366 papers
This study identifies synovial fibroblasts as primary targets of JAK inhibition in rheumatoid arthritis, revealing how specific fibroblast subsets and cytokine-driven signaling mechanisms (such as TNF/IL-6 synergy and STAT uncoupling) determine the therapeutic efficacy, functional ceiling, and withdrawal risks of JAK inhibitors.
This study demonstrates that in the green alga *Chlamydomonas reinhardtii*, starvation-induced autophagy proceeds independently of the canonical ATG1 kinase complex, challenging the established model of autophagy regulation.
By integrating single-cell RNA sequencing and spatial transcriptomics across human and mouse models, this study identifies a conserved, spatially localized activated valvular interstitial cell population that drives fibrotic remodeling in myxomatous mitral valve degeneration, offering a potential therapeutic target.
By combining statistical analysis of 14,000 SNARE transmembrane domains with molecular dynamics simulations, this study reveals that distinct amino acid compositions—specifically bulky phenylalanine in early secretory pathways versus smaller isoleucine in late pathways—have evolved to optimize protein anchoring within the unique biophysical environments of different eukaryotic membranes.
This paper presents a foundation model-based approach using Parameter-Efficient Fine-Tuning that enables accurate, assembly-free detection of CRISPR arrays directly from raw DNA sequences, effectively overcoming the limitations of existing tools in handling short reads and degenerate repeats.
By combining cryo-focused ion beam milling with cryo-electron tomography, researchers resolved the ~4.7 Å in situ structure of cytoplasmic lattices in mouse embryos, revealing them to be massive ~4.5 MDa scaffolds that organize ubiquitin-charged E2-E3 ligase assemblies to regulate protein homeostasis during early development.
This study demonstrates that physically coupling the TFIIH core and kinase modules via the Tfb3 subunit is essential for restricting RNA Polymerase II CTD Serine 5 phosphorylation to promoter-proximal regions, as uncoupling these modules leads to widespread, misregulated phosphorylation across transcribed genes despite normal core module recruitment.
This study reveals that sexual dimorphism in the *Drosophila* circadian network arises from sex-specific gene expression in distinct clock neuron subtypes, which utilize differential cell adhesion molecules (dpr9 in males and dpr3 in females) to establish unique synaptic connections with downstream regulators of dimorphic behaviors.
This study identifies the AddAB complex as a critical factor for resolving head-on replication-transcription conflicts in *Bacillus subtilis* by using its helicase activity to unwind reversed replication forks, thereby re-establishing intact forks for replication restart.
This study demonstrates that targeted epigenetic modulation, delivered via Arcturus LUNAR lipid nanoparticles, achieves superior and durable PCSK9 silencing in mice compared to cytosine base editing, CRISPR-Cas9, and GalNAc-siRNA, establishing it as a promising strategy for long-lasting hepatic therapy.
This study provides evidence that the "transertion" mechanism, which couples transcription and translation to physically shift genes from the nucleoid to the plasma membrane, also occurs in the Gram-positive bacterium *Bacillus subtilis*, suggesting conserved principles of cellular regulation across bacterial types.
This study reveals that PARP1 directly disassembles nucleosomes by evicting histone dimers to form open hexasomes, a process dependent on the H2A C-terminal tail that facilitates efficient DNA repair and serves as a critical recruitment hub for repair factors.
This study reveals that DAXX utilizes distinct functional modules to uncouple histone H3.3 nucleosome assembly from endogenous retrovirus (ERV) silencing, demonstrating that while a conserved basic patch is essential for H3.3 deposition, ERV repression relies primarily on the C-terminal SUMO-interacting motif to recruit repressive complexes like MORC3.
This paper presents a comprehensive, standardized end-to-end protocol for isolating high-quality nuclei from frozen human heart tissue, which significantly improves yield and reproducibility for single-nucleus RNA sequencing applications compared to existing methods.
ProAR introduces a probabilistic autoregressive framework with a dual-network system and anti-drifting sampling strategy to generate flexible, long-length molecular dynamics trajectories that better capture time-dependent conformational diversity and reduce reconstruction errors compared to existing state-of-the-art methods.
Pirfenidone ameliorates obesity-driven steatohepatitis by differentially remodeling adipose tissue through mTORC1 signaling, specifically inhibiting lipogenesis in subcutaneous fat and suppressing fibrosis in visceral fat to improve liver health.
This study reveals that the nuclear speckle protein SON safeguards the efficient splicing of short, GC-rich introns with weak splice sites by stabilizing core splicing factor recruitment, thereby enabling the high expression of evolutionarily expanded essential genes.
This study reveals that ATM safeguards DNA replication by preventing aberrant PRIMPOL-dependent repriming at spontaneous oxidative base lesions, and its absence creates replication gaps that require homologous recombination for repair, thereby driving synthetic lethality with PARP inhibitors.
FreeTrace is a novel single-molecule tracking framework that utilizes fractional Brownian motion and deep learning to overcome the limitations of traditional Brownian motion assumptions, enabling robust and accurate analysis of anomalous diffusion even in short, crowded intracellular trajectories.
This study reveals that free-roaming dogs and diverse rodent species in rural Tha Wang Pha, Thailand, serve as reservoirs for multiple pathogenic *Leptospira* species, including the first confirmed detection of *L. weilii* in Thai rodents, highlighting a complex transmission cycle that bridges animal habitats and human settlements and underscores the need for integrated One Health surveillance.