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The clinical application of inhibitors targeting checkpoint kinase 1 (CHK1) is challenged by limited efficacy. Here, the authors identify that thioredoxin (Trx) system inhibition mediates sensitivity to CHK1 inhibitor via regulating the activity of ribonucleotide reductase, demonstrating the synergistic effect of CHK1 inhibitor and inhibitors targeting Trx system in lung cancer models.
The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.
Histone H2AX is a central regulator in DNA repair. Here, the authors show that the H2AX C-terminal linker mediates recruitment of 53BP1, a mechanism which evolved to function independently of the canonical phospho-ubiquitin axis important for DNA repair regulation.
Perception methods that enable control systems to understand and adapt to unstructured environments are desired. Wang et. al. develop a memristor-based differential neuromorphic computing, perceptual signal processing, and online adaptation method providing neuromorphic style adaptation to external sensory stimuli.
The transcription factor WUSCHEL is essential for stem cell function, but factors that directly modulate WUS stability are unclear. This work discovers that the peptidase DA1 cleaves and destabilizes WUS to control shoot apical meristem size.
The TREK K2P channel activity is dynamically regulated by protein kinase-dependent signaling pathways involved in the development of various human diseases. Here, the authors report how phosphorylation at the proximal C-terminus induces allosteric deactivation of the selectivity filter gate.
Here, the authors develop a graphene plasmonic infrared sensor to probe the secondary structure of nanoscale assembly intermediates and the morphological evolution of silk nanofibrils, the fundamental building blocks of silk fibres.
How folded proteins are translocated across membranes is unknown for eukaryotes. Here, the authors propose a concerted translocation mechanism used by the AAA-ATPase Bcs1 to retro-translocate fully folded Rieske iron-sulfur protein across mitochondrial inner membrane.
The mechanical properties of spider silk are a consequence of the structural organisation of proteins known as spidroins. Here the authors investigate the structure of the fibers formed by a C-terminal domain of a major spidroin: the study elucidates the mechanisms by which spidroins are transformed from soluble form into a fiber.
There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein.
Estimating weather-induced shocks on food production requires reliable global weather datasets. Here, the authors compare global (GMFD and ERA5-Land) and regional (PRISM) datasets, showing that global datasets can uncover non-linear temperature relationships despite their lower predictive skill.
How fMRI resting-state functional connectivity (rs-FC) in fronto-limbic circuits relates to neural activity is unclear. Here the authors show that rs-FC in these circuits is related to local field potential coherency in the alpha band.
AgRP neurons control appetite, but their transcriptional regulation remains a mystery. Here, the authors generate AgRP neuron transcriptional and chromatin accessibility profiles and show that IRF3 mediates the acute hunger-suppressing effects of leptin.
The precise cellular localization of the SARS-CoV-2 RNA and replication partners has been elusive. Here, the authors use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscale structure of viral replication organelles.
Antifungal azoles inhibit ergosterol biosynthesis, but how that leads to fungistatic or fungicidal activities in many pathogenic fungi is poorly understood. Here, Schuster, Kilaru & Steinberg show that azole lethality in the plant pathogens Zymoseptoria tritici and Magnaporthe oryzae is due to a combination of reactive oxygen species-induced apoptosis and macroautophagy.
The relevance of post-translational modifications in pancreatic cancer remains insufficiently explored. Here, the authors report that ZDHHC20-mediated S-Palmitoylation of the m6A reader YTHDF3 stabilizes MYC mRNA to promote the progression of KRAS-mutant pancreatic cancer.
Zhang et al. propose the ecological status of the ocean by considering microbial diversity, structure, and biogeochemical potential. Ecological status of 32.44% surface ocean will change due to climate change in 2100, assuming no policy intervention.
On-chip optical sensing and metrology systems are rapidly progressing, but CMOS-compatible silicon light sources remain a challenge. This work demonstrates a broadband, foundry integrated silicon waveguide emitter and the theory that describes it.
It has long been believed that diffusion as individual atoms is the primary way for carbon to enter Fe crystals from outside. Here, the authors report an unusual mass transport way in solids, through which diamond nanoparticles can enter Fe spontaneously and translate inward for a long distance.
Evolutionary models can help understand how the spatial arrangement of a population shapes its evolutionary dynamics. This study presents such a method and shows that the spatial architectures of stem cell populations in bone marrow are suppressors of selection, hinting at a potential evolutionary design.