Fate transitions in Drosophila neural lineages: a single cell road map to mature neurons.

Brain development requires the formation of thousands of neurons and glia and their coordinated maturation to ensure correct circuit formation. Neuronal fate is determined by several layers of gene regulatory networks during neuronal lineage progression. Once specified, neurons must still undergo a critical maturation period, involving the stepwise expression of functional feature genes such as cell surface molecules, ion channels or neurotransmitter receptors. The precise mechanisms that govern neuronal maturation remain however poorly understood. Here, we use single-cell RNA sequencing combined with a conditional genetic strategy to select and analyse neural lineages and their young progeny at a restrictive timepoint to investigate the transcriptional trajectories in young developing secondary neurons in the Drosophila larval brain. Our findings reveal that neuron maturation starts very quickly after neuronal birth, and sub-divide the process of maturation into 3 distinct phases: Phase 1 is composed by immature neurons that have yet to start expressing mRNA of mature neuronal features; Phase 2 includes neurons that start transcribing but not translating maturation markers such as neurotransmitter genes; Phase 3 neurons start translating mature neuronal features, in a coordinated fashion with the animal developmental stage. This dataset represents a complete transcriptomic characterization of the neural lineages generated at this larval stage in the central brain and ventral nerve cord. Its analysis has also allowed for the characterization of a yet undefined transitional state, the immature ganglion mother cells, and has proven useful for the identification of known and novel fate regulators.

Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4–7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia–Reperfusion

The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.

The jellyfish genome sheds light on the early evolution of active predation

BackgroundUnique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column. One of the first animals to become free-swimming, jellyfish employ pulsed jet propulsion and venomous tentacles to capture prey.ResultsTo understand these key innovations, we sequenced the genome of the giant Nomura’s jellyfish (Nemopilema nomurai), the transcriptomes of its bell and tentacles, and transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains; possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes, and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation).ConclusionsTaken together, the jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits that have combined to make these animals one of the world’s earliest and most successful multi-cellular predators.

The epidemiology and genetics of binge eating disorder (BED)

This narrative review provides an overview of the epidemiology of binge eating disorder (BED), highlighting the medical history of this disorder and its entry as an independent condition in the Feeding and Eating Disorders section of the recently publishedDiagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Estimates of prevalence are provided, as well as recognition that the female to male ratio is lower in BED than in other eating disorders. Evidence is also provided of the most common comorbidities of BED, including mood and anxiety disorders and a range of addiction disorders. In addition, discussion of the viewpoint that BED itself may be an addiction — at least in severe cases — is presented. Although the genetic study of BED is still in its infancy, current research is reviewed with a focus on certain neurotransmitter genes that regulate brain reward mechanisms. To date, a focal point of this research has been on the dopamine and the μ-opioid receptor genes. Preliminary evidence suggests that a predisposing risk factor for BED may be a heightened sensitivity to reward, which could manifest as a strong dopamine signal in the brain’s striatal region. Caution is encouraged, however, in the interpretation of current findings, since samples are relatively small in much of the research. To date, no genome-wide association studies have focused exclusively on BED.

A Framework to Examine the Role of Epigenetics in Health Disparities among Native Americans

Background. Native Americans disproportionately experience adverse childhood experiences (ACEs) as well as health disparities, including high rates of posttraumatic stress, depression, and substance abuse. Many ACEs have been linked to methylation changes in genes that regulate the stress response, suggesting that these molecular changes may underlie the risk for psychiatric disorders related to ACEs.Methods. We reviewed published studies to provide evidence that ACE-related methylation changes contribute to health disparities in Native Americans. This framework may be adapted to understand how ACEs may result in health disparities in other racial/ethnic groups.Findings. Here we provide evidence that links ACEs to methylation differences in genes that regulate the stress response. Psychiatric disorders are also associated with methylation differences in endocrine, immune, and neurotransmitter genes that serve to regulate the stress response and are linked to psychiatric symptoms and medical morbidity. We provide evidence linking ACEs to these epigenetic modifications, suggesting that ACEs contribute to the vulnerability for developing psychiatric disorders in Native Americans.Conclusion. Additional studies are needed to better understand how ACEs contribute to health and well-being. These studies may inform future interventions to address these serious risks and promote the health and well-being of Native Americans.