376 papers
This study utilizes large-scale mutational analysis to reveal how IStrons balance their dual functions of RNA-guided DNA cleavage and self-splicing, identifying a molecular convergence point at the transposon right end and demonstrating that guide RNA structural stability governs the trade-off between these competing pathways.
This study utilizes cryo-electron microscopy to reveal the structural mechanisms of DNA-PKcs-independent Non-Homologous End-Joining in yeast, demonstrating how Dnl4-mediated synaptic complexes achieve continuous DNA-end protection and strand-specific ligation on microhomology substrates while explaining the inefficiency of blunt-end joining through a non-aligned, ligation-incompatible configuration.
By integrating bulk and single-cell transcriptomic data from 200 patients, this study identifies a clinically relevant "neuroimmunome" signature within leukocytes that correlates with HTLV-1 proviral load and disease severity, offering new biomarkers and therapeutic targets for HTLV-1-associated disorders like ATL and HAM/TSP.
Using the C26 cancer cachexia model, this study demonstrates that while anorexia is the primary driver of body weight, fat, and muscle loss, physical performance impairment is caused by anorexia-independent mechanisms, highlighting the critical need to distinguish between these effects to better understand cachexia pathophysiology.
This study presents a temporal ribosome-profiling atlas of the mouse ischemic brain, revealing that stroke triggers a staged translational injury response characterized by hyperacute stop-codon readthrough and GC-biased translation, followed by widespread reading frame disruption and alternative ORF usage.
This study challenges the historical view of *Molossus molossus* as a short-lived species by documenting a female surviving to 13 years and revealing that this tropical bat exhibits minimal age-related telomere shortening with parallel ageing trajectories in both sexes.
This study presents a novel zebrafish model for LGMDR1 that, while phenotypically subtle on its own, successfully recapitulates human disease gene expression patterns when treated with the Wnt inhibitor pyrvinium, offering a promising platform for therapeutic discovery.
This study reveals that microRNAs, canonically known as post-transcriptional repressors, can drive transcriptional activation by binding to m6A-modified chromatin-associated RNAs to recruit AGO proteins and subsequently recruit chromatin remodelers and DNA demethylases, thereby establishing a permissive chromatin environment.
This study demonstrates that in *Haloferax volcanii*, the paralog AliA serves as the primary enzyme for lipoprotein lipidation, while AliB plays a minor, non-redundant role, thereby establishing distinct functions for these enzymes and advancing the understanding of archaeal lipoprotein biogenesis.
This study reveals that eukaryotic transcription factors achieve rapid target search in living cells not through facilitated diffusion, but via cooperative self-interactions mediated by intrinsically disordered regions that work synergistically with structured dimerization domains to stabilize binding.
The human GRK4 65L variant causes salt-sensitive hypertension by inhibiting the HDAC1 pathway, which subsequently upregulates renal SLC4A5 and AT1R expression to enhance sodium transport and increase blood pressure.
This study identifies the transcription factor MEF2A as a negative regulator of pancreatic beta cell maturation and function, demonstrating that its stress-induced upregulation during endoplasmic reticulum stress suppresses key beta cell identity genes and impairs insulin secretion, while its inhibition preserves beta cell function under metabolic stress.
This study demonstrates that the TOP2B-selective inhibitor topobexin effectively phenocopies the effects of TOP2B gene knockout in hiPSC-derived cardiomyocytes, establishing it as a viable alternative to genetic deletion for investigating TOP2B function and screening cardioprotectants against anthracycline-induced cardiotoxicity.
This study challenges the traditional view of mutually exclusive hepatic metabolic states by identifying a novel, naturally insulin-resistant subset of periportal hepatocytes that simultaneously perform gluconeogenesis and de novo lipogenesis in the fed state, a phenomenon that expands in high-fat diet conditions and suggests a new paradigm for understanding liver insulin resistance.
This study demonstrates that endometrial epithelial organoids serve as a robust model to reveal how microbial-derived D-lactate and LPS differentially modulate epithelial growth and inflammatory signaling, respectively, without significantly disrupting key markers of uterine receptivity.
This study comprehensively evaluates eleven plasma EV isolation methods to demonstrate that no single approach is universally optimal, instead providing an evidence-based framework to guide method selection based on specific downstream analytical goals such as proteome coverage, purity, or throughput.
This study utilizes a time-controllable CRISPR screening system to map the regulatory networks of key immunosuppressive surface molecules in cancer, identifying the membrane-trafficking factor DNAJC13 as a critical regulator whose suppression enhances T-cell-mediated tumor destruction and improves survival in pancreatic cancer models.
This study establishes a tamoxifen-gated system in embryonic stem cells to demonstrate that while the pioneer transcription factor GRHL2 can bind target sites independently, the histone mono-methyltransferases KMT2C and KMT2D function as crucial co-activators that amplify enhancer activation and transcriptional output.
This paper introduces TFU72, a novel and potent DNA-PKcs inhibitor that significantly enhances homology-directed repair gene editing efficiency by up to 30-fold while providing strategies to mitigate associated genotoxic risks for safe therapeutic and research applications.
This study identifies that the loss of FMRP in Fragile X syndrome disrupts m⁶A-dependent translation of DGKκ, leading to its depletion which directly drives core phenotypic abnormalities including hyperactivity, dendritic spine defects, and excessive protein synthesis.