ZHX2 REGULATION OF LIPID METABOLISM AND THE BALANCE BETWEEN CARDIOVASCULAR AND HEPATIC HEALTH

The growing obesity epidemic in America carries with it numerous health risks, including diabetes, increased serum lipid levels, and excess fat accumulation in the liver. If these conditions persist or become exacerbated, they may lead to the development of cardiovascular disease, the current leading cause of death among Americans, or to nonalcoholic fatty liver disease (NAFLD) which can progress to hepatocellular carcinoma (HCC), one of the deadliest forms of cancer. Better understanding of the genes involved in these diseases can lead to improved identification of at-risk individuals and treatment strategies. Our lab previously identified zinc fingers and homeoboxes 2 (Zhx2) as a regulator of hepatic gene expression. The BALB/cJ mouse strain has a hypomorphic mutation in the Zhx2 gene, causing a 95% reduction in Zhx2 protein expression. The near ablation of Zhx2 in BALB/cJ mice confers protection from cardiovascular disease when fed a high fat diet, yet these mice show increased hepatic lipid accumulation and liver damage. Microarray data indicates Zhx2 may be involved in the regulation of numerous genes involved in lipid metabolism. Recent GWAS studies indicate ZHX2 may contribute to the risk of cardiovascular disease and liver damage in humans as well. In this dissertation, I characterize the role of Zhx2 expression in the liver and how it affects the risk of both cardiovascular disease and liver damage. I generated liver-specific Zhx2 knockout mice and confirmed Zhx2 regulates several novel targets that could contribute to the fatty liver phenotype seen in BALB/cJ mice. Further studies revealed that hepatic Zhx2 expression is necessary for proper sex-specific expression of several Cyptochrome P450 (CYP) genes and could contribute to gender differences in disease susceptibility. Lastly, I performed studies into the functional role of the Zhx2 target gene Elovl3. A mouse model of HCC revealed that Elovl3 is completely repressed in HCC tumors. Cell viability and cell cycle assays indicate that Elovl3 expression slows cell proliferation and may be important for proper cell cycle checkpoints. Together, these data indicate that Zhx2 and/or its targets could be clinically relevant in the detection, prevention, or treatment of cardiovascular disease, fatty liver, and HCC

Faculty\u27s relationship to the identity problem of the community college : a study of faculty support for specific institutional directions for the Virginia community college system

The purpose of this study was to determine Virginia Community College System (VCCS) faculty preferences for four possible institutional directions for the VCCS and to explore possible relationships between specific faculty characteristics and preferences for the individual directions. Information derived from the study was to be used to clarify whether or not community college faculty support the broad institutional directions by community college leaders in their efforts to instill a strong identity for this institution.;The population for this study was all full-time teaching faculty in the VCCS for the academic year 1982-83. 323 faculty were systematically selected after first being stratified along the variable of institutional size as determined by full-time student enrollment. Those selected for the sample received a survey questionnaire primarily asking them to rank order their preferences for four possible institutional directions for the VCCS and requesting information about specific faculty characteristics.;It was hypothesized that (1) the majority of VCCS faculty would rank first the direction of Comprehensive Community College, (2) that they would least prefer the direction of Community-Based Learning Center, and (3) that specific faculty characteristics would affect specific preferences.;Information derived from the completed questionnaires (70 percent response rate) was statistically analyzed using multiple discriminant function analysis. The results supported the first two hypotheses but failed to show any correlation between specific faculty characteristics and specific directions with one exception: faculty teaching the majority of their courses in occupational-technical courses were likely to most prefer the institutional direction of Comprehensive Community College.;The results also support the overall conclusion that the heterogeneity of community college faculty negatively affects their unanimity for any one institutional direction desired by national and state leaders of the community college. The lack of support for any one institutional direction may be an important factor in the community college\u27s continuing identity problem with the general public, legislators, and those in higher education.;Further study is needed to clarify which faculty characteristics, if any, affect preferences for institutional directions. In addition, student, administrator, and alumni preferences should also be investigated

Speaking the body, representing the self : hysterical rhetoric on stage

This thesis centres on the twin discourses of hysteria and theatre, and contends that an examination of hysteria, which is above all a performative disease, can illuminate our understanding of performance on the public stage. My analysis of the history of hysteria shows that our modern understanding of the condition developed out of the interactions between the physician/analyst and the live body of the hysteric, with all its symptomatic acts, this thesis, which has as its central concern the live body of staged performance, uses the history of those interactions to re-centre attention on the symptomatic acts of the performing body on stage, and on the process of reading such acts. Drawing its material from a number of stage performances from the nineteenth and twentieth centuries - from the texts of melodrama such as The Dumb Man of Manchester(l837) or The Bells (1871) through the work of the American actress Elizabeth Robins in Ibsen's Hedda Gabler (1891) and her own play Alan's Wife (1893) to modem texts such as Helne Cixous's Portrait of Dora (1976) - this thesis reads those performances, and the relationship of those performances to their audiences, through the lens of hysteria: using an understanding of hysteria to read those texts anew and, in reverse, using the texts to develop, and critique, a model of hysterical performance rhetoric. Such a model, this thesis argues, with its very basis in a condition of rejection of or failure to fit into the dominant discourses of society, is not limited in application to performance texts which take hysteria as their subject. Instead it can be more widely employed as a key part of a radical theatrical politics by those who today find themselves silenced by the dominant discourses and values of our own era

Addressing Inequality: Framing Social Protection in National Development Strategies

It is important to address different inequalities and one way to achieve this is through social protection as a mechanism for redistribution. Achieving social justice and a reduction in inequalities through social protection will also require other policies to be in place. This article suggests that social protection will be most effective at reducing inequalities if it is integrated in a coherent national development strategy (NDS), which provides a framework for policy formulation and linkages, and if policies are rooted in solid analysis to enable them to target specific inequalities. It also argues that NDSs need to be formulated so that they are based on alternative visions of development that give voice to various groups, notably the excluded. ActionAid's NDS project is provided as an example of how to reduce inequalities and advance redistributive and transformative social protection

Term Harvesting & Generation Guide

The "Term Harvesting & Generation Guide" outlines term harvesting strategies to help build the list of search terms for advanced literature reviews, such as systematic reviews. The Guide was developed by a team of Taubman Health Sciences Library Informationists as an instructional tool for the Systematic Reviews: Opportunities for Librarians Workshop and Advanced Literature Searching in the Health Sciences Massive Open Online Course.https://deepblue.lib.umich.edu/bitstream/2027.42/153785/4/Term_Harvesting_and_Generation_Guide.pd

Zhx2 (Zinc Fingers and Homeoboxes 2) Regulates Major Urinary Protein Gene Expression in the Mouse Liver

The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. Zhx2 is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ Zhx2 allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with in vitro assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes

Estimation of the prevalence of cholesteryl ester storage disorder in a cohort of patients with clinical features of familial hypercholesterolaemia

Background and aim Familial hypercholesterolaemia is caused by variants in the low-density lipoprotein cholesterol metabolic pathway involving LDLR, APOB and PCSK9 genes. A national genetic testing service in Wales, UK has observed that no familial hypercholesterolaemia variant is found in almost 80% patients with the familial hypercholesterolaemia phenotype. It has recently been suggested that some adult patients with a familial hypercholesterolaemia phenotype may have cholesteryl ester storage disease which can also present as a mixed hyperlipidaemia. The commonest genetic cause of cholesteryl ester storage disease is an exon 8 splice junction variant in the LIPA gene (rs116928232, c.894G>A; E8SJM) previously found to have an allele frequency of 0.0011 (1 in 450 individuals) in a large European population. This study investigated the prevalence of the E8SJM in patients with a familial hypercholesterolaemia phenotype in Wales, UK. Method A total of 1203 patients with a clinical suspicion of familial hypercholesterolaemia but no familial hypercholesterolaemia variant were invited to participate. Of these, 668 patients provided informed written consent. Stored DNA samples from 663 patients were genotyped for the E8SJM variant. Results Three heterozygotes were identified (allele frequency 0.0023). Whole gene sequencing of the LIPA gene was undertaken in these three individuals, but no other variants were found. Therefore, there were no cholesteryl ester storage disease patients (homozygote or compound heterozygote) identified in this cohort. Conclusion The allele frequency 0.0023 (1 in 221 individuals) for the E8SJM variant was more prevalent in this cohort than in a European population study; however, no cholesteryl ester storage disease homozygotes were identified. We found no evidence to support routine testing for cholesteryl ester storage disease in adult patients with a familial hypercholesterolaemia phenotype

23 Things: Online Training for Social Media and Public Health

http://deepblue.lib.umich.edu/bitstream/2027.42/94443/1/23 Things Online Training for Social Media and Public Health.pd

Reading for Charles Burchfield

Featuring poets who participated in the March 8th Heat Waves in a Swamp workshop

Exile Vol. XXXI No. 2

Plenty of Space by Carol Contiguglia (cover) Dénouement by Jeff Masten 3 The Ballad of Old Bill Brown by Amy Becker 4-5 Elegy by Ann Townsend 6 Untitled by Karen Koch 7 Dénouement by Carol Mason 9-14 Untitled by N. R. B. III 15 A Lot in Common We Two, by David Zivan 17 The Sidewalk Taken, Kate Anthony 18 Upon Hearing Two Male Poets Read by Karen J. Hall 19 Leaves by Amy Becker 20 To Dad by Carrie Jordan 21 Attie Mae by Theresa Copeland 23-25 Oh, Henry by T. S. Elliott 26-38 Solitude; Normandy, France by Margie Boll 39 In Edgartown, Drunk, Stranded in the A.M. by Karen Kearney 41 Pink Feet by Catherine DuBois 42 Ensign in the Naval Corps of Engineers by Betsy Oster 43 Morning Haze by Stephanie Athey 44-45 Just Thought You\u27d Like to Know by Joan DeWitt 46-53 Art Class, A Study of Still-Lifes by Margie Boll 55 Contributor Notes 57 Editorial decision is shared equally among the Editorial Board members -cover page (credited here as editors ) PRINTING BY / PRINTING ARTS PRESS / MOUNT VERNON, OHIO -back cove