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.
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.
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.
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.