Oligodendrocyte Precursor Cells Synthesize Neuromodulatory Factors

NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting and major glial cell population in the adult mammalian brain. Direct synaptic innervation of OPC by neurons throughout the brain together with their ability to sense neuronal network activity raises the question of additional physiological roles of OPC, supplementary to generating myelinating oligodendrocytes. In this study we investigated whether OPC express neuromodulatory factors, typically synthesized by other CNS cell types. Our results show that OPC express two well-characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are influenced in cultured OPC by the NG2 intracellular region which can be released by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after isolation by cell sorting and direct analysis. These results show that OPC can contribute to the expression of these proteins within the CNS and suggest PTGDS expression as a downstream target of NG2 signaling

A multipole-Taylor expansion for the potential of gravitational lens MG J0414+0534

We employ a multipole-Taylor expansion to investigate how tightly the gravitational potential of the quadruple-image lens MG J0414+0534 is constrained by recent VLBI observations. These observations revealed that each of the four images of the background radio source contains four distinct components, thereby providing more numerous and more precise constraints on the lens potential than were previously available. We expand the two-dimensional lens potential using multipoles for the angular coordinate and a modified Taylor series for the radial coordinate. After discussing the physical significance of each term, we compute models of MG J0414+0534 using only VLBI positions as constraints. The best-fit model has both interior and exterior quadrupole moments as well as exterior m=3 and m=4 multipole moments. The deflector centroid in the models matches the optical galaxy position, and the quadrupoles are aligned with the optical isophotes. The radial distribution of mass could not be well constrained. We discuss the implications of these models for the deflector mass distribution and for the predicted time delays between lensed components.Comment: 44 pages, 5 figures, 11 tables, accepted for publication in Ap

Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules

Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon–glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binding to the cis-acting A2 response element (A2RE). Release of this repression of MBP mRNA translation is thus essential for myelination. Mice deficient in the Src family tyrosine kinase Fyn are hypomyelinated and contain reduced levels of MBP. Here, we identify hnRNP A2 as a target of activated Fyn in oligodendrocytes. We show that active Fyn phosphorylates hnRNP A2 and stimulates translation of an MBP A2RE–containing reporter construct. Neuronal adhesion molecule L1 binding to oligodendrocytes results in Fyn activation, which leads to an increase in hnRNP A2 phosphorylation. These results suggest that Fyn kinase activation results in the localized translation of MBP mRNA at sites of axon–glia contact and myelin deposition

Daily Eastern News: March 03, 2017

https://thekeep.eiu.edu/den_2017_mar/1002/thumbnail.jp

Model for End‐Stage Liver Disease‐Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163652/3/hep31199.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163652/2/hep31199_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163652/1/hep31199-sup-0001-Supinfo.pd

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century