ER Stress-Induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin

A hallmark of Huntington's disease is the pronounced sensitivity of striatal neurons to polyglutamine-expanded huntingtin expression. Here we show that cultured striatal cells and murine brain striatum have remarkably low levels of phosphorylation of translation initiation factor eIF2 alpha, a stress-induced process that interferes with general protein synthesis and also induces differential translation of pro-apoptotic factors. EIF2 alpha phosphorylation was elevated in a striatal cell line stably expressing pathogenic huntingtin, as well as in brain sections of Huntington's disease model mice. Pathogenic huntingtin caused endoplasmic reticulum (ER) stress and increased eIF2 alpha phosphorylation by increasing the activity of PKR-like ER-localized eIF2 alpha kinase (PERK). Importantly, striatal neurons exhibited special sensitivity to ER stress-inducing agents, which was potentiated by pathogenic huntingtin. We could strongly reduce huntingtin toxicity by inhibiting PERK. Therefore, alteration of protein homeostasis and eIF2 alpha phosphorylation status by pathogenic huntingtin appears to be an important cause of striatal cell death. A dephosphorylated state of eIF2 alpha has been linked to cognition, which suggests that the effect of pathogenic huntingtin might also be a source of the early cognitive impairment seen in patients

The Mediating Role of Attachment Avoidance in the Association between Sexual Orientation and Mental Health

The current study examined whether attachment avoidance mediates the association between being a sexual minority (gay men or lesbian women) and poorer mental health outcomes. For this purpose a community-dwelling sample of 350 gay men and lesbian women (M = 30.39, SD = 6.82) and 445 heterosexual men and women (M = 26.95, SD = 3.11) completed measures of attachment avoidance, depressive symptoms, anxiety symptoms and life satisfaction. Results showed that gay men and lesbians reported poorer mental health. Moreover, attachment avoidance had a mediating effect on the association between being a sexual minority and depressive symptoms, anxiety symptoms and life satisfaction. These findings are some of the first to suggest empirical support for the role of attachment avoidance in accounting for the mental health vulnerability of gay men and lesbians. The results contribute to a better understanding of the minority stress model and should be addressed by practitioners

Of Citizen Suits and Citizen Sunstein

After briefly summarizing Lujan and addressing Sunstein\u27s critique, we explore the concept of accountability underlying the creation of a single executive in Article II. We then apply our theory of the unitary executive to several examples of broad grants of statutory standing, concluding that Congress can confer standing on private citizens only if it specifically articulates and individuates the interests whose violation gives rise to a cognizable case. Although we agree with Sunstein\u27s view that broad grants of statutory standing do not necessarily trench upon constitutional values, we ultimately side with Justice Scalia in concluding that universal citizen standing, as in Lujan itself, cannot be reconciled with the Constitution - not because of any definition of injury, but because of Article H\u27s establishment of a unitary executive

Prop-fan data support study

Updated parametric prop-fan data packages are presented and the rationale used in developing the new prop-fan data is detailed. These data represent Hamilton Standard's projections of prop-fan characteristics for aircraft that are expected to be in-service in the 1985 to 1990 time frame. The basic prop-fan configuration was designed for efficient cruise operation at 0.8 Mach number and 10,668M altitude. The design blade tip speed is 244 mps and the design power loading is 301 KW/M squared

LGBTQ parents and their children during the family life cycle

none4siopenNicola Carone, Henny M. W. Bos, Geva Shenkman, Fiona TaskerCarone, Nicola; Bos, Henny M. W.; Shenkman, Geva; Tasker, Fion

Deciding to Parent or Remain Childfree: Comparing Sexual Minority and Heterosexual Childless Adults from Israel, Portugal and the UK

This study compared Israeli, Portuguese, and British childless lesbian, gay, bisexual (LGB) and heterosexual adults on parenthood aspirations as indicated by their desire and intent to become a parent and their concern about childlessness. For this purpose, 168 childless adults (57 self-reported as LGB) in Portugal were matched on socio-demographic variables with 168 participants from the UK and 168 participants from Israel, resulting in a sample of n=504 (Mage = 28.26, SD = 6.17). Participants were recruited through convenience sampling and completed online questionnaires assessing parenthood desire, intent, and concern about childlessness. Results indicated that participants from Israel and Portugal reported higher levels of parenthood desire, intent, and concern about childlessness than participants from the UK. Parallel patterns also appeared separately for LGB and heterosexual participants between the countries. Heterosexual participants from Israel scored higher than counterparts from Portugal on parenthood intention and concern about childlessness. Additionally, LGB participants in general reported lower levels of parenthood desire, intentions, and concern about childlessness than did heterosexual participants. The findings are interpreted in light of the different socio-cultural contexts of the countries, i.e., the individualistic values characterizing the UK versus the familistic values characterizing the Israeli and Portuguese contexts, alongside a strongly pronatalist stance evident in Israel and economic context in Portugal. The study contributes to the scant comparative literature on parenthood aspirations among LGB individuals as a function of cultural context by providing a multicontextual viewpoint on parenthood aspirations, sexual orientation, and diverse socio-cultural contexts. Implications for clinicians are discussed