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Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Hodgkin’s lymphoma has a genetic component that is poorly understood. In this study, Frampton et al. perform a genome-wide association study in German patients and combine the results with a previously published UK genome-wide association study to identify susceptibility loci at 3p24.1 and 6q23.3.

Psoriasis is a partially heritable skin disorder, the genetic basis of which is not fully understood. Here, the authors use genome-wide association meta-analysis to discover psoriasis susceptibility loci and genes, which encode existing and potential new drug targets.

Andreas Janecke and colleagues identify mutations in MYO5B, encoding the type Vb myosin motor protein, in individuals with microvillus inclusion disease, implicating myosin Vb as a key regulator of epithelial cell polarity.

The nature of the ferryl intermediate generated in reactions catalysed by heme-containing enzymes is uncertain, due to the ambiguity of X-ray crystallography data. Here, the authors apply neutron diffraction, kinetics and other spectroscopy to directly observe a protonated ferryl intermediate in a heme peroxidase.

The interplay between dark and bright excitons has a significant impact on the optical properties of semiconducting transition metal dichalcogenides. Here, the authors perform computational and experimental studies which unveil the microscopic origin of the excitonic coherence lifetime in WS₂ and MoSe₂.

Thermometry using scanning probe techniques allows for the thermal imaging and characterization of devices with nanoscale resolution, however can be hindered by contact-related artefacts. Here, the authors demonstrate a thermal scanning probe approach which eliminates contact-resistance effects.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

Repeat expansions in the FGF14 gene can cause late-onset cerebellar ataxia (SCA27B), however the defining features of pathogenic expansions remain uncertain. Here, the authors compare the sequence and structure of FGF14 repeat expansions in patients and controls, leading them to suggest a lower pathogenic threshold and emphasizing the importance of sequencing the full expansion for accurate interpretation.

Building kinetic models from time-resolved data can be challenging due to the presence of unknown intermediate states. Here, the authors introduce a deep- learning-based framework that provides a kinetic reaction network and outperforms conventional fitting in determining time constants and amplitude parameters.

Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.

Optimizing COVID-19 vaccination strategies for patients under immunosuppressive medication is of high importance. In this clinical trial including non-seroconverted immunosuppressed patients, a homologous mRNA booster vaccination resulted in higher seroconversion rate than a switch to a vector-based vaccine.

The first experimental demonstration of saturable absorption in core-electron transitions in aluminium paves the way for investigating warm dense matter, which potentially has an important role in planetary science and the realization of inertial confinement fusion.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

This study identifies distinct eating behavior profiles and links them to eating disorder symptoms, genetic predispositions for high body mass index and brain maturation during adolescence.

Longitudinal analysis of neuroimaging data are useful for analysing heterogeneity in adolescent brain development. Here the authors cluster adolescent participants of the IMAGEN study into groups based on gray matter volume developmental patterns and investigate genome-wide and epigenome-wide associations with these groups.

Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGFβ instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Molecular photoswitches provide an extremely simple solution for solar energy conversion and storage. Here, the authors report on the assembly of an operational solar energy-storing organic-oxide hybrid interface, which consists of a tailor-made molecular photoswitch and an atomically-defined semiconducting oxide film.

Trypsin is a serine protease. Here the authors present the high resolution X-ray and neutron diffraction structures of uncomplexed and inhibitor bound trypsin that provide insights into the geometry of H-bonds in the active site of the enzyme and molecular dynamics simulations reveal the kinetics of ligand binding induced desolvation.

A study reporting the results of a clinical trial co-administering the GDF-15-blocking antibody visugromab with the anti-PD-1 antibody nivolumab demonstrates that neutralizing GDF-15 can overcome resistance to immune checkpoint inhibition in cancer.

Compositionally complex alloys have attracted significant attention recently, but the role of electronic correlations in these materials is unknown. Redka et al. study the CrMnFeCoNi alloy using a combination of experimental and theoretical techniques, revealing strong correlation effects far from the Fermi edge.

The neurobiology of human brain development and aging is hard to study in vivo. The authors report on distinct spatial associations between brain morphology and cellular as well as molecular brain properties throughout neurodevelopment and aging.

Viruses manipulate host cell pathways to support infection. Here the authors show that SARS-CoV-2 infection modulates cellular metabolism and limits autophagy, and identify druggable host pathways for virus inhibition.

In a birth cohort, Holz et al. found widespread structural brain changes at the age of 25 years as a function of adversity. This pattern was replicated at the age of 33 years and in another cohort. Individual-level volume reductions on top of this pattern predicted anxiety.

Roquin is an RNA-binding protein that prevents autoimmunity by limiting expression of receptors such as Ox40. Here, the authors identify an RNA structure that they describe as an alternative decay element, and they characterise its interaction with Roquin using structural and biochemical techniques.

Clonal expansion of helper T lymphocytes initially requires inactivation of the transcription factor Foxo1 by post-translational modifications. Mashreghi and colleagues now show in the late phase of clonal expansion, Foxo1 is inhibited post-transcriptionally by the microRNA miR-182.

The improper timing of transforming growth factor-β production is a hallmark of severe COVID-19 that may impede natural killer cell function and early control of infection.

Genome-wide analyses identify variants near HDAC9 associated with abdominal aortic calcification and other cardiovascular phenotypes. Functional work shows that HDAC9 promotes an osteogenic vascular smooth muscle cell phenotype, enhancing calcification and reducing contractility.

Susac syndrome is an inflammatory pathology of the brain endothelium. Here the authors show that the pathology is driven by CD8 T cells attacking the endothelium, and that blocking T cell-endothelial adhesion ameliorates the disease in a mouse model, and associates with improved clinical score in 4 patients.

The Origin Recognition Complex (ORC) plays conserved and diverse roles in eukaryotes. Here the authors present the structure of a chromatin interacting ___domain of yeast Orc1 in complex with the nucleosome core particle, revealing that Orc1 interacts with the histone H4 tail irrespective of K16 acetylation; a modification that regulates accessibility to chromatin.