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Regulation of the Gap Junction Interplay in the Rat Epididymis

Abstract During postnatal development of the epididymis, a change in the expression of gap junction proteins, or connexins (Cxs), occurs, in which Gjb2 (Cx26) and Gja1 (Cx43) levels in the proximal epididymis are decreased, while Gjb1(Cx32), Gjb4 (Cx30.3) and Gjb5 (Cx31.1) levels increase. The mechanism(s) responsible for the switch in Cx expression is unknown. The aims of this study are: 1) to identify the mechanisms responsible for the decrease in GJB2 protein levels and the increase in other Cxs during postnatal development. Results indicate that decreased Gjb2 expression does not induce changes in the expression of other Cxs in rat RCE-1 principal cells, suggesting a lack of compensatory expression. Sequence analysis of both Gjb2 and Gjb1 promoters identified common multiple response elements to steroid hormones. Using RCE-1 cells, we showed that glucocorticoids increased Gjb2 expression, while estradiol had no effect. Orchidectomy in rats resulted in a significant increase in GJB2 and decreased GJB1 in the caput and corpus epididymidis. Changes in Cxs protein levels were prevented by administering testosterone in orchidectomized rats. Similar results were observed in the prostate, another androgen-receptive organ. LNCaP cells, which are androgen-responsive, showed that exogenous dihydrotestosterone (DHT) exposure resulted in a decrease in Gjb2mRNA levels concomitant with increased Gjb1 levels. Using a GJB1 promoter construct we showed that DHT could induce transactivation of the luciferase transgene, while transactivation using two GJB2 promoters were not altered. Together, our results suggest that androgens and glucocorticoids regulate the expression of Cxs in the epididymis.

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TeenGrowth: Individualized Expected Body Weights for Young People with Eating Disorders

Significant weight loss among teens may indicate eating disorder (ED) onset, and weight restoration and/or stabilization is crucial for successful treatment and sustained recovery from restrictive EDs. While achieving and sustaining a restored body weight is necessary during ED recovery, it is often challenging to define an individual's expected healthy body weight (EBW) due to diverse premorbid growth trajectories. Population-based norms fall short in capturing the nuances of illness and recovery across individuals, and there are no current tools that offer personalized, reproducible, and statistically-driven EBW estimations. This paper introduces the TeenGrowth package and its web-based application, designed to calculate and forecast expected body mass index (eBMI) and EBW across adolescence. With input from individual growth charts, demographic data, and age of ED onset, TeenGrowth offers a reproducible method for determining EBWs. The package includes functions for data cleaning, BMI and BMI z-score calculations, and growth forecasting, accommodating various data inputs. The accompanying Shiny web application provides a user-friendly interface for researchers and providers, enabling the identification of EBWs for individual patients and weight restoration planning. Through a series of simulation studies, the package's various options for predictive models are evaluated, highlighting its potential for use in ED screening and improving accuracy of EBW estimations. The introduction of TeenGrowth represents a significant step towards personalized medicine in ED treatment, with potential to promote individualized care and enhance clinical outcomes.

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Genomic diversity of phages infecting the globally widespread genus Sulfurimonas

Abstract The bacterial genus Sulfurimonas is globally widespread and occupies a key ecological niche in different habitats. However, phages infecting Sulfurimonas have never been isolated and characterized. Here we systematically investigated the genetic diversity, taxonomy and interaction patterns of Sulfurimonas-associated phages based on sequenced microbial genomes and metagenome datasets. High-confidence phage contigs related to Sulfurimonas were identified from various ecosystems, clustered into 61 viral operational taxonomic units across 3 viral realms. Most Sulfurimonas-associated phages were tailed viruses of Caudoviricetes; these were assigned to 19 genus-level viral clusters, the majority of which were distantly related to previously known viruses. Phages encoding double jelly-roll major capsid proteins represented another group of double-stranded DNA phage with diverse gene compositions. Inovirus-like single-stranded DNA phages were primarily identified as integrated prophages or extrachromosomal viral genomes, suggesting chronic infections in hosts. Historical and current phage-host interactions were revealed, implying the viral impact on host evolution. Additionally, phages encoding auxiliary metabolic genes might benefit the infected bacteria by compensating or augmenting host metabolisms. This study highlights the remarkable diversity and novelty of Sulfurimonas-associated phages with highly divergent tailless lineages, providing basis for further investigation of phage-host interactions within this genus.

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