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Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

The authors highlight the importance of kinetics in GPCR activation. Using solution NMR, they show that the transducer βarrestin1 and the β-arrestin1biased ligand ML314 kinetically tune the conformational ensemble of the neurotensin receptor 1.

The ages and geochemical compositions of inclusions of sublithospheric diamonds indicate additions to the mantle keel of Gondwana by the underplating of buoyant subducted material, originating from 300–700-km depth, which may have contributed to supercontinent stability during long-distance migration.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

A fully formed, Neptune-sized planet is observed orbiting a young star, demonstrating that planets can form in less than 10 million years and may also experience inward migration on these timescales.

Biomass is a renewable source of carbon that can be exploited to produce valuable chemicals and fuels. This Perspective discusses the electrochemical valorization of biomass, identifying specific chemical transformations in which the approach can excel.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

The flavoenzyme nicotine oxidoreductase degrades nicotine in the bloodstream. Now, genetic selection in bacteria has been used to improve the catalytic performance of nicotine oxidoreductase, isolating variants with increased O₂ reactivity that were more effective at degrading nicotine in the blood of rats.

Neurons derived from stem cells are rapidly matured with a GENtoniK cocktail.

The interface between the Li metal electrode and inorganic solid electrolyte is crucial for developing reliable all-solid-state Li batteries. Here, the authors show that the Li plating current density distinctly affects the chemistry and morphology of interphase components formed at the interface.

Marais and colleagues report that checkpoint inhibitor treatment of patients with melanoma leads to dynamic changes in peripheral T cells and expansion of immune effector cells. This awakening of the immune system occurs early after treatment and could be exploited in the clinic.

Microglia rely on mitochondrial respiration to respond to demyelinating injury. However, mitochondrial respiration is not required to support microglial proliferation.

Supramammillary nucleus (SuM) neurons have been studied in the context of REM sleep but their possible role in mediating wakefulness is not known. Here the authors elucidate the distinct functional contributions of three subpopulations in the SuM on electrographical and behavioral arousal in mice using genetically targeted approaches.

The formation of atherosclerotic plaques involves the aggregation of calcifying extracellular vesicles and the formation of microcalcifications.

The role of ancestry in target discovery remains to be systematically explored. Here, the authors analyse data from 611 genome scale CRISPR/Cas9 viability experiments in human cell line models as part of The Cancer Dependency Map and identify ancestry-associated genetic dependencies.

Very early observations of a type Ia supernova—from within one hour of explosion—show a red colour that develops and rapidly disappears. These data provide information on the initial explosion mechanism: surface nuclear burning on the white dwarf or extreme mixing of the nuclear burning process.

The synchronization of fast-spiking cortical interneurons (FS) produces gamma-like oscillations or ‘FS-gamma’. In this study, Siegle and colleagues found that the induction of FS gamma in the primary sensory cortex of mice performing a tactile task could enhance their detection of less salient stimuli.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Dendritic protein synthesis is implicated in synaptic plasticity and memory storage. Ainsley et al., develop a method for collecting ribosome-bound mRNAs from mouse brain dendrites, and use RNA sequencing to characterize dendritic mRNAs that bind to ribosomes after mice experience a novel environment.

The molecular characteristics of myocarditis associated with immune checkpoint inhibitors are described and potential biomarkers of onset and severity are identified.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

Horizontal gene transfer could stabilize cooperation in bacteria because plasmids could promote the transfer of genes encoding public goods. However, the authors use comparative analysis and theoretical modelling to show that, while horizontal gene transfer may help cooperative genes invade a population initially, they have less of a role in long-term maintenance of cooperation.

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.

Analysis from a population cohort in Israel found that a third booster dose of the BNT162b2 mRNA vaccine in mothers before or during pregnancy was associated with greater protection against COVID-19 hospitalization in their infants compared to two doses.

The civil war in Mozambique led to the collapse of large-mammal populations and the spread of the invasive plant Mimosa pigra. Experimental exclosures and DNA metabarcoding are used to show how trophic rewilding since the end of the war has reduced the invasive population.

Oxygen reduction to hydrogen peroxide is a promising alternative to replace the energy-intensive anthraquinone process in industry. Now, the hydrogen peroxide electrosynthesis performance of a carbon-supported cobalt phthalocyanine catalyst is tuned via the introduction of oxygen functional groups to the support, which optimize the electronic structure of cobalt active sites.

Exome-wide genetic analysis on >300,000 individuals identifies associations with plasma lipid traits. Loci significantly associated with cholesterol and triglycerides are examined together to determine the effects of alleles on type 2 diabetes and coronary artery disease risk.

Type 2 diabetes is associated with insulin resistance, impaired insulin secretion and liver steatosis. Here the authors report a proof-of-concept study for small molecule SWELL1 modulators as a therapeutic approach to treat diabetes and associated liver steatosis by enhancing systemic insulin-sensitivity and insulin secretion in mice.

Karam and colleagues report a phase I/Ib trial in patients with HNSCC treated with neoadjuvant SBRT and anti-PD-L1, and perform high-dimensional analyses of immune correlates of response in the tissue microenvironment and peripheral blood.

Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.

Most steps in peptidoglycan biosynthesis are understood, but the lipid II binding properties to the flippases MurJ and FtsW remain unknown. Now, it has been shown that lipid II exhibits preferential binding to MurJ, which is modulated by ramoplanin and cardiolipins. These insights into the lipid II binding determinants suggest roles for lipids in regulating substrate binding.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Single-cell intracellular recordings have been used as the primary tool for estimating driving forces across inhibitory receptors within the nervous system. Here, the authors present ORCHID as an all-optical method to measure inhibitory receptor driving forces in targeted brain cell types.

Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Time-resolved cryo-EM captured transient intermediates during E. coli RNAP promoter melting, revealing conformational changes affecting stepwise transcription bubble opening. Results inform how DNA sequence controls bacterial transcription initiation.

Clonal hematopoiesis, often caused by mutations in DNMT3A and TET2, is associated with blood cancer and coronary artery disease. Here, the authors conduct an epigenome-wide association study, finding that clonal hematopoiesis caused by DNMT3A vs. TET2 mutations has directionally opposing changes in DNA methylation profiles, with both promoting stem cell self-renewal.

How sensory systems are organized during development remains unclear. Here, the authors used electron microscopy to examine the gravity-sensing system in zebrafish, finding that directional tuning and developmental age are organizing principles of the transformation from vestibular sensation to motor control.

Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

Chemical disequilibrium is a known biosignature, and it is important to determine the conditions for its remote detection. A thermodynamical model coupled with atmospheric retrieval shows that a disequilibrium can be inferred for a Proterozoic Earth-like exoplanet in reflected light at a high O₂/CH₄ abundance case and signal-to-noise ratio of 50.

A previous human HIV-1 vaccine clinical trial, boosting with HIV envelope protein from two strains, demonstrated moderate vaccine efficacy. Here, Bradleyet al. show that a pentavalent HIV envelope protein boost improves protection from viral challenge in non-human primates and they identify immune correlates of protection.

Radionuclide brachytherapy delivered via an injectable biopolymer depot conjugated with iodine-131 and combined with systemically delivered paclitaxel induced the complete regression of multiple subcutaneous and orthotopic pancreatic tumours in mice.

The daily accumulation of the ZEITLUPE (ZTL) photoreceptor/E3 ubiquitin ligase relies on a light-dependent interaction with GIGANTEA (GI). Here the authors show that GI recruits two deubiquitylases to help stabilize the ZTL-GI complex during the day and likely counterbalance the activity of ZTL.