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Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Class I and II benzoyl-coenzyme A reductases offer a mild biological alternative to the alkali metal- and ammonia-dependent Birch reduction, a classical synthetic method for achieving dihydro additions to arenes. Here, the authors characterize double-cubane [8Fe-9S] and active site aqua-[4Fe-4S] clusters of a class I benzoyl-CoA reductase and provide evidence for a radical mechanism.

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.

Lung tissue-resident memory T cells (T_RM) are important for controlling respiratory infections, but how they are regulated is still unclear. Here the author compare mouse lung T_RM induced by either intranasal vaccination or direct H1N1 infection to find distinct phenotypes that converge on protecting the mice from H1N1-induced lung pathology.

A climate sensitive permafrost region (Yedoma domain) was found to contain globally relevant N stock of >40 Gt nitrogen, of which 4 to 16 Gt of the N could become available by thaw until 2100. This study increases the current estimates by nearly 50%.

The acidic tumour microenvironment in melanoma drives immune evasion by cAMP in tumor-infiltrating monocytes. Here, the authors show that the release of an adenylate cyclase inhibitor from micelles restores antitumor immunity and, when combined with regulatory T cell depletion, leads to remission of established B16-F10-OVA tumors.

Microbial communities are shaped by their environment. Here, the authors demonstrate temporal structuring of microbial communities in the pelagic Arctic Ocean, using remote, long-term sampling with long-read metagenomics and SSU ribosomal metabarcoding.

The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.

A modelling approach predicts SARS-CoV-2 variant dynamics on the basis of immunity and cross-neutralization, which was shaped by a region’s SARS-CoV-2 infection history.

Brain tumours are difficult to treat because of their propensity to infiltrate brain tissue; here long processes, or tumour microtubes, extended by astrocytomas are shown to promote brain infiltration and to create an interconnected network that enables multicellular communication and that protects the tumours from radiotherapy-induced cell death, suggesting that disruption of the network could be a new therapeutic approach.

In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.

While current COVID-19 vaccines provide certain protection, more effective vaccination strategies are still desirable. Here the authors show, using mouse vaccination models, that priming with a systemic mRNA and boosting with an intranasal adenoviral vector vaccine induces comprehensive T cell and mucosal immunity.

Replication stress has been associated with transient remodelling of replication intermediates into reversed forks, followed by efficient fork restart. Here the authors systematically analyse the role of RAD51 paralogs in these transactions, providing insights on the mechanistic role of different complexes of these proteins.

The axon initial segment (AIS) is a specialized location in neurons with clustered ion channels which regulates the distribution of neuronal materials. Here, the authors use proximity biotinylation to examine the AIS proteome and better define its molecular organization.

Vaccines induce beneficial immunity for COVID-19, but immune waning prompts boosting vaccination. Here, the authors show that a third, boosting dose of COVID-19 mRNA vaccine induces transient CD8 + T effector cell response while conserving the CD8 memory T cell pool, thereby permitting reactivation of spike-specific CD8 + T cells upon breakthrough infection or 4th vaccination.

The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

High-intensity X-ray sources such as synchrotrons and free-electron lasers need large particle accelerators to drive them. The demonstration of a synchrotron X-ray source that uses a laser-driven particle accelerator could widen the availability of intense X-rays for research in physics, materials science and biology.

A competitive inhibitor of the lipase ATGL reduces the availability of adipocyte fatty acids, causing insulin resistance in insulin-sensitive tissues.

Heart failure is a major public health issue but due to our poor disease understanding the current therapies are symptomatic. Here the authors identify Myoscape as a novel cardiac protein regulating membrane localization of the L-type calcium channel and heart's contractile force, thus promising new therapeutic avenues for heart failure.

Brown adipose thermogenesis increases energy expenditure and relies on uncoupling protein 1 (UCP1), however, UCP1 knock-out mice show resistance to diet-induced obesity at room temperature. Here, the authors show that this resistance relies on FGF21-signaling, inducing the browning of white adipose tissue.

Monooxygenases catalyse the hydroxylation of C-H bonds using oxygen as a co-substrate, which, in turn, is unavailable for anaerobic bacteria. Here, the authors report a three-step reaction cascade involving two hydroxylases and one dehydratase which hydroxylate the C26 methyl group of cholesterol with water as a co-substrate.

Scolaro et al. identify the enzyme cytidine deaminase (CDA) as upregulated in immunotherapy-resistant tumors and find it contributes to the UDP pool, which in turn modulates tumor-associated macrophages to instruct an immune-evasive TME.

Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies which destabilize cell adhesion of keratinocytes. The phosphodiesterase 4 inhibitor apremilast prevents skin blistering by stabilizing the keratin filament anchorage of desmosomes.

Neumüller and colleagues identify and characterize potent HER2 exon 20 insertion-selective inhibitors with efficacy, which preserve wild-type epidermal growth factor receptor signaling in preclinical models of non-small cell lung cancer in vivo.

Implementation of a genomics-informed prebreeding strategy in a global winter wheat collection enhances the use of genebank accessions and uncovers the value of genetic resources for wheat improvement.

The Magnus effect refers to rotating objects developing a lift force when travelling through a fluid. It normally vanishes at microscopic length scales but now a very large Magnus effect is demonstrated for spinning colloids in viscoelastic fluids.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

PU.1 is a master TF of hematopoietic lineage differentiation. Here the authors analyse properties of PU.1 DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression, and uncover the mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1.

Until recently, it was though that the microbial degradation of aromatic compounds was absolutely dependent on the use of molecular oxygen for ring cleavage. However, as described here by Fuchs and colleagues, microorganisms have other ways of breaking down these compounds when oxygen is scarce or absent.

The regulatory role of calcitonin in bone homeostasis is well studied, yet its molecular activity is poorly understood. The authors show that calcitonin regulates bone cells function by inhibiting the osteoclast secretion of sphingosine 1-phosphate, a lipid mediator of osteoclast–osteoblast crosstalk.

Radiation–matter interactions can become highly nonlinear when using high-intensity X-ray free-electron lasers. Under such conditions, it is shown that nonlinear Compton scattering has an anomalous redshift, whose origin remains unclear.

HMBG1 is a protein expressed in natural killer cells and is important in immunosurveillance. In this study, the authors show that HMGB1 binds to and inhibits PKM2, resulting in a block in aerobic glycolysis and ultimately cell death.

IFN-γ signalling inhibits production of IL-9, the defining cytokine of the Th9 cell subset. Here the authors show that IFN-γ does this by driving IRF1 to compete with IRF4 forIl9promoter binding and skewing these cells towards a Th1 phenotype, an effect that reduces asthmatic inflammation in mice.

Optical antennas are able to concentrate light on a scale much smaller then the wavelength. Bow–tie–shape nanostructures are one example. It is now possible to tune the response of such an antenna by precisely moving one half of the bow tie.

Ubiquitin modification also occurs in archaea. Here, the authors characterize an archaeal ancestral ubiquitination system, present the crystal structure of the archaeal deubiquitinase Rpn11 from Caldiarchaeum subterraneum bound to ubiquitin and provide insights into evolutionary relationships.

Trans-neuronal transfer of pathogenic proteins has been demonstrated in multiple neurodegenerative diseases. Here the authors show in vitro and in a mouse model that mutant Huntingtin is also transferred from one neuron to another. This transfer requires exocytosis machinery and contributes to neurodegeneration.