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Linking prior epigenetic status to future outcomes remains a challenge. Here, authors show recording neuronal enhancer activity across postnatal development in mice reveals loci that predict and can be manipulated to modify acute seizure response.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The authors selectively modify chromatin in a specific gene in vivo to examine the link between chromatin dynamics and drug- and stress-evoked responses. They report that histone methylation or acetylation at the FosB locus in nucleus accumbens is sufficient to control drug- and stress-evoked transcriptional and behavioral responses.

An apparent redundant role with EZH2 has rendered EZH1 as a secondary player in PRC2-mediated homeostasis regulation. Here, the authors report that gain- and loss-of-function variants in EZH1 cause neurodevelopmental disorders, highlighting its functional relevance.

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.

High-resolution manometry (HRM) has transformed our understanding of oesophageal motility disorders, in particular achalasia. In this Consensus Statement, the authors explore the effect HRM has had on the diagnosis and management of achalasia and related syndromes.

Morphogens such as chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

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.

Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.

Multiple sclerosis is characterized by the activation of microglia cells. Davalos et al. investigate the early stages of neuroinflammation in mice and reveal that the plasma protein fibrinogen induces microglial clustering around the brain vasculature, which facilitates lesion formation and focal axonal damage.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

Using meta-analysis of previous genome-wide association studies against the latest reference variant databases, this work identifies five new risk loci for glioblastoma and non-glioblastoma type of glioma.

APJ is shown to be a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin, a finding that is important for the development of APJ agonists to treat heart failure.

The fluvial response in western Colorado to the Palaeocene/Eocene thermal maximum involves a large increase in sediment flux that lasted much longer than the vegetation, monsoon and carbon dioxide changes of the thermal maximum.

Cancer-associated mutations in isocitrate dehydrogenase are proposed to impair TET2-dependent DNA demethylation. By comparing the methylomes of IDH-mutant cancers, the authors identify the transcription factor EBF1 as a partner of TET2, suggesting a possible means for targeting TET2 to specific DNA sequences.

The current bottleneck for DNA data storage systems is the cost and speed of synthesis. Here, the authors use inexpensive, massively parallel light-directed synthesis and correct for a high error rate with a pipeline of encoding and reconstruction algorithms.

Ubiquinone is an essential component of electron transfer chains found both in bacteria and in mitochondria; the bacterial enzyme UbiX involved in ubiquinone biosynthesis is a flavin prenyltransferase, and the flavin-derived cofactor synthesized by UbiX is used by the UbiD decarboxylase in the ubiquinone biosynthetic pathway.

We launched the ENIGMA-Neuroendocrinology working group with the aim to address knowledge gaps about the role of sex hormones in the brain, which lead to prevalent sex- and gender-based health disparities in biomedical research. We approach this by adopting a lifespan perspective to explore the interplay of hormonal dynamics and mental health in the brain.

In this Perspective, the authors present a framework, context and guidelines for accelerating the translation of machine-learning-based interventions in health care.

Post-therapy prostate-specific antigen (PSA) changes have been associated with improved survival in castrate metastatic patients, but currently no drug has been approved strictly on the basis of a post-treatment decline in PSA, as it is unproven that such PSA changes are surrogates for true clinical benefits. Fleming and coauthors address the critical question of whether PSA post-therapy decline reflects true clinical benefit, and if it should be used as an intermediate endpoint for accelerated approval. The authors emphasize the importance of recognizing that there are a range of clinical benefits to patients that can favorably improve the quality and possibly the duration of survival independent of PSA.

The authors here show that two completely different classes of spinal premotor interneurons drive motoneurons during slow and fast swimming of zebrafish larvae. As the fish accelerate, the 'slow' interneurons are progressively silenced, while the 'fast' interneurons take over, and vice versa.

Merlini, Rafalski et al. show that dynamic microglial brain surveillance prevents hyperexcitability and seizures by G_i-dependent microglia–neuron interactions in response to evoked neuronal activity to maintain physiological network synchronization.

All disciplines should follow the geosciences and demand best practice for publishing and sharing data, argue Shelley Stall and colleagues.

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.

Efficient siRNA delivery remains a key challenge to realizing the full potential of RNAi-based therapeutics. Semple et al. accomplish unprecedented potency for liposome-mediated siRNA delivery by applying rational design to refine an empirically identified cationic lipid widely regarded as the benchmark for use in lipid nanoparticles.