We examined the function of heparan-sulfate-modified proteoglycans (HSPGs) in pathways affecting Alzheimer disease (AD)-related cell pathology in human cell lines and mouse astrocytes. Mechanisms of HSPG influences on dependent cell loss were evaluated in using knockdown of the homolog, , together with partial loss-of-function of , a gene specifically affecting HS sulfation HSPG modulation of autophagy, mitochondrial function, and lipid metabolism were shown to be conserved in human cell lines, , and mouse astrocytes. RNA interference (RNAi) of reduced intracellular lipid levels in wild-type mouse astrocytes or those expressing humanized variants of , , and Neuron-directed knockdown of in produced apoptosis and cell loss in the brain, phenotypes suppressed by reductions in expression.
View Article and Find Full Text PDFThe genome of eukaryotes exists as chromatin which contains both DNA and proteins. The fundamental unit of chromatin is the nucleosome, which contains 146 base pairs of DNA associated with two each of histones H2A, H2B, H3, and H4. The N-terminal tails of histones are rich in lysine and arginine and are modified post-transcriptionally by acetylation, methylation, and other post-translational modifications (PTMs).
View Article and Find Full Text PDFPluripotent cells of the blastocyst inner cell mass (ICM) and their in vitro derivatives, embryonic stem (ES) cells, contain genomes in an epigenetic state that are poised for subsequent differentiation. Their chromatin is hyperdynamic in nature and relatively uncondensed. In addition, a large number of genes are expressed at low levels in both ICM and ES cells.
View Article and Find Full Text PDFLipoteichoic and wall teichoic acids (TA) are highly anionic cell envelope-associated polymers containing repeating polyglycerol/ribitol phosphate moieties. Substitution of TA with D-alanine is important for modulation of many cell envelope-dependent processes, such as activity of autolytic enzymes, binding of divalent cations, and susceptibility to innate host defenses. D-Alanylation of TA is diminished when bacteria are grown in medium containing increased NaCl concentrations, but the effects of increased salt concentration on expression of the dlt operon encoding proteins mediating D-alanylation of TA are unknown.
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