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Here the authors show that protein phase separation is a key mechanism in cellular receptor internalization via fast endophilin mediated endocytosis (FEME). Phase separation facilitates multivalent FEME-protein assembly in this clathrin-independent pathway.

VAMP-seq is a scalable assay that measures the effects of missense variants on intracellular protein abundance. Applying VAMP-seq to thousands of PTEN and TPMT variants helps to classify them as pathogenic or benign.

This study uses high-throughput chromosome conformation capture (Hi-C) to identify phage–host relationships in soil. By coupling Hi-C with DNA and RNA sequencing, the authors demonstrate the impact of soil drying on phage–host interactions and the downstream effects on abundances and interspecies interactions within bacterial communities.

Total in vitro biosynthesis can reveal unusual pathways evolved by nature to produce natural products. Here the authors report on enzymatic cascades, comprising a cryptic methylation sequence, efficiently delivering β-lactone-containing peptide proteasome inhibitors with promising anticancer activity.

How entorhinal grid cells control hippocampal coding and behavior remains elusive. The authors report that increasing the spatial scale of grid cells expands the scale and reduces the stability of place fields, impairing spatial memory in mice.

GPAT1 is a mitochondrial outer membrane protein that catalyzes the first step of glycerolipid biosynthesis. Cryo-EM structures and functional studies of human GPAT1 uncover the molecular architecture and mechanism of this important acyltransferase.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Use of immobilized enzymes in bioremediation has potential in water treatment, but limited enzymatic activity and stability can cause issues. Here, the authors report the development of a strategy to immobilize enzymes within a hydrogel while maintaining good activity against a range of pollutants.

A complete revolution of exo-Neptune LTT 9779 b was observed with the NIRISS/SOSS instrument onboard the JWST. The resulting full phase curve is indicative of an equatorial jet that transports heat from the dayside to the colder nightside, resulting in an asymmetric distribution of clouds on the planet.

Hagenbeek et al. identify a small-molecule pan-TEAD inhibitor that blocks the interaction between YAP/TAZ and TEAD proteins. They demonstrate that treatment with the inhibitor leads to antitumor activity and can synergize with KRAS G12C inhibition.

Experimental manipulation of the gut microbiome in animal models impacts fear behaviours. Here, the authors show in a pilot study that features of the human infant gut microbiome are associated with non-social fear behaviours during a laboratory based assessment.

Abnormal CSF accumulation in the brain can lead to hydrocephalus. The mechanisms regulating CSF clearance during early development are unclear. Here, the authors show that NKCC1 regulates the clearance of both CSF K⁺ and fluid volume through the choroid plexus during postnatal development in mice.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Hyper-phosphorylated tau accumulates in Alzheimer’s disease; but the roles of these phosphorylation sites are unclear. Here the authors show that phosphorylation of a single site, pSer416, limits its turnover and promotes accumulation.

The structure of the ligand-free HIV-1–Env trimer allows conformational fixation of Env and generation of an antigen that binds CD4 with high affinity and is recognized by broadly neutralizing antibodies but not poorly neutralizing ones.

In their complex, the SARS-CoV-2 nsp13 helicase and RNA polymerase would translocate on RNA in opposite directions. Cryo-EM and MD simulations resolve this conundrum, suggesting an allosteric mechanism to turn the helicase on and off.

Matoba, Le, Valone et al. characterized context-dependent genetic effects on gene regulatory activity during Wnt stimulation, finding that genetic variant function during neurodevelopment patterning can lead to differences in adult brain traits.

Targeted protein degradation of cell-surface glycoproteins suppresses cancer in mice.

Neely et al. investigated the regeneration of different oligodendrocytes after demyelination. They found that newly generated cells exhibit much more proficient remyelination than those that survive demyelination, with implications for MS.

Structural, biochemical and cellular analyses show that bacterial antigens can mimic gliadin epitopes involved in celiac disease being presented by HLA-DQ2.5 and recognized by T cells derived from patients.

Ewing sarcoma (ES) is driven by the oncogenic fusion-protein EWSR1::FLI1. Here the authors identify that a galactosyltransferase C1GALT1 stabilizes Smoothened protein to activate Hedgehog signaling and promote EWSR1::FLI1 transcription in ES cells, which could be therapeutically targeted by an anti-fungal drug itraconazole that inhibits C1GALT1.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Whole-genome resequencing of 445 Lactuca accessions, including major lettuce crop types and wild relative species, provides a comprehensive map of lettuce genome variations and sheds light on the domestication history of cultivated lettuce.

Treatment of patients with advanced hepatocellular carcinoma with a personalized DNA vaccine in combination with anti-PD-1 therapy was safe and led to encouraging clinical efficacy, with immunological analyses confirming the induction of tumor antigen-specific T cell responses.

MNK2 was identified as the target of a small molecule named CID661578 that can stimulate pancreatic β-cell generation in zebrafish, pig and human organoids. CID661578 prevents MNK2 from binding to eIF4G in the translation initiation complex.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

CIM-seq offers an unsupervised deconvolution method to profile cell–cell interactions by sequencing cell multiplets of a given tissue, and was employed to analyze diverse tissues such as the intestinal epithelium, lung and spleen.

New microgrid recordings on the human hippocampal surface reveal that oscillations travel in reversing directions. The route of travel at a given moment was related to behavior and topographic patterns of activity strength, suggesting directions may be biomarkers of hippocampal cognitive processes.

Nsp15 is a uridine specific endoribonuclease present in all coronaviruses. Here, the authors determine the cryo-EM structures of SARS-CoV-2 Nsp15 in the apo and UTP-bound states, which together with biochemical experiments, mass spectrometry and molecular dynamics simulations provide insights into the catalytic mechanism of Nsp15 and its conformational dynamics.

A mitochondrial complex I inhibitor exhibited dose-limiting toxicities, including neurotoxicity, in patients with acute myeloid leukemia and solid tumors, warranting further studies to evaluate the mechanism linking oxidative phosphorylation inhibition and neurotoxicity.

Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.

The crystal structure of the full-length ileS T-box–tRNA complex from Mycobacterium tuberculosis provides a complete high-resolution explanation of tRNA decoding and aminoacylation sensing by this riboregulator.

The role of the immune system in tissue regeneration remains poorly understood. Here, in bone marrow transplantation and organoid culture models, T-cell-derived Interferon-γ is shown to promote STAT1-dependent intestinal stem cell c-MYC expression and epithelial regeneration.

Cryo-EM structures of simian immunodeficiency virus (SIV) envelope trimers with neutralizing antibodies reveal mechanisms—conserved throughout SIV evolution—of immune evasion through extended variable loops and glycan shielding, involving both N- and O-linked glycans.

Due to the limited wavelength coverage of measurements to date, some aspects of the composition of Pluto’s largest moon, Charon, remain unresolved. Here, the authors detect carbon dioxide and hydrogen peroxide on the surface of Charon’s northern hemisphere using JWST data.

Mammalian megafaunal biodiversity has declined since the Plio-Pleistocene. Here, the authors apply ecometric methods to evaluate the functional link between eastern African herbivorous megafauna and their environments, showing that some biodiversity loss coincided with community ecological function disturbance.

Research on racial and ethnic influence on breast cancer mortality is stymied by a lack of genomic studies in diverse populations. Here, the authors genomically interrogate 194 Nigerian breast cancers, unveiling molecular features that could explain the high mortality rate from breast cancer in an indigenous African population.

The link between stiffness heterogeneity and tumor cell heterogeneity remains poorly understood. Here, authors propose an AI-informed method that reveals correlations between stromal stiffness and breast cancer cells with a heterogeneous EMT phenotype.

Functional interplay of sex hormones in estrogen receptor–positive breast cancer unveils the therapeutic potential of androgen receptor agonists.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Multi-modal profiling reveals major alterations in colonic B cells in patients with ulcerative colitis, including reduced clonal diversity of plasma cells, and suggests that circulating gut-homing plasmablasts could serve as a biomarker for disease activity.

Cryo-EM structures of the multienzyme complex between the endoribonuclease Las1 and the polynucleotide kinase Grc3 reveal two molecular switches that coordinate nuclease and kinase function.

Chromosomal instability occurs frequently in cancer, making it an attractive therapeutic target. Here, the authors identify KIF18A as a targetable vulnerability of cancer cells with chromosomal instability and target this using VLS-1272, a selective KIF18A inhibitor.

The C termini sequences recognized by E3 ubiquitin ligase CHIP were identified via a peptide library screen. Caspase cleavage caused the exposure of aspartic acid at the C termini of Tau and caspase-6 that made them accessible to CHIP.

A number of orphan GPCRs show high constitutive activity. Here, the authors show that the high basal activity of some receptors can be explained by their sensitivity to naturally abundant lipids or by penetration of ECL2 in the orthosteric binding pocket.

After infection with SARS-CoV-2 a diverse set of symptoms remain or develop longer term in a condition termed long-CoVID, yet an accurate and tractable model has remained elusive. Here the authors present a non-human primate model of long-CoVID and show persistent hyperglycemia following acute infection.

Atlantic Niño, the Atlantic counterpart of the Pacific El Niño, increases the likelihood of powerful hurricanes developing near the Cape Verde islands, elevating associated risks for the Caribbean islands and the U.S.

Duplications of gene segments can allow novel physiological adaptations to evolve. A detailed analysis of the TCAF gene family in primates and archaic humans suggest rapid duplication and diversification in this gene family is associated with cold or dietary adaptations.