Browse Articles

A hidden predictor of sudden cardiac death uncovered by deep learning

A CDK1 phospho-switch reprograms TRAIP to unload replisomes in mitosis

Cells entering mitosis with incompletely replicated DNA face catastrophic chromosome segregation failure. During interphase, the replisome-associated E3 ubiquitin ligase TRAIP ubiquitylates barriers in front of the fork to allow replisome progression. In mitosis, TRAIP is reprogrammed from a  trans -acting to a  cis -acting ligase that can ubiquitylate the replisome itself. This enables the processing of unreplicated DNA by promoting replisome disassembly, fork breakage, and joining of the broken chromosome arms. Here, we describe a mechanism for this reprogramming: the ATPase TTF2 is recruited to the replisome, where its noncatalytic N-terminal domain tethers Cyclin B-CDK1-phosphorylated TRAIP to the leading strand DNA polymerase ε in a geometry that allows replisome ubiquitylation. Thus, a phospho-regulated architectural switch alters replisome organization in mitosis to safeguard genome integrity before chromosome segregation.

Germline pathogenic variants associated with prostate cancer susceptibility in a Spanish cohort: emergence of new key players

Abstract Prostate cancer (PCa) is one of the most heritable common malignancies, yet data on germline genetic susceptibility in the Spanish population remain limited, and testing indications vary across guidelines. We aimed to characterize germline pathogenic variants (PVs) in Spanish PCa patients and identify predictors of carrier status. We retrospectively analyzed 360 PCa patients referred for genetic counseling. Multigene panel testing of 13 cancer predisposition genes was performed. PV frequencies were compared with internal pseudo-controls and public population controls. Associations with age at diagnosis, clinical risk group, and family history (FH) were evaluated. Overall, 6.4% of patients carried a germline PV. BRCA2 and ATM were the most frequently mutated genes (1.67% each), showing significant enrichment compared with all control groups. TP53 and PALB2 were also significantly associated with PCa risk. High-risk or metastatic disease, age < 60 years, and FH of hereditary breast/ovarian or Lynch syndrome-spectrum tumors were the best predictors for the presence of PV. Our findings suggest an unexpected major role for TP53 and PALB2 as key PCa susceptibility genes, reinforce the role of BRCA2 and ATM , and question the role of BRCA1 . Genetic testing may be most informative when focused on younger patients with non-low-risk disease and relevant FH.

On Zeppelin Mountain, sensors sniff Russian air

4-Octyl itaconate ameliorates cigarette smoke-induced chronic obstructive pulmonary disease by suppressing necroptosis in alveolar macrophages via Nrf2 activation

Fourier pixels for bidirectional light control

American science at 250

The ubiquitin ligase LONRF2 inhibits glycolysis and malignant phenotypes in endometrial cancer through aldolase A degradation

Biosynthesis of the Selenium-Substituted [FeFe]-Hydrogenases

Deletion of a YEDL sequence in SLC35D3 perturbs its targeting to platelet dense granule precursors

The Src family kinase YES regulates DNAJB6b chaperone activity to modulate tau aggregation in Alzheimer’s disease

Pressure-Induced Stabilization of Terbium(IV) in CsTb(CrO ₄ ) ₂ Characterized by X-ray Absorption Spectroscopy

Does SLC17A9 (VNUT) function as a stand-alone nucleotide and/or phosphate transporter?

Computational Exploration of Molecular Solar Thermal Energy Storage via Substituted Anthracenes [4 + 4] Photodimerizations and Thermal Retro-Cycloadditions in Solution and Crystalline States

Cryo-EM structure of the complex between transglutaminase 2 and the 45 kDa domain of fibronectin

Spatiotemporally Precise Chemical Neuromodulation through MOF-Mediated Near-Infrared Control of Endogenous Signaling

Ago1 is required for the regulation of mitochondrial translation under heat stress in Schizosaccharomyces pombe

Beyond C–C Cleavage: CO Detoxification as a Key Step in Ethanol Electrooxidation Revealed by In Situ SERS

Making Commodity Polymers SuFExable: A Versatile Platform by Bridging SuFEx Click Chemistry and Photo‐Modification

ABSTRACT A central challenge in polymer development lies in the dilemma between the inherent limitations of each polymer and the diverse requirements for material properties and functionalities in practical applications. Developing new methods to introduce functional groups into polymer backbones could innovatively evolve the way of endowing commodity polymers with new properties. Herein, inspired by the new generation of click chemistry, sulfur(VI) fluoride exchange (SuFEx), we found that SuFEx click chemistry can be effectively bridged with photocatalytic hydrogen atom transfer post‐modification of polymers to introduce clickable sulfonyl fluoride groups, thus forging a facile and useful platform for the functionalization, transformation, and diversification of commodity polymers.

Tail-anchored protein C-terminal domains stimulate ATP hydrolysis by the P5A-ATPase Spf1p