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A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

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.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Reduced BMP receptor II signalling underlies pulmonary arterial hypertension (PAH). Here, Hurstet al. show that TNFα subverts BMP signalling by increasing BMP6 expression and signalling via an alternative BMP receptor, ALK2, in pulmonary artery smooth muscle cells to drive abnormal proliferation and PAH.

Pulmonary arterial hypertension is a complex disease characterised by high morbidity and mortality. Here, the authors report methylation profiling of patients, finding disease associations in genes CTSZ, COG6 and ZNF678.

Pulmonary arterial hypertension (PAH) is a rare lung disorder characterised by narrowing and obliteration of small pulmonary arteries ultimately leading to right heart failure. Here, the authors sequence whole genomes of over 1000 PAH patients and identify likely causal variants in GDF2, ATP13A3, AQP1 and SOX17.

BMP9 activates signaling through the BMPR-II receptor in endothelial cells and reverses established disease in three animal models of pulmonary hypertension, thus pointing to a potential new treatment for this disease.

Prabhakar et al. demonstrate in rats with mitomycin C-caused pulmonary veno-occlusive disease activation of protein kinase R (PKR) and the integrated stress response (ISR), leading to the depletion of VE-cadherin and RAD51 from endothelial junctions, endothelial barrier disruption and vascular remodeling. Inhibiting the PKR–ISR axis protects against mitomycin C-induced endothelial damage.

Mutations in BMPR2 is the major genetic cause for pulmonary arterial hypertension (PAH). Here by solving crystal structures of BMPRII in binary and ternary receptor complexes with BMP10, the authors report the molecular recognition between BMPRII and BMP10, and its implication in PAH.

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.

Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production.

The 33 minute change in the orbital period of Dimorphos after the DART kinetic impact suggests that ejecta contributed a substantial amount of momentum to the asteroid compared with the DART spacecraft alone.

A genetic atlas of the human plasma proteome, comprising 1,927 genetic associations with 1,478 proteins, identifies causes of disease and potential drug targets.

The molecular basis of activin receptor-like kinase 1 (ALK1)-mediated endothelial bone morphogenetic protein (BMP) signalling is not fully understood. Here, the authors present crystal structures of the BMP10:ALK1 and prodomain-bound BMP9:ALK1 complexes, providing mechanistic insights into ALK1 signalling specificity.

Colocalization of regulatory quantitative trait loci from the BLUEPRINT project with genetic association data aids fine-mapping of putative causal variants for 12 immune-mediated diseases.

Isolating the neural mechanisms of consciousness is complicated by task report and other irrelevant signals. Here, the authors removed report and eye movement confounds to uncover large scale cortical-subcortical networks specific for human visual consciousness.

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.

Pulmonary arterial hypertension (PAH) is characterised by progressive pulmonary vascular remodelling. Here, Arnold et al. develop a therapeutic antibody targeting osteoprotegerin and find it attenuates pulmonary vascular remodelling in multiple rodent models of PAH, alone or in combination with standard of care vasodilator therapy.

Bone morphogenetic proteins (BMPs) and their receptors are important for the development and modulation of cardiovascular structure and function. Morrell and colleagues discuss physiological roles and regulation of BMP signalling in cardiovascular health and disease, and based on this advancing knowledge, they suggest opportunities for therapeutic intervention for a range of cardiovascular diseases, such as atherosclerosis and pulmonary arterial hypertension.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Pulmonary arterial hypertension (PAH) is characterized by right ventricular hypertrophy and the absence of underlying cardiac or pulmonary disease. In this Review, Southgate and colleagues discuss the latest advances in the identification of genetic variants underlying PAH development and progression.

Novoyatleva et al investigate the role of receptor tyrosine kinase Axl in Pulmonary arterial hypertension (PAH), finding that the small molecule inhibitor R428 reduces human pulmonary arterial smooth muscle cells proliferation and migration, but causes toxicity in human pulmonary arterial endothelial cells. They further show that Axl enhances endothelial BMPR2 signaling, altogether providing insights into mechanisms of PAH.

Sanna Vattulainen-Collanus et al. report that mutations in the BMPR2 gene, which is associated with pulmonary arterial hypertension, result in a deficit of RAD51 and altered DNA repair and replication. They were able to rescue the RAD51-deficient phenotype by restoring BMPR2 activity in cell culture.