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Here, the authors conduct a metagenomic-based study of England’s rivers to show that biofilm bacteria are taxonomically and functionally diverse and are key to biogeochemical cycling, highlighting the importance of river biofilm bacteria in understanding and monitoring freshwater ecosystem health.

The biogenesis and stereochemical origin of many natural products remain unknown. Now the biosynthetic pathway of brevianamide A is elucidated. An isomerase is discovered that can catalyse pinacol rearrangement without a cofactor and determine the stereochemistry of the bicyclo[2.2.2]diazaoctane ring.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

Methods to demonstrate genomic linkages between pathogens across One Health compartments have not been established. Here, the authors compile a collection of E coli genomes from humans, animals, and the environment in Australia and investigate genomic evidence of cross-source clusters.

A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.

Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.

In an analysis of long-term safety events in 783 patients treated with T cell therapy in 38 trials, 2.3% of patients developed second primary malignancies, and vector integration analyses revealed no pathological insertions.

Factors controlling cancer and neoplasia prevalence across species are unclear. Here, the authors investigate the impact of diet and plasma glucose levels across 273 vertebrate species, finding no association between glucose levels and cancer within birds, mammals, or reptiles.

In a phase 1 dose-escalation trial in patients with nine different types of solid tumors, MAGE-A4-specific T cells had an acceptable safety profile and exhibited an encouraging overall response rate in patients with synovial sarcoma.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

There is increasing evidence of a functional interaction between acute myeloid leukemia (AML) and immune cells, influencing disease outcome. Here the authors study how distinct oncogenes differentially affect the host immune response to leukemic cells in preclinical models of AML.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

Peptide antibiotics often display a very narrow therapeutic index. Here, the authors present an optimized peptide antibiotic with broad-spectrum in vitro activities, in vivo efficacy in multiple disease models against multidrug-resistant Gram-negative infections, and reduced toxicity.

Diel study revealed fine scale coupling between microbial activity and DOM biogeochemistry in the oligotrophic ocean.

The caudal-related homeobox transcription factor CDX2 is expressed in leukemic cells in the majority of patients with leukemia but not during normal blood formation. Here, the authors report a mouse model with conditional Cdx2 expression showing de novo leukemic transformation, and use it to optimize treatment in high-risk AML.

Bruedigam et al. explore the mechanism of action and therapeutic benefit of telomerase inhibitor imetelstat in a collection of PDXs from patients with AML and demonstrate that, in combination with chemotherapy, it re-sensitizes treatment-resistant AML cells.

Richter’s Transformation is a treatment-resistant and fatal progression from Chronic Lymphocytic Leukemia (CLL) to an aggressive lymphoma. Here, the authors show that PRMT5 is upregulated months prior to and after transformation, PRMT5 overexpression in a CLL mouse model leads to increased risk of transformation, and that targeted PRMT5 inhibition prolongs survival and delays disease development.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening severe cutaneous drug reaction mediated by CD8⁺ T cells. Here the authors characterise the immune response in skin samples at the site of tissue damage from patients affected with SJS/TEN and compare this to healthy skin or blister fluid and find populations of CD8⁺ T cell clonotypes expressing cytotoxic mediator molecules.

Forecasts of risks of invasion by non-native species are challenging to obtain. Here, the authors show that mechanistic models based on functional traits related to species’ capacity to generate and retain body heat identify areas at risk of invasion by non-native birds in Europe.

Using metabolomics and shotgun metagenomics on stool samples from individuals with and without inflammatory bowel disease, metabolites, microbial species and genes associated with disease were identified and validated in an independent cohort.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Analysis of SLOS patient-derived iPSCs reveals that cellular accumulation of the cholesterol precursor 7DHC, rather than cholesterol deficiency, causes dysregulation of Wnt/β-catenin signaling and aberrant neural differentiation.

Exome sequencing of 2,871 probands with congenital heart disease (CHD) provides new insights into the genetic architecture of these disorders. The results implicate new genes in CHD pathogenesis and highlight striking overlap between genes with damaging de novo mutations in individuals with CHD and autism.

Exome sequencing of patients with congenital heart disease (CHD) and their unaffected parents reveals an excess of strong-effect, protein-altering de novo mutations in genes expressed in the developing heart, many of which regulate chromatin modification in key developmental genes; collectively, these mutations are predicted to account for approximately 10% of severe CHD cases.

Global groundwater resources are under strain, with cascading effects on producers, food and fibre production systems, communities and ecosystems. In this Perspective, the authors call for a major shift in research, extension and policy priorities to build polycentric governance capacity and strategic planning tools to sustain aquifer-dependent communities.

A prospective clinical study of cancer patients (I-PREDICT) demonstrated the feasibility of matching genomic alterations found in tumors to combined drug treatments.