Results 31 to 40 of about 27,549 (205)
Loss of IGF‐1R impairs DNA‐PKcs recruitment to chromatin leading to defective end‐joining
IGF‐1R promotes radioresistance by facilitating DNA‐PKcs recruitment to chromatin, enabling non‐homologous end‐joining (NHEJ) repair of double‐strand breaks. Inhibition or loss of IGF‐1R disrupts this recruitment to damage sites, driving compensatory reliance on microhomology‐mediated end‐joining (MMEJ) repair.
Matthew O. Ellis +3 more
wiley +1 more source
Sign epistasis caused by hierarchy within signalling cascades
Sign epistasis clearly constrains evolution, but its causes are difficult to decipher. Here, the authors study epistasis in a signalling cascade, and arrive at a general criterion and understanding of sign epistasis as arising from the inherent hierarchy
Philippe Nghe +2 more
doaj +1 more source
Epistasis: obstacle or advantage for mapping complex traits? [PDF]
Identification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype.
Koen J F Verhoeven +2 more
doaj +1 more source
Deep Contrastive Learning for High‐Throughput Prediction of Drug Resistance Mutations from Sequences
This study presents DeepMutDTA, a deep learning framework aimed at predicting mutation‐induced changes in protein‐drug interactions and prioritizing variants potentially linked to drug resistance. Trained on large‐scale data, it incorporates SimSiam‐MuTF, a label‐aware contrastive fine‐tuning strategy that encourages separation between WT and MT ...
Xiaowen Hu +7 more
wiley +1 more source
Cross Kingdom Metabolic Engineering Paradigm Elevating Sustainable Protein Production
ABSTRACT Confronting the dual crisis of escalating global protein demand and unsustainable agriculture necessitates transformative solutions. Here, we pioneer evolutionary insights from maize nitrogen optimization via asparagine synthetase (ASNS) to rewire metabolism in Pichia pastoris.
Yuanyuan Du +4 more
wiley +1 more source
We present an integrated workflow that predicts activity‐enhancing mutation combinations from minimal experimental data. By proposing in vivo unit yield (yield/expression) as a surrogate for kcat/Km through causal inference, and visualizing local activity landscape, it effectively guides product yield improvement. ABSTRACT Designing enzyme sequences to
Lin Guo +15 more
wiley +2 more sources
UCHL3 Regulates Subgenomic Flaviviral RNA Condensates to Promote Virus Propagation
ABSTRACT Flavivirus subgenomic RNAs (sfRNAs) antagonise antiviral defences, yet how sfRNAs are organized and maintained in cells remains poorly understood. Here we identify ubiquitin C‐terminal hydrolase L3 (UCHL3) as a post‐translational regulator of flavivirus sfRNA stability and function.
Oscar Trejo‐Cerro +7 more
wiley +1 more source
SLC25A13 is identified as an immunometabolic driver of triple‐negative breast cancer that sustains ferroptosis resistance and immune evasion through a STAT3–IFI6 circuit. Pharmacologic degradation of SLC25A13 restores ferroptosis sensitivity and enhances anti‐PD‐1 efficacy, highlighting a strategy to convert immune‐cold tumors into immunotherapy ...
Yingze Zhu +8 more
wiley +1 more source
The consistency of beneficial fitness effects of mutations across diverse genetic backgrounds. [PDF]
Parallel and convergent evolution have been remarkably common observations in molecular adaptation but primarily in the context of the same genotype adapting to the same conditions.
Victoria M Pearson +2 more
doaj +1 more source
Summary: We compare two previously introduced notions of epistasis and prove that they are essentially equivalent.
van Hove, H., Verschoren, A.
openaire +3 more sources

