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Permafrost in Europe’s mountains has warmed by more than 1 °C per decade in certain places, matching the levels in Arctic lowlands. The strongest warming occurred at cold bedrock at the highest elevations and latitudes or after permafrost degraded.

T cells are highly dynamic and their spatial and cellular interactions can influence their differentiation program. Groom and colleagues use three-dimensional spatial imaging to show that effector and stem-like memory cell fates are imposed within distinct lymph node regions.

A series of recent studies have revealed similarities in the characteristics of non-infectious neurodegenerative diseases and prionopathies. Frost and Diamond consider what these findings may tell us about disease pathogenesis and treatment strategies.

Proton conduction is a fundamental process for fuel cell development, but three-dimensional proton conduction in crystalline porous solids is rare. Here, the authors report organic molecular cages in which the structure imposes three-dimensional proton conductivity competing with metal-organic frameworks.

Kinetochores must interact with both polymerizing (straight) and depolymerizing (curved) microtubules to ensure correct mitotic chromosome segregation. Abad et al. reveal how this flexibility is achieved through structural characterization of the interactions between microtubules and the kinetochore protein Ska1.

Catabolizing lignin-derived aromatic compounds requires an aryl-O-demethylation step. Here the authors present the structures of GcoA and GcoB, a cytochrome P450-reductase pair that catalyzes aryl-O-demethylations and show that GcoA displays broad substrate specificity, which is of interest for biotechnology applications.

Diacylglycerol kinase is a small bacterial membrane-bound trimer that catalyses diacylglycerol conversion to phosphatidic acid. Here, the authors solve the crystal structure of the kinase bound to a lipid substrate and an ATP analogue, and show that the active site arose through convergent evolution.

Killing bacteria in tumors boosts survival in a mouse model of colon cancer.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

C9orf72 ALS/FTD polyGR and polyPR knock-in mice show cortical hyperexcitability and motor neuron loss accompanied by an increase in extracellular matrix proteins in the spinal cord that is conserved in patient iPS cell-derived neurons and is neuroprotective.

Fumarate metabolism regulates the innate immune response through a mechanism in which high levels of fumarate result in the generation of mitochondrial-derived vesicles and the release of mitochondrial DNA into the cytosol, which activates inflammatory pathways.

This study reveals near-atomic interfacial details of an Alzheimer’s Positron Emission Tomography (PET) molecule MK-6240 with its target disease marker, tau amyloid, showing MK-6240 mostly interacts with itself, like a pancake stack, which stabilizes an otherwise small interface with the amyloid.

Th17 cells are critical players in the immunopathology of a range of autoimmune diseases. Here the authors implicate Hedgehog signaling in Th17 polarization and in the immunopathology of intestinal inflammation in murine models and suggest therapeutic targeting of Hedgehog signaling in the context of inflammatory bowel disease.

The genomes of two fern species, Azolla filiculoides and Salvinia cucullata, are reported and provide insights into fern-specific whole-genome duplications, fern-specific insect-resistant gene evolution and fern–cyanobacterial symbiosis.

The actin cytoskeleton is crucial for cell and organelle motility. Here, the authors show that actin acts upstream of the mitochondrial fusion machinery to bridge two fusing mitochondria.

Although gas bubble dynamics during electrochemical processes dramatically affect performance, the fundamental understanding and manipulation of such dynamics have been limited. Now, electrolyte composition is found to be a key factor in inducing a solutal Marangoni instability that impacts both H₂ gas detachment and coalescence between H₂ microbubbles.

Idiopathic pulmonary arterial hypertension is a rare and fatal disease with a heterogeneous treatment response. Here the authors show that unsupervised machine learning of whole blood transcriptomes from 359 patients with idiopathic pulmonary arterial hypertension identifies 3 subgroups (endophenotypes) that improve risk stratification and provide new molecular insights.

Far-field mid-infrared spectroscopy reveals both the electroluminescence of hyperbolic phonon polaritons of hexagonal boron nitride excited by strongly biased graphene, and the associated radiative energy transfer through the material.

The use of biomaterial scaffolds-based cartilage grafts could potentially innovate the Osteoarthritis (OA) treatment, but has been limited by toxicity concerns and invasive surgical procedures. Here, the authors report an injectable and biodegradable piezoelectric hydrogel with ultrasound activation to offer a minimally invasive approach for OA treatment.

Helgeland et al. characterize genetic loci associated with early childhood body mass index, highlighting roles of genes involved in monogenic obesity, appetite regulation and energy expenditure, many of which show age-specific association patterns.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

The structure of a Stig cyclase, HpiC1, reveals how it catalyzes Cope rearrangement and 6-exo-trig cyclization, including how it controls the position of electrophilic aromatic substation that distinguishes hapalindole from fischerindole alkaloids.

A comparison of copper and zinc isotopic measurements between the Ryugu samples and various carbonaceous chondrites excludes any genetic link between the two except for the CI (Ivuna-type) chondrites. Ryugu-like material might have accounted for ~5% of Earth’s mass.

Cancers often harbor mutations in genes encoding important regulatory proteins, but therapeutic targeting of these molecules proves difficult due to their high structural similarity to their non-mutated counterpart. Here authors show the engineering of T cell engaging bispecific protein able to selectively target cancer cells with a high-frequency mutation in the KRAS oncogene.

The colocation of all RNAs in the nucleus is determined with a droplet sequencing method.

The extrusion-based three-dimensional printing of polymers, metals, and composites requires elevated temperatures and may lead to diverse undesirable defects on printed parts. Here, the authors develop a vapor-induced phase separation printing technique to construct polymeric, metallic, and composite parts by using a polymer as a binder.

It is known that skin has a large tear resistance, but little is known of the mechanism behind this. Here, the authors carry out a structural analysis of rabbit skin to show how the deformation of collagen fibrils in the skin results in a strong resistance to tear propagation.

Templates are widely used to arrange molecular components so they can be covalently linked into complex molecules that are not readily accessible by classical synthetic methods. But, as larger structures are targeted, the synthesis of the templates themselves becomes challenging. It is now shown that 'molecular Verniers' can solve this problem: using a template with six binding sites and molecular building blocks with four porphyrins acting as binding sites, a 12-porphyrin nano-ring with a diameter of 4.7 nm is created. The ease and efficiency of this synthesis establishes Vernier templating as a powerful new strategy for producing large monodisperse macromolecules.

Risk variants for ALS and FTD in the synaptic gene UNC13A increase the expression of an UNC13A cryptic exon in neurons with TDP-43 depletion.

Small molecules are identified that inhibit the ubiquitin-specific protease USP7 with high affinity and specificity as explained by co-crystal structures, and are shown to reduce tumour growth in mice.

Coiled-coil assemblies have served as a rich resource for testing fundamental principles of protein structure and function. A semi-empirical design strategy now yields the first parallel hexamer, which also displays an internal channel that can be manipulated to direct assembly.

Single-cell RNA-seq analysis of iPSC neural differentiation identifies markers that predict line-to-line differences in cell fate potential and eQTLs that are specific to different stages of differentiation and that overlap with GWAS risk variants for neurological traits.

The ubiquitin E3 ligase UBR4 is a key component of the ubiquitin N-degron pathway, but the domain that catalyzes ubiquitin transfer remains unknown. Here the authors identify its unorthodox E3 module and characterize its structure and ubiquitin transfer mechanism.

Gram-negative bacteria assemble biofilms from amyloid fibres, which translocate across the outer membrane as unfolded amyloid precursors through a secretion system. Here, the authors characterise the structural details of the amyloid transporter FapF in Pseudomonas.

A protocol in which monomers are pre-organized using a reversible and removable urea linkage enables the production of covalent organic frameworks with higher crystallinity and porosity than those produced using standard approaches with randomly aligned monomers.

Previous studies suggested a role for CARD9 pathway in atherosclerosis but the underlying mechanisms remain poorly understood. Here, the authors show that the pro-atherogenic effects of Card9 deficiency are mediated by CD36-dependent defective autophagy that can be reversed by rapamycin and metformin.

Large-area, high-quality AB-stacked bilayer and ABA-stacked trilayer graphene films have been achieved, with fine control of Ni content, on single-crystal Cu/Ni(111) alloy foils.

Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice.

The approximately 5-Gb tuatara (Sphenodon punctatus) genome assembly provides a resource for analysing amniote evolution, and highlights the imperative for meaningful cultural engagement with Indigenous communities in genome-sequencing endeavours.

Lymphocytes encounter fluctuations in nutrient availability at sites of infection and inflammation. Wang et al. report that inosine can fulfil the metabolic needs of glucose-restricted anti-tumour effector CD8⁺ T cells.

Atomic point defects formed by irradiation can dramatically alter material properties, but are difficult to probe, limiting understanding of their impact. Here, the authors introduce an x-ray microscopy approach, based on Bragg ptychography, to visualise the distortion caused by these otherwise invisible defects.

Crystal structures of a chimeric GABA_A receptor define new allosteric binding sites for inhibitory and potentiating neurosteroids within the α subunit transmembrane domain.