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Neutrophils are increased in response to injury and infection but how they form from a common granulocyte-macrophage progenitor is unclear. Here, the authors identify a role for the transcriptional repressor ZBTB11 in zebrafish, which is regulated by master myeloid regulators and repressesTP53.

This study investigates the effects of forestation on temperature in Europe using climate model experiments. The findings indicate that conversion from coniferous to broadleaved trees in currently forested areas can provide cooling for summer hot extremes.

Here, the authors discuss explanations for missing disease-causing variants in Alport syndrome, how clinicians and laboratories might manage missing variants and how to care for patients when a clinical suspicion of Alport syndrome exists but no disease-causing variant has been identified.

The role of CXCR2 in epithelial and endothelial cells on lung infection remains unclear. The authors here use conditional CXCR2 knockout mice to manifest that epithelial and vascular CXCR2 mediates transcytosis of CXCL1, leading to neutrophil infiltration and controlled lung inflammation.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

Disruption of neocortical circuitry and architecture causes neurodevelopmental disorders. Here the authors find that migration and axon projection of upper layer neurons are dependent on Sema7A-Sema4D heterodimerization, and that insufficient transcription of Sema7A or incomplete glycosylation of Sema4D inhibit these processes.

Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours.

Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Serino et al. show that seeing an infectious avatar approach the body in virtual reality triggers an immune response, indicating that the brain prepares the body to fight infections even for perceived, but not real, threats.

This study reveals that brain aberrations after preterm birth are highly individual yet shaped by early injury and social environment, influencing long-term cognitive outcomes.

Loss-of-function variants of ABCA7, associated with Alzheimer’s disease, result in disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways in the human brain.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Castleman disease encompasses a group of disorders characterised by abnormal lymph node morphology. Here the authors use single cell and spatial transcriptomics to assess the stromal, immune and interaction architecture of different subtypes of Castleman disease, indicating potential ligand-receptor interactions between immune cells.

The authors present a characterization of complex X-linked lncRNA loci with sex- and allele-specific epigenetic signatures that serve as a platform for the largest chromatin structures in mammals, thereby elucidating diverse phenotypes and combinatorial effects on autosomes.

Master transcription factors dominantly direct cell fate and barriers ensuring their tissue specific silencing are not clearly defined. Here, the authors demonstrate that inefficient targeted transactivation of Sox1 in neural progenitor cells is surmountable through targeted promoter demethylation using dCas9-Tet1.

Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

Genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2 identify mucins as key host factors restricting viral infection.

Clonal hematopoiesis of indeterminate potential (CHIP) was found to be associated with a protective effect from Alzheimer’s disease (AD) in large population-based cohorts.

Linterman and colleagues examine germinal center formation in older individuals. They find that aged T_FH cells have dysregulated CXCR4 expression, which causes spatial mislocalization of these cells in germinal centers, impairing their ability to provide help to B cells and to promote antibody production.

Parsons and colleagues characterize age-associated changes in the tumor microenvironment of triple-negative and estrogen receptor-positive breast cancer using computational analysis of transcriptomic data, paired with immunostaining of independently collected samples.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Single-nucleus and spatial, whole-transcriptome profiling of 43 pancreatic adenocarcinomas provides a refined molecular and cellular classification, highlighting a new neoadjuvant treatment-associated neural-like progenitor tumor cell state.

The prognostic value of OCT in progressive vs relapsing multiple sclerosis (MS) is not clear. Analyzing 2651 OCTs of 407 MS patients, OCT predicted activity in all MS subtypes cross sectionally but longitudinal changes were not predictive in a multicenter setting.

Microglia in the aging hippocampus accumulate lipid droplets, and are functionally impaired and inflamed. Lipid droplet formation in microglia is regulated by genes linked to neurodegeneration such as progranulin.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

HAESA and HSL2 are receptors for IDA/IDL-family signaling peptides in plants. Here the authors show that HSL1, previously shown to recognize CLE9, preferentially binds IDA/IDL peptides and regulates leaf epidermal patterning independently of CLE peptides.

Twelve early-career researchers who embarked on their independent research paths in 2024 reflect on their experience from their journey so far, describe the opportunities they received and the challenges they faced, and share their hopes and plans for the future.

Whole genome sequencing (WGS) holds promise to solve a subset of Mendelian disease cases for which exome sequencing did not provide a genetic diagnosis. Here, Wells et al. report a supervised machine learning model trained on functional, mutational and structural features for rank-scoring and interpreting variants in non-coding regions from WGS.

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.

Simultaneous activation of Wnt and Shh pathways in murine neural precursor cells results in the formation of embryonal tumors with multilayered rosettes (ETMR) that recapitulate the histological and molecular features of human tumors. This novel mouse model represents a platform for evaluating therapeutic approaches for this rare malignant pediatric brain tumor, and provides novel insights into the cell of origin and molecular mechanisms driving the disease.

CD32 has been previously shown to be expressed preferentially by CD4 T cells latently harbouring HIV-1. Here the authors show that CD32 expression in CD4 T cells is associated with T cell activation, is up-regulated by HIV-1 infection and importantly does not appear to represent an enriched cellular niche for latent HIV-1.