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The mechanisms underlying the chronic stress-induced increased risk for major depressive disorder and anxiety are unclear. Here, the authors show the transcriptional changes occurring in neocortical neurons and identify YY1 as a regulator of chronic stress-induced maladaptive behavior in mice.

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

Said et al. used cryoEM, biochemistry and bioinformatics to uncover how the Sm-like protein Rof regulates transcription termination. Rof binds termination factor ρ, inhibiting ρ ring closure and its association with RNA or transcription complexes.

The costimulatory molecule CD40 expressed on B cells has an important role in B cell-mediated immunity but some aspects of CD40-mediated signalling remain unknown. Here the authors show that the ubiquitin ligase NEDD4 is a part of a CD40 signalling complex required for CD40-induced Akt activation.

COBRA1 is a BRCA1-binding protein and, as part of the negative elongation factor, regulates RNA polymerase II pausing and transcription elongation. Here, the authors show that tissue-specific deletion of mouse Cobra1 inhibits postnatal mammary gland development and that the mammary defects can be rescued by additional deletion of Brca1in a DNA repair-independent manner.

Yang, Zhang et al. identify a non-canonical form of necroptosis driven by nuclear RIPK1-mediated nuclear membrane rupture as a result of ZMPSTE24 deficiency and defective prelamin A processing commonly observed in progeroid disorders.

Intracellular detection of viral invasion triggers activation of the transcription factor IRF3 and antiviral interferon production. Fangfang Zhou and colleagues report that the transcription regulator YAP in the host restrains this process by preventing inadvertent spontaneous dimerization of IRF3 and its translocation to the nucleus.

With the example of the paraspeckle protein PSPC1, Shao et al. demonstrated the synergistic interplay of promoter-associated RNA and its binding proteins in promoting transcription condensate formation and Pol II engagement and activity via phase separation.

Proteins are transported among eukaryotic organelles along the cytoskeleton in membrane carriers. Here authors find that the Dopey1-Mon2 complex functions as a dual-lipid-regulated cargo-adaptor to recruit kinesin-1 to secretory and endocytic organelles or membrane carriers.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

The retention of 53BP1 at DNA double strand breaks (DSBs) is inhibitory to homologous recombination repair. Following ionising radiation, the authors demonstrate that TRABID-mediated deubiquitination of 53BP1 promotes its retention, sensitising prostate cancer to PARP inhibition.

CRY2 mediates photoperiod-responsive floral initiation in Arabidopsis. Here the authors show that CRY2 also regulates temperature sensitive flowering and that CRY2 can interact with and regulate the splicing factor CIS1 to affect alternative splicing of transcripts that regulate flowering.

This paper shows that the uniformity of vitreous ice thickness relies on the surface flatness of the supporting film, and presents a method to use ultraflat graphene as the support for cryo-EM specimen preparation.

Exercise increases energy expenditure and suppresses obesity, but the effector mechanisms are not still unclear. Here the authors profile serum proteomics in exercised mice to find reduced parvalbumin levels that correlate with increased M2 macrophage and suppressed diet-induced obesity to hint parvalbumin as a potential therapy target against obesity.

ILC2s are heterogeneous, dependent on tissue location. Here the authors show that TGFβ-induced neuropilin-1 specifically marks lung ILC2s and controls their function in pulmonary fibrosis by inducing expression of the ST2 IL-33 receptor.

Human Treg cells are central to immune tolerance, yet their heterogeneity and differentiation remain incompletely understood. Here the authors perform single-cell RNA and T cell receptor sequencing to resolve Treg cells from healthy individuals and patients with or without acute graft-versus-host disease revealing Treg complexity in health and disease.

Sleep-disordered breathing (SDB) is a prevalent disorder linked to higher cardiovascular disease risk. Here, the authors show that summary scores reflecting SDB metabolite signatures are associated with increased risks for incident hypertension and diabetes, potentially useful in guiding risk stratification.

The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, the authors show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics, such as lefamulin.

The deacetylase SIRT1 regulates IRF3/IRF7-mediated antiviral interferon signaling. Here the authors show that SIRT1 deactylates the DNA-binding domain resulting in liquid–liquid phase separation of IRF3/IRF7 and that this signaling is inhibited in aging, an effect that can be reversed with a SIRT1 agonist to restore antiviral response.

The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune responses. Here, the authors report structures of the Kv1.3 potassium channel with and without immunoglobulin modulators, shedding light on the mechanisms of Kv1.3 gating and modulation.

The tyrosine kinase receptor EphB4 is shown to interact with the insulin receptor to facilitate its endocytosis and degradation, thereby decreasing insulin signaling and promoting insulin resistance.

Polygenic risk scores have potential to predict an individual’s risk of disease based on genetic markers. Here, the authors develop a polygenic risk score for hypertension and test it in a multi-ethnic cohort, finding that the score is associated with higher likelihood of hypertension development 4-6 years later.

Sun and colleagues describe that the secretion of interleukin-33 is dependent on a p40 N-terminal fragment of gasdermin D, whose generation is independent of inflammatory caspase-1 and caspase-11.

Immunogenicity concerns preclude the use of bacterial kynureninases for cancer immunotherapy, while the human variant lacks the desired therapeutic effect. A human kynureninase enzyme has now been evolved to reach the activity and substrate specificity of its bacterial counterpart.

Rice yield is boosted by overcoming a trait tradeoff.

Through an analysis of global differences in human exposure to greenspace, a new study identifies a contrasting pattern of greenspace exposure between Global South and North cities and finds seasonal variations in greenspace exposure inequality.

Imaging and sequencing approaches are combined to show that extrachromosomal DNA (ecDNA) in cancer is circular and has unique chromatin structure that amplifies oncogene output.

Accurate localization of abnormalities is crucial in the interpretation of chest X-rays. Here the authors present a deep learning framework for simultaneous localization of 14 thoracic abnormalities and calculation of cardiothoracic ratio, based on large X-ray dataset with bounding boxes created via a human-in-the-loop approach.

Innate immunity protects the central nervous system against fungal pathogens. Lionakis and colleagues identify Candidalysin, a Candida virulence factor that elicits microglial expression of the cytokine IL-1β and chemokine CXCL1 and facilitates neutrophil recruitment. Alteration of this pathway impairs antifungal responses.

Toll-like receptors are involved in pathogen recognition by the innate immune system and rely on the molecular chaperone, gp96, for correct folding. In this article, the chaperone activity of gp96 is shown to be dependent on an additional endoplasmic reticulum protein, CNPY3, for some Toll-like receptors.

TIP60-mediated crotonylation of the microtubule plus-end tracking protein EB1 at Lys66 regulates attachment of astral microtubules to the lateral cell cortex and spindle positioning.

Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage.

An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

Autophagy is essential for cellular homeostasis which decreases with age. Here, the authors identify aging-induced reduction of DHHC5-mediated beclin 1 palmitoylation as an underlying mechanism by which aging induces autophagy decline in the brain.

Mao et al. reported ribosomal frameshifting events shortly after start codon selection, which is influenced by the sequence context and controlled by initiation factor eIF5B. This translational ‘noise’ is increased in response to nutrient starvation.

PtpA is a secreted mycobacterial protein and virulence factor. Liu and colleagues demonstrate that PtpA suppresses signaling by cells of the innate immune system by coopting the activity of host ubiquitin.

Space-to-ground infrared camouflage with radiative heat dissipation is achieved via novel multilayer structure.

Clostridium difficile causes diarrhea and colitis by producing up to three different protein toxins. Here, Tam et al. show that an anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for toxin entry into host cells, without disrupting the gut microbiota.

The endothelial glucocorticoid receptor plays a key role in the regulation of many diseases, including diabetes. Loss of this receptor results in accelerated renal fibrosis, a heightened inflammatory milieu, augmented Wnt signaling and suppression of fatty acid oxidation in diabetic kidneys.

A silk-fibroin hydrogel converts rat quiescent ventricular cardiomyocytes into pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin.

Post transcriptional modifications to RNA may be important in the function of NK cells but this is not fully known. Here the authors show that m⁶A-methyltransferase METTL3 deletion in NK cells leads to reduced function and protection against tumour challenge through suppressing response to IL-15.

Start codon selection is commonly thought to occur through the unidirectional scanning of the mRNA by the 40 S ribosome. Here the authors provide evidence that the pre-initiation complex can backslide on the mRNA to initiate translation at upstream AUG codons.