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Inherent asymmetry of Rpd3S coordinates its nucleosome engagement and association with elongating RNA polymerase II.
Nat Struct Mol Biol
January 2025
Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The Rpd3S histone deacetylase complex has a crucial role in genomic integrity by deacetylating transcribed nucleosomes following RNA polymerase (Pol) II passage. Cryo-EM studies highlight the importance of asymmetrical Rco1-Eaf3 dimers in nucleosome binding, yet the interaction dynamics with nucleosomal substrates alongside elongating Pol II are poorly understood. Here we demonstrate the essential function of the Rco1 N-terminal intrinsically disordered region (IDR) in modulating Pol II association, in which K/R mutations within the Rco1 IDR impair interaction of Rpd3S with the C-terminal domain (CTD) of Rpb1, without affecting nucleosome recognition or complex integrity.
View Article and Find Full Text PDFEndocytic Uptake of Self-Assembled Iridium(III) Nanoaggregates for Holistic Treatment of Metastatic 3D Triple-Negative Breast Tumor Spheroids.
Small
November 2024
Department of Chemistry, IIT Kanpur, Kanpur, UP, 208016, India.
Article Synopsis
- Triple-negative breast cancer (TNBC) is aggressive and has few treatment options; this study explores organometallic Ir(III) complexes as a potential therapy for TNBC cell line MDA-MB-231.
- The lead compound, IrL, shows effective cellular uptake and stability in culture media, along with strong photo-responsive imaging properties and a low inhibitory concentration (IC) value when exposed to specific light.
- In vivo studies in mice suggest that IrL can effectively reduce tumors, showcasing its potential for use in nanomedicine against challenging metastatic TNBC.
Halving premature death and improving quality of life at all ages: cross-country analyses of past trends and future directions.
Lancet
December 2024
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Background: Although death in old age is unavoidable, premature death-defined here as death before age 70 years-is not. To assess whether halving premature mortality by 2050 is feasible, we examined the large variation in premature death rates before age 70 years and trends over the past 50 years (1970-2019), covering ten world regions and the 30 most-populous nations. This analysis was undertaken in conjunction with the third report of The Lancet Commission on Investing in Health: Global Health 2050: the path to halving premature death by mid-century.
View Article and Find Full Text PDFPersonal Testimony About Dealing with Loss and Self-Care.
J Pastoral Care Counsel
December 2024
HJ International Graduate School for Peace and Public Leadership.
As an interfaith hospital chaplain and a Christian, navigating the profound emotional terrain of grief and loss is both a professional duty and a deeply personal journey. Attending the funerals of two close friends has brought out the interplay between my role as a spiritual caregiver and my own vulnerability. In reflection, I realize the importance of self-care and the reminder that in offering comfort and empathy, I must first find it within myself.
View Article and Find Full Text PDFSpartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC.
BMC Cancer
October 2024
Department of Medical Oncology, Highlands Oncology Group, Fayetteville, AZ, USA.
Article Synopsis
- A multicenter phase 1b study explored the effectiveness and tolerability of combining spartalizumab with various platinum-doublet chemotherapy regimens in treatment-naïve patients with non-small cell lung cancer (NSCLC) that were not selected based on PD-L1 expression.
- The study found that the maximum tolerated dose for spartalizumab was 300 mg every 3 weeks, and overall response rates to the treatment generally ranged from 51.5% to 57.6%, indicating a good level of efficacy across different chemotherapy combinations.
- Notably, patients receiving pemetrexed/cisplatin showed the longest median progression-free survival and overall survival compared to other treatment groups, highlighting the potential of this regimen in
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