A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis.

Functional inactivation of tumor suppressor genes drives cancer initiation, progression, and treatment responses. Most tumor suppressor genes are inactivated through 1 of 2 well-characterized mechanisms: DNA-level mutations, such as point mutations or deletions, and promoter DNA hypermethylation. Here, we report a distinct third mechanism of tumor suppressor inactivation based on alterations to the histone rather than DNA code.

Superprotonic Conductivity by Synergistic Blending of Coordination Polymers with Organic Polymers: Fabrication of Durable and Flexible Proton Exchange Membranes.

Creation of an efficient and cost-effective proton exchange membrane (PEM) has emerged as a propitious solution to address the challenges of renewable energy development. Coordination polymers (CPs) have garnered significant interest due to their multifunctional applications and moldability, along with long-range order. To leverage the potential of CPs in fuel cells, it is essential to integrate microcrystalline CPs into organic polymers to prepare membranes and avoid grain boundary issues.

β-catenin, PAX2, and PTEN Aberrancy Across the Spectrum of Endometrioid Ovarian Lesions.

Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis-particularly in the ovary-is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia.

Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice.

In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism.

Anti-Müllerian hormone treatment enhances oocyte quality, embryonic development and live birth rate†.

The anti-Müllerian hormone (AMH) produced by the granulosa cells of growing follicles is critical for folliculogenesis and is clinically used as a diagnostic and prognostic marker of female fertility. Previous studies report that AMH-pretreatment in mice creates a pool of quiescent follicles that are released following superovulation, resulting in an increased number of ovulated oocytes. However, the quality and developmental competency of oocytes derived from AMH-induced accumulated follicles as well as the effect of AMH treatment on live birth are not known.

Jumonji Domain-containing Protein-3 (JMJD3/Kdm6b) Is Critical for Normal Ovarian Function and Female Fertility.

In females, reproductive success is dependent on the expression of a number of genes regulated at different levels, one of which is through epigenetic modulation. How a specific epigenetic modification regulates gene expression and their downstream effect on ovarian function are important for understanding the female reproductive process. The trimethylation of histone3 at lysine27 (H3K27me3) is associated with gene repression.

Role of fibulin-5 insufficiency and prolapse progression on murine vaginal biomechanical function.

The vagina plays a critical role in supporting the pelvic organs and loss of support leads to pelvic organ prolapse. It is unknown what microstructural changes influence prolapse progression nor how decreased elastic fibers contributes to vaginal remodeling and smooth muscle contractility. The objective for this study was to evaluate the effect of fibulin-5 haploinsufficiency, and deficiency with progressive prolapse on the biaxial contractile and biomechanical function of the murine vagina.

Lipopolysaccharide induces lipolysis and insulin resistance in adipose tissue from dairy cows.

Intense and protracted adipose tissue (AT) fat mobilization increases the risk of metabolic and inflammatory periparturient diseases in dairy cows. This vulnerability increases when cows have endotoxemia-common during periparturient diseases such as mastitis, metritis, and pneumonia-but the mechanisms are unknown. Fat mobilization intensity is determined by the balance between lipolysis and lipogenesis.

Androgens regulate ovarian gene expression by balancing Ezh2-Jmjd3 mediated H3K27me3 dynamics.

Conventionally viewed as male hormone, androgens play a critical role in female fertility. Although androgen receptors (AR) are transcription factors, to date very few direct transcriptional targets of ARs have been identified in the ovary. Using mouse models, this study provides three critical insights about androgen-induced gene regulation in the ovary and its impact on female fertility.

Developmental programming: prenatal testosterone-induced epigenetic modulation and its effect on gene expression in sheep ovary†.

Maternal perturbations or sub-optimal conditions during fetal development can predispose the offspring to diseases in adult life. Animal and human studies show that prenatal androgen excess may be an underlying cause of polycystic ovary syndrome (PCOS) later in life. In women, PCOS is a common fertility disorder with comorbid metabolic dysfunction.

Oocyte-Derived Factors (GDF9 and BMP15) and FSH Regulate AMH Expression Via Modulation of H3K27AC in Granulosa Cells.

Anti-Müllerian hormone (AMH) produced by ovarian granulosa cells (GCs) plays a crucial role in ovarian function. It is used as a diagnostic and/or prognostic marker of fertility as well as for pathophysiological conditions in women. In this study, we investigated the underlying mechanism for regulation of AMH expression in GCs using primary mouse GCs and a human GC tumor-derived KGN cell line.

Characterization of the gluconate utilization system of Vibrio cholerae with special reference to virulence modulation.

Orthologs search identified that the Vibrio cholerae gluconate (Gnt) utilization system minimally consisted of the Entner-Doudoroff (ED) pathway (edd and eda) and three other genes, namely gntU, gntK and gntR This system appeared unique by genomic organization of component genes into two operons transcribed in opposite directions. In silico analysis indicated GntU as an inner-membrane protein functioning for transport and GntK as a kinase with cytosolic localization that generates Gnt6P, which is then metabolized through the ED pathway. Enzyme 6-phosphogluconate dehydratase encoded by edd converts Gnt6P to 2-keto-3-deoxy-6-phosphogluconate (KDPG), which is metabolized by the action of KDPG-aldolase encoded by eda Transcriptional upregulation of the Gnt utilization genes in the gntR mutant matched well to a predicted repressor role of GntR.

High-throughput screening and whole genome sequencing identifies an antimicrobially active inhibitor of Vibrio cholerae.

Background: Pathogenic serotypes of Vibrio cholerae cause the life-threatening diarrheal disease cholera. The increasing development of bacterial resistances against the known antibiotics necessitates the search for new antimicrobial compounds and targets for this pathogen.

Results: A high-throughput screening assay with a Vibrio cholerae reporter strain constitutively expressing green fluorescent protein (GFP) was developed and applied in the investigation of the growth inhibitory effect of approximately 28,300 structurally diverse natural compounds and synthetic small molecules.