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Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

A spinal cord neuroprosthesis targeting leg motor neurons in real time improves walking and reduces freezing of gait in non-human primate models and in one individual with advanced Parkinson’s disease.

The relationship between striatal vascular and neural activity is not fully understood. Here the authors found neuronal activity inadequately explains striatal hemodynamic polarity, challenging classic fMRI interpretations.

Exponential growth of toxigenic Streptococcus pyogenes M1_UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1_UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.

Many microRNA encoding regions are within introns of other coding genes, and yet the molecular or functional interaction between the two is unclear. This study shows that miR-128′s function is opposed by its host gene ARPP21, and they have complementary effects on neuronal development.

Rapid insertion and extraction of lithium ions from a cathode material is imperative for lithium-ion battery function. Here, the authors present evidence of inhomogeneities in charge localization, local structural distortions and polaron formation induced upon lithiation using scanning transmission X-ray microscopy.

Taxonomy classification of amplicon sequences is an important step in investigating microbial communities in microbiome analysis. Here, the authors show incorporating environment-specific taxonomic abundance information can lead to improved species-level classification accuracy across common sample types.

Cas9 base editors are promising tools for correcting pathogenic single nucleotide mutations. Here the authors chemically modify mRNA encoding the editor and the gRNA to enhance editing and broaden its application.

Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

The antibiotic enacyloxin IIa is assembled by a modular polyketide synthase, and released from it by condensation of the enacyloxin acyl chain with 3,4-dihydroxycyclohexane carboxylic acid. A multipronged approach shows the structural basis for recognition between the peptidyl carrier protein domain that bears the acyl chain and the non-ribosomal peptide synthetase condensation domain that ligates it with the carboxylic acid.

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

Microtubule-targeting agents are used successfully as anticancer therapeutics. Here authors develop a fluorescence-anisotropy-based assay to identify and characterize ligands for the maytansine site of tubulin and provide crystal structures of identified ligands in complex with tubulin.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Changes in the leaf area index alter the distribution of heat and moisture. The change in energy partitioning related to leaf area, increasing latent and decreasing sensible fluxes over the observational period 1982–2016, is moderated by plant functional type and background climate.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

The transcription factor PU.1 is an essential regulator of the pro-fibrotic gene expression program in fibroblasts; PU.1 expression is upregulated in various fibrotic diseases, whereas inactivation of PU.1 induces regression of fibrosis in a number of organs.

The impact of late Pleistocene climate change on ecosystems has been hard to assess. Here, the authors sequence ancient DNA from Hall’s Cave, Texas and find that both plant and vertebrate diversity decreased with cooling, and though plant diversity recovered with rewarming, megafauna went extinct.

Molecular networking connects molecules based on their fragment ion mass spectra (MS²), but may leave adduct species from the same molecular family separate. To address this issue, the authors develop a networking approach that fuses MS¹- and MS²-based networks and integrate it into the GNPS environment.

In genome-wide association meta-analysis, it is often difficult to find an independent dataset of sufficient size to replicate associations. Here, the authors have developed MAMBA to calculate the probability of replicability based on consistency between datasets within the meta-analysis.

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.

Active DNA demethylation is required for sexual reproduction in plants, but the underlying mechanisms are unknown. Here, the authors show that the DNA glycosylases DEMETER and REPRESSOR OF SILENCING 1 enable the DNA demethylation-dependent activation of genes involved in pollen tube progression.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Forces that lead to stable bipolar organization of mitotic spindles are poorly understood. Here the authors show that growing interpolar microtubules make a unique contribution to the overall force balance, distinct from all other motors in the spindle.

The process of electronic energy transfer between molecules has long fascinated chemists. Femtosecond spectroscopy measurements of a series of molecular dimers now reveal signals that arise from non-Born–Oppenheimer coupling, suggesting a new mechanism to enhance energy transfer.

This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.

The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.

Here, the authors assess performance and limitations to polygenic risk scores in different race/ethnic groups. They find that polygenic risk score performance improves with diverse training data, and a better understanding of varying genetic backgrounds, social and environmental factors, and gene-environment interactions, is needed to enhance PRS performance for all groups.

A reliable digital bridge restored communication between the brain and spinal cord and enabled natural walking in a participant with spinal cord injury.

Altered expression and function of the extracellular matrix protein PRG4 have been associated with osteoarthritis. Here, the authors show that mast cell tryptase β cleaves PRG4, resulting in a reduction of lubrication and activation of inflammation in this context.

Federated learning can be used to train medical AI models on sensitive personal data while preserving important privacy properties; however, the sensitive nature of the data makes it difficult to evaluate approaches reproducibly on real data. The MedPerf project presented by Karargyris et al. provides the tools and infrastructure to distribute models to healthcare facilities, such that they can be trained and evaluated in realistic settings.

Here the authors combine a multimodal imaging-snRNAseq transcriptomics strategy to provide insight into the distribution of a neurotropic tick-borne flavivirus in the brain, and show that absence of interferon signaling increases infection of resident microglia.

Here, the authors show the amyloid formation of a low-complexity domain of NCAP, and its potential for guiding the design of antiviral agents.

Single cell profiling of tissue from patients undergoing therapy has the potential to identify drug-induced immune changes. Here the authors show a skin scRNA-seq study of psoriasis patients treated with an IL-23 inhibitor and characterize changes in cell states during early treatment.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Large-scale, multimodal phenotypic characterisation is a valuable tool to explore brain function. Poldrack et al. collect and relate MRI, psychological, physiological, metabolic and gene expression data from a single human over an 18 month period, providing a rich resource for future studies.

Adaptation in diploids is poorly understood. Here, the authors show a slower rate of adaptation and a shift towards adaptive dominant mutations in long-term experimental evolution of diploid strains of the yeast Saccharomyces cerevisiae.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

This paper examines eight individual genomes using a clone-based sequencing approach, for structural variants of 8,000 nucleotides or more. One of the first high-quality inversion maps for the human genome is generated, and it is demonstrated that previous estimates of variation of this sort have been too high.

The selection of polymeric dielectric materials for energy storage applications is not trivial, as several criteria must be satisfied simultaneously. Here, Sharma et al.present a high-throughput hierarchical strategy using the band gap and dielectric constant to screen and identify good candidates.

Identifying the mutational landscape of tumours from cell-free DNA in the blood could help diagnostics in cancer. Here, the authors present ichorCNA, software that quantifies tumour content in cell free DNA, and they demonstrate that cell-free DNA whole-exome sequencing is concordant with metastatic tumour whole-exome sequencing.

Previous genome-wide association studies have identified loci associated with the risk of multiple myeloma. Here, the authors present a meta-analysis of six genome wide association studies of the disease and identify eight new loci; functional studies identify genes as candidates for the basis of these associations.