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Objective: Loss of function of the phospholipid scramblase (PLS) TMEM16F results in Scott Syndrome, a hereditary bleeding disorder generally attributed to intrinsic platelet dysfunction. The role of TMEM16F in endothelial cells, however, is not well understood. We sought to test the hypothesis that endothelial TMEM16F contributes to hemostasis by measuring bleeding time and venous clotting in endothelial-specific knockout (ECKO) mice.

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Coding Variants of the Genitourinary Development Gene Carry High Risk for Prostate Cancer.

JCO Precis Oncol

January 2025

Medical Research Service, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN.

Purpose: Considerable genetic heterogeneity is currently thought to underlie hereditary prostate cancer (HPC). Most families meeting criteria for HPC cannot be attributed to currently known pathogenic variants.

Methods: To discover pathogenic variants predisposing to prostate cancer, we conducted a familial case-control association study using both genome-wide single-allele and identity-by-descent analytic approaches.

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Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers.

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Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.

Proc Natl Acad Sci U S A

February 2025

Center for Medical Research and Innovation, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, Chinese Academy of Medical Sciences (RU069), Medical College of Fudan University, Shanghai 201399, China.

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.

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Transcription Regulation of Flagellins: A Structural Perspective.

Biochemistry

January 2025

Transcription Regulation Lab, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Third Milestone, Faridabad-Gurgaon Expressway, Faridabad 121001, India.

Bacterial flagella are complex molecular motors that are essential for locomotion and host colonization. They consist of 30 different proteins expressed in varying stoichiometries. Their assembly and function are governed by a hierarchical transcriptional regulatory network with multiple checkpoints primarily regulated by sigma factors.

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