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Proteomics must target specific synapse types to reveal how molecules shape their unique functions. Here, authors show that hippocampal synapses differ in proteome and that neuron-specific glutamate receptor regulation shapes synaptic diversity.

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).

Higgins et al. present an AI tool that uses patient data to personalise treatment for Helicobacter pylori, the leading agent of gastric cancer, demonstrating improved eradication rates over prescribed therapies in retrospective clinical analysis.

Approaches describing how the brain changes to accomplish cognitive tasks tend to rely on collapsed data. Here, authors present a new approach that maintains high dimensionality and use it to describe individual differences in how brain activity is represented and organized across different cognitive tasks.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

In this study, authors identify the omentum, a tertiary lymphoid organ part of the fat tissue, as a reservoir for Brucella abortus, which promotes bacterial persistence and causes CD4⁺ and CD8⁺ T cell immunosuppression by IL-1RA secreted by PD-L1⁺ Sca-1⁺ neutrophils.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

Allergen specific immunotherapy (AIT) is both, safe and effective in reducing systemic symptoms of venom allergy in individuals. Here the authors examine the underlying immune cell changes after venom specific AIT in early time points after therapy initiation showing indicative changes in specific immune cell populations.

Overexpression of c-MYC regulates tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). Here the authors identify ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target of PDAC.

In this work, authors show that β-lactamase enzymes not only confer antibiotic resistance but also increase susceptibility to other antibiotics.

Consciousness may be inferred in others through observable behaviours such as facial expressions and vocalizations. However, such overt reporting has limitations, leading to research on physiological signals that disclose consciousness without relying on overt behaviour. In this Review, Kronemer, Bandettini and Gonzalez-Castillo explore such covert measures of consciousness in humans.

A study reporting the results of a clinical trial co-administering the GDF-15-blocking antibody visugromab with the anti-PD-1 antibody nivolumab demonstrates that neutralizing GDF-15 can overcome resistance to immune checkpoint inhibition in cancer.

YAP signaling has been established as a mechanotransductive pathway in multiple contexts, but its developmental roles are still being explored. Here they show that YAP signaling sustains intracellular tension to direct cell migration during embryonic axis assembly.

Studying the natural wanderings of the living brain is extremely challenging. Bolt et al. describe a new framework for considering the brain’s intrinsic activity based on the geophysical concepts of standing and traveling waves.

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Highly pathogenic avian influenza (HPAI) A/H5N1 has recently emerged in the Americas and has been implicated in mass die-off events of pelicans and sea lions. Here, the authors report sampling and characterisation of HPAI A/H5N1 genomes from five marine mammal and seabird species in Peru.

The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.

Genetic and Structural analysis of COVID patients cohort reveals a correlation between mitochondrial haplogroup and SARS-CoV-2 severity.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease with a substantial burden worldwide. In this Consensus Statement, a global multidisciplinary group of experts develop consensus statements and recommendations addressing a broad range of topics on NAFLD to raise awareness and spur action.

In NOTCH-induced T cell acute lymphoblastic leukemia, the resistance to anti-NOTCH therapy conferred by loss of the Pten tumor suppressor is linked to reversal of the effects of NOTCH inhibition on leukemic cell metabolism.

City-level analysis of data from the SALURBAL project shows vast heterogeneity in life expectancy across cities within the same country, in addition to substantive differences in causes of death among nine Latin American countries, revealing modifiable factors that could be leveraged by municipal-level policies aimed toward improving health in urban environments.

Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality.