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Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Santos et al found that the ubiquitin ligase adaptor Fbxo42 is a critical regulator of terminal Unfolded Protein Response signaling through its control of Ataxin-2 granules containing Xbp1 mRNA.

Structurally convergent antibodies targeting the conserved influenza HA anchor epitope have provided a template for next-generation vaccine development. The authors identified four anchor antibodies encoded by diverse germline genes with broad neutralizing activity against influenza H1N1 viruses.

This study examines the outcomes of dietary shifts across intrinsic and instrumental conservation perspectives, finding that most conservation benefits already come from a partial shift to healthier, more plant-based diets, whereas greater benefits depend on more targeted conservation action.

Here the authors show that MRAP2 tunes the melanocortin-4 receptor by boosting its G-protein signaling while limiting β-arrestin2 interaction and destabilizing receptor oligomers, shaping appetite regulation.

Bovine H5N1 viruses are lethal in laboratory animals, but they retain avian traits including limited transmission. Their responsiveness to approved antivirals and candidate vaccines lowers human risk, but ongoing surveillance is critically needed.

Climate change threatens mountain ash (Eucalyptus regnans) forests, which are among Earth’s most carbon-dense ecosystems. This study finds that a projected 3^∘C warming by 2080 could reduce tree density and carbon storage in these forests by 24%

LYMTACs are heterobifunctional small molecules that take advantage of lysosomal membrane proteins to degrade membrane targets via relocalization and lysosomal degradation, offering a modular approach to drug otherwise intractable membrane proteins.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

January 2022 saw the first observations of a tsunami resulting from a large emergent volcanic eruption (Hunga Tonga) captured using modern instrumentation, with broad implications for hazard management in similar geophysical settings.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

Logging and agricultural conversions led to the loss of 46% of montane forests in Kenya’s Central Highlands between 1910 and 1975, while legacies of postcolonial resettlement resulted in a further 20% loss between 1975 and 2024, according to historical maps, satellite imagery, and resettlement datasets.

This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

The recently identified Wuhan spiny eel influenza virus (WSEIV) sequence is more closely related to influenza B than A viruses. Here, the authors functionally characterize the putative surface glycoproteins of WSEIV and show that its NA-like protein has sialidase activity and its HA-like protein binds monosialic ganglioside 2.

Drought is a growing issue in tropical rainforests. Here, the authors revisit a long-term rainfall manipulation experiment in the Amazon to show that tree mortality was followed by community-level adjustments to reduced precipitation.

A summary of CAR T-cell engineering approaches, including functional screening methods, gene editing and delivery advances, and optimization of metabolic fitness.

This study shows that the soluble guanylate cyclase GCY-35 responds to increased oxygen and that a neural globin, GLB-5, is involved in sensing reduced oxygen. The behavioural response to GLB-5 activation involves the neuropeptide receptor NPR-1, and both glb-5 and npr-1 show natural variation amongst different Caenorhabditis elegans strains.

Although IWS1 has been implicated in transcription-coupled processes, its direct role in RNA polymerase II function remained undefined. Here, the authors demonstrate that IWS1 enhances Pol II elongation velocity by acting as a structural scaffold and promoting co-transcriptional H3K36me3 deposition.

Controlled manipulation of particles from very large volumes of fluid at high throughput is critical for many real-world applications. Here, the authors show bioparticle focusing in a microchannel for a previously unattained regime of inertio-elastic flow at Reynolds numbers up to 10,000.

A distinct class of broadly neutralizing antibodies to the influenza virus target a membrane-proximal anchor epitope of the haemagglutinin stalk domain.

The inner scaffold is key for centriole stability but its organization is unclear. Here, the authors show the formation of POC1A-POC1B heterodimers, where POC1B resides near the centriole wall and POC1A associates with a POC5 tetramer/Centrin complex.

An examination of the receptor-binding properties of the H7N9 virus, which has recently emerged in China, shows that the virus has acquired the ability to bind the human α-2,6-linked sialic acid receptor while retaining binding to the avian α-2,3-linked receptor, and therefore does not have the preference for human versus avian receptors characteristic of pandemic viruses.

Influenza B virus (IBV) co-circulates with influenza A virus to cause annual epidemics. Here, Chaiet al. isolate a human monoclonal antibody that binds to a conserved epitope in the viral HA protein, neutralizes IBV strains in vitro, and protects mice against IBV infection.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

Implant-associated infections with Staphylococcus aureus pose serious clinical challenges. Here, the authors develop a biosensor based on toxin-responsive liposomes encapsulating gold nanoclusters, providing a non-invasive, colourimetric diagnostic tool for bacterial infection detection with urinary readout.

Barney Graham and colleagues have developed a hemagglutinin stem–based nanoparticle as a vaccine that confers protection against different influenza strains in mice and ferrets.

VRN1 is a central regulator of flowering following prolonged cold exposure in cereals. Here Deng et al. combine ChIP-seq and RNA-seq to identify downstream targets of VRN1 in barley and demonstrate direct links between the flowering pathway and genes controlling other important agronomic traits.

Metabolic and alcohol-related liver disease presents challenges in clinical trials due to complex pathophysiology. This Review discusses noninvasive imaging, serum biomarkers and adaptive designs as modalities to enhance patient-centric end points, aiming to refine diagnostics and improve drug development.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

Building on previous work that identified a mutant avian H5 virus that is transmissible between ferrets, the authors present an algorithm to predict virus avidity from the affinity of single haemagglutinin (HA)–receptor interactions; these studies predict that the mutant has a 200-fold preference for the human over the avian receptor, and crystal structures of the mutant HA in complex with human and avian receptors shed light on the molecular basis for these altered binding properties.

New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.

Computational modeling and design of G Protein-Coupled Receptor quaternary structures reveals a signaling bias switch at the receptor dimer interface that selectively controls G protein vs β-arrestin activation.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

Despite fishing-induced biomass depletion on coral reefs, fisheries persist. This study presents a framework to evaluate potential reef fisheries productivity across a major fishing pressure gradient and shows evidence of compensatory ecological responses triggered by fishing on coral reefs.

Adeno-associated viruses can be secreted in a pre-lytic manner as free or extracellular vesicle (EV)-associated particles. Here, Elmore et al. show that the recently identified membrane-associated accessory protein (MAAP) functions as an AAV egress factor via association to EVs.

Antibodies that bind to both H1 and H3 influenza strains exist in the pre-vaccination serum repertoire of healthy adults; most vaccine-elicited clonotypes bind either H1 or H3 strains.

Here, the authors solve a series of cryo-electron microscopy structures that show how transfer RNAs (tRNAs) can guide the assembly of the multisubunit poxvirus RNA polymerase, uncovering a role of tRNA as an assembly chaperone.

Unlike Amazonian forests, African forests have maintained their carbon sink until recently but by 2030 the African carbon sink will have shrunk by 14 per cent and the Amazonian sink will reach almost zero.

The M₅ muscarinic acetylcholine receptor represents a promising therapeutic target for neurological disorders. Here, the authors reveal a 2.1 Å cryo-EM structure of the M₅ bound to a selective positive allosteric modulator site that enables structure-based drug design.

Asthma is characterized by abnormal airway hyperresponsiveness. Here the authors identify BPIFA1 as a factor secreted by airway epithelial cells, and show that it regulates contractility of airway smooth muscle cells by binding to and regulating the Orai1 Ca²⁺channel.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.