Single-Nucleus Transcriptional Profiling of GAD2-Positive Neurons From Mouse Lateral Habenula Reveals Distinct Expression of Neurotransmission- and Depression-Related Genes.

Background: Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understanding control of motivated behaviors.

Methods: A small population of neurons within the medial subnucleus of the mouse LHb express the GABAergic (gamma-aminobutyric acidergic)-synthesizing enzyme GAD2, and they can inhibit nearby LHb projection neurons; however, these neurons lack markers of classic inhibitory interneurons, and they coexpress the vesicular glutamate transporter VGLUT2.

Single-nucleus transcriptional profiling of GAD2-positive neurons from mouse lateral habenula reveals distinct expression of neurotransmission- and depression-related genes.

Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understanding control of motivated behaviors. A small population of neurons within the medial subnucleus of the mouse LHb express the GABAergic synthesizing enzyme GAD2, and they can inhibit nearby LHb projection neurons; however, these neurons lack markers of classic inhibitory interneurons and they co-express the vesicular glutamate transporter VGLUT2.

Streptomyces spiramenti sp. nov., isolated from a deep-sea microbial mat.

Strain 5675061 was isolated from a deep-sea microbial mat near hydrothermal vents within the Axial Seamount caldera on the Juan de Fuca Ridge (NE Pacific Ocean) and was taxonomically evaluated using a polyphasic approach. Morphological and chemotaxonomic properties are consistent with characteristics of the genus Streptomyces: aerobic Gram-stain-positive filaments that form spores, L,L-diaminopimelic acid in whole-cell hydrolysates, and iso-C as the major fatty acid. Phylogenetic analysis, genomic, and biochemical comparisons show close evolutionary relatedness to Streptomyces lonarensis NCL716, S.

Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine.

Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei from the NAc of male and female mice following acute or repeated exposure to amphetamine (AMPH) and sequenced for cell type-specific RNA expression and chromatin accessibility. AMPH regulated the transcription of hundreds of genes in PV+ interneurons, and this program was largely distinct from that regulated in other NAc GABAergic neurons.

Draft Genome Sequence of sp. Strain ventii, Isolated from a Microbial Mat near Hydrothermal Vents within the Axial Seamount in the Pacific Ocean, and Resequencing of the Type Strains Streptomyces lonarensis NCL 716 and Streptomyces bohaiensis 11A07.

The draft genome of sp. strain ventii, an environmental isolate recovered from deep-sea hydrothermal vents in the Pacific Ocean, is presented along with the resequenced draft genomes of the type strains 11A07 and NCL 716.

Athletic trainers' unique clinical and teamwork skills contribute on the frontlines during the COVID-19 pandemic: A discussion paper.

Crises such as pandemics create stresses on the health-care system that often produce innovation and changes in roles and delivery methods. In the current pandemic, and with the interruption of organized sport activities, athletic trainers have moved beyond traditional hierarchies and scopes of practice to roles that fully leverage their knowledge, skills, and abilities. Through background literature, discussion, and examples, this paper shows how the Athletic Training profession has made an impact in the response to the COVID-19 pandemic.

A striatal interneuron circuit for continuous target pursuit.

Most adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here, we show that in the sensorimotor striatum, parvalbumin-positive fast-spiking interneurons (FSIs) can represent the distance between self and target during pursuit behavior, while striatal projection neurons (SPNs), which receive FSI projections, can represent self-velocity.

Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes.

Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained unknown. We used single-cell in situ transcriptional analysis to show that Fos and Npas4 are transcribed in stochastic bursts in mouse neurons and that membrane depolarization increases mRNA expression by increasing burst frequency.

Jizanpeptins, Cyanobacterial Protease Inhibitors from a Symploca sp. Cyanobacterium Collected in the Red Sea.

Jizanpeptins A-E (1-5) are micropeptin depsipeptides isolated from a Red Sea specimen of a Symploca sp. cyanobacterium. The planar structures of the jizanpeptins were established using NMR spectroscopy and mass spectrometry and contain 3-amino-6-hydroxy-2-piperidone (Ahp) as one of eight residues in a typical micropeptin motif, as well as a side chain terminal glyceric acid sulfate moiety.

Chromatin Regulation of Neuronal Maturation and Plasticity.

Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons.

New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors.

Mandelalides A-D (1-4) are macrocyclic polyketides known to have an unusual bioactivity profile influenced by compound glycosylation and growth phase of cultured cells. The isolation and characterization of additional natural congeners, mandelalides E-L (5-12), and the supply of synthetic compounds 1 and 12, as well as seco-mandelalide A methyl ester (13), have now facilitated mechanism of action and structure-activity relationship studies. Glycosylated mandelalides are effective inhibitors of aerobic respiration in living cells.

Parvalbumin Interneurons of the Mouse Nucleus Accumbens are Required For Amphetamine-Induced Locomotor Sensitization and Conditioned Place Preference.

To determine the requirement for parvalbumin (PV) expressing GABAergic interneurons of the nucleus accumbens (NAc) in the behavioral adaptations induced by amphetamine (AMPH), we blocked synaptic vesicle release from these neurons using Cre-inducible viral expression of the tetanus toxin light chain in male and female PV-Cre mice. Silencing PV+ interneurons of the NAc selectively inhibited the expression of locomotor sensitization following repeated injections of AMPH and blocked AMPH-induced conditioned place preference (CPP). AMPH induced significantly more expression of the activity-dependent gene Fos in both D1 and D2 dopamine receptor-expressing medium spiny neurons (MSNs) of the NAc of PV+ interneuron silenced mice, suggesting a function for PV+ interneuron-mediated MSN inhibition in the expression of AMPH-induced locomotor sensitization and CPP.

Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways.

Short-term incubation with insulin increases the L-arginine transport in HUVECs.Short-term incubation with insulin increases the NO synthesis in HUVECs.Insulin induces relaxation in human placental vascular bed.

Cardiovascular Action of Insulin in Health and Disease: Endothelial L-Arginine Transport and Cardiac Voltage-Dependent Potassium Channels.

Impairment of insulin signaling on diabetes mellitus has been related to cardiovascular dysfunction, heart failure, and sudden death. In human endothelium, cationic amino acid transporter 1 (hCAT-1) is related to the synthesis of nitric oxide (NO) and insulin has a vascular effect in endothelial cells through a signaling pathway that involves increases in hCAT-1 expression and L-arginine transport. This mechanism is disrupted in diabetes, a phenomenon potentiated by excessive accumulation of reactive oxygen species (ROS), which contribute to lower availability of NO and endothelial dysfunction.

Bimodal regulation of an Elk subfamily K+ channel by phosphatidylinositol 4,5-bisphosphate.

Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates Shaker K+ channels and voltage-gated Ca2+ channels in a bimodal fashion by inhibiting voltage activation while stabilizing open channels. Bimodal regulation is conserved in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, but voltage activation is enhanced while the open channel state is destabilized. The proposed sites of PIP2 regulation in these channels include the voltage-sensor domain (VSD) and conserved regions of the proximal cytoplasmic C terminus.