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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).

Structural studies of certain Tn and STn antigen-targeting antibodies reveal that their V_H and V_L domains recognize the glycan antigen and the adjacent peptide region, respectively, enabling a V_H domain-focused and V_L domain-varying phage display library to generate antibodies targeting diverse glycopeptide epitopes.

A combination of analysis of plasmid diversity in the gut of hospitalized patients with experimental evolution shows that the evolution of plasmid-mediated antibiotic resistance involves a trade-off between antibiotic resistance levels and bacterial fitness.

A complete pre-agricultural European human genome from a ∼7,000-year-old Mesolithic skeleton suggests the existence of a common genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic, and ancestral alleles in several skin pigmentation genes suggest that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times.

Critical regulators of RAS signaling pathways in oncogenic RAS-driven tumors remain to be explored. Here, the authors show the development of KRAS(G12D)-driven lung adenocarcinoma is dependent on SOS1, with dual roles in both tumor and stroma.

This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.

Synthesis and maturation of Okazaki fragments is crucial for lagging strand DNA replication. Here the authors find that the ubiquitin-specific protease Ubp10 works with the DNA synthesis machinery to promote Okazaki fragments joining by removal of PCNA through deubiquitylation of PCNA-K164.

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

Perception can be explained by predictive coding, but it is unclear how this theory applies at the single-neuron level. Here, authors describe how auditory patterns are encoded and detected by single neurons along the auditory pathway, demonstrating that prediction error exists in single auditory neurons.

High-resolution time differences between six Middle Palaeolithic hearths from El Salt Unit x (Spain) obtained through archaeomagnetic and archaeostratigraphic analyses show sometimes decade-long intervals between hearths.

Common variable immunodeficiency (CVID) is a prevalent primary immunodeficiency characterized by hypogammaglobulinemia, poor antibody responses, and enhanced susceptibility to infection. Here the authors examine CVID patients infected by SARS-CoV-2 and describe broad immune dysregulation, sustained type I IFN responses, altered B/T cell signaling, impaired NK cell differentiation, and persistent inflammasome activation.

Infection or chronic inflammation is a risk factor for childhood B-cell precursor acute lymphoblastic leukemia. Here, the authors show that the DNA editing enzyme AID is expressed in infected B cells but using genetic mouse models show that it does not contribute to leukemia pathogenesis.

How adipose mitochondria activity is fine-tuned in response to obesity is an active area of study. Here, the authors show that mitochondrial protein MCJ can block thermogenesis and that silencing this gene can correct obesity-related comorbidities.

Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

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.

While Digital contact tracing (DCT) has been argued to be a valuable complement to manual tracing in the containment of COVID-19, no empirical evidence of its effectiveness is available to date. Here, the authors report the results of a 4-week population-based controlled experiment, where they assessed the impact of the Spanish DCT app.

This study describes a pathway in fission yeast that senses nutrient levels and maintains protein homeostasis during starvation by modifying tRNAs in the anticodon loop. These modifications enhance the translation of critical AAA-rich mRNAs, promoting gene silencing and the long-term survival of quiescent cells.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. Here the authors perform single-cell omics analyses in CVID-discordant monozygotic twins and show epigenetic and transcriptional alterations associated with activation in memory B cells.

Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

Modelling combined with epidemiological and genomic data analysis from a hospital in Spain reveals frequent transmission of high-risk pOXA-48-carrying enterobacteria clones between patients and horizontal transfer of pOXA-48 plasmid within patients.

Immunological stressors are linked to the transformation of preleukemic B cells to B-cell acute lymphoblastic leukemia. Here the authors show a dysregulation of innate immune signaling in preleukemic precursor B cells and link to the development of B-cell acute lymphoblastic leukemia in a murine model.

A comprehensive analysis of models of brain metastasis and multiple cohorts of patient samples identifies a targetable molecular mechanism underlying the resistance to whole-brain radiotherapy that can inform patient selection for personalized radiotherapy.

The Rho signalling pathway is frequently activated in squamous carcinomas. Here, the authors find that the Rho GEF VAV2 is over expressed in both cutaneous and head and neck squamous cell carcinomas and that at the molecular level VAV2 promotes a pro-tumorigenic stem cell-like signalling programme.

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.

Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.

NGTs glycosylate asparagine residues in proteins, crucial for bacterial adhesion and pathogenicity. Here, the authors provide insights via crystallography and simulations, showing acceptor asparagine uses imidic form for catalysis and UDP-glucose phosphate group acts as general base.

A Fourier-transform waveguide spectrometer is demonstrated by using HgTe-quantum-dot-based photoconductors with a spectral response up to a wavelength of 2 μm. The spectral resolution is 50 cm^–1. The total active spectrometer volume is below 100 μm × 100 μm × 100 μm.