Search

Unclear emissions and ice-sheet processes drive uncertainties in future sea-level rise. The authors show that the timing of emissions reductions drives the uncertainties during the twenty-first century, but geophysical uncertainties become more important with time, especially under optimistic scenarios.

The low-latitude western boundary current in the South Pacific Ocean strengthened as climate warmed over the past 100 years, according to a coral nitrogen isotope record from the Solomon Sea.

The role of bile acid receptor TGR5 in feeding regulation remains elusive. Here, authors show that physiological and pharmacological activation of TGR5 in the nucleus of the solitary tract lowers feeding and enhances leptin signaling in rats.

Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

Extreme warming 56 million years ago may have rendered parts of the subsurface Atlantic Ocean anoxic and toxic to fish due to ammonium and hydrogen sulfide accumulation – a scenario we must strive to prevent under current anthropogenic climate change.

Reverse electron transport is the mechanism behind excess mitochondrial reactive oxygen species in the livers of obese mice, which has implications for developing therapeutics for fatty liver disease in humans.

The gamma rays spat out by dying stars last an instant. Tony Reichhardt reports on the fast-response satellite that hopes to capture them.

Puissant and colleagues identify a myeloid-restricted PIK3CG/p110γ–PIK3R5/p101 axis as a therapeutic vulnerability in acute myeloid leukemia and develop a proteolysis-targeting chimera to potently degrade PIK3CG and suppress AML progression.

Elevated activity of the methionine cycle is essential for cancer stem cell tumorigenesis and represents a therapeutic vulnerability.

The essential DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) has both endonuclease and exonuclease activities. Here, the authors present DNA bound human APE1 crystal structures which give insights into its exonuclease mechanism.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

When jumbo Humboldt squid disappeared from Chilean waters, it led to the demise of a world-class electrophysiology laboratory. Now the creatures are back, finds Tony Scully, and so are the scientists.

The STORR gene fusion event is a key step in the evolution of benzylisoquinoline alkaloid metabolism in opium poppy. Here, the authors combine phylogenetic, transcriptomic, metabolomic, biochemical and genomic analyses to show the STORR gene fusion occurred only once between 16.8-24.1 million years ago in Papaver species.

Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.

Tony McMichael welcomes an overview of an under-recognized climate issue: the threat to human health.

Measurements of the conformations adopted by isolated proteins at low temperatures show remarkable plasticity including substantial cold induced restructuring and complex frozen conformational landscapes for disordered proteins in the absence of solvent.

The homologous recombination machinery needs to be recruited at replication intermediates for accurate functioning. Here, the authors reveal that a Rad51 paralog-containing complex, called the Shu complex, recognizes and enables tolerance of predominantly lagging strand abasic sites.

Here, the authors show structural, biochemical, and functional insights into the discovery of epichaperome‐ directed chemical probes for use in central nervous system diseases. Probes emerging from this work have translated to human clinical studies in Alzheimer’s disease and cancer.

Characterization of the polysaccharide utilization loci from two Bacteroides species from the human gut microbiota define biochemical and structural features underlying the catabolism of a hybrid algal polysaccharide found in edible seaweed.

Determining which covalent binding events impact protein function is challenging. Now, a strategy has been reported that integrates base editing and chemical proteomics to infer the functionality of ligandable cysteines in cancer dependency proteins by quantifying the impact of their missense mutation on cancer cell proliferation.

TMEPro profiles the glycosylated secreted and plasma membrane proteome of 100 human pancreatic tissue samples, defines cell type origins and identifies potential paracrine cross-talk mediated through tyrosine phosphorylation.

A resource of multiple reaction monitoring–mass spectrometry transitions for quantitative analysis of biological small molecules is provided in METLIN-MRM, along with automated tools for analyzing such data in XCMS-MRM.

A company in Massachusetts is seeking permission to market salmon genetically modified to grow faster than normal. Tony Reichhardt explores the potential ecological risks, should the fish escape from salmon farms.

The translational elongation factor eIF5a may have a function in T cell protein translation. Here the authors show that hypusination of eIF5a or deletion of eIF5a alters the profile of mRNA translation in T cells and that eIF5 regulates the proliferation and effector function of these T cells.

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).

Germline small RNAs in plants and mammals are marked by pseudouridine. In plants, Exportin-t is required for pseudouridylation, transport and localization of small RNAs in pollen, as well as for epigenetic inheritance in the form the triploid block.

NME3 is a member of NDPK family. Here, Chen et. al., discover that histidine phosphorylatable NME3 is required for hypoxia-induced mitophagy via PA-dependent interaction with Drp1, which is protected from MUL1-mediated ubiquitination for mitophagy.

SRPK1, a kinase involved in splicing regulation, is a potential therapeutic target for AML patients. Here, the authors show that SRPK1 inhibition changes isoform levels of key epigenetic regulators, including BRD4, and it has anti-tumor effects specifically against MLL-rearranged AML cells.

Reproduction in numerous marine organisms is timed to specific moon phases, but the mechanisms for sensing moon phases are incompletely understood. Here the authors report that an ancient, light-sensitive protein L-Cryptochrome in a marine bristle worm can discriminate between sun- and moonlight, enabling the animals to properly decode moon phases.

Treatment with a specific inhibitor of the N⁶-methyladenosine methyltransferase METTL3 leads to reduced growth of cancer cells, indicating the potential of approaches targeting RNA-modifying enzymes for anticancer therapy.

Plasma from voluntarily running mice reduces baseline expression of neuroinflammatory genes and experimentally induced brain inflammation when infused into sedentary mice.

Sarry and colleagues demonstrate that adaptive resistance to venetoclax + cytarabine therapy in acute myeloid leukemia relies on mitochondrial respiration and show that combination with electron transport chain complex inhibitors delays relapse in patient-derived xenograft models in vivo.

Cryo-EM reveals one mechanism of action of the antimalarial mefloquine: mefloquine binds to the Plasmodium falciparum 80S ribosome, inhibiting protein synthesis in the parasite.

Hurricane Larry deposited substantial amounts of microplastic particles over Newfoundland, Canada in 2021, probably derived from the garbage patch in the North Atlantic gyre, according to sample collection and analysis as well as back-trajectory modelling.

The Plasmodium falciparum protease plasmepsin V forms a complex for the translocation of PEXEL effector proteins into the endoplasmic reticulum that is distinct from the Sec61–signal peptidase complex that regulates the translocation of proteins destined for the classical secretory pathway.

Academic experts say they were all too aware of the devastation that would claim New Orleans and its surroundings in the wake of a fierce hurricane. Could they have done any more to convince politicians of the need to protect the city?

Planetary scientists debate where to land next.

Plasmodium falciparum is known to secrete an aspartic protease called plasmepsin X. Here, Triglia et al present a characterisation of plasmepsin X function in the context of erythrocyte invasion and its regulation of PCRCR, a complex that anchors the leading vaccine candidate PfRh5 to the parasite surface.