The Lawrence Berkeley National Laboratory , also known as the "Berkeley Lab", is a United States national laboratory located in the Berkeley Hills near Berkeley, California that conducts unclassified scientific research on behalf of the United States Department of Energy . It is managed and operated by the University of California, whose oldest campus, the University of California, Berkeley's main campus, it overlooks. Plans announced by the university in 2012 called for a second Berkeley Lab campus to be built on land it owns nearby at Richmond Field Station. Wikipedia.
Campisi J.,Buck Institute for Research on Aging |
Campisi J.,Lawrence Berkeley National Laboratory
Annual Review of Physiology | Year: 2013
For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. Copyright © 2013 by Annual Reviews. All rights reserved.
Zimmermann E.A.,Lawrence Berkeley National Laboratory
Nature communications | Year: 2013
Arapaima gigas, a fresh water fish found in the Amazon Basin, resist predation by piranhas through the strength and toughness of their scales, which act as natural dermal armour. Arapaima scales consist of a hard, mineralized outer shell surrounding a more ductile core. This core region is composed of aligned mineralized collagen fibrils arranged in distinct lamellae. Here we show how the Bouligand-type (twisted plywood) arrangement of collagen fibril lamellae has a key role in developing their unique protective properties, by using in situ synchrotron small-angle X-ray scattering during mechanical tensile tests to observe deformation mechanisms in the fibrils. Specifically, the Bouligand-type structure allows the lamellae to reorient in response to the loading environment; remarkably, most lamellae reorient towards the tensile axis and deform in tension through stretching/sliding mechanisms, whereas other lamellae sympathetically rotate away from the tensile axis and compress, thereby enhancing the scale's ductility and toughness to prevent fracture.
Blow M.J.,Lawrence Berkeley National Laboratory
Nature genetics | Year: 2010
Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used ChIP-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart enhancers genome wide. Compared to enhancers active in other tissues we studied at this time point, most candidate heart enhancers were less deeply conserved in vertebrate evolution. Nevertheless, transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.
Phillips C.M.,Lawrence Berkeley National Laboratory
ACS chemical biology | Year: 2011
The high cost of enzymes for saccharification of lignocellulosic biomass is a major barrier to the production of second generation biofuels. Using a combination of genetic and biochemical techniques, we report that filamentous fungi use oxidative enzymes to cleave glycosidic bonds in cellulose. Deletion of cdh-1, the gene encoding the major cellobiose dehydrogenase of Neurospora crassa, reduced cellulase activity substantially, and addition of purified cellobiose dehydrogenases from M. thermophila to the Δcdh-1 strain resulted in a 1.6- to 2.0-fold stimulation in cellulase activity. Addition of cellobiose dehydrogenase to a mixture of purified cellulases showed no stimulatory effect. We show that cellobiose dehydrogenase enhances cellulose degradation by coupling the oxidation of cellobiose to the reductive activation of copper-dependent polysaccharide monooxygenases (PMOs) that catalyze the insertion of oxygen into C-H bonds adjacent to the glycosidic linkage. Three of these PMOs were characterized and shown to have different regiospecifities resulting in oxidized products modified at either the reducing or nonreducing end of a glucan chain. In contrast to previous models where oxidative enzymes were thought to produce reactive oxygen species that randomly attacked the substrate, the data here support a direct, enzyme-catalyzed oxidation of cellulose. Cellobiose dehydrogenases and proteins related to the polysaccharide monooxygenases described here are found throughout both ascomycete and basidiomycete fungi, suggesting that this model for oxidative cellulose degradation may be widespread throughout the fungal kingdom. When added to mixtures of cellulases, these proteins enhance cellulose saccharification, suggesting that they could be used to reduce the cost of biofuel production.
Mills E.,Lawrence Berkeley National Laboratory
Science | Year: 2012
Insurance industry trends show how market-based mechanisms support climate change mitigation and adaptation.
Yano J.,Lawrence Berkeley National Laboratory |
Yachandra V.,Lawrence Berkeley National Laboratory
Chemical Reviews | Year: 2014
The current understanding of the structure of the Mn4CaO 5 cluster, as well as the water oxidation reaction based on the insights are reviewed. There are seven ligands directly ligated to the Mn 4CaO5 cluster, six carboxyl ligands (aspartate and glutamate) and one imidazole ligand (histidine). These ligands are from side chains from two domains of the D1 subunit, the interhelical CD luminal loop and the C-terminal region and one domain of CP43, the large helical EF luminal loop. Most of the ligands are arranged in a bidentate fashion bridging two metals. Simultaneous data collection of XRD and X-ray spectroscopy probes the overall protein structure from XRD and the electronic structure of the Mn 4CaO5 cluster in the oxygen-evolving complex from the spectroscopic data using the same samples under the same conditions. The use of the X-ray free electron laser (XFEL) pulses is critical for this approach.
Ritchie R.O.,Lawrence Berkeley National Laboratory
Nature Materials | Year: 2011
The attainment of both strength and toughness is a vital requirement for most structural materials; unfortunately these properties are generally mutually exclusive. Although the quest continues for stronger and harder materials, these have little to no use as bulk structural materials without appropriate fracture resistance. It is the lower-strength, and hence higher-toughness, materials that find use for most safety-critical applications where premature or, worse still, catastrophic fracture is unacceptable. For these reasons, the development of strong and tough (damage-tolerant) materials has traditionally been an exercise in compromise between hardness versus ductility. Drawing examples from metallic glasses, natural and biological materials, and structural and biomimetic ceramics, we examine some of the newer strategies in dealing with this conflict. Specifically, we focus on the interplay between the mechanisms that individually contribute to strength and toughness, noting that these phenomena can originate from very different lengthscales in a material's structural architecture. We show how these new and natural materials can defeat the conflict of strength versus toughness and achieve unprecedented levels of damage tolerance within their respective material classes. © 2011 Macmillan Publishers Limited. All rights reserved.
Biggin M.,Lawrence Berkeley National Laboratory
Developmental Cell | Year: 2011
To understand how transcription factors function, it is essential to determine the range of genes that they each bind and regulate in vivo. Here I review evidence that most animal transcription factors each bind to a majority of genes over a quantitative series of DNA occupancy levels. These continua span functional, quasifunctional, and nonfunctional DNA binding events. Factor regulatory specificities are distinguished by quantitative differences in DNA occupancy patterns. I contrast these results with models for transcription networks that define discrete sets of direct target and nontarget genes and consequently do not fully capture the complexity observed in vivo. © 2011 Elsevier Inc.
Sauter N.K.,Lawrence Berkeley National Laboratory
Journal of Synchrotron Radiation | Year: 2015
Serial crystallography, using either femtosecond X-ray pulses from free-electron laser sources or short synchrotron-radiation exposures, has the potential to reveal metalloprotein structural details while minimizing damage processes. However, deriving a self-consistent set of Bragg intensities from numerous still-crystal exposures remains a difficult problem, with optimal protocols likely to be quite different from those well established for rotation photography. Here several data processing issues unique to serial crystallography are examined. It is found that the limiting resolution differs for each shot, an effect that is likely to be due to both the sample heterogeneity and pulse-to-pulse variation in experimental conditions. Shots with lower resolution limits produce lower-quality models for predicting Bragg spot positions during the integration step. Also, still shots by their nature record only partial measurements of the Bragg intensity. An approximate model that corrects to the full-spot equivalent (with the simplifying assumption that the X-rays are monochromatic) brings the distribution of intensities closer to that expected from an ideal crystal, and improves the sharpness of anomalous difference Fourier peaks indicating metal positions. © 2015 International Union of Crystallography.
Clavero C.,Lawrence Berkeley National Laboratory
Nature Photonics | Year: 2014
Finding higher efficiency schemes for electron-hole separation is of paramount importance for realizing more efficient conversion of solar energy in photovoltaic and photocatalytic devices. Plasmonic energy conversion has been proposed as a promising alternative to conventional electron-hole separation in semiconductor devices. This emerging method is based on the generation of hot electrons in plasmonic nanostructures through electromagnetic decay of surface plasmons. Here, the fundamentals of hot-electron generation, injection and regeneration are reviewed, with special attention paid to recent progress towards photovoltaic devices. This new energy-conversion method potentially offers high conversion efficiencies, while keeping fabrication costs low. However, several considerations regarding the materials, architectures and fabrication methods used need to be carefully evaluated to advance this field. © 2014 Macmillan Publishers Limited.