Constitutional Law - Civil Rights

Public Accommodations Under the Civil Rights Act of 1964. Heart of Atlanta Motel, Inc. v. United States, 85 Sup. Ct. 348 (1964)

EP2, but not EP4, steadily stimulates the Gαs-protein pathway

EP2 and EP4 prostanoid receptors have long been considered to have similar roles, since they are known to couple with Gαs-protein and activate cAMP-mediated signaling pathways. In this study, we re-evaluated the results of cAMP assays with or without phosphodiesterase (PDE) inhibitor pretreatment. Here, we show that in the absence of PDE inhibitor pretreatment, prostaglandin E2 causes accumulation of cAMP in EP2 receptors, whereas markedly low levels of cAMP accumulated in EP4 receptors. By applying the Black/Leff operational model calculation, we found that EP2 receptors have a biased ability to intrinsically activate the Gαs-protein-mediated pathway, whereas EP4 receptors have strong biased activity for the Gαi-protein-mediated pathway. Thus, EP2 and EP4 receptors may not be similar Gαs-coupled receptors but instead substantially different receptors with distinct roles

Using Hubble Space Telescope Imaging of Nuclear Dust Morphology to Rule Out Bars Fueling Seyfert Nuclei

If AGN are powered by the accretion of matter onto massive black holes, how does the gas in the host galaxy lose the required angular momentum to approach the black hole? Gas easily transfers angular momentum to stars in strong bars, making them likely candidates. Although ground-based searches for bars in active galaxies using both optical and near infrared surface brightness have not found any excess of bars relative to quiescent galaxies, the searches have not been able to rule out small-scale nuclear bars. To look for these nuclear bars we use HST WFPC2-NICMOS color maps to search for the straight dust lane signature of strong bars. Of the twelve Seyfert galaxies in our sample, only three have dust lanes consistent with a strong nuclear bar. Therefore, strong nuclear bars cannot be the primary fueling mechanism for Seyfert nuclei. We do find that a majority of the galaxies show an spiral morphology in their dust lanes. These spiral arms may be a possible fueling mechanism.Comment: To be published in the Astronomical Journal, June 1999. 25 pages and 14 figures. Full resolution figures are available at ftp://www.ciw.edu/pub/mregan/fullfigs.tar.g

Disaster Exposure and Mental Health Among Puerto Rican Youths After Hurricane Maria

Importance: Quantifying the magnitude of disaster exposure and trauma-related symptoms among youths is critical for deployment of psychological services in underresourced settings. Hurricane Maria made landfall in Puerto Rico on September 20, 2017, resulting in massive destruction and unprecedented mortality. Objective: To determine the magnitude of disaster exposure and mental health outcomes among Puerto Rican youths after Hurricane Maria. Design, Setting, and Participants: Survey study in which a school-based survey was administered to each public school student at all schools in Puerto Rico between February 1 and June 29, 2018 (5-9 months after Hurricane Maria). Of the 226 808 students eligible to participate, 96 108 students completed the survey. Main Outcomes and Measures: Participants were assessed for exposure to hurricane-related stressors, posttraumatic stress disorder (PTSD), and depressive symptoms, using standardized self-report measures administered in Spanish. Descriptive statistics were compiled for all outcome variables, as was the frequency of individuals reporting clinically elevated symptoms of PTSD or depression. Differences in these statistics across sexes were also examined via t tests. Correlations between demographic, geographic, and main outcome variables were also calculated, and regressions were conducted to examine their association with symptoms of PTSD. Results: A total of 96 108 students participated in the study (42.4% response rate; 50.3% female), representative of grades 3 to 12 across all 7 educational regions of Puerto Rico. As a result of the hurricane, 83.9% of youths saw houses damaged, 57.8% had a friend or family member leave the island, 45.7% reported damage to their own homes, 32.3% experienced shortages of food or water, 29.9% perceived their lives to be at risk, and 16.7% still had no electricity 5 to 9 months after the hurricane. Overall, 7.2% of youths (n = 6900) reported clinically significant symptoms of PTSD; comparison of the frequency of reporting clinically elevated symptoms of PTSD across sex yielded a significant difference (t = 12.77; 95% CI of the difference, 0.018-0.025; P \u3c .001), with girls (8.2%) exceeding the clinical cutoff score more often than boys (6.1%). Finally, similar analysis of differences in depression between sexes was also significant (t = 17.56; 95% CI of the difference, 0.31-0.39; P \u3c .001), with girls displaying higher mean (SD) scores (2.72 [3.14]) than boys (2.37 [2.93]). Demographic and risk variables accounted for approximately 20% of variance in symptoms of PTSD (r2 = 0.195; 95% CI, 0.190-0.200). Conclusions and Relevance: Survey results indicate that Hurricane Maria exposed Puerto Rican youths to high levels of disaster-related stressors, and youths reported high levels of PTSD and depressive symptoms. Results are currently being used by the Puerto Rico Department of Education to inform targeted and sustainable evidence-based practices aimed at improving mental health outcomes for Puerto Rico\u27s youths

Receptor Number and Caveolar Co-Localization Determine Receptor Coupling Efficiency to Adenylyl Cyclase

Recent evidence suggests that many signaling molecules localize in microdomains of the plasma membrane, particularly caveolae. In this study, overexpression of adenylyl cyclase was used as a functional probe of G protein-coupled receptor (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat cardiomyocytes couple with different levels of efficiency to the activation of adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane fractions. Overexpression of AC6 enhanced the maximal cAMP response to β1-adrenergic receptor (β1AR)-selective activation 3.7-fold, to β2AR-selective activation only 1.6-fold and to prostaglandin E2 (PGE2) not at all. Therefore, the rank order of efficacy in coupling to AC6 is β1AR \u3e β2AR \u3e prostaglandin E2 receptor (EP2R). β2AR coupling efficiency was greater when we overexpressed the receptor or blocked its desensitization by expressing βARKct, an inhibitor of G protein-coupled receptor kinase activation, but was not significantly greater when cells were treated with pertussis toxin. Assessment of receptor and AC expression indicated co-localization of AC5/6, β1AR, and β2AR, but not EP2R, in caveolin-rich membranes and caveolin-3 immunoprecipitates, likely explaining the observed activation of AC6 by βAR subtypes but lack thereof by PGE2. When cardiomyocytes were stimulated with a βAR agonist, β2AR were no longer found in caveolin-3 immunoprecipitates; an effect that was blocked by expression of βARKct. Thus, agonist-induced translocation of β2AR out of caveolae causes a sequestration of receptor from effector and likely contributes to the lower efficacy of β2AR coupling to AC6 as compared with β1AR, which do not similarly translocate. Therefore, spatial co-localization is a key determinant of efficiency of coupling by particular extracellular signals to activation of GPCR-linked effectors