Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input.

The striatum integrates dopaminergic and glutamatergic inputs to select preferred versus alternative actions. However, the precise mechanisms underlying this process remain unclear. One way to study action selection is to understand how it breaks down in pathological states.

Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types.

The ventral pallidum (VP) contains GABA and glutamate neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the mechanisms by which VP cell types shape VTA activity and drive behavior. Here, we found that both VP GABA and glutamate neurons were activated during approach to reward or by delivery of an aversive stimulus.

Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion.

Levels of the opioid peptide dynorphin, an endogenous ligand selective for kappa-opioid receptors (KORs), its mRNA and pro-peptide precursors are differentially dysregulated in Parkinson's disease (PD) and following the development of l-DOPA-induced dyskinesia (LID). It remains unclear whether these alterations contribute to the pathophysiological mechanisms underlying PD motor impairment and the subsequent development of LID, or whether they are part of compensatory mechanisms. We sought to investigate nor-BNI, a KOR antagonist, 1) in the dopamine (DA)-depleted PD state, 2) during the development phase of LID, and 3) via measuring of tonic levels of striatal DA.

Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion.

Levels of the opioid peptide dynorphin, an endogenous ligand selective for kappa-opioid receptors (KORs), its mRNA and pro-peptide precursors are differentially dysregulated in Parkinson disease (PD) and following the development of L-DOPA-induced dyskinesia (LID). It remains unclear, whether these alterations contribute to the pathophysiological mechanisms underlying PD motor impairment and the subsequent development of LID, or whether they are part of compensatory mechanisms. We sought to investigate nor-BNI, a KOR antagonist, 1) in the dopamine (DA)-depleted PD state, 2) during the development phase of LID, and 3) with measuring tonic levels of striatal DA.

Violent victimization at the intersections of sexual orientation, gender identity, and race: National Crime Victimization Survey, 2017-2019.

Introduction: Prior research has found that experiences with violence in the U.S. differ across individual demographic characteristics, including race, gender, and sexual orientation.

Hate crimes against LGBT people: National Crime Victimization Survey, 2017-2019.

We estimate the prevalence and characteristics of violent hate crime victimization of lesbian, gay, bisexual, and transgender (LGBT) people in the United States, and we compare them to non-LGBT hate crime victims and to LGBT victims of violent non-hate crime. We analyze pooled 2017-2019 data from the National Crime Victimization Survey (n persons = 553, 925;n incidents = 32, 470), the first nationally representative and comprehensive survey on crime that allows identification of LGBT persons aged 16 or older. Descriptive and bivariate analysis show that LGBT people experienced 6.

Antidiscrimination Interventions, Political Ads on Transgender Rights, and Public Opinion: Results From Two Survey Experiments on Adults in the United States.

Political advertisements can shift attitudes and behaviors to become more exclusionary toward social out-groups. However, people who engage in an antidiscrimination exercise in the context of an experiment may respond differently to such ads. What interventions might foster inclusive attitudes in the presence of political communications about social policy issues like transgender rights? We examined two scalable antidiscrimination exercises commonly used in applied settings: describing a personal narrative of discrimination and perspective-taking.

A coculture-coproduction system designed for enhanced carbon conservation through inter-strain CO recycling.

Carbon loss in the form of CO is an intrinsic and persistent challenge faced during conventional and advanced biofuel production from biomass feedstocks. Current mechanisms for increasing carbon conservation typically require the provision of reduced co-substrates as additional reducing equivalents. This need can be circumvented, however, by exploiting the natural heterogeneity of lignocellulosic sugars mixtures and strategically using specific fractions to drive complementary CO emitting vs.

Potential differences between the political attitudes of people with same-sex parents and people with different-sex parents: An exploratory assessment of first-year college students.

Children were often near the center of public debates about legal marriage recognition for same-sex couples. Obergefell v. Hodges (2015), the case that resulted in legal same-sex marriage recognition, stressed the importance of these children as one of many factors compelling the opinion.

Gender Identity Disparities in Criminal Victimization: National Crime Victimization Survey, 2017-2018.

To estimate the prevalence of personal and household victimizations among transgender people in the United States. We analyzed pooled 2017 and 2018 data from the National Crime Victimization Survey, the first nationally representative sample that allows identification of transgender respondents. Transgender people experienced 86.

The Delta-Specific Opioid Glycopeptide BBI-11008: CNS Penetration and Behavioral Analysis in a Preclinical Model of Levodopa-Induced Dyskinesia.

In previous work we evaluated an opioid glycopeptide with mixed μ/δ-opioid receptor agonism that was a congener of leu-enkephalin, MMP-2200. The glycopeptide analogue showed penetration of the blood-brain barrier (BBB) after systemic administration to rats, as well as profound central effects in models of Parkinson's disease (PD) and levodopa (L-DOPA)-induced dyskinesia (LID). In the present study, we tested the glycopeptide BBI-11008 with selective δ-opioid receptor agonism, an analogue of deltorphin, a peptide secreted from the skin of frogs (genus ).

Preclinical evidence in support of repurposing sub-anesthetic ketamine as a treatment for L-DOPA-induced dyskinesia.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Pharmacotherapy with L-DOPA remains the gold-standard therapy for PD, but is often limited by the development of the common side effect of L-DOPA-induced dyskinesia (LID), which can become debilitating. The only effective treatment for disabling dyskinesia is surgical therapy (neuromodulation or lesioning), therefore effective pharmacological treatment of LID is a critical unmet need.

Catabolic Division of Labor Enhances Production of D-Lactate and Succinate From Glucose-Xylose Mixtures in Engineered Co-culture Systems.

Although biological upgrading of lignocellulosic sugars represents a promising and sustainable route to bioplastics, diverse and variable feedstock compositions (e.g., glucose from the cellulose fraction and xylose from the hemicellulose fraction) present several complex challenges.

The XylR variant (R121C and P363S) releases arabinose-induced catabolite repression on xylose fermentation and enhances coutilization of lignocellulosic sugar mixtures.

Microbial production of fuels and chemicals from lignocellulosic biomass provides a promising alternative to conventional petroleum-derived routes. However, the heterogeneous sugar composition of lignocellulose prevents efficient microbial sugar co-fermentation due to carbon catabolite repression, which negatively affects production metrics. We previously discovered that a mutant copy of the transcriptional regulator XylR (P363S and R121C; denoted as XylR*) in Escherichia coli has a higher DNA-binding affinity than wild-type XylR, leading to a stronger activation of the d-xylose catabolic genes and a release from glucose-induced repression on xylose fermentation.

Parallel experimental evolution reveals a novel repressive control of GalP on xylose fermentation in Escherichia coli.

Efficient xylose utilization will facilitate microbial conversion of lignocellulosic sugar mixtures into valuable products. In Escherichia coli, xylose catabolism is controlled by carbon catabolite repression (CCR). However, in E.

Engineering a Synthetic, Catabolically Orthogonal Coculture System for Enhanced Conversion of Lignocellulose-Derived Sugars to Ethanol.

Fermentation of lignocellulosic sugar mixtures is often suboptimal due to inefficient xylose catabolism and sequential sugar utilization caused by carbon catabolite repression. Unlike in conventional applications employing a single engineered strain, the alternative development of synthetic microbial communities facilitates the execution of complex metabolic tasks by exploiting the unique community features, including modularity, division of labor, and facile tunability. A series of synthetic, catabolically orthogonal coculture systems were systematically engineered, as derived from either wild-type Escherichia coli W or ethanologenic LY180.

Recent trends in integrated bioprocesses: aiding and expanding microbial biofuel/biochemical production.

Microbial biosynthesis of fuels and chemicals represents a promising route for their renewable production. Product toxicity, however, represents a common challenge limiting the efficacy of this approach. Integrated bioprocesses incorporating in situ product separation are poised to help address this intrinsic problem, but suffer their own unique shortcomings.

The combination of the opioid glycopeptide MMP-2200 and a NMDA receptor antagonist reduced l-DOPA-induced dyskinesia and MMP-2200 by itself reduced dopamine receptor 2-like agonist-induced dyskinesia.

Dopamine (DA)-replacement therapy utilizing l-DOPA is the gold standard symptomatic treatment for Parkinson's disease (PD). A critical complication of this therapy is the development of l-DOPA-induced dyskinesia (LID). The endogenous opioid peptides, including enkephalins and dynorphin, are co-transmitters of dopaminergic, GABAergic, and glutamatergic transmission in the direct and indirect striatal output pathways disrupted in PD, and alterations in expression levels of these peptides and their precursors have been implicated in LID genesis and expression.

Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy.

The discovery of biomarkers for Parkinson's disease (PD) is challenging due to the heterogeneous nature of this disorder, and a poor correlation between the underlying pathology and the clinically expressed phenotype. An ideal biomarker would inform on PD-relevant pathological changes via an easily assayed biological characteristic, which reliably tracks clinical symptoms. Human dermal (skin) fibroblasts are accessible peripheral cells that constitute a patient-specific system, which potentially recapitulates the PD chronological and epigenetic aging history.

CRISPR-Cas9-enabled genetic disruptions for understanding ethanol and ethyl acetate biosynthesis in .

Background: The thermotolerant yeast shows promise as an industrial host for the biochemical production of fuels and chemicals. Wild-type strains are known to ferment high titers of ethanol and can effectively convert a wide range of C, C, and C sugars into the volatile short-chain ester ethyl acetate. Strain engineering, however, has been limited due to a lack of advanced genome-editing tools and an incomplete understanding of ester and ethanol biosynthesis.

Disproportionality and Disparities among Sexual Minority Youth in Custody.

Research indicates that sexual minority youth are disproportionately criminalized in the U.S. and subjected to abusive treatment while in correctional facilities.

Incarceration Rates and Traits of Sexual Minorities in the United States: National Inmate Survey, 2011-2012.

Objectives: To report characteristics of sexual minority US inmates.

Methods: We drew our data from the National Inmate Survey, 2011-2012, a probability sample of inmates in US prisons and jails. We determined weighted proportions and odds ratios with 95% confidence intervals to estimate differences between sexual minority and heterosexual inmates.

Systemic human CD34(+) cells populate the brain and activate host mechanisms to counteract nigrostriatal degeneration.

Aim: Here we investigated the neuroprotective potential of systemic CD34(+) human cord blood cells (hCBCs) in a 6-hydroxydopamine rat model of Parkinson's disease.

Methods: Purified CD34(+) hCBCs were intravenously administered to rats subjected to 6-hydroxydopamine 24 h earlier, and behavioral and immunohistological analysis performed.

Results: CD34(+) hCBC administration significantly prevented host nigrostriatal degeneration inducing behavioral recovery in treated rats.