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| http://dx.doi.org/10.1093/nar/23.10.1647 | DOI Listing |
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Mechanism-guided engineering of a minimal biological particle for genome editing.
Proc Natl Acad Sci U S A
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Innovative Genomics Institute, University of California, Berkeley, CA 94720.
The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.
View Article and Find Full Text PDFMultiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.
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January 2025
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.
View Article and Find Full Text PDFTDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.
Cell Rep
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Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA. Electronic address:
The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.
View Article and Find Full Text PDFAssessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.
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Department of Otorhinolaryngology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.
View Article and Find Full Text PDFTungsten Diselenide Nanoparticles Produced via Femtosecond Ablation for SERS and Theranostics Applications.
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Emerging Technologies Research Center, XPANCEO, Internet City, Emmay Tower, Dubai, United Arab Emirates.
Due to their high refractive index, record optical anisotropy and a set of excitonic transitions in visible range at a room temperature, transition metal dichalcogenides have gained much attention. Here, we adapted a femtosecond laser ablation for the synthesis of WSe nanoparticles (NPs) with diameters from 5 to 150 nm, which conserve the crystalline structure of the original bulk crystal. This method was chosen due to its inherently substrate-additive-free nature and a high output level.
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