bluuebunny/crossref_metadata_2025 huggingface dataset:
Spermiogenesis and introsperm ultrastructure of Scoloplax distolothrix (Ostariophysi: Siluriformes: Scoloplacidae)
Authors: Spadella Maria Angélica , Oliveira Claudio , Quagio‐Grassiotto Irani
Published: September 2006

Spermiogenesis in scoloplacids is characterized by initial lateral development of the flagellum, nuclear rotation, medial nuclear fossa formation, complex centriolar migration, and cytoplasmic channel formation. The scoloplacid spermiogenesis is similar to those found in Diplomystidae, the most primitive siluriform family. The scoloplacid spermatozoa have all the main characteristics of introsperm. They exhibit a conic head, a symmetric midpiece, a medial flagellum, and no acrosome. The conic forward‐elongated nuclei contain homogeneous chromatin. The thin extremity of the nuclei is strongly curved and along its internal face there is a well‐developed membranous compartment. The centrioles are completely inside the medial nuclear fossa, perpendicular to each other and with an electron‐dense material between them. In a cross view of the midpiece, the mitochondria form a ring surrounding internally the cytoplasmic channel, and in a longitudinal view they are organized in a row along it. Several elongated vesicles are distributed peripherally, mainly concentrated in the mid‐piece basal region. The flagellum contains the classical axoneme (9 + 2) and has two lateral projections or fins. The spermatozoa of scoloplacids share several characteristics with those of Auchenipteridae. Since these two families are not phylogenetically related this similarity seems to be due to convergence once both families are, until now, the only known siluriform families with introsperm.
Caffeine improves barrier function in male skin
Authors: Brandner J. M. , Behne M. J. , Huesing B. , Moll I.
Published: September 2006

Synopsis

The influence of androgens, especially testosterone and its effector dihydrotestosterone, results in a constitutive disadvantage for male skin, e.g. reduced viability of hair at the scalp and reduced epidermal permeability barrier repair capacity. Dihydrotestosterone can act, among others, as an adenyl cyclase inhibitor. Caffeine on the other hand is an inexpensive and (in regular doses) harmless substance used in various cosmetic products, which can act as a phosphodiesterase inhibitor. To prove the hypothesis that caffeine as a phosphodiesterase inhibitor is able to override testosterone‐induced effects on barrier function, we performed a double‐blind placebo controlled study with healthy volunteers. In this study, 0.5% caffeine in a hydroxyethylcellulose gel preparation (HEC) was applied on one forearm, HEC without caffeine on the other forearm of male and female volunteers for 7 days and transepidermal water loss (TEWL) was measured before and at the end of the treatment period. Basal TEWL did not differ significantly between male and female subjects but the application of caffeine significantly reduced TEWL in male skin compared with female skin. We conclude that caffeine is beneficial for barrier function in male skin.
Education for Economic Life: The Role of Communicative Action
Authors: Endres Ben
Published: September 2006

This article addresses the tension between the need to prepare students for functional activity in organizations on the one hand, and the need to instill dispositions and competencies that transcend these determinate roles on the other. I take for granted that schools must fulfill both tasks, and I suggest that they are failing at the latter in part because these social and moral purposes of education have not been constructively developed in relation to its economic aims. I first use Max Weber's theory of social action to explain the role of functional activity in modern schooling and society. I then argue that a qualified form of Jürgen Habermas's theory of communicative action can provide a meaningful connection between functional activity and the kinds of participatory, open interactions and relationships that progressive educators seem to prioritize. I argue that communicative action plays a crucial role in a wide range of organizational contexts, even those that involve narrow functions within strict hierarchies. Communicative action thus shows how progressive educational ideals are relevant for work life, regardless of one's place in the economic hierarchy. It also exposes the common ground beneath a range of progressive ideals. I conclude by showing how the role of communicative action in functional work may motivate reform in the practices of teaching and learning.
Engendering Participation, Deliberating Dependence: Inner-City Adolescents’ Perceptions of Classroom Practice
Authors: Patchen Terri
Published: September 2006

This ethnographic study of high school students’ classroom practices and perceptions about participation reveals the extent to which students’ perceptions determine their understandings of practice, even when these understandings conflict with researcher observations and the bulk of the literature on gender and participation. This study shows, moreover, that although there were gender-stratified patterns of participation in the classroom between girls and boys, the underlying conceptualizations about what constituted a supportive environment for participation differed little between genders: Both girls and boys revealed themselves as dependent upon teachers, peers, and “knowing.” What did differ were the ways in which girls and boys described this dependence and the ways in which they understood what occurred in classrooms. Conducted at a large inner-city high school in California populated primarily by low-income, first-generation Latina/Latino students, classroom research took place over a period of 2 years in a series of Life Skills for the 21st Century classes. Dependent primarily upon formal interviews and participant observations, this research focus was on how particular participation strategies were understood and made manifest in the classroom. Beyond the contributions of new information on the importance of the relationship of perception to practice, this research shows that we need to be cautious when we think about gender issues, and how students, particularly ethnic minorities, understand the classroom dynamic.
“Girl, you Better go get you a Condom”: Popular Culture and Teen Sexuality as Resources for Critical Multicultural Curriculum
Authors: Ashcraft Catherine
Published: September 2006

Teens encounter a barrage of messages about sexuality in popular culture—messages that shape their identities and schooling experiences in profound ways. Meanwhile, teen sexuality, pregnancy, and sexually transmitted diseases (STDs) increasingly arouse public panic. To date, however, schools do little to help teens make sense of their sexualities. In this article, I argue that schooling will grow increasingly irrelevant and ineffective if educators fail to address teen sexuality and popular culture. My argument is twofold. First, I suggest that sex education in particular must attend to popular culture. Second, I contend that we can no longer confine efforts to address teen sexuality and popular culture to sex education; rather, we must extend such efforts across a wide range of classroom and schooling contexts. Doing so is important for accomplishing three educational goals: (1) to make a wide range of curriculum (e.g., literacy, social studies, sex education) more relevant and culturally responsive to diverse youth; (2) to develop critical multicultural curriculum that interrogates social inequities, and (3) to indirectly create conditions that would reduce teen pregnancy, sexually transmitted diseases, and HIV/AIDS. To make this argument, I draw from my 9-month ethnographic study of ESPERANZA, a progressive peer-driven sex education program. In contrast, I then analyze how two popular films deal with issues of sexuality in different ways. I conclude with a discussion of how the insights from these popular texts might inform research and practice in critical multicultural curriculum and in educational efforts to help youth address sexuality.
Transnational marriage among Ahmadi Muslims in the UK
Authors: BALZANI MARZIA
Published: September 2006

Abstract Ahmadi Muslims constitute a reformed sect of Islam founded in 1889 by a charismatic leader, Mirza Ghulam Ahmad. In this article I explore the character and processes of transnational marriage arrangements among Ahmadi Muslims over three generations in the UK. I suggest that the process of conversion to Ahmadiyyat and the organizational structure of Ahmadi mosques have combined to produce a flexible pattern of marriage among Ahmadis that is unusual among South Asians. A significant number of earlier and contemporary Ahmadi marriages are interethnic, reflecting an expansive Ahmadiya identity that is perceived to be independent of ethnicity. Further, analysis of marriage proposals accepted as well as rejected suggests gender differences in perceptions of and motivations for marriage. The analysis suggests that while gender differences in expectations of marriage may have parallels in some other South Asian transnational marriages, Ahmadi religious identity and organization plays a distinctive role in shaping the processes of Ahmadi marriage arrangements.
Gender Differences and Mental Health: An Exploratory Study of Knowledge and Attitudes to Mental Health Among Scottish Teenagers
Authors: Williams Brian , Pow Janette
Published: September 2006

Method:  A cross‐sectional survey of 496 teenagers was conducted in order to explore their knowledge and attitude towards mental health and people with mental health problems.

Results:  Boys reported lower levels of knowledge and different sources of stress than girls. Negative attitudes were more common among boys than girls. Boys were less likely to think that an understanding of mental health was important, less likely to want to know more about mental health issues and twice as likely to think that they had already been given enough education.

Conclusion:  Gender specific educational interventions may be more appropriate and effective than whole school approaches.
The Effect of an Education Program on Attitudes and Beliefs about Bullying and Bullying Behaviour in Junior Secondary School Students
Authors: Hunt Caroline
Published: September 2006

This study assessed an intervention targeting bullying. Six schools were recruited, with 444 children aged between 12 and 15 years. Schools were randomly allocated to an intervention comprising education to students, parents and teachers about bullying and strategies believed to prevent bullying, or wait‐list condition. Students reported bullying experiences on the Peer Relations Questionnaire and attitudes using the Attitude to Victim and Bully Scales, prior to the intervention and one year later. There was little difference between conditions on most measures. Short‐term educational approaches appear to have little impact on bullying behaviour, and schools may need to develop alternative approaches.
Managing sustainable farmed landscape through ‘alternative’ food networks: a case study from Italy
Authors: HOLLOWAY LEWIS , COX ROSIE , VENN LAURA , KNEAFSEY MOYA , DOWLER ELIZABETH , TUOMAINEN HELENA
Published: September 2006

This paper focuses on a case study of an ‘alternative’ food network based in the Abruzzo National Park, Italy, to explore how ideas of sustainable farmland management can be expressed through broader understandings of developing networks of care concerned with local economies and societies, high‐quality specialist food products, particular ‘traditional’ farming practices and livestock breeds, as well as the ecology of a farmed landscape. The scheme allows customers, internationally as well as in Italy, to ‘adopt’ a milking sheep on a large mountain farm. In return, adopters are sent food products from the farm. The adoption scheme is inter‐twined with an agri‐tourism project which provides accommodation, runs a restaurant and engages in educational activities. The scheme is the result of the individual initiative of its founder, and is associated with a strongly expressed ethical position concerning the value of sustaining valued local rural landscapes and lifestyles, and the importance of ‘reconnecting’ urban dwellers with rural areas, farming and ‘quality’ food production. Yet the localness of the scheme is sustained through wider national and international networks: volunteer and paid workers are drawn from several European countries, funding has been acquired from the EU LEADER programme, and internet and transport technologies are essential in connecting with and supplying an international customer base. The broader economy of care instanced in this case study draws attention to a need to develop strategies for sustainable farmland management constructed around wider programmes of social, economic and cultural, as well as environmental, concern.
Canada's environmental farm plans: transatlantic perspectives on agri‐environmental schemes
Authors: ROBINSON GUY M
Published: September 2006

Evaluation of Ontario's Environmental Farm Plan (EFP) scheme, launched in 1993, provides an opportunity for comparisons with agri‐environmental measures instituted in the European Union and other parts of North America. The EFP has a strong ‘bottom‐up’ dimension in that it is farmers’ organizations that have been central both to the scheme's instigation and to its ongoing management. This has affected the nature of the actions taken by individual farmers participating in the scheme. These actions are reviewed, especially in terms of the participants’ attitudes towards stewardship of the land, environmental outcomes, cross‐compliance measures, barriers to participation and the role of statutory regulation. Some contrasts are drawn with the greater ‘top‐down’ controls exerted in several EU agri‐environment schemes, with the latter's promotion of extensification and the changing role of farmers as ‘producers of countryside’ in a multi‐functional agricultural system. The diffusion of EFP schemes throughout Canada is noted and is cited as confirming the maintenance of fundamentally different attitudes to the development of farm‐based environmental actions compared with those adopted in the EU.
Can we sustain sustainable agriculture? Learning from small‐scale producer‐suppliers in Canada and the UK
Authors: MAXEY LARCH
Published: September 2006

There has been particular interest in ‘alternative’ food over the last 10 years, with many policymakers and researchers throughout the Minority World following a growing number of consumers and producers in supporting organic farming and a host of ‘alternative’ food networks. To date, there has been a tendency for theory and policy to emerge somewhat divorced from the grounded practices and experiences of producer‐suppliers themselves within these networks. Urging a shift from ‘alternativity’ to ‘sustainability’ as a more critical and valuable tool to analyse food networks, this paper draws upon in‐depth ethnographic research with small‐scale producer‐supplier case studies in south Wales and southern Ontario. In so doing it explores often overlooked voices and stories within sustainable food discourses. Focusing on the value of farmer‐led understandings and responses, the paper highlights important implications for policymakers and consumers and outlines future research on sustainable food networks.
Structure and Opportunity: Committee Jurisdiction and Issue Attention in Congress
Authors: Sheingate Adam D.
Published: September 2006

This article explores how the congressional committee system shapes the dynamics of issue attention. Consisting of what is referred to as a congressional opportunity structure, it describes how committee jurisdictions provide an important institutional context for the attention paid to new issues in congressional hearings. This is illustrated through an examination of congressional attention to biotechnology over a 30‐year period. This article finds that committees with broader jurisdictions were more active in biotechnology than committees with a narrow policy remit. However, these institutional effects varied widely, even within a single policy domain. This variation suggests that issue attention depends on the degree of fit between issue characteristics and the congressional opportunity structure. More broadly, the findings here illustrate the virtues of public policy research in studies of Congress.
Veto Players and Civil War Duration
Authors: Cunningham David E.
Published: September 2006

Civil wars show a remarkable variation in how long they last. Some end within days; others continue for decades. What explains the extreme intractability of some wars while others are resolved quickly? This article argues that conflicts with multiple actors who must approve a settlement (veto players) are longer because there are fewer acceptable agreements, information asymmetries are more acute, and shifting alliances and incentives to hold out make negotiation more difficult. This veto player approach to explaining variation in civil war duration is tested using a new dataset containing monthly data on all parties to each civil war begun since World War II. The statistical analysis shows a strong correlation between the number of veto players and the duration of civil war.
Descriptive Representation and the Composition of African American Turnout
Authors: Griffin John D. , Keane Michael
Published: September 2006

Though many studies have focused on African Americans' turnout levels in descriptively represented electoral districts, few have examined the composition of African‐American turnout in these districts, compared to districts that are not descriptively represented. This study contends that descriptive representation should conditionally affect African Americans' political participation, given preference heterogeneity among this group. It then examines the extent to which the ideological orientations of African Americans condition the effect of their Representative's race in the 104th House on their probability of participating in the 1996 national election. The study finds that when liberal African Americans are descriptively represented, they are more likely to vote, while moderate and conservative African Americans are less likely to vote. These findings not only help to resolve prior studies' disparate conclusions concerning descriptive representation's participatory effects, but they also show that descriptive representation affects which African Americans' interests are communicated to elected officials through voting.
Bayesian Alphas and Mutual Fund Persistence
Authors: BUSSE JEFFREY A. , IRVINE PAUL J.
Published: September 2006

We use daily returns to compare the performance predictability of Bayesian estimates of mutual fund performance with standard frequentist measures. When the returns on passive nonbenchmark assets are correlated with fund holdings, incorporating histories of these returns produces a performance measure that predicts future performance better than standard measures do. Bayesian alphas based on the Capital Asset Pricing Model (CAPM) are particularly useful for predicting future standard CAPM alphas. Over our sample period, priors consistent with moderate to diffuse beliefs in managerial skill dominate more skeptical prior beliefs, a result that is consistent with investor cash flows.
HLA markers in familial Lichen Sclerosus
Authors: Aslanian Flavia M. N. P. , Marques Maria Teresa Q. , Matos Haroldo J. , Pontes Luciane F. S. , Porto Luis Cristóvão S. , Azevedo Lucia M. S. , Filgueira Absalom L.
Published: September 2006

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases.

Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS.

Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.
Biochemical and structural analyses of a higher plant photosystem II supercomplex of a photosystem I‐less mutant of barley
Authors: Morosinotto Tomas , Bassi Roberto , Frigerio Sara , Finazzi Giovanni , Morris Edward , Barber James
Published: September 2006

Photosystem II of higher plants is a multisubunit transmembrane complex composed of a core moiety and an extensive peripheral antenna system. The number of antenna polypeptides per core complex is modulated following environmental conditions in order to optimize photosynthetic performance. In this study, we used a barley (Hordeum vulgare) mutant, viridis zb63, which lacks photosystem I, to mimic extreme and chronic overexcitation of photosystem II. The mutation was shown to reduce the photosystem II antenna to a minimal size of about 100 chlorophylls per photosystem II reaction centre, which was not further reducible. The minimal photosystem II unit was analysed by biochemical methods and by electron microscopy, and found to consist of a dimeric photosystem II reaction centre core surrounded by monomeric Lhcb4 (chlorophyll protein 29), Lhcb5 (chlorophyll protein 26) and trimeric light‐harvesting complex II antenna proteins. This minimal photosystem II unit forms arrays in vivo, possibly to increase the efficiency of energy distribution and provide photoprotection. In wild‐type plants, an additional antenna protein, chlorophyll protein 24 (Lhcb6), which is not expressed in viridis zb63, is proposed to associate to this minimal unit and stabilize larger antenna systems when needed. The analysis of the mutant also revealed the presence of two distinct signalling pathways activated by excess light absorbed by photosystem II: one, dependent on the redox state of the electron transport chain, is involved in the regulation of antenna size, and the second, more directly linked to the level of photoinhibitory stress perceived by the cell, participates in regulating carotenoid biosynthesis.
Diabetic foot screening: why is it neglected?
Authors: Abu‐Qamar Ma’en Zaid
Published: September 2006

Understanding reasons for the neglect of foot screening during the annual review of people with diabetes enables the development of solutions for this omission. This study explores the reasons within the context of health care delivery systems in terms of the professional, social, political and economic aspects of this screening. Information was obtained through reviewing publications on diabetic foot and health care reform. The omission of annual foot examination for people with diabetes is attributed to the nature of diabetes‐related foot problems, people with diabetes, health care professionals and the current structure of health care delivery systems. Increasing the adherence to foot screening for those with diabetes requires short‐ and long‐term strategies. Short‐ and long‐term strategies for reminding patients and staff about foot screening are suggested.
THE PREDICTION OF FAT PERCENTAGE IN THE LONGISSIMUS DORSI MUSCLE IN FED BEEF USING NUCLEAR MAGNETIC RESONANCE
Authors: GARCIA L.G. , LAWRENCE T.E. , MONTGOMERY T.H. , PARKER D.B. , BROWN M.S.
Published: September 2006

The objective of this study was to develop predictive equations to estimate the percentage of crude fat in beef longissimus dorsi muscles from subjective marbling evaluations or objective visual evaluations. Forty beef ribs and loins representing four U.S. Department of Agriculture (USDA) quality grades – USDA Prime (n = 10); USDA Premium Choice [upper 2/3 of Choice] (n = 10); USDA Low Choice (n = 10); and USDA Select (n = 10) – were fabricated into 3.17‐cm transverse slices for subjective and objective visual evaluations. Additional 0.63‐cm slices were removed for crude fat analysis. Mean crude fat percentages were as follows: USDA Prime = 11.90, USDA Premium Choice = 9.78, USDA Low Choice = 7.08 and USDA Select = 5.29. Regression analysis indicated that crude fat can be estimated with the following equation using a subjective marbling score: = (–0.58) + 0.17 × marbling score (R2 = 0.55); furthermore, crude fat = (3.47) + 0.73 × objective visual percent fat (R2 = 0.54).
Immunohistochemical Expressions of Ki-67, Cyclin D1, β-Catenin, Cyclooxygenase-2, and Epidermal Growth Factor Receptor in Human Colorectal Adenoma: A Validation Study of Tissue Microarrays
Authors: Su Yinghao , Shrubsole Martha J. , Ness Reid M. , Cai Qiuyin , Kataoka Nobuhiko , Washington Kay , Zheng Wei
Published: September 2006

Background: Tissue microarray (TMA) holds promise as a high-throughput method for the analysis of biomarkers in tissue specimens. The validity and reliability of this method, however, may vary for different biomarkers in different tissue specimens.

Objectives: In this study, we evaluated the validity and reliability of using TMA to assess biomarkers in colorectal adenomas.

Methods: Sixty-three consecutive patients with colorectal adenomas were recruited in this study. Two TMA blocks were constructed using four punches from each adenoma (one periphery, one deep, and two middle zones). The immunostaining of five markers (Ki-67, cyclin D1, β-catenin, cyclooxygenase-2, and epidermal growth factor receptor) was analyzed, and the concordance between data obtained from TMAs and standard whole-tissue sections was evaluated by Spearman's correlation and kappa analysis.

Results: Colorectal adenoma exhibited zonal, heterogeneous expression patterns for all five markers. The concordance rates for the semiquantitative evaluation of markers between data from TMAs and whole sections ranged from 87% to 93% with corresponding kappa statistics of 77% to 90%. In addition, both quantitative and semiquantitative methods were used to score TMA sections, and good correlations between these two methods were shown for all five markers with intraclass correlation coefficients ranging from 0.5 to 0.8.

Conclusion: Our study indicates that TMA can be used to reliably assess the expression levels of Ki-67, cyclin D1, β-catenin, cyclooxygenase-2, and epidermal growth factor receptor in colorectal adenoma tissues. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1719–26)
Estrogens, Enzyme Variants, and Breast Cancer: A Risk Model
Authors: Crooke Philip S. , Ritchie Marylyn D. , Hachey David L. , Dawling Sheila , Roodi Nady , Parl Fritz F.
Published: September 2006

Oxidative metabolites of estrogens have been implicated in the development of breast cancer, yet relatively little is known about the metabolism of estrogens in the normal breast. We developed a mathematical model of mammary estrogen metabolism based on the conversion of 17β-estradiol (E2) by the enzymes cytochrome P450 (CYP) 1A1 and CYP1B1, catechol-O-methyltransferase (COMT), and glutathione S-transferase P1 into eight metabolites [i.e., two catechol estrogens, 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2); three methoxyestrogens, 2-methoxyestradiol, 2-hydroxy-3-methoxyestradiol, and 4-methoxyestradiol; and three glutathione (SG)-estrogen conjugates, 2-OHE2-1-SG, 2-OHE2-4-SG, and 4-OHE2-2-SG]. When used with experimentally determined rate constants with purified enzymes, the model provides for a kinetic analysis of the entire metabolic pathway. The predicted concentration of each metabolite during a 30-minute reaction agreed well with the experimentally derived results. The model also enables simulation for the transient quinones, E2-2,3-quinone (E2-2,3-Q) and E2-3,4-quinone (E2-3,4-Q), which are not amenable to direct quantitation. Using experimentally derived rate constants for genetic variants of CYP1A1, CYP1B1, and COMT, we used the model to simulate the kinetic effect of enzyme polymorphisms on the pathway and identified those haplotypes generating the largest amounts of catechols and quinones. Application of the model to a breast cancer case-control population identified a subset of women with an increased risk of breast cancer based on their enzyme haplotypes and consequent E2-3,4-Q production. This in silico model integrates both kinetic and genomic data to yield a comprehensive view of estrogen metabolomics in the breast. The model offers the opportunity to combine metabolic, genetic, and lifetime exposure data in assessing estrogens as a breast cancer risk factor. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1620–9)
Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies
Authors: Lim Unhee , Subar Amy F. , Mouw Traci , Hartge Patricia , Morton Lindsay M. , Stolzenberg-Solomon Rachael , Campbell David , Hollenbeck Albert R. , Schatzkin Arthur
Published: September 2006

Background: In a few animal experiments, aspartame has been linked to hematopoietic and brain cancers. Most animal studies have found no increase in the risk of these or other cancers. Data on humans are sparse for either cancer. Concern lingers regarding this widely used artificial sweetener.

Objective: We investigated prospectively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas (malignant brain cancer).

Methods: We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort. Daily aspartame intake was derived from responses to a baseline self-administered food frequency questionnaire that queried consumption of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea, and aspartame added to hot coffee and tea) during the past year. Histologically confirmed incident cancers were identified from eight state cancer registries. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that adjusted for age, sex, ethnicity, body mass index, and history of diabetes.

Results: During over 5 years of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained. Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer (RR for ≥600 mg/d, 0.98; 95% CI, 0.76-1.27), glioma (RR for ≥400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear trend = 0.05), or their subtypes in men and women.

Conclusions: Our findings do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1654–9)
Polymorphisms in Nucleotide Excision Repair Genes and DNA Repair Capacity Phenotype in Sisters Discordant for Breast Cancer
Authors: Shen Jing , Desai Manisha , Agrawal Meenakshi , Kennedy David O. , Senie Ruby T. , Santella Regina M. , Terry Mary Beth
Published: September 2006

Interindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro–induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were available. Overall, there were no statistically significant differences in average DRC for most of the genotypes. A final multivariate conditional logistic model, including three single nucleotide polymorphisms (XPA +62T>C, XPC Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC after adjusting for case-control status and age of blood donation. The overall predictive accuracy was 61% in the model with a sensitivity of 78% and specificity of 39%. These findings suggest that those polymorphisms we have investigated to date in nucleotide excision repair pathway genes explain only a small amount of the variability in DRC. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1614–20)
Effect of a 12-Month Exercise Intervention on Patterns of Cellular Proliferation in Colonic Crypts: A Randomized Controlled Trial
Authors: McTiernan Anne , Yasui Yutaka , Sorensen Bess , Irwin Melinda L. , Morgan Angela , Rudolph Rebecca E. , Surawicz Christina , Lampe Johanna W. , Ayub Kamran , Potter John D. , Lampe Paul D.
Published: September 2006

Background: Colon crypt architecture and proliferation may be appropriate biomarkers for testing prevention interventions. A hypothesized mechanism for exercise-induced colon cancer risk reduction might be through alterations in colon crypt cell architecture and proliferation.

Methods: Healthy, sedentary participants with a colonoscopy within the previous 3 years were recruited through gastroenterology practices and media. We randomly assigned 100 women and 102 men, ages 40 to 75 years, to a control group or a 12-month exercise intervention of moderate-to-vigorous aerobic exercise, 60 minutes per day, 6 days per week, and assessed change in number and relative position of Ki67-stained cells in colon mucosal crypts.

Results: Exercisers did a mean 370 min/wk (men) and 295 min/wk (women) of exercise (seven dropped the intervention). In men, the mean height of Ki67-positive nuclei relative to total crypt height was related to amount of exercise, with changes from baseline of 0.0% (controls), +0.3% (exercisers <250 min/wk), −1.7% (exercisers 250-300 min/wk), and −2.4% (exercisers >300 min/wk; Ptrend = 0.03). In male exercisers whose cardiopulmonary fitness (VO2max) increased >5%, the mean height of Ki67-positive nuclei decreased by 2% versus 0.9% in other exercisers, and versus no change in controls (Ptrend = 0.05). Similar trends were observed in other proliferation markers. In women, increased amount of exercise or VO2max did not result in notable changes in proliferation markers.

Conclusions: A 12-month moderate-to-vigorous intensity aerobic exercise intervention resulted in significant decreases in colon crypt cell proliferation indices in men who exercised a mean of ≥250 min/wk or whose VO2max increased by ≥5%. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1588–97)
PGR+331 A/G and Increased Risk of Epithelial Ovarian Cancer
Authors: Risch Harvey A. , Bale Allen E. , Beck Patricia A. , Zheng Wenxin
Published: September 2006

Childbearing and use of oral contraceptives are known to lower the risk of ovarian cancer, and it has been suggested that progesterone or progestin exposures play a role in these associations. The effects of progesterone may be mediated in part through the progesterone receptor, which exists in two functionally distinct protein isoforms, hPR-A and hPR-B. It is known that individuals carrying the A allele of the progesterone receptor gene (PGR) polymorphism, +331 A/G (rs10895068), have greater production of the hPR-B receptor isoform. We therefore examined the association between PGR +331 A/G genotype and risk of ovarian cancer in a population-based study of 490 cases and 534 controls in the state of Connecticut. Adjusted for various reproductive and other factors, a statistically significant increased risk was seen for carriage of the A allele compared with GG genotype [odds ratio (OR), 1.68; 95% confidence interval (95% CI), 1.09-2.59]. When subjects were considered separately according to menopausal status, no increased risk with the A allele was seen for premenopausal women (OR, 0.96; 95% CI, 0.46-2.02) but significantly increased risk was found for postmenopausal women (OR, 2.31; 95% CI, 1.31-4.06). Similar increased risks particularly among postmenopausal women were seen for all histologic tumor types. These findings have been observed before for breast and endometrial cancer, although not for ovary, but still suggest that an hPR-B mechanism may be involved in ovarian neoplasia. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1738–41)
Folate Metabolism Polymorphisms Influence Risk of Colorectal Adenoma Recurrence
Authors: Hubner Richard A. , Muir Kenneth R. , Liu Jo-Fen , Sellick Gabrielle S. , Logan Richard F.A. , Grainge Matthew , Armitage Nicholas , Chau Ian , Houlston Richard S. ,   The United Kingdom Colorectal Adenoma Prevention Consortium
Published: September 2006

Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1607–13)
Establishing a Cancer Center Data Bank and Biorepository for Multidisciplinary Research
Authors: Ambrosone Christine B. , Nesline Mary K. , Davis Warren
Published: September 2006

The establishment of a biorepository with linkage to clinical and epidemiologic data will provide an invaluable resource for cancer research, including studies of cancer etiology, progression, and prognosis, as well as development of biomarkers for early detection. Developing an infrastructure for a biorepository linked to clinical, pathologic, and epidemiologic data requires significant efforts in strategic planning for efficient means to ascertain, identify, and consent participants, as well as guidelines for blood collection, processing, and storage while maintaining participant privacy rights. In this report, we present an approach to developing a Data Bank and Biorepository at our own institution, with discussion of elements to be considered when establishing such a bank. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1575–7)
Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer
Authors: Choi Kang Hyun , Park Min Woo , Lee Seung Yeon , Jeon Mi-Ya , Kim Mee Young , Lee Hee Kyu , Yu Jaehoon , Kim Hong-Jin , Han Kyungsook , Lee Heviran , Park Keerang , Park Woong June , Jeong Sunjoo
Published: September 2006

T-cell factor (TCF)-1 protein forms the transcriptional complex with β-catenin and regulates the expression of diverse target genes during early development and carcinogenesis. We have selected previously an RNA aptamer that binds to the DNA-binding domain of TCF-1 and have shown that it interfered with binding of TCF-1 to its specific DNA recognition sequences in vitro. As an approach to modulate the transcription by TCF/β-catenin complex in the cells, we have developed the RNA expression vector for stable expression of RNA aptamer inside of the mammalian cells. High level of RNA was expressed as an intramer in the fusion with the stable RNA transcript. The RNA intramer inhibited TCF/β-catenin transcription activity as shown by luciferase assay. It also modulated the expression of TCF/β-catenin target genes, such as cyclin D1 and matrix metalloproteinase-7, as predicted to be as an effective inhibitor of the TCF function. In addition, it efficiently reduced the growth rate and tumorigenic potential of HCT116 colon cancer cells. Such RNA intramer could lead to valuable gene therapeutics for TCF/β-catenin-mediated carcinogenesis. [Mol Cancer Ther 2006;5(9):2428–34]
Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding
Authors: Jones Dylan T. , Harris Adrian L.
Published: September 2006

Hypoxia-inducible factor-α (Hif-α) plays an important role in tumor growth by increasing resistance to apoptosis and the production of angiogenic factors, such as vascular endothelial growth factor (VEGF). Therefore, Hif-α is an attractive target for development of novel cancer therapeutics. We have generated Chinese hamster ovary cells, which stably express luciferase reporter construct under the control of a hypoxia response element to screen 15,000 compounds. We identified 40 compounds that inhibited hypoxic up-regulation of luciferase, and the top 30 compounds were further screened in a secondary assay using MDA-468 breast cancer cell line. Eight compounds were shown to inhibit VEGF expression in hypoxic cells at subtoxic concentrations. Three top putative Hif inhibitors, DJ12, DJ15, and DJ30, were chosen for further analysis. Transient transfection of cells with hypoxia-regulated luciferase reporter plasmids further validated that these compounds inhibit hypoxia up-regulated genes. All three compounds failed to inhibit Hif-1α protein levels but they did inhibit induction of downstream targets of Hif-α under hypoxia. Two of the three compounds were cell type specific, whereas compound DJ12 inhibited VEGF at subtoxic levels in breast cancer cell lines MDA-468 and ZR-75, melanoma cell line MDA-435, and pVHL mutant renal cancer cell lines RCC4 and 786-0. Compound DJ12 down-regulated mRNA of downstream targets of Hif-α, and significantly inhibited Hif-1α transactivation activity by blocking Hif-1α hypoxia response element-DNA binding. Our cell-based approach and deconvolution of the inhibitory effect of DJ12 has identified a novel compound that targets the hypoxia pathway by inhibiting Hif-α–inducible transcription. [Mol Cancer Ther 2006;5(9):2193–202]
Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells
Authors: Hrzenjak Andelko , Moinfar Farid , Kremser Marie-Luise , Strohmeier Bettina , Staber Philipp B. , Zatloukal Kurt , Denk Helmut
Published: September 2006

Covalent modifications of histone proteins, in particular deacetylation of lysine residues, are important for the regulation of gene transcription both in normal and malignant cells. These processes are controlled by histone acetyltransferases and histone deacetylases (HDAC) and have up to now not been described in solid mesenchymal tumors. The present study shows differences in the HDAC1 and HDAC2 expression in endometrial stromal sarcomas (ESS) and a cognate cell line (ESS-1) compared with nonneoplastic endometrial stroma. We show for the first time that HDAC2 expression is consistently increased in ESS. In contrast, HDAC1 expression is generally lower than HDAC2 both in nonneoplastic stroma and in ESS, suggesting that these two proteins, although closely related, are regulated in different ways. In vitro experiments with an ESS cell line showed that valproate, an inhibitor of the class I HDACs, led to significant HDAC2 decrease and to cell differentiation. HDAC2 inhibition in ESS-1 cells caused significant changes in the cell cycle by inhibiting G1-S transition and influencing expression of p21WAF1 and cyclin D1. Moreover, in ESS-1 cells, increased expression of the p21WAF1 was associated with reduction of HDAC2 expression after transfection with small interfering RNA directed against HDAC2. Our results suggest that HDAC2 might be considered as potential drug target in the therapy of ESS and that HDAC inhibitors should be further evaluated in clinical trials in ESS. [Mol Cancer Ther 2006;5(9):2203–10]
Intracellular inhibition of carboxylesterases by benzil: modulation of CPT-11 cytotoxicity
Authors: Hyatt Janice L. , Tsurkan Lyudmila , Wierdl Monika , Edwards Carol C. , Danks Mary K. , Potter Philip M.
Published: September 2006

Carboxylesterases are ubiquitous proteins responsible for the detoxification of xenobiotics. However, these enzymes also activate prodrugs, such as the anticancer agents capecitabine and CPT-11. As a consequence, overexpression of carboxylesterases within tumor cells sensitizes these cells to CPT-11. We have recently identified two classes of carboxylesterase inhibitors based on either a benzil (diphenylethane-1,2-dione) or a benzene sulfonamide scaffold and showed that these compounds inhibit carboxylesterases with Kis in the low nanomolar range. Because both classes of inhibitors show reversible enzyme inhibition, conventional in vitro biochemical assays would not accurately reflect the in situ levels of carboxylesterase activity or inhibition. Therefore, we have developed a novel assay for the determination of intracellular carboxylesterase activity using 4-methylumbelliferone as a substrate. These studies show that benzil and a dimethylbenzil analogue efficiently enter cells and inhibit human intestinal carboxylesterase and rabbit liver carboxylesterase intracellularly. This inhibition results in reduced cytotoxicity to CPT-11 due to the lack of carboxylesterase-mediated conversion of the prodrug to SN-38. These results suggest that intracellular modulation of carboxylesterase activity with benzil or its analogues may be applied to minimize the toxicity of normal cells to CPT-11. [Mol Cancer Ther 2006;5(9):2281–8]