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Autophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 T cells

Autophagy shapes CD8 T cell fate; yet the timing, triggers and targets of this process are poorly defined. Herein, we show that naive CD8 T cells have high autophagic flux, and we identify an autophagy checkpoint whereby antigen receptor engagement and inflammatory cytokines acutely repress autophagy by regulating amino acid transporter expression and intracellular amino acid delivery. Activated T cells with high levels of amino acid transporters have low autophagic flux in amino-acid-replete conditions but rapidly reinduce autophagy when amino acids are restricted. A census of proteins degraded and fueled by autophagy shows how autophagy shapes CD8 T cell proteomes. In cytotoxic T cells, dominant autophagy substrates include cytolytic effector molecules, and amino acid and glucose transporters. In naive T cells, mitophagy dominates and selective mitochondrial pruning supports the expression of molecules that coordinate T cell migration and survival. Autophagy thus differentially prunes naive and effector T cell proteomes and is dynamically repressed by antigen receptors and inflammatory cytokines to shape T cell differentiation.

Photometric detection at 7.7 μm of a galaxy beyond redshift 14 with JWST/MIRI

The James Webb Space Telescope (JWST) has spectroscopically confirmed numerous galaxies at z > 10. While weak rest-frame ultraviolet emission lines have only been seen in a handful of sources, the stronger rest-frame optical emission lines are highly diagnostic and accessible at mid-infrared wavelengths with the Mid-Infrared Instrument (MIRI) of JWST. We report the photometric detection of the distant spectroscopically confirmed galaxy JADES-GS-z14-0 at (z=14.3{2}_{-0.20}^{+0.08}) with MIRI at 7.7 μm. The most plausible solution for the stellar-population properties is that this galaxy contains half a billion solar masses in stars with a strong burst of star formation in the most recent few million years. For this model, at least one-third of the flux at 7.7 μm originates from the rest-frame optical emission lines Hβ and/or [O iii]λλ4959, 5007. The inferred properties of JADES-GS-z14-0 suggest rapid mass assembly and metal enrichment during the earliest phases of galaxy formation. This work demonstrates the unique power of mid-infrared observations in understanding galaxies at the redshift frontier.

Prediction of thermal conductivity in CALF-20 with first-principles accuracy via machine learning interatomic potentials

Understanding the thermal transport properties of CALF-20, a recent addition to the metal-organic framework family, is crucial for its effective utilization in greenhouse gas capture. Here, we report the thermal transport study of CALF-20 using artificial neural network-based machine learning potentials. We use the Green-Kubo approach based on equilibrium molecular dynamics, with a heat-flux renormalization technique, to determine the thermal conductivity (κ) of CALF-20. We predict that the anisotropic thermal transport in CALF-20, with κ below 1 Wm−1K−1 at 300 K, is ideal for thermoelectric applications. Our analysis reveals a weak temperature dependence (κ ~ 1/T0.56) and near invariance with pressure in κ value of CALF-20, which stands out from the typical trend observed in crystalline materials. The outcome of the study, leveraging advanced computational techniques for predictive modeling, offers valuable insights into more suitable applications of CALF-20 with tailored thermal properties.

Emergent quantum Majorana metal from a chiral spin liquid

We propose a mechanism to explain the emergence of an intermediate gapless spin liquid phase in the antiferromagnetic Kitaev model in an externally applied magnetic field, sandwiched between the well-known gapped chiral spin liquid and the gapped partially polarized phase. We propose that, in moderate fields, π-fluxes nucleate in the ground state and trap Majorana zero modes. As these fluxes proliferate with increasing field, the Majorana zero modes overlap creating an emergent ({{mathbb{Z}}}_{2}) quantum Majorana metallic state with a “Fermi surface” at zero energy. We further show that the Majorana spectral function captures the dynamical spin and dimer correlations obtained by the infinite Projected Entangled Pair States method, thereby validating our variational approach.

Biallelic variants in RYR1 and STAC3 are predominant causes of King-Denborough Syndrome in an African cohort

King-Denborough Syndrome (KDS) is a congenital myopathy (CM) characterised by myopathy, dysmorphic features and susceptibility to malignant hyperthermia. The objective of this study was to investigate the genotype-phenotype correlation in Black African patients presenting with CM, specifically those with KDS-like phenotypes, who remained undiagnosed for over 25 years. A cohort of 67 Black African patients with CM was studied, of whom 44 were clinically evaluated and diagnosed with KDS. Whole-exome sequencing (WES) was performed as part of an international genomics study (ICGNMD) to identify potential pathogenic mutations. Genomic assessments focused on identifying relevant genes, including RYR1 and STAC3, and establishing genotype-phenotype correlations. The study identified RYR1 and STAC3 mutations as the predominant genetic causes of KDS in this cohort, with mutations in both genes exhibiting autosomal recessive inheritance. While RYR1 has previously been linked to autosomal dominant mutations, STAC3, which was formerly associated exclusively with Native American Myopathy/Bailey-Bloch Myopathy, congenital hypotonia, and susceptibility to malignant hyperthermia, is now newly associated with CM-KDS in this study. This establishes the first genotype-phenotype correlation for 44 Black African individuals with KDS. This study marks a significant milestone in research on understudied African populations with CM, emphasising the lengthy diagnostic journey these patients endured. The findings highlight the pressing need for improved access to genomic medicine in underserved regions and underscore the importance of expanding research and diagnostic capabilities in Africa. This work contributes to the advancement of genetic medicine in underrepresented populations, facilitating better diagnostic and therapeutic outcomes.

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