Constitutive notch signaling in adult transgenic mice inhibits bFGF-induced angiogenesis and blocks ovarian follicle development

Notch signaling is important in angiogenesis during embryonic development. However, the embryonic lethal phenotypes of knock-out and transgenic mice have precluded studies of the role of Notch post-natally. To develop a mouse model that would bypass the embryonic lethal phenotype and investigate the possible role of Notch signaling in adult vessel growth, we developed transgenic mice with Cre-conditional expression of the constitutively active intracellular domain of Notch1 (IC-Notch1). Double transgenic IC-Notch1/Tie2-Cre embryos with endothelial specific IC-Notch1 expression died at embryonic day 9.5. They displayed collapsed and leaky blood vessels and defects in angiogenesis development. A tetracycline-inducible system was used to express Cre recombinase postnatally in endothelial cells. In adult mice, IC-Notch1 expression inhibited bFGF-induced neovascularization and female mice lacked mature ovarian follicles, which may reflect the block in bFGF-induced angiogenesis required for follicle growth. Our results demonstrate that Notch signaling is important for both embryonic and adult angiogenesis and indicate that the Notch signaling pathway may be a useful target for angiogenic therapies.

Segmentation and Segregation Patterns of Women-Owned High-Tech Firms in Four Metropolitan Regions in the United States

Mayer H. Segmentation and segregation patterns of women-owned high-tech firms in four metropolitan regions in the United States, Regional Studies. The number of women starting and owning a business has increased dramatically and female entrepreneurs are entering non-traditional sectors such as high technology, construction and manufacturing. This paper investigates the trends in high-tech entrepreneurship by women in four US metropolitan regions (Silicon Valley, California; Boston, Massachusetts; Washington, DC; and Portland, Oregon). The research examines the sectoral and spatial segmentation patterns of women-owned high-tech firms. Although women are entering non-traditional sectors, the research finds that women entrepreneurs tend to own businesses in female-typed high-tech sectors. In established high-tech regions like Silicon Valley and Boston, male-typed and female-typed women-owned high-tech firms differ significantly in terms of sectoral and spatial segmentation regardless of firm age. While differences between male-typed and female-typed firms are not significant at the regional level for Washington, DC, the analysis shows significant intra-metropolitan differences for the female-typed high-tech firms. The paper concludes that sectoral and spatial segmentation are powerful dynamics that shape business ownership by women in high technology.

Mechanisms of rapid sympatric speciation by sex reversal and sexual selection in cichlid fish

Mechanisms of speciation in cichlid fish were investigated by analyzing population genetic models of sexual selection on sex-determining genes associated with color polymorphisms. The models are based on a combination of laboratory experiments and field observations on the ecology, male and female mating behavior, and inheritance of sex-determination and color polymorphisms. The models explain why sex-reversal genes that change males into females tend to be X-linked and associated with novel colors, using the hypothesis of restricted recombination on the sex chromosomes, as suggested by previous theory on the evolution of recombination. The models reveal multiple pathways for rapid sympatric speciation through the origin of novel color morphs with strong assortative mating that incorporate both sex-reversal and suppressor genes. Despite the lack of geographic isolation or ecological differentiation, the new species coexists with the ancestral species either temporarily or indefinitely. These results may help to explain different patterns and rates of speciation among groups of cichlids, in particular the explosive diversification of rock-dwelling haplochromine cichlids.

Gender-Specific Associations between Circulating T-Cadherin and High Molecular Weight-Adiponectin in Patients with Stable Coronary Artery Disease.

Close relationships exist between presence of adiponectin (APN) within vascular tissue and expression of T-cadherin (T-cad) on vascular cells. APN and T-cad are also present in the circulation but here their relationships are unknown. This study investigates associations between circulating levels of high molecular weight APN (HMW-APN) and T-cad in a population comprising 66 women and 181 men with angiographically proven stable coronary artery disease (CAD). Plasma HMW-APN and T-cad were measured by ELISA and analysed for associations with baseline clinical characteristics and with each other. In multivariable analysis BMI and HDL were independently associated with HMW-APN in both genders, while diabetes and extent of coronary stenosis were independently associated with T-cad in males only. Regression analysis showed no significant association between HMW-APN and T-cad in the overall study population. However, there was a negative association between HMW-APN and T-cad (P=0.037) in a subgroup of young men (age <60 years, had no diabetes and no or 1-vessel CAD) which persisted after multivariable analysis with adjustment for all potentially influential variables (P=0.021). In the corresponding subgroup of women there was a positive association between HMW-APN and T-cad (P=0.013) which disappeared after adjustment for HDL. After exclusion of the young men, a positive association (P=0.008) between HMW-APN and T-cad was found for the remaining participants of the overall population which disappeared after adjustment for HDL and BMI. The existence of opposing correlations between circulating HMW-APN and T-cad in male and female patient populations underscores the necessity to consider gender as a confounding variable when evaluating biomarker potentials of APN and T-cad.

Function and regulation of the Pem homeobox gene in vivo

Pem, a member of the PEPP homeobox family, is expressed in somatic cells in male and female reproductive tissues. In the adult murine testis, Pem is specifically expressed in Sertoli cells, where it is restricted to stages IV–VIII of the seminiferous epithelial cycle. To identify Pem's function in Sertoli cells, transgenic mice were generated that express Pem in Sertoli cells during all stages of the seminiferous epithelial cycle. This resulted in an increase in double-strand DNA breaks in preleptotene spermatocytes and single-strand DNA breaks in elongating spermatids. My results suggest that Pem regulates Sertoli-cell genes that encode secreted or cell-surface proteins that serve to control premeiotic DNA replication, DNA repair, and/or chromatin remodeling in the adjacent germ cells. Three additional transgenic mouse containing varying lengths of the Pem male-specific promoter (Pp) were generated to identify the sequences responsible for regulating Pem expression in the testis and epididymis. My analysis suggests that there are at least two regulatory regions in the Pem Pp. In the testis, region II directs androgen-dependent expression specifically in Sertoli cells whereas region I fine-tunes stage-specific expression by acting as a negative regulator. In the epididymis, region II confers androgen-dependent, developmentally-regulated expression in the caput whereas region I prevents inappropriate expression in the corpus. I also report the identification and characterization of two human PEPP family members related to Pem that I have named hPEPP1 and hPEPP2. The hPEPP1 and hPEPP2 homeodomains are more closely related to PEPP subfamily homeodomains than to any other homeodomain subfamily. Both genes are localized to the specific region of the human X chromosome that shares synteny with the region on the murine X chromosome containing three PEPP homeobox genes, Pem, Psx-1, and Psx-2. hPEPP1 and hPEPP2 mRNA expression is restricted to the testis but is aberrantly expressed in tumor cells of different origins, analogous to the expression pattern of Pem but not of Psx-1 or Psx-2. Unlike all known PEPP members, neither hPEPP1 nor hPEPP2 are expressed in placenta, which suggests that the regulation of the PEPP family has undergone significant alteration since the split between hominids and rodents. ^

Productivity and Market Integration in American Communal Dairying, 1830-1875

In our late twentieth century experience, survival of an economy seems critically dependent on well established rights to private property and a return to labor that rewards greater effort. But that need not be so. History provides examples of micro-socialist economies that internally, at least, allow for little private property for participants and a constant return to labor that is independent of effort. Some such economies may even be termed 'successful,' if success is taken to mean survival over several generations. If these communities survived without conditions that are generally thought to be necessary for success, a question worth asking is how this occurred, for we can then shed some light on what really is necessary for economic survival. Addressing this issue emphasizes the critical role of time, for even if the microsocialist economies that we study here eventually became the merest shadow of their former selves, the fact that they did flourish for so long makes them a valuable counterexample, and hence, a phenomenon in need of explanation. We consider here the dairy industry of the Shakers, which was characterized by intensive efforts to increase productivity, in part through the use of market signals, but efforts that were also limited by the ideological goals of the community. The Shakers were (and are, but since it is the historical Shakers that concern this paper, the past tense will be used) a Christian communal group. Some of their distinctive beliefs included the existence of a male and female Godhead, from which followed sexual equality, and active communication between Believers (a Shaker term for members of the sect) and denizens of the spirit world. Practices of the Society (their official name is the United Society of Believers in Christ's Second Appearing, the second appearing being in the body of their foundress, an illiterate Englishwoman named Ann Lee) included pacifism, celibacy, confession of sins to elders, and joint or communal ownership of the Society's assets. Each Shaker received the same return for his or her labor: room, board, clothing, and the experience of divine proximity in a community of like minded Believers (Stein 1992).

Gender associated risk factors of aortic aneurysms and dissections

Objectives. Predict who will develop a dissection. To create male and female prediction models using the risk factors: age, ethnicity, hypertension, high cholesterol, smoking, alcohol use, diabetes, heart attack, congestive heart failure, congenital and non-congenital heart disease, Marfan syndrome, and bicuspid aortic valve. ^ Methods. Using 572 patients diagnosed with aortic aneurysms, a model was developed for each of males and females using 80% of the data and then verified using the remaining 20% of the data. ^ Results. The male model predicted the probability of a male in having a dissection (p=0.076) and the female model predicted the probability of a female in having a dissection (p=0.054). The validation models did not support the choice of the developmental models. ^ Conclusions. The best models obtained suggested that those who are at a greater risk of having a dissection are males with non-congenital heart disease and who drink alcohol, and females with non-congenital heart disease and bicuspid aortic valve.^

Hepatitis B and C infections in U.S. incarcerated populations: Prevalence and related mortality

Published reports have consistently indicated high prevalence of serologic markers for hepatitis B (HBV) and hepatitis C (HCV) infection in U.S. incarcerated populations. Quantifying the current and projected burden of HBV and HCV infection and hepatitis-related sequelae in correctional healthcare systems with even modest precision remains elusive, however, because the prevalence and sequelae of HBV and HCV in U.S. incarcerated populations are not well-studied. This dissertation contributes to the assessment of the burden of HBV and HCV infections in U.S. incarcerated populations by addressing some of the deficiencies and gaps in previous research. ^ Objectives of the three dissertation studies were: (1) To investigate selected study-level factors as potential sources of heterogeneity in published HBV seroprevalence estimates in U.S. adult incarcerated populations (1975-2005), using meta-regression techniques; (2) To quantify the potential influence of suboptimal sensitivity of screening tests for antibodies to hepatitis C virus (anti-HCV) on previously reported anti-HCV prevalence estimates in U.S. incarcerated populations (1990-2005), by comparing these estimates to error-adjusted anti-HCV prevalence estimates in these populations; (3) To estimate death rates due to HBV, HCV, chronic liver disease (CLD/cirrhosis), and liver cancer from 1984 through 2003 in male prisoners in custody of the Texas Department of Criminal Justice (TDCJ) and to quantify the proportion of CLD/cirrhosis and liver cancer prisoner deaths attributable to HBV and/or HCV. ^ Results were as follows. Although meta-regression analyses were limited by the small body of literature, mean population age and serum collection year appeared to be sources of heterogeneity, respectively, in prevalence estimates of antibodies to HBV antigen (HBsAg+) and any positive HBV marker. Other population characteristics and study methods could not be ruled out as sources of heterogeneity. Anti-HCV prevalence is likely somewhat higher in male and female U.S. incarcerated populations than previously estimated in studies using anti-HCV screening tests alone without the benefit of repeat or additional testing. Death rates due to HBV, HCV, CLD/cirrhosis, and liver cancer from 1984 through 2003 in TDCJ male prisoners exceeded state and national rates. HCV rates appeared to be increasing and disproportionately affecting Hispanics. HCV was implicated in nearly one-third of liver cancer deaths. ^

Examination of the influence of behavioral, normative and control beliefs on the adherence to a prescribed renal diet among elderly populations with chronic to end-stage renal disease

The 1999-2004 prevalence of chronic kidney disease in adults 20 year or older (15.5 million) is an estimated 7.69%. The risk of developing CKD is exacerbated by diabetes, hypertension and/or a family history of kidney disease. African Americans, Hispanics, Pacific Islanders, Native Americans, and the elderly are more susceptible to higher incidence of CKD. The challenges of aging coupled with co-morbidities such as kidney disease raises the potential for malnutrition among elderly (for the purpose of this study 55 years or older) populations. Lack of adherence to prescribed nutrition guidelines specific to renal failure jeopardizes body homeostasis and increases the likelihood of future morbidity and resultant mortality. The relationship and synergy that exists between diet and disease is evident. Clinical experience with renal patients has indicated the importance of adherence to diet therapy specific to kidney disease. Extension investigation of diet adherence among endstage renal disease patients revealed a sizeable dearth in the current literature. This thesis study was undertaken to help reduce that void. The study design is qualitative and descriptive. Support, cooperation, and collaboration were provided by the University of Texas Nephrology Department, University of Texas Physicians, and DaVita Dialysis Centers. Approximately 105 male and female chronic to end-stage kidney disease patients were approached to participate in elicitation interviews in dialysis treatment facilities regarding their present diet beliefs and practices. Eighty-five were recruited and agreed to participate. Inclusion criteria required individuals to be between 35-90 years of age; capable of completing a 5-10 minute interview; and English speaking. Each kidney patient was asked seven (7) non-leading questions developed from the constructs of the Theory of Planned Behavior. The study presents a descriptive comparison of behavioral, normative, and control beliefs that influence adherence to renal diets by age, race, and gender. The study successfully concluded that behavioral, normative, and control beliefs of chronic to end-stage renal patients promoted execution and adherence to prescribed nutrition. This study provides valuable information for dietitians, technicians, nurses, and physicians to assess patient compliance toward prescribed nutrition and the means to support or improve that performance. ^

The association between classroom characteristics and student physical activity in physical education classrooms

Background. With the rapid rise in childhood obesity, physical activity participation among young children has become the subject of much recent attention. Physical education classes have been specifically targeted as a method of providing opportunities for all children to be active. Unfortunately, student participation in moderate-to-vigorous physical activity during these classes still falls far below the current recommendations. While some research to date has reported the levels of activity among elementary-aged children, research is limited on the relationship between these activity levels and the environmental characteristics that exist within the PE classroom. ^ Purpose. The purpose of this study is to examine the association between specific classroom characteristics and contextual characteristics (lesson context, class size, class location, teacher gender, and teacher encouragement for PA) with elementary aged children's moderate-to-vigorous activity during PE class. ^ Methods. A secondary analysis of 211 3rd, 4th and 5th grade physical education classes amongst 39 elementary schools in Harris County, TX and 35 elementary schools in Travis County, TX was conducted using cross-sectional data from the evaluation of a school-based health program. Lesson context and student activity levels were measured using a direct observation measurement tool. Additionally, these variables were further analyzed against a number of classroom characteristics to determine any significant associations. ^ Results. Overall, elementary PE classes are still participating in low levels of moderate-to-vigorous physical activity averaging only 38% of class time. Additionally, close to 25% of class time is spent in classroom management. Male directed classes spent significantly more time in game activities and female directed classes spent more time in fitness, knowledge, and skill activities. Classes that took place outdoors were more active and spent more time in games than those that took place indoors. Significant correlations were demonstrated between class size and time spent in management context. Time spent in management context was also correlated with time spent sitting and standing. Additionally, positive correlations were demonstrated between time very active and teachers that praised students and encouraged physical activity among their classes.^

Gender differences in life circumstances, monthly income, risky sexual and drug behaviors among injection drug users in Dar es Salaam, Tanzania

This study investigated the gender difference between male and female injection drug users’ (IDUs) life circumstances, income and risky sexual and drug behaviors. The study sample comprised of 318 male and 249 female injection drug users in Dar es Salaam, Tanzania. There were gender differences between male and female IDUs in terms of life circumstances and sexual behaviors. There were no differences in the drug behaviors among the two sexes. Women were more likely to be 21-25 years of age, have had more sexual partners in the last 30 days, traded sex for money, and have been sexually abused as a child. On the other hand, the males were more likely to be 26-30 years of age and have never used a condom during sex in the last 30 days. Regardless of the differences in sexual risk behaviors by gender, both male and female injection drug users in Dar es Salaam are at risk of HIV/AIDS, blood borne and other sexually transmitted diseases associated with drug use.^

Sexual initiation of U.S. Latino and Colombian high school students: Toward a new theory of adolescent sexuality and implications for sexual health prevention and promotion

The general research question for this dissertation was: do the data on adolescent sexual experiences and sexual initiation support the explicit or implicit adolescent sexuality theories informing the sexual health interventions currently designed for youth? To respond to this inquiry, three different studies were conducted. The first study included a conceptual and historical analysis of the notion of adolescence introduced by Stanley Hall, the development of an alternative model based on a positive view of adolescent sexuality, and the rationale for introducing to adolescent sexual health prevention programs the new definitions of sexual health and the social determinants of health approach. The second one was a quantitative study aimed at surveying not only adolescents' risky sexual behaviors but also sexual experiences associated with desire/pleasure which have been systematically neglected when investigating the sexual and reproductive health of the youth. This study was conducted with a representative sample of the adolescents attending public high schools in the State of Caldas in the Republic of Colombia. The third study was a qualitative analysis of 22 interviews conducted with male and female U.S. Latino adolescents on the reasons for having had or having not had vaginal sex. The more relevant results were: most current adolescent sexual health prevention programs are still framed in a negative approach to adolescent sexuality developed a century ago by Stanley Hall and Sigmund Freud which do not accept the adolescent sexual experience and propose its sublimation. In contrast, the Colombian study indicates that, although there are gender differences, adolescence is for males and females a normal period of sexual initiation not limited to coital activity, in which sexual desire/pleasure is strongly associated with sexual behavior. By the same token, the study about the reasons for having had or not had initiated heterosexual intercourse indicated that curiosity, sexual desire/pleasure, and love are basic motivations for deciding to have vaginal sexual intercourse for the first time and that during adolescence, young women and men reach the cognitive development necessary for taking conscious decisions about their sexual acts. The findings underline the importance of asking pertinent questions about desire/pleasure when studying adolescent sexuality and adopting an evidence-based approach to sexual health interventions.^

The contribution of change in ethnic composition to prevalence of obesity and overweight

Objective. The prevalence of overweight and obesity differs substantially among children of different ethnic origin in the United States. The objective of this project is to estimate to what extent changes in ethnic composition since 1980 have contributed to the current general “obesity epidemic” in the childhood population of the United States.^ Methods. Populations by single year of age, 0 to 19, male and female, for Hispanics, non-Hispanic whites, and non-Hispanic blacks, from the US Census’ July estimates for 1985, 1990, 1995, 2000 and 2005 were taken and compared to the population and percentage of those groups from 1980. Age, sex, and ethnicity specific prevalence rates for overweight in 1980 were then applied to the populations by age for the specified year and differences in expected and actual overweight populations were assessed.^ Result. The results from this investigation provide estimates of the contribution that different ethnic groups have made to the overall prevalence of overweight and obesity in the childhood population of the United States. Assuming that the 1976-1980 prevalence rates had remained unchanged, and then comparing the population had there been no change in ethnic composition with the population given the actual change in ethnicity, the percentage increase was 1.06% in 1985, 1.72% in 1990, 2.57% in 1995, 3.95% in 2000, and 4.39% in 2005.^ Conclusion. The changes in ethnic composition of the population, independent of changes in ethnicity-specific prevalence, have contributed substantially to the current overall prevalence of obesity in the United States childhood population. There are a number of factors that may be responsible for the apparent susceptibility of Mexican-Americans and non-Hispanic blacks to overweight and obesity. Further research is needed on specific characteristics of those populations.^

African American and Hispanic adolescent STI and pregnancy prevention: Whose responsibility is it, anyway?

This dissertation utilized quantitative and qualitative methods to examine the role of responsibility in the prevention of sexually transmitted infections (STIs) and pregnancy through condom use and other sexual behaviors among young adolescents. Data were analyzed across race and gender and three papers were developed. The quantitative portion used logistic regression to assess associations between personal responsibility, as well as other know correlates, and reported condom use and condom use intentions as a means of STI and pregnancy prevention among 445 inner-city, high school adolescents. Responsibility to prevent pregnancy by providing the condom was associated with condom use at last sex and consistent condom use. Responsibility to prevent acquiring a STI by using a condom was significantly associated with consistent condom use. No significant associations were found between responsibility and condom use intentions. ^ The qualitative section of the dissertation project involved conducting 28 in-depth interviews among 9th and 10th grade, African American and Hispanic students who attended a large urban school district in South Central Texas. Perceptions of responsibility for preventing STIs and unintended pregnancy, as well as for condom use, were explored. Male and female adolescents expressed joint responsibility to prevent a STI or pregnancy. Perceptions of responsibility for providing and using the condoms were mixed. Despite the indication of both partners, mostly all participants implied that females, more so than the males, had the final responsibility to prevent contracting a STI, a pregnancy, to provide a condom, and to make sure a condom was used. Participants expressed the role of parents' involvement for preventing these outcomes as well as the need for more sexual health education and access to preventative methods. ^ The last section of this dissertation involved qualitative inquiry to ascertain perceptions of reasons why adolescents engage in anal and oral (non-coital) sex. Pleasure-seeking and giving as well social influence and pressure were described as the main reasons why teenagers have non-coital sex. Other reasons included conveniences of participating in these behaviors such as ease of performing oral sex and anal sex as a convenient alternative to vaginal sex. Sexual inexperience was an indicator for why anal sex occurs. Many of the reasons involved misperceptions and adolescents who practice these sexual behaviors place themselves at-risk for contracting a STI. ^ This dissertation increased the current knowledge base about adolescent sexual responsibility and non-coital behaviors. Future studies should explore perceptions of responsibility and actual sexual activity practices among adolescents to reduce the burden of STIs and pregnancy as well as help public health professionals develop programs for adolescent populations, schools, and communities where these issues persist.^

BENZENE MYELOCLASTOGENICITY AND METABOLISM IN CD-1 MICE: A CORRELATION

Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase chromosomal analysis. Groups of 5 or 10, male and female CD-1 mice were treated with one or two p.o. or i.p. doses of benzene (440 mg/kg) or toluene (430, 860 or 1720 mg/kg) or both, and sacrificed 30 or 54h after the first dose. Benzene-treated animals were pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), (beta)-naphthoflavone ((beta)NF), SKF-525A, or Aroclor 1254. Toluene showed no clastogenic activity and reduced the clastogenic effect of co-administered benzene. None of the pretreatments protected against benzene clastogenicity. 3MC and (beta)NF greatly promoted benzene myeloclastogenicity. Dose response curves for benzene myeloclastogenicity were much steeper with 3MC induction than without. Micronuclei (MN) were 4-6 times higher by p.o. than i.p. benzene administration. This was not due to bacterial flora since no difference was found between germ-free and conventional males gavaged with benzene. A sensitive high-pressure liquid chromatographic method was developed and used to explore the relation between metabolic profiles of benzene in urine and MN after various pretreatments. Phenol (PH), trans-trans-muconic acid (MA) and hydroquinone (HQ) in the 48h male mouse urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the single oral dose of benzene (880, 440 and 220 mg/kg). Catechol (CT) was seen in trace amounts. MA was identified by ultraviolet and infrared spectroscopy and elemental analysis. Urinary metabolites--especially MA, HQ, and phenol glucuronide--correlated well with MN and were dependent on both the dose and the metabolism of benzene. Benzene metabolism was most inducible by cytochrome P-448 enzyme inducers, by p.o. > i.p., in males > females, and inhibited by toluene. Ph, CT or HQ administered p.o., 250, 150 and 250 mg/kg, respectively, or at 150 mg/kg x 2 after 3MC pretreatment, failed to reproduce the potent myeloclastogenicity of benzene. In fact, only HQ was mildly clastogenic. ^