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Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

This study shows how the same brain networks may support resilience differently in individuals with varying genetic risks, enabling more personalized mental health approaches.

In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

This study reveals that an outer membrane protein from the predator Bdellovibrio bacteriovorus forms a pentameric assembly that traps a lipid monolayer within. This allows the discovery of two superfamilies, distributed across a wide range of bacteria, likely to adopt a similar architecture.

The COMPASS trial is a prospective observational study seeking to establish biomarkers in advanced pancreatic cancer through in-depth profiling prior to commencing chemotherapy. Here, the authors report the final data for the complete cohort of 268 patients enrolled in the COMPASS trial.

Palmitoylation at C64 in stimulator of interferon genes (STING) is reported and, along with engagement of C91, is involved in dynamic cross talk with C148 to alter STING oligomer states and ultimately control STING activation.

Infection of mosquito immune cells by dengue and Zika virus enhances the spread of virus infection to mosquito tissues, such as the salivary glands, to promote virus transmission and highlights conserved roles of immune cells in virus dissemination.

A national classification system of wetland hydrologic connectivity to streams, which could be applied globally, demonstrates and advances current understanding of how wetland connectivity affects surface water quality.

The authors identify a single main-chain hydrogen bond required to keep GABA_A receptors closed in the absence of neurotransmitter. Electrophysiology and molecular dynamics simulations suggest disruption of this bond is a key component of channel opening during inhibitory synaptic signaling in the brain.

BMAL1–HIF2α heterodimer was recently shown to modulate circadian variations in myocardial injury. Here, the authors show that BMAL1 can form a heterodimer with HIF2α in clear cell renal cell carcinoma, contributing to tumor progression and response to HIF2α antagonist drugs.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Nickel(II) dihalide precatalysts with bidentate nitrogen ligands are widely used in cross-coupling reactions, notably in combination with photosensitizers, forming catalytic systems that currently drive major conceptual and synthetic thrusts within organic chemistry. Here the authors show a general mechanism by which these precatalysts are converted to the reduced, catalytically active species, using a range of characterization and spectroscopic techniques.

Hepatitis E virus exists in two forms in patients: naked and quasi-enveloped. Using a new imaging method, the authors found that these forms enter cells through different pathways, directed by interaction of the capsid protein with integrin beta 1.

Analysis of data from multiple instruments reveals a giant exoplanet in orbit around the 0.2-solar-mass star TOI-6894. The existence of this exoplanetary system challenges assumptions about planet formation and it is an excellent target for atmospheric characterization.

Bai and colleagues present MapDiff, a discrete diffusion-based framework for generating amino acid sequences conditioned on a target protein structure, with strong performance in predicting uncertain regions and achieving high in silico foldability.

New archaeological and ancient genomic data from humans in Papua New Guinea and the Bismarck Archipelago shed light on regional human admixture and genetic isolation over the past 2,500 years.

This study demonstrates that high alcohol concentrations during binge drinking activate a small GABAergic neuronal ensemble in the medial orbitofrontal cortex, which subsequently reduces further alcohol consumption. This effect is mediated by the ensemble’s projections to the mediodorsal thalamus.

This study reports on excavations of hearths and stone artefacts from 20,000-year-old deposits at Dargan Shelter, which at an elevation of 1,073 m is believed to be the oldest occupied high-altitude site in Australia.

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).

An IgE antibody recognising Folate Receptor-alpha has been tested in clinical trials for ovarian cancer and preclinical studies show macrophage involvement in the anti-tumoural functions of IgE. Here the authors demonstrate that IgE induces proinflammatory activation of ovarian cancer patient macrophages, which reverses their immunosuppressive induction of Treg cells and promotes CD8⁺ T cell function.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

During tissue injury blood cells in the microvasculature and tissue resident cells have differing phenotypes. Here the authors use single cell transcriptomics in mice models to assess the differences in phenotype of immune cells in multiple organs and the tissue resident cells before, after and during acute kidney infection.

Resting T cells are difficult to manipulate, and are a reservoir for latent HIV. Here, the authors develop a lipid nanoparticle formulation with the ability to transfect resting primary human T cells, enabling delivery of mRNAs that result in reactivation of latent HIV. This could help development of HIV cure strategies.

Clinical translation of cell products is impeded by the lack of clinically predictive potency assays. Here, the authors report a microfluidic system to evaluate patient-derived cells used in a clinical trial for osteoarthritis pain, and use the results and patient-matched clinical data to build prediction models, showing improved clinical prediction and higher correlative power with pain scores compared to 2D culture.

The predicted increase in frequency of droughts and rising temperatures in Europe will lead core populations of a temperate plant to an evolutionary dead-end unless they acquire genetic alleles that are present only in extreme edge Mediterranean, Scandinavian, or Siberian populations.

Arctic marine ecosystems have experienced significant change through the Holocene. Here, the authors used sedaDNA from Northern Greenland to reconstruct marine mammal occurrence, demonstrating the impact of air temperature and sea ice cover over the past 12000 years.

Here, the authors perform a machine learning meta-analysis of Parkinson’s disease (PD) classification based on microbiome features, showing that the accuracy of models can be generalizable and improve disease specificity when trained on multiple datasets, identifying PD-associated microbial pathways, including those involved in solvent and pesticide biotransformation.

In this Perspective, the authors and the members of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group discuss specific considerations for the use of chimeric antigen receptor (CAR) T cell therapies in paediatric patients with rheumatic diseases.

The sub-continental lithospheric mantle passively degasses volatiles to Earth’s surface, including from regions unaffected by volcanism, according to a study of helium and argon isotopes in young groundwater.

Beck et al. conducted single-cell and spatial profiling of embryonal tumors with multilayered rosettes, finding that malignant cellular hierarchies are driven by developmental programs and specific members of the chromosome 19 microRNA cluster.

Conditional cysteine restriction in mice causes substantial weight loss, exceeding that seen with essential amino acid restriction, by activating the integrated stress and oxidative stress responses, and by unexpectedly depleting coenzyme A, leading to metabolic inefficiency.

Recent studies have shown that energy transfer photoenzymes can be engineered to promote stereocontrolled [2 + 2] cycloadditions; however, existing systems rely on ultraviolet light and display limited photochemical efficiencies. A generation of thioxanthone-containing photoenzymes now harnesses visible light to drive challenging photochemical conversions with high efficiencies and selectivities.

In this study, Marshall et al. studied early immune responses in the lung and blood after an aerosol infection with BCG. Understanding which cells respond to this infection can help us understand how to design new tuberculosis vaccines.

Checkpoint inhibitor (CPI) therapy is modestly effective in Glioblastoma patients, with some patients not benefitting at all. Authors here present the outcomes of single arm prospective clinical trial employing combination CPI therapy in newly diagnosed GBM and identify the pre-treatment genetic, microbiome and immunological factors that might contribute to sensitivity.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

A study reports on the DNA methylation dynamics during embryogenesis in marsupials, showing that these differ from those occurring during embryogenesis in eutherian mammals.

The Global Flourishing Study provides a comprehensive view of the distribution and determinants of well-being by assessing domains such as health, happiness, meaning, character, relationships and financial security. Initial findings reveal significant variations in flourishing across countries and demographic groups, with factors such as age, marital status and religious service attendance showing strong associations with well-being.

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.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

While anti-retroviral therapy (ART) helps contain HIV, whether adoptive T cell therapy further improve the prognosis is unclear. Here the authors conduct an open-label, single-arm phase 1 study to assess the safety (primary outcome) and characteristic (secondary outcome) of autologous, HIV-specific T cell therapy to find it safe to warrant further efficacy assessment.

The authors assess the risk of overshoot beyond 1.5 °C warming, using three scenarios with minimal overshoot, brief overshoot and sustained overshoot. They show a risk of long-term Amazon dieback, which begins as early as 1.3 °C warming but is largely mitigated by reducing temperature below 1.5 °C.

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.

Examination of a complete structural phase diagram of twisted trilayer graphene shows that several large-scale moiré ___domain lattices can be formed, the physical properties of which can be tuned by the twist angles between layers.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.