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In a mouse model of multiple sclerosis, trafficking into the brain parenchyma of the peripheral myeloid cells that are involved in the symptomaptology is shown to occur predominantly via the velum interpositum, a leptomeningeal tract that runs underneath the hippocampal formation.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

A polyA-tail-directed RNA sequencing approach that was used to investigate transcriptomic changes in dorsal root ganglia following nerve crush revealed unexpected upregulation of a specific set of B2-SINE transcriptional regulators that facilitate neuronal repair by co-ordinating axon transport and local translation.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The hypothalamic preoptic area is involved in numerous homeostatic and social behaviours, and the neurons of this area are shown in this study to consist of numerous subtypes that show diverse maturational profiles that correlate with periods of substantial behavioural change such as weaning and puberty.

A possible mechanism underlying the worsening of asthma symptoms after eating is found in mice, where type 2 immunity in the lung (which is a primary driver of asthma) is found to be potentiated by food intake.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A possible mechanism for the increased incidence of mood disorders in people with immune system disorders such as psoriasis is revealed where, in mice, elevated serum levels of the cytokines IL-17A and IL-17C induce anxiety-like symptoms via activation of neurons in the anterior basolateral amygdala.

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.

A population of macrophages has been found in muscle spindles that release glutamate, activate primary sensory afferents that are part of the stretch reflex, and have a role in regulating locomotion.

Interoceptive, feeding-related inputs are integrated by BDNF-expressing neurons in the ventromedial hypothalamus that project to the brainstem and regulate food intake and feeding-associated jaw movements.

After injury, regeneration of retinal ganglion cells and reconnection to their original target — the suprachiasmatic nucleus —is achieved by manipulating guidance cues, leading to the formation of a functional circuit that supports functional recovery.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

An anterior cingulate cortex to lateral septum circuit underlies the drive of spiny mice to affiliate with larger groups in preference to smaller ones.

Most astrocytes in the mouse brain have a primary cilium that transduces local cues to drive distinct astrocytic transcriptomic programmes that determine regional astrocytic subtypes, and, in turn, shape local circuits and influence behaviour.

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.

The maladaptive reward learning associated with morphine administration is shown here to be mediated by changes in dopamine-release dynamics in reward circuitry resulting from increased myelination specifically in the ventral tegmental area.

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.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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.

The main direction of motor skill-specific information between rat primary motor cortex and dorsolateral striatum is shown to switch from cortex-predominant before learning to striatum-predominant after learning.

One of the long-term sequelae associated with SARS-CoV-2 infection is ‘brain fog’, which is shown in this study to be linked to systemic inflammation and leakiness of the blood–brain barrier.

Innate fear-like responses are thought to involve the amygdala, but here a tetra-synaptic pathway is identified that mediates odour-evoked innate fear in mice.

Glucagon is hormone that signals via a dedicated g-protein coupled receptor, but downstream signaling is poorly understood. Here, Wu et al. uncover liver glucagon signaling using phosphoproteomics and define a role for the vesicle trafficking protein SEC22B in distinct metabolic actions.

Around 10% of individuals with frontotemporal lobar dementia have amyloid filament inclusions that lack tau and TDP-43 and were thought to contain the protein FUS, but are found instead to contain the FUS homologue TAF15.