Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice.

Volatile organic compounds, colloquially referred to as "terpenes", have been proposed to impact the therapeutic qualities that are traditionally ascribed to cannabis. However, the contribution of these terpenes in anxiety, at relevant levels and exposure methods common with cannabis use, is lacking empirical assessment. We tested the anxiolytic properties of two prominent cannabis terpenes, linalool and β-myrcene, in male and female mice using short duration vapor pulls to model human inhalation when combusting flower or vaping cannabis oil.

Epitope tagging with genome editing in mice reveals that the proton channel OTOP1 is apically localized and not restricted to Type III "sour" taste receptor cells.

The gustatory system allows animals to assess the nutritive value and safety of foods prior to ingestion. The first step in gustation is the interaction of taste stimuli with one or more specific sensory receptors, that are generally believed to be present on the apical surface of the taste receptor cells. However, this assertion is rarely tested.

Predictors of evidence-based psychotherapy initiation among veterans with co-occurring PTSD and substance use disorder.

Objective: To compare initiation of PTSD evidence-based psychotherapy (EBP) between Veterans with and without a co-occurring substance use disorder (SUD), and identify factors associated with EBP initiation among Veterans with PTSD-SUD.

Method: A national sample of Veterans with PTSD ( = 301,872) and PTSD-SUD ( = 94,515) were identified from VA Electronic Health Record data. Treatment initiation was defined as having at least one mental health encounter associated with Cognitive Processing Therapy or Prolonged Exposure therapy.

Voltage-induced calcium release in body muscles.

Type 1 voltage-activated calcium channels (CaV1) in the plasma membrane trigger calcium release from the sarcoplasmic reticulum (SR) by two mechanisms. In voltage-induced calcium release (VICR), CaV1 voltage sensing domains are directly coupled to ryanodine receptors (RYRs), an SR calcium channel. In calcium-induced calcium release (CICR), calcium ions flowing through activated CaV1 channels bind and activate RYR channels.

Post-synaptic GABA receptors potentiate transmission by recruiting CaV2 channels to their inputs.

We describe a retrograde synaptic signal at the C. elegans GABAergic neuromuscular junction. At this synapse, GABA release is controlled by two voltage-activated calcium channels (UNC-2/CaV2 and EGL-19/CaV1), and muscle responses are mediated by a single GABA receptor (UNC-49/GABA).

Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder.

Introduction: Cannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling.

Zinc activation of OTOP proton channels identifies structural elements of the gating apparatus.

Otopetrin proteins (OTOPs) form proton-selective ion channels that are expressed in diverse cell types where they mediate detection of acids or regulation of pH. In vertebrates there are three family members: OTOP1 is required for formation of otoconia in the vestibular system and it forms the receptor for sour taste, while the functions of OTOP2 and OTOP3 are not yet known. Importantly, the gating mechanisms of any of the OTOP channels are not well understood.

The serine hydrolase ABHD6 controls survival and thermally induced seizures in a mouse model of Dravet syndrome.

Evidence suggests that inhibition of α/β hydrolase-domain containing 6 (ABHD6) reduces seizures; however, the molecular mechanism of this therapeutic response remains unknown. We discovered that heterozygous expression of Abhd6 (Abhd6) significantly reduced the premature lethality of Scn1a mouse pups, a genetic mouse model of Dravet Syndrome (DS). Both Abhd6 mutation and pharmacological inhibition of ABHD6 reduced the duration and incidence of thermally induced seizures in Scn1a pups.

Cannabidiol's neuroprotective properties and potential treatment of traumatic brain injuries.

Cannabidiol (CBD) has numerous pharmacological targets that initiate anti-inflammatory, antioxidative, and antiepileptic properties. These neuroprotective benefits have generated interest in CBD's therapeutic potential against the secondary injury cascade from traumatic brain injury (TBI). There are currently no effective broad treatment strategies for combating the damaging mechanisms that follow the primary injury and lead to lasting neurological consequences or death.

The ADRENAL score: A comprehensive scoring system for standardized evaluation of adrenal tumor.

Objectives: To propose an original and standardized scoring system to quantify the functional and anatomical characteristics of adrenal tumor.

Materials And Methods: Four groups of consecutive adrenalectomies (n = 458) with heterogeneity in tumor characteristics and surgical approaches, including 212 laparoscopic cases (Group 1) and 105 robotic cases (Group 2) from The First Affiliated Hospital of Nanchang University, 28 robotic cases from Temple University Hospital (Group 3) and 113 laparoscopic cases from The First Affiliated Hospital of Guangxi Medical University (Group 4). All patients were followed up for 4.

Stereotyped behavioral maturation and rhythmic quiescence in embryos.

Systematic analysis of rich behavioral recordings is being used to uncover how circuits encode complex behaviors. Here, we apply this approach to embryos. What are the first embryonic behaviors and how do they evolve as early neurodevelopment ensues? To address these questions, we present a systematic description of behavioral maturation for embryos.

Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels.

Otopetrin (OTOP) channels are proton-selective ion channels conserved among vertebrates and invertebrates, with no structural similarity to other ion channels. There are three vertebrate OTOP channels (OTOP1, OTOP2, and OTOP3), of which one (OTOP1) functions as a sour taste receptor. Whether extracellular protons gate OTOP channels, in addition to permeating them, was not known.

Functional Status and Engagement in Physical Activity Among Maintenance Dialysis Patients: A Mixed Methods Study.

Rationale & Objective: People receiving maintenance hemodialysis (HD) experience significant activity barriers but desire the ability to do more and remain independent. To learn about how to help people who require dialysis stay active, a mixed methods study was designed to assess functional status and explore participants' lived activity experiences.

Study Design: A concurrent mixed methods design was chosen to increase understanding of the real-life activity experiences of people who require dialysis through in-depth interviews paired with functional status measures.

Shank promotes action potential repolarization by recruiting BK channels to calcium microdomains.

Mutations altering the scaffolding protein Shank are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. Among its many binding partners, Shank directly binds CaV1 voltage activated calcium channels. Here, we show that the SHN-1/Shank promotes CaV1 coupling to calcium activated potassium channels.

Generalizable Compositional Features Influencing the Proteostatic Fates of Polar Low-Complexity Domains.

Protein aggregation is associated with a growing list of human diseases. A substantial fraction of proteins in eukaryotic proteomes constitutes a proteostasis network-a collection of proteins that work together to maintain properly folded proteins. One of the overarching functions of the proteostasis network is the prevention or reversal of protein aggregation.

Presynaptic Gαo (GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying in Caenorhabditis elegans.

Egg laying in the nematode worm Caenorhabditis elegans is a two-state behavior modulated by internal and external sensory input. We have previously shown that homeostatic feedback of embryo accumulation in the uterus regulates bursting activity of the serotonergic HSN command neurons that sustains the egg-laying active state. How sensory feedback of egg release signals to terminate the egg-laying active state is less understood.

Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

Background: Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.

Methods: This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries.

Caenorhabditis elegans junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin.

The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole Caenorhabditis elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions.

Male pheromones modulate synaptic transmission at the neuromuscular junction in a sexually dimorphic manner.

The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The synaptic transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of synaptic transmission remains poorly understood.

MRI demonstration of gadolinium deposition in bone after monthly triple-dose gadopentetate dimeglumine and correlation with frequency of hypophosphatemia.

Objectives: We retrospectively analyzed data of the BECOME trial to investigate whether serial administration of triple-dose (3-dose) gadopentetate dimeglumine would result in the development of T1 signal-to-noise (S/N) changes in the cranial diploic space and whether S/N changes correlated with on-study hypophosphatemia.

Methods: Signal intensity analysis was performed on the first year's data of the BECOME trial using 3-dose Gd (14 months, maximum number of doses, 39, mean: 36). Routine blood and urine tests were obtained each month for safety monitoring.