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Mitochondrial respiration provides reducing power to the electron transport chain (ETC), driving proton pumping and ATP synthesis required for T cell activation and differentiation. Here, the authors use alternative oxidase (AOX) as a mechanistic probe to bypass cytochrome c oxidase deficiency and thereby isolate the role of respiration and demonstrate that intact mitochondrial respiration is important for T cell proliferation, effector function, memory formation, and regulation of apoptotic and metabolic signaling pathways.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Suberizing plant cells export suberin monomers outside of the cell to form a hydrophobic barrier. Here the authors propose a role for extracellular vesiculo-tubular structures in the deposition of suberin monomers.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Endoplasmic reticulum (ER)-interorganelle membrane contact sites have emerged as key regulators of organelle dynamics. Here, the authors report that the ER-resident protein SNX19 mediates ER-endolysosome membrane contacts to maintain the perinuclear distribution of endolysosomes and restrict their motility.

Chronic stress responses can be as damaging as the hazards they counteract. Here the authors show how a blindness-induced brain-wide stress response is dampened by sequestration of transcription factors in cytosolic granules.

Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) in type 2 alveolar epithelial (AT2) cells is thought to aggravate alveolar inflammation in acute lung injury. Here, the authors show that the mtLCFAO rate limiting enzyme CPT1a is decreased in AT2 cells in acute respiratory distress syndrome, highlighting the role of mtLCFAO in immunometabolism in this context.

A new carbonate phase calcium carbonate hemihydrate was recently discovered and characterized, but exclusively as a synthetic material. Here the authors find that it exists in nature, albeit transiently, on the surface of growing nacre and coral skeletons, and show that 2 amorphous and 2 metastable crystalline nano-minerals form before biominerals settle into their stable crystals.

A number of human African trypanosomiasis, or sleeping sickness, patients suffer from respiratory symptoms commonly attributed to cardiac insufficiency. Here, the authors characterise the role of pulmonary Trypanosoma brucei in respiratory infection.

It is unclear how circuit specificity and function are maintained during organismal growth. In this study, authors show that connectivity between primary nociceptors and their downstream neurons scales with animal size and that Ste20-like kinase Tao acts as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity.

Mitochondrial diseases lead to chronic health impairment, aggravated by infections and other environmental exposures. Here authors show, in a mouse model of polymerase gamma (Polg)-related mitochondrial disease, that Pseudomonas aeruginosa infection prompts innate immune hyperreactivity via interferon-mediated upregulation of caspase11 and guanylate-binding proteins, leading to lung inflammation.

Here, combining X-ray crystallography, cryo-electron tomography and animal studies, the authors show that the monoclonal antibody against Ebola virus glycoprotein (GP1,2) 3A6 exerts protection via binds to a conformation of GP1,2 that is lifted from the virion membrane, providing insights into the mechanism of action with implications for the design of anti-Ebola therapeutics.

Adenosine is an immunosuppressive metabolite known to limit anti-tumor immune responses. Here the authors report the characterization of an adenosine A2A receptor (A2AR) eGFP reporter mouse, providing immunological insights into the biology of A2AR expression in the context of anti-tumor immunity.

A hybrid model that combines a differentiable solver for atmospheric dynamics with machine-learning components is capable of weather forecasts and climate simulations on par with the best machine-learning and physics-based methods.

Auxin-binding protein 1 (ABP1) is an auxin receptor that, in complex with transmembrane kinase 1 (TMK1), has a key role in the auxin-induced global phosphorylation of proteins and downstream responses such as vascular regeneration.

Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14⁺CD1c⁺ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Severe SARS-CoV-2 infection has been associated with extensive diffuse alveolar damage and fibrin formation. Here, Erickson et al describe an infection-induced coagulation mechanism which involves activation of prothrombin by members of TMPRSS genes.

It is unclear what role mitochondrial function plays in maintaining intestinal epithelial cell (IEC) homeostasis. Here, the authors deplete a mitochondrial chaperone, heat shock protein 60 (HSP60) in IEC and observe a loss of stemness and cell proliferation, and suggest this is accompanied by a compensatory release of WNT-related factors.

During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.

Perfluorinated organic molecules have shown many uses, including as imaging agents. Here, the authors report that fluorinated gold nanoparticles offer an effective means of mass spectrometry tissue imaging, in addition to facilitating X-ray analysis providing complementary information to mass spectral images.

Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have provided largely negative results, so far. Here, the authors present a machine learning framework that quantifies potential associations between the pathology of AD severity and gene-based molecular mechanisms to enable drug repurposing.

Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGFβ instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.

The role of long non-coding RNAs (lncRNAs) in metastatic colorectal cancer (mCRC) and treatment resistance is unclear. Here, the authors use transcriptome sequencing of matched normal, primary, and metastatic CRC tissues to discover and validate that lncRNA RAMS11 promotes metastasis and resistance to topoisomerase inhibitors in mCRC.

Nicholas Katsanis and colleagues show that biallelic mutations in TTC21B, encoding the retrograde intraflagellar transport protein IFT139, are associated with diverse ciliopathy phenotypes in humans. They further show that pathogenic alleles of TTC21B are present in as many as 5% of ciliopathy cases, supporting an oligogenic model of disease.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Neural coding for motion direction has been studied intensively in the visual cortex of non-human primates. Here, the authors establish an origin for direction selectivity in the retina of the macaque monkey.

Repeat-rich sequences play a role in 3D genome architecture in higher eukaryotes; however, this remains unexplored in brain cells. Here, the authors show that upregulation of endogenous retroviral (ERV) sequences is linked to changes in the 3D structure in the brain, which is also observed by comparison of mouse strains with recent retrotransposon expansion.

Na+-H+ exchanger 1 (Nhe1) regulates extracellular pH by extruding protons in exchange for extracellular Na+ . Here, Liu et al. show that Nhe1 promotes the development and acidification of atherosclerotic lesions and that pH-sensitive probes can be used to monitor plaque growth and acidification.

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.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.

Mutations in VPS35 that are associated with Parkinson's disease increase the interaction of VPS35 with mitochondrial DLP1, leading to removal of the DLP1 complexes and mitochondrial fragmentation. Structural and functional mitochondrial impairments caused by mutant VPS35 are observed in vitro using cultured neurons and fibroblasts from individuals with PD and in vivo in mouse substantia nigra neurons, where they induce neurodegeneration.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

Brucellosis is a zoonotic disease with high prevalence in the Middle East. Here the authors identify camels as an important source of brucellosis among livestock-owning households in Jordan, due to widespread consumption of raw camel milk.

Macrophages survey their surroundings using macropinocytosis, but its regulation is unclear. Here, the authors report that SLIT2, a known inhibitor of Rac GTPases, is an endogenous inhibitor of macropinocytosis, and that SLIT2 limits the uptake of NOD2 ligands into immune cells and subsequent release of the inflammatory chemokine, CXCL1, in vivo.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

Spectroscopy from the JWST Advanced Deep Extragalactic Survey of a galaxy at redshift 13 shows a singular, bright emission line identified as Lyman-α, suggesting the onset of reionization only 330 Myr after the Big Bang.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.