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Deep brain stimulation tuned to cue-reactivity within the nucleus accumbens region reduced drug cravings, heralding an evocation-based programming strategy for opioid use disorder.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

KMT2A rearranged infant acute lymphoblastic leukemia patients have a poor prognosis. Here, the authors use high throughput drug screening on primary infant specimens to identify a clinically active chemotherapy combination.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

The caudal ventrolateral medulla was thought to be involved in pain control, but its pathway was unknown. Here, Gu et al. identify the molecular components of a caudal ventrolateral medulla–locus coeruleus–spinal cord pathway and show it has a role in counter-stimulus pain control.

To better understand the etiology of frailty, the authors perform a large genetic study. They identified 45 additional variants and implicated MET, CHST9, ILRUN, APOE, CGREF1 and PPP6C as potential causal genes, linking frailty to immune regulation, metabolism and cellular signaling.

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

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Catecholaminergic neurons of the ventrolateral medulla are known to drive diverse glucose counterregulatory responses to hypoglycemia. Here, the authors show that projections from these neurons onto nucleus accumbens-targeting neurons of the midline thalamus selectively mediate hypoglycemic feeding.

The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

The analysis of mammalian transcriptomes could provide new insights into human biology. Here the authors carry out RNA sequencing in a large collection of mouse tissues and compare these data to human transcriptome profiles, identifying a set of constrained genes that carry out basic cellular functions with remarkably constant expression levels across tissues and species.

Genome-wide association studies of individuals from an isolated population (data from the Finnish biobank study FinnGen) and consequent meta-analyses facilitate the identification of previously unknown coding variant associations for both rare and common diseases.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Huang et al. demonstrate that somatostatin (Sst)-expressing primary afferents are pruriceptors. In spinal cord, they show that Sst potentiates itch by disinhibition involving dynorphin-expressing spinal neurons and that Sst also suppresses pain.

In this study authors use morphological profiling and CRISPR/Cas9 genetic screens to investigate the mechanisms by which BiDACs induce the degradation of plasma membrane receptor tyrosine kinases (RTKs) EGFR and Her2.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

A genome-wide association study suggests 41 previously unreported loci on top of the 23 known loci that influence the disease risk for lumbar disc herniations. Many of these loci harbour genes implicated in disc structure and inflammation, as well as genes related to the nervous system and nerve function.

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

A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs.

The authors show how concepts from metasurface flat optics and folded optics can be combined to push the limits in miniaturization of optical systems. Such optical systems can be fabricated using low-index materials, opening up a path for large-area fabrication using nanoimprint lithography.

Mouse fibroblasts can be simultaneously directly reprogrammed into cardiomyocytes, endothelial cells and smooth muscle cells to form cardiac tissue structures that improve cardiac function on implantation into infarcted mouse hearts.

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.

The use of chalcogenide glasses in simple electronic devices, such as a p-n junction, is hindered by the lack of n-type material. Here, Hughes et al.demonstrate n-type doping of GeTe and GaLaSO amorphous films using bismuth-ion implantation.

A microchannel made from InSb, which has current–voltage characteristics that are strongly dependent on the sign and magnitude of an applied magnetic field, is used to demonstrate that circuits made from such structures can be programmed — and reprogrammed — to perform elementary logic functions, such as AND, OR, NAND and NOR.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking Aβ fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.

Many genetic factors that contribute to uterine leiomyomata (UL) - the most common tumours of the female genital tract - remain to be discovered. Here, the authors conduct a UL meta-genome-wide association study, and find loci related to altered muscle tissue biology that are associated with UL.

A universal mechanical exfoliation method of creating freestanding membranes of complex-oxide materials with different crystal structures and orientations and stacking them to produce a range of artificial heterostructures with hybridized physical properties is described.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

A systematic analysis of lignin biosynthetic genes to quantitatively understand their effect on wood properties is still lacking. Here, the authors integrate transcriptomic, proteomic, fluxomic and phenomic data to quantify the impact of perturbations of transcript abundance on lignin biosynthesis and wood properties.

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement.

Vessels used mainly for seabed surveys will expand in focus.

The design and implementation of a high-yielding enzymatic route to 1,4-butanediol—a compound not known to be produced naturally—provides a compelling example of how metabolic engineering can be harnessed for the microbial conversion of carbohydrate feedstocks to desired small molecules.

Using in vivo spinal cord two-photon calcium imaging, the authors provide the first comprehensive characterization of the representations of temperature in the spinal cord and reveal that spinal neurons encode temperature change for cold and absolute temperature for heat.

Hypoxia in germinal centres regulates B cell class switching via its effects on mTOR complex 1 and activation-induced cytosine deaminase activity.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

Pain and itch are very distinct sensations that rely on both overlapping and orthogonal mechanisms in primary sensory afferents and in the spinal cord. In this article, Bautista, Wilson and Hoon review recent advances in our understanding of the molecular, cellular and circuit basis of acute and chronic itch in the peripheral and central nervous systems.

On wounding, scar formation in mammals arises causing no hair follicle regeneration, but it is unclear if scarring precludes regeneration. Here, the authors show that if Sonic hedgehog signaling is activated in the wound, an inductive dermal niche forms, enabling regeneration and hair follicle formation.