA1(+/-) mouse hearts had decreased fractional shortening, cardiac output, and myocyte contraction. This coincided with the onset of blindness. In addition to small fragmented mitochondria, aged OPA1(+/-) mice had impaired cardiac mitochondrial function compared with wild-type littermates. OPA1 mutation leads to deficiency in antioxidant transcripts, increased reactive oxygen species, mitochondrial dysfunction, and late-onset cardiomyopathy.


Starr D.A.,University of California at Davis | Fridolfsson H.N.,University of California at Davis
Annual Review of Cell and Developmental Biology | Year: 2010

The nuclear envelope links the cytoskeleton to structural components of the nucleus. It functions to coordinate nuclear migration and anchorage, organize chromatin, and aid meiotic chromosome pairing. Forces generated by the cytoskeleton are transferred across the nuclear envelope to the nuclear lamina through a nuclear-envelope bridge consisting of SUN (Sad1 and UNC-84) and KASH (Klarsicht, ANC-1 and SyneNesprin homology) proteins. Some KASH-SUN combinations connect microtubules, centrosomes, actin filaments, or intermediate filaments to the surface of the nucleus. Other combinations are used in cell cycle control, nuclear import, or apoptosis. Interactions between the cytoskeleton and the nucleus also affect global cytoskeleton organization. SUN and KASH proteins were identified through genetic screens for mispositioned nuclei in model organisms. Knockouts of SUN or KASH proteins disrupt neurological and muscular development in mice. Defects in SUN and KASH proteins have been linked to human diseases including muscular dystrophy, ataxia, progeria, lissencephaly, and cancer. Copyright © 2010 by Annual Reviews. All rights reserved.


Cornell H.V.,University of California at Davis
Biological Reviews | Year: 2013

Two conflicting hypotheses have been proposed to explain large-scale species diversity patterns and dynamics. The unbounded hypothesis proposes that regional diversity depends only on time and diversification rate and increases without limit. The bounded hypothesis proposes that ecological constraints place upper limits on regional diversity and that diversity is usually close to its limit. Recent evidence from the fossil record, phylogenetic analysis, biogeography, and phenotypic disparity during lineage diversification suggests that diversity is constrained by ecological processes but that it is rarely asymptotic. Niche space is often unfilled or can be more finely subdivided and still permit coexistence, and new niche space is often created before ecological limits are reached. Damped increases in diversity over time are the prevalent pattern, suggesting the need for a new 'damped increase hypothesis'. The damped increase hypothesis predicts that diversity generally increases through time but that its rate of increase is often slowed by ecological constraints. However, slowing due to niche limitation must be distinguished from other possible mechanisms creating similar patterns. These include sampling artifacts, the inability to detect extinctions or declines in clade diversity with some methods, the distorting effects of correlated speciation-extinction dynamics, the likelihood that opportunities for allopatric speciation will vary in space and time, and the role of undetected natural enemies in reducing host ranges and thus slowing speciation rates. The taxonomic scope of regional diversity studies must be broadened to include all ecologically similar species so that ecological constraints may be accurately inferred. The damped increase hypothesis suggests that information on evolutionary processes such as time-for-speciation and intrinsic diversification rates as well as ecological factors will be required to explain why regional diversity varies among times, places and taxa. © 2012 Cambridge Philosophical Society.


Webster D.W.,Johns Hopkins University | Wintemute G.J.,University of California at Davis
Annual Review of Public Health | Year: 2015

This article summarizes and critiques available evidence from studies published between 1999 and August 2014 on the effects of policies designed to keep firearms from high-risk individuals in the United States. Some prohibitions for high-risk individuals (e.g., those under domestic violence restraining orders, violent misdemeanants) and procedures for checking for more types of prohibiting conditions are associated with lower rates of violence. Certain laws intended to prevent prohibited persons from accessing firearms - rigorous permit-to-purchase, comprehensive background checks, strong regulation and oversight of gun dealers, and requiring gun owners to promptly report lost or stolen firearms - are negatively associated with the diversion of guns to criminals. Future research is needed to examine whether these laws curtail nonlethal gun violence and whether the effects of expanding prohibiting conditions for firearm possession are modified by the presence of policies to prevent diversion. Copyright © 2015 by Annual Reviews. All rights reserved.


Cardiff R.D.,University of California at Davis
Journal of Mammary Gland Biology and Neoplasia | Year: 2010

Epithelial-mesenchymal-transition (EMT) tumorigenesis in the mouse was first described over 100 years ago using various terms such as carcinosarcoma and without any comprehension of the underlying mechanisms. Such tumors have been considered artifacts of transplantation and of tissue culture. Recently, EMT tumors have been recognized in mammary glands of genetically engineered mice. This review provides a historical perspective leading to the current status in the context of some of the key molecular biology. The biology of mouse mammary EMT tumorigenesis is discussed with comparisons to human breast cancer. © 2010 The Author(S).


Delucchi M.A.,University of California at Davis
Annals of the New York Academy of Sciences | Year: 2010

Governments worldwide are promoting the development of biofuels in order to mitigate the climate impact of using fuels. In this article, I discuss the impacts of biofuels on climate change, water use, and land use. I discuss the overall metric by which these impacts have been measured and then present and discuss estimates of the impacts. In spite of the complexities of the environmental and technological systems that affect climate change, land use, and water use, and the difficulties of constructing useful metrics, it is possible to make some qualitative overall assessments. It is likely that biofuels produced from crops using conventional agricultural practices will not mitigate the impacts of climate change and will exacerbate stresses on water supplies, water quality, and land use, compared with petroleum fuels. Policies should promote the development of sustainable biofuel programs that have very low inputs of fossil fuels and chemicals that rely on rainfall or abundant groundwater, and that use land with little or no economic or ecological value in alternative uses. © 2010 New York Academy of Sciences.


Chen X.,University of California at Davis | Varki A.,University of California at San Diego
ACS Chemical Biology | Year: 2010

Sialic acids are a subset of nonulosonic acids, which are ninecarbon α-keto aldonic acids. Natural existing sialic acid-containing structures are presented in different sialic acid forms, various sialyl linkages, and on diverse underlying glycans. They play important roles in biological, pathological, and immunological processes. Sialobiology has been a challenging and yet attractive research area. Recent advances in chemical and chemoenzymatic synthesis, as well as large-scale E. coli cell-based production, have provided a large library of sialoside standards and derivatives in amounts sufficient for structure-activity relationship studies. Sialoglycan microarrays provide an efficient platform for quick identification of preferred ligands for sialic acid-binding proteins. Future research on sialic acid will continue to be at the interface of chemistry and biology. Research efforts not only will lead to a better understanding of the biological and pathological importance of sialic acids and their diversity but also could lead to the development of therapeutics. © 2010 American Chemical Society.


Polymer-matrix composite structures in service may be affected by different environmental conditions that modify their mechanical performance, thermal stability, and flammability potential. In this study, epoxy-based structural adhesive and carbon/epoxy specimens were degraded at three conditioning temperatures, by water and commercial fluids typical of aerospace operations: jet fuel, anti-icing additive and hydraulic fluid. Two well-established simple diffusion models (Fickian, Langmuir) were used to interpret the mass uptake data and assess the suitability of such models for these tests. Despite limitations inherent in these models, reasonably good fits were obtained for adhesive and carbon/epoxy specimens immersed in water or anti-icing additive. We report the respective strengths of association of the two models with the individual specimens' data, and boxplots for the diffusivity changes among the three conditioning temperatures. An Arrhenius trend for the diffusivity of adhesive specimens treated in anti-icing shows that this temperature dependence may not be a good approximation for this problem. The degradation of these materials in hydraulic fluid is very complex, as indicated by the extensive swelling and the color change, and these models could not successfully fit the gravimetric data. These new results could aid researchers in multiphysics modeling of degraded composite structures. © 2011 Elsevier Ltd.


Ju K.-S.,University of California at Davis | Ju K.-S.,Urbana University | Parales R.E.,University of California at Davis
Microbiology and Molecular Biology Reviews | Year: 2010

Nitroaromatic compounds are relatively rare in nature and have been introduced into the environment mainly by human activities. This important class of industrial chemicals is widely used in the synthesis of many diverse products, including dyes, polymers, pesticides, and explosives. Unfortunately, their extensive use has led to environmental contamination of soil and groundwater. The nitro group, which provides chemical and functional diversity in these molecules, also contributes to the recalcitrance of these compounds to biodegradation. The electron-withdrawing nature of the nitro group, in concert with the stability of the benzene ring, makes nitroaromatic compounds resistant to oxidative degradation. Recalcitrance is further compounded by their acute toxicity, mutagenicity, and easy reduction into carcinogenic aromatic amines. Nitroaromatic compounds are hazardous to human health and are registered on the U.S. Environmental Protection Agency's list of priority pollutants for environmental remediation. Although the majority of these compounds are synthetic in nature, microorganisms in contaminated environments have rapidly adapted to their presence by evolving new biodegradation pathways that take advantage of them as sources of carbon, nitrogen, and energy. This review provides an overview of the synthesis of both man-made and biogenic nitroaromatic compounds, the bacteria that have been identified to grow on and completely mineralize nitroaromatic compounds, and the pathways that are present in these strains. The possible evolutionary origins of the newly evolved pathways are also discussed. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Best R.J.,University of California at Davis | Caulk N.C.,University of California at Davis | Stachowicz J.J.,University of California at Davis
Ecology Letters | Year: 2013

Field studies of community assembly patterns increasingly use phylogenetic relatedness as a surrogate for traits. Recent experiments appear to validate this approach by showing effects of correlated trait and phylogenetic distances on coexistence. However, traits governing resource use in animals are often labile. To test whether feeding trait or phylogenetic diversity can predict competition and production in communities of grazing amphipods, we manipulated both types of diversity independently in mesocosms. We found that increasing the feeding trait diversity of the community increased the number of species coexisting, reduced dominance and changed food availability. In contrast, phylogenetic diversity had no effect, suggesting that whatever additional ecological information it represents was not relevant in this context. Although community phylogenetic structure in the field may result from multiple traits with potential for phylogenetic signal, phylogenetic effects on species interactions in controlled experiments may depend on the lability of fewer key traits. © 2012 Blackwell Publishing Ltd/CNRS.


Coping with perturbations of the environment such as severe storms and other climatic extremes, habitat degradation, changes in predator numbers, invasive species and social disruption is one of the most essential physiological and behavioural processes. The palaeontological record shows that organisms have had to cope with environmental perturbations throughout the history of life on Earth. These ancient processes show highly conserved mechanisms, but also great flexibility in responses to social and physical environment challenges. Adrenocortical responses to perturbations can trigger a coping response called the emergency life history stage (EHLS). However, if the adaptive value of the ELHS declines because of trade-offs with other life history stages such as breeding, then the adrenocortical response to acute perturbations (stress) can be modulated. Mechanisms involve allostasis and reactive scope with three foci of regulation: hormone secretion, transport and response. It is now well known that modulation of the adrenocortical responses to perturbations occur through gene-environment interactions during development and throughout the life cycle. These modulations involve individual differences in gender, age, experience and condition as well as latitudinal, altitudinal and hemispheric variations. Dramatic consequences of human-induced rapid environmental change such as increasing frequency and intensity of environmental perturbations will likely have implications for continued adaptation to extreme events. Note that modulation of the stress response also involves three major processes: modulation of robustness (i.e. become more resistant to acute stress); modulation of responsiveness (i.e. modulate the actual response to stress for more flexibility); and modulation of resilience (i.e. how quickly and completely the recovery is after the perturbation has passed). Mechanisms underlying these modulations remain largely unexplored. © 2013 The Association for the Study of Animal Behaviour.


Human milk lactoferrin (hmLF) is the most abundant glycoprotein present in human milk and displays a broad range of protective functions in the gut of newborn infants. hmLF is N-glycosylated, but little is known about the lactation stage-related development of the glycosylation phenotype. hmLF glycosylation from milk samples from five donors during the first 10 weeks of lactation was assessed and observed to be more diverse than previously reported. During this period dynamic changes in glycosylation were observed corresponding to a decrease in glycosylation in the second week followed by an increase in total glycosylation as well as higher order fucosylation thereafter. Gene expression analysis was performed in milk somatic cells from a sixth subject. It was found that fucosyltransferase expression increased during entire period, whereas expression of genes for the oligosaccharyl transferase complex decreased in the second week. The effect of hmLF glycosylation was examined for the protein's ability to affect bacterial binding to epithelial cells. hmLF significantly inhibited pathogen adhesion and purified hmLF glycans significantly reduced Salmonella invasion of colonic epithelial cells to levels associated with non-invasive deletion mutants. This study indicates that hmLF glycosylation is tightly regulated by gene expression and that glyco-variation is involved in modulating pathogen association.


Denny M.W.,Stanford University | Gaylord B.,University of California at Davis
Annual Review of Marine Science | Year: 2010

The emerging field of marine ecomechanics provides an explicit physical framework for exploring interactions among marine organisms and between these organisms and their environments. It exhibits particular utility through its construction of predictive, mechanistic models, a number of which address responses to changing climatic conditions. Examples include predictions of (a) the change in relative abundance of corals as a function of colony morphology, ocean acidity, and storm intensity; (b) the rate of disturbance and patch formation in beds of mussels, a competitive dominant on many intertidal shores; (c) the dispersal and recruitment patterns of giant kelps, an important nearshore foundation species; (d) the effects of turbulence on external fertilization, a widespread method of reproduction in the sea; and (e) the long-term incidence of extreme ecological events. These diverse examples emphasize the breadth of marine ecomechanics. Indeed, its principles can be applied to any ecological system. © 2010 by Annual Reviews.


Hastings A.,University of California at Davis
Ecology | Year: 2010

Explicit consideration of timescales and dynamics is required for an understanding of fundamental issues in ecology. Endogenous dynamics can lead to transient states where asymptotic behavior is very different from dynamics on short timescales. The causes of these kinds of transients can be placed in one of three classes: linear systems with different timescales embedded or exhibiting reactive behavior, the potentially long times to reach synchrony across space for oscillating systems, and the complex dynamics of systems with strong density-dependent (nonlinear) interactions. It is also important to include the potentially disparate timescales inherent in ecological systems when determining the endogenous dynamics. I argue that the dynamics of ecological systems can best be understood as the response, which may include transient dynamics, to exogenous influences leading to the observed dynamics on ecologically relevant timescales. This view of ecosystem behavior as responses of ecological systems governed by endogenous dynamics to exogenous influences provides a synthetic way to unify different approaches to population dynamics, to understand mechanisms that determine the distribution and abundance of species, and to manage ecosystems on appropriate timescales. There are implications for theoretical approaches, empirical approaches, and the statistical approaches that bridge theory and observation. © 2010 by the Ecological Society of America.


Dasu M.R.,University of California at Davis | Jialal I.,University of California at Davis
American Journal of Physiology - Endocrinology and Metabolism | Year: 2011

Type 2 diabetes (T2DM) is characterized by hyperglycemia, dyslipidemia, and increased inflammation. Previously, we showed that high glucose (HG) induces Toll-like receptor (TLR) expression, activity, and inflammation via NF-κB followed by cytokine release in vitro and in vivo. Here, we determined how HG-induced inflammation is affected by free fatty acids (FFA) in human monocytes. THP-1 monocytic cells, CD14+ human monocytes, and transiently transfected HEK293 cells were exposed to various FFA (0-500 μM) and glucose (5-20 mM) for evaluation of TLR2, TLR4, NF-κB, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and superoxide release. In THP-1 cells, palmitate increased cellular TLR2 and TLR4 expression, generated reactive oxygen species (ROS), and increased NF-κB activity, IL-1β, and MCP-1 release in a dose- and time-dependent manner. Similar data were observed with stearate and FFA mixture but not with oleate. Conversely, NADPH oxidase inhibitor treatment repressed glucose-and palmitate-stimulated ROS generation and NF-κB activity and decreased IL-1β and MCP-1 expression. Silencing TLR2, TLR4, and p47phox with small inhibitory RNAs (siRNAs) significantly reduced superoxide release, NF-κB activity, IL-1β, and MCP-1 secretion in HG and palmitate-treated THP-1 cells. Moreover, data from transient transfection experiments suggest that TLR6 is required for TLR2 and MD2 for TLR4 to augment inflammation in FFA- and glucose-exposed cells. These findings were confirmed with human monocytes. We conclude that FFA exacerbates HG-induced TLR expression and activity in monocytic cells with excess superoxide release, enhanced NF-κB activity, and induced proinflammatory factor release.


Blaimer B.B.,University of California at Davis
Molecular Phylogenetics and Evolution | Year: 2012

This study unravels the evolution and biogeographic history of the globally distributed ant genus Crematogaster on the basis of a molecular phylogeny, reconstructed from five nuclear protein-coding genes and a total of 3384. bp of sequence data. A particular emphasis is placed on the evolutionary history of these ants in the Malagasy region. Bayesian and likelihood analyses performed on a dataset of 124 Crematogaster ingroup taxa lend strong support for three deeply diverging phylogenetic lineages within the genus: the Orthocrema clade, the Global Crematogaster clade and the Australo-Asian Crematogaster clade. The 15 previous subgenera within Crematogaster are mostly not monophyletic. Divergence dating analyses and ancestral range reconstructions suggest that Crematogaster evolved in South-East Asia in the mid-Eocene (40-45. ma). The three major lineages also originated in this region in the late Oligocene/early Miocene (∼24-30. ma). A first dispersal out of S-E Asia by an Orthocrema lineage is supported for 22-30. ma to the Afrotropical region. Successive dispersal events out of S-E Asia began in the early, and continued throughout the late Miocene. The global distribution of Crematogaster was achieved by subsequent colonizations of all major biogeographic regions by the Orthocrema and the Global Crematogaster clade. Molecular dating estimates and ancestral range evolution are discussed in the light of palaeogeographic changes in the S-E Asian region and an evolving ocean circulation system throughout the Eocene, Oligocene and Miocene. Eight dispersal events to/from Madagascar by Crematogaster are supported, with most events occurring in the late Miocene to Pliocene (5.0-9.5. ma). These results suggest that Crematogaster ants possess exceptional dispersal and colonization abilities, and emphasize the need for detailed investigations of traits that have contributed to the global evolutionary success of these ants. © 2012 Elsevier Inc.


Jacobson M.Z.,Stanford University | Delucchi M.A.,University of California at Davis
Energy Policy | Year: 2011

Climate change, pollution, and energy insecurity are among the greatest problems of our time. Addressing them requires major changes in our energy infrastructure. Here, we analyze the feasibility of providing worldwide energy for all purposes (electric power, transportation, heating/cooling, etc.) from wind, water, and sunlight (WWS). In Part I, we discuss WWS energy system characteristics, current and future energy demand, availability of WWS resources, numbers of WWS devices, and area and material requirements. In Part II, we address variability, economics, and policy of WWS energy. We estimate that ~3,800,000 5 MW wind turbines, ~49,000 300. MW concentrated solar plants, ~40,000 300. MW solar PV power plants, ~1.7 billion 3 kW rooftop PV systems, ~5350 100. MW geothermal power plants, ~270 new 1300. MW hydroelectric power plants, ~720,000 0.75. MW wave devices, and ~490,000 1. MW tidal turbines can power a 2030 WWS world that uses electricity and electrolytic hydrogen for all purposes. Such a WWS infrastructure reduces world power demand by 30% and requires only ~0.41% and ~0.59% more of the world's land for footprint and spacing, respectively. We suggest producing all new energy with WWS by 2030 and replacing the pre-existing energy by 2050. Barriers to the plan are primarily social and political, not technological or economic. The energy cost in a WWS world should be similar to that today. © 2010 Elsevier Ltd.


Delucchi M.,University of California at Davis
Biomass and Bioenergy | Year: 2011

In this paper I discuss general conceptual issues in the estimation of the impacts of CO2 emissions from soils and biomass, over time, as a result of land-use change (LUC) due to increased demand for energy crops. The effect of LUC on climate depends generally on the magnitude and timing of changes in soil and plant carbon, and in particular on the timing and extent of the reversion of land to original ecosystems at the end of the bioenergy program. Depending on whether one counts the climate impacts of any reversion of land uses, and how one values future climate-change impacts relative to present impacts, one can estimate anywhere from zero to very large climate impacts due to land-use change (LUC). I argue that the best method is to estimate the net present value (NPV) of the impacts of climate change due to LUC. With this approach, one counts the reversion impacts at the end of the program and applies a continuous discounting function to future impacts to express them in present terms. In this case, the impacts of CO2 emissions from the initial LUC then are at least partially offset by the impacts of CO2 sequestration from reversion. © 2010 Elsevier Ltd.


Sharma M.K.,University of California at Davis
PloS one | Year: 2012

The perennial grass, switchgrass (Panicum virgatum L.), is a promising bioenergy crop and the target of whole genome sequencing. We constructed two bacterial artificial chromosome (BAC) libraries from the AP13 clone of switchgrass to gain insight into the genome structure and organization, initiate functional and comparative genomic studies, and assist with genome assembly. Together representing 16 haploid genome equivalents of switchgrass, each library comprises 101,376 clones with average insert sizes of 144 (HindIII-generated) and 110 kb (BstYI-generated). A total of 330,297 high quality BAC-end sequences (BES) were generated, accounting for 263.2 Mbp (16.4%) of the switchgrass genome. Analysis of the BES identified 279,099 known repetitive elements, >50,000 SSRs, and 2,528 novel repeat elements, named switchgrass repetitive elements (SREs). Comparative mapping of 47 full-length BAC sequences and 330K BES revealed high levels of synteny with the grass genomes sorghum, rice, maize, and Brachypodium. Our data indicate that the sorghum genome has retained larger microsyntenous regions with switchgrass besides high gene order conservation with rice. The resources generated in this effort will be useful for a broad range of applications.


Sela D.A.,University of California at Davis | Mills D.A.,University of California at Davis
Trends in Microbiology | Year: 2010

As the sole nutrition provided to infants, bioactive molecules dissolved in milk influence the development of our gut microbiota. Accordingly, human milk oligosaccharides (HMOs) are minimally digested by the infant and persist to negatively and positively regulate gut microbiota. Infant-type bifidobacteria utilize these soluble carbohydrate oligomers by convergent mechanisms. Bifidobacterium longum subsp. infantis efficiently consumes several small mass HMOs and possesses a large gene cluster and other loci dedicated to HMO metabolism. In contrast, adult-associated bifidobacteria such as the closely related B. longum subsp. longum are deficient for HMO utilization, although they retain the capacity to ferment plant oligosaccharides and constituent pentose sugars. Thus, the ability to subsist on HMO could demark infant-associated ecotypes potentially adapted to colonize the nursing infant. © 2010 Elsevier Ltd.


Mcbride C.S.,University of California at Davis | Singer M.C.,University of Texas at Austin
PLoS Biology | Year: 2010

Gene flow between populations that are adapting to distinct environments may be restricted if hybrids inherit maladaptive, intermediate phenotypes. This phenomenon, called extrinsic postzygotic isolation (EPI), is thought to play a critical role in the early stages of speciation. However, despite its intuitive appeal, we know surprisingly little about the strength and prevalence of EPI in nature, and even less about the specific phenotypes that tend to cause problems for hybrids. In this study, we searched for EPI among allopatric populations of the butterfly Euphydryas editha that have specialized on alternative host plants. These populations recall a situation thought typical of the very early stages of speciation. They lack consistent host-associated genetic differentiation at random nuclear loci and show no signs of reproductive incompatibility in the laboratory. However, they do differ consistently in diverse host-related traits. For each of these traits, we first asked whether hybrids between populations that use different hosts (different-host hybrids) were intermediate to parental populations and to hybrids between populations that use the same host (same-host hybrids). We then conducted field experiments to estimate the effects of intermediacy on fitness in nature. Our results revealed strong EPI under field conditions. Different-host hybrids exhibited an array of intermediate traits that were significantly maladaptive, including four behaviors. Intermediate foraging height slowed the growth of larvae, while intermediate oviposition preference, oviposition site height, and clutch size severely reduced the growth and survival of the offspring of adult females. We used our empirical data to construct a fitness surface on which different-host hybrids can be seen to fall in an adaptive valley between two peaks occupied by same-host hybrids. These findings demonstrate how ecological selection against hybrids can create a strong barrier to gene flow at the early stages of adaptive divergence. © 2010 McBride, Singer.


Myers T.W.,University of California at Davis | Berben L.A.,University of California at Davis
Chemical Science | Year: 2014

Herein, we report that molecular aluminium complexes of the bis(imino)pyridine ligand, (PhI2P2-)Al(THF)X, X = H (1), CH3 (2), promote selective dehydrogenation of formic acid to H2 and CO2 with an initial turnover frequency of 5200 turnovers per hour. Low-temperature reactions show that reaction of 1 with HCOOH affords a complex that is protonated three times: twice on the PhI2P2- ligand and once to liberate H 2 or CH4 from the Al-hydride or Al-methyl, respectively. We demonstrate that in the absence of protons, insertion of CO2 into the Al-hydride bond of 1 is facile and produces an Al-formate. Upon addition of protons, liberation of CO2 from the Al-formate complex affords an Al-hydride. Deuterium labelling studies and the solvent dependence of the reaction indicate that outer sphere β-hydride abstraction supported by metal-ligand cooperative hydrogen bonding is a likely mechanism for the C-H bond cleavage. © 2014 the Partner Organisations.


D'Souza R.M.,University of California at Davis | Nagler J.,ETH Zurich
Nature Physics | Year: 2015

The emergence of large-scale connectivity on an underlying network or lattice, the so-called percolation transition, has a profound impact on the system's macroscopic behaviours. There is thus great interest in controlling the location of the percolation transition to either enhance or delay its onset and, more generally, in understanding the consequences of such control interventions. Here we review explosive percolation, the sudden emergence of large-scale connectivity that results from repeated, small interventions designed to delay the percolation transition. These transitions exhibit drastic, unanticipated and exciting consequences that make explosive percolation an emerging paradigm for modelling real-world systems ranging from social networks to nanotubes. © 2015 Macmillan Publishers Limited. All rights reserved.


Mittler R.,University of Nevada, Reno | Mittler R.,Hebrew University of Jerusalem | Blumwald E.,University of California at Davis
Annual Review of Plant Biology | Year: 2010

Abiotic stress conditions such as drought, heat, or salinity cause extensive losses to agricultural production worldwide. Progress in generating transgenic crops with enhanced tolerance to abiotic stresses has nevertheless been slow. The complex field environment with its heterogenic conditions, abiotic stress combinations, and global climatic changes are but a few of the challenges facing modern agriculture. A combination of approaches will likely be needed to significantly improve the abiotic stress tolerance of crops in the field. These will include mechanistic understanding and subsequent utilization of stress response and stress acclimation networks, with careful attention to field growth conditions, extensive testing in the laboratory, greenhouse, and the field; the use of innovative approaches that take into consideration the genetic background and physiology of different crops; the use of enzymes and proteins from other organisms; and the integration of QTL mapping and other genetic and breeding tools. Copyright © 2010 by Annual Reviews. All rights reserved.


Mcsorley S.J.,University of California at Davis
Immunological Reviews | Year: 2014

Salmonella are a common source of food- or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of host immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T- and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection, but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Donadio D.,University of California at Davis | Galli G.,University of California at Davis
Nano Letters | Year: 2010

We compute the lattice thermal conductivity (k) of silicon nanowires as a function of temperature by molecular dynamics simulations. In wires with amorphous surfaces k may reach values close to that of amorphous silicon and is nearly constant between 200 and 600 K; this behavior is determined by the presence of a majority of nonpropagating vibrational modes. We develop a parameter-free model that accounts for the temperature dependence observed in our simulations and provides a qualitative explanation of recent experiments. © 2010 American Chemical Society.


Changes in phenology are correlated with climate change. However, we still struggle to understand the traits making species susceptible to climate change, and the implications of species' reactions for communities and food webs. Butterflies and moths are an ecologically important group that have shown pronounced phenological changes over the last decades. Tests using a > 150-year dataset from 566 European butterfly and moth species demonstrated that variation in phenological change was strongly related to traits describing plant-herbivore interactions (larval diet breadth, diet composition), and the life cycle. The results indicate that climate change related shifts in phenology are correlated with the seasonal availability and palatability of food plants. Lepidopterans feeding on herbaceous plants showed smaller shifts in flight periods but larger increases in voltinism than lepidopterans feeding on woody plants. Consequently, the effect of herbivorous lepidopterans may increase in herb-rich grassland ecosystems under warmer conditions, and not in forest ecosystems. © 2010 Blackwell Publishing Ltd/CNRS.


Richardson D.M.,Stellenbosch University | Rejmanek M.,University of California at Davis
Diversity and Distributions | Year: 2011

Aim Woody plants were not widely considered to be important invasive alien species until fairly recently. Thousands of species of trees and shrubs have, however, been moved around the world. Many species have spread from planting sites, and some are now among the most widespread and damaging of invasive organisms. This article presents a global list of invasive alien trees and shrubs. It discusses taxonomic biases, geographical patterns, modes of dispersal, reasons for introductions and key issues regarding invasions of non-native woody plants around the world. Location Global. Methods An exhaustive survey was made of regional and national databases and the literature. Correspondence with botanists and ecologists and our own observations in many parts of the world expanded the list. Presence of invasive species was determined for each of 15 broad geographical regions. The main reasons for introduction and dissemination were determined for each species. Results The list comprises 622 species (357 trees, 265 shrubs in 29 plant orders, 78 families, 286 genera). Regions with the largest number of woody invasive alien species are: Australia (183); southern Africa (170); North America (163); Pacific Islands (147); and New Zealand (107). Species introduced for horticulture dominated the list (62% of species: 196 trees and 187 shrubs). The next most important reasons for introduction and dissemination were forestry (13%), food (10%) and agroforestry (7%). Three hundred and twenty-three species (52%) are currently known to be invasive in only one region, and another 126 (20%) occur in only two regions. Only 38 species (6%) are very widespread (invasive in six or more regions). Over 40% of invasive tree species and over 60% of invasive shrub species are bird dispersed. Main conclusions Only between 0.5% and 0.7% of the world's tree and shrub species are currently invasive outside their natural range, but woody plant invasions are rapidly increasing in importance around the world. The objectively compiled list of invasive species presented here provides a snapshot of the current dimensions of the phenomenon and will be useful for screening new introductions for invasive potential. © 2011 Blackwell Publishing Ltd.


Cappa C.D.,University of California at Davis | Wilson K.R.,Lawrence Berkeley National Laboratory
Atmospheric Chemistry and Physics | Year: 2011

Vacuum Ultraviolet (VUV) photoionization mass spectrometry has been used to measure the evolution of chemical composition for two distinct organic aerosol types as they are passed through a thermodenuder at different temperatures. The two organic aerosol types considered are primary lubricating oil (LO) aerosol and secondary aerosol from the α-pinene + O3 reaction (αP). The evolution of the VUV mass spectra for the two aerosol types with temperature are observed to differ dramatically. For LO particles, the spectra exhibit distinct changes with temperature in which the lower peaks, corresponding to compounds with higher vapor pressures, disappear more rapidly than the high peaks. In contrast, the αP aerosol spectrum is essentially unchanged by temperature even though the particles experience significant mass loss due to evaporation. The variations in the LO spectra are found to be quantitatively in agreement with expectations from absorptive partitioning theory whereas the αP spectra suggest that the evaporation of αP derived aerosol appears to not be governed by partitioning theory. We postulate that this difference arises from diffusivity within the ±P particles being sufficiently slow that they do not exhibit the expected liquid-like behavior and perhaps exist in a glassy state. To reconcile these observations with decades of aerosol growth measurements, which indicate that OA formation is described by equilibrium partitioning, we present a conceptual model wherein the secondary OA is formed and then rapidly converted from an absorbing form to a non-absorbing form. The results suggest that, although OA growth may be describable by equilibrium partitioning theory, the properties of organic aerosol once formed may differ significantly from the properties determined in the equilibrium framework. © 2011 Author(s).


Baumgarth N.,University of California at Davis
Advances in Experimental Medicine and Biology | Year: 2013

Antibodies are an integral part of the immune system. They are produced in response to an infection or insult but are also present prior to any encounter with antigen as so-called natural antibodies. This review focuses on the tissues and cellular origins of natural antibodies. It summarizes recent data showing that B-1 cells, an innate-like B cell population distinct in development, repertoire, and tissue location from the majority conventional or B-2 cells, are the main contributors of natural antibodies in mice in steady state. Furthermore, they show that natural IgM production appears largely confined to B-1 cell populations in the spleen and bone marrow. In contrast, B-1 cells in the body cavities, sites of predominance of this population, harbor B-1 cells that do not constitutively produce antibodies. Instead, these cells act as rapid immune responders that relocate to secondary lymphoid tissues and differentiate to cytokine and antibodysecreting cells shortly after an infection. Thus, the process of B-1 cell response participation is distinct from that of B-2 cell activation as the accumulation of effector B-1 cells does not rely on extensive clonal expansion, but instead on their rapid migration and redistribution, a process that appears under the control of infection-induced innate signals. © Springer Science+Business Media New York 2013.


Sukumar N.,University of California at Davis
Computer Methods in Applied Mechanics and Engineering | Year: 2013

In this paper, we present the development of quadratic serendipity shape functions on planar convex and nonconvex polygons. Drawing on the work of Bompadre et al. (2012) [1] and Hormann and Sukumar (2008) [2], we adopt a relative entropy measure for signed (positive or negative) shape functions, with nodal prior weight functions that have the appropriate zero-set on the boundary of the polygon. We maximize the objective functional subject to the constraints for quadratic completeness proposed by Rand et al. (2013) [3]. Along an edge of a polygon, the approximation is identical to univariate Bernstein polynomials: the choice of the nodal prior weight function ensures that the shape functions satisfy a weak Kronecker-delta property on each edge. The shape functions are well-defined for arbitrary planar polygons without self-intersections. On using a modified numerical integration scheme, we show that the quadratic patch test is passed on polygonal meshes with convex and nonconvex elements. Numerical tests for the Poisson equation on self-similar trapezoidal meshes and quasiuniform polygonal meshes are presented, which reveal the sound accuracy of the method, and optimal rates of convergence in the L2 norm and the H1 seminorm are established. © 2013.


He Y.,University of California at Davis | Galli G.,University of California at Davis
Physical Review Letters | Year: 2012

We designed nanowires with a tailored surface structure and composition and with specific core defects to investigate the microscopic origin of the reduced thermal conductivity of Si at the nanoscale. We considered a diameter (15 nm) comparable to that of systems fabricated in recent experiments and we computed the thermal conductivity using equilibrium molecular dynamics simulations. We found that the presence of a native oxide surface layer may account for a tenfold to ∼30-fold decrease in conductivity, with respect to bulk Si, depending on the level of roughness. However it is only the combination of core defects and surface ripples that enables a decrease close to 2 orders of magnitude, similar to that reported experimentally. © 2012 American Physical Society.


Murray I.D.,University of California at Davis | Galli G.,University of California at Davis
Physical Review Letters | Year: 2012

We present a first principles theoretical framework that accurately accounts for several properties of ice, over a wide pressure range. In particular, we show that, by using a recently developed nonlocal van der Waals functional and by taking into account hydrogen zero point motion, one can properly describe the zero temperature equation of state, the vibrational spectra, and the dielectric properties of ice at low pressure and of ice VIII, a stable phase between 2 and 60GPa. While semilocal density functionals yield a transition pressure from ice XI to VIII that is overestimated by almost an order of magnitude, we find good agreement with experiments when dispersion forces are taken into account. Zero point energy contributions do not alter the computed transition pressure, but they affect structural properties, including equilibrium volumes and bulk moduli. © 2012 American Physical Society.


Starr D.A.,University of California at Davis
Current Biology | Year: 2012

SUN proteins accelerate the pathological progression of laminopathies. Although the mechanisms remain to be elucidated, an intriguing possibility is that high levels of SUN proteins lead to a hyperactive DNA damage response. © 2012 Elsevier Ltd. All rights reserved.


Sanford E.,University of California at Davis
Proceedings. Biological sciences / The Royal Society | Year: 2014

There is growing concern that global environmental change might exacerbate the ecological impacts of invasive species by increasing their per capita effects on native species. However, the mechanisms underlying such shifts in interaction strength are poorly understood. Here, we test whether ocean acidification, driven by elevated seawater pCO2, increases the susceptibility of native Olympia oysters to predation by invasive snails. Oysters raised under elevated pCO2 experienced a 20% increase in drilling predation. When presented alongside control oysters in a choice experiment, 48% more high-CO2 oysters were consumed. The invasive snails were tolerant of elevated CO2 with no change in feeding behaviour. Oysters raised under acidified conditions did not have thinner shells, but were 29-40% smaller than control oysters, and these smaller individuals were consumed at disproportionately greater rates. Reduction in prey size is a common response to environmental stress that may drive increasing per capita effects of stress-tolerant invasive predators.


Zheng J.,University of California at Davis
Comprehensive Physiology | Year: 2013

Transient receptor potential (TRP) channels are cellular sensors for a wide spectrum of physical and chemical stimuli. They are involved in the formation of sight, hearing, touch, smell, taste, temperature, and pain sensation. TRP channels also play fundamental roles in cell signaling and allow the host cell to respond to benign or harmful environmental changes. As TRP channel activation is controlled by very diverse processes and, in many cases, exhibits complex polymodal properties, understanding how each TRP channel responds to its unique forms of activation energy is both crucial and challenging. The past two decades witnessed significant advances in understanding the molecular mechanisms that underlie TRP channels activation. This review focuses on our current understanding of the molecular determinants for TRP channel activation. © 2013 American Physiological Society.


Baar K.,University of California at Davis
Sports Medicine | Year: 2014

Very few sports use only endurance or strength. Outside of running long distances on a flat surface and power-lifting, practically all sports require some combination of endurance and strength. Endurance and strength can be developed simultaneously to some degree. However, the development of a high level of endurance seems to prohibit the development or maintenance of muscle mass and strength. This interaction between endurance and strength is called the concurrent training effect. This review specifically defines the concurrent training effect, discusses the potential molecular mechanisms underlying this effect, and proposes strategies to maximize strength and endurance in the high-level athlete. © 2014, The Author(s).


Crawley J.N.,University of California at Davis
Dialogues in Clinical Neuroscience | Year: 2012

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics. © 2012, LLS SAS.


Biro P.A.,University of New South Wales | Stamps J.A.,University of California at Davis
Trends in Ecology and Evolution | Year: 2010

Consistent individual differences (CIDs) in behavior are a widespread phenomenon in animals, but the proximate reasons for them are unresolved. We discuss evidence for the hypothesis that CIDs in energy metabolism, as reflected by resting metabolic rate (RMR), promote CIDs in behavior patterns that either provide net energy (e.g. foraging activity), and/or consume energy (e.g. courtship activity). In doing so, we provide a framework for linking together RMR, behavior, and life-history productivity. Empirical studies suggest that RMR is (a) related to the capacity to generate energy, (b) repeatable, and (c) correlated with behavioral output (e.g. aggressiveness) and productivity (e.g. growth). We conclude by discussing future research directions to clarify linkages between behavior and energy metabolism in this emerging research area. © 2010 Elsevier Ltd.


Singh R.R.P.,University of California at Davis
Physical Review Letters | Year: 2010

We present a theory for site dilution in the kagome lattice Heisenberg model. The presence of an empty site leads to strong singlet bonds opposite to the impurity. It also creates a free spin which delocalizes near the impurity. Finite impurity concentration leads to a valence bond glass phase with no spin gap, large spin susceptibilities, linear specific heat due to two-level systems, as well as singlet and triplet excitations that decompose into kink-antikink pairs. It provides a framework for a comprehensive understanding of thermodynamic, neutron, and Raman measurements in the herbertsmithite material ZnCu3(OH)6Cl2, including recently reported H/T and ω/T scaling. © 2010 The American Physical Society.


Carter C.S.,University of California at Davis | Barch D.M.,Washington University in St. Louis
Schizophrenia Bulletin | Year: 2012

The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative, funded by an R13 conference grant from the National Institute of Mental Health, has sought to facilitate the translation of measures from the basic science of cognition into practical brain-based tools to measure treatment effects on cognition in schizophrenia. In this overview article, we summarize the process and products of the sixth meeting in this series, which focused on the identification of promising imaging paradigms, based on the measurement of cognitive evoked potentials (event-related potential) of cognition-related time-frequency analyses of the electroencephalography as well as functional magnetic resonance imaging. A total of 23 well-specified paradigms from cognitive neuroscience that measure cognitive functions previously identified as targets for treatment development were identified at the meeting as being recommended for the further developmental work needed in order to validate and optimize them as biomarker measures. Individual paradigms are discussed in detail in 6 domain-based articles in this volume. Ongoing issues related to the development of these and other measures as valid, sensitive and reliable measurement, and assessment tools, as well as the steps necessary for the development of specific measures for use as biomarkers for treatment development and personalized medicine, are discussed. © 2011 The Author.


Raybould H.E.,University of California at Davis
Autonomic Neuroscience: Basic and Clinical | Year: 2010

Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on a new data on endocrine cells in chemosensing in the GI tract, in particular on new findings on glucose-sensing by gut EEC cells and the importance of incretin peptides and vagal afferents in glucose homeostasis, on the role of G protein coupled receptors in gut chemosensing, and on the possibility that gut endocrine cells may be involved in the detection of a luminal constituent other than nutrients, the microbiota. The role of vagal afferent pathways as a downstream target of EEC cell products will be considered and, in particular, exciting new data on the plasticity of the vagal afferent pathway with respect to expression of receptors for GI hormones and how this may play a role in energy homeostasis will also be discussed. © 2009 Elsevier B.V. All rights reserved.


Williams P.D.,University of California at Davis
Trends in Parasitology | Year: 2010

From the seemingly inevitable emergence of antibiotic resistance following drug use to the necessity of annual influenza vaccine updates, the ability of pathogens to evolve appears to preclude the development of effective, long-term interventions for many diseases. Despite this gloomy forecast, recent research explores how various principles and concepts from evolutionary ecology might inform practical attempts to bring these disease-causing agents under greater human control. By utilizing evolutionary and ecological information at various scales, these works investigate some promising avenues of disease intervention, from trapping pathogens in evolutionary dead ends, through slowing or inhibiting the process of pathogen adaptation, to more accurate forecasting of pathogen evolutionary trajectories. Thus, an evolutionary ecology perspective might ultimately provide powerful new tools in the pursuit of enduring solutions to the problem of treatment-driven pathogen evolution. © 2009 Elsevier Ltd. All rights reserved.


Rogawski M.A.,University of California at Davis
Epilepsia | Year: 2013

Pharmacoresistance to antiepileptic drugs (AEDs) is a barrier to seizure freedom for many persons with epilepsy. For nearly two decades, pharmacoresistance has been framed in terms of factors affecting the access of AEDs to their molecular targets in the brain or the actions of the drugs on these targets. Shortcomings in this prevailing view led to the formulation of the intrinsic severity hypothesis of pharmacoresistance to AEDs, which is based on the recognition that there are neurobiologic factors that confer phenotypic variation among individuals with etiologically similar forms of epilepsy and postulates that more severe epilepsy is more difficult to treat with AEDs. In recent years, progress has been made identifying potential genetic mechanisms of variation in epilepsy severity, including subclinical mutations in ion channels that increase or reduce epilepsy severity in mice. Efforts are underway to identify clinically important genetic modifiers. If it can be demonstrated that such severity factors play a role in pharmacoresistance, treatments could be devised to reverse severity mechanisms. By overcoming pharmacoresistance, this new approach to epilepsy therapy may allow drug refractory patients to achieve seizure freedom without side effects. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.


Ekstrom A.,University of California at Davis
Brain Research Reviews | Year: 2010

Functional magnetic resonance imaging (fMRI) has become the dominant means of measuring behavior-related neural activity in the human brain. Yet the relation between the blood oxygen-level dependent (BOLD) signal and underlying neural activity remains an open and actively researched question. A widely accepted model, established for sensory neo-cortex, suggests that the BOLD signal reflects peri-synaptic activity in the form of the local field potential rather than the spiking rate of individual neurons. Several recent experimental results, however, suggest situations in which BOLD, spiking, and the local field potential dissociate. Two different models are discussed, based on the literature reviewed to account for this dissociation, a circuitry-based and vascular-based explanation. Both models are found to account for existing data under some testing situations and in certain brain regions. Because both the vascular and local circuitry-based explanations challenge the BOLD-LFP coupling model, these models provide guidance in predicting when BOLD can be expected to reflect neural processing and when the underlying relation with BOLD may be more complex than a direct correspondence. © 2009 Elsevier B.V.


Hamilton A.M.,University of California at Davis
Neural plasticity | Year: 2013

The ubiquitin-proteasome system (UPS) is most widely known for its role in intracellular protein degradation; however, in the decades since its discovery, ubiquitination has been associated with the regulation of a wide variety of cellular processes. The addition of ubiquitin tags, either as single moieties or as polyubiquitin chains, has been shown not only to mediate degradation by the proteasome and the lysosome, but also to modulate protein function, localization, and endocytosis. The UPS plays a particularly important role in neurons, where local synthesis and degradation work to balance synaptic protein levels at synapses distant from the cell body. In recent years, the UPS has come under increasing scrutiny in neurons, as elements of the UPS have been found to regulate such diverse neuronal functions as synaptic strength, homeostatic plasticity, axon guidance, and neurite outgrowth. Here we focus on recent advances detailing the roles of the UPS in regulating the morphogenesis of axons, dendrites, and dendritic spines, with an emphasis on E3 ubiquitin ligases and their identified regulatory targets.


Raychaudhuri S.P.,University of California at Davis
Journal of Rheumatology | Year: 2012

Psoriatic arthritis (PsA) is associated with serious comorbidities such as increased cardiovascular risk, hypertension, depression, and reduced quality of life. Patients with psoriasis have been observed to have an increased incidence of metabolic syndrome compared with the general population; recently, this has also been observed in patients with PsA. This review focuses on the comorbidities associated with PsA, with an emphasis on risks of coronary artery disease and metabolic syndrome. We also discuss the development of a comprehensive approach for the management of comorbidities of PsA. The review summarizes a presentation at the 2010 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis). The Journal of Rheumatology Copyright © 2012. All rights reserved.


Comai L.,University of California at Davis
PLoS Biology | Year: 2014

During the course of our history, humankind has been through different periods of agricultural improvement aimed at enhancing our food supply and the performance of food crops. In recent years, it has become apparent that future crop improvement efforts will require new approaches to address the local challenges of farmers while empowering discovery across industry and academia. New plant breeding approaches are needed to meet this challenge to help feed a growing world population. Here I discuss how a basic research discovery is being translated into a potential future tool for plant breeding, and share the story of researcher Simon Chan, who recognized the potential application of this new approach-genome elimination-for the breeding of staple food crops in Africa and South America. © 2014 Luca Comai.


Chang C.,University of California at Davis
Journal of Autoimmunity | Year: 2010

Ultrafine particles and engineered nanoparticles have unique aerodynamic and biochemical properties that affect the immune system and human health in ways that are different from or exceed those seen with gases or larger particulates. These effects result from a unique set of physical characteristics and surface moieties, which generate an ability of UFPs to enter tissues and cells, interact with proteins and DNA at a molecular level and directly and indirectly modulate the immune system by novel mechanisms. In recent years, a new field known as nanotechnology has impacted multiple industries by taking advantage of the special qualities of these small "atomic-sized" particles. Nanomedicine has already opened up a new avenue of research in cancer therapy, drug delivery and immune regulation. While the benefits of this new science to human civilization are seemingly immeasurable, it is also important to appreciate that these particles can also lead to harmful effects on human health. In vitro and animal studies are showing that nanoparticles and UFPs are capable of activating proinflammatory cytokines, chemokines and adhesion molecules, with recruitment of inflammatory cells including basophils, macrophages, dendritic cells, T cells, neutrophils and eosinophils. These changes may have an impact on immune defense, but also on the Th1/Th2 balance, and even on non-immunologic function. Resulting immune system derangement can lead to increases in incidence of autoimmune, allergic and even neoplastic diseases. Cardiorespiratory effects have been observed to occur in humans. Much further research is needed to establish safe exposure levels for this important new class of particulates. © 2009 Elsevier Ltd. All rights reserved.


Anacker B.L.,University of California at Davis
American Journal of Botany | Year: 2014

Serpentine soils are a model system for the study of plant adaptation, speciation, and species interactions. Serpentine soil is an edaphically stressful, low productivity soil type that hosts stunted vegetation and a spectacular level of plant endemism. One of the first papers on serpentine plant endemism was by Arthur Kruckeberg, titled "Intraspecific variability in the response of certain native plant species to serpentine soil. " Published in the American Journal of Botany in 1951, it has been cited over 100 times. Here, I review the context and content of the paper, as well as its impact. On the basis of the results of reciprocal transplant experiments in the greenhouse, Kruckeberg made three important conclusions on the nature of serpentine plant endemism: (1) Plants are locally adapted to serpentine soils, forming distinct soil ecotypes; (2) soil ecotypes are the first stage in the evolutionary progression toward serpentine endemism; and (3) serpentine endemics are restricted from more fertile nonserpentine soils by competition. Kruckeberg's paper inspired a substantial amount of research, especially in the three areas reviewed here: local adaptation and plant traits, speciation, and the interaction of climate and soil in plant endemism. In documenting soil ecotypes, Kruckeberg identi-fied serpentine soils as a potent selective factor in plant evolution and helped establish serpentine soils as a model system in evolution and ecology. © 2014 Botanical Society of America.


Eisen D.B.,University of California at Davis
Journal of the American Academy of Dermatology | Year: 2011

Surgical site infections are an important complication resulting from surgery. Before the 20th century a significant number of surgeries resulted in death from sepsis. One of the rituals resulting from efforts to reduce infection is the donning of surgical garb. A large body of literature has developed on the efficacy of these specialized garments. The available evidence for the efficacy of each individual garb at reducing surgical site infections will be explored. The relevance of this evidence to the outpatient dermatologic surgery setting will also be discussed. © 2010 by the American Academy of Dermatology, Inc.


Berben L.A.,University of California at Davis
Chemistry - A European Journal | Year: 2015

Non-Innocent ligand complexes of aluminum are described in this Concept article, beginning with a discussion of their synthesis, and then structural and electronic characterization. The main focus concerns the ability of the ligands in these complexes to mediate proton transfer reactions. As examples, aluminum-ligand cooperation in the activation of polar bonds is described, as is the importance of hydrogen bonding to stabilization of a transition state for b-hydride abstraction. Taken together these reactions enable catalytic processes such as the dehydrogenation of formic acid. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA.


Townsend M.S.,University of California at Davis
American Journal of Clinical Nutrition | Year: 2010

Nutrient profiling is defined as the science of ranking or categorizing foods on the basis of their nutritional composition. Validity is a general term meaning accuracy. Nutrient profiling systems in the United States have not undergone any systematic validation effort to assess their accuracy against a comparison measure or group of measures. Different types of validation studies should be conducted: content, face, convergent, criterion, and predictive. This article provides a conceptual framework for establishing the validity of nutrient profiling systems with the desired objective of assisting US consumers with food selection to improve diet quality. For a profiling system to work successfully in the American marketplace, it must function well with consumers from most or all cultural groups, from all racial groups, and with low-literate as well as highly literate people. Emphasis should be placed on conducting different types of validation studies and multiple studies with different subpopulation groups. The use of consistent standards to assess the accuracy and usefulness of multiple profiling systems is imperative to successfully identify a nutrient profiling intervention that will have the potential to lead to improved diet quality and eventually to an improved health status in US consumers. © 2010 American Society for Nutrition.


Espiritu E.B.,University of California at Davis
Developmental biology | Year: 2012

Microtubule dynamics are thought to play an important role in regulating microtubule interactions with cortical force generating motor proteins that position the spindle during asymmetric cell division. CLASPs are microtubule-associated proteins that have a conserved role in regulating microtubule dynamics in diverse cell types. Caenorhabditis elegans has three CLASP homologs in its genome. CLS-2 is known to localize to kinetochores and is needed for chromosome segregation at meiosis and mitosis; however CLS-1 and CLS-3 have not been reported to have any role in embryonic development. Here, we show that depletion of CLS-2 in combination with either CLS-1 or CLS-3 results in defects in nuclear rotation, maintenance of spindle length, and spindle displacement in the one-cell embryo. Polarity is normal in these embryos, but reduced numbers of astral microtubules reach all regions of the cortex at the time of spindle positioning. Analysis of the microtubule plus-end tracker EB1 also revealed a reduced number of growing microtubules reaching the cortex in CLASP depleted embryos, but the polymerization rate of astral microtubules was not slower than in wild type. These results indicate that C. elegans CLASPs act partially redundantly to regulate astral microtubules and position the spindle during asymmetric cell division. Further, we show that these spindle pole-positioning roles are independent of the CLS-2 binding proteins HCP-1 and HCP-2. Copyright © 2012 Elsevier Inc. All rights reserved.


Rodriguez-Fortea A.,Rovira i Virgili University | Balch A.L.,University of California at Davis | Poblet J.M.,Rovira i Virgili University
Chemical Society Reviews | Year: 2011

In this tutorial review taking X-ray crystallographically characterized compounds as a starting point a walk is taken through the electronic and structural properties of endohedral metallofullerenes. After classification of the fullerenes according to the encapsulated guest, particular attention is given to identifying factors that determine the selection of a particular carbon cage network by the internal metal cluster. Some of the physical rules that determine which particular fullerene cage is formed will be discussed. Concepts such as charge transfer between the cage and the guest metal ions, the topology of the cage, the separations between the 12 pentagons on the fullerene surface, and the effect of entropic factors are used to rationalize the selection of a particular cage. The roles of electrochemistry and vibrational spectroscopy in combination with theoretical calculations are considered in understanding the structures of the endohedral fullerenes. © 2011 The Royal Society of Chemistry.


Saxton M.J.,University of California at Davis
Biophysical Journal | Year: 2012

Anomalous subdiffusion in cells and model systems is an active area of research. The main questions are whether diffusion is anomalous or normal, and if it is anomalous, its mechanism. The subject is controversial, especially the hypothesis that crowding causes anomalous subdiffusion. Anomalous subdiffusion measurements would be strengthened by an experimental standard, particularly one able to cross-calibrate the different types of measurements. Criteria for a calibration standard are proposed. First, diffusion must be anomalous over the length and timescales of the different measurements. The length-scale is fundamental; the time scale can be adjusted through the viscosity of the medium. Second, the standard must be theoretically well understood, with a known anomalous subdiffusion exponent, ideally readily tunable. Third, the standard must be simple, reproducible, and independently characterizable (by, for example, electron microscopy for nanostructures). Candidate experimental standards are evaluated, including obstructed lipid bilayers; aqueous systems obstructed by nanopillars; a continuum percolation system in which a prescribed fraction of randomly chosen obstacles in a regular array is ablated; single-file diffusion in pores; transient anomalous subdiffusion due to binding of particles in arrays such as transcription factors in randomized DNA arrays; and computer-generated physical trajectories. © 2012 Biophysical Society.


Marcu L.,University of California at Davis
Annals of Biomedical Engineering | Year: 2012

This article presents an overview of time-resolved (lifetime) fluorescence techniques used in biomedical diagnostics. In particular, we review the development of time-resolved fluorescence spectroscopy (TRFS) and fluorescence lifetime imaging (FLIM) instrumentation and associated methodologies which allow in vivo characterization and diagnosis of biological tissues. Emphasis is placed on the translational research potential of these techniques and on evaluating whether intrinsic fluorescence signals provide useful contrast for the diagnosis of human diseases including cancer (gastrointestinal tract, lung, head and neck, and brain), skin and eye diseases, and atherosclerotic cardiovascular disease. © 2012 Biomedical Engineering Society.


Kim S.H.,University of California at Davis
Arthritis care & research | Year: 2012

To evaluate the recent epidemiology of hip fractures in the US. We identified hip fracture cases from the 2008 Nationwide Emergency Department Sample, which contains more than 28 million emergency department (ED) records. In 2008, approximately 341,000 (95% confidence interval 323,000-358,000) patients visited EDs with hip fractures. Of those, 90% were age >60 years. Between ages 60-85 years, the risk of fracture doubled for every 5- to 6-year increase in age. However, the hip fracture risk increased slowly after age 85 years. The overall trochanteric-to-cervical fracture ratio was nearly 2:1. The risk of trochanteric fracture increased faster with age compared with the risk of cervical fracture. At age 85 years, the rates of trochanteric and cervical fractures (per 100,000) were 1,300 and 700, respectively, among women and 800 and 500, respectively, among men. The slowed growth of hip fracture risk after age 85 years suggests that the eldest old group may have a distinct hip fracture risk. Our study showed that trochanteric fractures were twice as common as cervical fractures. Because trochanteric fractures are more closely related to severe and generalized bone loss than cervical fractures, we hypothesize that the high incidence rate of trochanteric fractures in the US suggests that osteoporosis is a health problem that is linked to hip fracture. In addition to improved safety measures to reduce falls, rigorous preventive treatments of osteoporosis may be needed. Copyright © 2012 by the American College of Rheumatology.


Fridolfsson H.N.,University of California at Davis | Starr D.A.,University of California at Davis
Journal of Cell Biology | Year: 2010

Kinesin-1 and dynein are recruited to the nuclear envelope by the Caenorhabditis elegans klarsicht/ANC-1/Syne homology (KASH) protein UNC-83 to move nuclei. The mechanisms of how these motors are coordinated to mediate nuclear migration are unknown. Time-lapse differential interference contrast and fluorescence imaging of embryonic hypodermal nuclear migration events were used to characterize the kinetics of nuclear migration and determine microtubule dynamics and polarity. Wild-type nuclei display bidirectional movements during migration and are also able to roll past cytoplasmic granules. unc-83, unc-84, and kinesin-1 mutants have severe nuclear migration defects. Without dynein, nuclear migration initiates normally but lacks bidirectional movement and shows defects in nuclear rolling, implicating dynein in resolution of cytoplasmic roadblocks. Microtubules are highly dynamic during nuclear migration. EB1::green fluorescence protein imaging demonstrates that microtubules are polarized in the direction of nuclear migration. This organization of microtubules fits with our model that kinesin-1 moves nuclei forward and dynein functions to move nuclei backward for short stretches to bypass cellular roadblocks. © 2010 Fridolfsson and Starr.


Ng C.-Y.,University of California at Davis
Annual Review of Physical Chemistry | Year: 2014

Recent advances in high-resolution photoionization, photoelectron, and photodissociation studies based on single-photon vacuum ultraviolet (VUV) and two-color infrared (IR)-VUV, visible (Vis)-ultraviolet (UV), and VUV-VUV laser excitations are illustrated with selected examples. VUV laser photoionization coupled with velocity-map-imaging threshold photoelectron (VMI-TPE) detection can achieve comparable energy resolution but has higher-detection sensitivities than those observed in VUV laser pulsed field ionization photoelectron (PFI-PE) measurements. For molecules with known intermediate states, IR-VUV and Vis-UV excitation schemes are highly sensitive for rovibronically selected and resolved PFI-PE studies. The successful applications of the VUV-PFI-PE, VUV-VMI-TPE, and Vis-UV-PFI-PE methods to state-resolved and state-to-state photoelectron studies of transient radicals and transitional metal-containing molecules are highlighted. The most recently established VUV-VUV pump-probe time-slice VMI photoion method is shown to be promising for state-to-state photodissociation studies of small molecules relevant to planetary atmospheres and for the fundamental understanding of photodissociation dynamics. Copyright © 2014 by Annual Reviews.


Lonnerdal B.,University of California at Davis
Journal of Paediatrics and Child Health | Year: 2013

Human milk contains many proteins that have been shown to be bioactive, but it is still not known whether these activities are exerted in breast-fed infants. These bioactivities include enzyme activities, enhancement of nutrient absorption, growth stimulation, modulation of the immune system and defence against pathogens. The antimicrobial activities are very diverse, ranging from stimulation of beneficial microorganisms (i.e. prebiotic effects), killing or inhibition of growth of pathogens, to mechanisms preventing attachment or invasion of harmful microorganisms. Among the bioactive proteins are lactoferrin, lysozyme, secretory immunoglobulin A, haptocorrin, lactoperoxidase, α-lactalbumin, bile salt stimulated lipase, β- and κ-casein, and tumour growth factor β. Human milk proteins may be largely resistant against digestion in the gastrointestinal tract, be partially digested into bioactive peptides, or be more or less completely digested and utilised as a source of amino acids. These events can be studied using an in vitro digestion model, which is useful for predicting results in human infants. Some bovine milk proteins, for example, lactoferrin and tumour growth factor β, may also resist proteolysis and be capable of exerting bioactivities similar to those of human milk proteins. © 2013 The Author. Paediatrics and Child Health Division (Royal Australasian College of Physicians).


Yang L.H.,University of California at Davis | Rudolf V.H.W.,Rice University
Ecology Letters | Year: 2010

Climate change is altering the phenology of many species and the timing of their interactions with other species, but the impacts of these phenological shifts on species interactions remain unclear. Classical approaches to the study of phenology have typically documented changes in the timing of single life-history events, while phenological shifts affect many interactions over entire life histories. In this study, we suggest an approach that integrates the phenology and ontogeny of species interactions with a fitness landscape to provide a common mechanistic framework for investigating phenological shifts. We suggest that this ontogeny-phenology landscape provides a flexible method to document changes in the relative phenologies of interacting species, examine the causes of these phenological shifts, and estimate their consequences for interacting species. © 2009 Blackwell Publishing Ltd/CNRS.


Heil M.,CINVESTAV | Karban R.,University of California at Davis
Trends in Ecology and Evolution | Year: 2010

In spite of initial doubts about the reality of 'talking trees', plant resistance expression mediated by volatile compounds that come from neighboring plants is now well described. Airborne signals usually improve the resistance of the receiver, but without obvious benefits for the emitter, thus making the evolutionary explanation of this phenomenon problematic. Here, we discuss four possible non-exclusive explanations involving the role of volatiles: in direct defense, as within-plant signals, as traits that synergistically interact with other defenses, and as cues among kin. Unfortunately, there is a lack of knowledge on the fitness consequences of plant communication for both emitter and receiver. This information is crucial to understanding the ecology and evolution of plant communication via airborne cues. © 2009 Elsevier Ltd. All rights reserved.


Grosholz E.,University of California at Davis
Ecology Letters | Year: 2010

Biological invasions greatly increase the potential for hybridization among native and non-native species. Hybridization may influence the palatability of novel hybrids to consumers potentially influencing invasion success; however, the palatability of non-native hybrids relative to the parent species is poorly known. In contrast, studies of native-only hybrids find they are nearly always more palatable to consumers than the parent species. Here, I experimentally demonstrate that an invasive hybrid cordgrass (Spartina) is dramatically less palatable to grazing geese than the native parent species. Using field and aviary experiments, I show that grazing geese ignore the hybrid cordgrass and preferentially consume native Spartina. I also experimentally demonstrate that reduced herbivory of the invasive hybrid may contribute to faster spread in a California estuary. These results suggest that biological invasions may increase future opportunities for creating novel hybrids that may pose a greater risk to natural systems than the parent species. © 2009 Blackwell Publishing Ltd/CNRS.


Hoffman M.D.,University of California at Davis
International Journal of Sports Medicine | Year: 2010

This report documents performance-related trends in 100-mile (161-km) ultramarathon running competitions in North America. A retrospective analysis of results from 1977 through 2008 revealed that annual finish rates increased initially and then plateaued by the early 1990s at nearly 60%. The fastest times were produced by the 3039 year age group among the men and the 4049 year age group for the women. Finish times of women improved relative to men through the 1980s, but were then stable over the past two decades with the fastest women running about 20% slower than the fastest men. Additionally, the average times of the fastest runners did not change over the past two decades for any age group for either sex. The percentage difference in finish times between the first and fifth place runners has remained lower (p<0.0001) for men than women, and has shown an upward trend (p=0.003) across time for men. It is concluded that increasing participation in 161-km ultramarathons in North America has not been associated with improvements in performance or depth of competition with the exception of the relative improvements in finish times for women compared with men that was evident through the 1980s. © Georg Thieme Verlag KG Stuttgart - New York.


Adaptive phenotypic plasticity and adaptive genetic differentiation enable plant lineages to maximize their fitness in response to environmental heterogeneity. The spatial scale of environmental variation relative to the average dispersal distance of a species determines whether selection will favor plasticity, local adaptation, or an intermediate strategy. Habitats where the spatial scale of environmental variation is less than the dispersal distance of a species are fine grained and should favor the expression of adaptive plasticity, while coarse-grained habitats, where environmental variation occurs on spatial scales greater than dispersal, should favor adaptive genetic differentiation. However, there is relatively little information available characterizing the link between the spatial scale of environmental variation and patterns of selection on plasticity measured in the field. I examined patterns of spatial environmental variation within a serpentine mosaic grassland and selection on an annual plant (Erodium cicutarium) within that landscape. Results indicate that serpentine soil patches are a significantly finer-grained habitat than non-serpentine patches. Additionally, selection generally favored increased plasticity on serpentine soils and diminished plasticity on non-serpentine soils. This is the first empirical example of differential selection for phenotypic plasticity in the field as a result of strong differences in the grain of environmental heterogeneity within habitats. © 2011 by The University of Chicago.


Banan Sadeghian R.,University of California at Davis | Saif Islam M.,University of California at Davis
Nature Materials | Year: 2011

Several hundred million volts per centimetre of electric-field strength are required to field-ionize gas species. Such fields are produced on sharp metallic tips under a bias of a few kilovolts. Here, we show that field ionization is possible at dramatically lower fields on semiconductor nanomaterials containing surface states, particularly with metal-catalysed whiskers grown on silicon nanowires. The low-voltage field-ionization phenomena observed here cannot be explained solely on the basis of the large field-amplification effect of suspended gold nanoparticles present on the whisker tips. We postulate that field penetration causes upward band-bending at the surface of exposed silicon containing surface states in the vicinity of the catalyst. Band-bending enables the valence electron to tunnel into the surface states at reduced fields. This work provides a basis for development of low-voltage ionization sensors. Although demonstrated on silicon, low-voltage field ionization can be detected on any sharp semiconductor tip containing proper surface states. © 2011 Macmillan Publishers Limited. All rights reserved.


Kliebenstein D.J.,University of California at Davis
Annual Review of Phytopathology | Year: 2012

Systems biology attempts to answer biological questions by integrating across diverse genomic data sets. With the increasing ability to conduct genomics experiments, this integrative approach is being rapidly applied across numerous biological research communities. One of these research communities investigates how plants utilize secondary metabolites or defense metabolites to defend against attack by pathogens and other biotic organisms. This use of systems biology to integrate across transcriptomics, metabolomics, and genomics is significantly enhancing the rate of discovery of genes, metabolites, and bioactivities for plant defense compounds as well as extending our knowledge of how these compounds are regulated. Plant defense compounds are also providing a unique proving platform to develop new approaches that enhance the ability to conduct systems biology with existing and previously unforseen genomics data sets. This review attempts to illustrate both how systems biology is helping the study of plant defense compounds and vice versa. © 2012 by Annual Reviews. All rights reserved.


Saiz L.,University of California at Davis
Journal of Physics Condensed Matter | Year: 2012

Protein-DNA interaction networks play a central role in many fundamental cellular processes. In gene regulation, physical interactions and reactions among the molecular components together with the physical properties of DNA control how genes are turned on and off. A key player in all these processes is the inherent flexibility of DNA, which provides an avenue for long-range interactions between distal DNA elements through DNA looping. Such versatility enables multiple interactions and results in additional complexity that is remarkably difficult to address with traditional approaches. This topical review considers recent advances in statistical physics methods to study the assembly of protein-DNA complexes with loops, their effects in the control of gene expression, and their explicit application to the prototypical lac operon genetic system of the E.coli bacterium. In the last decade, it has been shown that the underlying physical properties of DNA looping can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including the balance between robustness and sensitivity of the induction process. These physical properties are largely dependent on the free energy of DNA looping, which accounts for DNA bending and twisting effects. These new physical methods have also been used in reverse to uncover the actual invivo free energy of looping double-stranded DNA in living cells, which was not possible with existing experimental techniques. The results obtained for DNA looping by the lac repressor inside the E.coli bacterium showed a more malleable DNA than expected as a result of the interplay of the simultaneous presence of two distinct conformations of looped DNA. © 2012 IOP Publishing Ltd.


Hagerman R.,University of California at Davis | Hagerman P.,University of California at Davis
The Lancet Neurology | Year: 2013

Fragile X syndrome, the most common heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (. FMR1) gene owing to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, so-called premutation expansions (55-200 repeats) can cause a family of neurodevelopmental phenotypes (attention deficit hyperactivity disorder, autism spectrum disorder, seizure disorder) and neurodegenerative (fragile X-associated tremor/ataxia syndrome [FXTAS]) phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Results of basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the range of clinical manifestations. Advances of knowledge on both mechanistic and clinical fronts are driving new approaches to targeted treatment, but two important necessities are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in view of its differing presentations and associated features. © 2013 Elsevier Ltd.


Ringelman K.M.,University of California at Davis
Ecological Modelling | Year: 2014

Mammalian predator foraging behavior is an important, but understudied determinant of avian nest success. Predator behavior may also affect the nest-site selection decisions of females: when predators respond strongly to prey density (e.g. through area-restricted search), the optimal strategy may be for birds to disperse their nests widely across the landscape. Conversely, clustered nests may benefit from dilution effects in the presence of incidental nest predators. In dabbling ducks, nest distributions range from clustered to dispersed and there is conflicting evidence about whether clustering enhances or reduces nest success, although presumably this depends on predator behavior. Here, I present results from an agent-based model designed to answer two qualitative questions: are clustered nests more or less successful than dispersed nests, and how does that relative benefit vary depending on predator behavior? I modeled three types of waterfowl nest predators (to emulate the foraging behavior of skunks and foxes) that differ in their degree of spatial memory and their capacity for area-restricted search, foraging on different distributions of nests. As hypothesized, well-dispersed nests survived better with fox-like predators that performed area-restricted searches. On the other hand, clustered nests survived better when incidental skunk-like predators were present, but survival was dramatically reduced in the presence of foxes; thus, small changes in the predator community (e.g. introduction of foxes) without commensurate changes in nest clustering could have important effects on waterfowl populations. On simulated landscapes containing both clustered and dispersed nests and a mixed predator community, average nest success for clustered versus randomly placed nests was the same across possible predator mixes, but the variance in success for clustered nests was much higher; this suggests that there may be risk-reward tradeoffs when nesting near conspecifics. That said, the degree to which ducks can actually assess and respond to the presence of conspecifics is largely unknown, and it is believed that nest sites are selected based on habitat. Results from this model, combined with empirical data suggest that commonly used management strategies that promote nest clustering, such as restoration of small parcels of habitat, can actually create ecological traps for nesting ducks, driven by predator behavior. © 2013 Elsevier B.V.


Savoca M.S.,University of California at Davis | Nevitt G.A.,University of California at Davis
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Tritrophic mutualistic interactions have been best studied in plant- insect systems. During these interactions, plants release volatiles in response to herbivore damage, which, in turn, facilitates predation on primary consumers or benefits the primary producer by providing nutrients. Here we explore a similar interaction in the Southern Ocean food web, where soluble iron limits primary productivity. Dimethyl sulfide has been studied in the context of global climate regulation and is an established foraging cue for marine top predators. We present evidence that procellariiform seabird species that use dimethyl sulfide as a foraging cue selectively forage on phytoplankton grazers. Their contribution of beneficial iron recycled to marine phytoplankton via excretion suggests a chemically mediated link between marine top predators and oceanic primary production.


Leal W.S.,University of California at Davis
Current Opinion in Insect Science | Year: 2015

Repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET is a safe, broad spectrum repellent, which provides complete protection over a long period of time. Despite its low cost, more affordable alternatives are highly desirable, particularly for those in endemic areas where cost is an impediment. Alternative compounds like IR 3535 and picaridin have been developed using molecular modeling, but the lack of knowledge of the molecular target(s) for DEET has retarded progress toward low cost alternatives. It is known that DEET acts at a distance as an odorant as well as by direct contact, that is, as a tastant, although DEET reception is primarily mediated by the olfactory system. There is unambiguous evidence that olfactory receptor neurons are involved, and that an odorant receptor co-receptor Orco is essential for DEET reception. In the southern house mosquito, Culex quinquefasciatus, DEET triggers repellence by direct activation of an odorant receptor, CquiOR136, which is also sensitive to a plant defense compound, methyl jasmonate. © 2014 Elsevier Inc.


Anderes E.,University of California at Davis
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The reconstruction of the cosmic microwave background lensing potential is based on a Taylor expansion of lensing effects which is known to have poor convergence properties. For lensing of temperature fluctuations, an understanding of the higher order terms in this expansion which is accurate enough for current experimental sensitivity levels has been developed in Hanson et al. (2010), as well as a slightly modified Hu and Okamoto quadratic estimator which incorporates lensed rather than unlensed spectra into the estimator weights to mitigate the effect of higher order terms. We extend these results in several ways: (1) we generalize this analysis to the full set of quadratic temperature/polarization lensing estimators, (2) we study the effect of higher order terms for more futuristic experimental noise levels, (3) we show that the ability of the modified quadratic estimator to mitigate the effect of higher order terms relies on a delicate cancellation which occurs only when the true lensed spectra are known. We investigate the sensitivity of this cancellation to uncertainties in or knowledge of these spectra. We find that higher order terms in the Taylor expansion can impact projected error bars at experimental sensitivities similar to those found in future ACTpol/SPTpol experiments. © 2013 American Physical Society.


Nevitt G.A.,University of California at Davis
Integrative and Comparative Biology | Year: 2011

Information transfer influences food-web dynamics in the marine environment, but infochemicals involved in these processes are only beginning to be understood. Dimethylsulfoniopropionate (DMSP) is produced by phytoplankton and other marine algae, and has been studied primarily in the context of sulfur cycling and regulation of global climate. My laboratory has been investigating DMSP and its breakdown product, dimethyl sulfide as infochemicals associated with trophic interactions in marine habitats, including sub-Antarctic and coral reef ecosystems. Using a neuroecological approach, our work has established that these biogenic sulfur compounds serve as critical signal molecules in marine systems and provides us with a more mechanistic understanding of how climate change may impact information transfer within marine food webs. © The Author 2011. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.


Maclachlan N.J.,University of California at Davis
Preventive Veterinary Medicine | Year: 2011

Bluetongue is an arthropod-transmitted viral disease of ruminants and certain other animals that was recognized and described more than 100 years ago in southern Africa. Bluetongue virus (BTV) infection of ruminants and vector Culicoides insects is enzootic throughout tropical and temperate regions of the world; however, there have been drastic recent regional alterations in the global distribution of BTV infection, particularly in Europe since 1998. Multiple novel BTV serotypes also have been detected since 1998 in the south-eastern United States, apparently encroaching from the adjacent Caribbean ecosystem, and novel serotypes of BTV have been identified recently in other historically enzootic regions of the world, including the Middle East and Australia. It has been proposed, but certainly not proven, that global climate change is responsible for these events. BTV infection of ruminants is often subclinical, but outbreaks of severe disease occur with regular frequency especially at the upper and lower limits of the virus' global range where infection is highly seasonal - occurring in the late summer and autumn. Bluetongue disease results from vascular injury, likely through a process analogous to that of human hemorrhagic viral fevers in which production of vasoactive mediators from virus-infected macrophages and dendritic cells results in enhanced endothelial paracellular permeability with subsequent vascular leakage and hypovolemic shock. © 2011 Elsevier B.V.


Despite the described central role of jasmonate signaling in plant defense against necrotrophic pathogens, the existence of intraspecific variation in pathogen capacity to activate or evade plant jasmonate-mediated defenses is rarely considered. Experimental infection of jasmonate-deficient and jasmonate-insensitive Arabidopsis thaliana with diverse isolates of the necrotrophic fungal pathogen Botrytis cinerea revealed pathogen variation for virulence inhibition by jasmonate-mediated plant defenses and induction of plant defense metabolites. Comparison of the transcriptional effects of infection by two distinct B. cinerea isolates showed only minor differences in transcriptional responses of wild-type plants, but notable isolate-specific transcript differences in jasmonate-insensitive plants. These transcriptional differences suggest B. cinerea activation of plant defenses that require plant jasmonate signaling for activity in response to only one of the two B. cinerea isolates tested. Thus, similar infection phenotypes observed in wild-type plants result from different signaling interactions with the plant that are likely integrated by jasmonate signaling.


Osterloh F.E.,University of California at Davis | Parkinson B.A.,University of Wyoming
MRS Bulletin | Year: 2011

Although photovoltaic cells have great potential for supplying carbon-free energy, they suffer from the lack of an efficient and cost-effective energy storage process that can supply energy for transportation and nighttime use. A direct way to convert solar energy into chemical fuels would solve this problem. Of several possible schemes, the photon-driven electrolysis of water to produce hydrogen and oxygen has been studied most. Photoelectrolysis of water can be achieved with either self-supported catalysts or with photoelectrochemical cells. This article will introduce the basic principles of solar water splitting and highlight recent developments with semiconductor light absorbers and co-catalysts. The role of combinatorial approaches in identifying new metal oxide visible light-absorbing semiconductors will be briefly described, and the potential of using nanomaterials for more efficient devices will be discussed. Separate articles in this special issue will focus on recent developments in watersplitting concepts. © 2011 Materials Research Society.


Lodewyk M.W.,University of California at Davis | Siebert M.R.,Texas Tech University | Tantillo D.J.,University of California at Davis
Chemical Reviews | Year: 2012

Key background information, examples, and more recent techniques of computational prediction of 1H and 13C chemical shifts, are presented. A major step in calculating chemical shifts is to compute the NMR isotropic shielding constants for the various nuclei in the molecule. Migda and Rys noted that subtracting computed 13C isotropic shielding constants from TMS values resulted in mean absolute errors 2-3 times greater than when they used the intercept of a linear regression plot. An option for locating conformers involves running relaxed or rigid potential energy surface scans around the various rotatable bonds in the molecule of interest. In 2007, Zhang et al. compiled optimized bond lengths and angles for small organic molecules for which experimental bond distances and angles were also available and found that even HF can reproduce bond distances to about 0.01 Å resolution and bond angles to approximately 0.5.


Garen J.W.,University of California at Davis
Annual Review of Public Health | Year: 2015

This brief review summarizes the basic epidemiology of firearm violence, a large and costly public health problem in the United States for which the mortality rate has remained unchanged for more than a decade. It presents findings for the present in light of recent trends. Risk for firearm violence varies substantially across demographic subsets of the population and between states in patterns that are quite different for suicide and homicide. Suicide is far more common than homicide and its rate is increasing; the homicide rate is decreasing. As with other important health problems, most cases of fatal firearm violence arise from large but low-risk subsets of the population; risk and burden of illness are not distributed symmetrically. Compared with other industrialized nations, the United States has uniquely high mortality rates from firearm violence. Copyright © 2015 by Annual Reviews. All rights reserved.


Hilty D.M.,University of California at Davis
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2013

The effectiveness of any new technology is typically measured in order to determine whether it successfully achieves equal or superior objectives over what is currently offered. Research in telemental health-in this article mainly referring to telepsychiatry and psychological services-has advanced rapidly since 2003, and a new effectiveness review is needed. The authors reviewed the published literature to synthesize information on what is and what is not effective related to telemental health. Terms for the search included, but were not limited to, telepsychiatry, effectiveness, mental health, e-health, videoconferencing, telemedicine, cost, access, and international. Telemental health is effective for diagnosis and assessment across many populations (adult, child, geriatric, and ethnic) and for disorders in many settings (emergency, home health) and appears to be comparable to in-person care. In addition, this review has identified new models of care (i.e., collaborative care, asynchronous, mobile) with equally positive outcomes. Telemental health is effective and increases access to care. Future directions suggest the need for more research on service models, specific disorders, the issues relevant to culture and language, and cost.


Bevins C.L.,University of California at Davis | Salzman N.H.,Childrens Research Institute
Cellular and Molecular Life Sciences | Year: 2011

Animals, ranging from basal metazoans to primates, are host to complex microbial ecosystems; engaged in a symbiotic relationship that is essential for host physiology and homeostasis. Epithelial surfaces vary in the composition of colonizing microbiota as one compares anatomic sites, developmental stages and species origin. Alterations of microbial composition likely contribute to susceptibility to several distinct diseases. The forces that shape the colonizing microbial composition are the focus of much current investigation, and it is evident that there are pressures exerted both by the host and the external environment to mold these ecosystems. The focus of this review is to discuss recent studies that demonstrate the critical importance of host factors in selecting for its microbiome. Greater insight into host-microbiome interactions will be essential for understanding homeostasis at mucosal surfaces, and developing useful interventions when homeostasis is disrupted. © Springer Basel AG 2011.


Gomes H.,University of California at Davis
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Shape dynamics is a theory of gravity that waives refoliation invariance in favor of spatial Weyl invariance. It is a canonical theory, constructed from a Hamiltonian, 3+1 perspective. One of the main deficits of shape dynamics is that its Hamiltonian is only implicitly constructed as a functional of the phase space variables. In this paper, I write down the equations of motion for shape dynamics to show that over a curve in phase space representing a Minkowski space-time, shape dynamics possesses Poincaré symmetry for appropriate boundary conditions. The proper treatment of such boundary conditions leads us to completely formulate shape dynamics for open manifolds in the asymptotically flat case. We study the charges arising in this case and find a new definition of total energy, which is completely invariant under spatial Weyl transformations close to the boundary. We then use the equations of motion once again to find a nontrivial solution of shape dynamics, consisting of a flat static Universe with a pointlike mass at the center. We calculate its energy through the new formula and rederive the usual Schwarzschild mass. © 2013 American Physical Society.


Yoo S.J.B.,University of California at Davis
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2011

This paper reviews the energy efficiency of optical-packet-switching (OPS) systems in comparison with electronic packet switching and hybrid packet switching in the context of future networks. The paper will first discuss the energy efficiency metrics that should include considerations for life-cycle analysis, applications, and network-wide goodput. The state-of-the-art electronic packet switching router is currently energy-limited in scalability as it is difficult to implement a router with more than 1MW power consumption. The OPS router that imitates electronic router's store-and-forward schemes is expected to suffer poor energy efficiency due to the complexity in the high-speed control plane necessary to control many optical buffer stages. The hybrid optical router achieves easier buffer management but its energy efficiency is still limited by the store-and-forward approach. The OPS router based on all-optical contention resolution without relying on store-and-forward method can keep the control plane very simple and achieve very high energy efficiency. Network-wide performance and energy efficiency in the context of generalized multiprotocol label switching (GMPLS)- and multiprotocol label switching (MPLS)-based networking are also discussed. © 2010 IEEE.


St.clair D.A.,University of California at Davis
Annual Review of Phytopathology | Year: 2010

Quantitative disease resistance (QDR) has been observed within many crop plants but is not as well understood as qualitative (monogenic) disease resistance and has not been used as extensively in breeding. Mapping quantitative trait loci (QTLs) is a powerful tool for genetic dissection of QDR. DNA markers tightly linked to quantitative resistance loci (QRLs) controlling QDR can be used for marker-assisted selection (MAS) to incorporate these valuable traits. QDR confers a reduction, rather than lack, of disease and has diverse biological and molecular bases as revealed by cloning of QRLs and identification of the candidate gene(s) underlying QRLs. Increasing our biological knowledge of QDR and QRLs will enhance understanding of how QDR differs from qualitative resistance and provide the necessary information to better deploy these resources in breeding. Application of MAS for QRLs in breeding for QDR to diverse pathogens is illustrated by examples from wheat, barley, common bean, tomato, and pepper. Strategies for optimum deployment of QRLs require research to understand effects of QDR on pathogen populations over time. © 2010 by Annual Reviews. All rights reserved.


Tiffin P.,University of Minnesota | Ross-Ibarra J.,University of California at Davis
Trends in Ecology and Evolution | Year: 2014

Local adaptation shapes species diversity, can be a stepping stone to ecological speciation, and can facilitate species range expansion. Population genetic analyses, which complement organismal approaches in advancing our understanding of local adaptation, have become widespread in recent years. We focus here on using population genetics to address some key questions in local adaptation: what traits are involved? What environmental variables are the most important? Does local adaptation target the same genes in related species? Do loci responsible for local adaptation exhibit trade-offs across environments? After discussing these questions we highlight important limitations to population genetic analyses including challenges with obtaining high-quality data, deciding which loci are targets of selection, and limits to identifying the genetic basis of local adaptation. © 2014 Elsevier Ltd.


Pedersen N.C.,University of California at Davis
Veterinary Journal | Year: 2014

This review is concerned with what has been learned about feline infectious peritonitis (FIP) diagnostics and therapeutics since the publication of an extensive overview of literature covering the period 1963-2009. Although progress has been made in both areas, obtaining a definitive diagnosis of FIP remains a problem for those veterinarians and/or cat owners who require absolute certainty. This review will cover both indirect and direct diagnostic tests for the disease and will emphasize their limitations, as well as their specificity and sensitivity. There is still no effective treatment for FIP, although there are both claims that such therapies exist and glimmers of hope coming from new therapies that are under research. FIP has also been identified in wild felids and FIP-like disease is now a growing problem among pet ferrets. © 2014 The Author.


Vermeij G.J.,University of California at Davis
Annual Review of Earth and Planetary Sciences | Year: 2013

Organisms have been important agents of selection throughout the history of life. The processes and outcomes of this selection are the subject of this review. Among these, escalation is the most widespread. The primary selective agents are powerful competitors and consumers, which together push many populations toward higher performance in acquiring and defending resources while relegating less competitive species to physiologically marginal settings, where escalation also ensues. The extent to which performance standards rise depends on enabling factors, which control availability of and access to resources. By establishing positive feedbacks between species and enabling factors, effective competitors regulate and enhance resource supply. The pace of escalation toward greater power and reach is dictated by geological factors as well as by growing interdependencies between species and their resources. Evolutionary events on land related to the production of oxygen may have been instrumental in triggering the major episodes of escalation. © Copyright ©2013 by Annual Reviews. All rights reserved.


Seldin M.F.,University of California at Davis
Journal of Autoimmunity | Year: 2015

Progress in defining the genetics of autoimmune disease has been dramatically enhanced by large scale genetic studies. Genome-wide approaches, examining hundreds or for some diseases thousands of cases and controls, have been implemented using high throughput genotyping and appropriate algorithms to provide a wealth of data over the last decade. These studies have identified hundreds of non-HLA loci as well as further defining HLA variations that predispose to different autoimmune diseases. These studies to identify genetic risk loci are also complemented by progress in gene expression studies including definition of expression quantitative trait loci (eQTL), various alterations in chromatin structure including histone marks, DNase I sensitivity, repressed chromatin regions as well as transcript factor binding sites. Integration of this information can partially explain why particular variations can alter proclivity to autoimmune phenotypes. Despite our incomplete knowledge base with only partial definition of hereditary factors and possible functional connections, this progress has and will continue to facilitate a better understanding of critical pathways and critical changes in immunoregulation. Advances in defining and understanding functional variants potentially can lead to both novel therapeutics and personalized medicine in which therapeutic approaches are chosen based on particular molecular phenotypes and genomic alterations. © 2015 Elsevier Ltd.


DeCarli C.,University of California at Davis
Journal of Alzheimer's Disease | Year: 2013

Cerebrovascular risk factors and stroke are highly prevalent with advancing age, and stroke may be more common than Alzheimer's disease, particularly among older men. While stroke mortality continues to decline, the prevalence of individuals with various vascular risk factors continues to rise and many are undiagnosed or undertreated. Asymptomatic cerebrovascular brain injury that includes asymptomatic brain infarction and white matter hyperintensities as well as accelerated brain atrophy is even more frequent than clinical stroke. Moreover, the impact of cerebrovascular risk factors on brain injury appears to begin in middle life and additively increases the likelihood of later life dementia. This review focuses on the use of neuroimaging and genetics to understand the impact of asymptomatic vascular risk factors on the trajectories of cognitive aging as well as incident cognitive impairment, stroke, and mortality. Results of this review emphasize the need for early detection and treatment of vascular risk factors to improve the cognitive health of our rapidly aging population. © 2013 - IOS Press and the authors. All rights reserved.


Breast-fed infants and young children need complementary foods with a very high nutrient density (particularly for iron andzinc), especially at ages 6-12 mo. However, in low-income countries, their diet is usually dominated by cereal-based porridges with low nutrient density and poor mineral bioavailability. Complementary feeding diets typically fall short in iron andzinc and sometimes in other nutrients. These gaps in nutritional adequacy of infant diets have likely been a characteristic of human diets since the agricultural revolution ~10,000 y ago. Estimates of nutrient intakes before then, based on hypothetical diets of preagricultural humans, suggest that infants had much higher intakes of key nutrients than is true today and would have been able to meet their nutrient needs from the combination of breast milk and premasticated foods provided by their mothers. Strategies for achieving adequate nutrition for infants and young children in modern times must address the challenge of meeting nutrient needs from largely cereal-based diets. © 2013 American Society for Nutrition.


Telander D.G.,University of California at Davis
Seminars in Ophthalmology | Year: 2011

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. The cause of AMD is complex and many risk factors have been implicated including age, family history (genetics), diet, smoking, and other environmental risk factors. Over the past decade, studies has found that inflammation play a large role in the pathogenesis of age-related macular degeneration (AMD). In fact, the main genetic changes (polymorphism) associated with AMD were found to be genes that regulate inflammation, most notably complement Factor H. This review ties together many studies done over the past decade to give us new insight into the role inflammation plays in the development of AMD. © 2011 Informa Healthcare USA, Inc.


Rodriguez G.M.,University of California at Davis | Tashiro Y.,University of California at Davis | Atsumi S.,University of California at Davis
Nature Chemical Biology | Year: 2014

To expand the capabilities of whole-cell biocatalysis, we have engineered Escherichia coli to produce various esters. The alcohol O-acyltransferase (ATF) class of enzyme uses acyl-CoA units for ester formation. The release of free CoA upon esterification with an alcohol provides the free energy to facilitate ester formation. The diversity of CoA molecules found in nature in combination with various alcohol biosynthetic pathways allows for the biosynthesis of a multitude of esters. Small to medium volatile esters have extensive applications in the flavor, fragrance, cosmetic, solvent, paint and coating industries. The present work enables the production of these compounds by designing several ester pathways in E. coli. The engineered pathways generated acetate esters of ethyl, propyl, isobutyl, 2-methyl-1-butyl, 3-methyl-1-butyl and 2-phenylethyl alcohols. In particular, we achieved high-level production of isobutyl acetate from glucose (17.2 g l -1). This strategy was expanded to realize pathways for tetradecyl acetate and several isobutyrate esters. © 2014 Nature America, Inc. All rights reserved.


German J.B.,University of California at Davis
Maternal and Child Nutrition | Year: 2011

Lipids are a complex group of biomolecules whose precise functions remain poorly understood. As a result of this poor understanding, it is difficult to make mechanistically based recommendations for appropriate dietary intakes. It is equally difficult to develop methods that are capable of diagnosing functional impairments because of insufficiencies or excesses in particular fatty acids. Lipids are abundant building blocks of cellular membranes, supply components for lipid particle assembly and substrates for metabolic fuel, and provide a precursor pool for an astonishingly diverse range of signalling molecules. In each of these broad functions, the functional consequences of different structures of fatty acids are not fully understood. According to research on membrane functions through early evolution, docosahexaenoic acid provides two biophysical properties to membranes - accelerating the lateral motion of lipids and proteins within the plane of the membrane and simultaneously slowing the rate of diffusion/leakage of charged species across the plane of the membrane. The range of fatty acid structures used as substrates for assembly of either lipoproteins or milk fat globules is broad, yet the functional consequences of differences are not known. Different lipids signal into a remarkable range of biological processes. Saturated and monounsaturated fatty acids are becoming recognized as signal molecules in their own right. The complex composition of human milk lipids implies that diets with a diversity of fatty acids in complex lipid forms and structures is more beneficial than a narrow range of any particular group of fatty acids. © 2011 Blackwell Publishing Ltd.


Knoepfler P.S.,University of California at Davis | Knoepfler P.S.,California Institute for Regenerative Medicine
Advanced Drug Delivery Reviews | Year: 2015

The phrase "bench-to-bedside" is commonly used to describe the translation of basic discoveries such as those on stem cells to the clinic for therapeutic use in human patients. However, there is a key intermediate step in between the bench and the bedside involving governmental regulatory oversight such as by the Food and Drug Administration (FDA) in the United States (US). Thus, it might be more accurate in most cases to describe the stem cell biological drug development process in this way: from bench to FDA to bedside. The intermediate development and regulatory stage for stem cell-based biological drugs is a multifactorial, continually evolving part of the process of developing a biological drug such as a stem cell-based regenerative medicine product. In some situations, stem cell-related products may not be classified as biological drugs in which case the FDA plays a relatively minor role. However, this middle stage is generally a major element of the process and is often colloquially referred to in an ominous way as "The Valley of Death". This moniker seems appropriate because it is at this point, and in particular in the work that ensues after Phase 1, clinical trials that most drug product development is terminated, often due to lack of funding, diseases being refractory to treatment, or regulatory issues. Not surprisingly, workarounds to deal with or entirely avoid this difficult stage of the process are evolving both inside and outside the domains of official regulatory authorities. In some cases these efforts involve the FDA invoking new mechanisms of accelerating the bench to beside process, but in other cases these new pathways bypass the FDA in part or entirely. Together these rapidly changing stem cell product development and regulatory pathways raise many scientific, ethical, and medical questions. These emerging trends and their potential consequences are reviewed here. © 2014 Elsevier B.V.


Delye C.,CNRS Agroecology Lab | Jasieniuk M.,University of California at Davis | Le Corre V.,CNRS Agroecology Lab
Trends in Genetics | Year: 2013

Resistance to herbicides in arable weeds is increasing rapidly worldwide and threatening global food security. Resistance has now been reported to all major herbicide modes of action despite the development of resistance management strategies in the 1990s. We review here recent advances in understanding the genetic bases and evolutionary drivers of herbicide resistance that highlight the complex nature of selection for this adaptive trait. Whereas early studied cases of resistance were highly herbicide-specific and largely under monogenic control, cases of greatest concern today generally involve resistance to multiple modes of action, are under polygenic control, and are derived from pre-existing stress response pathways. Although 'omics' approaches should enable unraveling the genetic bases of complex resistances, the appearance, selection, and spread of herbicide resistance in weed populations can only be fully elucidated by focusing on evolutionary dynamics and implementing integrative modeling efforts. © 2013 Elsevier Ltd.


Borowsky A.D.,University of California at Davis
Cold Spring Harbor perspectives in biology | Year: 2011

Genetically engineered mice are critical experimental models for the study of breast cancer biology. Transgenic mice, employing strong mammary epithelial promoters to drive oncogenes, develop carcinomas with phenotypes corresponding to the molecular pathway activated. Gene-targeted (knockout) mice, in which tumor suppressors are deleted, develop mammary neoplasms with phenotypes primarily including patterns seen in spontaneous mouse mammary tumors, albeit at higher rates. Improved genetic engineering, using inducible gene expression, somatic gene transduction, conditional alleles, and crossbreeding for combined/compound genetic engineering yields precise molecular models with exquisite experimental control and phenotypes with comparative pathologic validity. Mammary gland transplantation technology adds a practical and validated method for assessing biologic behavior of selected mammary tissues. Overall, the many mouse models available are a rich resource for experimental biology with phenocopies of breast cancer subtypes, and a variety of practical advantages. The challenge is matching the model to the experimental question.


Wang I.J.,University of California at Berkeley | Bradburd G.S.,University of California at Davis
Molecular Ecology | Year: 2014

The interactions between organisms and their environments can shape distributions of spatial genetic variation, resulting in patterns of isolation by environment (IBE) in which genetic and environmental distances are positively correlated, independent of geographic distance. IBE represents one of the most important patterns that results from the ways in which landscape heterogeneity influences gene flow and population connectivity, but it has only recently been examined in studies of ecological and landscape genetics. Nevertheless, the study of IBE presents valuable opportunities to investigate how spatial heterogeneity in ecological processes, agents of selection and environmental variables contributes to genetic divergence in nature. New and increasingly sophisticated studies of IBE in natural systems are poised to make significant contributions to our understanding of the role of ecology in genetic divergence and of modes of differentiation both within and between species. Here, we describe the underlying ecological processes that can generate patterns of IBE, examine its implications for a wide variety of disciplines and outline several areas of future research that can answer pressing questions about the ecological basis of genetic diversity. © 2014 John Wiley & Sons Ltd.


Baumgarth N.,University of California at Davis
Immunological Reviews | Year: 2013

Influenza virus infection induces robust and highly protective B-cell responses. Knowledge gained from the analysis of such protective humoral responses can provide important clues for the design of successful vaccines and vaccination approaches and also provides a window into the regulation of fundamental aspects of B-cell responses that may not be at play when responses to non-replicating agents are studied. Here, I review features of the B-cell response to viruses, with emphasis on influenza virus infection, a highly localized infection of respiratory tract epithelial cells, and a response that is directed against a virus that continuously undergoes genetic changes to its surface spike protein, a major target of neutralizing antibodies. Two aspects of the B-cell response to influenza are discussed here, namely polyreactive natural antibodies and the role and function of germinal center responses. Both these features of the B-cell response raise the question of how important antibody fine-specificity is for long-term protection from infection. As outlined, the pathogenesis of influenza virus and the nature of the antiviral B-cell response seem to emphasize repertoire diversity over affinity maturation as driving forces behind the influenza-specific B-cell immunity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Simonton D.K.,University of California at Davis
Dialogues in Clinical Neuroscience | Year: 2012

Because the cognitive neuroscientists have become increasingly interested in the phenomenon of creativity, the issue arises of how creativity is to be optimally measured. Unlike intelligence, which can be assessed across the full range of intellectual ability, creativity measures tend to concentrate on different sections of the overall spectrum. After first defining creativity in terms of the three criteria of novelty, usefulness, and surprise, this article provides an overview of the available measures. Not only do these instruments vary according to whether they focus on the creative process, person, or product, but they differ regarding whether they tap into "little-c" versus "Big-C" creativity; only productivity and eminence measures reach into genius-level manifestations of the phenomenon. The article closes by discussing whether various alternative assessment techniques can be integrated into a single measure that quantifies creativity across the full spectrum. © 2012, LLS SAS.


Oberbauer A.M.,University of California at Davis
Frontiers in Endocrinology | Year: 2013

It is commonly known that the insulin-like growth factor-I gene contains six exons that can be differentially spliced to create multiple transcript variants. Further, there are two mutually exclusive leader exons each having multiple promoter sites that are variably used. The mature IGF-I protein derived from the multiplicity of transcripts does not differ suggesting a regulatory role for the various transcript isoforms. The variant forms possess different stabilities, binding partners, and activity indicating a pivotal role for the isoforms. Research has demonstrated differential expression of the IGF-I mRNA transcripts in response to steroids, growth hormone, and developmental cues. Many studies of different tissues have focused on assessing the presence, or putative action, of the transcript isoforms with little consideration of the transcriptional mechanisms that generate the variants or the translational use of the transcript isoforms. Control points for the latter include epigenetic regulation of splicing and promoter usage in response to development or injury, RNA binding proteins and microRNA effects on transcript stability, and preferential use of two leader exons by GH and other hormones. This review will detail the current knowledge of the mechanical, hormonal, and developmental stimuli regulating IGF-1 promoter usage and splicing machinery used to create the variants. © 2013 Oberbauer.


Frankel E.N.,University of California at Davis
Journal of Agricultural and Food Chemistry | Year: 2010

Much analytical work has been published on the chemistry of extra virgin olive oil (EVOO) as a basis for the detection and quantitative analyses of the type and amount of adulteration with cheaper vegetable oils and deodorized olive oils. The analysis and authentication of EVOO represent very challenging analytical chemical problems. A significant amount of literature on EVOO adulteration has depended on sophisticated statistical approaches that require analyses of large numbers of samples. More effort is needed to exploit reliable chemical and instrumental methods that may not require so much statistical interpretation. Large assortments of methods have been used to determine lipid oxidation and oxidative stability and to evaluate the activity of the complex mixtures of phenolic antioxidants found in EVOO. More reliable chemical methods are required in this field to obviate excessive dependence on rapid antiradical methods that provide no information on the protective properties of antioxidants. The extensive literature on olive oil sensory tests, using many descriptors varying in different countries, should be supplemented by more precise gas chromatographic analyses of volatile compounds influencing the odor and flavors of EVOO. © 2010 American Chemical Society.


Cocanour C.S.,University of California at Davis
Surgical Infections | Year: 2011

Background: Clostridium difficile infection (CDI) is the primary cause of antibiotic-associated colitis and 15-25% of nosocomial antibiotic-associated diarrhea. Its clinical manifestations can range from mild diarrhea to toxic megacolon, bowel perforation, septic shock, and death. Over the past decade, more virulent strains have become increasingly common causes, and the incidence of CDI has risen, especially in elderly patients. These developments have led to an increase in recurrent CDI, which is more difficult to treat. This review focuses on recurrent CDI and its treatment. Methods: MEDLINE review using search terms Clostridium difficile, Clostridium difficile infection, recurrent Clostridium difficile infection. Results: A first recurrence may be treated with the same regimen as the first episode. Metronidazole 500 mg q 8 h for 10-14 days is the drug of choice for moderate infection, and vancomycin 125 mg q 6 h for 10-14 days is the drug of choice for severe CDI. Metronidazole should not be used for treatment of subsequent recurrences because of potential neurotoxicity and hepatic toxicity. Second recurrences should be treated with an oral vancomycin course and taper: 125 mg q 6 h × 10-14 days, 125 mg q 12 h × 7 days, 125 mg q 24 h × 7 days, 125 mg q 48-72 h × 2-8 weeks. Alternative agents are fecal bacteriotherapy, a "rifaximin chaser," nitazoxanide, probiotics, and intravenous immunoglobulin. Fidaxomicin has been approved recently. Monoclonal antibodies against C. difficile toxin remain investigational. Conclusion: Treatment of recurrent CDI remains challenging. Because of the lack of high-quality studies, recommendations for treatment are based on expert opinion. Metronidazole and vancomycin are the mainstays of treatment for both the initial infection and the first recurrence. For second recurrences, a vancomycin course plus taper is recommended. For subsequent recurrences, treatment options are many, with no one approach being entirely satisfactory. New drugs (fidaximicin) and treatments (monoclonal antibodies against the causative toxin) appear promising. © Copyright 2011, Mary Ann Liebert, Inc.


Power P.P.,University of California at Davis
Accounts of Chemical Research | Year: 2011

We showed in 2005 that a digermyne, a main group compound with a digermanium core and aromatic substituents, reacted directly with hydrogen at 25 °C and 1 atm to give well-defined hydrogen addition products. This was the first report of a reaction of main group molecules with hydrogen under ambient conditions. Our group and a number of others have since shown that several classes of main group molecules, either alone or in combination, react directly (in some cases reversibly) with hydrogen under mild conditions. Moreover, this reactivity was not limited to hydrogen but also included direct reactions with other important small molecules, including ammonia, boranes, and unactivated olefins such as ethylene. These reactions were largely unanticipated because main group species were generally considered to be too unreactive to effect such transformations.In this Account, we summarize recent developments in the reactions of the multiple bonded and other open shell derivatives of the heavier main group elements with hydrogen, ammonia, olefins, or related molecules. We focus on results generated primarily in our laboratory, which are placed in the context of parallel findings by other researchers. The close relationship between HOMO-LUMO separations, symmetry considerations, and reactivity of the open shell in main group compounds is emphasized, as is their similarity in reactivity to transition metal organometallic compounds.The unexpectedly potent reactivity of the heavier main group species arises from the large differences in bonding between the light and heavy elements. Specifically, the energy levels within the heavier element molecules are separated by much smaller gaps as a result of generally lower bond strengths. In addition, the ordering and symmetries of the energy levels are generally different for their light counterparts. Such differences lie at the heart of the new reactions. Moreover, the reactivity of the molecules can often be interpreted qualitatively in terms of simple molecular orbital considerations. More quantitative explanations are accessible from increasingly sophisticated density functional theory (DFT) calculations.We open with a short description of the background developments that led to this work. These advances involved the synthesis and characterization of numerous new main group molecules involving multiple bonds or unsaturated configurations; they were pursued over the latter part of the last century and the beginning of the new one. The results firmly established that the structures and bonding in the new compounds differed markedly from those of their lighter element congeners. The knowledge gained from this fundamental work provided the framework for an understanding of their structures and bonding, and hence an understanding of the reactivity of the compounds discussed here. © 2011 American Chemical Society.


Gepts P.,University of California at Davis
Current Opinion in Plant Biology | Year: 2014

The application of genomic approaches to the phenomenon of plant domestication promises a better understanding of the origins of agriculture, but also of the way plant genomes in general are organized and expressed. Building on earlier genetic research, more detailed information has become available on the organization of genetic diversity at the genome level and the effects of gene flow on diversity in different regions of the genome. In addition, putative domestication genes have been identified through population genomics approaches (selective sweeps or divergence scanning). Further information has been obtained on the origin of domestication syndrome mutations and the dispersal and adaptation of crops after domestication. For the future, increasingly multidisciplinary approaches using combinations of genomics and other approaches will prevail. © 2014 Elsevier Ltd.


Kliebenstein D.J.,University of California at Davis | Kliebenstein D.J.,Copenhagen University
Current Opinion in Plant Biology | Year: 2014

A goal of metabolic engineering is to take a plant and introduce new or modify existing pathways in a directed and predictable fashion. However, existing data does not provide the necessary level of information to allow for predictive models to be generated. One avenue to reverse engineer the necessary information is to study the genetic control of natural variation in plant primary and secondary metabolism. These studies are showing that any engineering model will have to incorporate information about 1000s of genes in both the nuclear and organellar genome to optimize the function of the introduced pathway. Further, these genes may interact in an unpredictable fashion complicating any engineering approach as it moves from the one or two gene manipulation to higher order stacking efforts. Finally, metabolic engineering may be influenced by a previously unrecognized potential for a plant to measure the metabolites within it. In combination, these observations from natural variation provide a beginning to help improve current efforts at metabolic engineering. © 2014 Elsevier Ltd.


Kaloper N.,University of California at Davis | Padilla A.,University of Nottingham
Physical Review Letters | Year: 2014

We propose a very simple reformulation of general relativity, which completely sequesters from gravity all of the vacuum energy from a matter sector, including all loop corrections and renders all contributions from phase transitions automatically small. The idea is to make the dimensional parameters in the matter sector functionals of the 4-volume element of the Universe. For them to be nonzero, the Universe should be finite in spacetime. If this matter is the standard model of particle physics, our mechanism prevents any of its vacuum energy, classical or quantum, from sourcing the curvature of the Universe. The mechanism is consistent with the large hierarchy between the Planck scale, electroweak scale, and curvature scale, and early Universe cosmology, including inflation. Consequences of our proposal are that the vacuum curvature of an old and large universe is not zero, but very small, that wDE-1 is a transient, and that the Universe will collapse in the future. © 2014 American Physical Society.


Thomases B.,University of California at Davis | Guy R.D.,University of California at Davis
Physical Review Letters | Year: 2014

A computational model of finite-length undulatory swimmers is used to examine the physical origin of the effect of elasticity on swimming speed. We explore two distinct target swimming strokes: one derived from the motion of Caenorhabditis elegans, with large head undulations, and a contrasting stroke with large tail undulations. We show that both favorable stroke asymmetry and swimmer elasticity contribute to a speed-up, but a substantial boost results only when these two effects work together. We reproduce conflicting results from the literature simply by changing relevant physical parameters. © 2014 American Physical Society.


Canter R.J.,University of California at Davis
Current opinion in oncology | Year: 2015

PURPOSE OF REVIEW: This review highlights the ongoing importance of surgical resection as the primary treatment modality for localized soft tissue sarcomas (STSs) in all locations and for the majority of histologic types. Accomplishing this goal in an oncologic fashion is of paramount importance for all patients eligible for treatment with curative intent and for selected patients with metastatic disease.RECENT FINDINGS: Ongoing advances in combined modality therapy and improved knowledge regarding the natural history and disease biology of individual sarcoma subtypes have allowed for better surgical planning and tailoring of the extent of resection depending on individual clinical, radiographic, and pathologic factors.SUMMARY: Successful therapy for localized STS remains contingent on surgical resection with tumor-free margins. It is hoped that ongoing advances in the molecular and genetic understanding of the pathogenesis and biology of STS will lead to sustained improvements in the care of these patients, and success will come from the ongoing development of targeted therapies and immunotherapies specific to histologic type.


Insulin resistance progressing to type 2 diabetes mellitus (T2DM) is marked by a broad perturbation of macronutrient intermediary metabolism. Understanding the biochemical networks that underlie metabolic homeostasis and how they associate with insulin action will help unravel diabetes etiology and should foster discovery of new biomarkers of disease risk and severity. We examined differences in plasma concentrations of >350 metabolites in fasted obese T2DM vs. obese non-diabetic African-American women, and utilized principal components analysis to identify 158 metabolite components that strongly correlated with fasting HbA1c over a broad range of the latter (r = -0.631; p<0.0001). In addition to many unidentified small molecules, specific metabolites that were increased significantly in T2DM subjects included certain amino acids and their derivatives (i.e., leucine, 2-ketoisocaproate, valine, cystine, histidine), 2-hydroxybutanoate, long-chain fatty acids, and carbohydrate derivatives. Leucine and valine concentrations rose with increasing HbA1c, and significantly correlated with plasma acetylcarnitine concentrations. It is hypothesized that this reflects a close link between abnormalities in glucose homeostasis, amino acid catabolism, and efficiency of fuel combustion in the tricarboxylic acid (TCA) cycle. It is speculated that a mechanism for potential TCA cycle inefficiency concurrent with insulin resistance is "anaplerotic stress" emanating from reduced amino acid-derived carbon flux to TCA cycle intermediates, which if coupled to perturbation in cataplerosis would lead to net reduction in TCA cycle capacity relative to fuel delivery.


Clevers H.C.,University Utrecht | Bevins C.L.,University of California at Davis
Annual Review of Physiology | Year: 2013

Paneth cells are highly specialized epithelial cells of the small intestine, where they coordinate many physiological functions. First identified more than a century ago on the basis of their readily discernible secretory granules by routine histology, these cells are located at the base of the crypts of Lieberkühn, tiny invaginations that line the mucosal surface all along the small intestine. Investigations over the past several decades determined that these cells synthesize and secrete substantial quantities of antimicrobial peptides and proteins. More recent studies have determined that these antimicrobial molecules are key mediators of host-microbe interactions, including homeostatic balance with colonizing microbiota and innate immune protection from enteric pathogens. Perhaps more intriguing, Paneth cells secrete factors that help sustain and modulate the epithelial stem and progenitor cells that cohabitate in the crypts and rejuvenate the small intestinal epithelium. Dysfunction of Paneth cell biology contributes to the pathogenesis of chronic inflammatory bowel disease. Copyright © 2013 by Annual Reviews. All rights reserved.


Deser S.,California Institute of Technology | Deser S.,Brandeis University | Waldron A.,University of California at Davis
Physical Review Letters | Year: 2013

We show, by analyzing its characteristics, that the ghost-free, 5 degree of freedom, Wess-Zumino massive gravity model admits superluminal shock wave solutions and thus is acausal. Ironically, this pathology arises from the very constraint that removes the (sixth) Boulware-Deser ghost mode. © 2013 American Physical Society.


Geisseler D.,University of California at Davis | Scow K.M.,University of California at Davis
Soil Biology and Biochemistry | Year: 2014

Increasing nutrient inputs into terrestrial ecosystems affect not only plant communities but also associated soil microbial communities. Studies carried out in predominantly unmanaged ecosystems have found that increasing nitrogen (N) inputs generally decrease soil microbial biomass; less is known about long-term impacts in managed systems such as agroecosystems. The objective of this paper was to analyze the responses of soil microorganisms to mineral fertilizer using data from long-term fertilization trials in cropping systems. A meta-analysis based on 107 datasets from 64 long-term trials from around the world revealed that mineral fertilizer application led to a 15.1% increase in the microbial biomass (Cmic) above levels in unfertilized control treatments. Mineral fertilization also increased soil organic carbon (Corg) content and our results suggest that Corg is a major factor contributing to the overall increase in Cmic with mineral fertilization. The magnitude of the effect of fertilization on Cmic was pH dependent. While fertilization tended to reduce Cmic in soils with a pH below 5 in the fertilized treatment, it had a significantly positive effect at higher soil pH values. Duration of the trial also affected the response of Cmic to fertilization, with increases in Cmic most pronounced in studies with a duration of at least 20 years. The input of N per se does not seem to negatively affect Cmic in cropping systems. The application of urea and ammonia fertilizers, however, can temporarily increase pH, osmotic potential and ammonia concentrations to levels inhibitory to microbial communities. Even though impacts of fertilizers are spatially limited, they may strongly affect soil microbial biomass and community composition in the short term. Long-term repeated mineral N applications may alter microbial community composition even when pH changes are small. How specific microbial groups respond to repeated applications of mineral fertilizers, however, varies considerably and seems to depend on environmental and crop management related factors. © 2014 Elsevier Ltd.


Segal D.J.,University of California at Davis | Meckler J.F.,University of California at Davis
Annual Review of Genomics and Human Genetics | Year: 2013

Genome engineering-the ability to precisely alter the DNA information in living cells-is beginning to transform human genetics and genomics. Advances in tools and methods have enabled genetic modifications ranging from the "scarless" correction of a single base pair to the deletion of entire chromosomes. Targetable nucleases are leading the advances in this field, providing the tools to modify any gene in seemingly any organism with high efficiency. Targeted gene alterations have now been reported in more than 30 diverse species, ending the reign of mice as the exclusive model of mammalian genetics, and targetable nucleases have been used to modify more than 150 human genes and loci. A nuclease has also already entered clinical trials, signaling the beginning of genome engineering as therapy. The recent dramatic increase in the number of investigators using these techniques signifies a transition away from methods development toward a new age of exciting applications. Copyright © 2013 by Annual Reviews. All rights reserved.


Despa S.,University of California at Davis | Bers D.M.,University of California at Davis
Journal of Molecular and Cellular Cardiology | Year: 2013

In the heart, intracellular Na+ concentration ([Na+]i) is a key modulator of Ca2+ cycling, contractility and cardiac myocyte metabolism. Several Na+ transporters are electrogenic, thus they both contribute to shaping the cardiac action potential and at the same time are affected by it. [Na+]i is controlled by the balance between Na+ influx through various pathways, including the Na+/Ca2+ exchanger and Na+ channels, and Na+ extrusion via the Na+/K+-ATPase. [Na+]i is elevated in HF due to a combination of increased entry through Na+ channels and/or Na+/H+ exchanger and reduced activity of the Na+/K+-ATPase. Here we review the major Na+ transport pathways in cardiac myocytes and how they participate in regulating [Na+]i in normal and failing hearts. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes.". © 2013 Elsevier Ltd.


Caro T.,University of California at Davis
Seminars in Cell and Developmental Biology | Year: 2013

In this review I survey pelage and skin colouration patterns of the 29 orders of extant mammals and assess their functional significance. The vast majority of mammals are shades of grey or brown. Concealment is probably the principal evolutionary driver of pelage colouration in this Class likely through background matching and self-shadow concealment. A small minority of species are aposematic while many others have distinctive markings used in intraspecific and interspecific communication although the meaning of these markings is unclear. Colouration in mammals also has physiological consequences but these are barely understood as yet. © 2013 Elsevier Ltd.


McNally F.J.,University of California at Davis
Journal of Cell Biology | Year: 2013

Accurate positioning of spindles is essential for asymmetric mitotic and meiotic cell divisions that are crucial for animal development and oocyte maturation, respectively. The predominant model for spindle positioning, termed "cortical pulling," involves attachment of the microtubulebased motor cytoplasmic dynein to the cortex, where it exerts a pulling force on microtubules that extend from the spindle poles to the cell cortex, thereby displacing the spindle. Recent studies have addressed important details of the cortical pulling mechanism and have revealed alternative mechanisms that may be used when microtubules do not extend from the spindle to the cortex. © 2013 McNally.


Davies A.E.,University of California at Davis | Kaplan K.B.,University of California at Davis
Journal of Cell Biology | Year: 2010

The formation of functional kinetochores requires the accurate assembly of a large number of protein complexes. The Hsp90-Sgt1 chaperone complex is important for this process; however, its targets are not conserved and its exact contribution to kinetochore assembly is unclear. Here, we show that human Hsp90-Sgt1 interacts with the Mis12 complex, a so-called keystone complex required to assemble a large fraction of the kinetochore. Inhibition of Hsp90 or Sgt1 destabilizes the Mis12 complex and delays proper chromosome alignment due to inefficient formation of microtubule-binding sites. Interestingly, coinhibition of Sgt1 and the SCF subunit, Skp1, increases Mis12 complexes at kinetochores and restores timely chromosome alignment but forms less-robust microtubule-binding sites. We propose that a balance of Mis12 complex assembly and turnover is required for the efficient and accurate assembly of kinetochore-microtubule binding sites. These findings support a novel role for Hsp90-Sgt1 chaperones in ensuring the fidelity of multiprotein complex assembly. © 2010 Davies and Kaplan.


Montanez I.P.,University of California at Davis
Geochimica et Cosmochimica Acta | Year: 2013

Paleosol carbonate-based estimates of paleo-atmospheric CO2 play a prominent role in constraining radiative-forcing and climate sensitivity in the deep-time. Large uncertainty in paleo-CO2 estimates made using the paleosol-carbonate CO2-barometer, however, arises primarily from their sensitivity to soil-respired CO2 (S(z)). This parameter is poorly constrained due to a paucity of soil CO2 measurements during carbonate formation in modern soils and a lack of widely applicable proxies of paleo-soil CO2. Here the δ13C values of carbonate and soil organic matter (SOM) pairs from 130 Holocene soils are applied to a two-component CO2-mixing equation to define soil order-specific ranges of soil CO2 applicable for constraining S(z) in their corresponding paleosol analogs.Equilibrium carbonate-SOM pairs, characterized by Δ13Ccarb-SOM values of 12.2-15.8‰, define a mean effective fractionation of 14.1‰ and overall inferred total soil CO2 contents during calcite formation of <1000-10,000ppmv. For those Aridisols and Alfisols, characterized by a net soil-moisture deficit, and their paleosol analogs (Calcisols and Argillisols), a best estimate of S(z) during calcite formation is 1500-2000ppmv (range of 500-2500ppmv). Overall higher values (2000-5000ppmv) are indicated by the subset of these soils characterized by higher moisture content and productivity. Near atmospheric levels (400±200ppmv) of estimated S(z) are indicated by immature soils, recording their low soil productivity. Vertisols define the largest range in total soil CO2 (<1000 to >25,000ppmv) reflecting their seasonally driven dynamic hydrochemistry. A S(z) range of 1000-10,000ppmv is suggested for paleo-Vertisols for which calcite precipitation can be constrained to have occurred in an open system with two-component CO2 mixing, with a best estimate of 2000ppmv±1000ppmv appropriate for paleo-Vertisols for which evidence of protracted water saturation is lacking. Mollisol pairs define a best estimate of S(z) of 2500ppmv (range of 600-4000ppmv) for late Cretaceous and Cenozoic analogs.Non-equilibrium pairs with Δ13C values >16‰ make up 51% of the dataset, lending support to the hypothesis that pedogenic carbonate precipitation occurs during periods of low productivity in a soil atmosphere with a large component of atmospheric CO2. Predictable scaling between estimated soil CO2 and the difference in δ13C between measured pedogenic carbonate and that predicted to have formed from soil-respired CO2 (inferred from measured SOM) can be used to further constrain appropriate ranges of S(z) for reconstruction of paleo-atmospheric pCO2. Soil CO2 estimates are poorly correlated to mean annual precipitation likely reflecting that for carbonate-bearing soils, where moisture limits CO2 production, total soil CO2 is most strongly influenced by actual evapotranspiration. © 2012 Elsevier Ltd.


Thomson R.C.,University of California at Davis | Shaffer H.B.,University of California at Davis
Systematic Biology | Year: 2010

As phylogenetic data sets grow in size and number, objective methods to summarize this information are becoming increasingly important. Supermatrices can combine existing data directly and in principle provide effective syntheses of phylogenetic information that may reveal new relationships. However, several serious difficulties exist in the construction of large supermatrices that must be overcome before these approaches will enjoy broad utility. We present analyses that examine the performance of sparse supermatrices constructed from large sequence databases for the reconstruction of species-level phylogenies. We develop a largely automated informatics pipeline that allows for the construction of sparse supermatrices from GenBank data. In doing so, we develop strategies for alleviating some of the outstanding impediments to accurate phylogenetic inference using these approaches. These include taxonomic standardization, automated alignment, and the identification of rogue taxa. We use turtles as an exemplar clade and present a well-supported species-level phylogeny for two-thirds of all turtle species based on a ∼50 kb supermatrix consisting of 93% missing data. Finally, we discuss some of the remaining pitfalls and concerns associated with supermatrix analyses, provide comparisons to supertree approaches, and suggest areas for future research.


Roth J.R.,University of California at Davis | Andersson D.I.,Uppsala University
Cell | Year: 2012

A multistep process of gene amplification, mutation, and reduction allows poxvirus to overcome host antiviral defenses. The mechanism speeds genetic adaptation and promises to be broadly applicable in many biological settings. © 2012 Elsevier Inc.


Haskell M.J.,University of California at Davis
American Journal of Clinical Nutrition | Year: 2012

β-Carotene is an important dietary source of vitamin A for humans. However, the bioavailability and vitamin A equivalency of β-carotene are highly variable and can be affected by food- and diet-related factors, including the food matrix, food-processing techniques, size of the dose of β-carotene, and the amounts of dietary fat, fiber, vitamin A, and other carotenoids in the diet as well as by characteristics of the target population, such as vitamin A status, nutrient deficiencies, gut integrity, and genetic polymorphisms associated with β-carotene metabolism. The absorption of β-carotene from plant sources ranges from 5% to 65% in humans. Vitamin A equivalency ratios for β-carotene to vitamin A from plant sources range from 3.8:1 to 28:1, by weight. Vitamin A equivalency ratios for β-carotene from biofortified Golden Rice or biofortified maize are 3.8:1 and 6.5:1, respectively, and are lower than ratios for vegetables that have more complex food matrices (10:1 to 28:1). The vitamin A equivalency of β-carotene is likely to be context-specific and dependent on specific food- and diet-related factors and the health, nutritional, and genetic characteristics of human populations. Although the vitamin A equivalency of β-carotene is highly variable, the provision of vegetable and fruit sources of β-carotene has significantly increased vitamin A status in women and children in community settings in developing countries; these results support the inclusion of dietary interventions with plant sources of β-carotene as a strategy for increasing vitamin A status in populations at risk of deficiency. © 2012 American Society for Nutrition.


The sensory outer segments (OS) of vertebrate retinal photoreceptors, which detect photons of light, resemble the distal segments of Caenorhabditis elegans sensory cilia, which detect chemical ligands that influence the chemotactic movements of the animal. Based on fluorescence microscopy assays performed in sensory cilia of living, transgenic " wild type" and mutant C. elegans, combined with in vitro motility assays using purified motors, we have proposed that two types of kinesin-2 motor, heterotrimeric kinesin-II and homodimeric OSM-3, cooperate to build amphid and phasmid sensory cilia on chemosensory neurons. Specifically, we propose that these motors function together in a redundant manner to build the axoneme core (aka middle segments (MS)), whereas OSM-3 alone serves to build the distal segments (DS). Furthermore, our data suggest that these motors accomplish this by driving two sequential steps of anterograde transport of cargoes consisting of IFT-particles, retrograde dynein motors, and ciliary tubulin subunits, from the transition zone to the tips of the axonemal microtubules (MTs). Homologs of kinesin-II (KIF3) and OSM-3 (KIF17) are also proposed to contribute to the assembly of vertebrate photoreceptors, although how they do so is currently unclear. Here I review our work on kinesin-2 motors, intraflagellar transport (IFT) and cilium biogenesis in C. elegans sensory cilia, and comment on its possible relevance to current research on vertebrate photoreceptor cilia assembly and function. © 2012 Elsevier Ltd.


Cytidine 5'-monophosphate (CMP)-sialic acid synthetases (CSSs) catalyze the formation of CMP-sialic acid from CTP and sialic acid, a key step for sialyltransferase-catalyzed biosynthesis of sialic acid-containing oligosaccharides and glycoconjugates. More than 50 different sialic acid forms have been identified in nature. To facilitate the enzymatic synthesis of sialosides with diverse naturally occurring sialic acid forms and their non-natural derivatives, CMP-sialic acid synthetases with promiscuous substrate specificity are needed. Herein we report the cloning, characterization, and substrate specificity studies of a new CSS from Pasteurella multocida strain P-1059 (PmCSS) and a CSS from Haemophillus ducreyi (HdCSS). Based on protein sequence alignment and substrate specificity studies of these two CSSs and a Neisseria meningitidis CSS (NmCSS), as well as crystal structure modeling and analysis of NmCSS, NmCSS mutants (NmCSS_S81R and NmCSS_Q163A) with improved substrate promiscuity were generated. The strategy of combining substrate specificity studies of enzymes from different sources and protein crystal structure studies can be a general approach for designing enzyme mutants with improved activity and substrate promiscuity.


Markowska A.I.,Tufts University | Liu F.-T.,University of California at Davis | Panjwani N.,Tufts University
Journal of Experimental Medicine | Year: 2010

Recent studies have shown that a carbohydrate-binding protein, galectin-3, is a novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate here that galectin-3 is a mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-mediated angiogenic response. Angiogenesis assays revealed that galectin-3 inhibitors, β-lactose and dominant-negative galectin-3, reduce VEGF- and bFGF-mediated angiogenesis in vitro and that VEGF- and bFGF-mediated angiogenic response is reduced in galectin-3 knockdown cells and Gal3 -/- animals. Integrin αvβ3 was identified as the major galectin-3-binding protein and anti-αv, -β3, and -αvβ3 integrin function-blocking antibodies significantly inhibited the galectin-3-induced angiogenesis. Furthermore, galectin-3 promoted the clustering of integrin αvβ3 and activated focal adhesion kinase. Knockdown of GnTV, an enzyme that synthesizes high-affinity glycan ligands for galectin-3, substantially reduced: (a) complex N-glycans on αvβ3 integrins and (b) VEGF- and bFGF-mediated angiogenesis. Collectively, these data suggest that galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding via its carbohydrate recognition domain, to the GnTV synthesized N-glycans of integrin αvβ3, and subsequently activating the signaling pathways that promote the growth of new blood vessels. These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis. © 2010 Markowska et al.


Yan W.,University of California at Davis
Oncogene | Year: 2013

Mutation of the p53 gene is the most common genetic alteration in human cancer and contributes to malignant process by enhancing transformed properties of cells and resistance to anticancer therapy. Mutant p53 is often highly expressed in tumor cells at least, in part, due to its increased half-life. However, whether mutant p53 expression is regulated by other mechanisms in tumors is unclear. Here we found that histone deacetylase (HDAC) inhibitors suppress both wild-type and mutant p53 transcription in time- and dose-dependent manners. Consistent with this, the levels of wild-type and mutant p53 proteins are decreased upon treatment with HDAC inhibitors. Importantly, we found that upon knockdown of each class I HDAC, only HDAC8 knockdown leads to decreased expression of wild-type and mutant p53 proteins and transcripts. Conversely, we found that ectopic expression of wild-type, but not mutant HDAC8, leads to increased transcription of p53. Furthermore, we found that knockdown of HDAC8 results in reduced expression of HoxA5 and consequently, attenuated ability of HoxA5 to activate p53 transcription, which can be rescued by ectopic expression of HoxA5. Because of the fact that HDAC8 is required for expression of both wild-type and mutant p53, we found that targeted disruption of HDAC8 expression remarkably triggers proliferative defect in cells with a mutant, but not wild-type, p53. Together, our data uncover a regulatory mechanism of mutant p53 transcription via HDAC8 and suggest that HDAC inhibitors and especially HDAC8-targeting agents might be explored as an adjuvant for tumors carrying a mutant p53.


Marcu L.,University of California at Davis
Journal of Biomedical Optics | Year: 2010

We review fluorescence lifetime techniques including timeresolved laser-induced fluorescence spectroscopy (TR-LIFS) and fluorescence lifetime imaging microscopy (FLIM) instrumentation and associated methodologies that allow for characterization and diagnosis of atherosclerotic plaques. Emphasis is placed on the translational research potential of TR-LIFS and FLIM and on determining whether intrinsic fluorescence signals can be used to provide useful contrast for the diagnosis of high-risk atherosclerotic plaque. Our results demonstrate that these techniques allow for the discrimination of important biochemical features involved in atherosclerotic plaque instability and rupture and show their potential for future intravascular applications. © 2010 Society of Photo-Optical Instrumentation Engineers.


de Lartigue G.,University of California at Davis
Physiology and Behavior | Year: 2014

The vagus nerve is a major pathway by which information is communicated between the brain and peripheral organs. Sensory neurons of the vagus are located in the nodose ganglia. These vagal afferent neurons innervate the heart, the lung and the gastrointestinal tract, and convey information about peripheral signals to the brain important in the control of cardiovascular tone, respiratory tone, and satiation, respectively. Glutamate is thought to be the primary neurotransmitter involved in conveying all of this information to the brain. It remains unclear how a single neurotransmitter can regulate such an extensive list of physiological functions from a wide range of visceral sites. Many neurotransmitters have been identified in vagal afferent neurons and have been suggested to modulate the physiological functions of glutamate. Specifically, the anorectic peptide transmitters, cocaine and amphetamine regulated transcript (CART) and the orexigenic peptide transmitters, melanin concentrating hormone (MCH) are differentially regulated in vagal afferent neurons and have opposing effects on food intake. Using these two peptides as a model, this review will discuss the potential role of peptide transmitters in providing a more precise and refined modulatory control of the broad physiological functions of glutamate, especially in relation to the control of feeding. © 2014.


Chichlowski M.,University of California at Davis
Annual review of food science and technology | Year: 2011

In addition to a nutritive role, human milk also guides the development of a protective intestinal microbiota in the infant. Human milk possesses an overabundance of complex oligosaccharides that are indigestible by the infant yet are consumed by microbial populations in the developing intestine. These oligosaccharides are believed to facilitate enrichment of a healthy infant gastrointestinal microbiota, often associated with bifidobacteria. Advances in glycomics have enabled precise determination of milk glycan structures as well as identification of the specific glycans consumed by various gut microbes. Furthermore, genomic analysis of bifidobacteria from infants has revealed specific genetic loci related to milk oligosaccharide import and processing, suggesting coevolution between the human host, milk glycans, and the microbes they enrich. This review discusses the current understanding of how human milk oligosaccharides interact with the infant microbiota and examines the opportunities for translating this knowledge to improve the functionality of infant formulas.


Kliebenstein D.J.,University of California at Davis | Osbourn A.,John Innes Center
Current Opinion in Plant Biology | Year: 2012

Plants have adapted to their environments by diversifying in various ways. This diversification is reflected at the phytochemical level in their production of numerous specialized secondary metabolites that provide protection against biotic and abiotic stresses. Plant speciation is therefore intimately linked to metabolic diversification, yet we do not currently have a deep understanding of how new metabolic pathways evolve. Recent evidence indicates that genes for individual secondary metabolic pathways can be either distributed throughout the genome or clustered, but the relative frequencies of these two pathway organizations remain to be established. While it is possible that clustering is a feature of pathways that have evolved in recent evolutionary time, the answer to this and how dispersed and clustered pathways may be related remain to be addressed. Recent advances enabled by genomics and systems biology are beginning to yield the first insights into network evolution in plant metabolism. This review focuses on recent progress in understanding the evolution of clustered and dispersed pathways for new secondary metabolites in plants. © 2012 Elsevier Ltd.


Schreiber S.J.,University of California at Davis
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

It is an ecological truism that population persistence depends on a population's growth rate when rare. To understand the interplay between temporal correlations, spatial heterogeneity and dispersal on persistence, an analytic approximation for this growth rate is derived for partially mixing populations. Partial mixing has two effects on population growth. In the absence of temporal correlations in relative fitness, greater movement to patches with, on average, higher relative fitness increases population growth rates. In the absence of spatial heterogeneity in the average relative fitnesses, lower dispersal rates enhance population growth when temporal autocorrelations of relative fitness within a patch exceed temporal cross-correlations in relative fitness between patches. This approximation implies that metapopulations whose expected fitness in every patch is less than 1 can persist if there are positive temporal autocorrelations in relative fitness, sufficiently weak spatial correlations and the population disperses at intermediate rates. It also implies that movement into lower quality habitats increases the population growth rate whenever the net temporal variation in per capita growth rates is sufficiently larger than the difference in the means of these per capita growth rates. Moreover, temporal autocorrelations, whether they be negative or positive, can enhance population growth for optimal dispersal strategies © 2010 The Royal Society.


Pedersen N.C.,University of California at Davis
Veterinary Journal | Year: 2014

Feline infectious peritonitis (FIP) continues to be one of the most researched infectious diseases of cats. The relatively high mortality of FIP, especially for younger cats from catteries and shelters, should be reason enough to stimulate such intense interest. However, it is the complexity of the disease and the grudging manner in which it yields its secrets that most fascinate researchers. Feline leukemia virus infection was conquered in less than two decades and the mysteries of feline immunodeficiency virus were largely unraveled in several years. After a half century, FIP remains one of the last important infections of cats for which we have no single diagnostic test, no vaccine and no definitive explanations for how virus and host interact to cause disease. How can a ubiquitous and largely non-pathogenic enteric coronavirus transform into a highly lethal pathogen? What are the interactions between host and virus that determine both disease form (wet or dry) and outcome (death or resistance)? Why is it so difficult, and perhaps impossible, to develop a vaccine for FIP? What role do genetics play in disease susceptibility? This review will explore research conducted over the last 5years that attempts to answer these and other questions. Although much has been learned about FIP in the last 5years, the ultimate answers remain for yet more studies. © 2014 The Author.


Peleg Z.,University of California at Davis | Blumwald E.,University of California at Davis
Current Opinion in Plant Biology | Year: 2011

Plant hormones play central roles in the ability of plants to adapt to changing environments, by mediating growth, development, nutrient allocation, and source/sink transitions. Although ABA is the most studied stress-responsive hormone, the role of cytokinins, brassinosteroids, and auxins during environmental stress is emerging. Recent evidence indicated that plant hormones are involved in multiple processes. Cross-talk between the different plant hormones results in synergetic or antagonic interactions that play crucial roles in response of plants to abiotic stress. The characterization of the molecular mechanisms regulating hormone synthesis, signaling, and action are facilitating the modification of hormone biosynthetic pathways for the generation of transgenic crop plants with enhanced abiotic stress tolerance. © 2011 Elsevier Ltd.


Frankel E.N.,University of California at Davis
Journal of Agricultural and Food Chemistry | Year: 2011

The nutritional benefits generally recognized for the consumption of extra virgin olive oil (EVOO) are based on a large number of dietary trials of several international populations and intervention studies. Unfortunately, many authors in this field used questionable analytical methods and commercial kits that were not validated scientifically to evaluate the complex bioactive constituents of EVOO and lipid oxidation and decomposition products. Many questionable antiradical methods were commonly used to evaluate natural polyphenolic antioxidants, including an indirect method to determine low-density lipoprotein (LDL) cholesterol. Extensive differences were observed in experimental design, diet control, populations of different ages and problems of compliance intervention, and questionable biomarkers of oxidative stress. Analyses in many nutritional studies were limited by the use of one-dimensional methods to evaluate multifunctional complex bioactive compounds and plasma lipid profiles by the common applications of commercial kits. Although EVOO contains polyphenolic compounds that exhibit significant in vitro antioxidant activity, much more research is needed to understand the absorption and in vivo activity. Many claims of in vivo human beneficial effects by the consumption of EVOO may be overstated. No distinctions were apparently made between in vivo studies based on general health effects in large populations of human subjects and smaller scale well-controlled feeding trials using either pure or mixtures of known phenolic constituents of EVOO. More reliable protocols and testing methods are needed to better validate the complex nutritional properties of EVOO. © 2011 American Chemical Society.


Chen X.,University of California at Davis | Ronald P.C.,University of California at Davis
Trends in Plant Science | Year: 2011

Advances in studies of rice innate immunity have led to the identification and characterization of host sensors encoding receptor kinases that perceive conserved microbial signatures. Receptor kinases that carry the non-orginine-aspartate domain, are highly expanded in rice (Oryza sativa) compared with Arabidopsis (Arabidopsis thaliana). Researchers have also identified a diverse array of microbial effectors from bacterial and fungal pathogens that triggers immune responses upon perception. These include effectors that indirectly target host Nucleotide binding site/Leucine rich repeat proteins and transcription activator-like effectors that directly bind promoters of host genes. Here we review the recognition and signaling events that govern rice innate immunity. © 2011 Elsevier Ltd.


Inoue K.,University of California at Davis
Trends in Plant Science | Year: 2011

The chloroplast is essential for the viability of plants. It is enclosed by a double-membrane envelope that originated from the outer and plasma membranes of a cyanobacterial endosymbiont. Chloroplast biogenesis depends on binary fission and import of nuclear-encoded proteins. Our understanding of the mechanisms and evolutionary origins of these processes has been greatly advanced by recent genetic and biochemical studies on envelope-localized multiprotein machines. Furthermore, the latest studies on outer envelope proteins have provided molecular insights into organelle movement and membrane lipid remodeling, activities that are vital for plant survival under diverse environmental conditions. Ongoing and future research on the chloroplast outer envelope should add to our knowledge of organelle biology and the evolution of eukaryotic cells. © 2011 Elsevier Ltd.


Hayward A.P.,Yale University | Dinesh-Kumar S.P.,University of California at Davis
Annual Review of Phytopathology | Year: 2011

Autophagy plays an established role in the execution of senescence, starvation, and stress responses in plants. More recently, an emerging role for autophagy has been discovered during the plant innate immune response. Recent papers have shown autophagy to restrict, and conversely, to also promote programmed cell death (PCD) at the site of pathogen infection. These initial studies have piqued our excitement, but they have also revealed gaps in our understanding of plant autophagy regulation, in our ability to monitor autophagy in plant cells, and in our ability to manipulate autophagic activity. In this review, we present the most pressing questions now facing the field of plant autophagy in general, with specific focus on autophagy as it occurs during a plant-pathogen interaction. To begin to answer these questions, we place recent findings in the context of studies of autophagy and immunity in other systems, and in the context of the mammalian immune response in particular. © 2011 by Annual Reviews. All rights reserved.


Carlip S.,University of California at Davis
Classical and Quantum Gravity | Year: 2015

Several recent results have hinted that black hole thermodynamics in loop quantum gravity simplifies if one chooses an imaginary Barbero-Immirzi parameter γ = i. This suggests a connection with SL(2, ℂ) or SL(2, ℝ) conformal field theories at the 'boundaries' formed by spin network edges intersecting the horizon. I present a bit of background regarding the relevant conformal field theories, along with some speculations about how they might be used to count black hole states. I show, in particular, that a set of unproven but plausible assumptions can lead to a boundary conformal field theory whose density of states matches the Bekenstein-Hawking entropy. © 2015 IOP Publishing Ltd.


LaSalle J.M.,University of California at Davis
Epigenetics | Year: 2011

The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent genomic, environmental and epigenetic findings that suggest a new paradigm of "integrative genomics" in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored. In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, nonmutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches. © 2011 Landes Bioscience.


Thompson R.A.,University of California at Davis
Future of Children | Year: 2014

Children's early social experiences shape their developing neurological and biological systems for good or for ill, writes Ross Thompson, and the kinds of stressful experiences that are endemic to families living in poverty can alter children's neurobiology in ways that undermine their health, their social competence, and their ability to succeed in school and in life. For example, when children are born into a world where resources are scarce and violence is a constant possibility, neurobiological changes may make them wary and vigilant, and they are likely to have a hard time controlling their emotions, focusing on tasks, and forming healthy relationships. Unfortunately, these adaptive responses to chronic stress serve them poorly in situations, such as school and work, where they must concentrate and cooperate to do well. But thanks to the plasticity of the developing brain and other biological systems, the neurobio-logical response to chronic stress can be buffered and even reversed, Thompson writes, especially when we intervene early in children's lives. In particular, warm and nurturing relationships between children and adults can serve as a powerful bulwark against the neurobiological changes that accompany stress, and interventions that help build such relationships have shown particular promise. These programs have targeted biological parents, of course, but also foster parents, teachers and other caregivers, and more distant relatives, such as grandparents. For this reason, Thompson suggests that the concept of two-generation programs may need to be expanded, and that we should consider a "multigenerational" approach to helping children living in poverty cope and thrive in the face of chronic stress.


Celli J.,Washington State University | Tsolis R.M.,University of California at Davis
Nature Reviews Microbiology | Year: 2015

The unfolded protein response (UPR) is a cytoprotective response that is aimed at restoring cellular homeostasis following physiological stress exerted on the endoplasmic reticulum (ER), which also invokes innate immune signalling in response to invading microorganisms. Although it has been known for some time that the UPR is modulated by various viruses, recent evidence indicates that it also has multiple roles during bacterial infections. In this Review, we describe how bacteria interact with the ER, including how bacteria induce the UPR, how subversion of the UPR promotes bacterial proliferation and how the UPR contributes to innate immune responses against invading bacteria. © 2015 Macmillan Publishers Limited. All rights reserved.


Dumit J.,University of California at Davis
Frontiers in Human Neuroscience | Year: 2014

Drawing on Allan Newell's "You can't play 20 questions with nature and win," this article proposes that neuroscience needs to go beyond binary hypothesis testing and design experiments that follow what neurons care about. Examples from Lettvin et. al. are used to demonstrate that one can experimentally play with neurons and generate surprising results. In this manner, brains are not confused with persons, rather, persons are understood to do things with their brains. © 2014 Dumit.


Estes M.L.,University of California at Davis | McAllister A.K.,University of California at Davis
Nature Reviews Neuroscience | Year: 2015

Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors - including autoimmunity, infection and fetal reactive antibodies - are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and in animal models of this disorder. Recently, several molecular signalling pathways - including pathways downstream of cytokines, the receptor MET, major histocompatibility complex class I molecules, microglia and complement factors - have been identified that link immune activation to ASD phenotypes. Together, these findings indicate that the immune system is a point of convergence for multiple ASD-related genetic and environmental risk factors. © 2015 Macmillan Publishers Limited. All rights reserved.


Oteiza P.I.,University of California at Davis
Free Radical Biology and Medicine | Year: 2012

Zinc, a redox-inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintaining the cell redox balance through various mechanisms including: (i) the regulation of oxidant production and metal-induced oxidative damage; (ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione, and other thiol oxidant species; (iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and acts per se as a scavenging oxidant; (iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and (v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue dysfunction in cell and animal models of zinc deficiency highlight the relevant role of zinc in the preservation of cell redox homeostasis. However, although the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the molecules, targets, and mechanisms involved are still partially known and the subject of active research. © 2012 Elsevier Inc. All rights reserved.


Powell J.S.,University of California at Davis
Journal of Thrombosis and Haemostasis | Year: 2015

Hemophilia, when severe, leads to spontaneous life-threatening bleeding episodes. Current therapy requires frequent intravenous infusions. Most patients must limit their physical activities to avoid bleeding when the factor activity levels are below normal. In 2014, new therapeutic factor VIII and IX products were approved in Canada and the U.S. Over the next couple of years, other new factor products will likely be approved. These new factors have been engineered to have improved pharmacokinetic properties, including extended half-life in circulation, thus providing major therapeutic advances for patients with hemophilia. In the completed clinical trials, over 700 patients have successfully used these longer acting products regularly for more than one year. These promising new therapies should allow patients with hemophilia to use fewer infusions to prevent spontaneous bleeding or to treat bleeding episodes, and to provide appropriate clotting factor levels for different physical activities. © 2015 International Society on Thrombosis and Haemostasis.


Wang G.,University of California at Davis
Journal of Power Sources | Year: 2011

Advanced vehicles and alternative fuels could play an important role in reducing oil use and changing the economy structure. We developed the Costs for Advanced Vehicles and Energy (CAVE) model to investigate a vehicle portfolio scenario in California during 2010-2030. Then we employed a computable general equilibrium model to estimate macroeconomic impacts of the advanced vehicle scenario on the economy of California. Results indicate that, due to slow fleet turnover, conventional vehicles are expected to continue to dominate the on-road fleet and gasoline is the major transportation fuel over the next two decades. However, alternative fuels could play an increasingly important role in gasoline displacement. Advanced vehicle costs are expected to decrease dramatically with production volume and technological progress; e.g., incremental costs for fuel cell vehicles and hydrogen could break even with gasoline savings in 2028. Overall, the vehicle portfolio scenario is estimated to have a slightly negative influence on California's economy, because advanced vehicles are very costly and, therefore, the resulting gasoline savings generally cannot offset the high incremental expenditure on vehicles and alternative fuels. Sensitivity analysis shows that an increase in gasoline price or a drop in alternative fuel prices could offset a portion of the negative impact. © 2010 Elsevier B.V.


Dawson W.A.,University of California at Davis
Astrophysical Journal | Year: 2013

Merging galaxy clusters have become one of the most important probes of dark matter, providing evidence for dark matter over modified gravity and even constraints on the dark matter self-interaction cross-section. To properly constrain the dark matter cross-section it is necessary to understand the dynamics of the merger, as the inferred cross-section is a function of both the velocity of the collision and the observed time since collision. While the best understanding of merging system dynamics comes from N-body simulations, these are computationally intensive and often explore only a limited volume of the merger phase space allowed by observed parameter uncertainty. Simple analytic models exist but the assumptions of these methods invalidate their results near the collision time, plus error propagation of the highly correlated merger parameters is unfeasible. To address these weaknesses I develop a Monte Carlo method to discern the properties of dissociative mergers and propagate the uncertainty of the measured cluster parameters in an accurate and Bayesian manner. I introduce this method, verify it against an existing hydrodynamic N-body simulation, and apply it to two known dissociative mergers: 1ES 0657-558 (Bullet Cluster) and DLSCL J0916.2+2951 (Musket Ball Cluster). I find that this method surpasses existing analytic models - providing accurate (10% level) dynamic parameter and uncertainty estimates throughout the merger history. This, coupled with minimal required a priori information (subcluster mass, redshift, and projected separation) and relatively fast computation (∼6 CPU hours), makes this method ideal for large samples of dissociative merging clusters. © 2013. The American Astronomical Society. All rights reserved.


Halsted C.H.,University of California at Davis
Clinical Chemistry and Laboratory Medicine | Year: 2013

Convincing evidence links aberrant B-vitamin dependent hepatic methionine metabolism to the pathogenesis of alcoholic liver disease (ALD). This review focuses on the essential roles of folate and vitamins B6 and B12 in hepatic methionine metabolism, the causes of their deficiencies among chronic alcoholic persons, and how their deficiencies together with chronic alcohol exposure impact on aberrant methionine metabolism in the pathogenesis of ALD. Folate is the dietary transmethylation donor for the production of S-adenosylmethionine (SAM), which is the substrate for all methyltransferases that regulate gene expressions in pathways of liver injury, as well as a regulator of the transsulfuration pathway that is essential for production of glutathione (GSH), the principal antioxidant for defense against oxidative liver injury. Vitamin B12 regulates transmethylation reactions for SAM production and vitamin B6 regulates transsulfuration reactions for GSH production. Folate deficiency accelerates the experimental development of ALD in ethanol-fed animals while reducing liver SAM levels with resultant abnormal gene expression and decreased production of antioxidant GSH. Through its effects on folate metabolism, reduced SAM also impairs nucleotide balance with resultant increased DNA strand breaks, oxidation, hepatocellular apoptosis, and risk of carcinogenesis. The review encompasses referenced studies on mechanisms for perturbations of methionine metabolism in ALD, evidence for altered gene expressions and their epigenetic regulation in the pathogenesis of ALD, and clinical studies on potential prevention and treatment of ALD by correction of methionine metabolism with SAM.


Lubell M.,University of California at Davis
Current Opinion in Environmental Sustainability | Year: 2015

Collaborative partnerships exist in the context of complex institutional systems that feature multiple institutions and actors interacting in the context of interconnected collective-action problems within ecosystems. How collaborative partnerships contribute to the overall capacity of complex institutional systems to sustainability govern natural resources remains an open question. This article reviews several theoretical approaches for studying complex institutional systems, and discusses how collaborative partnerships would be viewed from these perspectives. The approaches covered include neo-institutional economics, polycentric governance, complex adaptive systems, and evolutionary models of institutional change. The conclusion calls for synthetic theoretical frameworks that integrate many of these ideas, and identifies the research on social-ecological systems as a promising direction. © 2014 Published by Elsevier Ltd.


Bloom A.J.,University of California at Davis
Current Opinion in Plant Biology | Year: 2015

Many studies of plant nitrogen relations assess only the total amount of the element available from the soil and the total amount of the element within the plant. Nitrogen, however, is a constituent of diverse compounds that participate in some of the most energy-intensive reactions in the biosphere. The following characterizes some of these reactions, especially those that involve ammonium and nitrate, and highlights the importance of distinguishing both among the nitrogen sources available to plants and among the nitrogen forms within plants when considering plant responses to rising atmospheric CO2 concentrations. © 2015 Elsevier Ltd.


Wang R.,University of California at Davis | Mukherjee B.,University of California at Davis
Journal of Lightwave Technology | Year: 2013

How serious is spectrum fragmentation in an elastic optical network? It is addressed by the tremendous provisioning gain achieved by eliminating a particular kind of fragmentation, namely, one that could be removed by Hitless Optical Path Shift (HOPS), a non-disruptive defragmentation technology. We devised a series of HOPS-based defragmentation algorithms, ranging from proactive to reactive strategies. Analysis and simulation results show that for typical backbone networks operated with a light load, using our optimal reactive defragmentation scheme, 98% of the requested spectrum bandwidth, that is otherwise blocked, can be provisioned. Moreover, the corresponding defragmentation costs (in terms of impact on existing connections, and defragmentation delay) are kept at minimum. © 1983-2012 IEEE.


Potassium channels (KChs) are the most diverse ion channels, in part due to extensive combinatorial assembly of a large number of principal and auxiliary subunits into an assortment of KCh complexes. Their structural and functional diversity allows KChs to play diverse roles in neuronal function. Localization of KChs within specialized neuronal compartments defines their physiological role and also fundamentally impacts their activity, due to localized exposure to diverse cellular determinants of channel function. Recent studies in mammalian brain reveal an exquisite refinement of KCh subcellular localization. This includes axonal KChs at the initial segment, and near/within nodes of Ranvier and presynaptic terminals, dendritic KChs found at sites reflecting specific synaptic input, and KChs defining novel neuronal compartments. Painting the remarkable diversity of KChs onto the complex architecture of mammalian neurons creates an elegant picture of electrical signal processing underlying the sophisticated function of individual neuronal compartments, and ultimately neurotransmission and behavior. © 2015 Elsevier Inc.


Li L.-X.,University of California at Davis | McSorley S.J.,University of California at Davis
PLoS Pathogens | Year: 2013

B cells can contribute to acquired immunity against intracellular bacteria, but do not usually participate in primary clearance. Here, we examined the endogenous CD4 T cell response to genital infection with Chlamydia muridarum using MHC class-II tetramers. Chlamydia-specific CD4 T cells expanded rapidly and persisted as a stable memory pool for several months after infection. While most lymph node Chlamydia-specific CD4 T cells expressed T-bet, a small percentage co-expressed Foxp3, and RORγt-expressing T cells were enriched within the reproductive tract. Local Chlamydia-specific CD4 T cell priming was markedly reduced in mice lacking B cells, and bacteria were able to disseminate to the peritoneal cavity, initiating a cellular infiltrate and ascites. However, bacterial dissemination also coincided with elevated systemic Chlamydia-specific CD4 T cell responses and resolution of primary infection. Together, these data reveal heterogeneity in pathogen-specific CD4 T cell responses within the genital tract and an unexpected requirement for B cells in regulating local T cell activation and bacterial dissemination during genital infection. © 2013 Li, McSorley.


Feske S.,New York University | Wulff H.,University of California at Davis | Skolnik E.Y.,New York University
Annual Review of Immunology | Year: 2015

Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, and zinc have important roles as second messengers to regulate intracellular signaling pathways. By contrast, monovalent cations such as sodium and potassium mainly regulate the membrane potential, which indirectly controls the influx of calcium and immune cell signaling. Studies investigating human patients with mutations in ion channels and transporters, analysis of gene-targeted mice, or pharmacological experiments with ion channel inhibitors have revealed important roles of ionic signals in lymphocyte development and in innate and adaptive immune responses. We here review the mechanisms underlying the function of ion channels and transporters in lymphocytes and innate immune cells and discuss their roles in lymphocyte development, adaptive and innate immune responses, and autoimmunity, as well as recent efforts to develop pharmacological inhibitors of ion channels for immunomodulatory therapy. © 2015 by Annual Reviews. All rights reserved.


Olmstead A.L.,University of California at Davis | Rhode P.W.,University of Michigan
Proceedings of the National Academy of Sciences of the United States of America | Year: 2011

The Intergovernmental Panel on Climate Change projects that temperatures in the major grain-growing areas of North America will rise by 3-4 °C by 2100. Such abrupt changes will create major challenges, significantly altering the area suitable for wheat. The historical record offers insight into the capability of agriculture to adapt to climatic challenges. Using a new county-level dataset on wheat production and climate norms, we show that during the 19th and 20th centuries North American grain farmers pushed wheat production into environments once considered too arid, too variable, and too harsh to cultivate. As summary measures, the median annual precipitation norm of the 2007 distribution of North American wheat production was one-half that of the 1839 distribution, and the median annual temperature norm was 3.7 °C lower. This shift, which occurred mostly before 1929, required new biological technologies. The Green Revolution associated with the pioneering work of Norman Borlaug represented an important advance in this longer process of biological innovation. However, well before the Green Revolution, generations of North American farmers overcame significant climatic challenges.


Duleba A.J.,University of California at Davis
Steroids | Year: 2012

Polycystic ovary syndrome (PCOS) is associated with metabolic derangements including insulin resistance, dyslipidemia, systemic inflammation and endothelial dysfunction. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with PCOS. Medications that have been tested in patients with PCOS include metformin, thiazolidinediones, acarbose, naltrexone, orlistat, vitamin D and statins. Metformin decreases hepatic gluconeogenesis and free fatty acid oxidation while increasing peripheral glucose uptake. Early studies in PCOS suggested that metformin indirectly reduces insulin level, dyslipidemia and systemic inflammation; however, recent placebo-controlled trials failed to demonstrate significant metabolic benefit. Thiazolidinediones act primarily by increasing peripheral glucose uptake. Most studies in PCOS have demonstrated that thiazolidinediones reduce insulin resistance; however, effects on dyslipidemia were disappointing. Use of thiazolidinediones is associated with weight gain and major complications. Acarbose reduces digestion of polysaccharides. Studies in PCOS yielded inconsistent effects of acarbose on insulin sensitivity and no significant improvement of dyslipidemia. Naltrexone reduces appetite and modulates insulin release; its use in PCOS may reduce hyperinsulinemia. Orlistat decreases absorption of dietary fats; studies in PCOS suggest beneficial effects on insulin sensitivity. Vitamin D may improve insulin sensitivity but mixed results on lipid profile in PCOS have been reported. Statins are competitive inhibitors of the key enzyme regulating the mevalonate pathway; their effects are related to reduced cholesterol production as well as anti-inflammatory and anti-oxidant properties. In women with PCOS, statins reduce hyperandrogenism, improve lipid profile and reduce systemic inflammation while the effects on insulin sensitivity are variable. Use of statins is contraindicated in pregnancy. © 2011 Elsevier Inc. All rights reserved.


Bokulich N.A.,University of California at Davis | Thorngate J.H.,Constellation Brands Inc. | Richardson P.M.,MicroTrek Inc. | Mills D.A.,University of California at Davis
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Wine grapes present a unique biogeography model, wherein microbial biodiversity patterns across viticultural zones not only answer questions of dispersal and community maintenance, they are also an inherent component of the quality, consumer acceptance, and economic appreciation of a culturally important food product. On their journey from the vineyard to the wine bottle, grapes are transformed to wine through microbial activity, with indisputable consequences for wine quality parameters. Wine grapes harbor a wide range of microbes originating from the surrounding environment, many of which are recognized for their role in grapevine health and wine quality. However, determinants of regional wine characteristics have not been identified, but are frequently assumed to stem from viticultural or geological factors alone. This study used a high-throughput, short-amplicon sequencing approach to demonstrate that regional, site-specific, and grapevariety factors shape the fungal and bacterial consortia inhabiting wine-grape surfaces. Furthermore, these microbial assemblages are correlated to specific climatic features, suggesting a link between vineyard environmental conditions and microbial inhabitation patterns. Taken together, these factors shape the unique microbial inputs to regional wine fermentations, posing the existence of nonrandom "microbial terroir" as a determining factor in regional variation among wine grapes.


Schumann C.M.,University of California at Davis
Acta neuropathologica communications | Year: 2014

BACKGROUND: Abnormal connectivity across brain regions underlies many neurological disorders including multiple sclerosis, schizophrenia and autism, possibly due to atypical axonal organization within white matter. Attempts at investigating axonal organization on post-mortem human brains have been hindered by the availability of high-quality, morphologically preserved tissue, particularly for neurodevelopmental disorders such as autism. Brains are generally stored in a fixative for long periods of time (often greater than 10 years) and in many cases, already frozen and sectioned on a microtome for histology and immunohistochemistry. Here we present a method to assess the quality and quantity of axons from long-term fixed and frozen-sectioned human brain samples to demonstrate their use for electron microscopy (EM) measures of axonal ultrastructure.RESULTS: Six samples were collected from white matter below the superior temporal cortex of three typically developing human brains and prepared for EM analyses. Five samples were stored in fixative for over 10 years, two of which were also flash frozen and sectioned on a freezing microtome, and one additional case was fixed for 3 years and sectioned on a freezing microtome. In all six samples, ultrastructural qualitative and quantitative analyses demonstrate that myelinated axons can be identified and counted on the EM images. Although axon density differed between brains, axonal ultrastructure and density was well preserved and did not differ within cases for fixed and frozen tissue. There was no significant difference between cases in axon myelin sheath thickness (g-ratio) or axon diameter; approximately 70% of axons were in the small (0.25 μm) to medium (0.75 μm) range. Axon diameter and g-ratio were positively correlated, indicating that larger axons may have thinner myelin sheaths.CONCLUSION: The current study demonstrates that long term formalin fixed and frozen-sectioned human brain tissue can be used for ultrastructural analyses. Axon integrity is well preserved and can be quantified using the methods presented here. The ability to carry out EM on frozen sections allows for investigation of axonal organization in conjunction with other cellular and histological methods, such as immunohistochemistry and stereology, within the same brain and even within the same frozen cut section.


Neale D.B.,University of California at Davis | Kremer A.,University of Bordeaux 1
Nature Reviews Genetics | Year: 2011

Over the past two decades, research in forest tree genomics has lagged behind that of model and agricultural systems. However, genomic research in forest trees is poised to enter into an important and productive phase owing to the advent of next-generation sequencing technologies, the enormous genetic diversity in forest trees and the need to mitigate the effects of climate change. Research on long-lived woody perennials is extending our molecular knowledge of complex life histories and adaptations to the environment - enriching a field that has traditionally drawn biological inference from a few short-lived herbaceous species. © 2011 Macmillan Publishers Limited. All rights reserved.


Burke A.,University of California at Davis
International Journal of Energy Research | Year: 2010

This paper focuses on ultracapacitors (electrochemical capacitors) as energy storage in vehicle applications and thus evaluates the present state-of-the-art of ultracapacitor technologies and their suitability for use in electric and hybrid drivelines of various types of vehicles. A key consideration in determining the applicability of ultracapacitors for a particular vehicle application is the proper assessment of the energy storage and power requirements. For hybrid-electric vehicles, the key issues are the useable energy requirement and the maximum pulse power at high efficiency. For a Prius size vehicle, if the useable energy storage is about 125 Wh and needed efficiency is 90-95%, analysis shown in this paper indicate that vehicles can be designed using carbon ultracapacitors (both carbon/carbon and hybrid carbon) that yield high fuel economy improvements for all driving cycles and the cost of the ultracapacitors can be competitive with lithium-ion batteries for high volume production and carbon prices of less than $20 kg-1. The use of carbon/carbon devices in micro-hybrids is particularly attractive for a control strategy (sawtooth) that permits engine operation near its maximum efficiency using only a 6 kW electric motor. Vehicle projects in transit buses and passenger cars have shown that ultracapacitors have functioned as expected and significant fuel economy improvements have been achieved that are higher than would have been possible using batteries because of the higher round-trip efficiencies of the ultracapacitors. Ultracapacitors have particular advantages for use in fuel cell powered vehicles in which it is likely they can be used without interface electronics. Development of hybrid carbon devices is continuing showing energy densities of 12 Wh kg-1 and a high efficiency power density of about 1000 W kg-1 Vehicle simulations using those devices have shown that increased power capability in such devices is needed before full advantage can be taken of their increased energy density compared with carbon/carbon devices in some vehicle applications. Energy storage system considerations indicate that combinations of ultracapacitors and advanced batteries (Wh kg-1 >200) are likely to prove advantageous in the future as such batteries are developed. This is likely to be the case in plug-in hybrids with high-power electric motors for which it may be difficult to limit the size and weight of the energy storage unit even using advanced batteries. © 2009 John Wiley & Sons, Ltd.


Fasching C.L.,University of California at Davis | Cejka P.,University of California at Davis | Kowalczykowski S.C.,University of California at Davis | Heyer W.-D.,University of California at Davis
Molecular Cell | Year: 2015

The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops. © 2015 Elsevier Inc.


Baum W.M.,University of California at Davis
Journal of the experimental analysis of behavior | Year: 2012

The concept of reinforcement is at least incomplete and almost certainly incorrect. An alternative way of organizing our understanding of behavior may be built around three concepts: allocation, induction, and correlation. Allocation is the measure of behavior and captures the centrality of choice: All behavior entails choice and consists of choice. Allocation changes as a result of induction and correlation. The term induction covers phenomena such as adjunctive, interim, and terminal behavior-behavior induced in a situation by occurrence of food or another Phylogenetically Important Event (PIE) in that situation. Induction resembles stimulus control in that no one-to-one relation exists between induced behavior and the inducing event. If one allowed that some stimulus control were the result of phylogeny, then induction and stimulus control would be identical, and a PIE would resemble a discriminative stimulus. Much evidence supports the idea that a PIE induces all PIE-related activities. Research also supports the idea that stimuli correlated with PIEs become PIE-related conditional inducers. Contingencies create correlations between "operant" activity (e.g., lever pressing) and PIEs (e.g., food). Once an activity has become PIE-related, the PIE induces it along with other PIE-related activities. Contingencies also constrain possible performances. These constraints specify feedback functions, which explain phenomena such as the higher response rates on ratio schedules in comparison with interval schedules. Allocations that include a lot of operant activity are "selected" only in the sense that they generate more frequent occurrence of the PIE within the constraints of the situation; contingency and induction do the "selecting."


Bowlus C.L.,University of California at Davis | Gershwin M.E.,University of California at Davis
Autoimmunity Reviews | Year: 2014

Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by the immune mediated destruction of small intrahepatic bile duct epithelial cells leading to cholestasis and cirrhosis. The autoimmune basis of PBC is supported by the highly specific anti-mitochondrial antibodies (AMAs) and autoreactive T cells, the former being the basis for diagnosis in the vast majority of cases. Although a rare disease, the incidence rates of PBC have been increasing, possibly due to increased testing and diagnosis as opposed to a true increase in disease incidence. Presently, most cases are asymptomatic and only suspected based upon routine liver tests. Those with symptoms typically complain of pruritus and fatigue. The diagnosis of PBC is based on the presence of at least 2 of 3 key criteria including a persistently elevated serum alkaline phosphatase, the presence of serum AMAs, and liver histology consistent with PBC. Anti-nuclear antibodies specific to PBC are useful in cases in which AMAs are not detected and may indicate a more aggressive course. Ursodeoxycholic acid is the only proven therapy for PBC and in most cases can delay or prevent disease progression. However, a subgroup of patients does not adequately respond to ursodeoxycholic acid and for whom new therapies are needed. © 2014 Elsevier B.V.


Leache A.D.,University of California at Davis | Rannala B.,University of California at Davis
Systematic Biology | Year: 2011

Numerous simulation studies have investigated the accuracy of phylogenetic inference of gene trees under maximum parsimony, maximum likelihood, and Bayesian techniques. The relative accuracy of species tree inference methods under simulation has received less study. The number of analytical techniques available for inferring species trees is increasing rapidly, and in this paper, we compare the performance of several species tree inference techniques at estimating recent species divergences using computer simulation. Simulating gene trees within species trees of different shapes and with varying tree lengths (T) and population sizes (θ), and evolving sequences on those gene trees, allows us to determine how phylogenetic accuracy changes in relation to different levels of deep coalescence and phylogenetic signal. When the probability of discordance between the gene trees and the species tree is high (i.e., T is small and/or θ is large), Bayesian species tree inference using the multispecies coalescent (BEST) outperforms other methods. The performance of all methods improves as the total length of the species tree is increased, which reflects the combined benefits of decreasing the probability of discordance between species trees and gene trees and gaining more accurate estimates for gene trees. Decreasing the probability of deep coalescences by reducing θ also leads to accuracy gains for most methods. Increasing the number of loci from 10 to 100 improves accuracy under difficult demographic scenarios (i.e., coalescent units ≤ 4Ne), but 10 loci are adequate for estimating the correct species tree in cases where deep coalescence is limited or absent. In general, the correlation between the phylogenetic accuracy and the posterior probability values obtained from BEST is high, although posterior probabilities are overestimated when the prior distribution for θ is misspecified. © 2011 The Author(s).


Van Rompay K.K.A.,University of California at Davis
AIDS Research and Human Retroviruses | Year: 2012

Several nonhuman primate models are used in HIV/AIDS research. In contrast to natural host models, infection of macaques with virulent simian immunodeficiency virus (SIV) isolates results in a disease (simian AIDS) that closely resembles HIV infection and AIDS. Although there is no perfect animal model, and each of the available models has its limitations, a carefully designed study allows experimental approaches that are not feasible in humans, but that can provide better insights in disease pathogenesis and proof-of-concept of novel intervention strategies. In the early years of the HIV pandemic, nonhuman primate models played a minor role in the development of antiviral strategies. Since then, a better understanding of the disease and the development of better compounds and assays to monitor antiviral effects have increased the usefulness and relevance of these animal models in the preclinical development of HIV vaccines, microbicides, and antiretroviral drugs. Several strategies that were first discovered to have efficacy in nonhuman primate models are now increasingly used in humans. Recent trends include the use of nonhuman primate models to explore strategies that could reduce viral reservoirs and, ultimately, attempt to cure infection. Ongoing comparison of results obtained in nonhuman primate models with those observed in human studies will lead to further validation and improvement of these animal models so they can continue to advance our scientific knowledge and guide clinical trials. © Copyright 2012, Mary Ann Liebert, Inc.


Pu L.L.Q.,University of California at Davis
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2012

Background: Even though fat grafting has become widely used by plastic surgeons, most surgeons choose their method of fat grafting based almost entirely on anecdotal evidence. As more and more scientific studies appear in the literature, we now may have more objective, scientific evidence to support the use of specific techniques. Methods: The author critically reviewed all studies related to fat grafting research in the last 20 years in the English literature. To better summarize the findings of the studies, the fat grafting procedure was arbitrarily divided into 4 essential parts to determine the best donor sites and how the fat grafts should be harvested, processed, and placed. Results: While most studies show no difference in the viability of fat grafts harvested from different donor sites, one study shows that more adipose-derived stem cells (ADSCs) are found within the fat grafts harvested from the lower abdomen or inner thigh. Fat grafts harvested with syringe aspiration and processed with centrifugation at 1200 g for 3 min clearly have better viability. In addition, viable adipocytes and ADSCs as well as growth factors can be concentrated within the fat grafts after proper centrifugation. The studies also reinforce the principle that fat grafts, once placed, should have a maximal amount of contact with the vascularized tissue in the recipient site for better survival. Conclusions: Most scientific studies in fat grafting research support a more rationalized technique that should be selected by surgeons for fat grafting. The technique includes proper selection of donor sites, proper harvest and process of fat grafts, and proper placement of fat grafts. © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.


Mikulincer M.,The Interdisciplinary Center | Shaver P.R.,University of California at Davis
World Psychiatry | Year: 2012

In recent years, attachment theory, which was originally formulated to describe and explain infant-parent emotional bonding, has been applied to the study of adolescent and adult romantic relationships and then to the study of psychological processes, such as interpersonal functioning, emotion regulation, coping with stress, and mental health. In this paper, we offer a brief overview of the attachment perspective on psychopathology. Following a brief account of attachment theory, we go on to explain how the study of individual differences in adult attachment intersects with the study of psychopathology. Specifically, we review research findings showing that attachment insecurity is a major contributor to mental disorders, and that the enhancement of attachment security can facilitate amelioration of psychopathology.


Hart B.L.,University of California at Davis
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

No other theme in animal biology seems to be more central than the concept of employing strategies to survive and successfully reproduce. In nature, controlling or avoiding pathogens and parasites is an essential fitness strategy because of the ever-present disease-causing organisms. The disease-control strategies discussed here are: physical avoidance and removal of pathogens and parasites; quarantine or peripheralization of conspecifics that could be carrying potential pathogens; herbal medicine, animal style, to prevent or treat an infection; potentiation of the immune system; and care of sick or injured group members. These strategies are seen as also encompassing the pillars of human medicine: (i) quarantine; (ii) immune-boosting vaccinations; (iii) use of medicinal products; and (iv) caring or nursing. In contrast to animals, in humans, the disease-control strategies have been consolidated into a consistent and extensive medical system. A hypothesis that explains some of this difference between animals and humans is that humans are sick more often than animals. This increase in sickness in humans leading to an extensive, cognitively driven medical system is attributed to an evolutionary dietary transition from mostly natural vegetation to a meat-based diet, with an increase in health-eroding free radicals and a dietary reduction of free-radical-scavenging antioxidants. © 2011 The Royal Society.


Minzenberg M.J.,University of California at Davis
Neurotherapeutics | Year: 2012

Summary: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder of childhood and adulthood, with a considerable impact on public health. There is a substantial pharmacopoeia available for safe and effective treatment of ADHD, and newly available agents diversify the treatment options. With the burgeoning scientific literature addressing the genetic, neurochemical, and neural systems basis for this condition, increasing attention is directed at establishing the neural basis for the efficacy of existing treatments. ADHD remains the only highly prevalent, nondegenerative neuropsychiatric disorder for which effective medications remediate the principal cognitive disturbances in concert with clinical efficacy. Therefore, deeper insight into the neural mechanisms of cognitive remediation may serve to advance treatment development not only in ADHD, but across a wide range of neuropsychiatric disorders in which cognitive dysfunction is a cardinal feature and a strong predictor of clinical outcome. To date, all effective medications for ADHD act on 1 or both of the major catecholamine neurotransmitter systems in the brain. These 2 systems, which arise from subcortical nuclei and use norepinephrine (NE) or dopamine (DA) as transmitters, exert strong modulatory effects on widely distributed cortical-subcortical neural circuits, with important effects on cognition, mood, and behavior, in both health and illness. The present review outlines the actions of ADHD medications from subcellular effects to effects on neural systems and cognition in ADHD patients. This is a very active area of investigation at all phases of the translational cycle, and near-term work is poised to firmly link cellular neuropharmacology to large-scale effects, and point the way toward advances in treatment. © 2012 The American Society for Experimental NeuroTherapeutics, Inc.


Graf Estes K.,University of California at Davis
Journal of Experimental Child Psychology | Year: 2014

The current research investigated how infants apply prior knowledge of environmental regularities to support new learning. The experiments tested whether infants could exploit experience with native language (English) phonotactic patterns to facilitate associating sounds with meanings during word learning. Infants (14-month-olds) heard fluent speech that contained cues for detecting target words; the target words were embedded in sequences that occur across word boundaries. A separate group heard the target words embedded without word boundary cues. Infants then participated in an object label learning task. With the opportunity to use native language patterns to segment the target words, infants subsequently learned the labels. Without this experience, infants failed. Novice word learners can take advantage of early learning about sounds to scaffold lexical development. © 2014 Elsevier Inc.


Shi L.-X.,University of California at Davis | Theg S.M.,University of California at Davis
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

Chloroplasts are essential organelles in the cells of plants and algae. The functions of these specialized plastids are largely dependent on the ~. 3000 proteins residing in the organelle. Although chloroplasts are capable of a limited amount of semiautonomous protein synthesis - their genomes encode ~. 100 proteins - they must import more than 95% of their proteins after synthesis in the cytosol. Imported proteins generally possess an N-terminal extension termed a transit peptide. The importing translocons are made up of two complexes in the outer and inner envelope membranes, the so-called Toc and Tic machineries, respectively. The Toc complex contains two precursor receptors, Toc159 and Toc34, a protein channel, Toc75, and a peripheral component, Toc64/OEP64. The Tic complex consists of as many as eight components, namely Tic22, Tic110, Tic40, Tic20, Tic21 Tic62, Tic55 and Tic32. This general Toc/Tic import pathway, worked out largely in pea chloroplasts, appears to operate in chloroplasts in all green plants, albeit with significant modifications. Sub-complexes of the Toc and Tic machineries are proposed to exist to satisfy different substrate-, tissue-, cell- and developmental requirements. In this review, we summarize our understanding of the functions of Toc and Tic components, comparing these components of the import machinery in green algae through trees. We emphasize recent findings that point to growing complexities of chloroplast protein import process, and use the evolutionary relationships between proteins of different species in an attempt to define the essential core translocon components and those more likely to be responsible for regulation. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. © 2012 Elsevier B.V.


Carlip S.,University of California at Davis
Journal of High Energy Physics | Year: 2011

I rederive the Kerr/CFT correspondence without first taking the near-horizon extremal Kerr limit. This method extends easily to nonextremal black holes, for which the temperature and central charge behave poorly at the horizon but the entropy remains finite. A computation yields one-half of the standard Bekenstein-Hawking entropy, with hints that the other half may be related to a conformal field theory at the inner horizon. I then present an alternative approach, based on a stretched Killing horizon, in which the full entropy is obtained and the temperature and central charge remain well-behaved even in the nonextremal case. © SISSA 2011.


Kayhanian M.,University of California at Davis
Environmental Pollution | Year: 2012

This study presents the results of lead (Pb) concentrations from both highway runoff and contaminated soil along 32 and 23 highway sites, respectively. In general, the Pb concentration on topsoil (0-15 cm) along highways was much higher than the Pb concentration in subsurface soil (15-60 cm). The Pb deposited on soil appears to be anthropogenic and a strong correlation was found between the Pb concentration in surface soil and highway runoff in urban areas. The concentration of Pb measured during 1980s from highways runoff throughout the world was up to 11 times higher than the measured values in mid 1990s and 2000s. The current Pb deposited on soil near highways appears to be a mixture of paint, tire weight balance and old leaded gasoline combustion. Overall, the Pb phase-out regulation reduced the Pb deposits in the environment and consequently lowered Pb loading into receiving waters. © 2011 Elsevier Ltd. All rights reserved.


Plant cells assemble the bipolar spindle and phragmoplast microtubule (MT) arrays in the absence of the centrosome structure. Our recent findings in Arabidopsis thaliana indicated that AUGMIN subunit3 (AUG3), a homolog of animal dim γ-tubulin 3, plays a critical role in γ-tubulin-dependent MT nucleation and amplification during mitosis. Here, we report the isolation of the entire plant augmin complex that contains eight subunits. Among them, AUG1 to AUG6 share low sequence similarity with their animal counterparts, but AUG7 and AUG8 share homology only with proteins of plant origin. Genetic analyses indicate that the AUG1, AUG2, AUG4, and AUG5 genes are essential, as stable mutations in these genes could only be transmitted to heterozygous plants. The sterile aug7-1 homozygous mutant in which AUG7 expression is significantly reduced exhibited pleiotropic phenotypes of seriously retarded vegetative and reproductive growth. The aug7-1 mutation caused delocalization of γ-tubulin in the mitotic spindle and phragmoplast. Consequently, spindles were abnormally elongated, and their poles failed to converge, as MTs were splayed to discrete positions rendering deformed arrays. In addition, the mutant phragmoplasts often had disorganized MT bundles with uneven edges. We conclude that assembly of MT arrays during plant mitosis depends on the augmin complex, which includes two plant-specific subunits.


Williams P.D.,University of California at Davis
American Naturalist | Year: 2012

Many of the standard predictions in evolutionary epidemiology result from models in which all hosts are equally susceptible to acquiring an infection and equally capable of resisting pathogens once an infection has been established. This contrasts with the empirical reality that natural host populations are typically composed of individuals with various susceptibilities and vulnerabilities to pathogen exploitation that can influence all aspects of a given pathogen's transmission-virulence phenotype. In these structured host settings, host-dependent variation in the virulence-transmission trade-off plays an important role in determining pathogen evolution. By deriving some game-theoretic equilibrium expressions that describe pathogen evolution in heterogeneous host populations, the contribution of host heterogeneity to the direction of evolution in host exploitation is made explicit. Within this framework, qualitative departures from predictions derived from theory utilizing a homogeneous host assumption can be seen as a manifestation of Simpson's paradox in an evolutionary setting. By reconsidering some predictions from homogeneous host theory through the lens of this new perspective, it can be seen that many standard predictions are actually special cases that result when homogeneity in immunity parameters is imposed on host populations. © 2011 by The University of Chicago.


Bevins C.L.,University of California at Davis
Digestive Diseases | Year: 2013

The intestinal mucosa interfaces with a complex, dense community of microorganisms, including hundreds of species of resident microbiota and many transient microbes entering from food-and water-borne sources. In the small intestine, Paneth cells (specialized secretory epithelial cells) produce abundant quantities of defensins and several other antibiotic peptides. Human Paneth cells make two defensins: HD5 and HD6. Data from in vivo models indicate that Paneth cell defensins play a pivotal role in defense from food-and water-borne pathogens in the intestine. The mechanism by which these two defensins protect from enteric pathogens is quite distinct. HD5 is a potent antimicrobial that kills target microbes by membrane disruption, whereas HD6 is newly discovered to self-assemble to form fibrils and nanonets that surround and entangle bacteria. Recent data suggest that HD5 also serves to help shape the composition of the colonizing microbiota. Studies in humans suggest that reduced expression of HD5 and HD6 is a fundamental feature of ileal Crohn's disease. Mechanistically, the link between reduced Paneth cell defensin expression and ileal Crohn's disease pathogenesis may be a result of the weakened mucosal antimicrobial defense and/or alterations in the composition of commensal microbiota. © 2013 S. Karger AG, Basel.


Kaloper N.,University of California at Davis
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We argue that if the UV cutoff of an effective field theory with many low energy degrees of freedom is of the order, or below, the scale of the stretched horizon in a black hole background, which in turn is significantly lower than the Planck scale, the black hole radiance rate may not be enhanced by the emission of all the light IR modes. Instead, there may be additional suppressions hidden in the UV completion of the field theory, which really control which light modes can be emitted by the black hole. It could turn out that many degrees of freedom cannot be efficiently emitted by the black hole, and so the radiance rate may be much smaller than its estimate based on the counting of the light IR degrees of freedom. If we apply this argument to the Randall-Sundrum II (RS2) brane world, it implies that the emission rates of the low energy conformal field theory modes will be dramatically suppressed: its UV completion is given by the bulk gravity on AdS 5×S5, and the only bulk modes which could be emitted by a black hole are the 4-dimensional (4D) s waves of bulk modes with small 5-dimensional momentum, or equivalently, small 4D masses. Further, their emission is suppressed by bulk warping, which lowers the radiation rate much below the IR estimate, yielding a radiation flux ∼(T BHL)2L Hawking∼(T BH/M Pl)2NL Hawking, where L Hawking is the Hawking radiation rate of a single light species. This follows directly from low conformal field theory cutoff μ∼L -1M Pl, a large number of modes N1 and the fact that 4D gravity in RS2 is induced, MPl2Nμ2. © 2012 American Physical Society.


Keestra-Gounder A.M.,University of California at Davis | Tsolis R.M.,University of California at Davis | Baumler A.J.,University of California at Davis
Nature Reviews Microbiology | Year: 2015

Salmonella enterica serovars are associated with an estimated 1 million deaths annually and are also useful model organisms for investigating the mechanisms of host-bacterium interactions. The insights gained from studies on non-typhoidal Salmonella (NTS) serovars have provided a fascinating overview of the mechanisms by which the innate immune system detects and responds to bacterial pathogens. However, specific virulence factors and changes in virulence gene regulation in S. enterica subsp. enterica serovar Typhi alter the innate immune responses to this pathogen. In this Review, we compare and contrast the interactions of S. Typhi and NTS serovars with host innate immune receptors and discuss why the disease manifestations associated with S. Typhi infection differ considerably from those associated with the closely related NTS serovars. © 2015 Macmillan Publishers Limited.


Idrissa I.M.,University of California at Davis
Earthquake Spectra | Year: 2014

An empirical model for estimating the horizontal pseudo-absolute spectral accelerations (PSA) generated by shallow crustal earthquakes was published in 2008 using the recorded earthquake ground motion data collected and documented as part of the original Next Generation Attenuation (NGA) project. A significant number of additional recordings were collected over the past three years, and the 2008 model has been revised using the new data and is presented in this paper. The model was again selected to be simple, and the model parameters were estimated using the expanded database. The revised model incorporates VS30as an independent variable because, with the expanded database, it was found that VS30was required to be included as an independent parameter to allow for a reasonably unbiased fit to the recorded data. It is noted that VS30is not being used to account for nonlinear site response, but strictly to allow for a better fit to the data. These parameters are presented for sites with an average shear wave velocity in the upper 30 m, VS30, for sites with VS30≥ 450 m/s. Parameters for sites with VS30< 450 m/s are not included in this paper. For a site with VS30= 450 m/s, there is an overall increase in PGA averaging about 50% over a distance of about 100 km using the 2013 model in comparison to the 2008 model. On the other hand, for a site with VS30= 900 m/s, there is an overall decrease of about 10% using the 2013 model in comparison to the 2008 model. © 2014, Earthquake Engineering Research Institute.


Van Doorn W.G.,University of California at Davis
Journal of Experimental Botany | Year: 2011

Relatively little is known about programmed cell death (PCD) in plants. It is nonetheless suggested here that tonoplast rupture and the subsequent rapid destruction of the cytoplasm can distinguish two large PCD classes. One class, which is here called 'autolytic', shows this feature, whilst the second class (called 'non-autolytic') can include tonoplast rupture but does not show the rapid cytoplasm clearance. Examples of the 'autolytic' PCD class mainly occur during normal plant development and after mild abiotic stress. The 'non-autolytic' PCD class is mainly found during PCD that is due to plant-pathogen interactions. Three categories of PCD are currently recognized in animals: apoptosis, autophagy, and necrosis. An attempt is made to reconcile the recognized plant PCD classes with these groups. Apoptosis is apparently absent in plants. Autophagic PCD in animals is defined as being accompanied by an increase in the number of autophagosomes, autolysosomes, and small lytic vacuoles produced by autolysosomes. When very strictly adhering to this definition, there is no (proof for) autophagic PCD in plants. Upon a slightly more lenient definition, however, the 'autolytic' class of plant PCD can be merged with the autophagic PCD type in animal cells. The 'non-autolytic' class of plant PCD, as defined here, can be merged with necrotic PCD in animals. © 2011 The Author.


Karban R.,University of California at Davis
Functional Ecology | Year: 2011

1. Induced resistance is now widely accepted as a potent and widespread ecological force although several pieces of the story remain very poorly known. Theory predicts that induced defences should be favoured in variable environments especially when plants can use cues to reliably predict future conditions; however, this idea has not been seriously evaluated for plants. 2.Theory also predicts that plastic, induced defences should be favoured over permanent, constitutive defences if defences are costly and not always needed. This hypothesis has received considerable attention and limited support; resource allocation costs have been difficult to detect although ecological costs of defence may be more common. Recently, priming has emerged as a mechanism that may further reduce costs. Primed plants do not immediately produce the gene products associated with induced resistance but later respond more rapidly and strongly to severe or repeated attacks. It remains to be determined how common priming is. 3.Much of what we know about induced resistance is from the herbivore's point of view. Induced resistance will be beneficial from the plant's point of view if herbivores avoid induced plants, but the behavioural responses of herbivores to induced plant variation are still poorly studied. 4.Recent progress in understanding the detailed spatial and temporal extent of induced resistance has improved our appreciation of the phenomenon. Although some induced responses are systemic throughout entire plant individuals, many others have been found to be localized to damaged tissues. Plant vascular architecture and transpiration rates greatly constrain the distribution of vascular cues. Some plants rely on volatile cues that are active over relatively short distances and may be subject to eavesdropping by other plants, herbivores, and carnivores. Similarly, the temporal duration of induced responses may have important consequences on effectiveness although limited information is available concerning lag times before induction and relaxation times following induction. 5.Limited spatial and temporal scales of induced responses make plants more variable from the herbivore's point of view. Recent work suggests that plant heterogeneity may be difficult for herbivores to cope with although this hypothesis awaits further empirical testing. © 2010 The Author. Functional Ecology © 2010 British Ecological Society.


Cummings B.P.,University of California at Davis
Diabetes, Obesity and Metabolism | Year: 2013

There is a pressing need for new effective therapeutic strategies for addressing the epidemic of type 2 diabetes. Leptin has been shown to reduce hyperglycaemia in rodent models of type 1 diabetes and has recently been shown to normalize fasting plasma glucose concentrations in a rodent model of polygenic obesity and type 2 diabetes. Overall, these findings suggest that leptin may be an effective therapeutic option for both type 1 and type 2 diabetes. However, short-term human clinical studies in overweight and obese patients with recently diagnosed type 2 diabetes have reported minimal efficacy of leptin administration to lower blood glucose levels. Herein, the role of leptin in the maintenance of glucose homeostasis and the potential use of leptin in the treatment of type 2 diabetes are discussed. © 2012 Blackwell Publishing Ltd.


Pang D.,University of California at Davis
Neurosurgery | Year: 2010

OBJECTIVE: Atlantoaxial rotatory fixation (AARF) remains a recondite entity. Our normative study using CT motion analysis shows that there is a high degree of concordance for rotational behavior of C1 and C2 in children 0 to 18 years. C1 always crosses C2 at or near 0 degree. The predictable relationship between C1 and C2 is depicted by 3 distinct regions on the motion curve: when C1 rotates from 0 to 23 degrees, it moves alone while C2 remains stationary at 0 (the single-motion phase). When C1 rotates from 24 to 65 degrees, C1 and C2 move together (the double-motion phase), but C1 always moves faster as C2 is being pulled by yoking ligaments. From 65 degrees onward, C1 and C2 move in unison (the unison-motion phase) with a fixed, maximal separation angle of approximately 43 degrees, the head rotation being carried exclusively by the subaxial segments. Because of this high concordance among patients and a relatively narrow variance from the mean, the physiological composite motion curve can be used as a normal template for the diagnosis and classification of AARF. METHODS: Using a 3-position CT protocol to obtain the diagnostic motion curve, we identified 3 distinct types of AARF. Type I AARF patients show essentially unaltered ("locked") C1-C2 coupling regardless of corrective counterrotation, with curves that are horizontal lines in the upper 2 quadrants of the template. Type II AARF patients show reduction of the C1-C2 separation angle with forced correction, but C1 cannot be made to cross C2. Their curves slope downward from the right to left upper quadrants but never traverse the x axis. Type III AARF patients show C1-C2 crossover but only when the head is cranked far to the opposite side. Their motion curves traverse the x axis far left of 0 degree ( C1 < -20). Thus, type I, II, and III AARF are in descending degrees of pathological stickiness. A fourth group of patients showing motion curve features between normal and type III AARF are designated as belonging to a diagnostic gray zone (DGZ). The AARF patients are further classified as acute if treatment is started less than 1 month from the onset of symptoms, as subacute if the delay in treatment is 1 to 3 months, and chronic if treatment delay exceeds 3 months. The treatment protocol for AARF consists of reduction using either halter or caliper traction and then immobilization with brace or halo, depending on the AARF type and chronicity. Recurrent slippage and irreducibility are treated with C1-C2 fusion. RESULTS: The treatment course and outcome of AARF are analyzed according to the AARF type and chronicity. The difficulty and duration of treatment, the number of recurrent slippage, the rate of irreducibility, the need for halo and fusion, and the percentage ultimately losing normal C1-C2 rotation are significantly greater in type I patients than type III patients, with type II patients somewhere in between. Likewise, all parameters are much worse in patients with any type of chronic AARF than acute AARF. The worse subgroup is chronic type I versus the best subgroup of acute type III. Recurrent AARF patients do much worse than nonrecurrent AARF patients. Recurrence is, in turn, adversely influenced by both the severity (type) and chronicity of AARF. The symptoms of most DGZ patients will resolve with analgesics, but a few remain symptomatic or deteriorate to true AARF requiring the full treatment. CONCLUSION: Thus, children with painful torticollis should undergo the 3-position CT protocol not only to confirm the diagnosis of AARF but also to grade its severity. Closed reduction with traction should be instituted immediately to avoid the serious consequences of chronicity. Proper typing and reckoning of the pretreatment delay are requisites for selecting treatment modalities. Recurrent dislocation and incomplete reduction should be treated with posterior C1-C2 fusion in the best achievable alignment. Copyright © 2010 by the Congress of Neurological Surgeons.


Ralston K.S.,University of California at Davis
Trends in Parasitology | Year: 2015

Entamoeba histolytica was named 'histolytica' (from histo-, 'tissue'; lytic-, 'dissolving') for its ability to destroy host tissues. Direct killing of host cells by the amoebae is likely to be the driving factor that underlies tissue destruction, but the mechanism was unclear. We recently showed that, after attaching to host cells, amoebae bite off and ingest distinct host cell fragments, and that this contributes to cell killing. We review this process, termed 'amoebic trogocytosis' (. trogo-, 'nibble'), and how this process interplays with phagocytosis, or whole cell ingestion, in this organism. 'Nibbling' processes have been described in other microbes and in multicellular organisms. The discovery of amoebic trogocytosis in E. histolytica may also shed light on an evolutionarily conserved process for intercellular exchange. © 2015 Elsevier Ltd.


Wingfield J.C.,University of California at Davis
Frontiers in Neuroendocrinology | Year: 2015

The Earth has always been a changeable place but now warming trends shift seasons and storms occur with greater frequency, intensity and duration. This has prompted reference to the modern era as the Anthropocene caused by human activity. This era poses great challenges for all life on earth and important questions include why and how some organisms can cope and others cannot? It is of heuristic value to consider a framework for types of environmental signals and how they might act. This is especially important as predictable changes of the environment (seasonality) are shifting rapidly as well as unpredictable changes (perturbations) in novel ways. What we need to know is how organisms perceive their environment, transduce that information into neuroendocrine signals that orchestrate morphological, physiological and behavioral responses. Given these goals we can begin to address the questions: do neuroendocrine systems have sufficient flexibility to acclimate to significant change in phenology, are genetic changes leading to adaptation necessary, or both? © 2014 Elsevier Inc.


Recent documentation of a few compelling examples of sympatric speciation led to a proliferation of theoretical models. Unfortunately, plausible examples from nature have rarely been used to test model predictions, such as the initial presence of strong disruptive selection. Here I estimated the form and strength of selection in two classic examples of sympatric speciation: radiations of Cameroon cichlids restricted to Lakes Barombi Mbo and Ejagham. I measured five functional traits and relative growth rates in over 500 individuals within incipient species complexes from each lake. Disruptive selection was prevalent in both groups on single and multivariate trait axes but weak relative to stabilizing selection on other traits and most published estimates of disruptive selection. Furthermore, despite genetic structure, assortative mating, and bimodal species- diagnostic coloration, trait distributions were unimodal in both species complexes, indicating the earliest stages of speciation. Long waiting times or incomplete sympatric speciation may result when disruptive selection is initially weak. Alternatively, I present evidence of additional constraints in both species complexes, including weak linkage between coloration and morphology, reduced morphological variance aligned with nonlinear selection surfaces, and minimal ecological divergence. While other species within these radiations show complete phenotypic separation, morphological and ecological divergence in these species complexes may be slow or incomplete outside optimal parameter ranges, in contrast to rapid divergence of their sexual coloration. © 2012 by The University of Chicago.


Nguyen H.H.,University of California at Davis | Kurth M.J.,University of California at Davis
Organic Letters | Year: 2013

A variety of N-aryl β-nitroenamines were effectively transformed into 3-nitroindoles in good yields and with complete regioselectivity via a rapid microwave (μW) assisted intramolecular arene-alkene coupling reaction. This report further demonstrates the versatility of this method by constructing 3-carboalkoxy-and 3-cyanoindoles. Optimization data, substrate scope, and applications are discussed. © 2012 American Chemical Society.


Lonnerdal B.,University of California at Davis
American Journal of Clinical Nutrition | Year: 2014

Human milk contains an abundance of biologically active components that are highly likely to contribute to the short- and long-term benefits of breastfeeding. Many of these components are proteins; this article describes some of these proteins, such as α-lactalbumin, lactoferrin, osteopontin, and milk fat globule membrane proteins. The possibility of adding their bovine counterparts to infant formula is discussed as well as the implications for infant health and development. An important consideration when adding bioactive proteins to infant formula is that the total protein content of formula needs to be reduced, because formula-fed infants have significantly higher concentrations of serum amino acids, insulin, and blood urea nitrogen than do breastfed infants. When reducing the protein content of formula, the amino acid composition of the formula protein becomes important because serum concentrations of the essential amino acids should not be lower than those in breastfed infants. Both the supply of essential amino acids and the bioactivities of milk proteins are dependent on their digestibility: some proteins act only in intact form, others act in the form of larger or small peptides formed during digestion, and some are completely digested and serve as a source of amino acids. The purity of the proteins or protein fractions, potential contaminants of the proteins (such as lipopolysaccharide), as well as the degree of heat processing used during their isolation also need to be considered. It is likely that there will be more bioactive components added to infant formulas in the near future, but guidelines on how to assess their bioactivities in vitro, in animal models, and in clinical studies need to be established. The extent of testing needed is likely going to depend on the degree of complexity of the components and their bioequivalence with the human compounds whose effects they are intended to mimic. © 2014 American Society for Nutrition.


Ullrich P.A.,University of California at Davis
Quarterly Journal of the Royal Meteorological Society | Year: 2014

This article provides an intercomparison of the dispersive and diffusive properties of several standard numerical methods applied to the 1D linearized shallow-water equations without the Coriolis term, including upwind and central finite-volume, spectral finite-volume, discontinuous Galerkin, spectral element, and staggered finite-volume. All methods are studied up to tenth-order accuracy, where possible. A consistent framework is developed which allows for direct intercomparison of the ability of these methods to capture the behaviour of linear gravity waves. The Courant-Friedrichs-Lewy (CFL) condition is also computed, which is important for gauging the stability of these methods, and leads to a measure of approximate equal error cost. The goal of this work is threefold: first, to determine the shortest wavelength which can be considered 'resolved' for a particular method; second, to determine the effect of increasing the order of accuracy on the ability of a method to capture wave-like motion; and third, to determine which numerical methods offer the best treatment of wave-like motion. © 2013 Royal Meteorological Society.


Species distribution models are usually evaluated with cross-validation. In this procedure evaluation statistics are computed from model predictions for sites of presence and absence that were not used to train (fit) the model. Using data for 226 species, from six regions, and two species distribution modeling algorithms (Bioclim and MaxEnt), I show that this procedure is highly sensitive to "spatial sorting bias": the difference between the geographic distance from testing-presence to training-presence sites and the geographic distance from testing-absence (or testing-background) to training-presence sites. I propose the use of pairwise distance sampling to remove this bias, and the use of a null model that only considers the geographic distance to training sites to calibrate cross-validation results for remaining bias. Model evaluation results (AUC) were strongly inflated: the null model performed better than MaxEnt for 45% and better than Bioclim for 67% of the species. Spatial sorting bias and area under the receiver-operator curve (AUC) values increased when using partitioned presence data and random-absence data instead of independently obtained presence-absence testing data from systematic surveys. Pairwise distance sampling removed spatial sorting bias, yielding null models with an AUC close to 0.5, such that AUC was the same as null model calibrated AUC (cAUC). This adjustment strongly decreased AUC values and changed the ranking among species. Cross-validation results for different species are only comparable after removal of spatial sorting bias and/or calibration with an appropriate null model. © 2012 by the Ecological Society of America.


Montanez I.P.,University of California at Davis | Poulsen C.J.,University of Michigan
Annual Review of Earth and Planetary Sciences | Year: 2013

The late Paleozoic icehouse was the longest-lived ice age of the Phanerozoic, and its demise constitutes the only recorded turnover to a greenhouse state. This review summarizes evidence for the timing, extent, and behavior of continental ice on Pangea in addition to the climate and ecosystem response to repeated transitions between glacial and interglacial conditions. Combined empirical and climate modeling studies argue for a dynamic ice age characterized by discrete periods of glaciation separated by periods of ice contraction during intermittent warmings, moderate-size ice sheets emanating from multiple ice centers throughout southern Gondwana, possible glaciation of the Northern Hemisphere, and atmospheric CO2 as a primary driver of both ice sheet and climate variability. The glacioeustatic response to fluctuations of these smaller ice sheets was likely less extreme than previously suggested. Modeling studies, stratigraphic relationships, and changes in both the geographic patterns and community compositions of marine fauna and terrestrial flora indicate the potential for strong responses to high-latitude glacial conditions in both ocean circulation and low-latitude climate. The forcings and feedbacks of these linkages, as well as existing climate paradoxes, define research targets for future studies of the late Paleozoic. © Copyright ©2013 by Annual Reviews. All rights reserved.


Zhang S.,University of California at Davis | Pan N.,University of California at Davis
Advanced Energy Materials | Year: 2015

The performance of a supercapacitor can be characterized by a series of key parameters, including the cell capacitance, operating voltage, equivalent series resistance, power density, energy density, and time constant. To accurately measure these parameters, a variety of methods have been proposed and are used in academia and industry. As a result, some confusion has been caused due to the inconsistencies between different evaluation methods and practices. Such confusion hinders effective communication of new research findings, and creates a hurdle in transferring novel supercapacitor technologies from research labs to commercial applications. Based on public sources, this article is an attempt to inventory, critique and hopefully streamline the commonly used instruments, key performance metrics, calculation methods, and major affecting factors for supercapacitor performance evaluation. Thereafter the primary sources of inconsistencies are identified and possible solutions are suggested, with emphasis on device performance vs. material properties and the rate dependency of supercapacitors. We hope, by using reliable, intrinsic, and comparable parameters produced, the existing inconsistencies and confusion can be largely eliminated so as to facilitate further progress in the field. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Fischer R.C.,University of Graz | Power P.P.,University of California at Davis
Chemical Reviews | Year: 2010

A review of the study titled 'π-bonding and the lone pair effect in multiple bonds between heavier main group elements', focusing on the synthesis, structure, and bonding of stable compounds of heavier main group elements, is presented. It is found that the red aluminum derivative is generated in solution by a reduction process and this highly reactive molecule undergoes rapid cyclization in toluene. The parent metal amides and related derivatives are prepared by photolysis of Al, Ga, or In atoms and isolated in NH 3-doped frozen argon matrixes. The first experimental evidence for a transiently formed silicon-carbon double bond was depicted through pyrolysis of 1,1-dimethyl-1-silacyclobutane, forming 1,1-dimethylsilene as a transient intermediate. The trisila-allene is characterized by short Si-Si distances of 2.179(3) and 2.206(3) Å, in contrast to the lighter homologues which display a strictly linear arrangement of a bent trisila array.


Cappa C.D.,University of California at Davis | Wilson K.R.,Lawrence Berkeley National Laboratory
Atmospheric Chemistry and Physics | Year: 2012

A new model of secondary organic aerosol (SOA) formation is developed that explicitly takes into account multi-generational oxidation as well as fragmentation of gas-phase compounds, and assumes equilibrium gas-particle partitioning. The model framework requires specification of a limited number of tunable parameters to describe the kinetic evolution of SOA mass, the average oxygen-to-carbon atomic ratio and the mean particle volatility as oxidation proceeds. These parameters describe (1) the relationship between oxygen content and volatility, (2) the probability of fragmentation and (3) the amount of oxygen added per reaction. The time-evolution and absolute value of the simulated SOA mass depends sensitively on all tunable parameters. Of the tunable parameters, the mean O : C is most sensitive to the oxygen/volatility relationship, exhibiting only a weak dependence on the other relationships. The model mean particle O : C produced from a given compound is primarily controlled by the number of carbon atoms comprising the SOA precursor, with some sensitivity to the specified oxygen/volatility relationship. The model is tested against laboratory measurements of time-dependent SOA formation from the photooxidation of α-pinene and n-pentadecane and performs well (after tuning). The model can also accurately simulate the carbon-number dependence of aerosol yields previously observed for oxidation of straight-chain alkanes. This model may provide a generalized framework for the interpretation of laboratory SOA formation experiments in which explicit consideration of multiple-generations of products is required, which is true for all photo-oxidation experiments. © 2012 Author(s).


Kamel S.J.,University of California at Davis | Grosberg R.K.,University of California at Davis
Ecology Letters | Year: 2012

Males exhibit striking variation in the degree to which they invest in offspring, from merely provisioning females with sperm, to providing exclusive post-zygotic care. Paternity assurance is often invoked to explain this variation: the greater a male's confidence of paternity, the more he should be willing to provide care. Here, we report a striking exception to expectations based on paternity assurance: despite high levels of female promiscuity, males of a marine snail provide exclusive, and costly, care of offspring. Remarkably, genetic paternity analyses reveal cuckoldry in all broods, with fewer than 25% of offspring being sired by the caring male, although caring males sired proportionally more offspring in a given clutch than any other fathers did individually. This system presents the most extreme example of the coexistence of high levels of female promiscuity, low paternity, and costly male care, and emphasises the still unresolved roles of natural and sexual selection in the evolution of male parental care. © 2012 Blackwell Publishing Ltd/CNRS.


Nolin D.A.,University of California at Davis
Evolution and Human Behavior | Year: 2012

Costly signaling has been proposed as a possible mechanism to explain food sharing in foraging populations. This sharing-as-signaling hypothesis predicts an association between sharing and status. Using exponential random graph modeling, this prediction is tested on a social network of between-household food-sharing relationships in the fishing and sea-hunting village of Lamalera, Indonesia. Previous analyses (Nolin, 2010. Food-sharing networks in Lamalera, Indonesia: reciprocity, kinship, and distance. Human Nature 21, 243-268) have shown that most sharing in Lamalera is consistent with reciprocal altruism. The question addressed here is whether any additional variation may be explained as sharing-as-signaling by high-status households. The results show that high-status households both give and receive more than other households, a pattern more consistent with reciprocal altruism than costly signaling. However, once the propensity to reciprocate and household productivity are controlled, households of men holding leadership positions show greater odds of unreciprocated giving when compared to households of nonleaders. This pattern of excessive giving by leaders is consistent with the sharing-as-signaling hypothesis. Wealthy households show the opposite pattern, giving less and receiving more than other households. These households may reciprocate in a currency other than food, or their wealth may attract favor-seeking behavior from others. Overall, status covariates explain little variation in the sharing network as a whole, and much of the sharing observed by high-status households is best explained by the same factors that explain sharing by other households. This pattern suggests that multiple mechanisms may operate simultaneously to promote sharing in Lamalera and that signaling may motivate some sharing by some individuals even within sharing regimes primarily maintained by other mechanisms. © 2012 Elsevier Inc.


Day H.W.,University of California at Davis
American Mineralogist | Year: 2012

The transition from diamond to graphite is a key equilibrium for interpreting ultrahigh-pressure metamorphic rocks. Despite widespread interest, there remain significant systematic differences between the best available experimental determinations of P and T (Kennedy and Kennedy 1976) and numerous thermodynamic calculations of the transition. At temperatures below 1400 K, calculated equilibrium pressures are lower than extrapolations of the experiments by as much as 5 kbar. At 3000 K, calculated pressures vary from more than 8 kbar above to almost 20 kbar below the position of the extrapolated transition. A revised curve based on a critical review of the experimental and thermodynamic data is consistent with expanded experimental brackets and the preferred calorimetric data. It is steeper than the transition proposed by Kennedy and Kennedy (1976) and previous calculations and passes through 16.2 kbar, 298 K; 33.9 kbar, 1000 K; 63.5 kbar, 2000 K; and 98.4 kbar, 3000 K. The revised curve implies that the minimum pressure for formation of diamond-bearing crustal rocks is 3-4 kbar less than implied by extrapolation of the experiments. Because the revised transition is steeper than most previous calculations, the triple point among graphite, diamond, and liquid carbon may be as much as 40 kbar higher than previously estimated.


Leache A.D.,University of California at Davis
Molecular Phylogenetics and Evolution | Year: 2010

Spiny lizards (genus Sceloporus) represent one of the most diverse and species rich clades of squamate reptiles in continental North America. Sceloporus contains 90+ species, which are partitioned into 21 species groups containing anywhere from one to 15 species. Despite substantial progress towards elucidating the phylogeographic patterns for many species of Sceloporus, efforts to resolve the phylogenetic relationships among the major species groups remain limited. In this study, the phylogenetic relationships of 53 species of Sceloporus, representing all 21 species groups, are estimated based on four nuclear genes (BDNF, PNN, R35, RAG-1; >3.3 kb) and contrasted with a new mitochondrial DNA genealogy based on six genes (12S, ND1, ND4, and the histidine, serine, and leucine tRNA genes; >2.5 kb). Species trees estimated from the nuclear loci using data concatenation or a coalescent-based inference method result in concordant topologies, but the coalescent approach provides lower resolution and support. When comparing nuclear versus mtDNA-based topologies for Sceloporus species groups, conflicting relationships outnumber concordant relationships. Incongruence is not restricted to weak or unresolved nodes as might be expected under a scenario of rapid diversification, but extends to conflicts involving strongly support clades. The points of concordance and conflict between the nuclear and mtDNA data are discussed, and arguments for preferring the species trees estimated from the multilocus nuclear data are presented. © 2009 Elsevier Inc. All rights reserved.


Tapley E.C.,University of California at Davis
Current opinion in cell biology | Year: 2013

The nuclear-cytoskeleton connection influences many aspects of cellular architecture, including nuclear positioning, the stiffness of the global cytoskeleton, and mechanotransduction. Central to all of these processes is the assembly and function of conserved SUN-KASH bridges, or LINC complexes, that span the nuclear envelope. Recent studies provide details of the higher order assembly and targeting of SUN proteins to the inner nuclear membrane. Structural studies characterize SUN-KASH interactions that form the central link of the nuclear-envelope bridge. KASH proteins at the outer nuclear membrane link the nuclear envelope to the cytoskeleton where forces are generated to move nuclei. Significantly, SUN proteins were recently shown to contribute to the progression of laminopathies. Copyright © 2012 Elsevier Ltd. All rights reserved.


Allard J.,University of California at Davis
Current opinion in cell biology | Year: 2013

Much of current understanding of cell motility arose from studying steady treadmilling of actin arrays. Recently, there have been a growing number of observations of a more complex, non-steady, actin behavior, including self-organized waves. It is becoming clear that these waves result from activation and inhibition feedbacks in actin dynamics acting on different scales, but the exact molecular nature of these feedbacks and the respective roles of biomechanics and biochemistry are still unclear. Here, we review recent advances achieved in experimental and theoretical studies of actin waves and discuss mechanisms and physiological significance of wavy protrusions. Copyright © 2012 Elsevier Ltd. All rights reserved.


Kinnally E.L.,University of California at Davis
American Journal of Physical Anthropology | Year: 2014

Early life stress has been linked with poorer lifelong health outcomes across species, including modern and ancient humans. Epigenetic mechanisms, such as DNA methylation patterning of stress pathway genes in stress-responsive tissue, may play an important role in the long-term health effects of early stress across species. The relationships among early maternal care quality, DNA methylation patterns in a candidate stress pathway gene (serotonin transporter, 5-HTT) linked region in blood DNA, and adult health outcomes were examined in male and female rhesus macaques, excellent models of human health. Male (n512) and female (n532) infants were observed with their mothers for the first 12 weeks of life and 5-HTT linked DNA methylation was measured in blood at 12 weeks of age. Approximately 8 years later, health-related measures were collected for the 25 animals (6 male and 19 female) that were available for study. Health composite scores were generated using factor analysis of body condition, body weight, and diagnosis of diarrhea during the lifespan. Better quality maternal care predicted lower 5-HTT linked methylation at 12 weeks of age. Lower 5-HTT methylation, in turn, predicted better health composite scores in adulthood, including better body condition, greater body weight and absence of lifetime diarrhea. These data suggest that the epigenetic regulation of 5- HTT may be one biomarker of the link between early stress and lifetime health trajectories. Future studies will examine whether epigenetic signatures in modern and ancient human DNA lends insight into stress and health and natural selection in human evolutionary history. Am J Phys Anthropol 155:192-199, 2014. © 2014 WILEY PERIODICALS, INC.


Huang L.,University of California at Davis | Tepaamorndech S.,University of California at Davis
Molecular Aspects of Medicine | Year: 2013

Two families of zinc (Zn2 +) transporters are involved in zinc homeostasis in the body, SLC30 (ZnT, zinc transporter) and SLC39 (ZIP, Zinc(Zn2+)-Iron(Fe2+) Permease). The two zinc transporter family members function in opposite directions to maintain cellular zinc homeostasis. ZnT proteins contribute to the cytoplasmic zinc balance by exporting zinc out to the extracellular space or by sequestrating cytoplasmic zinc into intracellular compartments when cellular zinc levels are elevated. In contrast, ZIP proteins function to increase cytoplasmic zinc concentrations when cellular zinc is depleted. Since the cloning of the first zinc transporter (ZnT1) in 1995, there have been many advances in zinc transporter research including discovery of new members of zinc transporters, identification of gene expression patterns and regulations, recognition of protein distribution patterns in tissues and cells, and understanding of their physiological and pathological roles in humans and animal models. Ten members of the ZnT family have been identified so far. Here we give a review of these advances and discuss the pathological implications and future preventive or therapeutic applications of ZnTs. © 2012 Elsevier Ltd. All rights reserved.


Filiault D.L.,University of California at Davis | Maloof J.N.,University of California at Davis
PLoS Genetics | Year: 2012

Shade avoidance is an ecologically and molecularly well-understood set of plant developmental responses that occur when the ratio of red to far-red light (R:FR) is reduced as a result of foliar shade. Here, a genome-wide association study (GWAS) in Arabidopsis thaliana was used to identify variants underlying one of these responses: increased hypocotyl elongation. Four hypocotyl phenotypes were included in the study, including height in high R:FR conditions (simulated sun), height in low R:FR conditions (simulated shade), and two different indices of the response of height to low R:FR. GWAS results showed that variation in these traits is controlled by many loci of small to moderate effect. A known PHYC variant contributing to hypocotyl height variation was identified and lists of significantly associated genes were enriched in a priori candidates, suggesting that this GWAS was capable of generating meaningful results. Using metadata such as expression data, GO terms, and other annotation, we were also able to identify variants in candidate de novo genes. Patterns of significance among our four phenotypes allowed us to categorize associations into three groups: those that affected hypocotyl height without influencing shade avoidance, those that affected shade avoidance in a height-dependent fashion, and those that exerted specific control over shade avoidance. This grouping allowed for the development of explicit hypotheses about the genetics underlying shade avoidance variation. Additionally, the response to shade did not exhibit any marked geographic distribution, suggesting that variation in low R:FR-induced hypocotyl elongation may represent a response to local conditions. © 2012 Filiault, Maloof.


Scholey J.M.,University of California at Davis
Annual Review of Cell and Developmental Biology | Year: 2013

Kinesin-2 was first purified as a heterotrimeric, anterograde, microtubule-based motor consisting of two distinct kinesin-related subunits and a novel associated protein (KAP) that is currently best known for its role in intraflagellar transport and ciliogenesis. Subsequent work, however, has revealed diversity in the oligomeric state of different kinesin-2 motors owing to the combinatorial heterodimerization of its subunits and the coexistence of both heterotrimeric and homodimeric kinesin-2 motors in some cells. Although the functional significance of the homo- versus heteromeric organization of kinesin-2 motor subunits and the role of KAP remain uncertain, functional studies suggest that cooperation between different types of kinesin-2 motors or between kinesin-2 and a member of a different motor family can generate diverse patterns of anterograde intracellular transport. Moreover, despite being restricted to ciliated eukaryotes, kinesin-2 motors are now known to drive diverse transport events outside cilia. Here, I review the organization, assembly, phylogeny, biological functions, and motility mechanism of this diverse family of intracellular transport motors. © 2013 by Annual Reviews. All rights reserved.


Epanchin-Niell R.S.,University of California at Davis | Hastings A.,University of California at Davis
Ecology Letters | Year: 2010

We review studies that address economically optimal control of established invasive species. We describe three important components for determining optimal invasion management: invasion dynamics, costs of control efforts and a monetary measure of invasion damages. We find that a management objective that explicitly considers both costs and damages is most appropriate for determining economically optimal strategies, but also leads to large challenges due to uncertainty in components of the management problem. To address uncertainty, some studies have included stochasticity in their models; others have quantified the value of information or focused on decision-making with limited information. Our synthesis shows how invasion characteristics, such as costs, damages, pattern of spread and invasion and landscape size, affect optimal control strategies and goals in systematic ways. We find that even for simple questions, such as whether control should be applied at the centre of an invasion or to satellite patches, the answer depends on the details of a particular invasion. Future work should seek to better quantify key components of this problem, determine best management in the face of limited information, improve understanding of spatial aspects of invasion control and design approaches to improve the feasibility of achieving regional control goals. © 2010 Blackwell Publishing Ltd/CNRS.


Krimmel B.A.,University of California at Davis | Pearse I.S.,Cornell University
Ecology Letters | Year: 2013

Plant-provided foods for predatory arthropods such as extrafloral nectar and protein bodies provide indirect plant defence by attracting natural enemies of herbivores, enhancing top-down control. Recently, ecologists have also recognised the importance of carrion as a food source for predators. Sticky plants are widespread and often entrap and kill small insects, which we hypothesised would increase predator densities and potentially affect indirect defence. We manipulated the abundance of this entrapped insect carrion on tarweed (Asteraceae: Madia elegans) plants under natural field conditions, and found that carrion augmentation increased the abundance of a suite of predators, decreased herbivory and increased plant fitness. We suggest that entrapped insect carrion may function broadly as a plant-provided food for predators on sticky plants. © 2012 Blackwell Publishing Ltd/CNRS.


Dalrymple L.S.,University of California at Davis
Clinical Journal of the American Society of Nephrology | Year: 2013

Background and objectives Kidney disease is associatedwith physiologic changes thatmay predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. Design, setting, participants, & measurements CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFRcys). Secondary analyses examined eGFR using serum creatinine (eGFRSCr). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. Results Themean age was 75 years and themedian eGFRcys was 73ml/min per 1.73m2.Among participantswith an eGFRcys <45 ml/min per 1.73 m2, 24% had prevalent frailty. In multivariable analysis and compared with eGFRcys≥90 ml/min per 1.73m2, eGFRcys categories of 45-59 (odds ratio [OR], 1.80; 95%confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFRcys categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFRSCr were not associated with higher risk of prevalent or incident frailty. Conclusions In community-dwelling elders, lower eGFRcys was associated with a higher risk of prevalent and incident frailtywhereas lower eGFRSCr was not. These findings highlight the importance of considering non-GFR determinants of kidney function. © 2013 by the American Society of Nephrology.


Reisen W.K.,University of California at Davis
Annual Review of Entomology | Year: 2010

Landscape epidemiology describes how the temporal dynamics of host, vector, and pathogen populations interact spatially within a permissive environment to enable transmission. The spatially defined focus, or nidus, of transmission may be characterized by vegetation as well as by climate, latitude, elevation, and geology. The ecological complexity, dimensions, and temporal stability of the nidus are determined largely by pathogen natural history and vector bionomics. Host populations, transmission efficiency, and therefore pathogen amplification vary spatially, thereby creating a heterogeneous surface that may be defined by remote sensing and statistical tools. The current review describes the evolution of landscape epidemiology as a science and exemplifies selected aspects by contrasting the ecology of two different recent disease outbreaks in North America caused by West Nile virus, an explosive, highly virulent mosquito-borne virus producing ephemeral nidi, and Borrelia burgdorferi, a slowly amplifying chronic pathogen producing semipermanent nidi. © 2010 by Annual Reviews All rights reserved.


Cranston P.S.,University of California at Davis
Annual Review of Entomology | Year: 2010

Australasia, which consists of Australia and the adjacent islands of the southwestern Pacific Ocean, has an insect diversity approximately proportional to the land mass. This diversity is distinctive, with some major groups missing and others having radiated. Iconic species are familiar to most people living in Australia and New Zealand, and a range of insects once contributed to Aboriginal Australian culture and diet. Conservation of Australasian entomological biodiversity is an increasing challenge for contemporary scientists. Examples are provided of insect conservation schemes from New Guinea, New Zealand, and Australia. Funding for insect biodiversity studies beyond flagship species is needed. © 2010 by Annual Reviews All rights reserved.


Flytzani-Stephanopoulos M.,Tufts University | Gates B.C.,University of California at Davis
Annual Review of Chemical and Biomolecular Engineering | Year: 2012

Our aim in this review is to assess key recent findings that point to atomically dispersed noble metals as catalytic sites on solid supports, which may be viewed as ligands bonded to the metal. Both zeolites and open metal oxide supports are considered; the former offer the advantages of uniform, crystalline structures to facilitate fundamental understanding, and the latter offer numerous advantages in applications. The notion of strong interactions between metals and supports has resurfaced in the recent literature to explain how subnanometer clusters and even atoms of noble metals such as platinum and gold survive under often harsh reaction conditions on some supports, such as ceria and perovskites. Individual cations of platinum, palladium, rhodium, or other metals anchored to supports through MO bonds can be formed on these supports in configurations that are stable and catalytically active for several reactions illustrated here, notably, oxidation and reduction. The development of effective synthesis methods and the identification of suitable stabilizers and promoters are expected to lead to the increasing application of atomically dispersed noble metal catalysts for practical processes characterized by efficient resource utilization and cost savings. Copyright © 2012 by Annual Reviews. All rights reserved.


Altermatt F.,University of California at Davis
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

Climate change is altering geographical ranges, population dynamics and phenologies of many organisms. For ectotherms, increased ambient temperatures frequently have direct consequences for metabolic rates, activity patterns and developmental rates. Consequently, in many insect species both an earlier beginning and prolongation of seasonal duration occurred in parallel with recent global warming. However, from an ecological and evolutionary perspective, the number of generations (voltinism) and investment into each generation may be even more important than seasonality, since an additional generation per unit time may accelerate population growth or adaptation. Using a dataset extending back to the mid-nineteenth century, I report changes in the voltinism of butterfly and moth species of Central Europe. A significant proportion of 263 multi-voltine species showed augmented frequency of second and subsequent generations relative to the first generation in a warm period since 1980, and 44 species even increased the number of generations after 1980. Expected ecological consequences are diverse. Since multi-voltinism has been linked to insect outbreaks they include an increase in the abundance of herbivorous pests of agriculture and forestry. However, disruption of the developmental synchrony associated with multi-voltinism and host plant phenology may also reduce fitness, potentially having unexpected consequences for species of conservation concern. The ability of species to adapt evolutionarily to a changing environment may be facilitated by increased voltinism. © 2009 The Royal Society.


Caro T.,University of California at Davis | Sherman P.W.,Cornell University
Trends in Ecology and Evolution | Year: 2011

Behavioural ecologists often see little connection between the current conservation crisis and the future of their discipline. This view is myopic because our abilities to investigate and interpret the adaptive significance and evolutionary histories of behaviours are increasingly being compromised in human-dominated landscapes because of species extinctions, habitat destruction, invasive species, pollution, and climate change. In this review, we argue that many central issues in behavioural ecology will soon become prohibitively difficult to investigate and interpret, thus impeding the rapid progress that characterizes the field. To address these challenges, behavioural ecologists should design studies not only to answer basic scientific questions but also to provide ancillary information for protection and management of their study organisms and habitats, and then share their biological insights with the applied conservation community. © 2010 Elsevier Ltd.


Green R.,University of California at Davis
American Journal of Clinical Nutrition | Year: 2011

Deficiencies of folate or of vitamin B-12 are widespread and constitute a major global burden of morbidity that affect all age groups. Detecting or confirming the presence of folate or vitamin B-12 deficiency and distinguishing one from the other depends, ultimately, on laboratory testing. Tests to determine the presence of folate or vitamin B-12 deficiency are used singly or in combination to establish the nutritional status and prevalence of deficiencies of the vitamins in various populations. The efficacy of interventions through the use of fortification or supplements is monitored by using the same laboratory tests. Tests currently in use have limitations that can be either technical or have a biological basis. Consequently, each single test cannot attain perfect sensitivity, specificity, or predictive value. Laboratory indicators of vitamin B-12 or folate status involve the measurement of either the total or a physiologically relevant fraction of the vitamin in a compartment such as blood. Thus, assays to measure vitamin B-12 or folate in plasma or serum as well as folate in red blood cells are in widespread use, and more recently, methods to measure vitamin B-12 associated with the plasma binding protein transcobalamin (holotranscobalamin) have been developed. Alternatively, concentrations of surrogate biochemical markers that reflect the metabolic function of the vitamin can be used. Surrogates most commonly used are plasma homocysteine, for detection of either vitamin B-12 or folate deficiency, and methylmalonic acid for detection of vitamin B-12 deficiency. The general methods as well as their uses, indications, and limitations are presented. © 2011 American Society for Nutrition.


Jessoe K.,University of California at Davis
Journal of Environmental Economics and Management | Year: 2013

This paper tests the hypothesis that the expansion of improved drinking water supplies in rural India reduced household expenditure on water quality, offsetting some of the quality benefits from source protection. I estimate demand for in-home treatment using geological characteristics to predict a household's drinking water source. The probability of treatment and in particular boiling reduces by 18-27 percentage points in response to source protection, offsetting 4% of the water quality gains and saving households 0.5-1% in monthly expenditure. Behavioral choices partly counteract the water quality gains from source protection. © 2013 Elsevier Inc.


Hong Y.J.,University of California at Davis | Tantillo D.J.,University of California at Davis
Nature Chemistry | Year: 2014

Selectivity in chemical reactions that form complex molecular architectures from simpler precursors is usually rationalized by comparing competing transition-state structures that lead to different possible products. Herein we describe a system for which a single transition-state structure leads to the formation of many isomeric products via pathways that feature multiple sequential bifurcations. The reaction network described connects the pimar-15-en-8-yl cation to miltiradiene, a tricyclic diterpene natural product, and isomers via cyclizations and/or rearrangements. The results suggest that the selectivity of the reaction is controlled by (post-transition-state) dynamic effects, that is, how the carbocation structure changes in response to the distribution of energy in its vibrational modes. The inherent dynamical effects revealed herein (characterized through quasiclassical direct dynamics calculations using density functional theory) have implications not only for the general principles of selectivity prediction in systems with complex potential energy surfaces, but also for the mechanisms of terpene synthase enzymes and their evolution. These findings redefine the challenges faced by nature in controlling the biosynthesis of complex natural products. © 2014 Macmillan Publishers Limited. All rights reserved.


Harskamp C.T.,University of California at Davis
Seminars in cutaneous medicine and surgery | Year: 2013

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin condition that is associated with immune dysregulation and epidermal barrier dysfunction. The imbalance of the Th2 and Th1 pathways and their associated cytokines in AD presents as one facet of the pathogenic mechanisms. Changes in the T-cell populations and the associated cytokines during the acute and chronic phases of AD can cause variations in disease presentations and treatment responses. Continued discoveries in the immunopathogenesis of AD provide optimism for the development of efficacious therapeutic agents. Novel immunomodulatory therapies include apremilast, dupilumab, IL-37, omalizumab, rituximab, mepolizumab, infliximab, allergen-specific immunotherapy, Mycobacterium vaccae, and leflunomide. These agents serve as examples of how modulation in immunopathogenesis of AD can lead to therapeutic discoveries.


Natural killer (NK) cells express inhibitory receptors with varied binding affinities to specific major histocompatibility complex class I (MHC-I) haplotypes. NK cells can be classified as licensed or unlicensed based on their ability or inability to bind MHC-I, respectively. The role of donor vs host MHC on their development after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not known. Following reciprocal MHC-disparate allogeneic transplants and during de novo NK-cell recovery, depletion of the licensed and not unlicensed population of NK cells as determined by the licensing patterns of donor MHC-I haplotypes, resulted in significantly increased susceptibility to murine cytomegalovirus (MCMV) infection. A corresponding expansion of the licensed Ly49H(+) NK cells occurred with greater interferon γ production by these cells than unlicensed NK cells in the context of donor MHC-I. Thus, NK licensing behavior to MCMV corresponds to the donor, and not recipient, MHC haplotype after allo-HSCT in mice.


Govindan K.,University of California at Davis | Mohapatra P.,University of California at Davis
IEEE Communications Surveys and Tutorials | Year: 2012

Trust is an important aspect of mobile adhoc networks (MANETs). It enables entities to cope with uncertainty and uncontrollability caused by the free will of others. Trust computations and management are highly challenging issues in MANETs due to computational complexity constraints, and the independent movement of component nodes. This prevents the direct application of techniques suited for other networks. In MANETs, an untrustworthy node can wreak considerable damage and adversely affect the quality and reliability of data. Therefore, analyzing the trust level of a node has a positive influence on the confidence with which an entity conducts transactions with that node. In this work we present a detailed survey on various trust computing approaches that are geared towards MANETs. We highlight the summary and comparisons of these approaches. In addition, we analyze various works on trust dynamics including trust propagation, prediction and aggregation algorithms, the influence of network dynamics on trust dynamics and the impact of trust on security services. © 1998-2012 IEEE.


Cajka T.,University of California at Davis | Fiehn O.,University of California at Davis
TrAC - Trends in Analytical Chemistry | Year: 2014

Liquid chromatography-mass spectrometry (LC-MS)-based lipidomics has undergone dramatic developments over the past decade. This review focuses on state of the art in LC-MS-based lipidomics, covering all the steps of global lipidomic profiling.By reviewing 185 original papers and application notes, we can conclude that current advanced LC-MS-based lipidomics methods involve:. (1)lipid extraction schemes using chloroform/MeOH or methyl tert-butyl ether (MTBE)/MeOH, both with addition of internal standards covering each lipid class;(2)LC separation of lipids using short microbore C18 or C8 columns with sub-2-μm or 2.6-2.8-μm (fused-core) particle size with analysis time <30 min;(3)electrospray ionization in positive- and negative-ion modes with full spectra acquisition using high-resolution MS with capability to MS/MS.Phospholipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, phosphatidylglycerols) followed by sphingomyelins, di- and tri-acylglycerols, and ceramides were the most frequently targeted lipid species. © 2014 Elsevier B.V.


Schwartz M.W.,University of California at Davis
Biological Conservation | Year: 2012

Conservation science strives to inform management decisions. Applying niche models in concert with future climate projections to project species vulnerability to extinction, range size loss, or distribution shifts has emerged as a potentially useful tool for informing resource management decisions. Making climate change niche modeling useful to conservation decisions requires centering studies on the types of decisions that are made regarding the focal taxa of a niche model study. Recent recommendations for climate adaptation strategies suggest four types of decision makers: policy, habitat protection, habitat management, species management. Targeting research to questions relevant for management decisions will increase utility of a niche model study. Constraints to the accuracy and precision of niche models to project potential future distributions are well-recognized. How to incorporate these uncertainties into management decision-making remains a challenge. Refining estimates and making sound management recommendations is critical because species that are generally modeled to be the most vulnerable to climate change (i.e., narrow endemics), are also the most vulnerable to bad decisions based on uncertain models. I review uncertainties of niche models to assert that there is an inherent bias for models to over-estimate climate-driven vulnerability to extirpation. Explicit recognition of this bias leads to a decision framework that accommodates unbalanced uncertainty. Namely, niche models may be more useful for identifying conservation opportunities identifying newly available habitats under changing climate than they are for asserting where current habitat will no longer exist under future climate states. © 2012 Elsevier Ltd.


Weare B.C.,University of California at Davis
Climate Dynamics | Year: 2013

Teleconnections associated with warm El Niño/southern oscillation (ENSO) events in 20 climate model intercomparison project 5 (CMIP5) models have been compared with reanalysis observations. Focus has been placed on compact time and space indices, which can be assigned a specific statistical confidence. Nearly all of the models have surface temperature, precipitation and 250 hPa geopotential height departures in the Tropics that are in good agreement with the observations. Most of the models also have realistic anomalies of Northern Hemisphere near-surface temperature, precipitation and 500 hPa geopotential height. Model skill for these variables is significantly related to the ability of a model to accurately simulate Tropical 250 hPa height departures. Additionally, most models have realistic temperature and precipitation anomalies over North America, which are linked to a model's ability to simulate Tropical 250 hPa and Northern Hemisphere 500 hPa height departures. The skills of temperature and precipitation departures over the Northern Hemisphere and North America are associated with the ability to realistically simulate realistic ENSO frequency and length. Neither horizontal nor vertical resolution differences for either the model atmosphere or ocean are significantly related at the 95 % level to variations in El Niño simulation quality. Overall, recent versions of earlier models have improved in their ability to simulate El Niño teleconnections. For instance, the average model skills of temperature and precipitation for the Tropics, Northern Hemisphere and North America for 11 CMIP5 models are all larger than those for prior versions. © 2012 Springer-Verlag Berlin Heidelberg.


Cacioppo J.T.,University of Chicago | Cacioppo S.,University of Chicago | Capitanio J.P.,University of California at Davis | Cole S.W.,University of California at Los Angeles
Annual Review of Psychology | Year: 2015

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter of a century. Although the focus of research has been on objective social roles and health behavior, the brain is the key organ for forming, monitoring, maintaining, repairing, and replacing salutary connections with others. Accordingly, population-based longitudinal research indicates that perceived social isolation (loneliness) is a risk factor for morbidity and mortality independent of objective social isolation and health behavior. Human and animal investigations of neuroendocrine stress mechanisms that may be involved suggest that (a) chronic social isolation increases the activation of the hypothalamic pituitary adrenocortical axis, and (b) these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se. The relational factors and neuroendocrine, neurobiological, and genetic mechanisms that may contribute to the association between perceived isolation and mortality are reviewed. © 2015 by Annual Reviews. All rights reserved.


Nguyen H.H.,University of California at Davis
Clinical Infectious Diseases | Year: 2010

The cost of health care in the United States continues to increase as an aging population places increasing demands on institutions providing health care. Moreover, despite increases in the complexity and cost of health care, reimbursement for some services has been reduced or denied. Thus, the current challenge at many hospitals throughout the United States is to deliver high-quality health care while maximizing resource use and reducing costs without compromising clinical outcomes. We describe an answer to the challenge that combines 2 emerging treatment models in an academic setting: hospital-based physicians and outpatient parenteral antimicrobial therapy. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Louie A.,University of California at Davis
Chemical Reviews | Year: 2010

The design and challenges in multimodality imaging techniques are studied. One of the conceptually simplest approaches to generating multimodal contrast agents is to encapsulate more than one type of contrast agent into the aqueous phase of liposomes. Each approach relies on some method to disperse the lipid in a solution, typically after drying the lipids, so that the lipids may self-assemble into various forms of lipid spheres with aqueous centers. Tissue penetration can be achieved by modifying the lipid composition to one that allows uptake by cells or fusion to cell membranes and release of core contents. In addition to the use of synthetic lipids to form liposomal carriers, multimodal probes have been constructed by loading multiple types of probes to a naturally occurring lipoprotein vehicle, including low-density lipoprotein (LDL) 20 and high density lipoproteins (HDL). One of the most active areas of multimodality probe research has been in nanomaterials, which have proven to lend themselves well to the mixing required to generate multimodal functionality.


Hagiwara N.,University of California at Davis
Developmental Dynamics | Year: 2011

Approximately 20,000 genes are encoded in our genome, one tenth of which are thought to be transcription factors. Considering the complexity and variety of cell types generated during development, many transcription factors likely play multiple roles. Uncovering the versatile roles of Sox6 in vertebrate development sheds some light on how an organism efficiently utilizes the limited resources of transcription factors. The structure of the Sox6 gene itself may dictate its functional versatility. First, Sox6 contains no known regulatory domains; instead, it utilizes various cofactors. Second, Sox6 has a long 3'-UTR that contains multiple microRNA targets, thus its protein level is duly adjusted by cell type-specific microRNAs. Just combining these two characteristics alone makes Sox6 extremely versatile. To date, Sox6 has been reported to regulate differentiation of tissues of mesoderm, ectoderm, and endoderm origins, making Sox6 a truly multifaceted transcription factor. © 2011 Wiley-Liss, Inc.


Amaral D.G.,University of California at Davis
Brain Research | Year: 2011

The last decade has seen an enormous growth in the quantity of research directed at understanding the biological underpinnings of autism spectrum disorders. This increase has been spurred on, in part, by research funding provided through private, parent advocacy groups. While increased funding and entry into autism research by scientists from many disciplines has facilitated the speed of discoveries germane to establishing the etiologies of autism, there remain a number of roadblocks to understanding autism sufficiently well to foster new treatments. This short article provides a brief overview of some of the achievements and some of the difficulties in conducting autism research. © 2010 Elsevier B.V. All rights reserved.


Al-Bassam J.,University of California at Davis | Chang F.,Columbia University
Trends in Cell Biology | Year: 2011

The molecular mechanisms by which microtubule-associated proteins (MAPs) regulate the dynamic properties of microtubules (MTs) are still poorly understood. We review recent advances in our understanding of two conserved families of MAPs, the XMAP215/Dis1 and CLASP family of proteins. In vivo and in vitro studies show that XMAP215 proteins act as microtubule polymerases at MT plus ends to accelerate MT assembly, and CLASP proteins promote MT rescue and suppress MT catastrophe events. These are structurally related proteins that use conserved TOG domains to recruit tubulin dimers to MTs. We discuss models for how these proteins might use these individual tubulin dimers to regulate dynamic behavior of MT plus ends. © 2011 Elsevier Ltd.


Marcin J.P.,University of California at Davis
Pediatric Clinics of North America | Year: 2013

Telemedicine technologies involve real-time, live, interactive video and audio communication and allow pediatric critical care physicians to have a virtual presence at the bedside of any critically ill child. Telemedicine use is increasing and will be a common technology in remote emergency departments, inpatient wards, and pediatric intensive care units. There is mounting data that demonstrate that the use of telemedicine technologies can result in higher quality of care, more efficient resource use and improved cost-effectiveness, and higher satisfaction among patients, parents, and remote providers compared to current models of care. © 2013 Elsevier Inc.


Ronald P.,University of California at Davis
Genetics | Year: 2011

The United States and the world face serious societal challenges in the areas of food, environment, energy, and health. Historically, advances in plant genetics have provided new knowledge and technologies needed to address these challenges. Plant genetics remains a key component of global food security, peace, and prosperity for the foreseeable future. Millions of lives depend upon the extent to which crop genetic improvement can keep pace with the growing global population, changing climate, and shrinking environmental resources. While there is still much to be learned about the biology of plant-environment interactions, the fundamental technologies of plant genetic improvement, including crop genetic engineering, are in place, and are expected to play crucial roles in meeting the chronic demands of global food security. However, genetically improved seed is only part of the solution. Such seed must be integrated into ecologically based farming systems and evaluated in light of their environmental, economic, and social impacts-the three pillars of sustainable agriculture. In this review, I describe some lessons learned, over the last decade, of how genetically engineered crops have been integrated into agricultural practices around the world and discuss their current and future contribution to sustainable agricultural systems. © 2011 by the Genetics Society of America.


Moore P.F.,University of California at Davis
Veterinary Pathology | Year: 2014

Histiocytic proliferative disorders are commonly observed in dogs and less often cats. Histiocytic disorders occur in most of the dendritic cell (DC) lineages. Canine cutaneous histiocytoma originates from Langerhans cells (LCs) indicated by expression of CD1a, CD11c/CD18, and E-cadherin. When histiocytomas occur as multiple lesions in skin with optional metastasis to lymph nodes and internal organs, the disease resembles cutaneous Langerhans cell histiocytosis of humans. Langerhans cell disorders do not occur in feline skin. Feline pulmonary LCH has been recognized as a cause of respiratory failure due to diffuse pulmonary infiltration by histiocytes, which express CD18 and E-cadherin and contain Birbeck's granules. In dogs and cats, histiocytic sarcomas (HS) arise from interstitial DCs that occur in most tissues of the body. Histiocytic sarcomas begin as localized lesions, which rapidly disseminate to many organs. Primary sites include spleen, lung, skin, brain (meninges), lymph node, bone marrow, and synovial tissues of limbs. An indolent form of localized HS, progressive histiocytosis, originates in the skin of cats. Hemophagocytic HS originates in splenic red pulp and bone marrow macrophages in dogs and cats. In dogs, histiocytes in hemophagocytic HS express CD11d/CD18, which is a leuko-integrin highly expressed by macrophages in splenic red pulp and bone marrow. Canine reactive histiocytic diseases, systemic histiocytosis (SH) and cutaneous histiocytosis, are complex inflammatory diseases with underlying immune dysregulation. The lesions are dominated by activated interstitial DCs and lymphocytes, which invade vessel walls and extend as vasocentric infiltrates in skin, lymph nodes, and internal organs (SH). © The Author(s) 2013.


Rustad J.R.,Corning Inc. | Casey W.H.,University of California at Davis
Nature Materials | Year: 2012

Reactions involving minerals and glasses in water are slow and difficult to probe spectroscopically but are fundamental to the performance of oxide materials in green technologies such as automotive thermoelectric power generation, CO 2 capture and storage and water-oxidation catalysis; these must be made from geochemically common elements and operate in hydrous environments. Polyoxometalate ions (POMs) have structures similar to condensed oxide phases and can be used as molecular models of the oxide/water interface. Oxygen atoms in POM exchange isotopes at different rates, but, at present, there is no basis for predicting how the coordination environment and metal substitution influences rates and mechanisms. Here we identify low-energy metastable configurations that form from the breaking of weak bonds between metals and underlying highly coordinated oxygen atoms, followed by facile hydroxide, hydronium or water addition. The mediation of oxygen exchange by these stuffed structures suggests a new view of the relationship between structure and reactivity at the oxide/solution interface. © 2012 Macmillan Publishers Limited. All rights reserved.


Morisseau C.,University of California at Davis
Biochimie | Year: 2013

Epoxide hydrolases (EH), enzymes present in all living organisms, transform epoxide-containing lipids to 1,2-diols by the addition of a molecule of water. Many of these oxygenated lipid substrates have potent biological activities: host defense, control of development, regulation of blood pressure, inflammation, and pain. In general, the bioactivity of these natural epoxides is significantly reduced upon metabolism to diols. Thus, through the regulation of the titer of lipid epoxides, EHs have important and diverse biological roles with profound effects on the physiological state of the host organism. This review will discuss the biological activity of key lipid epoxides in mammals. In addition, the use of EH specific inhibitors will be highlighted as possible therapeutic disease interventions. © 2012 Elsevier Masson SAS. All rights reserved.


Graham R.,University of California at Davis | Yu D.,University of California at Davis
Nano Letters | Year: 2012

Ultrathin colloidal lead selenide (PbSe) nanowires with continuous charge transport channels and tunable bandgap provide potential building blocks for solar cells and photodetectors. Here, we demonstrate a room-temperature hole mobility as high as 490 cm 2/(V s) in field effect transistors incorporating single colloidal PbSe nanowires with diameters of 6-15 nm, coated with ammonium thiocyanate and a thin SiO 2 layer. A long carrier diffusion length of 4.5 μm is obtained from scanning photocurrent microscopy (SPCM). The mobility is increased further at lower temperature, reaching 740 cm 2/(V s) at 139 K. © 2012 American Chemical Society.


Anacker B.L.,University of California at Davis | Strauss S.Y.,University of California at Davis
Proceedings of the Royal Society B: Biological Sciences | Year: 2014

A goal of evolutionary biology is to understand the roles of geography and ecology in speciation. The recent shared ancestry of sister species can leave a major imprint on their geographical and ecological attributes, possibly revealing processes involved in speciation. We examined how ecological similarity, range overlap and range asymmetry are related to time since divergence of 71 sister species pairs in the California Floristic Province (CFP). We found that plants exhibit strikingly different age-range correlation patterns from those found for animals; the latter broadly support allopatric speciation as the primary mode of speciation. By contrast, plant sisters in the CFP were sympatric in 80% of cases and range sizes of sisters differed by a mean of 10-fold. Range overlap and range asymmetrywere greatest in younger sisters. These results suggest that speciation mechanisms broadly grouped under 'budding' speciation, in which a larger ranged progenitor gives rise to a smaller ranged derivative species, are probably common. The ecological and reproductive similarity of sisters was significantly greater than that of sister-non-sister congeners for every trait assessed. However, shifts in at least one trait were present in 93% of the sister pairs; habitat and soil shifts were especially common. Ecological divergence did not increase with range overlap contrary to expectations under character displacement in sympatry. Our results suggest that vicariant speciation is more ubiquitous in animals than plants, perhaps owing to the sensitivity of plants to fine-scale environmental heterogeneity. Despite high levels of range overlap, ecological shifts in the process of budding speciation may result in lowrates of fine-scale spatial co-occurrence. These results have implications for ecological studies of trait evolution and community assembly; despite high levels of sympatry, sister taxa and potentially other close relatives, may be missing from local communities. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Secchi F.,University of California at Davis | Zwieniecki M.A.,University of California at Davis
Plant Physiology | Year: 2014

During their lifecycles, trees encounter multiple events of water stress that often result in embolism formation and temporal decreases in xylem transport capacity. The restoration of xylem transport capacity requires changes in cell metabolic activity and gene expression. Specifically, in poplar (Populus spp.), the formation of xylem embolisms leads to a clear up-regulation of plasma membrane protein1 (PIP1) aquaporin genes. To determine their role in poplar response to water stress, transgenic Populus tremula 3 Populus alba plants characterized by the strong down-regulation of multiple isoforms belonging to the PIP1 subfamily were used. Transgenic lines showed that they are more vulnerable to embolism, with 50% percent loss of conductance occurring 0.3 MPa earlier than in wild-type plants, and that they also have a reduced capacity to restore xylem conductance during recovery. Transgenic plants also show symptoms of a reduced capacity to control percent loss of conductance through stomatal conductance in response to drought, because they have a much narrower vulnerability safety margin. Finally, a delay in stomatal conductance recovery during the period of stress relief was observed. The presented results suggest that PIP1 genes are involved in the maintenance of xylem transport system capacity, in the promotion of recovery from stress, and in contribution to a plant's control of stomatal conductance under water stress. © 2014 American Society of Plant Biologists. All rights reserved.


Federal and state policies on eligibility to purchase and possess firearms and background check requirements for firearm transfers are undergoing intensive review and, in some cases, modification. Our objective in this third report from the Firearms Licensee Survey (FLS) is to assess support among federally licensed firearms retailers (gun dealers and pawnbrokers) for a background check requirement on all firearm transfers and selected criteria for denying the purchase of handguns based on criminal convictions, alcohol abuse, and serious mental illness. The FLS was conducted by mail during June-August, 2011 on a random sample of 1,601 licensed dealers and pawnbrokers in 43 states who were believed to sell at least 50 firearms annually. The response rate was 36.9 %, typical of establishment surveys using such methods. Most respondents (55.4 %) endorsed a comprehensive background check requirement; 37.5 % strongly favored it. Support was more common and stronger among pawnbrokers than dealers and among respondents who believed that "it is too easy for criminals to get guns." Support was positively associated with many establishment characteristics, including sales of inexpensive handguns, sales that were denied when the purchasers failed background checks, and sales of firearms that were later subjected to ownership tracing, and were negatively associated with sales at gun shows. Support for three existing and nine potential criteria for denial of handgun purchase involving criminal activity, alcohol abuse, and mental illness exceeded 90 % in six cases and fell below 2/3 in one. Support again increased with sales of inexpensive handguns and denied sales and decreased with sales of tactical (assault-type) rifles. In this survey, which was conducted prior to mass shootings in Aurora, Colorado; Oak Creek, Wisconsin; Newtown, Connecticut; and elsewhere, licensed firearm sellers exhibited moderate support for a comprehensive background check requirement and very strong support for additional criteria for denial of handgun purchases. In both cases, support was associated with the intensity of respondents' exposure to illegal activities. © 2013 The New York Academy of Medicine.


Csaki C.,Cornell University | Hubisz J.,Syracuse University | Terning J.,University of California at Davis
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2016

We consider the phenomenology of a resonance that couples to photons but not gluons, and estimate its production rate at the LHC from photon-photon fusion in elastic pp scattering using the equivalent photon and narrow width approximations. The rate is sensitive only to the mass, the spin, the total width of the resonance, and its branching fraction to photons. Production cross sections of 3-6 fb at 13 TeV can be easily accommodated for a 750 GeV resonance with partial photon width of 15 GeV. This provides the minimal explanation of the reported diphoton anomaly in the early LHC Run II data. © 2016 American Physical Society.


Myers T.W.,University of California at Davis | Berben L.A.,University of California at Davis
Journal of the American Chemical Society | Year: 2013

Activation of N-H bonds by a molecular aluminum complex via metal-ligand cooperation is described. (PhI2P2-)AlH (1b), in which PhI2P2- is a tridentate bis(imino)pyridine ligand, reacts with anilines to give the N-H-activated products (PhHI2P-)AlH(NHAr) (2). When heated, 2 releases H2 and affords (PhI2P -)Al(NHAr) (3). Complex 1b catalyzes the dehydrogenative coupling of benzylamine to afford H2, NH3, and N-(phenylmethylene) benzenemethanamine. © 2013 American Chemical Society.


Kaila K.,University of Helsinki | Price T.J.,University of Texas at Dallas | Payne J.A.,University of California at Davis | Puskarjov M.,University of Helsinki | Voipio J.,University of Helsinki
Nature Reviews Neuroscience | Year: 2014

Electrical activity in neurons requires a seamless functional coupling between plasmalemmal ion channels and ion transporters. Although ion channels have been studied intensively for several decades, research on ion transporters is in its infancy. In recent years, it has become evident that one family of ion transporters, cation-chloride cotransporters (CCCs), and in particular K + -Cl â ' cotransporter 2 (KCC2), have seminal roles in shaping GABAergic signalling and neuronal connectivity. Studying the functions of these transporters may lead to major paradigm shifts in our understanding of the mechanisms underlying brain development and plasticity in health and disease. © 2014 Macmillan Publishers Limited. All rights reserved.


Bloom A.J.,University of California at Davis
Photosynthesis Research | Year: 2015

C3 carbon fixation has a bad reputation, primarily because it is associated with photorespiration, a biochemical pathway thought to waste a substantial amount of the carbohydrate produced in a plant. This review presents evidence collected over nearly a century that (1) Rubisco when associated with Mn2+ generates additional reductant during photorespiration, (2) this reductant participates in the assimilation of nitrate into protein, and (3) this nitrate assimilation facilitates the use of a nitrogen source that other organisms tend to avoid. This phenomenon explains the continued dominance of C3 plants during the past 23 million years of low CO2 atmospheres as well as the decline in plant protein concentrations as atmospheric CO2 rises. © 2014 Springer Science+Business Media Dordrecht.


Wang I.J.,University of California at Davis
Molecular Ecology | Year: 2010

The steadily advancing fields of landscape genetics and phylogeography share many goals. However, there are some very distinct differences between these two disciplines, including the kinds of data and analyses commonly used, the timescale over which these data are informative, and the hypotheses the data are used to examine. Recently, a number of studies appear to have confused or synonymized phylogeography and landscape genetics. The difference is not merely semantic; understanding the distinctions between these fields is important for ensuring that researchers are aware of the temporal scale over which their data are informative. © 2010 Blackwell Publishing Ltd.


Rabinovitch-Deere C.A.,University of California at Davis | Oliver J.W.K.,University of California at Davis | Rodriguez G.M.,University of California at Davis | Atsumi S.,University of California at Davis
Chemical Reviews | Year: 2013

Synthetic biology has been utilized to metabolically engineer a range of microbial hosts including yeast and photoautotrophic and heterotrophic bacteria, in order to produce many types of biofuels, including long-chain alcohols, fatty acids, alka(e)nes, and isoprenoids. The general method employed in the studies cited herein to develop microbial biofuels is to characterize the enzymes, regulation, and thermodynamics of relevant native metabolic pathways and then to adjust or redesign those pathways around catalytic capabilities, cofactor pools, and other driving forces toward production of the desired compound. In some cases, overlap of production of several types of biofuels is possible from a single strategy with minor adjustments.145,155 The majority of maximal titers have been produced from engineered E. coli (Table 1), likely due to the thoroughly studied metabolism, genetic tools, and fast growth rate of the bacterium. Yields for microbial production of some advanced biofuels have achieved the levels of industrial relevance, while most are not yet encouraging for industrial scale production (Table 1). However, the proof-of-concept studies and incremental improvements in production titers indicate great possibilities. Advances in technology allowing for microbial genetic manipulation have increased exponentially over the past decade, along with understanding of enzymatic mechanisms, the driving forces behind a catalytic reaction, and especially the energetic balance required for efficient growth and production. The collective application of that information has presented a great opportunity for biologically synthesizing a range of compounds for use as chemical feedstocks74,235-237 and a wide array of biofuels. Microbes, especially bacteria, provide an ideal metabolic "factory" due to their incredible malleability and resiliency and their toolbox of evolutionarily honed central and peripheral metabolic pathways. Although more fastidious than other bacteria, photosynthetic cyanobacteria in particular offer an opportunity to generate valuable and useful products from some of the simplest and most abundant starting molecules usable by a living organism, at the same time decreasing the amount of a detrimental compound (CO2). Some impressive accomplishments in microbial synthetic biology to generate biofuels have already been achieved. However, recent studies of driving forces, activity of key enzymes,238 and energetic balance88 suggest that the full capacity for microbial biofuel production is yet to be realized.


Kliebenstein D.J.,University of California at Davis
Current Opinion in Plant Biology | Year: 2013

Secondary metabolites are essential plant fitness within the natural environment by providing defense against attacking and competing organisms including bacteria, fungi, insects, animals and other plants. These compounds' defensive function is frequently intertwined with specific accumulation in novel developmental structures. While, the biochemical community is making great strides in identifying the genetic and biochemical mechanisms that allow these chemicals to be synthesized there is vastly less progress on understanding the developmental mechanisms that is equally key to their defensive function. In this review, I briefly delve into several novel developmental structures and provide evolutionary hypothesis for how they may have evolved and how they could be unique systems for studying key developmental processes that have heretofore been recalcitrant to study. © 2012 Elsevier Ltd.


Gomes H.,University of California at Davis
Annals of Physics | Year: 2015

There exist several ways of constructing general relativity from 'first principles': Einstein's original derivation, Lovelock's results concerning the exceptional nature of the Einstein tensor from a mathematical perspective, and Hojman-Kuchař-Teitelboim's derivation of the Hamiltonian form of the theory from the symmetries of space-time, to name a few. Here I propose a different set of first principles to obtain general relativity in the canonical Hamiltonian framework without presupposing space-time in any way. I first require consistent propagation of scalar spatially covariant constraints (in the Dirac picture of constrained systems). I find that up to a certain order in derivatives (four spatial and two temporal), there are large families of such consistently propagated constraints. Then I look for pairs of such constraints that can gauge-fix each other and form a theory with two dynamical degrees of freedom per space point. This demand singles out the ADM Hamiltonian either in (i) CMC gauge, with arbitrary (finite, non-zero) speed of light, and an extra term linear in York time, or (ii) a gauge where the Hubble parameter is conformally harmonic. © 2015 Elsevier Inc.


Simonton D.K.,University of California at Davis
Perspectives on Psychological Science | Year: 2014

The persistent mad-genius controversy concerns whether creativity and psychopathology are positively or negatively correlated. Remarkably, the answer can be “both”! The debate has unfortunately overlooked the fact that the creativity-psychopathology correlation can be expressed as two independent propositions: (a) Among all creative individuals, the most creative are at higher risk for mental illness than are the less creative and (b) among all people, creative individuals exhibit better mental health than do noncreative individuals. In both propositions, creativity is defined by the production of one or more creative products that contribute to an established domain of achievement. Yet when the typical cross-sectional distribution of creative productivity is taken into account, these two statements can both be true. This potential compatibility is here christened the mad-genius paradox. This paradox can follow logically from the assumption that the distribution of creative productivity is approximated by an inverse power function called Lotka’s law. Even if psychopathology is specified to correlate positively with creative productivity, creators as a whole can still display appreciably less psychopathology than do people in the general population because the creative geniuses who are most at risk represent an extremely tiny proportion of those contributing to the domain. The hypothesized paradox has important scientific ramifications. © The Author(s) 2014.


Reed R.,University of California at Davis
Journal of Physics G: Nuclear and Particle Physics | Year: 2011

Suppression of quarkonia in heavy-ion collisions with respect to proton-proton collisions due to the Debye screening of the potential between the heavy quarks was hypothesized to be a signature of the quark-gluon plasma (QGP) (Matsui and Satz 1986 Phys. Lett. B 178 146). However, other effects besides Debye screening, such as the statistical recombination of heavy-flavor QQ̄pairs, or co-mover absorption can also affect quarkonia production in heavy-ion collisions. Quantifying the suppression of an entire family of quarkonium mesons can give us a model-dependent constraint on the temperature. The suppression of Υ can be quantified by calculating the nuclear modification factor, RAA, which is the ratio of the production in Au+Au collisions to the production in p+p scaled by the number of binary collisions. We present our results for mid-rapidity Υ(1S+2S+3S) production in p+p and Au+Au collisions at √sNN √SNN= 200 GeV. The centrality dependence of RAA will be shown for the combined Υ(1S+2S+3S) yield. © 2011 IOP Publishing Ltd.


Huang T.-K.,University of California at Davis | McDonald K.A.,University of California at Davis
Biotechnology Advances | Year: 2012

Plant cells have been demonstrated to be an attractive heterologous expression host (using whole plants and in vitro plant cell cultures) for foreign protein production in the past 20. years. In recent years in vitro liquid cultures of plant cells in a fully contained bioreactor have become promising alternatives to traditional microbial fermentation and mammalian cell cultures as a foreign protein expression platform, due to the unique features of plant cells as a production host including product safety, cost-effective biomanufacturing, and the capacity for complex protein post-translational modifications. Heterologous proteins such as therapeutics, antibodies, vaccines and enzymes for pharmaceutical and industrial applications have been successfully expressed in plant cell culture-based bioreactor systems including suspended dedifferentiated plant cells, moss, and hairy roots, etc. In this article, the current status and emerging trends of plant cell culture for in vitro production of foreign proteins will be discussed with emphasis on the technological progress that has been made in plant cell culture bioreactor systems. © 2011.


Stanhope K.L.,University of California at Davis
Annual Review of Medicine | Year: 2012

There is controversy concerning the role of sugar in the epidemics of obesity and metabolic syndrome. There is less controversy concerning the effects of fructose on components of metabolic syndrome; consumption of fructose has been shown to increase visceral adipose deposition and de novo lipogenesis (DNL), produce dyslipidemia, and decrease insulin sensitivity in older, overweight/obese subjects. This review examines the potential mechanisms of these effects of fructose and considers whether these mechanisms are relevant to the effects of consuming sucrose or high-fructose corn syrup. Evidence demonstrating that the commonly consumed sugars increase visceral adipose deposition, DNL, and insulin insensitivity is limited or inconclusive. Evidence that sugar consumption promotes development of an unfavorable lipid profile is strong and suggests that the upper added sugar consumption limit of 25% of energy or less, suggested in the Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans 2010, may merit re-evaluation. © 2012 by Annual Reviews. All rights reserved.


Sela D.A.,University of California at Davis
International Journal of Food Microbiology | Year: 2011

A promising strategy to improve health is the rational manipulation of one's beneficial microbiota via dietary interventions. This is observed in nature where specific bifidobacteria utilize human milk oligosaccharides (HMOs) that are encountered within the breast-fed infant colon. Bifidobacterium longum subsp. infantis is regarded as the archetypical HMO consumer associated with the developing neonate. This review summarizes the known molecular mechanisms underlying HMO utilization, as determined for bifidobacterial commensals. In addition, future directions of HMO research are discussed with an emphasis on physiological, ecological and clinical approaches to understand bifidobacterial utilization of this intriguing substrate. © 2011 Elsevier B.V.


Gaikwad N.W.,University of California at Davis
Free Radical Biology and Medicine | Year: 2013

Homocysteine (HCys), a sulfur-containing amino acid, is formed during the metabolism of methionine. An imbalance between the rate of production and the use of HCys during methionine metabolism can result in an increase in the plasma and urinary levels of HCys. HCys has been shown to be toxic to vascular endothelial cells through several pathways. Many earlier clinical studies have revealed an association between plasma HCys and cardiovascular and other diseases. In contrast, estrogens are suggested to lower the risk of cardiovascular disease. Several studies indicate that estrogen metabolites could be responsible for cardiovascular protection. It has been demonstrated that electrophilic estrogen quinones, E1(E2)-2,3-Q and E 1(E2)-3,4-Q, can alkylate DNA as well as form conjugates with glutathione. I hypothesize that estrogen quinones generated in situ by oxidative enzymes, metal ions, or molecular oxygen can interact with HCys to form conjugates. This in turn could lower the levels of toxic HCys as well as quenching the reactive estrogen quinones, resulting in cardiovascular protective effects. To test the feasibility of a protective estrogen-HCys pathway, estrogen quinones were treated with HCys. Tandem mass spectrometry analysis of the assay mixture shows the formation of estrogen-HCys conjugates. Furthermore, incubation of catechol estrogens with myeloperoxidase (MPO) in the presence of HCys resulted in the formation of respective estrogen-HCys conjugates. The identities of estrogen-HCys conjugates in MPO assay extracts were confirmed by comparing them to pure synthesized estrogen-HCys standards. I propose that through conjugation estrogens could chemically regulate HCys levels; moreover these conjugates could be used as potential biomarkers in determining health. © 2013 Elsevier Inc.


Schenker M.B.,University of California at Davis
American Journal of Industrial Medicine | Year: 2010

Background: Global migration has dramatically increased over the past decade and is at an all-time high, approaching 200 million persons per year. Demographics and economic interdependence suggest that immigration will continue for the near future at record high levels. Methods: A review of the few studies that have investigated occupational injury and illness rates among immigrant populations. Results: Existing data indicate that higher rates of fatal and non-fatal injuries are common compared to native populations. This increase is in part due to immigrants working in higher risk occupations (e.g., agriculture, construction), but occupational morbidity and mortality is higher among immigrants than native-born workers within occupational categories. Conclusions: Research is needed to identify the causes of increased risk among immigrants and to provide direction to effective public health interventions. Research methods must be adapted to different epidemiologic characteristics of immigrant populations, including lack of standard sampling frames, different language and culture from the dominant culture, and precarious work status. Am. J. Ind. Med. 53:329-337, 2010. © 2010 Wiley-Liss, Inc.


Knowlton A.A.,University of California at Davis | Lee A.R.,University of California at Davis
Pharmacology and Therapeutics | Year: 2012

Estrogen is a potent steroid with pleiotropic effects, which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription factor, both activating and repressing gene expression. Several different ERs regulate the specificity of response to estrogen, and appear to have specific effects in cardiac remodeling and the response to injury. However, much remains to be understood about the selectivity of these receptors and their specific effects on gene expression. Basic studies have demonstrated that estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and not shown the clear-cut benefit of more basic investigations. This can be explained in part by differences in study design: in basic studies estrogen treatment was used immediately or shortly after ovariectomy, while in some key clinical trials, estrogen was given years after menopause. Further basic research into the underlying molecular mechanisms of estrogen's actions is essential to provide a better comprehension of the many properties of this powerful hormone. © 2012 Elsevier Inc. All rights reserved.


O'Donnell M.E.,University of California at Davis
Advances in Pharmacology | Year: 2014

Blood-brain barrier (BBB) endothelial cells form a barrier that is highly restrictive to passage of solutes between blood and brain. Many BBB transport mechanisms have been described that mediate transcellular movement of solutes across the barrier either into or out of the brain. One class of BBB transporters that is all too often overlooked is that of the ion transporters. The BBB has a rich array of ion transporters and channels that carry Na, K, Cl, HCO3, Ca, and other ions. Many of these are asymmetrically distributed between the luminal and abluminal membranes, giving BBB endothelial cells the ability to perform vectorial transport of ions across the barrier between blood and brain. In this manner, the BBB performs the important function of regulating the volume and composition of brain interstitial fluid. Through functional coupling of luminal and abluminal transporters and channels, the BBB carries Na, Cl, and other ions from blood into brain, producing up to 30% of brain interstitial fluid in healthy brain. During ischemic stroke cerebral edema forms by processes involving increased activity of BBB luminal Na transporters, resulting in "hypersecretion" of Na, Cl, and water into the brain interstitium. This review discusses the roles of luminal BBB Na transporters in edema formation in stroke, with an emphasis on Na-K-Cl cotransport and Na/H exchange. Evidence that these transporters provide effective therapeutic targets for reduction of edema in stroke is also discussed, as are recent findings regarding signaling pathways responsible for ischemia stimulation of the BBB Na transporters. © 2014 Elsevier Inc.


Bremer J.,University of California at Davis
Journal of Computational Physics | Year: 2012

We describe an approach to the numerical solution of the integral equations of scattering theory on planar curves with corners. It is rather comprehensive in that it applies to a wide variety of boundary value problems; here, we treat the Neumann and Dirichlet problems as well as the boundary value problem arising from acoustic scattering at the interface of two fluids. It achieves high accuracy, is applicable to large-scale problems and, perhaps most importantly, does not require asymptotic estimates for solutions. Instead, the singularities of solutions are resolved numerically. The approach is efficient, however, only in the low- and mid-frequency regimes. Once the scatterer becomes more than several hundred wavelengths in size, the performance of the algorithm of this paper deteriorates significantly. We illustrate our method with several numerical experiments, including the solution of a Neumann problem for the Helmholtz equation given on a domain with nearly 10000 corner points. © 2011 Elsevier Inc.


Cardiff R.D.,University of California at Davis
Cold Spring Harbor perspectives in biology | Year: 2011

For over a century, mouse mammary tumor biology and the associated mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed since the first demonstration in 1984. The GEM have attracted a new generation of molecular and cellular biologists eager to apply their skill sets to these surrogates of the human disease. Newcomers often enter the field without an appreciation of the origins of mouse mammary tumor biology and the basis for many of the prevailing concepts. Our purpose in writing this compendium is to extend an "olive branch" while simultaneously deepen the knowledge of the novice mouse mammary tumor biologist as they journey into a field rich in pathology and genetics spanning several centuries.


Shi L.-X.,University of California at Davis | Theg S.M.,University of California at Davis
Plant Cell | Year: 2010

Heat shock protein 70s (Hsp70s) are encoded by a multigene family and are located in different cellular compartments. They have broad-ranging functions, including involvement in protein trafficking, prevention of protein aggregation, and assis-tance in protein folding. Hsp70s work together with their cochaperones, J domain proteins and nucleotide exchange factors (e.g., GrpEs), in a functional cycle of substrate binding and release accompanied by ATP hydrolysis. We have taken advantage of the gene targeting capability of the moss Physcomitrella patens to investigate the functions of chloroplast Hsp70s. We identified four Hsp70 genes and two GrpE cochaperone homolog genes (CGE) in moss that encode chloroplast proteins. Disruption of one of the Hsp70 genes, that for Hsp70-2, caused lethality, and protein import into heat-shocked chloroplasts isolated from temperature-sensitive hsp70-2 mutants was appreciably impaired. Whereas the double cge null mutant was not viable, we recovered a cge1 null/cge2 knock down mutant in which Hsp70-2 was upregulated. Chloroplasts isolated from this mutant demonstrated a defect in protein import. In addition, two different precursors staged as early import intermediates could be immunoprecipitated with an Hsp70-2-specific antibody. This immunoprecipitate also contained Hsp93 and Tic40, indicating that it represents a precursor still in the Toc/Tic translocon. Together, these data indicate that a stromal Hsp70 system plays a crucial role in protein import into chloroplasts. © 2010 American Society of Plant Biologists.


Matthews M.M.,University of California at Davis
Nature Structural and Molecular Biology | Year: 2016

Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Kultz D.,University of California at Davis
Physiology | Year: 2012

Organisms exposed to altered salinity must be able to perceive osmolality change because metabolism has evolved to function optimally at specific intracellular ionic strength and composition. Such osmosensing comprises a complex physiological process involving many elements at organismal and cellular levels of organization. Input from numerous osmosensors is integrated to encode magnitude, direction, and ionic basis of osmolality change. This combinatorial nature of osmosensing is discussed with emphasis on fishes. © 2012 Int. Union Physiol. Sci./Am. Physiol. Soc.


Kelt D.A.,University of California at Davis
Journal of Mammalogy | Year: 2011

Rooted in the conceptual revolutions of the 1960s and 1970s, contemporary research on the ecology of desert small mammals has progressed markedly in recent decades. Areas of particular emphasis include the role of extrinsic (e.g., climate) compared with intrinsic (e.g., density-dependence) factors on population growth and associated metrics, the role of competition compared with predation in influencing foraging decisions and habitat selection, the influence of small mammals on community structure and composition via consumption and redistribution of plant materials, and as ecological engineers and keystone species (or guilds). Recent emphasis on the energetic basis of assemblage composition is intriguing and warrants further work, and the generality of zero-sum dynamics requires further assessment. Desert systems continue to be the focus of much ecological research, and small mammals remain central figures in understanding the interplay between biotic and abiotic factors and between intrinsic and extrinsic drivers. Small mammals in deserts worldwide exemplify the importance of diverse approaches to ecological research, including local manipulative field experiments, long-term demographic monitoring, and both laboratory and field-based studies on behavioral and foraging ecology. © 2011 American Society of Mammalogists.


Hoppins S.,University of California at Davis | Nunnari J.,University of California at Davis
Science | Year: 2012

Microdomains formed by the association of the ER with mitochondria during mitochondrial division may also be used to regulate cell death.


Tantillo D.J.,University of California at Davis
Natural Product Reports | Year: 2013

Covering: up to March, 2013. This article was invited following the 2012 NPR Lectureship presented to Professor Dean Tantillo at the 21st IUPAC International Conference on Physical Organic Chemistry (ICPOC 21) This Highlight describes applications of quantum chemical calculations to problems in natural products chemistry, including the elucidation of natural product structures (distinguishing between constitutional isomers, distinguishing between diastereomers, and assigning absolute configuration) and determination of reasonable mechanisms for their formation. © 2013 The Royal Society of Chemistry.


Hess S.Y.,University of California at Davis
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2010

Deficiencies of micronutrients are highly prevalent in low-income countries. Inadequate intake of iodine impairs thyroid function and results in a spectrum of disorders. Other common deficiencies of micronutrients such as iron, selenium, vitamin A, and possibly zinc may interact with iodine nutrition and thyroid function. Randomised controlled intervention trials in iodine- and iron-deficient populations have shown that providing iron along with iodine results in greater improvements in thyroid function and volume than providing iodine alone. Vitamin A supplementation given alone or in combination with iodised salt can have a beneficial impact on thyroid function and thyroid size. Despite numerous studies of the effect of selenium on iodine and thyroid metabolism in animals, most published randomised controlled intervention trials in human populations failed to confirm an impact of selenium supplementation on thyroid metabolism. Little evidence is available on interactions between iodine and zinc metabolism. © 2009 Elsevier Ltd. All rights reserved.


Patients with immune thrombocytopenia (ITP) who relapse after an initial trial of corticosteroid treatment present a therapeutic challenge. Current guidelines recommend consideration of splenectomy, despite the known risks associated with surgery and the postsplenectomy state. To better define these risks, we identified a cohort of 9976 patients with ITP, 1762 of whom underwent splenectomy. The cumulative incidence of abdominal venous thromboembolism (AbVTE) was 1.6% compared with 1% in patients who did not undergo splenectomy; venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus) after splenectomy was 4.3% compared with 1.7% in patients who did not undergo splenectomy. There was increased risk of AbVTE early (<90 days; hazard ratio [HR] 5.4 [confidence interval (CI), 2.3-12.5]), but not late (≥90 days; HR 1.5 [CI, 0.9-2.6]) after splenectomy. There was increased risk of VTE both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on comorbidities). We conclude that ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis.


Devakul T.,Princeton University | Singh R.R.P.,University of California at Davis
Physical Review Letters | Year: 2015

We introduce the numerical linked cluster expansion as a controlled numerical tool for the study of the many-body localization transition in a disordered system with continuous nonperturbative disorder. Our approach works directly in the thermodynamic limit, in any spatial dimension, and does not rely on any finite size scaling procedure. We study the onset of many-body delocalization through the breakdown of area-law entanglement in a generic many-body eigenstate. By looking for initial signs of an instability of the localized phase, we obtain a value for the critical disorder, which we believe should be a lower bound for the true value, that is higher than current best estimates from finite size studies. This implies that most current methods tend to overestimate the extent of the localized phase due to finite size effects making the localized phase appear stable at small length scales. We also study the mobility edge in these systems as a function of energy density, and we find that our conclusion is the same at all examined energies. © 2015 American Physical Society. © 2015 American Physical Society.


Zhang H.,University of California at Davis | Ekstrom A.,University of California at Davis
Human Brain Mapping | Year: 2013

Previous studies suggest the importance of medial temporal lobe, areas of parietal cortex, and retrosplenial cortex in human spatial navigation, though the exact role of these structures in representing the relations of elements within a spatial layout ("allocentric" representation) remains unresolved. Hippocampal i