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Torpor is a state of reduced metabolism and body temperature that conserves energy when food is scarce. Here the authors show that estrogen-sensitive neurons in the hypothalamus regulate torpor in mice, maintaining torpor in both sexes but initiating torpor and regulating core temperature differentially across sex.

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.

Engineered polyketide synthases (PKSs) have great potential as biocatalysts for the synthesis of chemically challenging molecules. Here the authors show a retrobiosynthesis approach to design and construct PKSs to produce a series of valerolactams for biopolymer production.

Lanthanide-doped upconverting nanoparticles exhibiting a 33,000 times increase in brightness and a 100 times increase in efficiency over bare upconverting nanoparticles are demonstrated. The findings are relevant in fields from solar energy to biophotonics.

Upgrading wasted carbon emissions to high-value, multi-carbon products provides an economic route to reduce carbon dioxide levels, but such conversions have proven challenging. Here, authors explore copper adparticles as highly active surfaces that convert CO to n-propanol with high selectivities.

The voltage-gated sodium channel Na_v1.7 has a dual role in osteoarthritis—in chondrocytes, it promotes joint damage, and in dorsal root ganglia neurons, it increases pain transmission.

OPCML is a tumour suppressor gene that is epigenetically silenced in ovarian cancer and is somatically mutated in various cancers. Here, the authors solve the X-ray crystal structure of OPCML and model clinically relevant mutations that could contribute to tumorigenesis.

This study uses zinc-finger nucleases to target an inducible XIST transgene into chromosome 21 from trisomic Down’s syndrome pluripotent stem cells; the XIST RNA coats one copy of chromosome 21 and triggers whole chromosome silencing, suggesting the potential of this approach for studying chromosomal disorders such as Down’s syndrome and for research into gene therapies.

QS-21—an FDA-approved vaccine adjuvant—and several structural analogues of QS-21 can be synthesized in engineered yeast strains, and this process is much less laborious compared with the conventional mode of extraction from the Chilean soapbark tree.

GATA2 regulatory mutations are associated with hereditary congenital facial paresis in humans. A genetically engineered mouse model recapitulates the human phenotype, showing altered neuron-specific Gata2 expression and a bias in formation of inner-ear efferent neurons over facial branchial motor neurons.

Determining the spatial and temporal activity patterns of enhancers remains a challenge in the functional annotation of the human genome. In this study, the genome-wide occupancy of the enhancer-associated protein p300 was determined in developing mouse tissues by using chromatin immunoprecipitation followed by massively parallel sequencing. Testing the p300-bound sequences in a transgenic mouse enhancer assay confirmed that p300 binding is a highly effective means to identify enhancers and to predict in which tissues they are active.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Batista, Schief and colleagues use a series of germline-targeting immunogens in knock-in mice expressing heavy chain sequences derived from the HIV broadly neutralizing antibody 10E8 to characterize the requirements of 10E8 B cell precursors for entry and maturation in the germinal center.

Long-term use of serotonin-reuptake inhibitors causes bone loss by acting centrally to counteract a peripheral, beneficial effect on bone.

A study reports the development and validation of a wrist-worn, consumer wearable-based system that identifies sudden loss of pulse events with a performance profile suitable for societal-scale use.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

Reduced-dimensional halide perovskites are promising for light-emitting diodes but suffer from photo-degradation. Here Quan et al. identify the edge of the perovskite nanoplatelets as the degradation channels and use phosphine oxides to passivate the edges and boost device performance and lifetime.

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.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Identification of non-coding variants has outstripped our ability to annotate and interpret them. Dickel et al. present a compendium of over 80,000 putative human heart enhancers and demonstrate that two conserved enhancers are required for proper cardiac function in mice.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Measurements from the heavily shielded Orion spacecraft during the uncrewed Artemis I mission show dose-rate reductions due to shielding and orientation for Van Allen belt crossings and quantify the interplanetary cosmic-ray radiation in a human-rated spacecraft.

Organic carbon in the top layer of mineral soils in cold regions is dominated by the particulate fraction, according to analyses in Arctic and alpine ecosystems.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

The efficiency and operating lifetimes of perovskite light-emitting diodes is improved by using a fluorinated triphenylphosphine oxide additive to control the cation diffusion during film deposition and passivate the surface.

Propionate addition is a common strategy for production of valuable polyketides by supplying the substrate methylmalonyl-CoA in the industrial microbe Corynebacterium glutamicum; however, propionate inhibits C. glutamicum growth, thus hampering polyketide production. In this study, Zhan et al. identify the reasons for propionate-elicited growth inhibition and metabolically engineer C. glutamicum to circumvent this roadblock and increase polyketide production.

The 2.0 Å crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals a fold similar to that of tyrosine hydroxylase. It provides the first structural view of where mutations occur and a rationale to explain molecular mechanisms of the enzymatic phenotypes in the autosomal recessive disorder phenylketoneuria.

Methyl jasmonate triggers saponin production in Saponaria vaccaria. Using transcriptome data and heterologous expression, the authors identify P450s and glycosyltransferases that modify triterpenoids. They also discover the pathway for UDP-D-fucose biosynthesis.

Lewis acid additive semicarbazide hydrochloride improves the formation of α-phase FAPbI₃-based films and promotes a homogeneous vertical distribution of A-site cations through a deprotonation–reprotonation process. The upgraded device performance reaches up to 26.12% with high stability, and mini-module perovskite solar cells achieving 21.47% (area, 11.52 cm²) demonstrate great scalability.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Ethylene glycol is a commodity chemical with an annual consumption of 20 million tonnes. Its production generates 1.6 tonnes of CO₂ per tonne of ethylene glycol. To reduce these CO₂ emissions, the authors report a one-step electrochemical route to selectively convert ethylene to ethylene glycol at ambient temperature and pressure in aqueous media.

The electroreduction of CO₂ to ethanol could enable the clean production of fuels using renewable power. This study shows how confinement effects from nitrogen-doped carbon layers on copper catalysts enable selective ethanol production from CO₂ with a Faradaic efficiency of up to 52%.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

Fungi from the Neocallimastigomycetes taxonomic class break bonds in lignin during the anaerobic deconstruction of whole plant cell walls. This finding challenges the paradigm that only certain aerobic organisms break down lignin.

Mutating natural enzymes is effective in broadening the substrate or product range, but generally leads to reduced titers. Here the authors engineer hybrid polyketide synthases for efficient production of short-chain ketones from plant biomass hydrolysates in Streptomyces, which can increase the octane of gasoline.

The bed bug, Cimex lectularius, is a ubiquitous human ectoparasite with global distribution. Here, the authors sequence the genome of the bed bug and identify reductions in chemosensory genes, expansion of genes associated with blood digestion and genes linked to pesticide resistance.

While perovskite solar cells with an inverted architecture hold great promise for operation stability, their power conversion efficiency lags behind that of conventional cells. Here, Zheng et al. achieve a certified 22.34% efficiency, exploiting alkylamine ligands as grain and interface modifiers.

Chassis-independent recombinase-assisted genome engineering (CRAGE) enables the integration of plasmids encoding biosynthetic gene clusters into the chromosomes of diverse bacteria to optimize production of natural products in non-native strains.

Mangroves are adapted to cope with tropical storms, but might be threatened by rising frequency and intensity of these events. Here the authors document one of the largest mangrove diebacks on record following Hurricane Irma in Florida, and show a greater role of storm surge and ponding rather than wind as a mechanism for mangrove dieback.