Proposed mechanisms by which disruption of endogenous dsRNA editing in β-cells leads to type 1 diabetes-like phenotypes in βAdarKO mice. Disruption of endogenous dsRNA editing in β-cells initiates IFN responses, thereby inducing pancreatic islet inflammation and β-cell dysfunction. Hyperglycemia induced by β-cell dysfunction further promotes islet inflammation, likely via increased dsRNA resulting from increased β-cell workload, thereby producing a vicious cycle. The mechanism by which impairment of dsRNA editing is integrated with autoimmune-mediated pathogenesis of type 1 diabetes remains to be clarified.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363094 | PMC |
| http://dx.doi.org/10.1111/jdi.14224 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Use of large language models as artificial intelligence tools in academic research and publishing among global clinical researchers.
Sci Rep
December 2024
Department of Dermatology, Niazi Hospital, Lahore, Pakistan.
With breakthroughs in Natural Language Processing and Artificial Intelligence (AI), the usage of Large Language Models (LLMs) in academic research has increased tremendously. Models such as Generative Pre-trained Transformer (GPT) are used by researchers in literature review, abstract screening, and manuscript drafting. However, these models also present the attendant challenge of providing ethically questionable scientific information.
View Article and Find Full Text PDFTransforming an azaarene into the spine of fusedbicyclics via cycloaddition-induced scaffold hopping of 5-Hydroxypyrazoles.
Nat Commun
December 2024
National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, P.R. China.
Skeleton editing for heteroarenes, especially pyrazoles, is challenging and remains scarce because these non-strained aromatics exhibit inert reactivities, making them relatively inactive for performing a dearomatization/cleavage sequence. Here, we disclose a cycloaddition-induced scaffold hopping of 5-hydroxypyrazoles to access the pyrazolopyridopyridazin-6-one skeleton through a single-operation protocol. By converting a five-membered aza-arene into a five-unit spine of a 6/6 fused-bicyclic, this work unlocks a ring-opening reactivity of the pyrazole core that involves a formal C = N bond cleavage while retaining the highly reactive N-N bond in the resulting product.
View Article and Find Full Text PDFThe mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition.
Nat Commun
December 2024
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA from tRNA solely based on the nucleotide at wobble position (N34), and a single substitution at N34 could exchange the aminoacylation specificity between two tRNAs. Here, we report the structural and biochemical mechanism of N34 recognition-based tRNA discrimination by Saccharomyces cerevisiae IleRS (ScIleRS).
View Article and Find Full Text PDFOrthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array.
Nat Commun
December 2024
Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.
Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation.
View Article and Find Full Text PDFStructural insights into how Cas9 targets nucleosomes.
Nat Commun
December 2024
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
The CRISPR-associated endonuclease Cas9 derived from prokaryotes is used as a genome editing, which targets specific genomic loci by single guide RNAs (sgRNAs). The eukaryotes, the target of genome editing, store their genome DNA in chromatin, in which the nucleosome is a basic unit. Despite previous structural analyses focusing on Cas9 cleaving free DNA, structural insights into Cas9 targeting of DNA within nucleosomes are limited, leading to uncertainties in understanding how Cas9 operates in the eukaryotic genome.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!