Background-Rats with extended daily cocaine access show escalating cocaine selfadministration and behavioral signs of dependence. Regulation of glutamatergic transmission by metabotropic glutamate receptors (mGluR) has emerged as a mechanism in the addictive actions of drugs of abuse. We examined here whether neuroadaptive dysregulation of mGluR function is a factor in escalating cocaine self-administration.

Brassica napus , an allotetraploid crop, is hypothesized to be a hybrid from unknown varieties of Brassica rapa and Brassica oleracea . Despite the economic importance of B. napus , much is unresolved regarding its phylogenomic relationships, genetic structure, and diversification. Here we conduct a comprehensive study among diverse accessions from 183 B. napus (including rapeseed, rutabaga, and Siberian kale), 112 B. rapa , and 62 B. oleracea and its wild relatives. Using RNA-seq of B. napus accessions, we define the genetic diversity and sub-genome variance of six genetic clusters. Nuclear and organellar phylogenies for B. napus and its progenitors reveal varying patterns of inheritance and post-formation introgression. We discern regions with signatures of selective sweeps and detect 8,187 differentially expressed genes with implications for B. napus diversification. This study highlights the complex origin and evolution of B. napus providing insights that can further facilitate B. napus breeding and germplasm preservation.

Polyploidy is increasingly seen as a driver of both evolutionary innovation and ecological success. One source of polyploid organisms’ successes may be their origins in the merging and mixing of genomes from two different species (e.g., allopolyploidy). Using POInT (the Polyploid Orthology Inference Tool), we model the resolution of three allopolyploidy events, one from the bakers’ yeast (Saccharomyces cerevisiae), one from the thale cress (Arabidopsis thaliana) and one from grasses including Sorghum bicolor. Analyzing a total of 21 genomes, we assign to every gene a probability for having come from each parental subgenome (i.e., derived from the diploid progenitor species), yielding orthologous segments across all genomes. Our model detects statistically robust evidence for the existence of biased fractionation in all three lineages, whereby genes from one of the two subgenomes were more likely to be lost than those from the other subgenome. We further find that a driver of this pattern of biased losses is the co-retention of genes from the same parental genome that share functional interactions. The pattern of biased fractionation after the Arabidopsis and grass allopolyploid events was surprisingly constant in time, with the same parental genome favored throughout the lineages’ history. In strong contrast, the yeast allopolyploid event shows evidence of biased fractionation only immediately after the event, with balanced gene losses more recently. The rapid loss of functionally associated genes from a single subgenome is difficult to reconcile with the action of genetic drift and suggests that selection may favor the removal of specific duplicates. Coupled to the evidence for continuing, functionally-associated biased fractionation after the A. thaliana At-α event, we suggest that, after allopolyploidy, there are functional conflicts between interacting genes encoded in different subgenomes that are ultimately resolved through preferential duplicate loss.

Assignment of cell types from single-cell RNA sequencing (scRNA-seq) data remains a time-consuming and error-prone process. Current packages for identity assignment use limited types of reference data and often have rigid data structure requirements. We developed the clustifyr R package to leverage several external data types, including gene expression profiles to assign likely cell types using data from scRNA-seq, bulk RNA-seq, microarray expression data, or signature gene lists. We benchmark various parameters of a correlation-based approach and implement gene list enrichment methods. clustifyr is a lightweight and effective cell-type assignment tool developed for compatibility with various scRNA-seq analysis workflows. clustifyr is publicly available at https://github.com/rnabioco/clustifyr

Objective: Oxytocin (OT) is synthesized within the paraventricular nucleus and supraoptic nucleus of the hypothalamus. In addition to its role in uterine contraction, OT plays an important antinociceptive role; however, the underlying molecular mechanisms of antinociceptive role of OT remain elusive. We hypothesized that the antinociceptive effect of OT on neuropathic pain may occur via inhibition of TRPV1 activation in the spinal cord. The present study explores the antinociceptive role of OT and its mechanisms in neuropathic pain.Methods: Partial sciatic nerve ligation (pSNL) was performed to induce neuropathic pain. Animal behaviors were measured using a set of electronic von Frey apparatus and hot plate. Electrophysiological recordings and molecular biological experiments were performed.Results: Intrathecal administration of OT alleviated both mechanical allodynia and thermal hyperalgesia in pSNL rats (n = 6, per group, P < 0.0001, saline vs. OT group). Electrophysiological data revealed that OT significantly inhibited the enhancement of frequency and amplitude of spontaneous excitatory post-synaptic currents induced presynaptically by TRPV1 activation in the spinal cord. Moreover, the inhibitory effect of OT on capsaicin-induced facilitation of excitatory transmission was blocked by co-treatment with saclofen, while intrathecal administration of OT dramatically inhibited capsaicin-induced ongoing pain in rats, (n = 6, per group, P < 0.0001, saline vs. OT group). The paw withdrawal latency in response to heat stimulation was significantly impaired in TRPV1KO mice 3 days after pSNL upon OT (i.t.) treatment, compared with wild type mice (n = 6, P < 0.05). Finally, OT prevented TRPV1 up-regulation in spinal cords of pSNL model rats.Conclusion: OT relieves neuropathic pain through GABA release and presynaptic TRPV1 inhibition in the spinal cord. OT and its receptor system might be an intriguing target for the treatment and prevention of neuropathic pain.