Results 61 to 70 of about 821,290 (231)

Synonymous Mutations in rpsT Lead to Ribosomal Assembly Defects That Can Be Compensated by Mutations in fis and rpoA

Frontiers in Microbiology, 2020
We previously described how four deleterious synonymous mutations in the Salmonella enterica rpsT gene (encoding ribosomal protein S20) result in low S20 levels that can be compensated by mutations that restore [S20].
Anna Knöppel, Dan I. Andersson, Joakim Näsvall   +2 more
doaj   +1 more source

Fitness-compensatory mutations in rifampicin-resistant RNA polymerase

, 2012
Mutations in rpoB (RNA polymerase β-subunit) can cause high-level resistance to rifampicin, an important first-line drug against tuberculosis. Most rifampicin-resistant (RifR) mutants selected in vitro have reduced fitness, and resistant clinical ...
Brandis, Gerrit,, Liljas, Lars,, Wrande, Marie,, Hughes, Diarmaid,   +3 more
core   +1 more source

A novel quinazolinone insulin receptor inhibitor and its synergy with an EGFR inhibitor in glucose‐driven glioblastoma

Molecular Oncology, EarlyView.
The novel styrylquinazolinone‐based molecule W1B effectively suppresses glioblastoma by inhibiting IGF1R and EGFR. In high‐glucose microenvironments driving tumor resistance, W1B acts synergistically with the EGFR inhibitor dacomitinib. This combination safely blocks compensatory survival signaling in zebrafish xenograft models. Showcasing promising in
Patryk Rurka, Wioleta Cieślik, Wojciech Płaziński, Katarzyna Stępnik, Anna Boguszewska‐Czubara, Elżbieta Kot, Robert Musioł, Mateusz Jasica, Anna Mrozek‐Wilczkiewicz, Katarzyna Malarz   +9 more
wiley   +1 more source

Modular epistasis and the compensatory evolution of gene deletion mutants. [PDF]

PLoS Genetics, 2019
Screens for epistatic interactions have long been used to characterize functional relationships corresponding to protein complexes, metabolic pathways, and other functional modules.
José I Rojas Echenique, Sergey Kryazhimskiy, Alex N Nguyen Ba, Michael M Desai   +3 more
doaj   +1 more source

Epigenetic heterogeneity and plasticity in therapy‐induced tumor states through single‐cell multi‐omics

Molecular Oncology, EarlyView.
Single‐cell multi‐omics reveals epigenetic heterogeneity across therapy‐adaptive tumor states, including quiescent/dormant, drug‐tolerant persister, and EMT‐like phenotypes. By linking regulatory features with state‐associated biomarkers, these approaches inform biomarker‐guided therapeutic strategies for evolving tumors.
Hee Jung Kim, Hwiyeong Lee, Jin Hong, Daechan Park   +3 more
wiley   +1 more source

Genomic epidemiology analysis of extremely drug-resistant tuberculosis in Shanghai, China

Emerging Microbes and Infections
Tuberculosis (TB), particularly extremely drug-resistant TB (EDR-TB), remains a significant public health concern worldwide. Understanding the transmission patterns and epidemiological characteristics of EDR-TB is vital for effective disease control ...
Xiaoyu Lu, Yuan Jiang, Yanping Liu, Junhong Chen, Yinglin Lao, Jing Li, Yangyi Zhang, Nan Li, Lili Wang, Chenlei Yu, Qi Ye, Wei Wei, Jiale Deng, Xin Shen, Chongguang Yang   +14 more
doaj   +1 more source

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

Molecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington, Divya L. Dayanidhi, Mohammad Zokaasadi, John B. Mantyh, Pelumi D. Olawuni, Gabrielle Rupprecht, Jeremy M. Force, Shannon McCall, Ashwani K. Bahl, David S. Hsu, Jason A. Somarelli   +10 more
wiley   +1 more source

Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease.

PLoS Genetics, 2020
Drug-resistant mutations often have deleterious impacts on replication fitness, posing a fitness cost that can only be overcome by compensatory mutations.
Tian-Hao Zhang, Lei Dai, John P Barton, Yushen Du, Yuxiang Tan, Wenwen Pang, Arup K Chakraborty, James O Lloyd-Smith, Ren Sun   +8 more
doaj   +1 more source

In vitro and in silico modelling of ROS1‐positive non‐small cell lung cancer reveals fusion‐dependent tyrosine kinase inhibitor responses

Molecular Oncology, EarlyView.
Drug resistance limits treatment success in a subset of lung cancers driven by ROS1 gene alterations. Using patient‐derived cells and computer simulations, we studied three key mutations and how they affect five targeted drugs. The mutations reduced drug effectiveness in different ways by altering protein structure and behavior.
Farhan Ul Haq, Marc Terrones, Felicia Rodrigues Fortes, Anne Schepers, Alessia Denis, Christophe Deben, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer   +8 more
wiley   +1 more source

Perspective:Sign Epistasis and Genetic Constraint on Evolutionary Trajectories

, 2005
Epistasis for fitness means that the selective effect of a mutation is conditional on the genetic background in which it appears. Although epistasis is widely observed in nature, our understanding of its consequences for evolution by natural selection ...
Weinreich, Daniel M., Watson, Richard A., Chao, Lin   +2 more
core   +1 more source