Koeppen A.H.,Albany Research Center |
Koeppen A.H.,Albany Medical College |
Mazurkiewicz J.E.,Albany Medical College
Journal of Neuropathology and Experimental Neurology | Year: 2013
Friedreich ataxia is an autosomal recessive disorder that affects children and young adults. The mutation consists of a homozygous guanine-adenine-adenine trinucleotide repeat expansion that causes deficiency of frataxin, a small nuclear genome-encoded mitochondrial protein. Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase, and iron dysmetabolism of the entire cell. This review of the neuropathology of Friedreich ataxia stresses the critical role of hypoplasia and superimposed atrophy of dorsal root ganglia. Progressive destruction of dorsal root ganglia accounts for thinning of dorsal roots, degeneration of dorsal columns, transsynaptic atrophy of nerve cells in Clarke column and dorsal spinocerebellar fibers, atrophy of gracile and cuneate nuclei, and neuropathy of sensory nerves. The lesion of the dentate nucleus consists of progressive and selective atrophy of large glutamatergic neurons and grumose degeneration of corticonuclear synaptic terminals that contain γ-aminobutyric acid (GABA). Small GABA-ergic neurons and their projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute a second intrinsic CNS lesion. In light of the selective vulnerability of organs and tissues to systemicfrataxin deficiency, many questions about the pathogenesis of Friedreich ataxia remain. © 2013 by the American Association of Neuropathologists, Inc.
Luo G.,Albany Research Center |
Yu F.,Albany Research Center
Atmospheric Chemistry and Physics | Year: 2010
A numerical evaluation of global oceanic emissions of α-pinene and isoprene based on both "bottom-up" and "top-down" methods is presented. We infer that the global "bottom-up" oceanic emissions of α-pinene and isoprene are 0.013 TgC yr-1 and 0.32 TgC yr -1, respectively. By constraining global chemistry model simulations with the shipborne measurement of Organics over the Ocean Modifying Particles in both Hemispheres summer cruise, we derived the global "top-down" oceanic α-pinene source of 29.5 TgC yr-1 and isoprene source of 11.6 TgC yr-1. Both the "bottom-up" and "top-down" values are subject to large uncertainties. The incomplete understanding of the in-situ phytoplankton communities and their range of emission potentials significantly impact the estimated global "bottom-up" oceanic emissions, while the estimated total amounts of the global "top-down" oceanic sources can be influenced by emission parameterizations, model and input data spatial resolutions, boundary layer mixing processes, and the treatments of chemical reactions. The global oceanic α-pinene source and its impact on organic aerosol formation is significant based on "top-down" method, but is negligible based on "bottom-up" approach. Our research highlights the importance of carrying out further research (especially measurements) to resolve the large offset in the derived oceanic organic emission based on two different approaches.
Silva C.J.,Albany Research Center
Prion | Year: 2014
Prions are molecular pathogens, able to convert a normal cellular prion protein (PrPC) into a prion (PrPSc). The information necessary for this conversion is contained in the conformation of PrPSc. Mass spectrometry (MS) and small-molecule covalent reactions have been used to study prions. Mass spectrometry has been used to detect and quantitate prions in the attomole range (10?18 mole). MS-based analysis showed that both possess identical amino acid sequences, one disulfide bond, a GPI anchor, asparagine-linked sugar antennae, and unoxidized methionines. Mass spectrometry has been used to define elements of the secondary and tertiary structure of wild-type PrPSc and GPI-anchorless PrPSc. It has also been used to study the quaternary structure of the PrPSc multimer. Small molecule reagents react differently with the same lysine in the PrPC conformation than in the PrPSc conformation. Such differences can be detected by Western blot using mAbs with lysine-containing epitopes, such as 3F4 and 6D11. This permits the detection of PrPSc without the need for proteinase K pretreatment and can be used to distinguish among prion strains. These results illustrate how two important chemical tools, mass spectrometry and covalent modification by small molecules, are being applied to the detection and structural study of prions. Furthermore these tools are or can be applied to the study of the other protein misfolding diseases such as lzheimer Disease, Parkinson Disease, or ALS.©2014 Landes Bioscience.
Sell S.,Albany Research Center
American Journal of Pathology | Year: 2010
In each major theory of the origin of cancer - field theory, chemical carcinogenesis, infection, mutation, or epigenetic change - the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth. Copyright © American Society for Investigative Pathology.
He X.,Albany Research Center
PloS one | Year: 2010
Ricin (also called RCA-II or RCA(60)), one of the most potent toxins and documented bioweapons, is derived from castor beans of Ricinus communis. Several in vitro methods have been designed for ricin detection in complex food matrices in the event of intentional contamination. Recently, a novel Immuno-PCR (IPCR) assay was developed with a limit of detection of 10 fg/ml in a buffer matrix and about 10-1000-fold greater sensitivity than other methods in various food matrices. In order to devise a better diagnostic test for ricin, the IPCR assay was adapted for the detection of ricin in biological samples collected from mice after intoxication. The limit of detection in both mouse sera and feces was as low as 1 pg/ml. Using the mouse intravenous (iv) model for ricin intoxication, a biphasic half-life of ricin, with a rapid t(1/2)α of 4 min and a slower t(1/2)β of 86 min were observed. The molecular biodistribution time for ricin following oral ingestion was estimated using an antibody neutralization assay. Ricin was detected in the blood stream starting at approximately 6-7 h post- oral intoxication. Whole animal histopathological analysis was performed on mice treated orally or systemically with ricin. Severe lesions were observed in the pancreas, spleen and intestinal mesenteric lymph nodes, but no severe pathology in other major organs was observed. The determination of in vivo toxicokinetics and pathological effects of ricin following systemic and oral intoxication provide a better understanding of the etiology of intoxication and will help in the future design of more effective diagnostic and therapeutic methods.
Fangqun Y.U.,Albany Research Center
Environmental Science and Technology | Year: 2010
The cloud condensation nuclei concentrations predicted by global aerosol models are sensitive to how new particle formation in subgrid anthropogenic SO2 plumes is parameterized. Using a state-of-the-art kinetic nucleation model, we carried out two case studies to investigate the large difference in the number concentrations of ultrafine particles observed in the plumes from the Home smelter: one in the summer and the other in the winter. Our model predicted that particle number concentrations are in good agreement with observations for both cases, showing that particle formation in the Home smelter plumes is dominated by binary homogeneous nucleation (BHN) in the winter case and by ion-mediated nucleation (IMN) in the summer case. Further sensitivity studies reveal significant diurnal and seasonal variations of sulfate particle formation in the anthropogenic SO2 plume, mainly associated with corresponding variations of two key parameters: hydroxyl radical concentration ([OH]) and temperature. Nucleation in the plume is negligible at night because of very low [OH]. BHN is significant when [OH] is relatively high or temperature is relatively low, and it is generally limited to the fresh plumes (within ∼15 km from source), but it can generate very high concentrations of ultrafine particles (peak values as high as 105-106 cm-3) under favorable conditions. IMN generally dominates nucleation in the plume when [OH] is relatively low or temperature is relatively high, and it extends from fresh plume to more aged plume and produces 2-3 × 104 cm-3 of nucleated particles. The implications of the results are discussed. © 2010 American Chemical Society.
Fiume E.,University of California at Berkeley |
Fletcher J.C.,University of California at Berkeley |
Fletcher J.C.,Albany Research Center
Plant Cell | Year: 2012
The plant seed is a major nutritional source for humans as well as an essential embryo development and dispersal unit. To ensure proper seed formation, fine spatial and temporal coordination between the embryo, endosperm, and maternal seed components must be achieved. However, the intercellular signaling pathways that direct the synchronous development of these tissues are poorly understood. Here we show that the Arabidopsis thaliana peptide ligand CLAVATA3/EMBRYO SURROUNDING REGION-RELATED8 (CLE8) is exclusively expressed in young embryos and endosperm, and that it acts cell and noncell autonomously to regulate basal embryo cell division patterns, endosperm proliferation, and the timing of endosperm differentiation. CLE8 positively regulates expression of the transcription factor gene WUSCHEL-LIKE HOMEOBOX8 (WOX8), and together CLE8 and WOX8 form a signaling module that promotes seed growth and overall seed size. These results demonstrate that seed development is coordinated by a secreted peptide ligand that plays a key early role in orchestrating cell patterning and proliferation in the embryo and endosperm. © 2012 American Society of Plant Biologists. All rights reserved.
Luo G.,Albany Research Center |
Yu F.,Albany Research Center
Atmospheric Chemistry and Physics | Year: 2011
The impact of primary sulfate emissions on cloud condensation nuclei (CCN) concentrations, one of the major uncertainties in global CCN predictions, depends on the fraction of sulfur mass emitted as primary sulfate particles (fsulfate), the fraction of primary sulfate mass distributed into the nucleation mode particles (fnucl), and the nucleation and growth processes in the ambient atmosphere. Here, we use a global size-resolved aerosol microphysics model recently developed to study how the different parameterizations of primary sulfate emission affect particle properties and CCN abundance. Different from previous studies, we use the ionmediated nucleation scheme to simulate tropospheric particle formation. The kinetic condensation of low volatile secondary organic gas (SOG) (in addition to H2SO4 gas) on nucleated particles is calculated based on our new scheme that considers the SOG volatility changes arising from the oxidation aging. Our simulations show a compensation effect of nucleation to primary sulfate emission. We find that the change of fnucl from 5% to 15% has a more significant impact on the simulated particle number budget than that of fsulfate within the range of 2.5-5%. Based on our model configurations, an increase of fsulfate from 0% to 2.5% (with fnucl =5%) does not improve the agreement between simulated and observed annual mean number concentrations of particles >10 nm at 21 stations but further increase of either fsulfate from 2.5% to 5% (with fnucl =5%) or fnucl from 5% to 15% (with fsulfate = 2.5%) substantially deteriorates the agreement. For fsulfate of 2.5%-5% and fnucl of 5%, our simulations indicate that the global CCN at supersaturation of 0.2% increases by 8-11% in the boundary layer and 3-5% in the whole troposphere (compared to the case with fsulfate =0). © 2011 Author(s).
Yu F.,Albany Research Center
Atmospheric Chemistry and Physics | Year: 2011
The widely used two-product secondary organic aerosol (SOA) formation model has been extended in this study to consider the volatility changes of secondary organic gases (SOG) arising from the aging process as well as the kinetic condensation of low volatile SOG (LV-SOG). In addition to semi-volatile SOG (SV-SOG) with saturation vapor pressure at 290K (C* 290) in the range of ∼3 ppt-3 ppb and medium-volatile SOG (MV-SOG) with C* 290 in the range of 0.3-300 ppb, we add a third component representing LVSOG with C* 290 below ∼3 ppt and design a scheme to transfer MV-SOG to SV-SOG and SV-SOG to LV-SOG associated with oxidation aging. This extended SOA formation model has been implemented in a global aerosol model (GEOSChem) and the co-condensation of H2SO4 and LV-SOG on pre-existing particles is explicitly simulated. We show that, over many parts of the continents, LV-SOG concentrations are generally a factor of ∼2-20 higher than those of H 2SO4 and the kinetic condensation of LV-SOG significantly enhances particle growth rates. Comparisons of the simulated and observed evolution of particle size distributions at a boreal forest site (Hyytïalä, Finland) clearly show that LVSOG condensation is critical in order to bring the simulations closer to the observations. With the new SOA formation scheme, annual mean SOA mass increases by a factor of 2-10 in many parts of the boundary layer and reaches above 0.5 μ gm-3 in most parts of the main continents, improving the agreement with aerosol mass spectrometer (AMS) SOA measurements. While the new scheme generally decreases the concentration of condensation nuclei larger than 10 nm by 3-30% in the lower boundary layer as a result of enhanced surface area and reduced nucleation rates, it substantially increases the concentration of cloud condensation nuclei at a water supersaturation ratio of 0.2%, ranging from ∼5-20% over a large fraction of oceans and high latitude continents to more than 50% over some parts of South America, Australia, and Indonesia. Our study highlights the importance for global aerosol models to explicitly account for the oxidation aging of SOGs and their contribution to particle growth. © 2011 Author(s).
Friedman M.,Albany Research Center
Journal of Agricultural and Food Chemistry | Year: 2015
Inhibition of cancer can occur via apoptosis, a genetically directed process of cell self-destruction that involves numerous biomarkers and signaling pathways. Glycoalkaloids are nitrogen-containing secondary plant metabolites found in numerous Solanaceous plants including eggplants, potatoes, and tomatoes. Exposure of cancer cells to glycoalkaloids produced by eggplants (α-solamargine and α-solasonine), potatoes (α-chaconine and α-solanine), and tomatoes (α-tomatine) or their hydrolysis products (mono-, di-, and trisaccharide derivatives and the aglycones solasodine, solanidine, and tomatidine) inhibits the growth of the cells in culture (in vitro) as well as tumor growth in vivo. This overview comprehensively surveys and consolidates worldwide efforts to define the following aspects of these natural compounds: (a) their prevalence in the three foods; (b) their chemistry and structure - activity relationships; (c) the reported factors (biomarkers, signaling pathways) associated with apoptosis of bone, breast, cervical, colon, gastric, glioblastoma, leukemia, liver, lung, lymphoma, melanoma, pancreas, prostate, and squamous cell carcinoma cell lines in vitro and the in vivo inhibition of tumor formation and growth in fish and mice and in human skin cancers; and (d) future research needs. The described results may make it possible to better relate the structures of the active compounds to their health-promoting function, individually, in combination, and in food, and allow the consumer to select glycoalkaloid-containing food with the optimal content of nontoxic beneficial compounds. The described findings are expected to be a valuable record and resource for further investigation of the health benefits of food-related natural compounds. © 2015 American Chemical Society.