Search

In the past three decades, fish abundance, richness and uniqueness have diverged across cold and warm streams, and the effects on native fish communities of stream warming and increases in introduced fishes have magnified each other.

Alveolar rhabdomyosarcoma is a clinically challenging disease due to the lack of druggable targets. Here the authors show preclinical evidence for ATR inhibitors as a therapeutic option for alveolar rhabdomyosarcoma.

Alfajaro et al identify that a bat MERS-like coronavirus HKU5 uses ACE2 as a receptor from its natural bat reservoir Pipistrellus abramus and American mink. Structural analyses demonstrate a unique interaction between the HKU5 receptor binding domain and bat ACE2. This highlights the receptor flexibility of merbecoviruses and identifies mink as potential intermediate hosts, informing viral surveillance and countermeasure development.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

This work shows that receptor use in merbecovirus is clade-specific by clustering them into clades based on the receptor-binding domain (RBD) of their spike proteins. While MERS-CoV and its close relatives use the DPP4 receptor, several other clades—including all HKU5 bat coronaviruses—rely on ACE2, the same receptor used by SARS-CoV and SARS-CoV-2.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

The EMDataResource Ligand Model Challenge aimed at assessing the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryo-EM maps determined at near-atomic resolution. This analysis presents the results and recommends best practices for assessing cryo-EM structures of liganded macromolecules.

Rhabdomyosarcoma is a paediatric tumour of the muscle. Here, the authors utilise single cell RNA-sequencing datasets to describe muscle-lineage and tumour-acquired cell states within rhabdomyosarcoma and identify cell states enriched during treatment.

Nanoparticle catalysts can be highly active, but are susceptible to deactivation due to sintering under operational conditions. The Pt and Pd–Pt catalysts synthesized here are stable under demanding reaction conditions with temperatures as high as 1,100 °C.

The authors test whether spatial scale (plot, local and landscape) affects the supply of various ecosystem services in grasslands, finding that some services are predicted by plot-level properties while others depend more on landscape-level management.

Authors carry out an immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples, finding that early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion.

Small CRISPR Cas9 proteins have potential in gene therapies but generally have poor editing efficiency or specificity and often recognize sub-optimal PAM sequences. Here the authors characterise four small nucleases and use protein engineering to create effective in vivo editors.

An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

The unusual crosslinks between cysteine residues and the peptide backbone in the antibiotic peptide subtilosin A are formed by a new member of the radical SAM enzyme superfamily that contains two functionally linked [4Fe-4S] clusters.

Visualizing the structural dynamics of isolated molecules would help to understand chemical reactions, but this is difficult for complex structures. Intense femtosecond X-ray pulses allow the full imaging of exploding photoionized molecules, in this case, with eleven atoms.

Dimetallocenes are a narrow class of compounds represented by the homobimetallic examples dizincocene and diberyllocene. Now a heterobimetallic dimetallocene featuring lithium and aluminium centres has been synthesized. The Al–Li bond is shown to cleave upon reaction with N-heterocyclic carbenes and heteroallenes.

Land use intensification is a major driver of biodiversity change. Here the authors measure diversity across multiple trophic levels in agricultural grassland landscapes of varying management, finding decoupled responses of above- and belowground taxa to local factors and a strong impact of landscape-level land use.

The cellular differentiation states of paediatric rhabdomyosarcoma (RMS) remain to be explored. Here, single-cell RNA sequencing analysis of RMS tumours reveals an immunosuppressive microenvironment and distinct transcriptional programs predictive of patient outcomes.

A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.

Triacylglycerides help to secure the impermeability of mycobacterial cell envelope to some drugs. Here, authors solve the structure of the triacylglyceride transporter Rv1410 and proposed a molecular mechanism for triacylglyceride extraction.

Human and bat coronaviruses replicate efficiently in immunodeficient mice implanted with human lung tissue, and treatment or prophylaxis using EIDD-2801 in this model suggests that this oral antiviral agent may be effective in preventing COVID-19.

Jean-Pierre Bourquin, Martin Stanulla and colleagues report whole genome, whole exome and transcriptome sequencing of TCF3-HLF fusion–positive acute lymphoblastic leukemia. Drug response profiling in patient-derived xenografts identified sensitivity to the BCL2-specific inhibitor ABT-199 (venetoclax) as a new option for treating this fatal disease.

De Solis and Del Río-Martín et al. investigate the reciprocal interplay between AgRP and POMC neurocircuits that governs the precise regulation of food intake and systemic metabolic homeostasis.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

The Kolbe electrolysis is a transformation renowned for forging C(sp³)–C(sp³) bonds. However, it is challenging to selectively make cross-products — that is, form new bonds from different partners — using this reaction. Now, a nickel-catalysed ‘reductive Kolbe’ reaction enables a decarboxylative cross-coupling approach.

BCL2-inhibitor venetoclax is used to treat relapsed/refractory chronic lymphocytic leukemia (CLL). Here, the authors show the clonal dynamics towards venetoclax resistance by performing whole-exome sequencing of 8 CLL patients undergoing venetoclax treatment.

Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.

Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat. Here, the authors demonstrate that real-time in vivodetection and imaging of these bacterial infections can be successfully performed with fluorescently labelled vancomycin.

Non-invasive monitoring of solid tumour growth in mice is difficult. In this study, the authors develop a system for monitoring the secretion of luciferase either from Gaussia princeps or Cypridina noctiluca in the blood of mice harbouring luciferase-labelled tumour cells, thus providing a system to monitor two different cell populations in vivo.

Using a haplotype-based approach, David-Alexandre Trégouët and colleagues report that the SLC22A3-LPAL2-LPA gene cluster is associated with risk of coronary artery disease.

Identification of venom insulins with A-chain elongations inspired hybrid analogs with similar activity to human insulin. Cryo-EM structure analysis revealed the basis of the hybrid peptide activity.

The authors use an integrative structural biology approach to elucidate molecular features of the RAS Q61 family of public tumor antigens. This information can be used to develop targeted therapeutics to combat a range of cancers.

Cryo-EM analysis with DEER spectroscopy and molecular dynamics simulations of the ABC exporter BmrCD reveal dual-mode substrate binding in an ATP- and substrate-bound state.

The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

Here the authors, by using data from three electrical companies in the USA, find that the recovery duration of an outage is connected with the downtime of its nearby outages and blackout intensity and present a cluster-based recovery framework.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

A hybrid incompatibility between Capsellaplant species is due to an interaction between two immune regulators. Here, the authors show that highly divergent haplotypes result from balancing selection in the ancestral lineage and their sorting into derived lineages facilitated the evolution of the incompatibility.

Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote T_FH cell differentiation and vaccine responses through the induction of a specific cytokine profile.