Mesenchymal stem cell senescence as a potency brake: causes, consequences, and cures. [PDF]
Zhou S, Xie Y, Guo Y, Zhang Y, Liu Y.
europepmc +1 more source
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
Development of pH-Sensitive β‑Adrenergic Receptor Antagonists. [PDF]
Braun T +4 more
europepmc +1 more source
We identify USP29 as the only DUB mirroring CA9 expression, a marker of hypoxia and HIF pathway activation associated with PCA aggressiveness. USP29 stabilizes HIF‐1α and HIF‐2α via a noncanonical mechanism that is independent of PHD/pVHL activity yet relies on proteasomal regulation, establishing USP29 as a previously unrecognized regulator of hypoxic
Amelie S Schober +16 more
wiley +1 more source
An Interpretable Multi-Objective Machine Learning Framework for In Silico Prioritization of Anti-<i>Staphylococcus aureus</i> Antimicrobial Peptides. [PDF]
Xu J +5 more
europepmc +1 more source
Finding novel vulnerabilities of hypomorphic BRCA1 alleles
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder +10 more
wiley +1 more source
Discovery of Novel Bicyclic Pyrazole Amides as Potent Neuronal K<sub>V</sub>7 Potassium Channel Openers with Strong Preclinical Antiseizure Activity. [PDF]
Sun S +24 more
europepmc +1 more source
MITF maintains genome stability in nonmelanocyte lineages
MITF is essential for melanocyte survival and acts as an oncogene in 10%–20% of melanomas. We show that MITF depletion causes genome instability in nonmelanocytic cells, leading to LATS2‐mediated P53 activation, cell cycle arrest, and apoptosis. This study highlights the role of MITF as a genome maintenance factor beyond the melanocyte lineage. Created
Drifa H. Gudmundsdottir +13 more
wiley +1 more source
Design of New Potent, Selective, and Long-Acting NOP Receptor Agonists through Multiple Sequential d-Amino Acid Substitutions of [Arg14 Lys15]N/OFQ(1-15)-NH2. [PDF]
Sturaro C +16 more
europepmc +1 more source
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 +9 more
wiley +1 more source

