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The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

Survey results suggest a rise in questioning of scientific evidence.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

In drug discovery and repurposing, systematic analysis of genome-wide gene expression of chemical perturbations on human cell lines is a useful approach, but is limited due to a relatively low experimental throughput. Computational, deep learning methods can help. In this work a graph neural network called Deep Chemical Expression is developed that can predict chemical-induced gene expression profiles. It is applied to identify drug repurposing candidates for COVID-19 treatments.

Sinha and colleagues present PERCEPTION, a precision oncology computational pipeline that can predict the response and resistance of patients by analyzing single-cell transcriptomic data from their tumor samples.

Pregnancy is associated with stress and multi-system physiological changes. This study used aging clock generated from lab tests to show pregnant females’ apparent age dropped in the first trimester, rose toward delivery, and recovered postpartum.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

A FRET-based assay using the conserved tryptophans of bacterial quorum-sensing LuxR-type proteins and synthetic fluorophore-acyl-homoserine lactone conjugates enables measurement of ligand-binding affinities either in vitro or in cells.

A continuum of acoustically varying speech sounds is not perceived as a continuum, but as distinct phonetic categories. Chang et al. recorded directly from human posterior superior temporal gyrus and found that this area has a similarly discontinuous coding of objectively continuous sound, matching perception and indicating higher-level processing.

Mouse study suggests stem-cell work could be made more efficient.

Here the authors combine clinical and metabolomics data to identify distinct metabotypes of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD). The results provide information regarding heterogeneity of MASLD presentation, but require validation in independent cohorts.

Chronic stress disrupts the brain vasculature and contributes to mood disorders, but mechanisms of resilience remain unclear. Here, the authors show that enriched environments increase astrocytic Fgf2 to prevent stress-induced vascular alterations and depressive behavior with relevance to human depression.

Here, the authors integrate genomic, proteomic, and phenotypic data from UK Biobank, identifying over 1,100 gene-environment interactions. They catalogue interactions between 101 blood proteins and 153 exposures, which may refine biomarker discovery.

In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.

Engineered DNA recombinases efficiently and specifically insert genetic cargos without the use of landing pads.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Inducible nitric oxide (NO) synthase (iNOS) is essential in the response to mycobacterial infection, yet NOS signalling can occur through NO-dependent or NO-independent pathways. Here the authors show macrophage Gch1 and tetrahydrobiopterin mediate NO-independent control of Mycobacterial infection.

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Which brain circuits are causally involved in depression? Using the human connectome as a wiring diagram, Siddiqi et al. combine data from lesions, deep brain stimulation and transcranial magnetic stimulation studies to show that these three methods converge in identifying a single depression circuit.

Here they generate a cell type atlas of the colonial cnidarian Hydractinia symbiolongicarpus, which reveals that distinct colony parts are mostly made from unique combinations of shared cell types, and identify novel cell types involved in biomineralization, and self/non-self recognition.

The authors present palaeoclimatic data in the form of stable isotope records from equid teeth spanning 12,500 years of human occupation at the site of Ilsenhöhle in Ranis, Germany, including the earliest occupation of the site by Homo sapiens ~45,000 years ago.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

A multiscale photoproximity labeling proteomics workflow captures dynamic neighborhoods of extracellular and intracellular epidermal growth factor (EGF) receptor interactomes during early, middle and late signaling upon activation by EGF.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

In the highly competitive world of cell and molecular biology, there are no prizes for coming second. But is the pressure to be the first to publish 'hot' results distorting scientific progress? Helen Pearson investigates.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Brain oscillations may be disrupted in children with autism spectrum disorder. The authors performed a longitudinal study of electroencephalography recordings and found that EEG recordings from the first year after birth can distinguish healthy children from children with autism spectrum disorder.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

How research could help reclaim months of lost education for billions of school students around the world.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.

Ultraendurance racers torture their bodies and minds to achieve near-impossible physical feats. Is it an exceptional genetic make-up or the vestiges of human evolution? Helen Pearson reports.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Autoimmune encephalitis (AIE) may involve neuron-specific cytotoxic T cells, but evidence is still lacking. Here the authors use induced pluripotent stem cells from patients with AIE and single cell RNA-sequencing of ex vivo CD8 T cells to find neuron-specific, KIR⁺CD8⁺ T cells with altered transcriptome that potentially contribute to AIE etiology.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

A single-cell transcriptomic analysis of endometriosis, endometriomas, eutopic endometrial samples and uninvolved ovary tissues highlights cell populations characteristic of these tissue types. Transcriptional and cellular heterogeneity across tissues suggests novel therapeutic targets and biomarkers for this disease.

A machine learning approach is used to analyse multi-omics (proteomics, metabolomics and transcriptomics) data, producing genetic scores for more than 17,000 biomolecular traits in human blood, and identifying possible associations with disease.

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma. Here we show that identification of clonal somatic copy number alterations in frequently amplified cancer genes could inform therapeutics for precision medicine.

The nucleus accumbens (NAc) controls reward learning and motivated behaviors. Here, authors show that the neuropeptide gastrin-releasing peptide regulates the excitability of subpopulations of NAc neurons and modulates motivated behavior in mice.

TUG protein localizes to the endoplasmic reticulum-Golgi intermediate compartment, forms biomolecular condensates, and organizes and stabilizes these membranes to support their function in diverse secretory and degradative trafficking pathways.

Copy number alterations in stem cells impair neural crest differentiation and set the stage for neuroblastoma-like traits and tumours. This study hints at early tumourigenesis mechanisms and finds developmental gene signatures linked to prognosis.

The first controlled human infection model of cutaneous leishmaniasis transmitted by sand flies enables assessment of immune responses and parasitism in infected participants that can inform future vaccine and therapeutic development.

Oncoprotein transcription factor MYC undergoes phase separation, forming transcriptionally active condensates. The chemogenetic tool SPARK-ON reveals that MYC phase separation selectively modulates the transcriptome and promotes cell proliferation.

To dissect evolution, Joe Thornton resurrects proteins that have been extinct for many millions of years. His findings rebut creationists and challenge polluters.

Saturation genome editing characterizes BAP1 variants and their association with disease presentation. A phenome-wide association analysis in the UK finds that BAP1 variants identified as deleterious in the study are associated with higher serum IGF-1 levels.