A Stronger IMPACT on Career Development for Early- and Mid-career Faculty.

Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.

Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.

Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development.

A highly conserved A-to-I RNA editing event within the glutamate-gated chloride channel GluClα is necessary for olfactory-based behaviors in .

A-to-I RNA editing is a cellular mechanism that generates transcriptomic and proteomic diversity, which is essential for neuronal and immune functions. It involves the conversion of specific adenosines in RNA molecules to inosines, which are recognized as guanosines by cellular machinery. Despite the vast number of editing sites observed across the animal kingdom, pinpointing critical sites and understanding their in vivo functions remains challenging.

The zebrafish as a potential model for vaccine and adjuvant development.

Introduction: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges.

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta.

The initial step in estrogen-regulated transcription is the binding of a ligand to its cognate receptors, named estrogen receptors (ERα and ERβ). Phytochemicals present in foods and environment can compete with endogenous hormones to alter physiological responses. We screened 224 flavonoids in our engineered biosensor ERα and ERβ PRL-array cell lines to characterize their activity on several steps of the estrogen signaling pathway.

Association of Quadriceps Tendon Harvest for ACL Reconstruction With Development of Osteochondritis Dissecans of the Patella in Pediatric Patients.

Background: There are various reported complications after primary anterior cruciate ligament reconstruction (ACLR) necessitating additional surgery in skeletally immature patients, regardless of technique and autograft type.

Purpose: To analyze the rate and type of complications encountered with soft tissue quadriceps tendon autograft (QTA) for ACLR in patients ≤18 years as well as the overall rate of second surgery, unrelated to the use of the QTA.

Study Design: Case series; Level of evidence, 4.

A novel ERβ high throughput microscopy platform for testing endocrine disrupting chemicals.

In this study we present an inducible biosensor model for the Estrogen Receptor Beta (ERβ), GFP-ERβ:PRL-HeLa, a single-cell-based high throughput (HT) assay that allows direct visualization and measurement of GFP-tagged ERβ binding to ER-specific DNA response elements (EREs), ERβ-induced chromatin remodeling, and monitor transcriptional alterations via mRNA fluorescence in situ hybridization for a prolactin (PRL)-dsRED2 reporter gene. The model was used to accurately (Z' = 0.58-0.

Mechanistic toxicology in light of genetic compensation.

Mechanistic toxicology seeks to identify the molecular and cellular mechanisms by which toxicants exert their deleterious effects. One powerful approach is to generate mutations in genes that respond to a particular toxicant, and then test how such mutations change the effects of the toxicant. CRISPR is a rapid and versatile approach to generate mutations in cultured cells and in animal models.

Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.

Introduction: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent.

Functional genomic analysis of non-canonical DNA regulatory elements of the aryl hydrocarbon receptor.

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that binds DNA and regulates genes in response to halogenated and polycyclic aromatic hydrocarbons. AHR also regulates the development and function of the liver and the immune system. In the canonical pathway, AHR binds a consensus DNA sequence, termed the xenobiotic response element (XRE), recruits protein coregulators, and regulates target gene expression.

Hemato-vascular specification requires arnt1 and arnt2 genes in zebrafish embryos.

During embryonic development, a subset of cells in the mesoderm germ layer are specified as hemato-vascular progenitor cells, which then differentiate into endothelial cells and hematopoietic stem and progenitor cells. In zebrafish, the transcription factor npas4l (cloche) is required for the specification of hemato-vascular progenitor cells. However, it is unclear whether npas4l is the sole factor at the top of the hemato-vascular specification cascade.

A randomized, double-blind, placebo-controlled, pharmacogenetic study of ondansetron for treating alcohol use disorder.

Background: In a previous study, ondansetron, a serotonin 5-HT receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European-ancestry (EA) participants with moderate-to-severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5-HT (HTR3A), and 5-HT (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron-treated individuals with population-specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B.

Methods: In this 16-week, double-blind, placebo-controlled, parallel-group clinical trial, adults with AUD were randomized to receive low-dose oral ondansetron (0.

Kratom: Substance of Abuse or Therapeutic Plant?

Kratom is the common term for Mitragyna speciosa and its products. Its major active compounds are mitragynine and 7-hydroxymitragynine. An estimated 2.

Policy Ahead of the Science: Medical Cannabis Laws Versus Scientific Evidence.

Forty-one US jurisdictions (37 states) have legalized comprehensive medical cannabis programs since 1996. The number of qualifying conditions per jurisdiction varies from 5 to 29. Five (12%) of 42 qualifying conditions have conclusive or substantial evidence of efficacy and are listed in more than half of all jurisdictions.

Validation of serotonin transporter mRNA as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide/ethyl sulfate: A randomized, double-blind, crossover trial.

Background: The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology-based biomarker of heavy drinking in 5HTTLPR:LL genotype-carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS).

Methods: Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12-day, in-patient, randomized, double-blind, crossover study, where they were administered three beverage doses (placebo, 0.

Strengthening Behavioral Health Services Through Partnerships and Data Integration.

Background There has been an increase in emergency medical service (EMS) use for behavioral health reasons. Detroit Wayne Integrated Health Network (DWIHN) and Detroit East Medical Control Authority (DEMCA) collaborated to study the rising number of behavioral health (mental disorders and substance use disorders) calls to EMS. Methodology To examine the trend, DWIHN and DEMCA partnered on a data-sharing project and identified that a high volume of EMS runs (responses by EMS as a result of an emergency call) involved individuals served by DWIHN.

The evolution and structure/function of bHLH-PAS transcription factor family.

Proteins that contain basic helix-loop-helix (bHLH) and Per-Arnt-Sim motifs (PAS) function as transcription factors. bHLH-PAS proteins exhibit essential and diverse functions throughout the body, from cell specification and differentiation in embryonic development to the proper function of organs like the brain and liver in adulthood. bHLH-PAS proteins are divided into two classes, which form heterodimers to regulate transcription.

Use of Reporter Genes to Analyze Estrogen Response: The Transgenic Zebrafish Model.

In vivo models to detect estrogenic compounds are very valuable for screening for endocrine disruptors. Here we describe the use of transgenic estrogen reporter zebrafish as an in vivo model for the identification of estrogenic properties of compounds. Live imaging of these transgenic fish provides knowledge of estrogen receptor specificity of different ligands as well as dynamics of estrogen signaling.

Factors Associated With Voluntary Refusal of Emergency Medical System Transport for Emergency Care in Detroit During the Early Phase of the COVID-19 Pandemic.

Importance: Emergency department (ED) and emergency medical services (EMS) volumes decreased during the COVID-19 pandemic, but the amount attributable to voluntary refusal vs effects of the pandemic and public health restrictions is unknown.

Objective: To examine the factors associated with EMS refusal in relation to COVID-19 cases, public health interventions, EMS responses, and prehospital deaths.

Design, Setting, And Participants: A retrospective cohort study was conducted in Detroit, Michigan, from March 1 to June 30, 2020.