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Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Cerebral lesions result in loss of upper-limb motor functions. Here, the authors show that electrical stimulation of the motor thalamus can immediately and significantly improve strength and volitional force control improving arm and hand functions.

The Eμ-Myc lymphoma mouse model has been invaluable in the study of this disease. Here, the authors use multiple sequencing strategies to analyse the tumours in these mice and find recurrent inactivating mutations in Bcor, suggesting that this gene has a negative role in Mycsignalling.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Telomere shortening is a hallmark of several disorders and aging. Here, the authors uncover that RIOK2 maintains telomerase activity, thereby preventing telomere shortening. Thus, increasing RIOK2 levels may help rescue telomere biology disorders.

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Analysis of habitat data, quantitative trait locus mapping of seed size and selective sweeps show parallel selection acting on inversions in two independent dune ecotypes of the prairie sunflower, Helianthus petiolaris.

Fonzo et al. found that brain activity during a form of emotional regulation predicted how well individuals with depression would respond to a common antidepressant. Brain function assays may herald a new era of precision medicine in psychiatry.

Displacement of water molecules from proteins can lead to higher affinity or selectivity of ligands, but measuring individual water binding energies is challenging. Here calculated binding free energies are used to estimate the stability of conserved water in 35 bromodomains and to predict the ease of displacement.

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Tissue fibrosis is a major contributor to mortality in the developed world. Here, the authors identify a genetic variant in the intronic region of interferon-λ4 that is a strong predictor of hepatic inflammation and fibrosis, independent of liver disease aetiology

Zinc finger design is facilitated with a deep-learning model.

The efficacy of an antidepressant is predicted from an EEG signature.

Sick heart and vessels skew hematopoiesis toward inflammatory myeloid cells. Rhode et al. show that hypertension, atherosclerosis and myocardial infarction cause endothelial dysfunction in bone marrow (BM), which in return causes overproduction of inflammatory myeloid cells and systemic leukocytosis in mice. This process is mediated by VEGF signaling, IL-6 and versican production by the BM endothelium.

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. In the largest study to date, we report the results of DNA methylation profiling, RNA-Seq and genomic sequencing of 32 RIG tumors, and an in vitro drug screen in two RIG cell lines.

Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.

Manju Kurian and colleagues report heterozygous variants in KMT2B in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance. Their findings highlight a clinically recognizable form of dystonia and demonstrate a crucial role for KMT2B in the physiological control of voluntary movement.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Saturation genome editing characterizes von Hippel–Lindau (VHL) coding variants and their associations with diseases. Function scores for 2,268 VHL single-nucleotide variants (SNVs) classify pathogenic alleles driving renal cell carcinoma and suggest new mechanisms by which variants impact function.

Lee et al. demonstrate the protein Meteorin-like can rejuvenate the body’s immune system to enhance muscle regeneration in old age – in part by inducing the death of pro-fibrotic mesenchymal progenitor cells within the muscle.

An anti-inflammatory enzyme fused with a tissue-anchoring protein and injected into inflamed tissues ameliorates local inflammation without causing systemic immune suppression, as shown in multiple rodent models of inflammatory diseases.

HER2+ breast cancer patients can often develop resistance to trastuzumab and therefore potential combination therapies need to be explored. Here, the authors report the results of a multi-center randomized phase II clinical trial evaluating the pathological and molecular responses associated with trastuzumab and/or lapatinib in combination with chemotherapy in HER2+ breast cancer patients.

A secure framework that harmonizes storage and querying of clinical and genetic data using blockchain technology was developed to support combined genotype–phenotype queries, improving transparency into how and when health information is used.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

Circulating liver enzymes, like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are highly heritable and predictive of disease. Here, the authors perform a genome-wide association study on ALT and AST, revealing a rare variant in SLC30A10 associated with elevated ALT and AST.

Genome complexity is a distinguishing feature of advanced cancers in contrast to precancerous conditions. Here, by analysing chromosomal copy-number evolution in early cancers and precancerous lesions of the oesophagus, the authors reveal signatures of ongoing chromosomal instability and its role in promoting tumour progression.

Micronuclei, which are common features of nuclei in cancer cells, can generate heritable sources of transcriptional suppression, a finding that establishes an inherent relationship between chromosomal instability and variation in chromatin state and gene expression.

Compact exoplanetary systems frequently experience spin–orbit coupling driven by secular resonances, which can shape their architecture, allowing the planet to maintain a large obliquity and inducing the piling up of planets just wide of the first-order resonance.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Risk variants for ALS and FTD in the synaptic gene UNC13A increase the expression of an UNC13A cryptic exon in neurons with TDP-43 depletion.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.