The G alpha q and G alpha 11 proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells

Thyrotropin-releasing hormone stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH3 cell membranes. The stimulation of the phosphoinositide phospholipase C (PI/PLC) activity can be blocked by incubation of GH3 membranes with polyclonal antibodies directed against a peptide derived from the C-terminal region of G alpha q and G alpha 11. Antibodies directed against the C- terminal region of other G alpha-subunits had no detectable effect. The inhibition was specific since addition of the peptide that was used to prepare the antibody completely reversed the inhibition. Further evidence for the coupling of the TRH receptor to G alpha q or G alpha 11 comes from a reconstitution experiment in which human embryonic kidney cells were transiently transfected with cDNAs corresponding to the TRH receptor, G alpha q or G alpha 11. The PIP2 hydrolysis detected with membranes from cells that over-expressed the TRH receptor alone was low, however, co-expression with the G alpha q or G alpha 11 subunits produced a synergistic stimulation of PI-PLC activity. In contrast, co-expression of these alpha-subunits with the M2 muscarinic acetylcholine receptor induced a weak stimulation of PIP2 hydrolysis. The results presented here suggest that the TRH-dependent stimulation of PI-PLC in GH3 cells is mediated through the G-protein alpha- subunits, G alpha q and/or G alpha 11

Why Counting Votes Doesn\u27t Add Up: A Response to Cox and Miles\u27 \u3cem\u3eJudging the Voting Rights Act\u3c/em\u3e

In Judging the Voting Rights Act, Professors Adam B. Cox and Thomas J. Miles report that judges are more likely to find liability under section 2 of the Voting Rights Act (VRA) when they are African American, appointed by a Democratic president, or sit on an appellate panel with a judge who is African American or a Democratic appointee. Cox and Miles posit that their findings “contrast” and “cast doubt” on much of the “conventional wisdom” about the Voting Rights Act, by which they mean the core findings we reported in Documenting Discrimination in Voting: Judicial Findings Under Section 2 of the Voting Rights Act Since 1982, and a related study by one of us, Not Like the South?: Regional Variation and Political Participation Through the Lens of Section 2

Do More Expensive Wines Taste Better? Evidence from a Large Sample of Blind Tastings

Individuals who are unaware of the price do not derive more enjoyment from more expensive wine. In a sample of more than 6,000 blind tastings, we find that the correlation between price and overall rating is small and negative, suggesting that individuals on average enjoy more expensive wines slightly less. For individuals with wine training, however, we find indications of a positive, or at any rate non-negative, correlation. Our results are robust to the inclusion of individual fixed effects, and are not driven by outliers: when omitting the top and bottom deciles of the price distribution, our qualitative results are strengthened, and the statistical significance is improved even further. Our results indicate that both the prices of wines and wine recommendations by experts may be poor guides for non-expert wine consumers.Wine; price/quality relation; expertise

Yoga May Ease Pain of Women with Fibromyalgia

An eight-week yoga program may decrease pain in women with fibromyalgia. It alters cortisol levels and, by making women more mindful, seems to encourage them to feel less helpless about their pain.York's Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

An eight-week yoga intervention is associated with improvements in pain, psychological functioning and mindfulness, and changes in cortisol levels in women with fibromyalgia

Objectives: Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, depression, and hypocortisolism. To date, published studies have not investigated the effects of yoga on cortisol in FM. This pilot study used a time series design to evaluate pain, psychological variables, mindfulness, and cortisol in women with FM before and after a yoga intervention. Methods: Participants (n = 22) were recruited from the community to participate in a 75 minute yoga class twice weekly for 8 weeks. Questionnaires concerning pain (intensity, unpleasantness, quality, sum of local areas of pain, catastrophizing, acceptance, disability), anxiety, depression, and mindfulness were administered pre-, mid- and post-intervention. Salivary cortisol samples were collected three times a day for each of two days, pre- and post-intervention. Results: Repeated measures analysis of variance (ANOVA) revealed that mean ± standard deviation (SD) scores improved significantly (p < 0.05) from pre- to post-intervention for continuous pain (pre: 5.18 ± 1.72; post: 4.44 ± 2.03), pain catastrophizing (pre: 25.33 ± 14.77; post: 20.40 ± 17.01), pain acceptance (pre: 60.47 ± 23.43; post: 65.50 ± 22.93), and mindfulness (pre: 120.21 ± 21.80; post: 130.63 ± 20.82). Intention-to-treat analysis showed that median AUC for post-intervention cortisol (263.69) was significantly higher (p < 0.05) than median AUC for pre-intervention levels (189.46). Mediation analysis revealed that mid-intervention mindfulness scores significantly (p < 0.05) mediated the relationship between pre- and post-intervention pain catastrophizing scores. Discussion: The results suggest that a yoga intervention may reduce pain and catastrophizing, increase acceptance and mindfulness, and alter total cortisol levels in women with FM. The changes in mindfulness and cortisol levels may provide preliminary evidence for mechanisms of a yoga program for women with FM. Future studies should use an RCT design with a larger sample size.JK is supported by a Canadian Institutes of Health Research (CIHR) Canada Research Chair (CRC) in Health Psychology. KC was supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship – Master’s Award and a CIHR Strategic Training Grant Fellowship in Pain: Molecules to Community. Funds to conduct this study were provided by JK’s CIHR CRC in Health Psychology

DO MORE EXPENSIVE WINES TASTE BETTER? EVIDENCE FROM A LARGE SAMPLE OF BLIND TASTINGS

Individuals who are unaware of the price do not derive more enjoyment from more expensive wine. In a sample of more than 6,000 blind tastings, we find that the correlation between price and overall rating is small and negative, suggesting that individuals on average enjoy more expensive wines slightly less. For individuals with wine training, however, we find indications of a positive relationship between price and enjoyment. Our results are robust to the inclusion of individual fixed effects, and are not driven by outliers: when omitting the top and bottom deciles of the price distribution, our qualitative results are strengthened, and the statistical significance is improved further. Our results indicate that both the prices of wines and wine recommendations by experts may be poor guides for non-expert wine consumers.wine quality, wire tasting, wine prices, Demand and Price Analysis,

Views of poetry as a competence expressed by students in teacher education

Since 2011 the Swedish curriculum has been oriented towards creating knowledge at school that is measurable and evidence-based. At the same time, there is still an overarching aim for education at school to stress equality by, among other things, letting all students use languages of their own to express themselves. This conflict, between knowledge that is measurable and goals aiming at maintaining democracy, also characterizes teacher education in Sweden. Hence, there are reasons to discuss the role of aesthetics at school by focusing on students’ views of the role of poetry in education. We present qualitative data consisting of interviews with eight student teachers being educated to work in primary school. In this way, a variety of conceptions of poetry, and the role of poetry at school, are captured and analyzed, which in turn, makes it possible to discuss what counts as a competence at school. The results show that lack of knowledge about aesthetic expressions limits the student teachers’ agency in several ways. They express a lack of self-confidence and they are afraid of being trapped by the school system in spite of their aspirations to work independently with poetry and other aesthetic expression

Carol Anne Bond v the United States of America: How a woman scorned threatened the Chemical Weapons Convention

The case of Carol Anne Bond v the United States of America stemmed from a domestic dispute when Ms. Bond attempted to retaliate against her best friend by attacking her with chemical agents. What has emerged is a much greater issue--a test of standing on whether a private citizen can challenge the Tenth Amendment. Instead of being prosecuted in state court for assault, Ms. Bond was charged and tried in district court under a federal criminal statute passed as part of implementation of the Chemical Weapons Convention (CWC). Ms. Bond\u27s argument rests on the claim that the statute exceeded the federal government\u27s enumerated powers in criminalizing her behavior and violated the Constitution, while the government contends legislation implementing treaty obligations is well within its purview. This question remains unanswered because there is dispute among the lower courts as to whether Ms. Bond, as a citizen, even has the right to challenge an amendment guaranteeing states rights when a state is not a party to the action. The Supreme Court heard the case on February 22, 2011, and, if it decides to grant Ms. Bond standing to challenge her conviction, the case will be returned to the lower courts. Should the court decide Ms. Bond has the standing to challenge her conviction and further questions the constitutionality of the law, it would be a significant blow to implementation of the CWC in the U.S. and the effort of the federal government to ensure we are meeting our international obligations

Documenting Discrimination in Voting: Judicial Findings Under Section 2 of the Voting Rights Act Since 1982

The Voting Rights Initiative ( VRI ) at the University of Michigan Law School was created during the winter of 2005 to help inform [...] the debates that led to this latest congressional reauthorization and the legal challenge to it that is certain to follow. A cooperative research venture involving 100 students working under faculty direction set out to produce a detailed portrait of litigation brought since 1982 under Section 2. This Report evaluates the results of that survey. The comprehensive data set may be found in a searchable form at http://www.votingreport.org or http://www.sitemaker.umich.edu/votingrights. The aim of this report and the accompanying website is to contribute to a critical understanding of current opportunities for effective political participation on the part of those minorities the Voting Rights Act seeks to protect

Functional analysis of the non-coding regions of RNA segments and the nucleocapsid protein of the Uukuniemi virus

The Uukuniemi virus (UUKV) is a member of the Bunyaviridae family (genus Phlebovirus). The virus was isolated from Ixodes ricinus ticks from Uukuniemi, Finland in 1959 and was found to be non-pathogenic for humans. UUKV has served for more than four decades as an excellent model to study the molecular and cellular biology of the serious human pathogens that reside within this group. UUKV has a segmented, single-stranded RNA genome of negative polarity. The three RNA segments (S, M, and L) encode four structural proteins: a nucleocapsid (N) protein, two glycoproteins (Gn and Gc), and an RNA-dependent RNA polymerase (L protein). In addition, a non-structural protein (NSs) is encoded from the S segment using an ambisense coding strategy. At the termini of the RNA segments, there are non-coding regions, which contain regulatory elements for viral transcription and replication. The very terminal 5' and 3' ends within all non-coding regions are complementary to each other, and highly conserved within the genus. In order to function as templates for transcription and replication, all three RNA segments must be encapsidated by the N protein. The N protein forms oligomers, in which N protein molecules are bound to each other; this oligomer associates with RNA. This study focused on analyzing the function of the non-coding regions in the termini of the RNA segments, and on locating amino acid residues or domains of the UUKV N protein, which could potentially be involved in the oligomerization or RNA-binding. The function of the non-coding regions was studied using a minigenome system developed for UUKV, where the viral protein coding sequence is replaced by sequences encoding a reporter protein. The cells are transfected with the minigenomes and helper plasmids, and after replication and transcription of the minigenomes, the reporter protein expression can be measured. The non-coding regions of all three RNA segments were analyzed and promoter strengths and packaging efficiencies were compared. The results showed that the non-coding regions in all three RNA segments contain all the necessary signals for initiation of transcription and replication and encapsidation and packaging of the RNA segments. The strongest promoter strength was observed in M segment, followed by L and S segments. The role of the intergenic region, which is located between the N and NSs genes in the UUKV S segment was also analyzed and was found to regulate termination of transcription. To study the oligomerization and RNA-binding of UUKV N protein, a set of N protein mutants were generated based on 2D and 3D predictions of the N protein. The functionality of these mutants was analyzed using mammalian two-hybrid-, minigenome-, and virus-like particle-assays, which showed that both the N- and C-termini of the N protein are needed for the oligomerization. A specific structure in the N-terminal region plays an important role in the N-N interactions. Some putative RNA-binding residues were found, which severely affected the N protein functionality in all three assays. These residues were located within the proposed RNA-binding cavity in the predicted UUKV N protein models. These results are in agreement with observations with other bunyaviruses, and could help to better understand the molecular biology of bunyaviruses. Moreover, understanding the details of the oligomerization and RNA-binding of the N protein could help in design of potential antivirals for the pathogenic phleboviruses.Uukuniemi-virus (UUKV) kuuluu suureen, maailmanlaajuiseen Bunyaviridae -virusheimoon, sukuun Phlebovirus. Monet bunyavirukset voivat aiheuttaa vakavia tauteja sekä ihmisille että eläimille, esimerkiksi verenvuotokuumetta ja aivotulehduksia. Suurin osa viruksista leviää hyttysten ja punkkien välityksellä, eikä tauteja vastaan vielä ole olemassa tehokkaita rokotteita. UUKV löydettiin Ixodes ricinus -puutiaisesta Itä-Suomessa v. 1959. Viruksen ei ole todettu aiheuttavan ihmiselle vaaraa, ja sitä onkin pitkään käytetty malliviruksena tutkittaessa vaarallisempien bunyavirusten rakennetta ja toimintaa. Viruksen perimä koostuu kolmesta yksijuosteisesta, negatiivisesti koodatusta RNA-juosteesta. Nämä kolme juostetta S, M, ja L koodaavat neljää rakenneproteiinia: nukleokapsidiproteiinia (N-proteiini), kahta viruksen pinnalla olevaa glykoproteiinia, sekä viruksen RNA-juosteiden monistamiseen tarvittavaa polymeraasia. Kaikilla bunyaviruksilla on RNA-juosteiden päissä säätelyalueet, jotka ohjaavat RNA-juosteiden replikaatiota ja transkriptiota, ja sitä miten eri RNA-juosteet pakataan muodostuviin viruspartikkeleihin. RNA-juosteista S (small) koodaa N-proteiinia: useista N-proteiineista muodostuu N-proteiinioligomeeri, joka puolestaan sitoutuu viruksen RNA:han suojaten sitä. Tämä ribonukleiinikompleksi toimii alukkeena viruksen replikaatiossa, ilman RNA:han sitoutunutta N-proteiinia virus ei pysty lisääntymään. Tässä väitöskirjatyössä tutkittiin, miten viruksen RNA-juosteiden päissä olevat säätelyalueet vaikuttavat RNA-juosteiden replikaatioon ja siiihen, miten RNA-juosteet pakataan muodostuvien viruspartikkelien sisään. Lisäksi tutkittiin N-proteiinin rakennetta, kuinka N-proteiini muodostaa RNA:ta suojaavan, useista N-proteiineista koostuvan oligomeerin, ja sitä, mitkä alueet N-proteiinista sitoutuvat RNA:han. Tutkimuksen kolme keskeisintä tulosta ovat: 1) viruksen RNA-juosteiden alussa ja lopussa olevat alueet sisältävät kaiken viruksen tarvitseman tiedon viruksen RNA-juosteiden monistamista ja säätelyä varten, sekä signaalit joiden avulla virus pakkaa RNA-juosteet muodostuvien viruspartikkelien sisälle. 2) Sekä N-proteiinin alku- että loppupää osallistuvat N-proteiineista koostuvan oligomeerin muodostamiseen, tässä prosessissa erityisesti N-proteiinin alkupään muodostama rakenne on tärkeä. 3) N-proteiinista kartoitettiin alueita ja yksittäisiä aminohappoja, jotka todennäköisesti osallistuvat ribonukleiinikompleksin muodostumiseen. Väitöskirjatyössä saavutettujen tutkimustulosten avulla voidaan ymmärtää paremmin myös muiden, vaarallisten bunyavirusten rakennetta ja toimintaa. N-proteiinin ja RNA:n välisen vuorovaikutuksen tunteminen voi esimerkiksi auttaa kehittämään lääkkeitä tai rokotteita vaarallisia bunyaviruksia vastaan