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The somitic mesoderm is seen as the main source of brown adipose tissue, although some depots are of partially unknown origin. Here, the authors show that Osr1 labels multipotent dorsal aorta progenitors at E9.5 that contribute to cartilage, muscle, and adipose tissues, revealing a non-somitic contribution to several brown adipose depots.

The hippocampus can replay long spatial sequences without ripples. When present, ripples cluster in spatially restricted zones as a function of replayed location that remap with barrier changes, implying a tagging role in consolidation.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Highly pathogenic avian influenza H5N1 viruses are of global concern. This study shows that a low-dose H5N1 clade 2.3.4.4b Alum/CpG-adjuvanted vaccine elicits broad, durable antibody and T cell responses and protects female mice against lethal homologous and heterologous H5N1 challenges.

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Integrated single-cell and spatial data analysis, combined with bidirectional CRISPR screens, identify the transcription factor GLIS3 as a key driver of chronic inflammation and fibrosis and a potential marker of disease severity in patients with ulcerative colitis.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

Molecular glue degraders eliminate cellular proteins by promoting their interaction with E3 ubiquitin ligases. Here, the authors identify molecular glue degraders targeting the E3 ligase TRIM21 and synthesize a heterobifunctional degrader that recruits TRIM21 to degrade an engineered protein aggregate.

Coagulation factor IX (FIX) contributes to hemostasis through both plasma activity and binding to extravascular collagen IV. Here, the authors show that collagen binding of albumin-fused hyperactive FIX can be engineered to tailor the pharmacokinetics, distribution, and functional properties in mice for tailored short- or long-term hemophilia B therapy.

In ancestral SARS-CoV-2 infection, NK cell interferon-stimulated gene (ISG)-driven activation correlated with poor antibody breadth. In vitro, NK cell ISG expression boosts cytotoxicity toward T_FH-like cells, suggesting a mechanism for impaired antibody responses.

Environmental justice and drinking water in the US: Higher proportions of Hispanic/Latino, American Indian/Alaskan Native, and non-Hispanic Black residents were associated with higher public water arsenic and uranium at the county-level, findings differed by region.

Synthetic Notch (SynNotch) receptors can be used to endow cells with custom sense-and-respond capabilities. Here, the authors introduce a fluorescein-binding SynNotch as a versatile tool for controlling gene expression responses to diverse stimuli via ligands based on fluorescein-conjugates.

Avian influenza jumped from wild birds into dairy cattle. Here, the authors report that two mutations in the viral polymerase helped the virus to quickly adapt to cattle. Mutations increased the polymerase activity and made the virus better at replicating in human cells.

Socially marginalized communities in the U.S. are at higher risk of contaminant releases due to sea level rise-related flooding of hazardous sites. By 2100, 5500 facilities are at risk of a 100-year flood under continued high greenhouse gas emissions.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

High-throughput molecular surveillance of mosquitoes carrying dangerous pathogens is currently challenging. Here the authors present Vectorchip, a low-cost microfluidic platform enabling multiplexed detection of mosquito DNA, viral RNA and infectious viral particles at single bite resolution.

In this study, the authors develop a flavivirus vaccine strategy by introducing mutations into envelope glycoproteins resulting in structural changes that conceal the ADE-prone fusion loop epitope. They show that the Zika virus-specific construct protects mice against viral challenge and prevents ADE by Dengue virus.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

Surgical sterilization alone cannot control global stray and feral domestic cat populations. Here, Godin et al. show that a single-dose injectable female sterilant administered before puberty safely and completely prevents pregnancy after maturity.

Optical coherence microscopy with AI assisted algorithms is used to track organoids and their viability longitudinally. Photoacoustic imaging adds rare cell detection function to the 3D cell culture analysis toolbox.

A Gifsy-1 prophage–encoded higher eukaryotes and prokaryotes nucleotide-binding protein, HepS, senses Siphoviridae infection, activates abortive defence by cleaving host transfer RNAs, blocks rival phages and avoids self-targeting via tail-tip variation.

Treatment with 4′-fluorouridine (also known as EIDD-2749) in an African green monkey (Chlorocebus aethiops) model of Lassa disease resulted in complete clearance of infectious virus in a high proportion of cases and prolonged survival to the pre-determined study end-point in all cases.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

CFAP20 has a key role in rescuing RNA polymerase II complexes that have arrested during DNA transcription, limiting the accumulation of R-loops and preventing collisions between the transcription and replication machinery.

The development of cancer is typically accompanied by changes in the tumor microenvironment that support tumor growth and affect therapy response. Here, the authors show that increased intratumoral temperature is an inherent feature of human pancreatic cancer and contributes to therapy resistance by altering the lipid content of the tumor.

The authors identify defective viral particles, in people with non-suppressible HIV-1, that can replicate through superinfection and interfere with the wild-type virus. However, they show no evidence of these preventing disease progression in the individuals studied.

Plant-parasitic nematodes have the potential to destroy crops globally, and limited options for managing nematode infestation are available. Here, the authors report the 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

The Akt-mTOR axis influences cell activation, differentiation and metabolism. Jordan and colleagues show that thymic and inducible T_H17 cells exhibit different requirements for mTORC1 and mTORC2 as well as Akt isoforms.

This study reveals that anti-NS1 IgA antibodies in plasma, induced by prior Zika virus infection, activate neutrophils, underlying severe dengue disease upon a subsequent DENV2 infection, uncovering a pathogenic mechanism relevant for vaccines and therapeutics.

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, but platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, the authors design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone, which exhibit the activity of both parent anticancer compounds and can overcome drug efflux effectively due to covalent binding to intracellular biomolecules.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

Intravesical bacillus Calmette–Guérin (BCG) is an established bacterial immunotherapy for bladder cancer. Here, the authors develop a personalized platform to identify microbial product cocktails that promote immune cell recruitment, infiltration, and activation for improving bladder cancer treatment.

GATA6 maintains epithelial traits and limits EMT in pancreatic cancer. Combined MEK and HDAC inhibition restores GATA6+ tumor cells, boosting MHCI expression and CD8+ T cellmediated anti-tumor immunity.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

Human challenge studies with SARS-CoV-2 have shown changes in the innate and adaptive immune response. Here the authors are examining potential correlates of infection in virus challenged recipients by assessing baseline immune parameters and how this predicts virus control.

Clade 2.3.4.4b highly pathogenic H5N1 is currently causing a panzootic and has the potential to become a pandemic. Here, Peña Alzua and colleagues develop specific monoclonal antibodies against this virus that could be used to prevent or treat human infections.

Structure-specific endonucleases play an important role in several DNA repair pathways. Here the authors present structures of the endonuclease XPF-ERCC1 in complex with SLX4, SLX4IP, and DNA. Combined with functional analysis, these results provide insight into the mechanisms of XPF-ERCC1 recruitment and activation during DNA repair.

Thermal contraction effect increases with time dominates the long-term deformation trend of the Heber geothermal field, while pressure effects of pressure fluctuation and poroelastic responses keep relatively stable and drive short-term changes.

A protein biomarker, the NOTCH3 extracellular domain, identifies individuals with idiopathic pulmonary hypertension, correlates with disease progression, improves mortality risk prediction and provides a readily implementable, noninvasive blood test for this disease.

A large proportion of methane emissions from natural gas production sites are released by a fraction of high-emitting sources. Here, using Monte Carlo simulations, the authors reveal that super-emitters occur due to abnormal process conditions, explaining component and site-based inventory discrepancies.

Stable adipocytes resist lipolysis in healthy states but are highly susceptible to a catecholamine-independent, neurosystemic pathway-driven catabolic state.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.