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Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Knowing whether a quantum phase transition is first- or second-order is crucial for understanding any associated exotic phenomena, but direct experimental evidence has been scarce. Here, Frandsen et al. report first-order magnetic quantum phase transitions in archetypal Mott systems, providing insight into the underlying quantum fluctuations.

Foldamers are synthetic oligomers that adopt folded conformations through non-covalent intramolecular interactions. Here, Cariniet al. describe a family of foldamers with a large number of anthracene units that are able to transport charge efficiently at the single-molecule level.

Here, the authors report a near-field study of hyperbolic phonon polaritons in linear antennas made of hexagonal boron nitride. Infrared nanospectroscopy and nanoimaging experiments reveal sharp Fabry-Perot resonances with large quality factors, exhibiting atypical modal behaviour.

Pump-probe spectroscopy is routinely used to interrogate ultrafast valence electronic and vibrational dynamics in complex systems. Here, the authors extend this technique to the X-ray regime using a sequence of femtosecond X-ray pulses to understand core-valence interactions in a solvated molecular complex.

Propagation-invariant wave packets confined in space and time can be useful for optical sensing, imaging, and nonlinear and quantum optics. Here the authors demonstrate control over the angular dispersion of optical wave packets in two-transverse dimensions to synthesize space-time wave packets localized in all dimensions.

TGFβ can function as both a tumour suppressor and tumour promoter under different cellular contexts. Here, the cleavage product of the TGFβ type I receptor is shown to be generated in a TGFβ-dependent manner, and can induce the expression of genes involved in tumour cell invasion.

Although factors regulating the assembly and disassembly of primary cilia have been identified, mechanisms controlling the steady-state length of the cilium remain poorly understood. Here, the authors show that Dido3 regulates cilium length by mediating the actin-dependent delivery of HDAC6 to the basal body.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Barley β-d-glucan glucohydrolase is a glycoside hydrolase family 3 (GH3) enzyme critical for growth and development. Here the authors carryout mutagenesis, structural analyses and multi-scale molecular dynamics to examine the binding and conformational behaviour of several β-d-glucosides during the substrate-product assisted catalysis that operates in GH3 hydrolases.

Copy number variations inferred from spatial transcriptomics data in benign and malignant tissue reveal clonal architecture at the organ-wide level.

Nik-Zainal and colleagues leverage CRISPR–Cas9 and whole-genome sequencing to examine mutational patterns following knockout of 42 human DNA repair genes. They further develop and validate a clinically relevant tool to detect mismatch repair-deficient tumors.

Acute kidney injury can progress to chronic kidney disease. Here Dehnadiet al. develop a post-ischaemic chronic kidney disease model in cynomolgus monkeys and show that prophylactic inhibition of CD11b/CD18 leukocyte receptor via a monoclonal antibody inhibits progression of kidney disease and fibrosis.

Artificial metalloenzymes (ArMs) combine the reaction scope of chemocatalysts with the selectivity of enzymes. This Review discusses the prospects and recent progress in utilizing ArMs in whole cells for applications in diverse areas such as drug therapy and integration with biosynthetic pathways.

In mouse models of pancreatic cancer, a cooperative interaction between tissue damage and Kras gene mutation rapidly induces cancer-associated chromatin states in pre-malignant tissue, leading to gene dysregulation and neoplastic transformation.

Distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, calibrating the ability of the immune system to respond to physical threats.

Barriga et al. develop MACHETE, a genome engineering strategy enabling the flexible modeling of megabase-sized deletions and show that the concomitant loss of the interferon cluster with CDKN2A/B deletions on 9p21.3 enhances immune evasion.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

The pilus type 1 of uropathogenic E. coli must resist mechanical forces to remain attached to the epithelium. Here the authors use single-molecule force spectroscopy to demonstrate a hierarchy of mechanical stability among the pilus domains and show that the oxidoreductase DsbA also acts as a folding chaperone on the domains.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Single-cell and spatial transcriptomic analysis of eight human heart tissues reveals the cellular profiles and tissue architecture of niches including the cardiac conduction system, and a new tool, drug2cell, identifies drug target expression.

Lamin A/C gene mutations cause dilated cardiomyopathy associated with cofilin-1 phosphorylation and actin destabilization. Here, the authors show that phosphorylated cofilin-1 blunts the MRTF-A/SRF axis, leading to decreased tubulin acetylation and altered cardiac structure and function.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

The translation of mechanical cues into gene expression changes is dependent on the nuclear import of mechanoresponsive transcriptional regulators. Here the authors identify that Importin-7 drives the nuclear import of one such regulator YAP while YAP then controls Importin-7 response to mechanical cues and restricts Importin-7 binding to other cargoes.

Tau aggregates are associated with several neurodegenerative disorders. In this work, I. Saha and colleagues show that valosin-containing protein (VCP) recruited to Tau fibrils disaggregates them. However, this process comes at a cost: it generates seeding-active Tau species as byproduct.

This study shows through a field experiment that tropical intertidal communities switch from a niche- to a dispersal-assembled regime as immigration rates rise.

Multimodal DNA methylation and transcriptome profiling of single glioma cells links tumor cell transcriptional states to epigenetics via interaction with PRC2 and shows that these states are heritable and important for tumor plasticity.

Optical anisotropy in a broad spectral range is pivotal to efficient light manipulation. Here, the authors measure a birefringence of 1.5 in the infrared range and 3 in the visible light for MoS₂.

Photonic crystals can steer, shape, and sculpture the flow of photons. Here, the author fabricate a deep-subwavelength photonic crystal slab that supports ultra-confined phonon polaritons, by patterning a nanoscale hole array in h-BN.

Cyanide-bridged CoFe coordination networks exhibit photomagnetism because of coupled charge-transfer and spin transition. Now, femtosecond X-ray and optical absorption spectroscopies have enabled the electronic and structural dynamics of this light-induced process to be disentangled and show that it is the spin transition on the cobalt atom, occurring within ~50 fs, that induces the Fe-to-Co charge-transfer within ~200 fs.

Pharmacophore-directed retrosynthesis targets a potential pharmacophore from early on in a natural product synthesis and incremental increases in the complexity of this minimal structure enable a SAR profile to develop over the course of the campaign. The method is applied to gracilin A, finding simplified derivatives displaying potent immunosuppressive effects or selective neuroprotective effects in cell-based assays.

Insulin receptor protein is present in pancreatic β-cells, but the consequences of β-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.

Graphene plasmons hold potential for infrared optoelectronic devices, but the interaction with the substrate often degrades their quality. Here, the authors report the characterization of plasmons in suspended graphene with tunable suspension height, showing enhanced quality factors and propagation lengths at room temperature.

Melanoma is the leading cause of death by skin cancer in industrialized countries. Identification of tumor markers may help to define molecular pathways involved in melanoma development and progression, and identify patients with early-stage melanoma who would benefit from additional therapies. Larson et al. overview the melanoma biomarkers that are most helpful for predicting patient outcomes, and discuss the biomarkers that have demonstrated prognostic significance independent of primary tumor thickness and other common clinical prognostic indicators.

Refraction between anisotropic media is still an unexplored phenomenon. Here, the authors investigate the propagation of hyperbolic phonon polaritons traversing α-MoO3 nanoprisms, showing a bending-free refraction effect and sub-diffractional focusing with foci size as small as 1/50 of the light wavelength in free space.

Solvent plays a critical role in electron-transfer reactions, but short-range solvation dynamics are challenging to observe. Now, femtosecond X-ray solution scattering has been used to directly monitor the reorganization of water upon ultrafast intramolecular electron transfer in a bimetallic complex. Coherent motions of the first-shell water molecules are observed, arising from changes in solute–solvent hydrogen bonding.

Observations and modelling of two plumes in Jupiter's atmosphere that erupted at the same latitude as the strongest jet (23° North) are reported. Based on dynamical modelling it is concluded that the data are consistent only with a wind that extends well below the level where solar radiation is deposited.

Of the more than 400 known exoplanets, about 70 transit their central star, most in small orbits (with periods of around 1 day, for instance). Here, observations are reported of the transit of CoRoT-9b, which orbits with a period of 95.274 days, on a low eccentricity, around a solar-like star. Its relatively large periastron distance yields a 'temperate' photospheric temperature estimated to be between 250 and 430 K, and its interior composition is inferred to be consistent with those of Jupiter and Saturn.

Enterococcus faecalis is a commensal microorganism of animals, insects and humans, but also a nosocomial pathogen. Here, the authors analyse genomic sequences from E. faecalis isolates from animals and humans, and find that the last common ancestors of multiple hospital-associated lineages date to the pre-antibiotic era.

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage disease typically with childhood onset of neurodegenerative symptoms. Here the authors report that in a mouse model of CLN7 disease neuronal reactive oxygen species and the activity of glycolytic enzyme PFKFB3 are increased, while PFKFB3 inhibition ameliorates hallmarks of pathology.

Elemento, Melnick and colleagues examine the chromatin and transcriptional changes that occur during differentiation of human primary B cells into antibody-secreting cells. In naive B cells, the transcription factor OCT2 is preloaded at high-affinity super-enhancer sites present in repressed ‘silent’ chromatin; upon activation, OCAB is recruited to these regions, where it facilitates arrays of OCT2 binding to lower-affinity octamer motifs, leading to active formation of germinal center B cell-specific super-enhancers.