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Microbial communities, exposed to early Earth-like conditions in a modern microbialite reef, change cyclically due to seasonal environmental variations, implying evolved metabolic processes in microbialites over time, based on multiple chemical, physical, and biological analyses.

SNURPORTIN-1, encoded by the SNUPN gene, plays a key role in the nuclear import of spliceosomal small nuclear ribonucleoproteins, however its physiological function remains unclear. Here the authors report that recessive SNUPN mutations cause a distinct subtype of childhood muscular dystrophy and reveal SNURPORTIN-1’s role in muscle homeostasis, offering insights for new therapeutic strategies.

A molecular glue induces CRBN homodimerization and degradation through degron mimicry, revealing a distinct glue mechanism and offering a tool to study CRBN biology.

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).

Nik-Zainal and colleagues leverage CRISPR–Cas9 and whole-genome sequencing to examine mutational patterns following knockout of 42 human DNA repair genes. They further develop and validate a clinically relevant tool to detect mismatch repair-deficient tumors.

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 use of bispecific antibodies to target tumour-specific epitopes presented by MHC molecules in tumour tissue is a promising avenue for cancer immunotherapy. Here the authors use a mass-spectrometry guided analysis to identify off-target MHC-peptide complexes that bind to TCR-like antibodies next to the target peptide, enabling a novel approach to monitoring of antibody specificity during clinical maturation and development.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

The underlying mechanisms driving colorectal cancer (CRC) through the serrated route are largely unknown. Here, the authors show that reduced aPKC levels increase cholesterol biosynthesis to promote aggressiveness in serrated tumours and targeting this pathway reduces tumourigenesis in preclinical models of serrated CRC.

Patritumab deruxtecan (HER3-DXd) is a promising therapy for breast cancer, targeting HER3. Here, the authors analyse the genomic factors that affect the response to HER3-DXd in patients with early-stage HER2-negative breast cancer as part of the SOLTI-1805 TOT-HER3 clinical trial and report outcomes for Part B of the trial using lower HER3-DXd dose in patients with HER2-negative breast cancer.

Long-term characterisation of SARS-CoV-2 antibody kinetics is needed to understand the protective role of the immune response. Here the authors describe antibody levels and neutralisation activity in healthcare workers over seven months and investigate the role of immunity to endemic human coronaviruses.

The evolution of the vertebrate head mesoderm involved the emergence of new structures and cell types. Here the authors generated a cell atlas of the cephalochordate neurula to study the origins of these novelties and propose a revised scenario for the evolution of the vertebrate head muscles.

The fibrinolytic system promotes the progression of solid tumors. Here, the authors show that the fibrinolytic agent plasmin supports B-cell acute lymphoblastic leukemia (B-ALL) progression via remodeling of the extracellular matrix, and the inhibition of plasmin activation with ε-aminocaproic acid prolongs survival in B-ALL mouse models.

TET3 is essential to postnatal development due to unknown reasons. Here Mulet et al. demonstrate that TET3 is required for ATP synthase assembly in differentiated cells and that its loss leads to an unphysiological metabolic profile.

The growth of a biofilm—a bacterial colony attached to a surface—is governed by a trade-off between horizontal and vertical expansion. Now, it is shown that this process significantly depends on the contact angle at the biofilm’s edge.

How do individual differences affect vulnerability to developing post-traumatic stress disorder (PTSD)? Here, using longitudinal testing in a rat model of PTSD, the authors show patterns of pre-trauma brain connectivity and behaviors that predict PTSD-like responses to trauma exposure.

Long-term experimental evolution and modelling show the evolution of small and large cluster-forming lineages of snowflake yeast that coexist over generations due to a trade-off between organismal size and competitiveness for dissolved oxygen.

A comprehensive meta-analysis of global terrestrial and marine genetic diversity covering more than three decades of research demonstrates rapid loss of genetic diversity and identifies conservation interventions that could mitigate this process.

Chimeric antigen receptor T (CAR-T) cell therapy is efficient in certain haematologic malignancies, but clinical success in solid tumours has been hampered by scarcity of tumour-specific antigens. Here authors show that combination therapy using CAR T cells targeting p95HER2 and bispecific antibodies against HER2 and CD3 consistently leads to complete regression in HER2-positive, patient-derived xenografts tumours in mouse models.

Several parameters in the bone marrow (BM) niche regulate leukaemic stem cell status and disease progression. Here, the authors show that calcium-sensing receptor affects the location of acute myeloid leukaemia (AML) cells in the BM niche which influences self-renewal of leukaemic stem cells and AML development

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

Anaplastic thyroid cancer (ATC) is a particularly aggressive cancer type with limited effective therapeutic options. Here, the authors identify the SUMO E3 ligase PIAS2 as a potential therapeutic target in ATC and mechanistically investigate its role in mitotic spindle and centrosome assembly.

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.

Clinical studies have suggested that the therapeutic potential of polyclonal convalescent plasma is highest in the first days of symptoms. Here, the authors present results from a pooled analysis of two clinical trials in COVID-19 outpatients that did not provide conclusive evidence in favor of convalescent plasma.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

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.

The status of the harlequin toads has not improved since 2004 despite species rediscoveries accompanied by increasing conservation efforts, and habitat destruction and degradation continue to threaten them today, according to an analysis of population status records over the period 2004–2022.

Mitochondrial metabolism is essential for the dynamic regulation of cardiac and vascular tissues, and the relevance of basic mitochondrial biology in cardiovascular disease is being increasingly recognized. In this Review, the authors explore the physical interaction between mitochondria and sarco/endoplasmic reticulum, discussing how the communication between these two organelles is involved in cardiovascular pathologies.