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Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

A large-scale migraine genetics study identifies 122 risk regions, including 35 previously unreported ones, and pinpoints likely causal genetic variants using an in silico fine-mapping method.

Meral Gunay-Aygun and colleagues report that NBEAL2 is mutated in gray platelet syndrome (GPS). GPS is a recessive platelet disorder that can lead to severe bleeding.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Neurons within high-grade human gliomas were more electronically active than those within low-grade ones, and glioma cells in high-grade glioma had smaller but longer-lasting synaptic responses. Heightened neuron–glioma activity was associated with faster proliferation.

This study reveals that excitatory–inhibitory imbalance in Alzheimer’s disease is diverse including both impaired long-range synaptic integration and altered local excitability, with distinct links to β-amyloid and tau pathology.

This review discusses human neuroimaging as well as cellular studies to describe how learning sculpts the brain.

The authors show that a bacterial histone, HLp from Leptospira perolatii, forms tetramers that wrap and compact DNA, revealing an unexpected mechanism by which bacteria organize their genetic material.

Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

The capacity of brain networks to retain information during aging is crucial but not yet known. This study shows that the brain’s memory capacity, modelled with reservoir computing, offers new insights into aging, brain function and cognitive decline.

Although previous work has shown that extensive training in the complex visuo-motor skills involved in juggling results in adult gray-matter changes, it is unclear whether such practice can produce similar changes in adult white matter. This paper now uses diffusion tensor imaging to demonstrate structural white-matter changes when adults practice juggling.

Cross-sectional and longitudinal PET imaging of amyloid beta and tau in the human brain is combined with gene expression profiles to define the interactions between Alzheimer’s disease-related pathology propagation and brain-region-specific vulnerability.

There is growing need for ways to slow or prevent Alzheimer’s disease (AD). Here, the authors demonstrate that a low protein diet can protect against metabolic dysfunction, slow AD progression, and preserve cognitive function in a mouse model of AD.

The role of olfactory pathways in the development of neurodegeneration in Alzheimer’s disease is not well understood. Here, the authors show odor identification deficits are predictive of tau accumulation and progression in olfactory pathways, and that tau spreads from medial temporal lobe structures towards the olfactory system.

Older individuals exhibiting diminished function of the locus coeruleus while learning new information show faster cognitive decline that is typical for Alzheimer’s disease.

This study shows that C9orf72 mutations impair immune activation in ALS, affecting how brain cells communicate, and highlights key differences in the cellular and molecular pathways underlying sporadic and genetic forms of the disease.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

Structural insights into SARS and MERS coronavirus membrane protein reveals differences and conserved sites of an inhibitor binding pocket, aiding in the design of broad-spectrum and specific antivirals.

It is unclear whether climate driven phenological shifts of tundra plants are consistent across the plant growing season. Here the authors analyse data from a network of field warming experiments in Arctic and alpine tundra, finding that warming differentially affects the timing and duration of reproductive and vegetative phenology.

Defective neoangiogenesis and blood–brain barrier leakiness are pathological hallmarks of neuroinflammation. Here the authors show that vascular endothelial growth factor A (VEGF-A) promotes venous endothelial cell proliferation, resulting in the formation of leaky vessels around demyelinating lesions in multiple sclerosis and experimental autoimmune encephalomyelitis.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

How and to what extent oligodendrocytes (OLs) contribute to learning and cognition is not well understood. Here, the authors show that the performance of mice in working memory-dependent cognitive tasks depends on OL genesis and is proportional to the number of OL precursors and OLs generated during training.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

The Cdc48 enzyme is an abundant and essential enzyme that functions in many cellular pathways as a protein unfoldase. Here, the authors determine an ensemble of Cdc48 structures that capture snapshots of its unfolding action using a ‘hand-over-hand’ mechanism.

Wetland vegetation is typically considered only in terms of enhancing sediment accretion and positively impacting land-building. Here, the authors show that the degree of enhancement has a strong dependence on vegetation density through the influence on sediment supply and retention.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Developmental and epileptic encephalopathies are devastating neurological disorders. Here, the authors establish a cohort of patients with variants in the gene DENND5A and use human stem cells to discover a disease mechanism involving altered cell division.

Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.

The blooming alga Emiliania huxleyi and its viruses are a model for density-dependent virulent dynamics. However, Knowles et al. show that this host–virus system exhibits temperate dynamics at natural host densities, in a manner dependent on host physiology.

There are currently no drugs available to treat SARS-CoV-2 infection. A promising alternative treatment for COVID-19 patients is convalescent plasma. Here, Gharbharan et al. collect covalescent plasma and report no overall clinical benefit for 86 patients hospitalized for COVID-19 and treated with 300 mL convalescent plasma.

Identification of specificity from antibody sequence is challenging especially when different clonotype lineages recognise antigens similarly in a process of convergence. Here using TREM2 reactive antibodies in rats as an example the authors characterise convergent antibodies and identify similarities in recognition between different lineages.

Scientists who specialize in uncommon diseases can find a research focus with a purpose.

Using longitudinal multimodal imaging data collected in healthy older individuals, Jacobs et al. provide in vivo evidence in humans that amyloid deposition facilitates tau spread along connected pathways and memory decline.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Using brain organoids models, Prigione and colleagues uncovered the impact of Huntington’s disease on human brain developmental and identified early dysregulation of CHCHD2, which disrupted mitochondria and might serve as a therapeutic target.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

In vivo human neuroimaging shows that locus coeruleus (LC) integrity changes precede medial temporal tau accumulation, and jointly predict future lower cognition in older people at risk for Alzheimer’s disease. A common transcriptomic profile underlies LC’s early vulnerability to tau.

The limited preservation duration of donor organs is a big problem. Here the authors report a method for the freezing of whole rat livers at temperatures between −10 °C to −15 °C for up to 5 days, based on freeze-tolerant wood frogs, and term this partial freezing.

In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes.

Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.

Due to the limited wavelength coverage of measurements to date, some aspects of the composition of Pluto’s largest moon, Charon, remain unresolved. Here, the authors detect carbon dioxide and hydrogen peroxide on the surface of Charon’s northern hemisphere using JWST data.

Hyper-activated STAT5B and its disease-causing variants are of interest as cancer drug targets. Here the authors combine cell based studies, X-ray crystallography, biophysical experiments and MD simulations to structurally and functionally characterize the STAT5B^N642H mutant found in aggressive T-cell leukemia and lymphomas and find that it has an increased affinity for self-dimerization.