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Telomere length varies across chromosome arms, but most studies measure only averages. Here, the authors use long‑read sequencing in >2,500 participants to map chromosome‑specific lengths, showing arm‑level variation, strong individual differences, and associations with aging and disease.

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Precise editing of DNA methylation has emerged as a promising tool in disease biology but most applications are limited to in vitro systems. Here, we develop two transgenic mouse lines harboring an inducible dCas9-DNMT3A or dCas9-TET1 editor to enable tissue-specific DNA methylation editing in vivo.

Establishment and maintenance of appropriate cell size is a prerequisite for cells to function efficiently. Here, Kiriakopulos et al. reveal that the lncRNA CISTR-ACT maintains cell size across cell types in humans and mice by regulating cell morphogenesis genes in trans via guidance of the transcription factor FOSL2.

Whether and how prefrontal astrocyte Ca²⁺ signaling modulates different neuronal populations in aiding or inhibiting anxiety-like behavior remains not fully understood. Here authors show that prefrontal astrocytes encode anxiogenic cues and modulate excitatory and inhibitory neurons differently. Silencing prefrontal astrocytes heightens anxiety-like behavior and induces proteomic changes in astrocytes and neurons.

Williams et al. report a growth arrest mechanism in residual cancer persister cells through targeted therapy-induced upregulation of type I interferon signalling, which is negatively regulated by apoptotic DNA endonuclease DFFB to allow tumour relapse.

Lysosomal storage diseases like mucopolysaccharidosis type I (MPS I) cause pathology before birth and result in early morbidity and mortality. Here, the authors show that in utero base editing mediates multi-organ phenotypic and survival benefits in a mouse model recapitulating a common human MPSI mutation.

An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid transport between organelles and lipid asymmetry across membrane leaflets.

Despite being an important driver of a subset of medulloblastomas, efforts to therapeutically target Sonic Hedgehog (SHH) signaling, such as with the use of Smoothened (SMO) inhibitors, have had limited success. Here, the authors find that SHH medulloblastomas are sensitive to netrin-1 inhibition and investigate netrin-1 as a mechanism of resistance to SMO inhibition.

Multiferroic BiFeO₃ is promising for applications where electric and magnetic fields need to be coupled, for example, in magnetic data storage. Here, combining theory and experiment the authors provide a microscopic insight into the switching of magnetization by electric fields in BiFeO₃.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Glycolysis is elevated in many cancers. In this study, the authors show that lactoylglutathione, a by-product of methylglyoxal produced from increased glycolysis, is elevated in lung cancer in mouse models and humans, arguing reactive metabolite production can be a liability for cancers.

Development of a biosensor for GPCR trafficking to the lysosome combined with a genome-wide CRISPR screen identified DNAJC13 as a critical regulator of agonist-induced trafficking of the δ-opioid receptor to the lysosome.

Here the authors isolate monoclonal antibodies specific for Plasmodium vivax apical membrane antigen 1, and characterize the epitope of one antibody that inhibits invasion of reticulocytes and hepatocytes, and reduces liver infection in a mouse model.

Antibodies that bind to both H1 and H3 influenza strains exist in the pre-vaccination serum repertoire of healthy adults; most vaccine-elicited clonotypes bind either H1 or H3 strains.

Apicomplexan parasites share complex cell pellicular structures that isolates the cytosol from most of the plasma membrane. Koreny et al show that, as an early adaptation to this barrier, dedicated stable endocytic structures occur at select sites in these cells. In Toxoplasma, plasma membrane homeostasis is particularly dependent on endocytosis.

Intratumoral hypoxia promotes cancer progression. Here, authors show that hypoxia upregulates RNA Polymerase I activity and ribosome biogenesis in breast cancer cells and targeting RNA Polymerase I with BMH-21 reduces tumor growth and metastasis in murine models.

GvpU regulates spatial organization of gas vesicles in the bacterial cytosol through tunable interactions with the core gas vesicle shell protein and phase transition, enabling future opportunities for engineering of cellular buoyancy.

Osteocytes are mechanoresponsive within skeletal tissue. Here, the authors show that class IIa histone deacetylases are phosphorylated by focal adhesion kinase, suggesting that HDAC5 may propagate mechanobiological cues to regulate cell type-specific gene expression.

A study presents a cross-species proteomic map of synapse development in neocortex and reveals that the human postsynaptic density assembly develops two to three times slower than that in macaques and mice.

Here Mukherjee et al. characterize the bidirectional communication between adipose tissue and ovarian cancer cells and show that adipocytes instruct cancer cells to divert glycolytic glycerol-3-phosphate towards lipid synthesis, thus promoting metastasis.

Crystal structures of HIV-1 Env V1V2 in complex with human broadly neutralizing antibodies and ontogeny analyses allow the engineering of Env trimers that are recognized by ancestor and intermediate antibody forms.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Kucharska, Ivanochko and Hailemariam and colleagues solved cryo-EM structures of Pfs48/45, needed for Plasmodium falciparum development, with potent antibodies. The work revealed conformational epitopes, with implications for design of therapies against malaria.

The chemosynthetic symbionts of the bivalve Loripes lucinalis and nematode Laxus oneistus are found to encode nitrogen fixation genes, with evidence for active nitrogen fixation.

B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.

Disruption of autophagy function in cellular and animal models of tauopathy increases tau aggregation. Here, the authors describe a small-molecule screen to identify compounds that promote autophagy clearance of tau and rescue disease-relevant phenotypes in tauopathy patient-derived neurons.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Armstrong and colleagues discover that combined targeting of IKAROS and MENIN is a therapeutic strategy for acute myeloid leukemia through disruption of essential leukemogenic transcriptional programs.

Small molecule drugs promise to remain a valuable tool in controlling the ongoing COVID-19 pandemic. Here the authors describe optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for potential treatment of COVID-19.

The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.

Rich and colleagues identify that lymphatic endothelial-like cells in glioblastoma drive the growth of cancer stem cells via CCL21–CCR7 signaling, inducing KAT5 to acetylate HMGSC1, which enhances its protein stability and cholesterol synthesis.

Pediatric brain cancers are lethal malignancies driven by less-differentiated stem-like cells. Here the authors show that these cells exhibit distinct mitochondrial metabolism programs with targetable vulnerabilities.

Fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with long COVID.

An extracorporeal cross-circulation approach enables, in a swine model, 36 hours of normothermic perfusion in healthy lungs, the recovery of injured lungs, and extended therapeutic interventions in all lungs.

Gastric aspiration severely injures donor lungs, frequently making them unacceptable for transplantation. Here the authors show that an interventional cross-circulation platform enables the regeneration of severely damaged lungs in a swine model of gastric aspiration injury.

A proteomics and computational approach was developed to map the proximal proteome of the activated μ-opioid receptor and to extract subcellular location, trafficking and functional partners of G-protein-coupled receptor activity.

Iterative Synthetically Phosphorylated Isomers (iSPI) is a proteome-scale library of human-derived phosphoserine-containing phosphopeptides with precisely known positions of phosphorylation. This multi-purpose resource is available for optimization, standardization, and benchmarking of key steps in phosphoproteomics workflows.

Beta-arrestins play central roles in the mechanisms regulating GPCR signalling and trafficking. Here the authors identify a selective inhibitor of the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP-2, which they use to dissect the role of the β-arrestin/β2-adaptin interaction in GPCR signalling.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Rodeheffer and colleagues show that a high-fat diet in mice activates Akt2 signalling in adipocyte precursors within white adipose tissue deposits, leading to their proliferation and differentiation into adipocytes, and to obesity.

The presentation of antigen by germinal-center B cells to follicular T cells engenders the process of antibody affinity maturation and humoral memory. Pierce and colleagues show that TLR9 signaling in B cells antagonizes B cell–mediated antigen presentation, which leads to the enhanced generation of short-lived plasma cells and the production of lower-affinity antibodies.

A screen of nutrient-derived compounds identified trans-vaccenic acid as a promoter of effector T cell function, and functional assays demonstrate that this occurs via inactivation of GPR43 on T cells.

THOC6 is required for TREX tetramer formation. Analysis of pathogenic THOC6 variants differentiate the conserved mRNA export functions of TREX dimers and RNA processing functions of TREX tetramers underlying THOC6 Intellectual Disability Syndrome.

Collignon et al. report that Mettl3-mediated m⁶A RNA methylation promotes developmental pausing in embryonic stem cells and blastocysts by establishing transcriptional dormancy.