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Alström syndrome (AöS) is a rare genetic disorder characterized by metabolic problems. Here, the authors show that in AöS models, defects in cilia and autophagy lead to ACBP accumulation, which drives obesity. An anti-ACBP antibody reduces weight gain and metabolic dysfunction, highlighting ACBP as a therapeutic target for this ciliopathy.

Hypoxic (low oxygen) water conditions are generally thought to be uncommon in rivers and result from human impacts. However, Dutton and colleagues show here that waste from hippos in the Mara River contributes to frequent hypoxic events, suggesting hypoxia is a natural aspect of this system.

Global shark and ray populations have declined sharply, driven by expanding fisheries and inequitable gaps in catch, trade and distribution data. This Review assesses global status, highlights drivers of decline, and outlines the regulatory, market-based and conservation actions needed to reduce mortality and reverse shark and ray biodiversity loss.

ATP synthase powers cells by converting proton translocation into energy. Here, authors reveal distinct structural features of the P. aeruginosa ATP synthase that regulate activity and may serve as targets for new antimicrobial therapies.

This multicenter study demonstrates use of dried and capillary blood as a minimally invasive, scalable approach for Alzheimer’s biomarker testing in research, with potential as a widely scalable population-based research approach, especially in resource-limited settings.

Transplantation of allogeneic hematopoietic stem cells (HSCs) is the only reported cure of HIV-1. Here, authors describe an autologous HSC transplant therapy with cells engineered for multilayered resistance to HIV-1 through CCR5 knockout and secretion of HIV inhibiting antibodies by B cell progeny.

In this work, fragments identified by 19F-NMR are optimized into submicromolar binders of the MITF transcription factor. These results support direct targeting of bHLH-LZ DNA binding domains and provide a foundation for the development of new melanoma therapies.

A species-level dataset of sediment-dwelling macrofauna, sampled 2 years before and 2 months after a test of a commercial deep-sea mining machine, reveals losses of macrofaunal density and species richness within the machine’s tracks and community-level effects in both the tracks and an area impacted by sediment plumes.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

This study shows that climate-driven hydrology primarily controls subsurface rock carbon weathering, with the groundwater table regulating the weathering depth and subsurface water fluxes determining the transported forms and rates of carbon released from rocks, based on measurements in the East River watershed, Rocky Mountains, United States.

Authors provide analysis of starch-binding protein Sas6, from Ruminococcus bromii, a bacterium that degrades resistant starch granules in the human gut, and demonstrate how carbohydrate-binding modules recognize different moieties within starch.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Metabolizing lignocellulosic feedstocks to industrial chemicals by microorganisms requires surmounting  the recalcitrance caused by lignin. Here, the authors pair transgenic lignin modified poplar lines with engineered Caldicellusiruptor bescii to achieve biomass solubilization and ethanol conversion without pretreatment.

Arsenic-rich globules are thought to be evidence of early microbial life. Here, the authors show how microbialite arsenic enrichment patterns vary with microbial activity and environmental conditions, reinforcing arsenic’s value as a biosignature.

CD388 is a first-in-class antiviral drug–Fc conjugate engineered for extended half-life that demonstrates potent prophylactic and therapeutic efficacy against lethal influenza A and B challenge in mice.

Malaria control and elimination require environmentally safe strategies. Here, the authors propose L-DOPA, a naturally occurring tyrosine derivative, as a mosquito dietary intervention that can shorten lifespan and reduce malaria parasite burden of female Anopheles gambiae mosquitoes.

Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Next generation precision lysine-specific histone demethylase 1A (LSD1) covalent inhibitors which selectively block LSD1 enzyme activity by forming a compact N-formyl-FAD adduct have been developed, but the mechanism of adduct formation was unclear. Here, the authors show that the covalent inhibitor-FAD adduct undergoes a Grob fragmentation and elucidate the structure-activity relationships that promote this transformation.

PBK is a mitotic kinase implicated in cancer. This study reveals how PBK evicts key C2H2-zinc finger transcription factors such as Ikaros, Aiolos and CTCF from DNA as cells divide, regulating mitotic chromatin accessibility and chromosome compaction.

To date, covariance of carbonate and organic carbon isotope records has been assumed to denote fidelity of the original signal. This study shows that post-depositional alteration can create strong correlations, raising doubts about the use of correlated records to imply important changes in past global carbon cycling.

Combination therapies simultaneously inhibiting different therapeutic targets in cancer is challenged by individual pharmacokinetic profiles. Here, the authors generate an orally provided multi-targeted kinase inhibitor that is lymphatic absorbed and increases survival in a murine model of myelofibrosis.

Ibogaine is a natural substance that interrupts opioid addiction but has cardiac risks. This article introduces novel ibogaine analogs that show reduced cardiac risk and enhanced neuroplasticity and therapeutic-like effects in models of opioid use disorder.

During wound induced hair follicle neogenesis (WIHN), stem cells regenerate hair follicles but how this arises is unclear. Here, the authors show that self-noncoding dsRNA activates the antiviral receptor TLR3 to induce intrinsic retinoic acid, which stimulates WIHN in mice, and in isolated human keratinocyte cells.

Studies on protein–protein interactions using proteins containing d- or l-amino acids show that stereoselectivity of binding varies with the degree of disorder within the complex.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

The network of proteins secreted for interorgan communication is poorly understood. Here, the authors develop a method, based on protein labeling, to study cell-specific secretomes and interorgan protein trafficking, and demonstrate their approach in Drosophila and mouse models.

Two side-by-side papers report that H3K27me3 deposited by polycomb repressive complex 2 represents an epigenetic barrier that restricts naive human pluripotent cell differentiation into alternative lineages including trophoblasts.

A pangenome of oat, assembled from 33 wild and domesticated oat lines, sheds light on the evolution and genetic diversity of this cereal crop and will aid genomics-assisted breeding to improve productivity and sustainability.

A genetically engineered microbial symbiosis based on synthetic auxotrophy is created, with potential implications as a biocontainment strategy.

Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

Conducting a simulated turtlegrass herbivory experiment across 650 experimental plots and 13 seagrass meadows, the authors show that the negative effects of herbivory increase with latitude, driven by low levels of light insolation at high latitudes.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Computational drug discovery is used to identify a 12-mer peptide derived from BRINP2 with potent anti-obesity effects that are independent of leptin, glucagon-like peptide 1 receptor and melanocortin 4 receptor.

Prostate cancer progression may be enhanced by a high-fat diet. Here the authors show that a diet high in saturated fats enhance the MYC-driven transcriptional program, a feature that independently predicts prostate cancer progression and death.

Surveys of reef change are combined with a unique 20-year time series of land–sea human impacts and the results show that integrated land–sea management could help achieve coastal ocean conservation goals and provide coral reefs with the best opportunity to persist in our changing climate.

Alterations of the mucosal microbiota, including Lactobacillus bacteria, are associated with infections caused by the fungus Candida albicans. Here, MacAlpine et al. show that some Lactobacillus strains produce a small molecule that blocks C. albicans filamentation and biofilm formation, and thus virulence, through inhibition of a fungal kinase.

Alamos et al. show that Agrobacterium engages in density-dependent interactions that dictate transformation efficiency and transgene expression. These findings enable a quantitative model to improve metabolic engineering in a predictive manner.

3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.

Analysis of plastic debris found in surface waters shows that lakes and reservoirs in densely populated and urbanized regions, as well as those with elevated deposition areas, are particularly vulnerable to plastic contamination.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

Sinclair et al. explore the contribution of chronic inflammation to cardiovascular symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC-CVS). The authors identify trace levels of inflammatory cytokines in individuals with PASC-CVS that impair the function of cardiomyocytes derived from induced pluripotent stem cells.

The LPD-3 complex structure reveals protein–lipid interactions that suggest a model for how the native LPD-3 complex mediates bulk lipid transport and provides a foundation for mechanistic studies of bridge-like lipid-transport proteins.