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  • Winkler Haslund posted an update 1 year, 3 months ago

    Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3 mg/kg every 3 days for 1 month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. selleck chemicals llc We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure significantly decreased bromodeoxyuridine (BrdU)-positive cells (39%) and Ki67+ cells (47%) in the DG of the hippocampus, indicating decreased cellular proliferation. In addition, deltamethrin-treated mice exhibited a 44% decrease in nestin-expressing neural progenitor cells and a 38% reduction in the expression of doublecortin (DCX), an early neuronal differentiation marker. Furthermore, deltamethrin-exposed mice exhibited a 25% reduction in total number of granule cells in the DG. These findings indicate that relatively short-term exposure to deltamethrin causes significant deficits in hippocampal neurogenesis that is associated with impaired learning and memory.

    There is emerging evidence to show that psychological interventions such as cognitive remediation therapy (CRT), psychoeducation, family therapy, and group psychotherapies may be useful for adolescents with psychosis. The current review is on the effects of various psychological interventions for adolescents with psychosis compared with treatment as usual (TAU) or other psychological interventions.

    We undertook a comprehensive search for all randomized controlled trials on the topic as per predefined criteria. For binary data, a standard estimation of risk ratio, and, for continuous data, the mean difference between groups were estimated. GRADE approach was used to assess studies. “Risk of Bias” was calculated, and finally random-effects model was used for analyses.

    The review included 7 studies (n = 317). Two studies compared CRT and TAU with TAU alone. CRT showed improvement in short-term memory compared with those in the TAU group (relative risk 0.58, 95% CI 0.37 to 0.89, participants = 31, very low-certainty evidence). When comparing group psychosocial therapy with TAU, global state scores measured using Children’s Global Assessment Scale (CGAS) were clearly higher in the intervention arm (mean difference 5.10, 95% CI 1.35 to 8.85, participants = 56, very low-certainty evidence) as compared with the TAU group. None of the other interventions were found to be significantly effective for the treatment of psychosis in adolescents.

    Evidence suggests that psychological interventions may have beneficial effects in the treatment of adolescents with psychosis, but the evidence is of low or very low certainty.

    Evidence suggests that psychological interventions may have beneficial effects in the treatment of adolescents with psychosis, but the evidence is of low or very low certainty.Alternative polyadenylation (APA) profoundly expands the transcriptome complexity. Perturbations of APA can disrupt biological processes, ultimately resulting in devastating disorders. A major challenge in identifying mechanisms and consequences of APA (and its perturbations) lies in the complexity of RNA 3′ end processing, involving poorly conserved RNA motifs and multi-component complexes consisting of far more than 50 proteins. This is further complicated in that RNA 3′ end maturation is closely linked to transcription, RNA processing and even epigenetic (histone/DNA/RNA) modifications. Here, we present TREND-DB (http//shiny.imbei.uni-mainz.de3838/trend-db), a resource cataloging the dynamic landscape of APA after depletion of >170 proteins involved in various facets of transcriptional, co- and post-transcriptional gene regulation, epigenetic modifications and further processes. TREND-DB visualizes the dynamics of transcriptome 3′ end diversification (TREND) in a highly interactive manner; it provides a global APA network map and allows interrogating genes affected by specific APA-regulators and vice versa. It also permits condition-specific functional enrichment analyses of APA-affected genes, which suggest wide biological and clinical relevance across all RNAi conditions. The implementation of the UCSC Genome Browser provides additional customizable layers of gene regulation accounting for individual transcript isoforms (e.g. epigenetics, miRNA-binding sites and RNA-binding proteins). TREND-DB thereby fosters disentangling the role of APA for various biological programs, including potential disease mechanisms, and helps identify their diagnostic and therapeutic potential.B-family DNA polymerases (PolBs) represent the most common replicases. PolB enzymes that require RNA (or DNA) primed templates for DNA synthesis are found in all domains of life and many DNA viruses. Despite extensive research on PolBs, their origins and evolution remain enigmatic. Massive accumulation of new genomic and metagenomic data from diverse habitats as well as availability of new structural information prompted us to conduct a comprehensive analysis of the PolB sequences, structures, domain organizations, taxonomic distribution and co-occurrence in genomes. Based on phylogenetic analysis, we identified a new, widespread group of bacterial PolBs that are more closely related to the catalytically active N-terminal half of the eukaryotic PolEpsilon (PolEpsilonN) than to Escherichia coli Pol II. In Archaea, we characterized six new groups of PolBs. Two of them show close relationships with eukaryotic PolBs, the first one with PolEpsilonN, and the second one with PolAlpha, PolDelta and PolZeta. In addition, structure comparisons suggested common origin of the catalytically inactive C-terminal half of PolEpsilon (PolEpsilonC) and PolAlpha.