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In response to lactate exposure, Candida albicans induces masking of β-glucan, a key PAMP, via a signalling pathway involving the Gpr1 receptor and Crz1 transcription factor.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Using in vitro reconstitution experiments with purified components, the authors show that five interacting ciliary tip proteins collectively form cork-like structures at microtubule tips and make microtubule growth very slow and processive.

SMARCB1 is frequently lost in solid cancer and reported to support tumourigenesis through STAT3 activation. Here, the authors show in several preclinical models that targeting IL6/JAK/STAT3 molecular pathway is a potential therapeutic approach for SMARCB1-deficient bladder cancer.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Late diagnosis and ineffective treatment of fungal infections lead to high mortality. Here, Rudkin et al. generate anti-Candida human monoclonal antibodies with diagnostic and therapeutic potential, by expressing recombinant antibodies from genes cloned from B cells of patients suffering candidiasis.

How does the brain balance specialization and integration? Using high-resolution MRI and a post-mortem atlas, this study reveals how local and global cortical organization are linked, shaping functional diversity across brain areas.

Sequencing the genomes of two enteropneusts reveals complex genomic organization and developmental innovation in the ancestor of deuterostomes, a group of animals including echinoderms (starfish and their relatives) and chordates (which includes humans).

X-ray crystallography, cryo-electron microscopy, structural modelling, biochemistry, cell biology, and evolutionary analysis enable characterization of ORF2p, the reverse transcriptase of the ancient ‘parasitic’ LINE-1 retrotransposon that has written around one-third of the human genome.

Neurodevelopmental disorders normally arise from intrinsic brain abnormality. Here the authors show that a motor-learning deficit in 22q11 deletion syndrome may arise from improper development of the skull structure housing a part of the cerebellum.

What’s happening inside a crow’s brain when it thinks about using a tool? Here the authors show that it depends on experience. Naïve crows activate sensory and higher-order processing centers, but experienced crows instead use motor learning and tactile control circuits.

Evybactin is an antimicrobial natural product that targets DNA gyrase, where it binds to a site overlapping with synthetic thiophene poisons and exerts selectivity for Mycobacterium tuberculosis via its transport mechanism into the cell.

Trials evaluating novel therapies in the neoadjuvant setting must have clearly defined study elements and appropriately selected end points to ensure the applicability of the trial and enable interpretation of the study results. In this Perspectives, the authors describe the findings of a public workshop jointly sponsored by the US Food and Drug Administration and the Bladder Cancer Advocacy Network, which discussed key elements and end points when designing trials of neoadjuvant therapy for muscle-invasive bladder cancer.

It is currently unclear if cell-free DNA samples from metastatic cancers are as informative as tissue ones for cancer profiling. Here the authors show that cell-free DNA samples from rapid autopsies capture clonal and subclonal alterations of metastatic tumours and reveal more driver alterations than single tissue samples.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Epigenetic regulation is critical for controlling gene expression during the transition from embryo to seedling in plants. Here Gao et al. report that in Arabidopsis, the SCARECROW-LIKE15 protein physically interacts with a histone deacetylase to repress expression of embryonic traits in seedlings.

Analyses of microbial communities that live 10–750 m below the seafloor at Atlantis Bank, Indian Ocean, provide insights into how these microorganisms survive by coupling energy sources to organic and inorganic carbon resources.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Imbalanced proteostasis is associated with diverse diseases, including ischemia/reperfusion injury in the heart. Here the authors show that the ATF6 arm of the unfolded protein response can be pharmacologically activated with a small molecule in vivo, providing protection from ischemia/reperfusion injury in the heart, the brain, and the kidney.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Genetic cardiomyopathies are complex diseases with heterogeneous clinical presentations and phenotypes, and mild pathology can overlap with physiological variation, particularly in athletes. In this Review, three of the most common and controversial areas are discussed, including left ventricular hypertrophy; left ventricular dilatation, noncompaction, and fibrosis; and arrhythmias originating from the right ventricle.

Cardiovascular genomics has evolved substantially in the past 2 decades. Numerous papers published in 2015 demonstrate that new genomic approaches, often used synergistically, can yield noteworthy findings. A range of laboratory, analytical, and bioinformatic techniques to uncover genetic contributors to coronary artery disease, myocardial infarction, and dilated cardiomyopathy are described.

Ballabio and colleagues report that the transcription factor TFEB, which has a known role in autophagy, is induced by starvation and promotes transcription of PGC1α and PPARα. Intriguingly, targeted expression of TFEB in the liver blocks the development of metabolic syndrome in mouse models of obesity.

A single-cell study integrating data from lung tissues from patients with fatal COVID-19 from Malawi, the United States and Europe identifies shared and distinct immune and inflammatory mechanisms of response.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.