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Exposure to a novel experience can ‘reset’ connections between the hippocampus and prefrontal cortex in mice, allowing them to overcome an existing learned behaviour and to replace it with a new one.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

VIP interneurons have been shown to disinhibit pyramidal neurons by inhibiting other interneuron types. Here, the authors report that ChAT-VIP subtype of interneurons directly excite pyramidal neurons in multiple layers via fast cholinergic neurotransmission.

Li-Fraumeni syndrome leads to an increased predisposition to tumour development. Here, the authors develop a support vector machine model to predict early cancer risk in individuals using peripheral blood DNA methylation profiles.

Specific gut microbiota constituents that affect the severity of malaria are unknown. Here, Mandal et al. identify specific Bacteroides species causing susceptibility to severe malaria in mice and correlate with the severity of malaria in Ugandan children.

The native anaplastic lymphoma kinase (ALK) oncofetal protein is expressed in neuroblastoma and in multiple pediatric and adult solid tumors. Here, the authors show an ALK-directed antibody-drug conjugate with therapeutic efficacy in ALK-expressing preclinical models.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Here the authors use single-cell RNA-seq to profile the transmission stages of the human malaria parasite Plasmodium falciparum as it progresses through the Anopheles mosquito. They highlight unique patterns of gene usage throughout this development and identify potential pleiotropic genes that function at multiple life cycle stages.

Sonic Hedgehog medulloblastoma (Shh-MB) comprises four subtypes each with distinct clinical traits. Here the authors characterize the genome, transcriptome, and methylome of Shh-MB subtypes, revealing a complex fusion landscape and the molecular convergence of MYCN and cAMP signaling pathways.

Analysis of blood pressure data from the Million Veteran Program trans-ethnic cohort identifies common and rare variants, and genetically predicted gene expression across multiple tissues associated with systolic, diastolic and pulse pressure in over 775,000 individuals.

A screen utilizing an environmental DNA library in Escherichia coli is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

Leukemic stem cells (LSCs) drive chemoresistance and relapse in acute myeloid leukemia. Here, the authors show that the splicing factor RBM17 supports LSCs through avoiding nonsense-mediated decay of pro-leukaemic factors such as the translation initiation factor EIF4A2.

Melanocortin action is known to regulate body weight. Here the authors report that while inhibition of the hypothalamic melanocortin action leads to obesity in mice, chronic activation of melanocortin action is not sufficient to cause weight loss.

Enhancing the kinetics and selectivity of CO₂/CO electroreduction towards valuable multi-carbon products poses a scientific challenge and is imperative for practical applicability. Here the authors report that modifying copper catalysts with surface thiol ligands significantly improves acetate selectivity.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Using stereotactic electroencephalography, the authors identified differential amygdala activation in response to emotional faces in participants with treatment-resistant depression compared with non-depressed participants with epilepsy, suggesting possible deep brain stimulation targets.

Maintenance of NADPH levels during environmental stress can prolong cell survival. Ding et al. identify MESH1 as a cytosolic NADPH phosphatase that is required for the metabolic commitment to ferroptosis in cancer cell lines.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Mutations in the type I ryanodine receptor (RYR1), a calcium channel, leads to stimulus-induced pathological muscle contractions, including malignant hyperthermia. Currently there are no pharmacological agents to protect against this condition, but Susan Hamilton and her colleagues have now identified AICAR as one possible candidate compound. To date, AICAR has been thought to be an AMPK activator, but her group shows that in a mouse model of malignant hyperthermia it does not target this kinase, but rather RYR1, to prevent improper calcium leakage and pathology.

Dopamine release occurs in spatiotemporal waves. Here the authors propose that dopamine waves arise locally in the striatum, and provide evidence for striatal acetylcholine waves.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.

In this disease mapping study, the authors estimate disability-adjusted life year rates for three of the major causes of mortality for children under five 43 countries in sub-Saharan Africa. They identify significant heterogeneity at the subnational level, highlighting the need for a targeted intervention approach.

Two-photon imaging and in situ transcriptomic analysis of the primary visual cortex in mice show that a single transcriptomic axis correlates with the state modulation of cortical inhibitory neurons.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

The direct electrosynthesis of acetic acid from CO₂ typically has the drawback of CO₂ crossover. Now, a cascade approach for the electroreduction of CO₂ to CO, followed by CO to acetic acid, is reported in which off-target intermediates are destabilized, leading to an acetic acid Faradaic efficiency of 70%.

Horizontal gene transfer could stabilize cooperation in bacteria because plasmids could promote the transfer of genes encoding public goods. However, the authors use comparative analysis and theoretical modelling to show that, while horizontal gene transfer may help cooperative genes invade a population initially, they have less of a role in long-term maintenance of cooperation.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Partitioning of FtsN and the septal peptidoglycan synthesis complex between an active synthesis track and an inactive denuded glycan track coordinates opposing peptidoglycan synthesis and degradation activities in E. coli.

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.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

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.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

Cocchi and coauthors report that continuous theta burst stimulation of the frontal pole shows no difference from sham in reducing symptoms of obsessive-compulsive disorder or frontostriatal connectivity.

Activating the spared neurons downstream of rods and cones is a potential therapeutic approach for retinal degeneration, but has been limited by the characteristics of the opsins available. Here, the authors use medium wavelength cone opsin which has faster kinetics than others and show that it resolves some of these difficulties in a mouse model.