Search

Whether a species declines under the current biodiversity crisis could partly depend on its range size. Here, the authors use replicated metacommunity data to identify global patterns in the relationship between species’ range size and changes in occupancy through time.

Suchacki et al. show that serotonin suppresses human brown adipose tissue (BAT) activation, and that inhibition of the serotonin transporter (SERT) potentiates the suppressive action of extracellular serotonin on BAT by preventing serotonin uptake.

Sea otters recolonizing an estuary in California indirectly reduce erosion by reducing burrowing crab abundance, suggesting that restoring predators could be a key mechanism to improve the stability of coastal wetlands and other ecosystems.

Traditional approaches used in the pharmaceutical industry are not precise or versatile enough for customized medicine formulation and manufacture. Here the authors produce a method to form coatings, with accurate dosages, as well as a means of closely controlling dissolution kinetics.

The structure of the major histocompatibility complex (MHC)-class-I-like molecule MR1 in complex with a vitamin B9 derivative is determined; metabolites of vitamin B2 are shown to activate MR1-restricted mucosal-associated invariant T cells, implicating them in microbial immunosurveillance.

In eukaryotic cells, the ubiquitylation system regulates several cellular processes central to protein homoeostasis. Here the authors demonstrate the existence of an eukaryotic-like ubiquitylation cascade requiring E1, E2 and E3-like enzymes in the archaeon C. subterraneum, shedding light on the evolution of the ubiquitin-proteasome system.

Structural elucidation and biochemical analysis of a cone snail insulin venom that binds and activates the human insulin receptor may permit design of ultrafast-acting insulin analogs for diabetes therapy.

Usp9x is a deubiquitinating enzyme with altered expression in melanoma; however its functional contribution in this context is not clear. Here the authors show that Usp9x regulates the stability of the transcription factor Ets-1 that in turn impacts metastatic melanoma through increased expression of NRAS.

Gain of function mutations in isocitrate dehydrogenase 1 (IDH1) have been detected in cases of acute myeloid leukemia (AML). The application of an allosteric IDH1 inhibitor in AML cells promotes blast differentiation and restores DNA cytosine methylation patterns.

Mutations in the enzyme glycine decarboxylase (GLDC) are associated with neural tube closure defects and non-ketotic hyperglycinemia in humans. Here the authors generate a mouse model with reduced Gldc expression and activity and study the direct effect of the enzyme in these diseases and the mechanisms responsible for neural tube closure defects.

A calixarene–protein host–guest complex has been characterized in detail by using a combination of NMR spectroscopy and X-ray crystallography. The water-soluble sulfonato-calix[4]arene binds to cytochrome c at various lysine residues to yield a dynamic complex. This interaction may serve to facilitate crystallization by mediating protein–protein contacts.

Arginine methylation is an abundant post-translational modification catalysed by protein arginine methyltransferases (PRMTs). Here the authors use quantitative mass spectrometry to globally profile the substrates of the PRMT CARM1 in breast cancer cells, and establish a role for CARM1’s N-terminus in substrate recognition.

Building crystal structures into the electron density is an important step in protein structure solution. Here, the authors recruit online game players, students, and experienced crystallographers to compete in a competition to solve a new structure, and find that crowdsourcing model-building works.

Given the growing and seemingly limitless capacity to industrialize the oceans, there is a need to reimagine how to effectively measure, monitor and sustainably manage this seventy-one per cent of the Earth's surface.

Analysis of 836 UK-stranded common dolphins (1990–2020) found that PCB concentration and sea temperature are linked to an increased risk of infectious disease mortality, highlighting the necessity of integrated strategies to address these concurrent threats.

Functional CRISPR screens in patient-matched pre-treatment and post-treatment glioblastoma models identify the PTP4A–ROBO1 axis as a driver of tumorigenicity and enriched ROBO1 expression in recurrent glioblastoma that can be targeted with CAR T cell therapy.

Vocalizations were recorded for over eight distinct whale species as they converged on a shoal of herring to feed; the predators divided the shoal into overlapping but species-specific foraging sectors and the activities of the whales changed between day and night.

A multiplexing strategy for data-independent acquisition (DIA)-based mass spectrometry addresses the limitation of low precursor selectivity to make DIA more practical for peptide analysis.

A bacteriophage may protect itself and its host against a deadly effect of bright sunlight.

Viana and colleagues evaluate the potential effects of expanding a subset of marine protected areas that allow some level of fishing within their borders (sustainable-use MPAs) to improve the nutrition of coastal communities. They estimate that, depending on site characteristics, expanding sustainable-use MPAs could increase catch by up to 20%, which could help prevent 0.3-2.85 million cases of inadequate micronutrient intake in coral reef nations.

The regulation of plasma glucose levels is effected by insulin. Here, the authors reveal atomic detail of how peptides distinct from insulin bind to and activate the insulin receptor, with implications for design of small-molecule insulin mimetics.

The use of atomic-level simulations reveals a molecular mechanism by which a ligand can achieve selectivity between nearly identical receptors, enabling the rational design of targeted drugs.

The design of complementary catalysts to target different C–H bonds in a specific molecule is challenging. Now, a pair of P450-based carbene transferase enzymes is engineered, which can selectively cyanomethylate either a C(sp³)–H or arene C(sp²)–H bond present in the same substrate.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Deubiquitinases (DUBs) are key signaling enzymes, many of which lack selective inhibitors. Chan et al. pair a DUB-focused covalent library to mass spectrometry activity-based protein profiling, leading to selective hits against 23 endogenous DUBs and a first-in-class VCPIP1 probe with nanomolar potency.

Global mercury emissions increased 330% from 1960–2021, with declines in the Global North and China offset by rapid growth in the Global South, which now produces two-thirds of emissions. Without urgent action, emissions could rise 10%–50% by 2030.

IL-15-driven NK cells mediate anti-tumor immunity, but how IL-15 is negatively regulated remains unclear. Huntington and colleagues find that CIS, a member of the suppressor of cytokine signaling family, suppresses the response to IL-15 and, as a result, CIS-deficient mice are more resistant to cancer metastasis.

Using ice sheet model and glacio-isostatic adjustment model simulations and paleoclimate proxies, this work demonstrates that the most likely cause of past West Antarctic grounding-line reversal was a regime shift from a warm to cold ocean cavity.

Understanding the vulnerability of different US coastal communities to the likely harmful effects of ocean acidification on shellfisheries should inform the development of effective adaptation measures.

ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy.

Increased meltwater from the Greenland and Antarctic ice sheets will slow the Atlantic overturning circulation and warm the subsurface ocean around Antarctica, further increasing Antarctic ice loss.

Two degraders targeting zinc finger transcription factor IKZF2 (Helios) were developed by reprogramming CRL4^CRBN E3 ligase, and the pharmacologic degradation of Helios results in T_reg destabilization.

The development of Sulfopin, a highly selective and potent, covalent Pin1 inhibitor that phenocopies Pin1 knockout and regresses tumors in murine and zebrafish models of neuroblastoma as well as in a pancreatic cancer mouse model.

The discovery of a specific CDK12 bivalent degrader, BSJ-4-116, reveals that chronic exposure of MOLT-4 and Jurkat cells to BSJ-4-116 leads to acquired resistance to the compound via point mutations in the CDK12 kinase domain.

Lysosome-targeting chimeras (LYTACs) based on glycan ligands of the asialoglycoprotein receptor facilitate the cell-specific targeting and turnover of proteins by lysosomal enzymes, expanding the scope of LYTAC-mediated targeted protein degradation.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

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.

Rare and extreme climate events have increasingly occurred in the Arctic since ~2000. This Review outlines the observed and projected changes in atmospheric, oceanic and cryospheric extremes and explains their increasing occurrence through a ‘pushing and triggering’ framework.

Lee et al. use three-dimensional cell reconstruction of focused ion beam scanning electron microscopy data and multi-omics to show that ether-lipid metabolism regulates inter-organelle biogenesis and dynamics.

Dietary restriction promotes healthy brain aging, but the mechanism is unknown. Here, the authors show that OXR1 is upregulated by dietary restriction and confers age-related neuroprotection by maintaining retromer-mediated protein and lipid trafficking.

Shifts in temperature alter the structure and dynamics of macromolecules. Now, infra-red laser-induced temperature jump is combined with X-ray crystallography to observe protein structural dynamics in real time. Using this method, motions related to the catalytic cycle of lysozyme, a model enzyme, are visualized at atomic resolution and across broad timescales.

Simon and colleagues show that liver cancer cells undergo cell cycle arrest and senescence upon deprivation of methionine and identify GSK3 inhibitors as a senolytic to selectively deplete MAT2A inhibited senescent liver cancer cells.

A small molecule inhibits CDK12 and CDK13 activity through covalent modification of Cys residues and reveals a role of the two kinases in regulating Pol II processivity and super-enhancer-driven transcription factor and DNA damage response gene expression.

Mass spectrometry facilitates large-scale glycosylation profiling but in-depth analysis of intact glycopeptides is still challenging. Here, the authors show that activated ion electron transfer dissociation is suitable for glycopeptide fragmentation and improves glycoproteome coverage.