Insights from the timber rattlesnake (Crotalus horridus) genome for MHC gene architecture and evolution in threatened rattlesnakes.

Conservation of threatened species can benefit from an evaluation of genes in the Major Histocompatibility Complex (MHC), whose loci encode proteins that bind pathogens and are often under strong selection to maintain diversity in immune response to diseases. Despite this gene family's importance to disease resistance, little is known about these genes in reptiles including snakes. To address this issue, we assembled and annotated a highly-contiguous genome assembly for the timber rattlesnake (Crotalus horridus), a pit viper which is threatened or endangered in parts of its range, and analyzed this new genome along with three other rattlesnake genomes to characterize snake MHC loci.

Altering heparan sulfate suppresses cell abnormalities and neuron loss in model of Alzheimer Disease.

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.

Heparan sulfate modified proteins affect cellular processes central to neurodegeneration and modulate function.

Mutations in are the most common cause of familial, early-onset Alzheimer's disease (AD), typically producing cognitive deficits in the fourth decade. A variant of , was found associated with protection from both cognitive decline and Tau accumulation in a 70-year-old bearing the disease-causing mutation. The amino acid change in ApoE3ch is within the heparan sulfate (HS) binding domain of APOE, and purified APOEch showed dramatically reduced affinity for heparin, a highly sulfated form of HS.