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Multiple myeloma involves alterations to T cell function, but mechanisms underlying disease evolution remain unclear. Here the authors find that, unlike solid cancers, multiple myeloma lacks exhausted T cells and is instead characterized by antigen-driven terminal memory T cell differentiation, which may be driven by tumour-intrinsic features including tumour burden and antigen-presentation gene expression.

Therapy to allergy often targets a specific allergen without addressing cross-reactivity. Here the authors develop a consensus, cross-reactive allergen, use mRNA-lipid nanoparticle immunization to induce specific, neutralizing IgG responses, but find no therapeutic effects in mouse allergy models, hinting the need for further optimization prior to translation.

This study quantifies the environmental impact associated with photovoltaics manufacturing and demonstrates significant CO₂ emissions savings, depending on solar cell technology and the composition of the electricity mix in the region of manufacture.

The authors realize two- and three-site Kitaev chains in semiconducting quantum dots coupled via superconductors and tune them to the sweet spot where zero-energy Majorana modes appear at the chain ends. To assess Majorana localization, they couple the system to an additional quantum dot.

Nuclear protein homeostasis relies on proteasome import into the nucleus. Here the authors identify how assembled human proteasomes are transported across the nuclear pore complex and reveal a mechanism enabling the large complex to bypass pore size limitations.

T cell activation requires major metabolic adaptation. Here authors find that in mice and humans, expression of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1) increases in CD4+ T cells upon activation, particularly within the cytoplasm, which impacts NADP/H and reactive oxygen species signalling, restraining activation and cytokine production while promoting CD4 + T cell survival during viral and fungal infections.

Repeated rapid structural MRI scans substantially improve the precision of individual differences in brain change. This allowed for individualized insight into subtle differences in the detected rates of brain aging and neurodegeneration to be detected.

This manuscript from Choquette and colleagues finds that sclerostin gene expression is up-regulated in bone by β3-adrenergic signaling via an adipose to bone relay and acts as an endocrine factor to inhibit adipose tissue beiging in mice.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Structural variants are an underexplored source of genetic diversity. Here, the authors use phased pangenome graphs to improve detection of these variants in dairy cattle and link these variants to traits of economic importance.

The role of mitochondrial supercomplexes in guiding redox proteins across membranes during energy conversion remains unclear. Here, authors integrate multiscale modeling and cryo-EM to examine mechanisms of electron transfer and energy conversion efficiency.

Here, using anatomy, transcriptomics, and functional assays, the authors reveal how Japanese wisteria climb using an unusual vascular architecture. Ectopic cambia arise from cortical cells and repurpose conserved cambium regulators, including KNOX genes.

It is currently unknown how uniform is signalling at the first synapse of vision in vivo. Here, the authors show neighbouring PR1 (red) cones differ in contrast sensitivity and timing due to locally stochastic horizontal-cell feedback, thereby extending total dynamic range.

Researchers show that twisting SnS₂ nanosheets and anchoring single Ni atoms strengthens spin-orbit coupling, reshaping CO₂ photoreduction to favor ethane by generating and coupling methyl radicals from CO₂ and water.

Momentum-entangled atom pairs are used to demonstrate quantum non-locality, where changing one atom in an entangled pair instantly alters the state of the other atom. This result paves the way to study interactions between quantum states and gravity.

Humans alter the daily timing of animal activity, potentially reshaping predator–prey interactions. This meta-analysis reveals that larger species tend to “lose” under human disturbance, with large predators overlapping less with their prey, and large prey overlapping more with their predators.

Peroxidases have long been considered to use ferryl heme intermediates (Fe(IV) = O) to catalyze oxidative chemistries. Here, Williams et al. find that ferric-oxyl (Fe^III–O^•–) excited states exist along the catalytic reaction coordinate of a peroxidase.

For proper mitochondrial inheritance, paternal sperm mitochondria must be eliminated. Here, authors identify ALKB-1 mediated tRNA demethylation as essential for this clearance in Caenorhabditis elegans, revealing an epitranscriptomic quality checkpoint tied to male fertility.

The authors describe a stacked generalization approach to predicting missing links in food webs that considers both species traits and network structure, achieving near-perfect performance on many empirical food webs.

Protein function is governed by more than abundance alone. Here, the authors introduce a supercharging-enhanced nDIA-MS workflow to map drug-induced solubility changes across the proteome, enabling high-throughput analysis of protein state transitions.

Prenatal Zika virus (ZIKV) exposure can lead to a spectrum of developmental issues, but the mechanisms remain unclear. Here the authors show that prenatal ZIKV exposure in macaques disrupts neurodevelopment, causing prolonged maternal attachment and visual deficits at 3 months that normalize by 12 months, independent of sensory function.

Johnson et al. link ARIA, a complication of anti-amyloid therapy, to clonal expansion of cytotoxic CD8 + T cells with glycolytic reprogramming and vascular trafficking potential, with implications for biomarker development and risk mitigation.

Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Here this trial evaluates the safety and efficacy of olutasidenib (mIDH1 inhibitor) on 23 patients with locally advanced or metastatic mIDH1 chondrosarcoma.

Baracchini et al. reveal that temporal variability in fMRI brain signals encodes biologically meaningful information across spatial and temporal scales, highlighting its role in healthy brain function and systems-level organization.

The longevity of leaves determines the overall duration of photosynthesis for plants. This study suggests that climate change drives leaf longevity convergence toward intermediate ranges, which, by altering leaf traits and enhancing photosynthetic capacity, strengthens ecosystem stability and is closely linked to vegetation diversity.

This trial found spinal cord stimulation was well tolerated in people with gait-impaired Parkinson’s disease. It suggests that longer use improved lower-body motor symptoms while reducing thalamic hypermetabolism and cholinergic overactivity.

The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

BiG-SCAPE and BiG-SLiCE are computational tools that enable exploring the diversity of metabolic gene clusters across microbial genomes. Here, the authors present major updates to these tools, providing essential infrastructure for studying the diversity of microbial metabolism.

Here, in a cross-sectional study of 209 individuals living in communities with contrasting Schistosoma mansoni endemicity in Uganda, the authors identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk.

Sixteen crystal structures of the non-heme iron enzyme Rv0097 reveal how protein motions are orchestrated in the two-step, α-ketoglutarate-dependent, biosynthesis of isonitrile functional groups from substrate glycyl moieties.

Most studies assessing food self-sufficiency look at calories and neglect nutrient gaps. Comparing food demand and potential food production under land and water constraints, this study quantifies 9 key nutrient gaps for each of African’s 54 countries.

This study shows that contrail avoidance can recover 9% of the global temperature budget by 2050. For every year of delay, the recoverable warming will diminish by 0.6%. This makes inaction (not fuel penalties) the most significant climate risk associated with avoidance.

Nitrogen and phosphorus in Greenland ice are present in measurable amounts and exceed algal needs, suggesting these nutrients do not limit glacier ice algae growth during the melt season.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

Energy gaps can be induced by spatial modulation of the electronic potential. Here, the authors demonstrate a large and robust energy gap in a free-standing carbon nanotube utilizing a 15-gate keyboard that spatially modulates the local potential.

Machine learning is used to understand emissions of the potent greenhouse gas nitrous oxide from the Southern Ocean. Low-pressure storms are found to drive emissions, leading to a revised picture of marine greenhouse gas cycling

This study develops and validates a prognostic staging framework for Alzheimer’s disease by integrating cognitive status with blood-based biomarkers, and neuroimaging data, to improve risk stratification across the disease continuum.

Neural crest cells are migratory cells unique to vertebrates. Here they show that NR6A1 is a key regulator of neural crest cell formation and survival by downregulating pluripotency-associated genes, while upregulating neural crest cell specifier genes and epithelial cell to mesenchyme cell transition.

Using the 2008 Wenchuan Earthquake, the authors show that earthquake-triggered landslides increased mountain carbon storage by ~10% from 2008 to 2020, as vegetation recovery and sediment burial retained carbon, revealing earthquakes and landslides function as long-term carbon capacitors.

Despite advances in enzyme design and engineering, the development of biocatalysts featuring a combination of tailored stereoselectivity with broad substrate scope has been very difficult. Focusing on a new-to-nature reaction, the authors report a mechanism-based, multi-state computational design workflow for the generation of ‘generalist’ cyclopropanases capable of transforming a broad range of substrates with tailored and divergent stereoselectivity.

Rare cells are often biologically and clinically important, but their low abundance makes them challenging to study using single-cell transcriptomics. Here, the authors develop PURE-seq which integrates FACS and PIP-seq to directly sequence ultra-rare cells. It captures cells at 1 in 1,000,000 rarity, which the authors demonstrate by profiling circulating tumor cells and identifying Egr1 as a regulator of mouse hematopoietic stem cell aging.

Diatoms are critical for carbon fixation and have strong biotechnology potential. Here, the authors optimized DNA and protein delivery methods for the model diatom Phaeodactylum tricornutum, also showing that DNA pieces can be stitched together directly in algal cells.

Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

Deep brain stimulation tuned to cue-reactivity within the nucleus accumbens region reduced drug cravings, heralding an evocation-based programming strategy for opioid use disorder.

A streamlined blood test using mass spectrometry improves measurement of amyloid-β for early Alzheimer’s disease diagnosis, requiring less sample volume and reagents while maintaining high accuracy, sensitivity and strong agreement with brain imaging.

Lipopeptides are used to combat drug-resistant infections, but drawbacks limit their application. Here, Lim et al. contrast the mechanisms of lipopeptides that are superficially similar yet disrupt membranes in distinctly different ways.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.