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Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

Bioenergetic capacity, the ability to maintain energy balance under stress, can be monitored using blood acylcarnitine profiles. Improving this capacity may slow Alzheimer’s disease progression.

Memory is a basic tenet of intelligent biological systems. Here the authors engineered a programmable and expandable iteration of recombinase-based synthetic memory (interception) that functions post-translation, resulting in faster recombination.

The eight-subunit augmin complex is required to nucleate branching microtubules and create a robust mitotic spindle during cell division. Here, the authors use cryo-EM, crosslinking mass spectrometry, and computational tools to build a structural model of the human augmin complex.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Three-terminal memtransistors can improve the neuromorphic performance of conventional two-terminal memristors. Here, the authors report the fabrication of high-yield large-scale crossbar array architectures incorporating up to 2,048 2D MoS₂ memtransistors per array, showing low-power memory and image recognition applications.

Biotic homogenization, which is increased similarity in the composition of species among communities, is rising due to human activities. Using North American mammal fossil records from the past 30,000 years, this study shows that this phenomenon is ancient, beginning between 12,000 and 10,000 years ago with the extinction of the mammal megafauna.

Hesitation—pausing in the face of uncertainty—is ubiquitous in daily life and disrupted in several psychiatric disorders. Unlike other forms of response inhibition, hesitation is mediated by indirect, but not direct, pathway striatal neurons.

Persisting symptoms after concussion (PSaC) present a complex neuropsychiatric challenge with limited treatment options due to inconsistent neuroimaging findings. Here the authors employ a multi-analytic approach to identify the salience network as a core dysfunction hub in PSaC, proposing specific cortical regions as potential targets for personalized neuromodulation therapies.

This study defined spatial gene expression in the human dorsolateral prefrontal cortex. It reveals layer-enriched expression of genes associated with schizophrenia and autism, highlighting the clinical relevance of spatially defined expression.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Laboratory simulation experiments with isomer selective photoionization detection techniques reveal that octasulfur (S₈) and sulfanes can be easily formed in low temperature H₂S interstellar ice analogues exposed to ionizing radiation, suggesting a critical link between sulfur chemistry on ice coated nanoparticles in molecular clouds and the inventory of sulfur compounds in our Solar System.

Efficient oxygen activation limits oxidative catalysis. Here, incorporating single-atom Zr into CeO₂-supported Pt catalysts creates Zr₁–O–Pt₁ structures, significantly enhancing catalytic performance via boosted surface and chemisorbed oxygen activation.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

Structural and morphological control of crystalline nanoparticles is crucial in heterogeneous catalysis. Applying DFT-assisted solid-state NMR spectroscopy, we determine the surface crystal and electronic structure of Ni₂P nanoparticles, unveiling NMR nanocrystallography as an emerging tool in facet-engineered nanocatalysts.

Here, the authors present cryoEMPEM, a method for high-resolution structural analysis of vaccine-elicited polyclonal antibody responses. They apply cryoEMPEM in combination with standard serology experiments to characterize the polyclonal antibody (pAb) responses elicited in rhesus macaques by HIV Env trimer immunogens and were able to determine up to 8 different polyclonal antibody structures in complex with their respective antigen from a single cryoEM dataset.

Van Hove singularities have the potential to drive unconventional magnetic states in Kagomes. Here, the authors provide experimental and theoretical results suggesting a van Hove singularity-assisted spin density wave in the Kagome metal CeTi₃Bi₄.

Mice flexibly shift attention between specific whiskers on a rapid timescale based on recent stimulus reward history in a detection task. Attention is correlated with a somatotopically precise enhancement of neural coding in somatosensory cortex.

Optical anapoles in nanoresonators result in strong suppression of the electromagnetic radiation, which is challenging to detect in ideal settings. Here, the authors show that fast electrons are a powerful tool to circumvent this challenge due to their ability to access dark modes.

Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.

Authors report MagNet, a plasma extracellular vesicle (EV) enrichment strategy using magnetic beads. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of mass spectrometry of unfractionated plasma.

The cryo-EM structure of immature Zika virus shows partially ordered capsid proteins and reveals differences between pre-epidemic and epidemic strains at protein interfaces within the trimeric spikes.

The supercontinent Rodinia has been hypothesised to have formed in a different manner from other supercontinents. Here, the authors report geochemical and mineralogical evidence for prevalence of non-arc magmatism and enhanced erosion of volcanic arcs and orogens during Rodinian assembly.

Cellular damage promotes sleep in C. elegans via Epidermal Growth Factor Receptors in sleep-promoting neurons, but the ligand was unknown. Here, the authors identify an EGFR ligand that is shed from damaged tissues by the protease ADM-4/ADAM17 to promote sleep.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Strategies to address the challenges associated with product manufacturing can improve chimeric antigen receptor (CAR) cell–based therapeutics. Here the authors report the results of two clinical trials in patients with B-cell malignancies, showing that place-of-care manufacturing has a low production failure rate with CD19-directed CAR-T cell products inducing high remission rates.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Mepolizumab (anti-IL-5 therapy) has been shown to reduce type 2 inflammation in asthma. Here the authors use bulk transcriptomics from nasal samples before and after mepolizumab treatment to assess the changes and associations with treatment outcomes.

Here, the authors report de novo design, optimization and characterization of tRNAs that decode UGA stop codons in E. coli. The structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon suggests that distinct A-site ligands (tRNAs versus release factors) induce distinct conformation of the stop codon within the mRNA in the decoding center.

Neutralizing antibodies (bNAbs) against HIV-1 are exclusively directed against the viral envelope protein (Env) and mainly target Env in a closed, prefusion state. Here, Yang et al. structurally characterize two heterologously-neutralizing CD4-binding site (CD4bs) antibodies isolated from sequentially immunized macaques, and show that these antibodies recognize the CD4bs on Env trimers in an „occluded-open‟ conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4.

White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Expansion microscopy, a technique for super-resolution imaging, is extended to clinical human tissue samples that are formalin fixed, paraffin embedded, stained and/or fresh frozen.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Tau pathology drives neuronal dysfunction in 4- repeat tauopathies. Here, the authors combine tau-PET, resting-state fMRI and histopathology data, to show that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.

In this study, Uldrich and colleagues describe the crystal structure of the Vγ9Vδ2 T cell antigen receptor (TCR) interacting with BTN2A1 and demonstrate the existence of a second ligand that co-binds to a distinct epitope on Vγ9Vδ2 TCR. Using these data, the authors suggest a model of Vγ9Vδ2 TCR activation in which BTN2A1 and BTN3A1 are tethered to each other at the steady state, and must disengage to allow TCR binding.

MUTYH removes A mis-incorporated opposite oxidized guanine to thwart mutations. Here, the authors present crystal structures and assess functional impacts and molecular dynamics of cancer-linked variants to illuminate how the [4Fe-4S] cofactor and active site are allosterically connected with significance for fidelity and clinical impact.

Experiments with human volunteers and macaques show that expectations produced by probabilistic cueing of future sensory inputs shape motor circuit dynamics in order to increase the efficiency of movement responses.

Sensor failures and limited resolution challenge many complex systems. Here, authors develop a multimodal AI method to generate super-resolution of a sensor using other available sensors in the system, revealing hidden dynamics in fusion plasmas and enabling cost-effective, high-resolution diagnostics.

The midbrain is a major site for gating vocalization in vertebrates. Here, the authors show midbrain periaqueductal gray neurons in teleost fish with properties like those in mammals, sculpt the acoustic features of context-specific vocal signals.

Bellaart et al. address how the ubiquitin ligase tripartite motif-containing protein 37, the gene for which is mutated in Mulibrey nanism, uses peptide motif recognition and substrate-directed oligomerization to prevent the formation of ectopic spindle poles that cause chromosome missegregation.