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Here the authors report that brown adipocyte-derived vaspin reduces heat-producing activity in brown fat by blocking adrenergic signals, helping to regulate energy expenditure and maintain metabolic balance.

MCM2-7 complexes drive genome duplication, but their assembly in human cells is not fully understood. Here, the authors identify the CRL4-DCAF12 ubiquitin ligase as crucial for MCM2-7 maturation, safeguarding accurate DNA replication, and genome stability.

Cancer patients are at increased risk for severe bacterial infections due to immune dysfunction. Here, the authors show that chronic tumor-derived G-CSF drives NAMPT/NAD-dependent neutrophil dysfunction from the progenitor stage, and that targeting this pathway restores infection control.

Single crystal diffraction is one of the most common and powerful tools for structural elucidation, but obtaining single crystals of adequate size and quality is not always trivial. Here, the authors report a method to crystallize inherently non-crystalline adamantane-like organic-inorganic clusters using π-π interactions between C₆₀ and nano-sized molecules.

For several decades the MCM2-7 proteins, the core of the DNA replicative helicase, eluded detection at DNA replication sites. Here, the authors solve this conundrum by gene editing, which enables visualization of replication dynamics in living cells.

Mirror image peptides are of interest for a range of biotechnology applications. Here, the authors report on the creation of fully functional mirror-image transmembrane pores made of D-amino acid peptides, which have potential in nanopore sensing technologies and cancer therapies.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

RNA-binding proteins are present in mitotic structures, but their role in cell division is unclear. Here, the authors provide an atlas of RNA-dependent mitotic proteins. They identify AURKA, KIFC1, and TPX2 as RNA-binding proteins and show that RNA regulates their interactions and functions.

Promoters are able to modulate the performance of catalysts for a given process, but this can be done through various mechanisms. Here the role of Mn as a promoter on Fe-based catalysts for CO₂ hydrogenation to olefins is comprehensively investigated via spectroscopic and kinetic analyses. The promoter induces a restructuring of the catalyst surface, balancing the strength of the adsorption of reactants and intermediates.

Fuks and colleagues report that downregulation of the FTO m⁶A RNA demethylase activates the Wnt pathway, promoting EMT-mediated progression of epithelial tumors and conferring sensitivity to Wnt inhibitors.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Influenza A virus must package eight separate genomic segments, called viral ribonucleoproteins (vRNPs). Using in situ cryo-electron tomography, the authors visualize how vRNPs are clustered on cell membranes containing the viral glycoprotein hemagglutinin or neuraminidase, and how the matrix protein M1 forms intracellular structures that reorganize during budding to support packaging.

Remdesivir is a nucleoside analog that inhibits the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and is used as a drug to treat COVID19 patients. Here, the authors provide insights into the mechanism of remdesivir-induced RdRp stalling by determining the cryo-EM structures of SARS-CoV-2 RdRp with bound RNA molecules that contain remdesivir at defined positions and observe that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation.

Quantitative biochemical assays and high-resolution cryo-EM analysis reveal how the COVID-19 antiviral drug candidate molnupiravir causes lethal viral mutagenesis by the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2.

It has been reported that human cancer cell lines present significant diversity across laboratories and become heterogeneous during long-term culture. Here, the authors show that oligo-mutated pediatric sarcoma cell lines are genetically and phenotypically more stable than the highly mutated adult carcinoma cell lines.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

CAR and PXR receptors are known to regulate metabolism, however, there is no dual human ligand suitable for therapy. Here, the authors show a CAR agonist/PXR antagonist, MI-883, which regulates cholesterol/bile acid homeostasis by leveraging CAR and PXR activations in plasma cholesterol regulation.

Grune et al. show that hypokalemic mice develop spontaneous ventricular tachycardia after myocardial infarction, and they use this model to dissect the role of immune cells in arrhythmia: neutrophils increase ventricular tachycardia, partly by promoting reactive oxygen species production, whereas efferocytic macrophages play a protective role.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.

Soil contamination is a pressing environmental concern due to increasing anthropogenic activity. Here, the authors developed a rapid and energy-efficient electrothermal process that simultaneously removes heavy metals and organic pollutants in soil.

Bacterial endospores are among the most resilient forms of life. Here, authors reveal ultrastructural details of the spore chromosome and the multiprotein, multilayered extracellular coat, shedding light on mechanisms contributing to spore resistance.

Endophilins-A are conserved membrane-associated proteins required for endocytosis. Here, the authors report that endophilins-A also promote exocytosis of neurosecretory vesicles by coordinating priming and fusion through intersectin-1, independently of their roles in different types of endocytosis.

The full-length structure of HUWE1 reveals the bipartite organization of a giant E3 ubiquitin ligase, comprising a catalytic HECT domain and a large, ring-shaped scaffold that provides docking sites for various substrates and regulates E3 activity.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Two-dimensional hybrid perovskites exhibiting Rashba/Dresselhaus spin-splitting can be potentially used for spin-selective transport and spin-orbitronics, yet the structural determinants of spin-splitting are not well-understood. Here, the authors reveal a specific inorganic layer distortion that correlates with bulk spin-splitting in these materials.

SARS-CoV-2 variants have accumulated multiple defining mutations within their spike glycoproteins. Here, the authors report a structural basis for broad neutralization of several variants by a heavy chain antibody fragment and provide a mutational analysis focusing on antibody evasion, receptor engagement, and spike protein structure.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Complex neuropathologies, like macular degeneration, are common but incompletely understood. Here the authors report a complex human retina pathology organoid model induced by HBEGF-TNF, causing PIEZO1-mediated photoreceptor degeneration by cell extrusion.

Constructing genome graphs directly from genome assemblies overcomes single-reference bias.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Applying the concept of ecosystem energetics to a grassland biodiversity experiment, the authors show that the storage and flow of energy across the whole trophic network, both above- and belowground, becomes more efficient as plant diversity increases.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

An oncometabolite produced by tumor cells acts as a paracrine immunosuppressant dampening antitumor T cell responses in glioma.

The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, but its spike protein doesn’t efficiently bind human ACE2. Here, the authors show that exchange of spike residue 403 between RaTG13 and SARS-CoV-2 spike proteins affects binding to human ACE2 and entry of pseudotyped viruses.

Modeling patient-individual resistance to immunotherapy is challenging. Here, the authors use a syngeneic experimental hypermutated orthotopic glioma model to define radiological and biological features that can predict or explain the mechanistic differences between responders and non-responders to immunotherapy.

Jochheim et al report an alternative, dimeric form of the coronavirus SARS-CoV-2 RNA dependent RNA polymerase (RdRp), which is used to replicate and transcribe its genome. They resolve its structure at 5.5 Å resolution and speculate that the dimer facilitates template switching during production of sub-genomic RNAs.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.