bluuebunny/crossref_metadata_2025 huggingface dataset:
Track Modulus Analysis of Railway Track System Using Finite Element Model
Authors: Ganesh Babu K. , Sujatha C.
Published: May 2010

With the development of ever faster trains, the problem of excessive ground vibrations has increased. Dealing with ground vibration from surface and underground trains is a challenging issue for the railway industry. In the present work, the analysis of a typical Indian railway track system has been done with special emphasis on “track modulus” for Prestressed Concrete (PSC) sleepers and Wooden (WOOD) sleepers. The track consists of two rails of standard length, rail pads and sleepers with constant sleeper spacing, ballast and subgrade covering the length of the rails as per the Indian Railways standards. Finite Element models have been developed for computer simulation of the dynamic behaviour of the railway track system for 52PSC, 60PSC, 52WOOD and 60WOOD track. In this model, subgrade, ballast and rail pad parameters have been considered for parametric analysis of the track modulus. Finally the track system is excited harmonically over a range of frequencies to predict the dynamic variation in the track modulus.
Estimation on Error Bound of Lag Synchronization of Chaotic Systems with Time Delay and Parameter Mismatch
Authors: Qi Han  , Chuandong Li  , Junjian Huang
Published: May 2010

This paper studies the effect of parameter mismatch on lag synchronization of chaotic systems with time delay in the framework of master-slave configuration. It shall be shown that lag synchronization of coupled systems may achieve weakly in the presence of small parameter mismatches. The error bound of lag-synchronization arising from the parameter mismatches is also estimated by rigorously theoretical analysis. Numerical simulations on a Lu oscillator are presented to verify the theoretical results.
Differential Effects of Methylphenidate on Problem Solving in Adults With ADHD
Authors: Tucha Lara , Tucha Oliver , Sontag Thomas A. , Stasik Dorota , Laufkötter Rainer , Lange Klaus W.
Published: May 2010

Objective: Two studies were performed to assess both divergent and convergent thinking in adults with ADHD. Method: The first study compared the problem-solving abilities of healthy participants ( N = 144) and unmedicated adults with ADHD ( N = 144). In the second study, problem-solving abilities of adults with diagnosed ADHD ( N = 22) were examined twice, that is, on and off methylphenidate (MPH), and compared with the performance of a healthy control group ( N = 22). Convergent thinking was measured using a Tower of London task, whereas divergent thinking was assessed using verbal fluency tasks. Results: Adults with ADHD off MPH displayed marked deficits of both divergent and convergent thinking. MPH treatment resulted in a marked improvement of convergent thinking, while no effect of medication was found regarding divergent thinking. Conclusion: Pharmacological treatment of adults with ADHD revealed a differential effect of MPH on problem solving abilities. ( J. of Att. Dis. 2011; 15(2) 161-173)
Review Article: To have and to hold: Personnel shortage in a Finnish healthcare organisation
Authors: Heilmann Pia
Published: May 2010

Aims: Retirements of baby boomers will create a talent shortage in Finnish health care. Concurrently, difficulties exist in recruiting new personnel. This paper provides an overview concerning the bottlenecks in talent management in a Finnish hospital, and finds solutions for recruitment and retention problems of healthcare professionals (nurses and physicians). Because the healthcare staffing shortage is worldwide, the results of this paper are also useful internationally. Methods: The research was a qualitative case study and the research method used was group interview. Background data was gathered from the public media and healthcare trade organisations. Results: The bottlenecks of talent management in hospital organisation seem to relate to retaining actions of senior personnel. Concurrently, the organisation should develop new practices for attracting new personnel. Very few efforts on image marketing and recruitment have been done. The Internet has not been fully exploited and recruitment information has not been sent even to the neighbouring nursing college. Job rotation has not been used as a help in recruitment and competence development. Difficulties exist in transmitting tacit knowledge from a retiring nurse to a junior nurse. Leadership skills of the superior seem to be important when retaining and committing senior personnel. Conclusions: Recruitment and retention problems encourage organisations to develop new recruitment and commitment practices as well as management and leadership skills.
Vocabulary acquisition in young children: The role of the story
Authors: Hepburn Emma , Egan Bridget , Flynn Naomi
Published: May 2010

Sharing storybooks with babies increases their future achievements in literacy, especially in reading (Hall, 2001; Moore and Wade, 1997, 2003; Scarborough et al., 1991; Wade and Moore, 1998; Wells, 1985). This study, focusing on case studies of two 20-month-old children, attempts to identify the role the storybook plays in children’s vocabulary acquisition. Their mothers adopted a regime of daily reading of specific picture books over a six-week period, and recorded the children’s acquisition of new vocabulary, in order to explore what specific contribution these texts made to the children’s speech. The findings demonstrate that storybooks form one source of children’s newly-acquired vocabulary. Factors that might account for this were more difficult to determine through a study of this scale.
Effects of a preschool bilingual family literacy programme
Authors: Hirst Kath , Hannon Peter , Nutbrown Cathy
Published: May 2010

This article reports a multi-method evaluation of a one-year small-scale preschool family literacy programme with bilingual Pakistani-origin families in the UK. The programme was implemented mostly through home visits and included provision of literacy resources, some postal communication and group meetings. The study was conducted in collaboration with the Sheffield REAL (Raising Early Achievement in Literacy) project. Take-up and participation were high (with significant involvement of older siblings) and no families dropped-out. Families’ views, obtained through interviews at the beginning and end of the programme, were extremely positive in terms of increased understanding of how to support their children’s literacy development, impact on their confidence and literacy achievements, and how they valued the programme. Outcomes for children showed significant gains over a control group. The family literacy programme was found to be both feasible and effective.
Governing through crime — the case of the European Union
Authors: Baker Estella
Published: May 2010

In Governing through Crime , Jonathan Simon offers an ‘interpretation’ of contemporary practices, discourses and experiences of the state in the USA that aims to provide a ‘thick’ account of the use of crime as a governance strategy. In support of his argument, he cites a variety of constitutional, cultural, economic, historical, political and social factors. Many of them are demonstrably US-specific. Therefore, any potential for exploring the application of his ideas to another governmental entity might appear to be precluded. This article challenges that supposition, investigating their possible relevance to an understanding of the European Union’s evolving, and increasingly significant, role as a penal actor.
Reaching Young Men: Lessons Learned in the Recruitment, Training, and Utilization of Male Peer Sexual Health Educators
Authors: Cupples Jacqueline B. , Zukoski Ann P. , Dierwechter Tatiana
Published: May 2010

The need to involve men in family planning and reproductive health services has gained increased recognition by health organizations and practitioners as an important strategy for reducing persistently high rates of sexually transmitted infections and unintended pregnancies. Peer education is one popular approach that has been shown to be effective in promoting healthy sexual behaviors as well as increasing sexual health knowledge, attitudes, and skills among young people. Although the efficacy of peer education programs is related to the recruitment, selection, and training of instructors, little information on these topics has been shared. Moreover, there is an even greater dearth in the literature regarding young male sexual health educators. This report addresses this gap and describes lessons learned about the selection, development, and contributions of young male health educators in a male-focused peer-based sexual health program.
Successes and Challenges of Teaching the Social Determinants of Health in Secondary Schools: Case Examples in Seattle, Washington
Authors: Gould Linn , Mogford Elizabeth , DeVoght Andra
Published: May 2010

This article describes a new curriculum developed by Just Health Action (JHA), which teaches the social determinants of health (SDOH) as a strategy to promote health equity. Motivated by the mounting evidence that improvements in health ultimately require taking action on the social, political, and economic determinants of health, JHA has worked since 2004 to teach adolescents critical health literacy, which combines the understanding of the SDOH with skills to take action. This article explains JHA’s curricular methodology, provides two case examples of school-based partnerships, and discusses the successes and challenges the authors have experienced in their efforts. JHA’s teaching has been enthusiastically received, but its biggest barrier in teaching the SDOH in secondary schools is general lack of awareness of the SDOH and their impact on health outcomes. The authors echo international and national calls to raise awareness of the SDOH through training and education. Incorporating the SDOH into secondary school curriculum first requires a citizenry convinced by its importance who will in turn influence curriculum change. The authors recommend that the SDOH be taught to health professionals in continuing education, as a required course in schools of public health, and in the new initiative to teach public health in undergraduate education.
Application of ADAPT-ITT: Adapting an Evidence-Based HIV Prevention Intervention for Incarcerated African American Adolescent Females
Authors: Latham Teaniese P. , Sales Jessica M. , Boyce Lorin S. , Renfro Tiffaney L. , Wingood Gina M. , DiClemente Ralph J. , Rose Eve
Published: May 2010

African American adolescent females are disproportionately affected by the HIV epidemic. Recent findings suggest that gender- and culturally appropriate HIV prevention interventions can significantly reduce HIV-associated sexual risk behaviors among this vulnerable population. Currently, there are no evidence-based interventions (EBIs) for this vulnerable subgroup. Thus, interventions specifically tailored for this subgroup are urgently needed. Effective interventions that reduce HIV risk behaviors remain one of the most powerful tools in curbing the HIV epidemic. The selected intervention (Horizons) was adapted using a coordinated and systematically guided adaptation process based on the ADAPT-ITT framework. This article serves as a starting point to support using the ADAPT-ITT model, which was beneficial when using an EBI in an alternative setting than originally created. Using this prescriptive method for adapting Horizons for incarcerated young girls proved to be a time- and cost-effective method.
Advocating for Schools to Provide Effective HIV and Sexuality Education: A Case Study in How Social Service Organizations Working in Coalition Can (and Should) Affect Sustained Policy Change
Authors: Ogusky Jeremy , Tenner Adam
Published: May 2010

Advocates believed that to slow an expanding HIV/ AIDS epidemic in Washington, D.C., a local effort could ensure that HIV prevention was brought to scale. Schools were chosen as the focus and a new coalition advocated for the city government to pass new academic standards for health education. HIV and sex education policies had not been revised in more than 12 years and HIV education in D.C. public schools varied greatly in quality. Metro TeenAIDS (MTA), a traditional social service organization with no real history of advocacy work, reached only 10% of D.C. adolescents with critical HIV/AIDS prevention information. Clearly, to make a sustained impact, system change was necessary. After deciding to pursue a campaign focused on updating health education policy and creating standards, MTA convened a variety of reproductive health, adolescent medicine, and other organizations to establish the DC Healthy Youth Coalition. The Coalition used three complementary strategies to achieve campaign goals: mobilizing grassroots community support, involving parents in the discussion, and educating city leaders. By building an alliance of social service organizations and influencing critical public policy, the coalition ensured that new educational standards were passed.
Navigating Partnerships and Addressing Tough Issues in Promoting Health Among GLBTQ Youth: An Interview With Jesus Ramirez-Valles
Authors: Head Carmen J.
Published: May 2010

Gay, lesbian, bisexual, transgendered, and questioning (GLBTQ) youth have a number of challenges to face as they develop socially and sexually. Acceptance, discrimination, violence, and a sense of belonging are just a number of issues that complicate the life of GLBTQs as they seek to establish their identity. Many of the challenges that GLBTQ youth are faced with make them more susceptible to practicing risky behaviors that can lead to HIV/AIDS and STDS. When GLBTQ youth of color are living in poor neighborhoods or suffer from some form of racial discrimination, they face even greater challenges.
Design for Data Quality in a Multisite Cross-Sectional and Panel Study
Authors: Jones Eric C. , Murphy Arthur D. , Perilla Julia L. , Pérez-Vargas Isabel , Norris Fran H.
Published: May 2010

The authors address the issues faced while collecting survey data as part of a large multisite, multidisciplinary long-term project using interviewers rather than self-administered questionnaires in a country in which the researchers are not native. The issues pertain to the collection of high-quality data that accurately measure the variables of interest from which generalizations can be made. Three issues were prominent: potential cross-cultural variation in the validity of measures; how to manage multiple control sites and multiple study sites; and how to control for problems presented by series/panel data (i.e., the influence of prior interviews or subsequent intervening events on later interviews). The authors addressed these issues through five strategies at different points in the study. This discussion concerns the challenges and benefits of using these techniques to address the three main issues.
Canvasser Affect and Voter Response: Results From National Focus Groups
Authors: Gillespie Andra
Published: May 2010

The experimental literature on voter mobilization establishes the efficacy of canvassing as a tool of voter mobilization. However, the current literature gives scant attention to the question of whether some types of canvassers may be more effective than others. This article takes the first step toward developing a positive theory of effective or ineffective canvassing. Using descriptive, qualitative data from 10 focus groups conducted in 2006, I find that voters have preferences for the types of campaign representatives they want to visit them. The results of these focus groups lay the groundwork for further experimental study and provide guidelines for practitioners instituting get-out-the-vote (GOTV) efforts.
Emotional Appeals in Environmental Group Communications
Authors: Merry Melissa K.
Published: May 2010

Although emotional appeals are commonplace in political rhetoric, they are often viewed as manipulative and therefore threatening to democratic governance. Interest groups, in particular, have been blamed for relying on emotionally charged rhetoric to achieve fundraising objectives. Through a focus on 210 national-level environmental organizations, the author reevaluates this critique, postulating that groups vary the emotive content of their communications in response to different audiences and purposes of communication. Using evidence from a content analysis of group communications across several media, the author shows that groups rely much more on positive rhetoric than previous studies have indicated, especially in communications designed to encourage participation. Furthermore, negative appeals are most prevalent in groups’ efforts to encourage learning through information provision.The results suggest that emotive rhetoric can be used in ways that complement reasoning processes.
Exploiting the Opportunity for Reconstructive Leadership: Presidential Responses to Enervated Political Regimes
Authors: Nichols Curt , Myers Adam S.
Published: May 2010

We seek to extend discourse on“the reconstructive presidency” to the edge of new frontiers in two interrelated ways. First, we argue that reconstructive presidents act within critical junctures in which they exploit periodic opportunities to revitalize enervated political regimes, but that failure to exploit such opportunities can also occur. Second, we clarify the tasks necessary for reconstructive success, contending that reconstructive presidents must (a) shift the main axis of partisan cleavage, (b) assemble a new majority coalition, and (c) institutionalize a new political regime.Through conducting typical and crucial case studies, we show how reconstructive dynamics unfold in either a straightforward or protracted manner depending on whether presidents initially handed reconstructive opportunities, via encountering enervated political conditions, succeed in accomplishing the tasks we delineate. In doing so, we depart from previous interpretations and recast the “System of 1896” as a successful reconstruction.
Executive Functions Deficit in Parkinson’s Disease With Amnestic Mild Cognitive Impairment
Authors: Petrova Mariya , Raycheva Margarita , Zhelev Yavor , Traykov Latchezar
Published: May 2010

Recent studies suggest that onset of dementia in Parkinson’s disease (PD) is preceded by a phase known as mild cognitive impairment (MCI). Different clinical subtypes of MCI in PD were found. The objective of this study was to investigate whether patients with PD diagnosed with amnestic MCI (aPD-MCI) have also subtle deficits in other cognitive domains and especially in attention/executive functions and, therefore to clarify whether all subcomponents of executive control are equally affected in aPD-MCI. We investigated 23 patients with aPD-MCI (modified Petersen’s criteria) and 25 normal controls. Relative to controls, the aPD-MCI group showed significant deficits with reference to tasks that encompass various aspects of attention/executive functions, including Trail Making Test, Stroop test, Modified Card Sorting Test, and digit span backward, as well as phonemic and semantic verbal fluency. This suggests that executive dysfunction is consistently presented in PD with MCI, even in ‘‘amnestic’’ PD-MCI due to cortical—subcortical dysfunction.
The structure and content of telephonic scripts found useful in a Medicaid Chronic Disease Management Program
Authors: Roth Alexis M. , Ackermann Ronald T. , Downs Stephen M. , Downs Anne M. , Zillich Alan J. , Holmes Ann M. , Katz Barry P. , Murray Michael D. , Inui Thomas S.
Published: May 2010

In 2003, the Indiana Office of Medicaid Policy and Planning launched the Indiana Chronic Disease Management Program (ICDMP), a programme intended to improve the health and healthcare utilization of 15,000 Aged, Blind and Disabled Medicaid members living with diabetes and/or congestive heart failure in Indiana. Within ICDMP, programme components derived from the Chronic Care Model and education based on an integrated theoretical framework were utilized to create a telephonic care management intervention that was delivered by trained, non-clinical Care Managers (CMs) working under the supervision of a Registered Nurse. CMs utilized computer-assisted health education scripts to address clinically important topics, including medication adherence, diet, exercise and prevention of disease-specific complications. Employing reflective listening techniques, barriers to optimal self-management were assessed and members were encouraged to engage in health-improving actions. ICDMP evaluation results suggest that this low-intensity telephonic intervention shifted utilization and lowered costs. We discuss this patient-centred method for motivating behaviour change, the theoretical constructs underlying the scripts and the branched-logic format that makes them suitable to use as a computer-based application. Our aim is to share these public-domain materials with other programmes.
Estimating Untracked Gaming Volumes by Hotel Occupancy Segment
Authors: Lucas Anthony F.
Published: May 2010

Many Las Vegas gaming properties also operate hotels with thousands of rooms, which cannot be filled with premium gamblers every night. Given the fierce competition for premium gamblers, hotel-casino executives must pursue other segments as well. To choose segments that optimize earnings, management must compute the total value of a room night for each target segment. Customer spending traverses several departments, including slots, table games, restaurants, and retail. Unfortunately, many of these transactions are not captured at the customer level. Therefore, equations must be derived to estimate critical values, such as the change in unrated slot play resulting from a one-unit increase in the wholesale room segment. Such equations allow executives to fill in crucial gaps in the segment valuation grid. Once the overall profit per room night is computed for each hotel segment, operators can rank segment values. This business intelligence identifies the most and least valuable segments, allowing management to move toward optimizing earnings. Performance data from a Las Vegas Strip hotel-casino are used to illustrate the tenability of models designed to predict critical pieces of this profit puzzle. Unique and important differences in the margins of hotel-casino profit centers are also highlighted.
Media Policy Silences: The Hidden Face of Communications Decision Making
Authors: Freedman Des
Published: May 2010

The analysis of media policy usually, and understandably, focuses on visible instances of policy action : of government intervention, regulatory activity, civil society engagement, and corporate initiatives. Less frequently considered is the process by which certain issues, frames, and proposals are neglected inside decision-making structures. This article reflects on the relationship between “industrial activism” and policy silences in relation to government desire to secure a digital communications infrastructure for the twenty-first century. It argues that policy analysts need to look beyond immediate and visible instances of decision making in the media field and examine the ideological processes of exclusion and marginalization that distort media policy making and undermine the emergence of alternative paradigms and policy outcomes.
The leader intron of AtMHX can elicit, in the absence of splicing, low-level intron-mediated enhancement that depends on the internal intron sequence
Authors: Akua Tsofit , Berezin Irina , Shaul Orit
Published: May 2010

Background

Introns stimulate gene expression in a wide range of organisms by increasing the levels of mature mRNA, without affecting mRNA stability. Although introns sometimes function as transcriptional enhancers, they usually stimulate expression by a process termed intron-mediated enhancement (IME). The mechanism of IME is largely unknown. While splicing per se is not sufficient for IME, as evident from the fact that not all introns increase expression, it is not clear yet whether splicing of the enhancing introns is essential for enhancement. The leader intron (LI) of the Arabidopsis AtMHX gene was previously shown to substantially increase the expression of the AtMHX promoter. Here we investigated whether this LI acts as a transcriptional enhancer and whether its splicing is essential for IME.

Results

Expression in transformed Arabidopsis plants of an AtMHX::GUS construct from which the LI was eliminated was similar to a construct that included only the minimal promoter fused to GUS. Yet, almost no expression was seen in constructs that included the LI in addition to the minimal promoter or the LI inserted in various locations in the promoter. While the LI enhanced 272-fold the expression of the weak AtMHX promoter, only a 3-fold enhancement was observed for the strong CaMV 35S promoter. In the context of the AtMHX promoter, an unspliceable version of the LI that had mutated 5' and 3' splice sites mediated a low-level (5-fold) enhancement. Eliminating the internal 320 nt of the 416 nt unspliceable intron resulted in loss of ability to mediate low-level enhancement.

Conclusions

Although AtMHX promoter shows almost no expression in the absence of its LI, this intron does not act as a transcriptional enhancer and is unable to support expression in the absence of the enhancer elements of the promoter. It is also shown that the same intron can have very different contributions to expression of different promoters. Our results also demonstrate that while splicing is essential for substantial IME, in the absence of splicing low-level enhancement can be obtained. Notably, it is shown that the internal intron sequence plays a significant role in mediating the low-level enhancement of unspliced introns.
Nutrigenomics Therapy of Hepatisis C Virus Induced-hepatosteatosis
Authors: Liu Qing , Bengmark Stig , Qu Shen
Published: May 2010

Nutrigenomics is a relatively new branch of nutrition science, which aim is to study the impact of the foods we eat on the function of our genes. Hepatosteatosis is strongly associated with hepatitis C virus infection, which is known to increase the risk of the disease progression and reduce the likelihood of responding to anti- virus treatment. It is well documented that hepatitis C virus can directly alter host cell lipid metabolism through nuclear transcription factors. To date, only a limited number of studies have been on the effect of human foods on the nuclear transcription factors of hepatitis C virus -induced hepatosteatosis.

Three nutrients, selected among 46 different nutrients: β-carotene, vitamin D2, and linoleic acid were found in a cell culture system to inhibit hepatitis C virus RNA replication. In addition, polyunsaturated fatty acids (PUFAs) especially arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) have been demonstrated to inhibit hepatitis C virus RNA replication. These PUFAs, in particular the highly unsaturated n-3 fatty acids change the gene expression of PPARa and SREBP, suppress the expression of mRNAs encoding key metabolic enzymes and hereby suppress hepatic lipogenesis and triglyceride synthesis, as well as secretion and accumulation in tissues. A recent prospective clinical trial of 1,084 chronic hepatitis C patients compared to 2,326 healthy subjects suggests that chronic hepatitis C patients may benefit from strict dietary instructions.

Increasing evidence suggest that some crucial nuclear transcription factors related to hepatitis C virus -associated hepatosteatosis and hepatitis C virus RNA itself can be controlled by specific anti- hepatitis C virus nutrition. It seems important that these findings are taken into account and specific nutritional supplements developed to be used in combination with interferon as adjunctive therapy with the aim to improve both the early as well as the sustained virological response.
The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer
Authors: Dai Fuqiang , Liu Lunxu , Che Guowei , Yu Nanbin , Pu Qiang , Zhang Shangfu , Ma Junliang , Ma Lin , You Zongbing
Published: May 2010

Background

Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time.

Methods

Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0).

Results

The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time.

Conclusions

The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.
Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence
Authors: Bravo-Cuellar Alejandro , Ortiz-Lazareno Pablo C , Lerma-Diaz Jose M , Dominguez-Rodriguez Jorge R , Jave-Suarez Luis F , Aguilar-Lemarroy Adriana , del Toro-Arreola Susana , de Celis-Carrillo Ruth , Sahagun-Flores Jose E , de Alba-Garcia Javier E Garcia , Hernandez-Flores Georgina
Published: May 2010

Background

Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells.

Methods

HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IκBα and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot.

Results

PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IκBα levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR.

Conclusion

PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.
The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein
Authors: Kim Jihoon , Harada Ryuichi , Kobayashi Masaki , Kobayashi Natsuki , Sode Koji
Published: May 2010

Background

Parkinson's disease (PD) involves the selective damage of dopaminergic neuron cells resulting from the accumulation and fibril formation of alpha-synuclein. Recently, it has been shown that not only full-length alpha-synuclein, but also C-terminal truncated forms exist in the normal brain, as well as Lewy bodies, which are cytoplasmic inclusions in PD. It is known that truncated alpha-synuclein has a much higher ability to aggregate and fibrillate than full-length alpha-synuclein. Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent the formation of oligomers and/or fibrils might open the way to a novel therapeutic approach to PD. However, no inhibitor for truncated alpha-synuclein has been reported yet.

Results

In this study, we first characterized the aggregation and cytotoxicity of C-truncated alpha-synuclein119 and alpha-synuclein133 which have been found in both the normal and the pathogenic brain. Alpha-synuclein119 aggregated more rapidly and enhanced significantly the fibril formation of alpha-synuclein. Although both of alpha-synuclein119 and alpha-synuclein133 showed a high cytotoxicity, alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. We showed that PQQ dramatically inhibits the fibril formation of C-terminal truncated alpha-synuclein110119, and 133 as well as the mixtures of full-length alpha-synuclein with these truncated variants. Moreover, PQQ decreases the cytotoxicity of truncated alpha-synuclein.

Conclusions

Our results demonstrate that PQQ inhibits the amyloid fibril formation and cytotoxicity of the C-truncated alpha-synuclein variants. We believe that PQQ is a strong candidate for a reagent compound in the treatment of PD.
Expression of migration-related genes is progressively upregulated in murine Lineage-Sca-1+c-Kit+ population from the fetal to adult stages of development
Authors: Ciriza Jesús , García-Ojeda Marcos E
Published: May 2010

Introduction

Hematopoietic stem cells (HSCs) follow a genetically programmed pattern of migration during development. Extracellular matrix and adhesion molecules, as well as chemokines and their receptors, are important in adult HSC migration. However, little is known about the role these molecules play at earlier developmental stages.

Methods

We have analyzed by quantitative polymerase chain reaction (qPCR) array the expression pattern of extracellular matrix and adhesion molecules as well as chemokines and chemokine receptors in Lineage-Sca-1+c-Kit+ (LSK) cells at different stages of development, in order to characterize the role played by these molecules in LSK. Data were represented by volcano plots to show the differences in expression pattern at the time points studied.

Results

Our results show marked changes in the expression pattern of extracellular matrix, adhesion molecules, chemokines and their receptors with developmental age, particularly in later stages of development. Ten molecules were significantly increased among the LSK populations studied. Our screen identified the upregulation of Col4a1, as well as molecules involved in its degradation (Mmp2, Timp2), with development. Other genes identified were Sell, Tgfbi, and Entpd1. Furthermore, we show that the expression of the chemokines Ccl4, Ccl9, Il18 and the chemokine receptor Cxcr4 increases in LSK cells during development.

Conclusions

Several genes are upregulated in the LSK population in their transition to the bone marrow microenvironment, increasing at later stages of development. This gene pattern should be emulated by embryonic stem cell-derived hematopoietic progenitors in order to improve their properties for clinical applications such as engraftment.
Geophysics Dissertation Abstracts
Authors: Akerberg Peeter
Published: May 2010

Recent Ph.D. graduates are invited to submit abstracts of their dissertations by completing and submitting the submission form ⟨ http://www.seg.org/SEGportalWEBproject/prod/SEG-Publications/Pub-Geophysics/Documents/dissertationform.pdf ⟩ at http://seg.org/dissertationabstracts . Abstracts are reviewed and accepted or rejected based on their relevance to the readers of Geophysics. Abstracts must be written in English and defended in 2009 or later.
Intellectual Property
Authors: Walker David A.
Published: May 2010

The Intellectual Property department in each issue of Geophysics provides U.S. patent abstracts, published patent abstracts of U.S. patent applications, and published abstracts filed under the Patent Cooperation Treaty (PCT).
Regulation of Islet β-Cell Pyruvate Metabolism: Interactions of Prolactin, Glucose, and Dexamethasone
Authors: Arumugam Ramamani , Horowitz Eric , Noland Robert C. , Lu Danhong , Fleenor Donald , Freemark Michael
Published: May 2010

Prolactin (PRL) induces β-cell proliferation and glucose-stimulated insulin secretion (GSIS) and counteracts the effects of glucocorticoids on insulin production. The mechanisms by which PRL up-regulates GSIS are unknown. We used rat islets and insulinoma (INS-1) cells to explore the interactions of PRL, glucose, and dexamethasone (DEX) in the regulation of β-cell pyruvate carboxylase (PC), pyruvate dehydrogenase (PDH), and the pyruvate dehydrogenase kinases (PDKs), which catalyze the phosphorylation and inactivation of PDH. PRL increased GSIS by 37% (P < 0.001) in rat islets. Glucose at supraphysiological concentrations (11 mm) increased PC mRNA in islets; in contrast, PRL suppressed PC mRNA levels in islets and INS-1 cells, whereas DEX was without effect. Neither PRL nor DEX altered PC protein or activity levels. In INS-1 cells, PRL increased PDH activity 1.4- to 2-fold (P < 0.05–0.001) at glucose concentrations ranging from 2.5–11 mm. DEX reduced PDH activity; this effect was reversed by PRL. PDK1, -2, -3, and -4 mRNAs were detected in both islets and insulinoma cells, but the latter expressed trivial amounts of PDK4. PRL reduced PDK2 mRNA and protein levels in rat islets and INS-1 cells and PDK4 mRNA in islets; DEX increased PDK2 mRNA in islets and INS-1 cells; this effect was reversed by PRL. Our findings suggest that PRL induction of GSIS is mediated by increases in β-cell PDH activity; this is facilitated by suppression of PDKs. PRL counteracts the effects of DEX on PDH and PDK expression, suggesting novel roles for the lactogens in the defense against diabetes.
Regulation of Placental Leptin Expression by Cyclic Adenosine 5′-Monophosphate Involves Cross Talk between Protein Kinase A and Mitogen-Activated Protein Kinase Signaling Pathways
Authors: Maymó Julieta L. , Pérez Pérez Antonio , Dueñas José L. , Calvo Juan Carlos , Sánchez-Margalet Víctor , Varone Cecilia L.
Published: May 2010

Leptin, a 16-kDa protein mainly produced by adipose tissue, has been involved in the control of energy balance through its hypothalamic receptor. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in placenta, where it was found to be expressed. In the current study, we examined the effect of cAMP in the regulation of leptin expression in trophoblastic cells. We found that dibutyryl cAMP [(Bu)2cAMP], a cAMP analog, showed an inducing effect on endogenous leptin expression in BeWo and JEG-3 cell lines when analyzed by Western blot analysis and quantitative RT-PCR. Maximal effect was achieved at 100 μM. Leptin promoter activity was also stimulated, evaluated by transient transfection with a reporter plasmid construction. Similar results were obtained with human term placental explants, thus indicating physiological relevance. Because cAMP usually exerts its actions through activation of protein kinase A (PKA) signaling, this pathway was analyzed. We found that cAMP response element-binding protein (CREB) phosphorylation was significantly increased with (Bu)2cAMP treatment. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor CREB caused a significant stimulation on leptin promoter activity. On the other hand, the cotransfection with a dominant negative mutant of the regulatory subunit of PKA inhibited leptin promoter activity. We determined that cAMP effect could be blocked by pharmacologic inhibition of PKA or adenylyl ciclase in BeWo cells and in human placental explants. Thereafter, we decided to investigate the involvement of the MAPK/ERK signaling pathway in the cAMP effect on leptin induction. We found that 50 μm PD98059, a MAPK kinase inhibitor, partially blocked leptin induction by cAMP, measured both by Western blot analysis and reporter transient transfection assay. Moreover, ERK 1/2 phosphorylation was significantly increased with (Bu)2cAMP treatment, and this effect was dose dependent. Finally, we observed that 50 μm PD98059 inhibited cAMP-dependent phosphorylation of CREB in placental explants. In summary, we provide some evidence suggesting that cAMP induces leptin expression in placental cells and that this effect seems to be mediated by a cross talk between PKA and MAPK signaling pathways.
Lipoatrophy Induced by Subcutaneous Insulin Infusion: Ultrastructural Analysis and Gene Expression Profiling
Authors: Milan G. , Murano I. , Costa S. , Pianta A. , Tiengo C. , Zulato E. , Centobene C. , Bruttomesso D. , Cinti S. , Vettor R.
Published: May 2010

Context and Objective: Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions.

Setting and Patients: Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro insulin by continuous sc insulin infusion was studied using magnetic resonance imaging, immunohistochemistry, electron microscopy, and quantitative PCR for adipose tissue-specific genes.

Results: SAT was present in LA lesions characterized by: 1) smaller, unilocular perilipin-positive adipocytes, with lipofuscin granules; 2) some “slimmed cells” losing lipid droplets as those we observed during starvation; and 3) numerous perivascular preadipocytes. We did not identify inflammatory cells. SAT in LA areas displayed a strong leptin down-regulation and an increase of AEBP1, a preadipocyte marker.

Conclusions: Our results clearly indicate that the remarkable reduction in fat cell lipid droplets and adipocyte size justifies the decrease of SAT without a reduction in adipocyte number because of necrosis or apoptosis. Thus, immune cells and any other toxic damaging fat cells were not involved in the generation of LA. We speculate that adipocytes chronically exposed to high local insulin concentrations could become severely insulin resistant, dramatically increasing lipolysis and giving rise to “slimmed cells.” Clinical LA regression could be explained by the active recruitment of preadipocytes, even if they were unable to differentiate and regenerate adipose tissue unless the insulin injection was removed.
An Acetylation Switch Modulates the Transcriptional Activity of Estrogen-Related Receptor α
Authors: Wilson Brian J. , Tremblay Annie M. , Deblois Geneviève , Sylvain-Drolet Guillaume , Giguère Vincent
Published: May 2010

Posttranslational modifications are instrumental to achieve gene- and tissue-specific regulatory outcomes by transcription factors. Nuclear receptors are dynamically modulated by several types of posttranslational modifications including phosphorylation, methylation, acetylation, ubiquitination, and sumoylation. The estrogen-related receptor α (ERRα, NR3B1) is phosphorylated on multiple sites, and sumoylated in the amino-terminal region in a phosphorylation-dependent manner. Here we demonstrate that ERRα interacts with and is acetylated by p300 coactivator associated factor (PCAF) in vitro and in mouse liver. Purified PCAF acetylated the DNA-binding domain of ERRα on four highly-conserved lysines. In addition, coexpression of PCAF reduced the transcriptional activity of ERRα and, reciprocally, a deacetylase screen identified histone deacetylase 8 (HDAC8) and sirtuin 1 homolog (Sirt1) as independent enhancers of ERRα transcriptional function. HDAC8 and Sirt1 were also demonstrated to interact directly with ERRα in vivo and to deacetylate and increase the DNA binding affinity of ERRα in vitro. The removal of PCAF increases the DNA binding of ERRα in vivo, whereas the removal of Sirt1 and HDAC8 decreases it as assessed by chromatin immunoprecipitation assay. Altogether, our results show that ERRα is an acetylated protein and imply the existence of a dynamic acetylation/deacetylation switch involved in the control of ERRα transcriptional activity.
cAMP-Dependent Activation of Mammalian Target of Rapamycin (mTOR) in Thyroid Cells. Implication in Mitogenesis and Activation of CDK4
Authors: Blancquaert Sara , Wang Lifu , Paternot Sabine , Coulonval Katia , Dumont Jacques E. , Harris Thurl E. , Roger Pierre P.
Published: May 2010

How cAMP-dependent protein kinases [protein kinase A (PKA)] transduce the mitogenic stimulus elicited by TSH in thyroid cells to late activation of cyclin D3-cyclin-dependent kinase 4 (CDK4) remains enigmatic. Here we show in PC Cl3 rat thyroid cells that TSH/cAMP, like insulin, activates the mammalian target of rapamycin (mTOR)-raptor complex (mTORC1) leading to phosphorylation of S6K1 and 4E-BP1. mTORC1-dependent S6K1 phosphorylation in response to both insulin and cAMP required amino acids, whereas inhibition of AMP-activated protein kinase and glycogen synthase kinase 3 enhanced insulin but not cAMP effects. Unlike insulin, TSH/cAMP did not activate protein kinase B or induce tuberous sclerosis complex 2 phosphorylation at T1462 and Y1571. However, like insulin, TSH/cAMP produced a stable increase in mTORC1 kinase activity that was associated with augmented 4E-BP1 binding to raptor. This could be caused in part by T246 phosphorylation of PRAS40, which was found as an in vitro substrate of PKA. Both in PC Cl3 cells and primary dog thyrocytes, rapamycin inhibited DNA synthesis and retinoblastoma protein phosphorylation induced by TSH and insulin. Although rapamycin reduced cyclin D3 accumulation, the abundance of cyclin D3-CDK4 complexes was not affected. However, rapamycin inhibited the activity of these complexes by decreasing the TSH and insulin-mediated stimulation of activating T172 phosphorylation of CDK4. We propose that mTORC1 activation by TSH, at least in part through PKA-dependent phosphorylation of PRAS40, crucially contributes to mediate cAMP-dependent mitogenesis by regulating CDK4 T172-phosphorylation.