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Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Inactivation of chromosomal genes through plasmid-encoded IS elements is an extended mechanism of antimicrobial resistance evolution in bacteria.

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.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.

In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.

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).

Monitoring of western chimpanzee populations in Guinea-Bissau and Côte d’Ivoire reveals the presence of rare and different genotypes of Mycobacterium leprae, suggesting greater circulation in wild animals than previously thought.

Despite frequent AKT/mTOR pathway activation in patient’s rhabdomyosarcoma (RMS), success of AKT inhibitors in the clinical has been limited. Here, using RMS patient-derived models, the authors demonstrate that the efficacy of the AKT inhibitor, ipatasertib, is in part due to its off-target effects on PRKG1, identifying PRKG1 as a potential biomarker for ipatasertib response.

Large groups of spawning fish can induce upper ocean mixing on the same scale as geophysical processes, according to observations of small-scale turbulence caused by anchovy spawning aggregations in a coastal upwelling area.

Genomic studies of attention-deficit/hyperactivity disorder (ADHD) have advanced the understanding of its neurobiology but are still constrained by one of the most pronounced Eurocentric biases in psychiatric genetics. Expanding ADHD genomics to under-represented populations, particularly in Latin America, offers a unique opportunity to yield transformative discoveries by capturing the genetic diversity of admixed individuals. We call for a global, coordinated effort to prioritize diversity in ADHD research, not only to foster innovation in precision psychiatry but also to ensure that these advancements benefit all populations equitably.

New treatments are essential for methicillin-susceptible Staphylococcus aureus bacteremia, but progress is slow. In this phase III–IV trial, cloxacillin plus fosfomycin failed to show superiority over cloxacillin alone, underscoring the challenges to improving patient outcomes.

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 authors identify pre-TCR as a key biomarker and therapeutic target in T-ALL. Targeting it with an anti-pTα antibody–drug conjugate inhibits leukemia-initiating cells and tumor growth in mice, offering promise for relapsed/refractory T-ALL treatment.

Antibodies that block the Wnt inhibitors sclerostin and DKK- 1 enhance bone formation and fracture repair. Here the authors show these monospecific antibodies induce compensatory mechanisms that limit efficacy, and have designed a sclerostin/DKK-1 bispecific antibody that promotes superior fracture repair in rodents and bone formation in primates.

Here, Cilleros-Portet et al. present a large placental methylation database as a tool to explore the genetic burden that acts in prenatal stages, giving insight into neuropsychiatric disorders, and with especial emphasis on schizophrenia.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Peinado and colleagues show that small extracellular vesicles and secreted NGFR cargo induce lymphangiogenesis and develop the lymph node pre-metastatic niche to promote melanoma metastasis, which could be targeted pre-clinically with NGFR inhibition.

While water electrolysis offers a renewable way to produce hydrogen, there are few Earth-abundant, acid-stable water oxidation catalysts. Here, authors show Co₃O₄, when protected by a partially hydrophobic environment, to sustain 40 h activity without structural or chemical transformations.

The hematopoiesis of patients with del(5q) Myelodysplastic Syndromes is composed of a mixture of cells with and without the deletion. Here, the authors show that del(5q) and non-del(5q) cells share similar transcriptional alterations, with del(5q) cells presenting additional lesions. Moreover, hematological response to lenalidomide is associated with the reversal of some transcriptional lesions in both del(5q) and non-del(5q) cells.

The efficacy of carbapenem antibiotics can be compromised by metallo-β-lactamases, but a high-throughput screen followed by optimization has now enabled the discovery of indole-2-carboxylates (InCs) as potent broad-spectrum metallo-β-lactamase inhibitors. The results highlight the potential of InC–carbapenem combinations for clinical use as well as mechanism-guided approaches to combatting globally disseminated antibiotic resistant mechanisms.

This study leverages the empirical datasets and microbial-explicit SOC model to show a thermal threshold of microbial CUE and heterotrophic respiration at 15 °C, implying a potential abrupt transition to more vulnerable SOC under climate warming.

This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and novel isoforms in 555 samples from 391 donors finds associations with genetic risk loci in Alzheimer’s and Parkinson’s diseases.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

This study reveals that in people with first episode of psychosis receiving oral antipsychotic medication, switching to long-acting injectable antipsychotic therapy may reduce psychotic relapses, especially in vulnerable subgroups, such as those with prior relapses or non-adherence to antipsychotic medication.

Direct observation of G-quadruplexes (G4s) in live cells is challenging. Here the authors report a method to identify G4s within the nuclei of live and fixed cells using a fluorescent probe combined with fluorescence lifetime imaging microscopy.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Polymerase Bcs3, which allows the fermentation-free synthesis of Haemophilus influenzae type b capsule for vaccine development, adopts a basket-like shape with all six active sites facing the interior, creating a protected environment for catalysis.

The diversity and impact of viruses in remote marine environments are less well understood. In this study, the authors analyse an -omics dataset to gain insights into the genomics and potential role of endemic viruses infecting ecologically important microbes inhabiting the ocean cavity beneath the Ross Ice Shelf.

Electron transfer between mitochondrial cytochrome c and subunit of cytochrome bc₁ can proceed at long distance. Here the authors investigate further the mechanism and show phosphorylation regulation of the interactions between the protein partners in the electron transport chain.

Lung resident memory T (T_RM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung T_RM cells that might be important to limit reinfection.

CLN7 neuronal ceroid lipofuscinosis is an inherited lysosomal storage disease typically with childhood onset of neurodegenerative symptoms. Here the authors report that in a mouse model of CLN7 disease neuronal reactive oxygen species and the activity of glycolytic enzyme PFKFB3 are increased, while PFKFB3 inhibition ameliorates hallmarks of pathology.

One hundred years ago, Camillo Golgi described the cellular apparatus that has since become synonymous with his name. Although its existence was questioned for 50 years, this organelle is now established as the cell's centre for the processing and secretion of proteins.