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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.

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).

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

Children with dyslexia show significant differences in Visual Word Form Area size and specialization compared to typical readers, suggesting enduring neural characteristics exist even after targeted intervention increases reading ability scores.

Monoclonal antibodies and ligands targeting CD40 exhibit diverse agonistic and antitumor activities that are influenced by their design. Here, the authors identify mechanistic differences between clinically relevant anti-CD40 subclasses and CD40L, focusing on the dynamics and strengths of multi-bond formation at the single-molecule level.

Combining high-speed AFM, single molecule recognition force spectroscopy, and molecular dynamics simulations Zhu, Canena, Sikora et al. characterize the interaction dynamics of the trimeric spike protein of SARS-CoV-2 wt, and delta and omicron variants with its entry receptor ACE2. While delta variant increases avidity by multivalent binding to ACE2, omicron variant shows an extended binding lifetime.

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.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Large quantum computers are likely to require methods of connecting devices by transmitting and absorbing photons. Entanglement between two superconducting qubit devices has now been established using a waveguide with tunable directionality.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

Military personnel face increased exposure to pandemic-related stressors, yet their mental health impacts remain underexplored. Here, the authors analyze data from the STARRS Longitudinal Study, revealing significant increases in mental health issues among soldiers during COVID-19, particularly among vulnerable groups, underscoring the need for targeted support during pandemics.

The authors report a meta-analysis of methylome-wide association studies, identifying 15 significant CpG sites linked to major depression, revealing associations with inflammatory markers and suggesting potential causal relationships through Mendelian randomization analysis.

Phase-resolved mid-infrared observations from JWST of the hot gas giant WASP-43b detect a day–night difference of 659 ± 19 K. Comparison with climate models shows that the observations are compatible with cloudy skies, at least on the nightside, and the lack of methane detection suggests the presence of disequilibrium chemistry.

The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO₂ and H₂O and detection of SO₂.

A double-strand DNA scaffold enables real-time observations of protein–protein interactions at the single-molecule level.

The authors generate genomic data from 30 ancient human individuals, spanning the Bronze Age and the Iron Age from four archaeological sites in the Mediterranean (located in Tunisia, Sardinia and central Italy). Comparing with additional published ancient genomes, they generate insights into mobility and admixture in this interconnected region

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

Acyl-CoA synthetase long-chain family 4 (ACSL4)-driven changes in lipid metabolism are shown to modulate the sensitivity of intestinal epithelial cells to ferroptosis, thereby exacerbating inflammatory bowel disease.

Enzymatic recycling is an emerging technology to circularize the ubiquitous polyester poly(ethylene terephthalate). Here the authors evaluate and implement multiple process changes to improve the scalability and viability of this recycling technology. Process modeling demonstrates that these changes could enable cost competitiveness and greatly reduce overall life cycle impacts.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

Cao et al. find that the mesenteric lymphatic system becomes dysfunctional during obesity in mice and humans, leading to visceral adipose tissue accumulation and insulin resistance.

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

Genome-wide analyses in over one million self-reported cases and controls identify genetic variants associated with stuttering and find genetic correlations with autism, depression and impaired musical rhythm, supporting a potential neurological basis for stuttering.

Antidepressant drugs are the most common treatment for depressive episodes but only a fraction of patients experience adequate response. Here the authors find dysregulation of miRNAs in peripheral blood samples from depressed patients after antidepressant treatment, and show that the miRNAs are regulators of psychiatrically relevant signalling pathways.

Cephalopods are an enigmatic animal group with complex and adaptive behaviors such as camouflage; however the genetic basis for these traits is not well understood. Here the authors reveal a set of cephalopod-restricted rearranged genomic loci, involving known neuronal regulators but also unexpected gene families, that confer topological organization and gene regulation.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Fernández-Chacón et al. use imaging and scRNA-seq after targeting multiple Notch genes and angiogenic signaling pathways to find that the function of these pathways in vascular pathophysiology cannot be predicted by assessing transcriptional states.

The function of zebra stripes remains unclear as none of the options have been validated ecologically. Here, the authors, matching striping patterns to environmental variables, test the main hypotheses against each other and find that biting fly avoidance best explains the presence of stripes in equids.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis.

Genome-wide association analysis of triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio within the UK Biobank identifies candidate insulin resistance-associated loci linked to metabolic pathways and insulin biology. A polygenic risk score derived from these results shows an association with multiple cardiometabolic traits.

Hypoxia induces ·NO-dependent hydrogen sulfide (H₂S) biogenesis by inhibiting the transsulfuration pathway. H₂S oxidation promotes endothelial cell proliferation to support neovascularization in tissue injury and tumor xenograft models.

Logic-based computation operates widely with discrete molecules of up to nanometric sizes, but artificial molecule-based meso-scale systems which intrinsically perform logic operations are rare. Here, the authors show that self-assembled systems consisting of cyclophaneoctacarboxylates and a cationic surfactant can perform such functions.

Budzinski et al use bivalent ligands, BRET assays and radioligand competition to demonstrate a specific interaction between two receptors associated with neuropsychiatric diseases and addiction, dopamine D3 (D₃R) and neurotensin receptor 1. They show that the bivalent ligands promote endosomal trafficking of D₃R, suggesting a potential role for dimerization in vivo.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.

Sweet corn is one of the most important vegetables in North America and has undergone different selection pressures than non-sweet cultivars. Here, the authors report its genome assembly and reveal the evolutionary history of modern sweet corn through population genomic analyses.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

The growth plate cartilage supports long bone growth. Here the authors identify FoxA2+ long term stem cells in the growth plate that are stratified with short term PTHrP+ cells, participate in production of hyaline cartilage, expand in response to trauma, and whose ablation impairs cartilage regeneration.

A catalogue of the vascular flora of New Guinea indicates that this island is the most floristically diverse in the world, and that 68% of the species identified are endemic to New Guinea.

Time-series observations from the JWST of the transiting exoplanet WASP-39b show gaseous water in the planet’s atmosphere and place an upper limit on the abundance of methane.

Sediment lenses trailing subducting seamounts could maintain long-lasting fluid pressures and support slow-slip behaviour at sediment-rich subduction zones, according to three-dimensional seismic surveys of the Hikurangi margin.