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Utilizing the resource model of political participation, we identify the antecedents of willingness to sign a petition supporting employment protections for lesbian, gay, bisexual, and transgender (LGBT) people among sexual minority and heterosexual college students. Through secondary data analysis, we investigate the role of sociodemographic, mobilizing context, and framing variables, including various LGBT-related attitudes that have never been integrated in a single regression of LGBT activism. Results from a sample of sexual minority (n = 367) and heterosexual (n = 1,707) college students suggest that the majority of students from both sexual orientation groups are willing to sign a petition for LGBT rights. Although the impact of framing variables, such as transphobia and liberal identity, were most influential among both groups, the relevance of some framing antecedents (i.e., heterosexist attitudes and the disclosure of sexual identities) was specific to each sexuality. Before the inclusion of framing factors, knowing LGBT peers and observing heterosexist discrimination inspired greater activism among both sexuality groups as did being female and a graduate student; however, the significance of religious factors were only important among heterosexual students. Implications for future research are discussed. more...

This study explores religious teachings about same-sex sexuality, religiosity, and contact with gay, lesbian, or bisexual (GLB) friends on attitudes toward lesbians and gay men among Catholic and Protestant social work students. Data from a convenience sample (n = 383) from four universities were analyzed. Hierarchical multiple regression results indicate that age, Protestant religious affiliation, religiosity, religious message about homosexuality, contact with GLB, and the cross product of religiosity and religious message were significant. The adjusted analysis for the latter variable indicates that those exposed to more accepting messages reported less bias, and the effect of antigay messages was greatest among highly religious students. Refereed/Peer-reviewed more...

Heterosexism contributes to an unsafe campus climate for lesbian, gay, and bisexual (LGB) college students. Intergroup dialogue courses about sexual orientation seek to build awareness, cross-group relationships, and commitment to social action to address anti-LGB prejudice and discrimination. Although dialogue courses are growing in popularity, few courses address sexual orientation. To advance knowledge of these dialogues, this qualitative study explores heterosexual students' motivations and expectations, challenges, and learning outcomes related to their participation in intergroup dialogue courses on sexual orientation. Core themes include desire to learn about the LGB community, concerns about offending classmates, anxiety around LGB stigma, conflict with classmates around controversial topics, affirming LGB people, and learning about heterosexism, privilege, and intersectionality of identity. Implications for intergroup dialogue pedagogy and research are discussed. more...

In the past decade, advocacy efforts to establish social policies that legally recognize same-sex relationships and protect lesbian, gay, bisexual, and transgender (LGBT) people from employment discrimination have increased considerably throughout the country. To inform these advocacy campaigns, we investigate endorsement for LGBT civil rights among heterosexual college students (n = 1,714). Students, overall, were moderately supportive of LGBT rights. Twenty-one variables were found to be significant in the initial analyses; however, only seven retained significance in the final analysis which controlled for all variables. Results suggest that political ideology and specific LGBT attitudes are most influential. Religiosity and having LGBT extended family members are also important. Implications for LGBT advocacy efforts are discussed. more...

N-formylated sugars are found on the lipopolysaccharides of various pathogenic Gram negative bacteria including Campylobacter jejuni 81116, Francisella tularensis, Providencia alcalifaciens O30, and Providencia alcalifaciens O40. The last step in the biosynthetic pathways for these unusual sugars is catalyzed by N-formyltransferases that utilize N10-formyltetrahydrofolate as the carbon source. The substrates are dTDP-linked amino sugars with the functional groups installed at either the C-3' or C-4' positions of the pyranosyl rings. Here we describe a structural and enzymological investigation of the putative N-formyltransferase, FdtF, from Salmonella enterica O60. In keeping with its proposed role in the organism, the kinetic data reveal that the enzyme is more active with dTDP-3-amino-3,6-dideoxy-d-galactose than with dTDP-3-amino-3,6-dideoxy-d-glucose. The structural data demonstrate that the enzyme contains, in addition to the canonical N-formyltransferase fold, an ankyrin repeat moiety that houses a second dTDP-sugar binding pocket. This is only the second time an ankyrin repeat has been shown to be involved in small molecule binding. The research described herein represents the first structural analysis of a sugar N-formyltransferase that specifically functions on dTDP-3-amino-3,6-dideoxy-d-galactose in vivo and thus adds to our understanding of these intriguing enzymes. more...

Direct practice social workers have potentially significant policymaking opportunities as mediators of top-down policy and as creators of policy where none exists. The power they possess stems from their ‘on the ground’ expertise and the discretion available to them in making practice decisions. By understanding their power as “street-level bureaucrats” they can significantly improve policy. Drawing on policy issues in mental health and addictions services, this article illustrates how social workers can use their power in an ethically sensitive manner to enhance policy outcomes for clients. more...

Social workers are expected to promote social justice for lesbian, gay, bisexual, and transgender (LGBT) people, and social work programs and their faculty are expected to prepare students for competent and ethical practice with LGBT people and communities. Faculty's LGBT social attitudes can play a central role in developing students’ competencies. Minimal attention has been given to the nature of faculty's LGBT social attitudes. This article presents the results of a national survey conducted in the United States with a random sample of graduate teaching faculty concerning their LGBT social attitudes (n = 161). Bivariate and multivariate predictors of LGBT social attitudes were identified. Although a number of factors were significant in bivariate analyses and initial multivariate analysis (controlling only for sociodemographics), the final estimated model suggests race and social attitudes about women and critical consciousness are significant. The authors outline recommendations to enhance fa... more...

Research suggests that contact with sexual minorities and etiology beliefs regarding the origins of homosexuality are associated with antigay bias; however, factors related to etiology beliefs have received little empirical attention. Our primary research question is: does closeness to someone who is gay, lesbian, or bisexual influence etiology beliefs? Students (n = 851) from four US universities completed an anonymous survey, and regression results indicated that contact and closeness were not significantly associated with etiology beliefs. Because both contact and relationship closeness were associated with antigay attitudes, and closeness demonstrated the largest effect, we tested three alternative structural equation models to determine if contact and closeness mediated etiology beliefs. Results suggested that contact and the degree of closeness are indirectly associated with students' etiology beliefs through antigay bias. Refereed/Peer-reviewed more...

Background/Aim: Only a minority of men succumb to prostate cancer (PCa). Therapy to prevent progression would change treatment paradigms. We investigated the effect of valproic acid (VPA) on PCa cell proliferation and the effects on both angiogenesis and PCa-specific signaling. Materials and Methods: LNCaP cells were treated with VPA for 72 h and proliferation was measured. Cellular RNA extracts were used to measure gene expression with RT-profiler2 arrays. Genes with alterations were validated using real-time polymerase chain reaction and western blot. Results: VPA led to a dose-dependent decrease in proliferation. Expression array data revealed an impact on modulators of angiogenesis. Additionally, several cell-cycle control transcripts were affected. There was a strong correlation between gene and protein expression levels for validated targets. Conclusion: VPA decreases cellular proliferation of PCa cells in vitro and also affects gene expression suggestive of anti-angiogenic effect with a concomitant decrease in proliferation-related genes. more...

INTRODUCTION AND OBJECTIVES: Currently one of the major goals of cancer therapy is selective killing of cancer cells. TRAIL has attracted considerable attention due to its ability to kill tumor cells while sparing the normal ones. When TRAIL induces apoptosis, it binds to death receptor 4 (DR4) and 5(DR5). After that, TRAIL induces trimerization of death receptors to form a complex named deathinducing signaling complex (DISC), which in turn activates caspase-8, leading to the further activation of caspase-3 and subsequent apoptosis. However, the development of resistance to TRAIL, which mechanism is still not fully understood, in many tumor types appears as a major roadblock for the application of TRAIL-based cancer therapy. In recent years, many studies indicated synergistic effect between TRAIL and numerous agents which can be applied to overcome resistance and therefore enhance the tumor-killing ability of TRAIL. Diosmetin is an O-methylated flavone, a compound which can be isolated in Caucasian vetch. In this study, we investigated whether diosmetin can increase the tumor-killing ability of TRAIL and looked into the mechanisms. METHODS: Anti-proliferative activity of diosmetin alone or in combination with TRAIL was investigated by cell viability assays. Cell death was evaluated using PI/Annexin V staining and flow cytometer. Furthermore, changes of protein were also investigated by Western Blot. RESULTS: We found that diosmetin was capable of promoting anti-tumor ability of TRAIL in renal carcinoma cells (Fig 1). Further investigation showed that diosmetin can up-regulate the expression of DR5 but not DR4 in Caki cells. Silencing of DR5 can abolish the synergistic effect between diosmetin and TRAIL. Mechanistically, induction of DR5 by diosmetin was found to be p53-independent but relied on the expression of CHOP. Knockdown of CHOP abrogated diosmetin-induced DR5 expression and the related enhancement of TRAIL-mediated cell death. In addition diosmetin could also down-regulate the expression of several cell survival proteins. CONCLUSIONS: Our results indicated that diosmetin potentiate TRAIL-induced apoptosis in renal carcinoma cells which relies on the CHOP-dependent up-regulation of DR5. Source of Funding: none more...

Attention to same-sex marriage has increased in the past decade. This study examines the perceptions of same-sex marriage among social work faculty. Faculty play a critical role in preparing future social workers for competent, ethical practice--including advocacy for social policies inclusive of sexual minorities. The present study investigates endorsement of same-sex marriage among teaching faculty in U.S. and English-speaking Canadian MSW programs. Twelve factors were found to be significant in the bivariate analyses; however, only four retained significance in the multivariate analysis. Specifically, the multivariate analysis found "other race" and religiosity to be negatively associated with support for same-sex marriage, whereas acceptance of same-sex relationships and understanding gender-based oppression as the root cause of domestic and sexual violence were positively associated with same-sex marriage support. The results highlight the importance of social attitudes concerning same-sex relationships and gender-based oppression for endorsement of same-sex marriage. Implications for social work education and future research are discussed. KEY WORDS: gay and lesbian people; heterosexism; same-sex marriage; social work faculty ********** Same-sex marriage is a controversial policy issue around the world. Currently, same-sex marriage is legal in 11 countries, nine U.S. states, and the District of Columbia. Given the legal and social significance that marriage holds in society, the issue of same-sex marriage raises many social justice and human fights questions for same-sex couples and the social work profession (Fredriksen-Goldsen, Hyun-Jun, Murraco, & Mincer, 2009; Woodford, 2010). Social workers have an ethical responsibility to advocate for social justice for sexual minorities (Canadian Association of Social Workers [CASW], 2005; NASW, 2000). Moreover, social work program educational accreditation standards mandate inclusion of content regarding sexual minorities and oppression related to sexuality (Canadian Association of Schools of Social Work, 2007; Council on Social Work Education [CASWE] Gay, Lesbian, Bisexual, Transgendered Caucus, 2008). However, recent research in the United States demonstrates that content on sexual orientation (and gender identity and expression) needs to be more comprehensively integrated into social work curriculums (Martin et al., 2009). Similar conclusions have been drawn in Canada (CASWE Gay, Lesbian, Bisexual, Transgendered Caucus, 2008). Researchers have devoted attention to social workers' (Berkman & Zinberg, 1997; Crisp, 2006; Green, 2005; Krieglstein, 2003), social work students' (Brownlee et al., 2005; Logie, Bridge, & Bridge, 2007), and social work educators' (Ben-Ari, 2001; Fredriksen-Goldsen, Woodford, Luke, & Gutierrez, 2011) attitudes toward homosexuality. However, minimal attention has been given to attitudes about same-sex marriage. Both CASW (Newman, Brotman, Ryan, & OASW, 2003) and NASW (Webb, n.d.) publicly support same-sex marriage. Although endorsement of same-sex marriage by these organizations is important in advancing same-sex couples' access to marriage, support for same-sex marriage among social work faculty is likely more important, as faculty play a central role in preparing students for competent and ethical practice--including advocacy for and with same-sex couples. Faculty who oppose or are unsure about same-sex marriage may avoid the topic in their courses, thereby negatively affecting students' preparedness to advocate for inclusive marriage policies and related social policies. Furthermore, faculty who oppose same-sex marriage may minimize its importance or advocate to students that marriage remain a heterosexual institution. Also, anti-gay marriage views among faculty may foster an unwelcoming, "chilly" learning environment for sexual-minority students. Given the role faculty play in developing students' professional values, knowledge, and skills, it is important to understand faculty's views about same-sex marriage. … more...

This study identifies the predictors of U.S. heterosexual undergraduate and graduate college students’ attitudes toward lesbian, gay, bisexual, and transgender (LGBT) people as a group rather than toward individual identities. Findings suggest that affirming LGBT attitudes are most strongly associated with liberal political ideology and whether one believes in biological causation of transgender identity. Understanding sexual orientation as biological and having LGB friends, LGB immediate family members, and transgender friends are also important, but to a lesser degree. Age, gender, and select races/ethnicities and select religious affiliations are marginally associated with LGBT attitudes. These findings clarify areas to target for improvement in campus climate for LGBT persons, and implications for campus programs and research are discussed. more...

Objective: The investigators examined the health and well-being correlates of hearing the popular phrase “that's so gay” among gay, lesbian, and bisexual (GLB) emerging adults. Participants: Participants were 114 self-identified GLB students aged 18 to 25 years. Methods: An online survey was distributed to students at a large public university in the Midwest during winter 2009. Results: Participants’ social and physical well-being was negatively associated with hearing this phrase, specifically feeling isolated and experiencing physical health symptoms (ie, headaches, poor appetite, or eating problems). Conclusions: College professionals and student leaders must acknowledge that the phrase is a form of heterosexist harassment. As such, policies addressing diversity and harassment should address students’ use of this phrase, aiming to reduce its use. Additionally, colleges and universities should develop practices that counteract poorer well-being associated with hearing the phrase. more...

Social work faculty's attitudes contribute to creating inclusive and productive classroom climates when discussing racism, sexism, and heterosexism. Little is known about faculty's attitudes toward marginalized groups and the intersection of these attitudes with religion. This study describes social work faculty's attitudes about people of Color, women, and lesbian and gay people, and the relationship among these attitudes, religious affiliation, and religiosity. Results indicate religiosity predicts less accepting attitudes towards lesbian and gay people for Christian faculty; religious affiliation and religiosity did not predict attitudes towards women or people of Color. Intergroup dialogue is recommended for social work faculty learning. more...

The acceleration of research with lesbian, gay, and bisexual (LGB) populations amid existing sexual prejudice and advancing human rights leads to sometime conflicting stances between researchers and ethics boards over acceptable methodological practices. Ethics boards, charged with ensuring the safety of research participants, may engage in ostensibly protective stances regarding potential risks and informed consent that are unwittingly founded upon negative stereotypes of LGB populations. We examine four case studies that demonstrate divergent stances between researchers and ethics boards, researchers’ responses to ethics reviews and their resolution. Based on these cases, we describe themes and strategies for researchers working with LGB populations in responsibly navigating ethics board concerns. more...

Although numerous studies have examined the role of religious tradition and religiosity on attitudes toward lesbian, gay, and bisexual people, the role of endorsement of denominational teachings has largely been overlooked, even though such teachings are often cited to explain study findings. To better understand the complex relationship between religion and sexual prejudice, this study explores the unique contributions of religious tradition, religiosity, and individual endorsement of denominational doctrine about same-sex sexuality in shaping these attitudes. Findings indicate that endorsement of denominational doctrine concerning same-sex sexuality is more influential than religiosity, and that endorsement of denominational doctrine is not simply a proxy for believing that same-sex sexuality is a sin. Implications for future research are discussed. more...

Citizen participation has a longstanding history in Canadian policy-making. Recently, strengthening citizen participation in national policy issues has been a priority. Most noteworthy is the introduction of citizen engagement which integrates deliberation-based methods into participatory policy initiatives. To enhance participation in other jurisdictions, we analyse efforts to transform participation in Canada. Also, to extend efforts to improve participation in Canada and beyond, we analyse specific developments related to institutionalising participation and fostering government accountability. We offer recommendations that we believe can contribute to future efforts to foster meaningful public participation around the world. more...

Objectives. We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research. Methods. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008. Results. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials. Conclusions. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research. more...

Kothi-identified men who have sex with men in India are highly marginalized and are at high-risk for HIV. This study examines HIV testing among 132 self-reported HIV-negative and unknown serostatus kothis recruited from public sex environments in Chennai, India. Using logistic regression we identified variables associated with HIV testing uptake (i.e., being tested and knowing the result). Sixty-one percent reported HIV testing uptake. At the bivariate level, married men, those with low HIV transmission knowledge, those who engaged in unprotected anal sex and unprotected receptive anal sex were at lower odds of reporting testing uptake. In multivariate analysis, married men and those with low levels of HIV transmission knowledge were at decreased odds of being tested, as were kothis who experienced forced sex. Culturally competent programs engaging married kothis are needed. Interventions to facilitate HIV prevention education and systemic interventions to combat sexual violence may facilitate HIV testing uptake among kothis. more...

Stakeholder participation can be a valuable component of program/policy development in the human services. However, service users and other stakeholders often experience it as tokenistic and having little effect. Although management literature recommends stakeholder participation and social work ethics promote it, agency leaders and practitioners are given little guidance on how to design participation initiatives that integrate stakeholders' input into agency decision making. This article focuses on creating a strategy that can foster meaningful stakeholder participation. We outline 7 principles of meaningful participation and present a 12-step process for formulating a participation strategy that applies these principles. more...

Reduction of dixanthylidene with potassium or lithium resulted in formation of the antiaromatic dianion in high yield. Attempts to form the dianion by excited-state deprotonation of dixanthene with n-butyllithium/TMEDA resulted in formation of the tetraanion from deprotonation ortho to the oxygen. Orientation of the sp(3) hydrogens presumably allows preferential deprotonation of the xanthene rings. more...

This article presents findings from the first national surveys of United States and English- speaking Canadian MSW social work faculty examining their support of curriculum content on sexual orientation and gender identity. Faculty in either country are generally supportive of including LGBT content but report significantly more support for content on LGBT populations as compared to the types of oppression experienced. Significant predictors of support for LGBT content include being female, younger, non-White/non-European, having positive LGBT social attitudes, and the availability of resources on transgenderrelated issues. The findings suggest that faculty development should address the social attitudes among faculty as well as integrate gender identity into diversity discourse in social work education. more...

Lesbian families are marginalized in contemporary society. Yet, shifting social mores and recent policy changes enable some lesbian couples to adopt children as a couple. Research is lacking about these unique families. The qualitative study presented here extends knowledge about lesbian couples’ internal and social experiences as they become adoptive parents. The findings indicate that these couples face unique challenges to internally held identities and in social relationships. They use, often simultaneously, normalizing and resisting strategies to address the challenges they face. The employment of strategies varies over time and across social contexts, adding to the complexity of tactics that lesbian families use to address heterosexism. more...

Collaborative policy making has considerable value in creating innovative, responsive policies; however, substantial barriers to collaboration exist within government. Little is known empirically about what is necessary to promote successful policy collaboration, especially when policy decision-making authority remains with the state. To help fill this knowledge gap, this article presents the results of a case study of a successful collaborative policy initiative concerning income support services for victims of intimate violence. Drawing from multiple data sources, I identify eight factors that facilitated the collaborative group's success, including realizing progressive policy change responsive to victims' needs. Related to several of these factors are the actions of strategic government actors indirectly and directly involved in the collaborative workgroup. more...

Social workers have an ethical and professional responsibility to promote social justice and equality for oppressed groups, including sexual minorities. Advocating for the legal recognition of same-sex marriage is one way to enact this responsibility. The legal recognition of same-sex marriage is a significant accomplishment toward equality for gay and lesbian Canadians—one in which the social work profession played a role by presenting a legislative brief to policymakers. Although legislative advocacy is cited as a social policy change tool, the literature gives little attention to it, especially in regard to equality and social justice for LGBT people. This statement, subsequently adopted by the Canadian Association of Social Workers, is presented here to help social service workers better understand the significance of legal recognition of same-sex marriage, particularly as a minority rights issue. It is also presented as an example of a legislative advocacy tool. To inform policy change efforts elsewh... more...

As part of the mystique associated with the concept of marriage is the myth of the “heterosexual assumption” that underpins all of the American legal and religious tenets and perpetuates the idea t... more...

Molecular chaperones are essential for guarding proteins that are indispensable for normal cellular functions. Heat shock protein 90 (Hsp90) is a vital molecular chaperone in eukaryotes that participates in stabilizing and activating approximately 200 target proteins, called "clients," many of which are involved in signal transduction pathways. Cancer cells however utilize Hsp90 to chaperone an array of mutated and overexpressed oncoproteins to protect them from misfolding and degradation. Therefore, Hsp90 is an attractive target in cancer therapy. Hsp90 chaperone function relies on ATP binding and hydrolysis, which in turn guides its carefully orchestrated conformational changes. This chaperone cycle is fine-tuned by another group of proteins called co-chaperones. They are able to accelerate or decelerate the cycle, allowing Hsp90 to chaperone different clients. Posttranslational modifications (PTMs) can also regulate the chaperone cycle at an epigenetic level thereby tailoring Hsp90 function to suit a specific cell type or environmental condition. Recent evidence suggests that inhibition of the enzymes that catalyze the PTM of Hsp90 can act synergistically with Hsp90 inhibitors, providing a novel therapeutic strategy to enhance the efficacy of Hsp90 inhibitors in cancer cells. more...

Molecular chaperones are essential for guarding proteins that are indispensable for normal cellular functions. Heat shock protein 90 (Hsp90) is a vital molecular chaperone in eukaryotes that participates in stabilizing and activating approximately 200 target proteins, called “clients,” many of which are involved in signal transduction pathways. Cancer cells however utilize Hsp90 to chaperone an array of mutated and overexpressed oncoproteins to protect them from misfolding and degradation. Therefore, Hsp90 is an attractive target in cancer therapy. Hsp90 chaperone function relies on ATP binding and hydrolysis, which in turn guides its carefully orchestrated conformational changes. This chaperone cycle is fine-tuned by another group of proteins called co-chaperones. They are able to accelerate or decelerate the cycle, allowing Hsp90 to chaperone different clients. Posttranslational modifications (PTMs) can also regulate the chaperone cycle at an epigenetic level thereby tailoring Hsp90 function to suit a specific cell type or environmental condition. Recent evidence suggests that inhibition of the enzymes that catalyze the PTM of Hsp90 can act synergistically with Hsp90 inhibitors, providing a novel therapeutic strategy to enhance the efficacy of Hsp90 inhibitors in cancer cells. more...

Social work faculty play an important role in preparing students to address sexism and engage in culturally competent practice with women. This study examines the nature of U.S. and Anglo-Canadian graduate social work faculty's support for content on women and on sexism. Although support appears high for both content areas, results suggest that faculty endorsement for content on women is significantly greater than that for sexism. Further, bivariate and multivariate analyses indicate that the nature of support differs for each content area. Implications for social work education are discussed. more...

Sexual minority college students report experiencing interpersonal heterosexism, ranging from subtle insults to blatant physical violence. Such negative experiences can complicate developmental tasks common to adolescence and emerging adulthood. Studies examining the nature of heterosexism on college campuses have focused on blatant manifestations, yet subtle forms are more prevalent. Guided by ecological theory, we investigate the microsystem (e.g., perceived social support from friends, ambient heterosexism on campus), mesosystem (e.g., interaction between social support and ambient heterosexism), and macrosystem level (e.g., knowledge of gay-straight alliances on campus) covariates of interpersonal microaggressions, avoidance behaviors, verbal threats, and physical threats. Participants consisted of 530 self-identified LGBQ college students from 37 states. Regression results suggest that at the microsystem level, ambient heterosexism was positively associated with interpersonal microaggressions, avoidance behaviors, and verbal threats. At the mesosystem level, perceptions of LGBQ student support within one’s institution moderated the effects of ambient heterosexism on three types of interpersonal heterosexism. At the macrosystem level, students who reported knowing that their campus had a sexual-orientation inclusive anti-discrimination policy reported encountering fewer verbal threats. Directions for future research and implications for campus programming are discussed. more...

INTRODUCTION AND OBJECTIVES: Abnormal chromosome segregation during mitosis causes aneuploidy, a hallmark of cancers associated with high risk for tumorigenesis. Mitotic checkpoint, or spindle assembly checkpoint prevents missegregation of chromosomes by arresting cells in metaphase until all the chromosomes are properly aligned. Mps1 kinase activity is essential for spindle checkpoint signaling. High levels of Mps1 serine/threonine kinase are found in colon cancer tissues and several cancer cell line. We found that Mps1 is over-expressed in ccRCC. We have further shown that Mps1 requires the molecular chaperone Hsp90 for its activity. Hsp90 protects an array of mutated, over-expressed and/or chimeric kinases that are vital for tumor growth and survival. The Hsp90 inhibitors are currently undergoing evaluation in human trials. We have previously shown that Hsp90 is a post-translationally modified protein and this regulates its chaperone activity. We hypothesize that Mps1 kinase targets and phosphorylates Hsp90 and therefore regulates its chaperone activity. This in turn impacts the tumor selectivity of Hsp90 inhibitors. METHODS: Functional genomics and quantitative proteomic (stable isotope labeling by amino acids in cell culture) was used to identify the Mps1 kinase that targets and phosphorylates Hsp90. ccRCC and adjacent normal tissue was obtained with written informed consent through the Upstate Department of Urology. 8-mm core of tissue was dissected into 3mm pieces and cultured in 24-well plates containing 1 mL RPMI-1640 with 10% FBS, antibiotic/antimycotic solution. Tissues were cultured at 37 C for 24 hours with or without Mps1 inhibitor NMS-P715 and for further 24 hours in the presence of fluorescently labeled Hsp90 inhibitor ganetespib (FL-ganetespib), then formalin-fixed and paraffin embedded. The tissues were immunostained for Hsp90. RESULTS: Mps1 kinase is over-expressed in ccRCC compared to normal adjacent tissue. Mps1 targets and phosphorylates T115 in the molecular chaperone Hsp90 and this regulates the chaperone activity. Ex vivo data showed that FL-ganetespib selectively accumulates in ccRCC and not in the normal tissue. Pharmacologic inhibition of Mps1 reverts this drug uptake by ccRCC. CONCLUSIONS: Mps1 protein kinase is an Hsp90 client and it is involved in post-translational regulation of the chaperone function. Over-expression of Mps1 in the ccRCC hyperphosphorylates Hsp90 and this is the molecular basis of the tumor selectivity of Hsp90 inhibitors. more...

Heat shock protein-90 (Hsp90) is a molecular chaperone critical to the folding, stability and activity of over 200 client proteins including many responsible for tumor initiation, progression and metastasis. Hsp90 chaperone function is linked to its ATPase activity and Hsp90 inhibitors interfere with this activity, thereby making Hsp90 an attractive target for cancer therapy. Also post-translational modification (PTM) and co-chaperone proteins modulate Hsp90 function, providing additional targets for secondary inhibition. Recent reports have shown that pathogens utilize both their own Hsp90 and that of their host for the propagation of infectious elements. In this review we will summarize our current knowledge of Hsp90 structure and function in both the pathogen and the host. We will focus on the role of Hsp90 in viral and parasitic diseases and the potential beneficial application of Hsp90 inhibitors alone and in combination with disease-specific inhibitors. more...

Previously we have found that mitogens stimulate proliferation of meningioma cells of all grades, in part, by activation of the PI3K-PKB/Akt-PRAS40-mTOR pathway regulated to some degree by the tumor suppressor phosphatase PP2A. PP2A activity is inhibited by the oncoprotein cancerous inhibitor of PP2A (CIP2A), which has not been studied in meningiomas to our knowledge. Six fetal and one adult human leptomeningeal samples and 38 meningiomas were evaluated by western blot. Fifteen adult arachnoid granulations and 58 formalin-fixed meningiomas (36 World Health Organization grade I, 15 grade II and seven grade III) were evaluated by immunohistochemistry. The effects of the mitogens platelet derived growth factor-BB (PDGF-BB) and cerebrospinal fluid on CIP2A were also studied. By western blot, CIP2A and PP2A were found in the five fetal and one adult leptomeninges and all meningiomas. By immunohistochemistry, CIP2A was detected in the arachnoid granulations and all meningiomas. CIP2A tended to be higher in grade III tumors. Three fetal leptomeningeal (two grade I and one grade II) and meningioma cells treated with PDGF-BB and/or human cerebrospinal fluid resulted in a slight increase in CIP2A in the leptomeningeal cells but not meningioma cells. Considered the mechanism of action and seen in other neoplasms, these findings raise the possibility that CIP2A may participate in the biology of meningiomas. more...

Introduction Lesbian, gay, bisexual, or queer/questioning (LGBQ) microaggressions refer to often-unintentional insults, assaults, and invalidations that denigrate sexual minorities. While experiencing hostile discrimination and violence has previously been associated with elevated rates of smoking cigarettes for LGBQ college students, the relationship between LGBQ microaggressions and smoking is unknown. Methods Data from a national anonymous online survey of sexual and gender minority college students were used to examine the relationship between past month cigarette smoking and interpersonal LGBQ microaggressions. Multivariable logistic regression assessed the relationship between smoking and frequent (chronic) experiences of microaggressions, using a hierarchical procedure to control for demographics, predictors of smoking, and academic factors. Results Past year frequent LGBQ microaggression was reported by 48% of respondents and was more common among students who smoked in past 30 days. Experiencing past year physical violence was reported by 15% and did not differ by smoking status. Past year frequent experience of microaggressions was associated with increased odds of 1.72 (95% CI 1.03-2.87) for past 30-day smoking after adjusting for age, gender, race, socioeconomic indicators, alcohol misuse, physical violence, as well as academic stress and engagement. Conclusions The results indicate that frequently experiencing LGBQ microaggressions is a risk factor for LGBQ college students smoking cigarettes. The mechanisms underlying this relationship require additional research, as does identifying positive coping strategies and institutional strategies to address LGBQ microaggressions on campuses. Tobacco control efforts should consider the impact of microaggression on the social environment for the prevention and treatment of tobacco use among LGBQ individuals. Implications Microaggressions related to sexual minority identity include subtle forms of discrimination experienced during daily interactions that can create hostile and stressful social environments for a socially disadvantaged group. Prior research has demonstrated that LGBQ college students have higher rates of cigarette smoking, and that experiencing identity-based violence is a risk factor. This study revealed that experiencing frequent LGBQ microaggressions on college campus is associated with increased likelihood of current smoking among LGBQ college students. more...

Background: The infratemporal fossa is an anatomically complex region. Lesions that arise in the infratemporal fossa are uncommon; however, their surgical resection remain challenging. Here we present a modified preauricular subtemporal approach initially described by Obwegeser et al. used in four patients with large skull base lesions. Methods: Retrospective case series of 4 patients Results: Four patients with various lesions of the infratemporal fossa (aneurysmal bone cyst, giant cell tumor of the bone, recurrent melanoma and recurrent clival chordoma) underwent surgical resection using the modified Obwegeser approach. A multidisciplinary team cared for patients consisting of maxillofacial surgery, otolaryngology and neurosurgery. After either nasotracheal intubation or tracheostomy, the patient’s jaw was temporarily wired shut. A curvilinear incision was fashioned and the root of zygoma was exposed (masseter attached) and osteotomized followed by inferior mobilization. The mandibular condyle is osteomized next and TMJ disarticulated with temporalis muscle still attached and reflected superiorly. Surgical resection of tumor then proceeded centered around the region bridging the temporal and infratemporal fossae. Reconstruction was carried out using plates and screws. Conclusions: The modified Obwegeser approach can provide safe and direct access to certain infratemporal fossa lesions with good cosmesis and functional outcome for patients without substantially increasing OR time. more...

“That’s so gay,” a popular expression on campuses, is a sexual orientation microaggression that can contribute to a hostile environment for lesbian, gay, and bisexual (LGB) students. Using data from a campus climate survey conducted at a large urban university, we investigated use of the phrase among heterosexual male undergraduates who are emerging adults (18–25 years). Multiple regression analysis suggested that saying the phrase is positively associated with hearing peers say it and with holding negative perceptions of feminine men, whereas having LGB acquaintances was negatively associated with use of this expression. We offer practice and policy recommendations for curbing its use, thereby enhancing campus climate. more...

Available trauma scoring systems that predict need for higher echelons of care require data not available in the field. We hypothesized that analysis of continuous vital sign data in comparison to trauma registry data predicts mortality early in trauma patient management.A real-time vital signs wave form and data capture system collected trauma patient data during prehospital management from Propaq 206E physiologic monitors. Analysis using statistical and mathematical software calculated receiver operator characteristic curves to evaluate the sensitivity and specificity of continuous vital sign waveforms in predicting mortality. The area under the curve (AUC) was calculated to determine nonsurvival by a particular vital sign (oxygen saturation [SpO2], heart rate, and systolic blood pressure) from these data, compared with a single value in the trauma registry, and to standard trauma scoring systems.The average transport time from field to hospital for all patients was 25 minutes. Eight of 120 patients (7%) died; 5 of 8 patients (62%) died within the first 24 hours. Receiver operator characteristic analysis of mean SpO290% versus mortality yielded an AUC of 0.76 (p = 0.005) with a sensitivity of 62% and specificity of 86% The initial SpO290% measurement from the trauma registry yielded an AUC of 0.59. Preadmission Glasgow Coma Scale score yielded an AUC of 0.74 (p = 0.009). Injury Severity Score and Trauma-Injury Severity Score produced AUCs of 0.91 and 0.96, respectively. Revised Trauma Score gave an AUC of 0.73, no different from automated predictions of mortality from SpO2.Injury Severity Score and Trauma-Injury Severity Score are predictive of mortality but rely on the inclusion of intra-abdominal and intrathoracic diagnostic data that are not readily available during field assessment. Automated vital signs data collection and analysis from a single noninvasive device with decision support has the potential to alleviate the dual burdens of patient triage and documentation required of the prehospital provider. more...

Qualitative researchers have a dual mission: to generate knowledge through rigorous research and to uphold ethical standards and principles. Qualitative researchers often conduct studies with small connected communities in which relationships exist among community members. When engaging such communities, researchers might face ethical issues in upholding confidentiality standards while they work to achieve their dual mandate. Qualitative scholars have paid little attention to the ethical challenges that might arise in this context. Drawing on our experiences conducting studies with such communities, we expand the dialogue concerning qualitative research ethics by making explicit conceptual and practical tensions that emerge at various stages of the research process; articulating our respective reflective processes; and exploring issues associated with strategies for upholding confidentiality. We conclude with lessons learned to guide researchers who might face similar challenges. more...

Intergroup dialogue is a method of social justice education. Most intergroup dialogue research explores race and gender identities. Sexual orientation dialogues are uncommon and not yet examined empirically. This qualitative study explores sexual orientation dialogue courses from the perspective of lesbian, gay, and bisexual (LGB) student participants. Understanding target, or marginalized, group perspective of planned intergroup experiences is important given concerns raised in the literature. We document student motivations for participating in dialogues, core outcomes, and main challenges that arose in dialogue. Core outcomes include learning about and accepting one's sexual identity and empowerment. Challenges include those stemming from invisibility of sexual orientation identity. Recommendations are made for intergroup dialogue practice and research. more...

This study explored HIV vaccine acceptability and strategies for culturally appropriate dissemination among sexually diverse Aboriginal peoples in Canada, among those at highest HIV risk. We conducted four focus groups (n=23) with Aboriginal male (1) and female (1) service users, peer educators (1) and service providers (1) in Ontario, Canada. Transcripts were analysed with narrative thematic techniques from grounded theory, using NVivo. Participants' mean age was 37 years; about half (52%) were female, half (48%) Two-spirit or lesbian, gay or bisexual (LGB)-identified, 48% had a high-school education or less and 57% were unemployed. Vaccine uptake was motivated by community survival; however, negative HIV vaccine perceptions, historically based mistrust of government and healthcare institutions, perceived conflict between western and traditional medicine, sexual prejudice and AIDS stigma within and outside of Aboriginal communities, and vaccine cost may present formidable obstacles to HIV vaccine acceptability. Culturally appropriate processes of engagement emerged on individual levels (i.e., respect for self-determination, explanations in Native languages, use of modelling and traditional healing concepts) and community levels (i.e., leadership by Aboriginal HIV advocates and political representatives, identification of gatekeepers, and procuring Elders' endorsements). Building on cultural strengths and acknowledging the history and context of mistrust and social exclusion are fundamental to effective HIV vaccine dissemination. more...

Precession of magnetization via the inverse Faraday effect is investigated with a view of determining the fundamental limit on the precession speed. Such a limit could have important consequences for ultrafast magnetic switching. The angular momentum required for precession is shown to be supplied by the light. This indicates that there is no fundamental obstruction to magnetization reversal on the time scale of a laser pulse provided that a material with a sufficiently strong magneto-optical response can be found. more...

Dephasing of quantum dots presents an intrinsic limitation on their use for quantum computing. We consider the dephasing of a double quantum dot caused by the Coulomb interaction with nearby gate electrodes and show that this occurs on a much longer time scale than dephasing due to phonons. However, the effect grows rapidly stronger as the system size decreases, and therefore it is expected to limit potential miniaturization of these systems. more...

The interaction between a Bloch and a Neel wall in the parametrically driven nonlinear Schrodinger equation is studied by following the dissociation of their unstable bound state. Mathematically, the analysis focuses on the splitting of a fourfold zero eigenvalue associated with a pair of infinitely separated Bloch and Neel walls. It is shown that a Bloch and a Neel wall interact as two classical particles, one with positive and the other one with negative mass. more...

The Faraday effect is an extremely useful probe of magnetization dynamics on an ultrafast scale. However, the measured Faraday rotation is difficult to interpret in birefringent media. We investigate the link between magnetization and Faraday rotation by solving Maxwell's equations in a magnetically ordered, birefringent material. We find that the Faraday rotation can depend nonlinearly on the magnetization, meaning that symmetric magnetic oscillations may lead to asymmetric Faraday measurements. Furthermore, sample alignment becomes important-if the incident light is not polarized along a birefringence axis of the sample, the Faraday rotation may be strongly enhanced or weakened, and the interpretation of the magnetization amplitude may be wrong by an order of magnitude. (c) 2007 American Institute of Physics. more...

We study interactions between the dark solitons of the parametrically driven nonlinear Schr\"odinger equation, Eq.(\ref{NLS}). When the driving strength, $h$, is below $\sqrt{\gamma^2 +1/9}$, two well-separated N\'eel walls may repel or attract. They repel if their initial separation $2z(0)$ is larger than the distance $2z_u$ between the constituents in the unstable stationary complex of two walls. They attract and annihilate if $2z(0)$ is smaller than $2z_u$. Two N\'eel walls with $h$ lying between $\sqrt{\gamma^2 + 1/9}$ and a threshold driving strength $h_{sn}$ attract for $2z(0)2z_u$. Finally, the N\'eel walls with $h$ greater than $h_{sn}$ attract and annihilate -- irrespective of their initial separation. Two Bloch walls of opposite chiralities attract, while Bloch walls of like chiralities repel -- except near the critical driving strength, where the difference between the like-handed and oppositely-handed walls becomes negligible. In this limit, similarly-handed walls at large separations repel while those placed at shorter distances may start moving in the same direction or transmute into an oppositely-handed pair and attract. The collision of two Bloch walls or two nondissipative N\'eel walls typically produces a quiescent or moving breather., Comment: 46 pages, 23 figures. To appear in Phys Rev E. A reference added more...

The parametrically driven Ginsburg-Landau equation has well-known stationary solutions -- the so-called Bloch and Neel, or Ising, walls. In this paper, we construct an explicit stationary solution describing a bound state of two walls. We also demonstrate that stationary complexes of more than two walls do not exist., Comment: 10 pages, 2 figures, to appear in Physical Review E more...

We show that unlike the bright solitons, the parametrically driven kinks are immune from instabilities for all dampings and forcing amplitudes; they can also form stable bound states. In the undamped case, the two types of stable kinks and their complexes can travel with nonzero velocities., Comment: 4 pages; 2 figures; to appear in PRL more...

We consider the one-dimensional anisotropic XY model in the continuum limit. Stability analysis of its Bloch wall solution is hindered by the non-diagonality of the associated linearized operator and the Hessian of energy. We circumvent this difficulty by showing that the energy admits a Bogomolnyi bound in elliptic coordinates and that the Bloch wall saturates it—that is, the Bloch wall renders the energy minimum. Our analysis provides a simple but nontrivial application of the BPS (Bogomolnyi–Prasad–Sommerfield) construction in one dimension, where its use is often believed to be limited to reproducing results obtainable by other means. more...