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Polygenic Priority Score (PoPS) prioritizes candidate effector genes at complex trait loci by integrating genome-wide association summary statistics with other data types. Combining PoPS with methods that leverage local genetic signals further improves the performance.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Electrons can be accelerated by astrophysical shocks if they are sufficiently fast to start with. As laboratory laser-produced shock experiments reveal, this can be achieved by lower-hybrid waves generated by a shock-reflected ion instability.

An infrared laser is used to activate gene expression from a heat shock promoter in single cells in Caenorhabditis elegans, and is shown to be more effective and less detrimental to cells than a visible laser used for this purpose.

During alveologenesis myofibroblasts contractions at terminal sacs produce alveoli in the lungs. Here they show that endothelial cells promote myofibroblast-driven alveologenesis by forming basement membranes via Rap1-induced integrin β1 activation.

IXPE has revealed how the spin of the accreting neutron star Hercules X-1 changes in three dimensions. The spin axis of the star moves both through the star and across the sky, hinting that the crust of the star is asymmetric by almost one part in a million.

Using a participatory cognitive paradigm based on gaze contingency, Kanakogi et al. show that eight-month-olds increased their selective gaze to antisocial others to punish them, suggesting that preverbal infants engage in third-party punishment.

Centromeres are defined by the histone variant CENP-A. Using single-molecule fluorescence and cryoEM, this study shows that CENP-A and the centromeric protein CENP-B collaborate to create dynamic and open chromatin, aiding centromeric factor binding.

Semaphorin 3A (Sema3A) is shown to function as a protector of bone, by synchronously inhibiting osteoclastic bone resorption and promoting osteoblastic bone formation.

DNA damage response (DDR) is activated in cardiomyocytes of the failing heart, but the type of DNA damage leading to DDR is unclear. Higoet al. show that in mice heart failure is caused in part by unrepaired DNA single-strand breaks in cardiomyocytes, which activate persistent DDR and trigger an NF-κB-dependent cardiac inflammation.

Binary toxin translocation system consists of an enzymatic subunit and translocation pore. Here, the authors report the high-resolution cryo-EM structure of Clostridioides difficile binary toxin, comprising ADP-ribosyltransferase CDTa bound to the CDTb pore and revealing translocational unfolding of CDTa in the CDTb-pore.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

Fast ignition is an interesting scheme for nuclear fusion reaction. Here the authors show electron generation using intense short laser pulses and energy transport by coupling the laser energy to the imploded plasma core as in the ICF conditions.

The transcription factor Pitx2 induces a dynamic morphological change in the outflow tract of the heart, which results in asymmetric blood supply to the branchial arch artery system. The uneven blood distribution results in differential signalling responses that cause the asymmetric remodelling of the great arteries

The rotary ATPases use a rotary catalytic mechanism to drive transmembrane proton movement powered by ATP hydrolysis. Here, the authors report a collection of V/A-ATPase V₁ domain structures, providing insights into rotary mechanism of the enzyme and potentially other rotary motor proteins driven by ATP hydrolysis.

Achieving unit-by-unit isomerization within a molecular array poses a significant challenge in chemistry. Here, the authors demonstrate tip-induced stereoisomerization of dehydroazulene and diradical units in three-dimensional organometallic compounds on Ag(111).

Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

Acquisition of dying tumor cell-associated antigens is an essential step for the initiation of anti-tumor immune response by conventional type 1 dendritic cells (cDC1). Here the authors show that the loss of TIM4 expression in lung tumor associated cDC1 is associated with less efficient uptake of cell associated antigens and reduction of CD8 + T cell activation in advanced lung tumors.

OqxB is an RND (Resistance-Nodulation-Division) transporter that contributes to the antibiotic resistance in Klebsiella pneumoniae. Here, the authors report structural and functional characterization of OqxB, with insights into its substrate binding pocket and the role in fluoroquinolone resistance.

The innate immune system and inflammation modulate bone homeostasis through complex regulation of bone remodelling cells including osteoblasts and osteoclasts. Here, the authors show that the type I interferon pathway and guanylate binding proteins functionally limit bone loss by inhibiting osteoclast functions.

A study reports the measurement of the polarization degree and angle of X-rays from Sagittarius A^* reflected off a nearby cloud, indicating an X-ray flare about 200 years ago.

Via structural and mutational-functional analyses, the BEC toxin from C. perfringens is shown to use a unique serine-lined pore structure critical for toxicity, distinguishing it from other binary toxins that rely on conserved phenylalanine residues.

Kawaguchi et al. show that mice deficient in lipocalin-type prostaglandin (PG) D synthase (L-PGDS) exhibit impaired light-induced phase advance, but normal phase delay and nonvisual light responses. This study suggests the role of L-PGDS for the light-induced phase advance possibly via a chemoattractant receptor DP2/CRTH2.

Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging.

Many causative genes are known for epileptic or developmental and epileptic encephalopathies (EE/DEE) yet a genetic diagnosis cannot be made for many patients. Here, the authors analyse whole exome sequencing data from a Japanese case−control cohort to identify common, rare and ultra-rare coding variants associated with EE/DEE.

Understanding vertical manipulation mechanisms in atomic-force microscopy applications is a serious challenge. Here, the authors report vertical extraction and deposition processes of copper atoms at an oxidized copper surface, and rationalize the processes with a multi-step manipulation mechanism.

Experimental autoimmune encephalomyelitis (EAE) involves inflammatory cell infiltration into the central nervous system (CNS) and models the human disease multiple sclerosis. Here the authors show that transferred CD4+ gut intraepithelial lymphocytes can migrate into the CNS and inhibit inflammation in recipient mice with EAE.