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In Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP), patients develop antibodies against ADAMTS13. The majority of patients exhibit inhibitory anti-spacer antibodies. Non-inhibitory antibodies binding to the carboxy-terminal CUB domains have been suggested to enhance the clearance of ADAMTS13 in iTTP.

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A negatively charged region within carboxy-terminal domain maintains proper CTCF DNA binding.

iScience

December 2024

Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.

As an essential regulator of higher-order chromatin structures, CCCTC-binding factor (CTCF) is a highly conserved protein with a central DNA-binding domain of 11 tandem zinc fingers (ZFs), which are flanked by amino (N-) and carboxy (C-) terminal domains of intrinsically disordered regions. Here we report that CRISPR deletion of the entire C-terminal domain of alternating charge blocks decreases CTCF DNA binding but deletion of the C-terminal fragment of 116 amino acids results in increased CTCF DNA binding and aberrant gene regulation. Through a series of genetic targeting experiments, in conjunction with electrophoretic mobility shift assay (EMSA), circularized chromosome conformation capture (4C), qPCR, chromatin immunoprecipitation with sequencing (ChIP-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq), we uncovered a negatively charged region (NCR) responsible for weakening CTCF DNA binding and chromatin accessibility.

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Background: As a group of more than 3.67 million people, the bone health of Chinese plasmapheresis donors, which the main population is also a risk group of osteoporosis (OP), has raised concerns. Therefore, this article investigates the relationship between bone mineral density (BMD), bone metabolism indicators, and plasmapheresis donation behavior among some high-risk plasmapheresis donors for OP in China, and further explores the mediating factors through reasonable statistical methods.

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The tubulin code hypothesis predicts that tubulin tails create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms that determine selective regulation and their relevance in cells are poorly understood. We report selective regulation of budding yeast kinesin-5 motors by the β-tubulin tail.

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Article Synopsis
  • * Researchers synthesized branched poly(ε-lysine) peptide dendrons that showed significant inhibition of HER2-overexpressing breast cancer cells, comparable to Trastuzumab.
  • * The findings suggest that these dendrons could be a cost-effective alternative treatment, demonstrating specificity in inhibiting cancer cell proliferation without cytotoxic effects.
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