Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Diagnostic yield of active case finding for tuberculosis at human immunodeficiency virus testing in Haiti

SETTING: The Groupe Haïtien d'étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Centres, Port-au-Prince, Haiti, facilitate “test and treat” strategies by screening all patients for tuberculosis (TB) at human immunodeficiency virus (HIV) testing.OBJECTIVE: 1) To determine the proportion of patients with chronic cough at HIV testing diagnosed with TB, stratified by HIV test results; and 2) to evaluate the additional diagnostic yield of Xpert® MTB/RIF vs. sputum microscopy.DESIGN: We conducted a retrospective cohort analysis including all adults tested for HIV at GHESKIO from August 2014 to July 2015.RESULTS: Of 29 233 adult patients tested for HIV, 2953 (10%) were diagnosed as HIV-positive. Chronic cough lasting ≥2 weeks was reported by 1116 (38%) HIV-positive patients; 984 (88%) were tested and 265 (27%) were diagnosed with TB. Chronic cough was reported by 5985 (23%) HIV-negative patients; 5654 (94%) were tested and 1179 (21%) were diagnosed with TB. Of all bacteriologically confirmed cases, 27% were smear-negative and Xpert-positive. Among all TB patients, 81% were HIV-negative.CONCLUSIONS: Screening for TB at HIV testing was high-yield, among both HIV-infected and HIV-negative individuals. Testing for both diseases should be conducted among patients who present with chronic cough at HIV testing.</jats:p

Genetic breaks caused by ancient forest fragmentation: phylogeography of Staudtia kamerunensis (Myristicaceae) reveals distinct clusters in the Congo Basin

Funder: Fondation Philippe Wiener - Maurice Anspach; doi: http://dx.doi.org/10.13039/501100003138Documenting species and population diversity is becoming increasingly important as the destruction and degradation of natural ecosystems are leading to a worldwide biodiversity loss. Despite the rapid development of genetic tools, many species remain undocumented and little is known about the diversity of individuals and populations, especially for tropical African plants. In this study, we aim to identify putative hidden species and/or differentiated populations in the tropical African tree Staudtia kamerunensis Warb. (Myristicaceae), a widespread species characterized by a high morphological diversity and a complex taxonomical history. Historical herbarium vouchers were sampled and leaf or cambium samples were collected in the field, dried in silica gel, and subsequently genotyped at 14 microsatellite loci (SSRs), as well as sequenced for two nuclear genes (At103, Agt1) and one plastid region (psbA-trnH). These genetic data were then analyzed using Bayesian clustering, population genetics, and the construction of haplowebs to assess genetic clustering patterns, the distribution of genetic diversity, and genetic differentiation among populations. Multiple genetically differentiated clusters were observed in parapatry throughout Central Africa. Genetic diversity was high and similar among these clusters, apart from the most differentiated populations in southeast Democratic Republic of the Congo (DR Congo), which showed lower levels of genetic diversity. The genetic breaks detected between S. kamerunensis populations are likely not indicative of hidden species but rather result from ancient rainforest fragmentation during cold and dry periods in the Pliocene and/or Pleistocene. The strong genetic divergence between populations in southeast DR Congo could be the result of an ongoing speciation linked to ecological niche differentiation

Genetic breaks caused by ancient forest fragmentation: phylogeography of Staudtia kamerunensis (Myristicaceae) reveals distinct clusters in the Congo Basin

Abstract Documenting species and population diversity is becoming increasingly important as the destruction and degradation of natural ecosystems are leading to a worldwide biodiversity loss. Despite the rapid development of genetic tools, many species remain undocumented and little is known about the diversity of individuals and populations, especially for tropical African plants. In this study, we aim to identify putative hidden species and/or differentiated populations in the tropical African tree Staudtia kamerunensis Warb. (Myristicaceae), a widespread species characterized by a high morphological diversity and a complex taxonomical history. Historical herbarium vouchers were sampled and leaf or cambium samples were collected in the field, dried in silica gel, and subsequently genotyped at 14 microsatellite loci (SSRs), as well as sequenced for two nuclear genes ( At103 ,Agt1 ) and one plastid region ( psbA-trnH ). These genetic data were then analyzed using Bayesian clustering, population genetics, and the construction of haplowebs to assess genetic clustering patterns, the distribution of genetic diversity, and genetic differentiation among populations. Multiple genetically differentiated clusters were observed in parapatry throughout Central Africa. Genetic diversity was high and similar among these clusters, apart from the most differentiated populations in southeast Democratic Republic of the Congo (DR Congo), which showed lower levels of genetic diversity. The genetic breaks detected between S. kamerunensis populations are likely not indicative of hidden species but rather result from ancient rainforest fragmentation during cold and dry periods in the Pliocene and/or Pleistocene. The strong genetic divergence between populations in southeast DR Congo could be the result of an ongoing speciation linked to ecological niche differentiation.info:eu-repo/semantics/publishe

The TP53INP2 Protein Is Required for Autophagy in Mammalian Cells

Using a bioinformatic approach, we identified a TP53INP1-related gene encoding a protein with 30% identity with tumor protein 53-induced nuclear protein 1 (TP53INP1), which was named TP53INP2. TP53INP1 and TP53INP2 sequences were found in several species ranging from Homo sapiens to Drosophila melanogaster, but orthologues were found neither in earlier eukaryotes nor in prokaryotes. To gain insight into the function of the TP53INP2 protein, we carried out a yeast two-hybrid screening that showed that TP53INP2 binds to the LC3-related proteins GABARAP and GABARAP-like2, and then we demonstrated by coimmunoprecipitation that TP53INP2 interacts with these proteins, as well as with LC3 and with the autophagosome transmembrane protein VMP1. TP53INP2 translocates from the nucleus to the autophagosome structures after activation of autophagy by rapamycin or starvation. Also, we showed that TP53INP2 expression is necessary for autophagosome development because its small interfering RNA-mediated knockdown strongly decreases sensitivity of mammalian cells to autophagy. Finally, we found that interactions between TP53INP2 and LC3 or the LC3-related proteins GABARAP and GABARAP-like2 require autophagy and are modulated by wortmannin as judged by bioluminescence resonance energy transfer assays. We suggest that TP53INP2 is a scaffold protein that recruits LC3 and/or LC3-related proteins to the autophagosome membrane by interacting with the transmembrane protein VMP1. It is concluded that TP53INP2 is a novel gene involved in the autophagy of mammalian cells