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Recent studies unexpectedly indicate involvement of ventral tegmental area dopamine neurons in Alzheimer’s disease (AD). Here, the authors identified the enzyme casein kinase 2 as a mechanistic link between abnormal firing activity and AD pathology.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Here, Myers and Gallagher et al. characterize the structural organization of commercial influenza vaccines. The vaccines differ in their structural composition and identify a “spiked nanodisc” arrangement of hemagglutinin (HA) with increased display and immunogenicity of the conserved stem region of HA.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Glioma tumours are known to be heterogenous in mutation and gene expression patterns, but sampling limitations can lead to inaccurate detection of evolutionary events. Here, the authors carry out multi-omics analysis of multi-regional biopsies from 68 patients and show differential mutations in non-enhancing regions.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Large language models (LLMs) can synthesize vast amounts of information. Luo et al. show that LLMs—especially BrainGPT, an LLM the authors tuned on the neuroscience literature—outperform experts in predicting neuroscience results and could assist scientists in making future discoveries.

This study shows that a multitrophic community model jointly recapitulates diel rhythms in abundances of Prochlorococcus picocyanobacteria, as well as viral infection, viral abundances and grazer abundances. Model-data integration implies that grazing predominantly controls Prochlorococcus abundances in surface waters of the North Pacific Subtropical Gyre, despite high viral densities.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

Antibiotic resistance in Neisseria gonorrhoeae is rising, yet sometimes strains emerge that have reverted to susceptibility. Here, the authors find that selective pressures from the host may influence susceptibility through loss-of-function mutations in genes that encode for efflux pumps.

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.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

A new resource for the analysis of population genomics and quantitative traits, the Drosophila melanogaster Genetic Reference Panel is presented.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Mineral-associated soil carbon buildup is poorly explained by microbial necromass production (a common hypothesis). During litter decomposition, these processes are decoupled by priming effects and alternate soil carbon formation pathways

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Heterozygous loss of chromosome 17p is a common genomic event in castration-resistant prostate cancers (CRPC). Here, the authors use CRISPR-based screen to identify RBX1 as a target gene for CRPC with 17p loss and targeting RBX1 sensitizes CRPC to the treatment of α-amanitin antibody conjugates.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Standard DNA is limited by low information density and functional diversity. Now it has been shown that an expanded genetic alphabet—incorporating a synthetic nucleotide, dZ—allows for the creation of stable three-dimensional DNA structures under mild alkaline conditions. Such stable structures enrich our understanding of DNA’s structural diversity and its potential in synthetic biology applications.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

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.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

In vivo silencing in specific cell types remains the main obstacle for therapeutic applications of siRNAs. Leuschner et al. now show that an optimized lipid nanoparticle delivers siRNA to inflammatory monocytes in mice and, when transporting CCR2 siRNA, has therapeutic effects in cardiovascular disease, cancer and transplant rejection.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

By implanting ¹¹⁷Sn, a fibre-packaged nanophotonic diamond waveguide with optically addressable hyperfine transitions separated by 452 MHz is demonstrated. This enables the formation of a spin-gated optical switch and achieving a waveguide-to-fibre extraction efficiency of 57%.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Pioneer transcription factor Pax7 specifies melanotrope cells, which then allows for the binding of Tpit transcription factor. Here, authors find that while binding of heterochromatin targeting by Pax7 is independent of Tpit, Pax7-dependent chromatin opening requires Tpit.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

An integrated nanoscale light-emitting diode is used as an electrically driven optical source for exciting two-dimensionally localized gap plasmon waveguides with a 0.016λ² cross-sectional area. Electrically driven subwavelength optical nanocircuits for routing, splitting and directional coupling are demonstrated in compact and relatively low-loss gap plasmon waveguide structures.

Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.

A modular quantum system-on-chip architecture integrates thousands of individually addressable spin qubits in two-dimensional quantum microchiplet arrays into an integrated circuit designed for cryogenic control, supporting full connectivity for quantum memory arrays across spin–photon channels.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Exportin-1 (XPO1) was identified as the target of small molecules suppressing T cell activation. Selective disruption of the chromatin scaffolding function of XPO1 without blocking nuclear export implicates XPO1 as a target in autoimmunity.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer.

Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.

In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species.

A study reports the distribution, replication and persistence of SARS-CoV-2 throughout the human body including in the brain at autopsy from acute infection to more than seven months following symptom onset.