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Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.

Despite their differences, the rarer sarcoma CIC::DUX4 sarcoma (CDS) is typically treated with therapies developed for Ewing Sarcoma (EwS) with limited success. Here, the authors develop a co-clinical drug response profiling platform to establish patient-derived CDS and EwS tumoroids, identifying MCL1 inhibition as a promising therapeutic approach in CDS.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The impact of neurodevelopmental mutations on functional brain connectivity is poorly understood. Here the authors identify thalamo-sensorimotor dysconnectivity dimensions shared across 16p11.2 and 22q11.2 copy number variants, autism and schizophrenia, but not ADHD.

A unique case from the Colombian cohort of autosomal dominant Alzheimer’s disease is reported in which disease progression is substantially delayed despite unusually high amyloid plaque pathology, possibly related to a rare mutation in APOE3.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Development of the classical lithium-ion technology based on liquid electrolytes has been limited to a certain extent by the intrinsic instability of liquid electrolytes and their mechanical properties. A multifunctional single-ion polymer electrolyte based on polyanionic block copolymers consisting of polystyrene segments is now shown to exhibit enhanced lithium-ion transport, mechanical properties and electrochemical stability window.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Improved biomarker-based tools for diagnosis and risk prediction of venous thromboembolism (VTE) are needed. Here, the authors show that Complement Factor H Related 5 protein, a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker in 5 independent cohorts.

Neisseria meningitidis is the causative agent of potentially fatal meningitis and septic shock, induced by bacterial colonization of blood vessels in the brain and the periphery. The endothelial cell receptor mediating meningococcal adhesion to blood vessels has previously been unknown. Here Sandrine Bourdoulous and colleagues report that CD147 expressed on human endothelial cells is a crucial mediator of N. meningitidis vascular colonization, providing new insight into some of the mechanisms that give rise to meningococcal disease.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Between around 5,000 to 2,000 years ago, a drying climate in the vast peatlands of the Congo Basin triggered peat decomposition and carbon release to the atmosphere, implying that this region may be vulnerable to future climate change.

Time-series observations from the JWST of the transiting exoplanet WASP-39b show gaseous water in the planet’s atmosphere and place an upper limit on the abundance of methane.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

In patient with glioblastoma, a major cause of resistance to chemotherapy and radiotherapy is the high degree to intratumoral heterogeneity and cell plasticity. Here, the authors demonstrate that chemoradiation induces the reprograming of glioblastoma cells into an invasive and vessel co-opting state, termed VC-Resist, capable of promoting resistance to therapy.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

DNA methylation is an epigenetic mark that plays a critical role in many biological processes. Here, we describe the development of SAM-DNMT3A a tool for induction of genome wide DNA methylation. Using SAM-DNMT3A we show that DNA methylation is a unique vulnerability in ER+ breast cancer.

Thymic epithelial tumors are associated with increased risk of immune checkpoint inhibitor (ICI)-induced myotoxicities, and the presence of anti-acetylcholine-receptor antibodies has the potential to serve as a biomarker for ICI-induced myocarditis in patients with cancer.

Agree what is needed, look for leaders with fire in their belly and emotional intelligence, and support them, advise Pierre-Alain Clavien and Joseph Deiss.

Nephrophthisis (NPH) is a common manifestation of ciliopathy diseases. Here the authors identify mutations in intraflagellar transport 54 (IFT54) in patients with NPH and discover an extra-ciliary role for IFT54 in regulating cytoplasmic microtubule dynamics, that contributes to the pathophysiology of this disease.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

The genomic sequences of 12 Drosophila species for conserved elements and describe the relationship between conservation and function for many specific sequence motifs.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

In this work, the authors study the immunological and virological effects of administering either wild-type anti-HIV-1 broadly neutralizing antibodies (bNAbs) or bNAbs with a mutation that increases binding to Fc-gamma receptors (FcγRs) to rhesus macaques in the acute phase of SHIV_AD8-EO infection.

Rocks and dust from the asteroid Bennu contain some of the molecular building blocks of life on Earth, such as amino acids and nucleobases. They also carry ammonia that formed billions of years ago in cold, distant regions of our Solar System.

Two studies published in Nature report the structure of apolipoprotein B100 on LDL using high-resolution, artificial intelligence-assisted cryo-electron microscopy and uncover its precise molecular interfaces with the LDL receptor. Dimers of LDL particles connected by a pair of receptors are also visualized for the first time. These studies provide key structural insights into the molecular defects linked to familial hypercholesterolaemia and open exciting avenues for translational research and drug development.

Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.

This study identifies an altered chromatin conformation associated to a cardiac disorder observed in 7 independent families. A deletion of 2 diverging CTCF binding sites on 4q25 induces TAD fusion and leads to PITX2 expression dysregulation.

Tumor-antigen-specific CD8⁺ T cells are generally thought to help fight against cancer, but here the authors identify a subpopulation of CD8⁺ T cells that are associated with a poor clinical outcome in melanoma. Although these cells can recognize tumor antigens, they suppress cancer immunity.

Genetically encoded voltage indicators need fast and large signals to allow widefield imaging of rapid neuronal activity. Here, the authors develop the indicator JEDI-1P and demonstrate pan-cortical voltage imaging and gamma-frequency tracking in awake mice in single trials.

The human pathogen Neisseria meningitidis colonizes blood vessels and causes vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, Manriquez et al. use a humanized mouse model to show that pathogen colonization of capillaries and arterioles creates an intravascular niche that precludes an effective action of neutrophils.