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Understanding degradation of platinum catalysts during oxygen reduction is vital for improving proton-exchange membrane fuel cells. Here, the authors identify intermediate stages in the oxidation of Pt(111) and Pt(100) in perchloric acid using in situshell-isolated nanoparticle-enhanced Raman spectroscopy.

Plasmodium falciparum moves by an atypical process called gliding motility which comprises of atypical myosin A (PfMyoA) and filaments of the dynamic and divergent PfActin-1 (PfAct1). Here authors present the cryo-EM structure of PfMyoA bound to filamentous PfAct1 stabilized with jasplakinolide and provide insights into the interactions that are required for the parasite to produce the force and motion required for infectivity.

Analyses of pretransplant omics data from different cohorts of African American recipients found that genetic polymorphisms at the LILRB3 gene are associated with kidney graft loss.

The structural basis of integrin signaling in health and disease is not fully understood. Here, the authors determine the cryoEM structure of full-length platelet integrin αIIbβ3 in its apo and eptifibatide-bound conformations in a native membrane environment.

The search for antivirals against SARS-CoV-2 continue due to the emergence of variants of concerns, able to escape the vaccinal humoral response. In this work, authors pre-clinically explore the potential of kinetin against SARS-CoV-2, which could be used alone or in combination with other antivirals.

P450 oxidoreductase (POR) selectively activates numerous cytochromes P450 (CYP), crucial for metabolism of drugs, steroids and xenobiotics and natural product biosynthesis. Here, the authors identify ligands that bind POR and bias its specificity towards CYP redox partners, activating distinct metabolic cascades in cells.

Rapid investigation of chemical reactions is a challenge in bio-medical analysis. Here, the authors demonstrate sensitive in-situ real-time reaction-monitoring of conformational changes in protein solution, based on a fingertip-sized mid-IR lab-on-a-chip.

Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted cancers and microsatellite-unstable cancers harbouring specific mutations.

The validation of inhibitors targeting PurF, a novel drug target for tuberculosis drug discovery, is described.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

Here the authors investigate the regulatory mechanisms of acetyl-CoA (Ac-CoA) biosynthesis in Bacillus subtilis, probing the interaction between acetyl-CoA synthetase (AcsA) and acetyltransferase (AcuA). They capture a stable AcsA-AcuA complex that inhibits AcsA activity in the absence of Ac-CoA.

Light energy transfer from abundant hydroxylated carotenoids to the retinal moiety of widespread light-driven proton pumps is detected.

Osteoporosis results from misregulation of bone catabolism and bone anabolism, resulting in severe bone loss. Most current therapies act by decreasing bone catabolism, but targeting bone anabolism is more desired, because once bone is lost, it is difficult to replace. In a new report by Gerard Karsenty and his colleagues, they show that orally delivered pharmacological targeting of serotonin synthesis in the gut is sufficient to increase bone anabolism and thus restore lost bone in rat and mouse models of well-established osteoporosis (pages 264–265).

Mycobacterium abscessus is considered an emerging pathogen, given its prevalence in patients with pulmonary diseases, such as cystic fibrosis. Here, authors perform a genomic analysis on sequential isolates obtained from patients with persistent infections of M. abscessus.

Chapeau et al. develop a nonallosteric inhibitor of the interaction between YAP and all four TEAD proteins. Treatment with the inhibitor, either as monotherapy or in combination with other treatment modalities, leads to induction of cell death in several in vivo cancer models.

Actin is crucial for nervous system function yet the role of microexons in its modulation is unclear. Here, the authors show that a microexon in DAAM1 has a role in actin dynamics, neuronal function and memory formation in mice.

Mechanisms governing adaptation of breast cancer to the brain metastatic microenvironment are unclear. Here, the authors use RNA-sequencing and Drosophila screening to identify Rab11b-mediated endosomal recycling as a unique mechanism for adaptation to a challenging metastatic microenvironment, which can be exploited by repurposing statins.

Moreno-Loaiza et al. found that interleukin-1β, acting upon cardiac resident macrophages, promotes atrial fibrillation in mice, and this mechanism may represent a common pathway connecting various risk factors to this arrhythmia.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

Gomez-Sintes et al. have developed small molecules that selectively activate chaperone-mediated autophagy by stabilizing the interaction between retinoic acid receptor alpha and its co-repressor N-CoR1. They demonstrate the protective effect of boosting chaperone-mediated autophagy against retinal degeneration.

Electrons in a quasicrystal cannot flow as freely as they do in normal metallic crystals because of its nonperiodic structure. It turns out that in a decagonal quasicrystal the electronic behaviour reflects the tenfold symmetry of the crystal structure. Patricia A. Thiel and Jean Marie Dubois

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

What is the role of disorder in non-homologous end-joining proteins? The authors use nuclear magnetic resonance to reveal that disordered regions mediate a network of multivalent interactions, promoting biomolecular condensation that accelerates DNA ligation kinetics.

Retrotransposons are mobile genetic elements normally repressed by DNA methylation in differentiated cells. Here, the authors show that DNA hypomethylation in mouse induced pluripotent stem cells allows retrotransposons to jump, but this can be blocked with a reverse transcriptase inhibitor.

Cryo-electron microscopy structures of human and nematode spliceosomes show that the disassembly of this complex is initiated by the licensing of the disassembly helicase to act on the catalytic U6 small nuclear RNA.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

HER2 acts an oncogenic driver in numerous cancers. Here, the authors design an anti-HER2 biparatopic and tetravalent IgG fusion with inhibitory effects in a xenograft model.

Spontaneous liquid–liquid phase-separation behaviour of high-aspect-ratio fibrils, obtained from supramolecular polymerizations of synthetic components, forms tactoids by means of an entropy-driven pathway.

Human leukocyte antigens (HLA) are multi-allelic and polymorphic genes that present antigens to immune cells for inducing protective immunity. Here, using systems biology and structural approaches, the authors show that micropolymorphism of three HLA has effects beyond the modulation of antigen diversity.

Sustainable synthesis of valuable organic compounds like lactams relies on efficient catalysts. Here, the authors report a bimetallic silver–rhenium catalyst that selectively converts cyclic imides to lactams with high efficiency, with close silver–rhenium contact being key to its performance.

MHC class II proteins from humans, pigs, ducks, swans and chickens can serve as alternative receptor for virus entry of H2N2 influenza A viruses. This trait is conserved in Eurasian avian H2 IAV.

New delivery platforms are needed to allow broader application of biotherapeutics for CNS diseases. Here, the authors show enhanced CNS delivery with a transport vehicle engineered to bind CD98hc, a highly expressed target at the blood-brain barrier.

Previously, the small molecule inhibitor of transcriptional enhanced associate domain (TEAD) MGH-CP1 has been described in stem cells. Here, the authors demonstrate the utility of MGH-CP1 in cancer therapy and find treatment to increase Akt pathway activation via TEAD-Vgll3 activation, presenting a rationale for combination with Akt inhibition.

Binding of the small-molecule inhibitor CGI1746 to Bruton's tyrosine kinase (Btk), a therapeutic target for rheumatoid arthritis, induces an inactive Btk conformation. Application of this specific chemical probe reveals two Btk signaling pathways involved in inflammatory arthritis.

Plasmacytoid dendritic cells (pDC) are the major IFN-I-producing cells, but this production returns to baseline soon after viral infection. Here the authors show that this decrease in IFN-I production and related pDC functions may be attributed to suppressed oxidative and glycolytic metabolism of pDCs, with lactate dehydrogenase B identified as a regulator.

Fiber optic implantation in deep areas of the rodent’s brain for MRI combined with optogenetics is challenging. Here the authors use an MRI-guided robotic arm as the navigation method for accurate fiber optic placement and precise microinjection during multi-modal fMRI, optogenetics and calcium recordings.

Recombinant MHC class II molecules are instrumental in antigen-specific T-cell identification assays and showed efficacy as experimental medicines. Here, the authors engineer MHC class II molecules with species-specific knob-into-hole heteromerization domains, enabling a translatable purification process with improved stability, yields, and biological potency.

The endometrium is activated by the pregnancy hormones estrogen and progesterone to facilitate embryo implantation, and errors in endometrial responsiveness can lead to reduced fertility or endometriosis. Here they show that GREB1 interacts with hormone receptors in the endometrium, leading to normal or pathological consequences depending on the hormones involved.