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Antibiotic resistance poses a significant threat to global health, necessitating new strategies to combat resistant pathogens. Here, the authors develop triazole analogues targeting the bacterial kinase APH(2”)-IVa, demonstrating promising selectivity, permeability, and moderate efficacy against P. aeruginosa, suggesting a potential pathway to restore the efficacy of aminoglycoside antibiotics.

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.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

A protein condensate formed by multivalent interactions between the long non-coding RNA Xist and specific RNA-binding proteins drives the compartmentalization required to perpetuate gene silencing on the inactive X chromosome.

Treatments to rescue vision are currently limited. Here, the authors identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in humans. They also show that activating laterally projecting cells results improved vision in two mouse models of retinal degeneration.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.

Astrocytes regulate synaptic transmission. Carlsen et al. report that spinal astrocytes activated by endocannabinoids inhibit excitatory synaptic transmission and, thereby, decrease tremor.

In many survivors of Ebola virus infection, antibody responses show long-term patterns of decline followed by restimulation, possibly owing to recrudescence of persisting virus.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Sleep is essential for homeostasis and insufficient or excessive sleep are associated with adverse outcomes. Here, the authors perform GWAS for self-reported habitual sleep duration in adults, supported by accelerometer-derived measures, and identify genetic correlation with psychiatric and metabolic traits

Patients with metastatic soft-tissue sarcoma can benefit from systemic therapy, but the best drug combinations for the different disease subtypes remain to be established. Recently, great emphasis has been placed on histology-based chemotherapy regimens. Herein, we discuss the results of a recently published study demonstrating that some of these regimens are not superior to standard-of-care chemotherapy in the neoadjuvant setting.

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.

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

In the geographically and taxonomically divided systems of vertebrates in the Living Planet Index, a small percentage of clusters showed extreme declines or increases, whereas most vertebrate populations across all systems showed no mean global trend.

An integrated genomic analysis of 456 human pancreatic ductal adenocarcinomas identifies four subtypes defined by transcriptional expression profiles and show that these are associated with distinct histopathological characteristics and differential prognosis.

Proteoforms arise as protein isoforms or as protein haplotypes, which are the result of genetic variation. Here, the authors develop Haplosaurus, a database that computes protein haplotypes genome-wide from existing genotype data and analyse protein haplotype variability in the 1000 Genomes dataset.

GWAS have previously found 24 genomic loci associated with chronotype, an individual’s preference for early or late sleep timing. Here, the authors identify 327 additional loci in a sample of 697,828 individuals and further explore the relationships of chronotype with metabolic and psychiatric diseases.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

A 471-metagenome time series from Lake Mendota in Wisconsin, USA, reveals seasonal and decadal shifts in bacterial functional and ecological dynamics, especially in response to environmental extremes.

Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Reduced GHG and air pollutant emissions during the COVID-19 lockdowns resulted in declines in NO_x emissions of up to 30%, causing short-term cooling, while ~20% SO₂ emissions decline countered this for overall minimal temperature effect.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Renin cells have traditionally been associated with the kidney where they regulate blood pressure and fluid electrolyte homeostasis. In this study, Belyea et al.describe a renin progenitor in the bone marrow that gives rise to B-cell leukaemia when RBP-J, the final effector of the Notch pathway, is deleted.

The assembly of the genome of the koala provides insights into its adaptive biology and identifies gene expansions that contribute to its ability to detoxify eucalyptus-derived compounds and perceive plant secondary metabolites.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The telomere position effect (TPE) can change gene expression at intermediate telomere lengths in cultured human cells, but it has not been previously implicated in disease pathogenesis. A gene implicated in facioscapulohumeral muscular dystrophy (FSHD) pathogenesis, and located adjacent to a chromosome end, is now shown to be upregulated in muscle cells with short telomeres, which suggests that TPE contributes to the late-onset phenotype of FSHD.

Multi-ancestry genome-wide association analyses for birth weight in 153,781 individuals identified 60 genomic loci in which birth weight and fetal genotype were associated and found an inverse genetic correlation between birth weight and cardiometabolic risk.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

The globally-distributed Ranidae (true frogs) are the largest frog family. Here, Hammond et al. present a draft genome of the North American bullfrog, Rana (Lithobates) catesbeiana, as a foundation for future understanding of true frog genetics as amphibian species face difficult environmental challenges.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

A massive compliation of molecular data to shows that not only did mammalian evolution have deep roots, but that the extant Orders of mammals did not become established until many millions of years after the dinosaurs had headed for their last round-up. In other words, the great end-Creatceous mass extinction had relatively little effect on mammal evolution.

The beetle Tribolium castaneum is a commonly used laboratory model, combining the ease of systematic RNAi experiments like those in Caenorhabditis elegans, with biology that is more representative of most insects than Drosophila melanogaster. A large consortium has sequenced and analysed the genome of the red flour beetle, creating a resource for biologists everywhere.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Comparative study of 81 genomes of parasitic and non-parasitic worms identifies gene family births and expanded gene families at key nodes in the phylogeny that are relevant to parasitism and proteins historically targeted for drug development.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.