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CRISPR–Cas9 screens in cultures of young and old neural stem cells (NSCs) and in vivo in old mice identify gene knockouts that can boost old NSC activation and neurogenesis, with Slc2a4, which encodes the glucose transporter GLUT4, showing particular efficacy.

Efstathiou et al. describe an Argonaute-dependent endoplasmic reticulum (ER)-associated RNA silencing pathway that acts together with ER-associated protein degradation to preserve ER homeostasis and function.

A high-resolution electron cryo-microscopy structure of the zebrafish α1 glycine receptor bound to agonists or antagonists reveals the conformational changes that take place when the channel transitions from closed to open state.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

Neuromodulatory neural mechanisms behind contextual processing are not fully understood. Here, the authors show how spatiotemporal dynamics of locus coeruleus-norepinephrine release in dentate gyrus modulate contextual discrimination, opening new avenues for treatment of stress-related disorders.

In the 12-week, phase 2a DUET study, treatment with TERN-501, a thyroid hormone receptor β agonist, as monotherapy or in combination with TERN-101, a farnesoid X receptor agonist, resulted in dose-dependent reductions in liver fat content as compared to placebo in patients with presumed metabolic dysfunction-associated steatohepatitis.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Two new phosphorylation sites, p-tau₂₆₂ and p-tau₃₅₆, detect the formation of prefibrillar tau aggregates and may serve as early-stage biofluid-based biomarkers of tau neurofibrillary tangle pathology in Alzheimer’s disease.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Here, authors report that local ionic transport across cathode catalyst layers is vital in improving CO production from CO₂. This work demonstrates the potential of a CO₂ electrolyzer constructed from materials free from platinum group metals.

Actinide electronic structure determination is fundamentally challenging. Here, the authors assemble a family of uranium(V)-nitrides and quantify the electronic structure of the molecules, defining the relative importance of spin orbit coupling and crystal field interactions.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Smac mimetics sensitize cancer cells to the extrinsic cell death pathway and stimulate anti-tumour immunity. In this study, the authors show that Smac mimetics can synergize with immune checkpoint inhibitors to control tumour growth in mouse cancer models, including aggressive CNS tumours, in a cytotoxic CD8⁺T-cell- and TNFα-dependent manner.

Utilising proteomic and transposon sequencing screens, Freiberg et al. identified arginine metabolism enzymes that impact tolerance to antibiotics in Staphylococcus aureus, including in animal models of skin and bone infections.

Miao et al. show that loss of neuronal Vps13d in mice leads to mitochondrial dysfunction, GSDME-mediated mitochondrial DNA release, cGAS–STING inflammatory signaling and activation of microglia, culminating in neuronal loss.

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Both lithium- and sodium-ion batteries could play an important role in combating climate change, but they often suffer structural instabilities in the cathodes, which degrade performance. Now a study on two cathode materials that function in either battery type sheds light on how their structure should be designed to suppress these instabilities.

Battery researchers are struggling to design viable all-solid batteries, which promise enhanced safety but are currently achievable only at a high cost and with complex cell designs. Now a study on a sulfide-based cathode material demonstrates that a radical redesign of the electrode using 100% active material may help address the issue.

Phagocytosis is regulated by the mechanical properties of both the phagocyte and its cargo. Here, the authors show that macrophages employ β2 integrins to sense the rigidity of phagocytic cargo and then mount the appropriate form of engulfment.

A lipid-nanoparticle-based formulation incorporating engineered lipids containing a blood–brain-barrier-crossing moiety effectively delivers mRNA to neurons and astrocytes following systemic administration in mice.

Soil microbes contribute to soil organic matter. Here, the authors explore how microbial traits contribute to organic matter accumulation, finding that synergies among fungal traits promote soil organic matter formation, functional complexity, and stability.

A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.

How resistance to different classes of AKT inhibitors can emerge is unclear. Here, the authors show that resistance to allosteric inhibitors is mainly due to mutation of AKT1 while the ATP competitive resistance is driven by activation of PIM kinases in prostate cancer models.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

The small molecule GS-6207, which disrupts the function of the HIV capsid protein, shows potential as a long-acting therapeutic agent for the treatment and prevention of HIV infection.

Whole-genome bisulfite sequencing along with whole-genome and transcriptome sequencing of 100 prostate cancer metastases identifies genomic regions that are differentially methylated during disease progression and a novel epigenomic subtype.

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

The Connectome Annotation Versioning Engine (CAVE) is a platform for proofreading, annotating and analyzing datasets reaching the petascale. Currently, CAVE is used for electron microscopy datasets, but it can potentially be used for other large-scale datasets.

Super spreading events are considered important contributors to the spread of COVID−19, but the extent to which superspreading varies by transmission setting is unclear. Here, the authors demonstrate heterogeneity in superspreading and the generation interval between COVID−19 cases in different settings using data from Hong Kong.

Here, Pala et al. show that mosquito salivary apyrase regulates hemostasis in the mosquito blood meal, boosting malaria transmission. They demonstrate that immunizing against apyrase inhibits parasite transmission.

Wong and colleagues show that LKB1-deficient lung tumors are sensitive to autophagy inhibition, which can restore impaired antigen presentation and antitumor immune responses, and propose dual targeting of ULK1 and PD-1 for these tumors.

Cryo-EM illuminates atomic binding details and far-ranging conformational effects of the inhibitor targocil-II on wall teichoic acid ABC transporter TarGH, a virulence target from the antibiotic resistant, often hospital acquired pathogen S. aureus.

The fast radio burst FRB 20200120E is shown to originate from a globular cluster in the galaxy M81, and may be a collapsed white dwarf or a merged compact binary star system.

Transcriptional changes occur in the dorsal root ganglion in response to nerve injury and may contribute to neuropathic pain. Here the authors show that the DNA methyltransferase DNMT3a is upregulated in rodents following nerve injury, and may contribute to pain-like behaviour by decreasing expression of the voltage-gated potassium channel Kv1.2.

Here β-catenin, which has been implicated in neurological and psychiatric diseases, including depression, is shown to mediate resilience to chronic stress in mice through induction of Dicer and microRNAs in nucleus accumbens, a key brain reward region.

The Airy-Talbot effect is experimentally demonstrated for spoof surface acoustic waves in a structured metasurface. Owing to its self-imaging and self-healing properties, the authors achieve robust multipath transmission of nonperiodic signals.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Little is known about how temperature anomalies affect people’s views about climate change. Research now shows that available information about today’s temperature, even though less relevant than evidence of global patterns, is used to formulate opinions. With experience of abnormal temperatures, people overestimate the frequency of similar past events and belief in global warming increases.

A unique case from the Colombian cohort of autosomal dominant Alzheimer’s disease is reported in which disease progression is substantially delayed despite unusually high amyloid plaque pathology, possibly related to a rare mutation in APOE3.