bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II Stimulates Protein Kinase D-Dependent Histone Deacetylase 5 Phosphorylation and Nuclear Export Leading to Vascular Smooth Muscle Cell Hypertrophy
Authors: Xu Xiangbin , Ha Chang-Hoon , Wong Chelsea , Wang Weiye , Hausser Angelika , Pfizenmaier Klaus , Olson Eric N. , McKinsey Timothy A. , Jin Zheng-Gen
Published: September 2007

Background—

Angiotensin II (Ang II) induces the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs), which is implicated in the pathogenesis of hypertension, atherosclerosis, and diabetes. In this study, we tested the hypothesis that histone deacetylases 5 (HDAC5) and its signal pathway play a role in Ang II-induced VSMC hypertrophy.

Methods and Results—

VSMCs were isolated from the thoracic aortas of male Sprague-Dawley rats and treated with Ang II. We found that Ang II rapidly stimulated phosphorylation of HDAC5 at Serine259/498 residues in a time- and dose- dependent manner. Ang II receptor-1, protein kinase C, and protein kinase D1 (PKD1) mediated HDAC5 phosphorylation. Furthermore, we observed that Ang II stimulated HDAC5 nuclear export, which was dependent on its PKD1-dependent phosphorylation. Consequently, both inhibiting PKD1 and HDAC5 Serine259/498 to Alanine mutant significantly attenuated Ang II-induced myocyte enhancer factor-2 (MEF2) transcriptional activity and protein synthesis in VSMCs.

Conclusion—

These findings demonstrate for the first time that PKD1-dependent HDAC5 phosphorylation and nuclear export mediates Ang II-induced MEF2 activation and VSMC hypertrophy, and suggest that PKD1 and HDAC5 may emerge as potential targets for the treatment of pathological vascular hypertrophy.
Carbon Monoxide Induces Heme Oxygenase-1 via Activation of Protein Kinase R–Like Endoplasmic Reticulum Kinase and Inhibits Endothelial Cell Apoptosis Triggered by Endoplasmic Reticulum Stress
Authors: Kim Ki Mo , Pae Hyun-Ock , Zheng Min , Park Raekil , Kim Young-Myeong , Chung Hun-Taeg
Published: September 2007

Carbon monoxide (CO), a reaction product of the cytoprotective heme oxygenase (HO)-1, is antiapoptotic in a variety of models of cellular injury, but the precise mechanisms remain to be established. In human umbilical vein endothelial cells, exogenous CO activated Nrf2 through the phosphorylation of protein kinase R–like endoplasmic reticulum kinase (PERK), resulting in HO-1 expression. CO-induced activation of PERK was followed by the phosphorylation of eukaryotic translation initiation factor 2α and the expression of activating transcription factor 4. However, CO fails to induce X-box binding protein-1 expression and activating transcription factor 6 cleavage. CO had no significant effect on synthesis of endoplasmic reticulum (ER) chaperone proteins such as the 78-kDa glucose-regulated proteins 78 and 94. Instead, CO prevented X-box binding protein 1 expression and activating transcription factor 6 cleavage induced by ER-stress inducers such as thapsigargin, tunicamycin and homocysteine. CO also prevented endothelial apoptosis triggered by these ER inducers through suppression of C/EBP homologous protein expression, which was associated with its activation of p38 mitogen-activated protein kinase. Similarly, endogenous CO produced from endothelial HO-1 induced by either exogenous CO or a pharmacological inducer was also cytoprotective against ER stress through C/EBP homologous protein suppression. Our findings suggest that CO renders endothelial cells resistant to ER stress not only by downregulating C/EBP homologous protein expression via p38 mitogen-activated protein kinase activation but also by upregulating Nrf2-dependent HO-1 expression via PERK activation. Thus, the HO-1/CO system might be potential therapeutics in vascular diseases associated with ER stress.
Smooth Muscle Cells and Myofibroblasts Use Distinct Transcriptional Mechanisms for Smooth Muscle α-Actin Expression
Authors: Gan Qiong , Yoshida Tadashi , Li Jian , Owens Gary K.
Published: September 2007

There has been considerable controversy regarding the lineage relationship between smooth muscle cells (SMCs) and myofibroblasts, because they express a number of common cell-selective markers including smooth muscle (SM) α-actin. We have shown previously that MCAT elements within the SM α-actin promoter confer differential activity in cultured SMCs versus myofibroblasts. In the present study, to determine the role of MCAT elements in vivo, we generated transgenic mice harboring an SM α-actin promoter–enhancer–LacZ reporter gene containing MCAT element mutations and compared transgene expression patterns with wild-type SM α-actin promoter–enhancer–LacZ transgenic mice. Results showed no differences in LacZ expression patterns in adult SMC-containing tissues. However, of interest, mutations of MCAT elements selectively abolished transgene expression in myofibroblasts within granulation tissue of skin wounds. In addition, mutations of MCAT elements caused a delay in the induction of transgene expression in SMCs, as well as loss of expression in cardiac and skeletal muscles during embryogenesis. Results of small interfering RNA–induced knockdown experiments showed that RTEF-1 regulated SM α-actin transcription in myofibroblasts, but not in differentiated SMCs. Moreover, quantitative chromatin immunoprecipitation assays revealed that RTEF-1 bound to the MCAT element–containing region within the SM α-actin promoter in myofibroblasts, whereas transcriptional enhancer factor (TEF)-1 was bound to the same region in differentiated SMCs. These results provide novel evidence that, although both SMCs and myofibroblasts express SM α-actin, they use distinct transcriptional control mechanisms for regulating its expression. Results also indicate that the MCAT element-mutated SM α-actin promoter–enhancer is a useful tool to direct gene expression selectively in differentiated SMCs.
Urinary Incontinence After Stroke
Authors: Dumoulin Chantale , Korner-Bitensky Nicol , Tannenbaum Cara
Published: September 2007

Background and Purpose—

Urinary incontinence (UI) is a common and distressing problem after stroke. Although there is evidence of new, effective UI poststroke rehabilitation intervention, it is unknown whether occupational therapists (OTs)’ and physical therapists (PTs)’ actual practices reflect best practices. We sought to determine the extent to which OTs and PTs identify, assess, and treat UI after stroke and to identify personal and organizational predictors of UI problem identification, best-practice assessment, and intervention.

Methods—

Six hundred sixty-three OTs (93% participation rate) and 656 PTs (87% participation rate) working in stroke rehabilitation in Canada were randomly selected and interviewed with a telephone-administered questionnaire. Each responded to a series of open-ended questions related to a generated case (vignette) of a typical client with stroke who was experiencing UI.

Results—

Only 39% of OTs and 41% of PTs identified UI after stroke as a problem. Fewer than 20% of OTs and 15% of PTs used best-practice assessments, and only 2% of OTs and 3% of PTs used best-practice interventions. Working in Ontario, having allocated learning time, and doing university teaching were among the variables explaining between 6% and 9% of the variability in UI identification and assessment.

Conclusions—

Canadian OTs and PTs do not routinely identify poststroke UI as a problem, and best-practice assessments and interventions are underused.
Access to Financial Capital among U.S. Businesses: The Case of African American Firms
Authors: Robb Alicia M. , Fairlie Robert W.
Published: September 2007

Using data from multiple sources, including the Characteristics of Business Owners Survey, the authors trace out the relationship between wealth and access to financial capital and the African American—owned business. African Americans are found to have levels of wealth that are one-eleventh those of whites. Starting with this disparity, blacks are much less likely to start businesses than are whites, which results in a substantially lower rate of business ownership. Even for those black entrepreneurs who are successful in starting businesses, the authors find that they invest much less capital at start-up on average than white entrepreneurs. Lower levels of start-up capital among black businesses appear to also limit their ability to grow and succeed. Racial disparities in start-up capital contribute to higher failure rates, lower sales and profits, less employment among black-owned businesses, and less survivability of the business.
Small Firm Credit Market Discrimination, Small Business Administration Guaranteed Lending, and Local Market Economic Performance
Authors: Craig Ben R. , Jackson William E. , Thomson James B.
Published: September 2007

In this article, the authors empirically test whether Small Business Administration (SBA) guaranteed lending has a greater impact on economic performance in markets with a high percentage of potential minority small businesses. This hypothesis is based on the assumptions that (1) credit rationing is more likely to occur in markets with a higher percentage of minority small businesses; and (2) SBA guaranteed lending is likely to reduce these credit rationing problems, thus improving economic performance in the local market. Using local market employment rates as the measure of economic performance, the authors find evidence consistent with this proposition. Specifically, the authors find a positive and significant impact of SBA guaranteed lending on the average employment rate in a local market. And, this impact is 200 percent larger in markets with a high percentage of potential minority small businesses. This result has important implications for public policy in general and SBA guaranteed lending in particular.
Traits and Performance of the Minority Venture-Capital Industry
Authors: Bates Timothy , Bradford William
Published: September 2007

This study analyzes the performance of investments made by venture-capital (VC) funds that specialize in financing minority business enterprises (MBEs). Existing studies document that MBEs have less access to financing—equity as well as debt—than similarly situated firms owned by nonminority whites. The apparent existence of a discriminatory financing environment creates an underserved market and, hence, attractive opportunities are available to firms capable of identifying and serving MBE financing needs. Analyzing cash-flow data on VC investments, we find that the minority-oriented funds earned yields on their realized equity investments that were slightly higher than the returns reported by mainstream VC funds. Considering differences in methodologies used to generate rate-of-return data for the MBE—as opposed to the nonminority-oriented funds—we conclude that the minority VC funds are earning yields on their realized investments that are at least equivalent to those of the broader VC industry.
Increasing Physical Exercise Levels
Authors: Scholz Urte , Sniehotta Falko F. , Burkert Silke , Schwarzer Ralf
Published: September 2007

Purpose: This study examines the differential age effects on physical exercise of two planning interventions, action planning (when, where, how) and coping planning (anticipating barriers, mental simulation of success scenarios), and examines the mediating mechanisms of the interventions. Methods: The study assigned the participants, 205 cardiac rehabilitation patients, to one of the intervention groups (action-planning only or combined-planning group) or to a control group. Baseline measurement and follow-up took place 2 months apart. Results: The interventions enhanced physical exercise independently of age. Pretreatment coping planning was higher in older (65-82 years) than in younger (38-54 years) or middle-aged (55-64 years) participants. At Time 2, older participants were the only ones without further increase in coping planning. Advancement in coping planning partially mediated the effect of the intervention. Conclusion: Coping planning facilitates improvement of physical exercise. Implications of age differences in planning are discussed.
Understanding the Supportive Care Needs of Parents of Children With Cancer: An Approach to Local Needs Assessment
Authors: Kerr Laura M. J. , Harrison Margaret B. , Medves Jennifer , Tranmer Joan E. , Fitch Margaret I.
Published: September 2007

The objective of this study was to conduct an assessment of supportive care needs from the perspective of parents of children diagnosed with cancer within an urban-rural region in Eastern Ontario, Canada. Guided by a conceptual framework for supportive care, the exploratory, mixed-method study used a standard needs survey and semistructured interviews. Fifteen parents completed (75% response rate) the survey, and 3 parents participated as key informants in the follow-up interview. Parents reported needs in all 6 of the need categories outlined within the Supportive Care Needs Framework. The proportion of parents expressing a need ranged from 23% to 39%. Dealing with the fear of their child's cancer spreading was frequently identified by parents. Emotional and informational needs were the 2 most frequently acknowledged categories of need. With further refinement, the use of the conceptual framework will provide a methodology for planning care based on the individual needs identified by parents of children with cancer.
The organizational effects of oxytocin on the central expression of estrogen receptor α and oxytocin in adulthood
Authors: Kramer Kristin M , Yoshida Shigeto , Papademetriou Eros , Cushing Bruce S
Published: September 2007

Background

Previous studies have demonstrated that neonatal manipulation of oxytocin (OT) has effects on the expression of estrogen receptor α (ERα) and the central production of oxytocin observed in juveniles (at weaning, 21 days of age). The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles (Microtus ochrogaster) received one of three doses of OT (High, 3 μg; Med, 0.3 μg; Low, 0.03 μg), an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ERα or OT using immunocytochemistry.

Results

In females, treatment with OT increased the expression of ERα immunoreactivity in the ventral lateral septum (0.03 μg) and the ventromedial nucleus of the hypothalamus and central amygdala (0.3 μg). In males, OT antagonist increased ERα expression in the bed nucleus of the stria terminalis. There was no apparent effect of OT on the number of cells producing OT in the paraventricular nucleus of the hypothalamus.

Conclusion

The current results suggest that neonatal manipulation of OT has long-term organizational effects on the expression of ERα in both males and females. The lack of effect on OT neurons in the paraventricular nucleus suggests that some developmental effects of OT previously observed in weanlings do not persist into adulthood. Developmental effects of OT on ERα patterns were sexually dimorphic, dose-dependent, and site-specific.
Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury
Authors: Radojicic Milan , Nistor Gabriel , Keirstead Hans S
Published: September 2007

Background

Chronic spinal cord injury (SCI) can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration.

Methods

Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4), 28 (n = 4), 120 (n = 4), 450 (n = 5), or 540 (n = 5) days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures.

Results

Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil.

Conclusion

Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of chronic SCI and provide novel targets for therapeutic intervention.
Antimetabolite Radiosensitizers
Authors: Shewach Donna S. , Lawrence Theodore S.
Published: September 2007

Radiosensitization with antimetabolites has improved clinical outcome for patients with solid malignancies, especially cancers of the GI tract, cervix, and head and neck. Fluorouracil (FU) and hydroxyurea have been widely used clinically during the last four decades, and promising results have been observed more recently with gemcitabine. Although the antimetabolites all target DNA replication, they differ with respect to the mechanisms by which they produce radiosensitization. The antimetabolite radiosensitizers may inhibit thymidylate synthase (TS) or ribonucleotide reductase, and the nucleoside/nucleobase analogs can be incorporated into DNA. Radiosensitization can result from chemotherapy-induced increase in DNA double-strand breaks or inhibition of their repair. Studies of repair pathways involved in radiosensitization with antimetabolites implicate base excision repair with the TS inhibitors, homologous recombination with gemcitabine, and mismatch repair with FU and gemcitabine. Gemcitabine can also stimulate epidermal growth factor receptor (EGFR) phosphorylation; inhibiting this effect with EGFR inhibitors can potentiate cytotoxicity and radiosensitization. Additional work is necessary to determine more precisely the processes by which antimetabolites act as radiation sensitizers and to define the optimal sequencing of these agents with EGFR inhibitors to provide better guidance for clinical protocols combining these drugs with radiotherapy.
Pharmacologic Approaches to Radiation Protection
Authors: Brizel David M.
Published: September 2007

The concept of the therapeutic ratio (TR) is central to understanding the rationale for using radioprotectors. The TR relates tumor control probabilities and normal tissue complication probabilities to one another. An ideal radioprotector will reduce the latter without compromising the former. It should also be minimally toxic itself. Radioprotective strategies can be classified under the categories of protection, mitigation, and treatment. Protectors are administered before radiotherapy (RT) and are designed to prevent radiation-induced injury. Amifostine is the prototype drug. Mitigants are administered after RT but before the phenotypic expression of injury and are intended to ameliorate injury. Palifermin can be considered as the prototype mitigant. Treatment is a strategy that is predominantly palliative and supportive in nature. Pharmacologic radioprotective strategies should be integrated with physical strategies such as intensity-modulated radiotherapy to realize their maximum clinical potential.
Use of Molecular Biomarkers for Predicting the Response to Radiotherapy With or Without Chemotherapy
Authors: Riesterer Oliver , Milas Luka , Ang K. Kian
Published: September 2007

Radiotherapy (RT), particularly when combined with chemotherapy, has progressively become the nonsurgical standard of care in the primary treatment of a variety of cancers. Likewise, hormonal therapy is routinely combined with RT for the treatment of hormone-sensitive tumors. In addition, the clinical efficacy of combining an epidermal growth factor receptor (EGFR) antagonist with RT was recently validated. In view of cancer heterogeneity and the availability of an increasing number of therapy options, identification of biomarkers that can predict tumor response to a given therapy is crucial in streamlining treatment and sparing patients from receiving often toxic and expensive therapies that are not likely to be effective. Well-established biomarkers for response to hormonal therapy and/or RT are tumor estrogen receptor and the receptor tyrosine kinase HER-2 for breast cancer and serum prostate-specific antigen for prostate carcinoma. Some markers of tumor hypoxia and the level of tumor EGFR expression have been shown to be independent predictors of tumor response to RT. The use of biomarkers for predicting tumor response to the combination of RT and chemotherapy has thus far been limited to the methylation status of O-6-methylguanine-DNA methyltransferase in patients with glioblastoma multiforme treated with the combination of RT plus temozolomide. No validated biomarkers for predicting the response to molecular therapeutics are currently available. In this review, we call for standardization and simplification of assay methods and stress the importance of conducting confirmatory prospective studies. Integrated plans for identifying molecular markers built into many ongoing trials will hopefully generate more insights in the near future.
Biology of Interactions: Antiepidermal Growth Factor Receptor Agents
Authors: Harari Paul M. , Allen Gregory W. , Bonner James A.
Published: September 2007

Epidermal growth factor receptor (EGFR) signaling inhibition represents a highly promising arena for the application of molecularly targeted cancer therapies. Evolving from several decades of systematic research in cancer cell biology, a series of EGFR inhibitors from both the monoclonal antibody (mAb) and tyrosine kinase inhibitor (TKI) class have been developed and promoted into clinical application. Several EGFR inhibitors have recently gained US Food and Drug Administration approval for cancer therapy in the United States (and many other countries), including the mAbs cetuximab and panitumumab, and the small molecule TKIs gefitinib, erlotinib, and lapatinib. The rapidly expanding preclinical and clinical data contributing to these US Food and Drug Administration drug registrations validates a central role of the EGFR as an important molecular target in epithelial malignancies. In this review, we focus primarily on the biology of EGFR interactions. Through improved understanding of EGFR biology in human cancers, there is anticipation that more tumor-selective therapy approaches with diminished collateral normal tissue toxicity can be advanced. Many questions remain to be answered, particularly with regard to how best combine EGFR inhibitors with conventional cancer therapies, and how to select those patients (tumors) most likely to benefit from EGFR inhibition strategies.
Chemoradiation in the Management of Esophageal Cancer
Authors: Kleinberg Lawrence , Forastiere Arlene A.
Published: September 2007

The combination of chemotherapy, fluorouracil and cisplatin, and radiation has improved outcome for patients with esophageal cancer. A randomized controlled trial confirmed a long-term survival benefit when this chemotherapy was added to radiotherapy for squamous cell carcinoma, but the approach has not been definitively assessed in patients with adenocarcinoma. Preoperative chemoradiotherapy has been tested in numerous phase II studies and underpowered or flawed phase III studies. Nevertheless, collectively, the evidence strongly suggests that preoperative chemoradiotherapy improves outcome, and thus, this strategy has become a standard treatment option. Attempts to improve outcome by intensifying conventional cytotoxic drugs or increasing the radiation dose have not been successful. Camptothecin and taxane-based regimens combined with radiation have altered the toxicity profile, but substantial improvement in survival outcomes has yet to be demonstrated. Future improvements will likely require the incorporation of targeted agents that add minimally to existing toxicity, the use of molecular predictors of response to individualize selection of the chemotherapeutic regimen, and early identification of responders such that therapy might be altered dynamically.
Evaluation of Early and Late Toxicities in Chemoradiation Trials
Authors: Bentzen Søren M. , Trotti Andrea
Published: September 2007

Combined chemoradiotherapy is increasingly becoming a standard of care for the nonoperative management of a variety of solid malignancies. A string of randomized controlled phase III trials have shown statistically significant and clinically relevant improvements in outcome, ostensibly without any apparent increase in late toxicity. However, the reliability and the sensitivity of toxicity reporting in most trials are questionable. Audits and phase IV studies suggest that the chemoradiotherapy success comes at a price in terms of late toxicity. This review presents some of the challenges in recording, analyzing, and reporting toxicity data. Methods for summarizing toxicity are reviewed, and a new investigational metric, the TAME reporting system, is discussed. The need for special vigilance in the era of molecular-targeted agents is emphasized because of the possibility that unexpected serious adverse events with a low incidence may occur. Finally, we discuss how progress in molecular pathology and radiation biology may provide novel opportunities for stratifying patients according to risk of adverse effects, interventional targets for reducing or treating adverse effects, and surrogate markers of normal-tissue injury.
Identification of Upstream Stimulatory Factor Binding Sites in the Human IGFBP3 Promoter and Potential Implication of Adjacent Single-Nucleotide Polymorphisms and Responsiveness to Insulin
Authors: Paquette Jean , Bessette Benoit , Ledru Elisabeth , Deal Cheri
Published: September 2007

The actions of IGFs are regulated at various levels. One mechanism involves binding to IGF-binding protein-3 (IGFBP-3) for transport, thus governing bioavailability. IGFBP3 transcription is modulated by many hormones and agents that stimulate or inhibit growth. We have previously shown in pediatric and adult cohorts a correlation between IGFBP-3 serum levels and two single-nucleotide polymorphisms (SNPs) located within the minimal promoter (−202 A/C and −185 C/T). Functionality of these SNPs was further explored in hepatic adenocarcinoma-derived SK-HEP-1 cells using transient transfections of luciferase constructs driven by different haplotypes of the IGFBP3 promoter. Basal luciferase activity revealed a significant haplotype-dependent transcriptional activity (at nucleotides −202 and −185, AC > CC, P < 0.001; AC > CT, P < 0.001; AC > AT, P < 0.001). Insulin treatment produced a similar haplotype dependence of luciferase activity (AC > CC, P = 0.002; AC > CT, P < 0.001; AC > AT, P = 0.011). However, induction ratios (insulin/control) for CC and AT were significantly higher compared with AC and CT (CC > AC, P = 0.03; CC > CT, P = 0.03; AT > AC, P = 0.03; AT > CT, P = 0.04). Gel retardation assays were used to identify upstream stimulatory factor (USF-1 and USF-2) methylation-dependent binding to E-box motifs located between the SNPs. Mutation of the USF binding site resulted in a significant loss of insulin stimulation of luciferase activity in the transfection assay. Chromatin immunoprecipitation with anti-USF-1/-2 showed an enrichment of IGFBP3 promoter in insulin-treated cells compared with unstimulated cells. Bisulfite sequencing of genomic DNA revealed that CpG methylation in the region of USF binding was haplotype dependent. In summary, we report a methylation-dependent USF binding site influencing the basal and insulin-stimulated transcriptional activity of the IGFBP3 promoter.
Tissue-Specific Effects of Central Leptin on the Expression of Genes Involved in Lipid Metabolism in Liver and White Adipose Tissue
Authors: Gallardo Nilda , Bonzón-Kulichenko Elena , Fernández-Agulló Teresa , Moltó Eduardo , Gómez-Alonso Sergio , Blanco Pablo , Carrascosa José Ma , Ros Manuel , Andrés Antonio
Published: September 2007

Leptin reduces adiposity and exerts antisteatotic effects on nonadipose tissues. However, the mechanisms underlying leptin effects on lipid metabolism in liver and white adipose tissue have not been fully clarified. Here, we have studied the effects of central leptin administration on key enzymes and transcription factors involved in lipid metabolism in liver and epididymal adipose tissue. Intracerebroventricular leptin infusion for 7 d did not change leptin plasma levels but decreased triacylglyceride content in liver, epididymal adipose tissue, and plasma. In both tissues this treatment markedly decreased the expression of key enzymes of the de novo fatty acid (FA) synthesis such as acetyl-coenzyme A-carboxylase, FA synthase, and stearoyl-coenzyme A desaturase-1, in parallel with a reduction in mRNA expression of sterol regulatory element binding protein-1c in liver and carbohydrate regulatory element binding protein in adipose tissue. In addition, leptin also decreased phosphoenol-pyruvate carboxykinase-C expression in adipose tissue, an enzyme involved in glyceroneogenesis in this tissue. Central leptin administration down-regulates delta-6-desaturase expression in liver and adipose tissue, in parallel with the decrease of the expression of sterol regulatory element binding protein-1c in liver and peroxisome proliferator activated receptor α in adipose tissue. Finally, leptin treatment, by regulating adipose triglyceride lipase/hormone sensitive lipase/diacylglycerol transferase 1 expression, also established a new partitioning in the FA-triacylglyceride cycling in adipose tissue, increasing lipolysis and probably the FA efflux from this tissue, and favoring in parallel the FA uptake and oxidation in the liver. These results suggest that leptin, acting at central level, exerts tissue-specific effects in limiting fat tissue mass and lipid accumulation in nonadipose tissues, preventing the development of obesity and type 2 diabetes.
Experimental study of teaching critical thinking in civic education in Taiwanese junior high school
Authors: Yang Shu Ching , Chung Tung‐Yu
Published: September 2007

BackgroundTo effectively respond to the need for greater CT (critical thinking) in the classroom, this study examines the effects of cultivating CT skills within civic education to maximize its potential. Despite realizing the importance of CT in education, schools do not tend to apply it. Furthermore, since students frequently do not raise questions or otherwise think critically, CT modules are incorporated into civic learning to encourage students to question facts, interpret and analyse evidence, make reasoned inferences regarding events, and independently develop informed opinions. These skills are fundamental to cultivating an informed and humane citizenry.

AimsThis investigation examines how teaching critical thinking in civic education affects the CT skills and disposition of junior high school students.

SampleThe participants were two classes of eighth grade students in southern Taiwan, and were distributed into experimental and control groups. Each group comprised 34 students, with the experimental group containing 16 boys and 18 girls and the control group containing 18 boys and 16 girls.

MethodThe teaching experiment in this study was initiated and performed using equivalent pre‐test and post‐test group design. During the 10‐week experiment, the experimental group was taught using CT instruction in civic education, while the control group was not taught with any CT programme. The data analysis included: quantitative statistics of the two main sets of instruments for measuring the CT ability and disposition of experimental treatment, qualitative analysis of learning sheets, and surveys of student perceptions of instruction in CT.

Results and conclusionsStatistical analysis showed that the experimental group significantly outperformed the control group on the scales of CT skill and disposition, but did not perform well on certain subscales (e.g. recognition of assumptions and deductions, truth‐seeking, analyticity, and inquisitiveness). Notably however, when triangulating with qualitative analysis of learner transcripts and surveys, learners attempted to perform various dimensions of CT skill and disposition to various degrees. Student surveys indicated that the CT programme fostered their active listening and respect for different ideas, and moreover they learned to tolerate divergent views and examine their ideas for possible bias. The programme boosted student learning interest and sense of accomplishment, and nurtured their teamwork/communicative skills. Furthermore, a few students experienced improvements in their speaking skills and courage as their confidence and ability to express themselves improved. Finally, limitations of this investigation and implications for further research are discussed.
Computer Waste: A Forgotten and Hidden Side to the Global Information Society
Authors: McKenna Alan
Published: September 2007

Whilst computer technology has radically impacted upon many facets of life, and continues almost relentlessly to do so, for several years questions have been raised about a particularly dark side to such technology, concerning its potential environmental implications where it is disposed of in an uncontrolled manner. This paper looks at the failure to date of the developed world to prevent the illegal movement of its hazardous computer waste to poorer regions, including the possible implications of the charitable provision of such equipment from developed to developing world, and puts forward proposals whereby hazardous computer waste can be dealt with in a manner that will help in part to ensure that developing countries can legitimately be seen as part of the digital age, and not merely a dumping ground, fed the rich world's digital toxic scraps.
Protection or Attack? Young People Carrying Knives and Dangerous Implements
Authors: Brown Jac , Sutton Jeanna
Published: September 2007

The incidence and circumstances of young people carrying knives and dangerous implements was investigated through surveys conducted with 150 ‘street youth’ and 184 ‘school youth’ in Sydney. It was found that a significant proportion of both samples carry and use knives/dangerous implements and that these implements had been used within the last week by many respondents. These implements are most commonly carried by young people between the ages of 13 and 14 years. A significant proportion of the sample reported having been threatened with knives/dangerous implements in the past. Police involvement was reported for both samples, but there was a higher proportion reported for the street sample. Young people report carrying knives/dangerous implements for safety, pressures from within and outside themselves, and to exert power and control over others. The research suggests that more emphasis needs to be placed on making young people feel safer in the community in order to address this problem.
Understanding and Managing Eating Disorders in the School Setting
Authors: Hellings Bridie , Bowles Terry
Published: September 2007

Children and adolescents suffering from an eating disorder will typically experience the adverse impact of such a disorder upon their education. These sufferers are often forced to defer their education whilst seeking treatment. However, there are a number of signs educators and school psychologists can look for to identify a student who may be struggling with an eating disorder, so as early intervention can be made to assist these students in the best possible manner. Based on a summary of recent research and literature, this article explains how eating disorders may be manifested in a school setting, how educators and school psychologists can help a student suffering from an eating disorder, and how schools can intervene to prevent eating disorders in students. Possible directions for future research in this area will also be explored.
Worry, General Self-Efficacy and School Achievement: An Exploratory Study With Chinese Adolescents
Authors: Tang Natalia Yuen Yi , Westwood Peter
Published: September 2007

This study identified issues in school – and in life outside school – that caused significant worry for 120 Chinese adolescents (72 males, 48 females) attending a secondary school in Hong Kong. The study explored relationships existing among 3 variables comprising degree of worry, students' general self-efficacy, and their academic achievement. Findings indicated that the students' principal worries centred on school-related matters such as examinations, promotion to higher classes, and getting a job after graduation. Students also worried significantly about the health status of family members, and family finances. Differences in patterns of worry and in self-efficacy beliefs were found between lower- and higher-achieving students. No significant correlations were found among students' degree of worry, general self-efficacy, and achievement. Results are discussed from the perspective of Chinese culture, the Hong Kong education system, and support for students.
Looking at Ourselves in our Mirror: Agency, Counter-Discourse, and the Nigerian Video Film
Authors: Okoye Chukwuma
Published: September 2007

The trouble is all the worse given that many Africans spend the greater part of their time looking at themselves in the mirror of the very people who imposed their condition on us in practically all areas of life on the pretext of a universalism that answered their own purposes. - Ambroise
Kom (2000a par 3.)
Institutional incentives for strategic voting and party system change in Portugal
Authors: Gschwend Thomas
Published: September 2007

Looking more closely at the way people form expectations about the possible outcome of the election in their electoral district I will provide evidence for the first time that strategic voting can be observed and predicted even in PR systems with large districts magnitudes, such as
in Portugal. Employing district-level data from 19752002 I estimate that a party, who is expected to win no seat, will be strategically deserted on average by about 3 per cent of the voters. This number does systematically vary with the district magnitude of each district. Nevertheless even
in Portugal's largest electoral district, Lisbon, strategic voting can be observed to have a systematic impact on parties vote shares. Moreover there is evidence that strategic voting can partly account for the majoritarian trend that can be observed within the Portuguese party system.
From melodrama to blockbuster: a comparative analysis of musical camouflage in Victorian theatre and twenty-first-century film
Authors: Dean Rob
Published: September 2007

This article explores the use of music as a functional device which disguises the artificial construction of narrative media. The identification of the principles behind the specific positioning of musical material in the presentation of film and theatre reveals that in certain scenarios
the aural accompaniment is not simply utilized as an emotive tool. Instead the polemic pursued in this article reveals that music also fulfils the practical purpose of camouflaging narrative leaps in time, space and dimension. Furthermore the comparative analysis of nineteenthcentury dramatic
texts penned by Dion Boucicault and twenty-first-century films written and directed by M. Night Shyamalan establishes both an interdisciplinary connection between the two media forms and highlights the parallel musical practices employed in the past and the present.
Imagining His Dark Materials as a Gesamtkunstwerk
Authors: MacDonald Laura
Published: September 2007

Using first-hand interviews conducted with playwright Nicholas Wright and composer Jonathan Dove, this article discusses the adaptation and production process behind the Royal National Theatre's staging of His Dark Materials. It suggests that an interdisciplinary, collaborative
approach was essential in bringing Pullman's epic to the stage. Different combinations of dialogue, music, scenic design, staging and puppetry allowed the production to convey detailed character histories and complex emotional experiences, and cover vast geographies, distilling the essence
of the compelling epic. In leaving the structure of the interdisciplinary collaboration transparent, this article argues that the director, Nicholas Hytner, and his team invited the audience to enter the worlds of the play as participants in the collaborative work, free to mould their own
experience of the heroes' adventures, and complete the adaptation with their own imagination. This twenty-first-century Gesamtkunstwerk bears comparison with Wagner's Ring cycle of music dramas.
Celiac artery compression syndrome – stepchild of abdominal angina?
Authors: Mucs Mihály , Székely Iván , Illés Iván , Juhász Árpád , Paál Balázs , Sárkány Ágnes , Madácsy László , Altorjay Áron
Published: September 2007

A krónikus, étkezéssel összefüggést nem mutató epigastrialis fájdalmak hátterében az esetek néhány százalékában a truncus coeliacus külső kompressziója áll.
Esetismertetés:
A szerzők egy 58 éves nőbeteg kórtörténetét ismertetik, akinél a hasi szervek ischaemiája, a felhasi fájdalom hátterében a preoperatív kivizsgálás a truncus coeliacuson rövid szakaszú stenosist okozó, a rekeszizom-hiátus aorticusát övező inas-izmos ívet igazolt. Előkészítést követően műtétet végeztünk, a trifurcatio eredésétől számított 8–10 mm-re levő heges, gyűrűszerű leszorítást felhasítottuk, a ganglion coeliacum egy részét eltávolítottuk. A beteg a posztoperatív 6. napon gyógyultan, panaszmentesen otthonába távozott.
Megbeszélés:
A klasszikus értelemben vett angina abdominalis a hasi szervek relatív ischaemiájának következménye. Ennek oka legtöbbször az érintett ér betegsége. Az artéria külső kompressziója csupán az esetek pár százalékát jelenti. A truncus coeliacus esetében ezt betegünknél a rekeszizom-hiátus aorticusát övező inas megerősödés okozta. A kivizsgálás során az erre utaló első jel az ér felett hallható „surranás” volt, a poststenoticus turbulens áramlás miatt. Az erre alapozott részletes radiológiai vizsgálatok igazolták a tényleges kórokot. Ennek ismeretében a felszabadító műtét teljes tünet- és panaszmentességet eredményezett.
Következtetés:
Bizonytalan hasi panaszok esetén gondolnunk kell az arteria coeliaca stenosisának lehetőségére is. Esetismertetésünkkel kívánjuk felhívni a figyelmet a hasi auscultatio jelentőségére, amely elengedhetetlen része a gasztroenterológiai vizsgálatoknak. A diagnózis felállításában a Doppler-duplexvizsgálat mellett komoly segítséget jelentettek az érfestési eljárások. A műtét lényegét képező érfelszabadítást célszerű mielőbb elvégezni, még mielőtt a tartós külső kompresszió degeneratív érfalelváltozást okoz.
Environmental dioxin compounds as the cause of endometriosis and other diseases
Authors: Simsa Péter , Járási Zsuzsanna Éva , Fülöp Vilmos
Published: September 2007

Régóta húzódó vita alakult ki, hogy vajon a dioxin, mely egy ipari toxin, lehet-e oki tényező egy alhasi fájdalommal és infertilitással járó nőgyógyászati kórkép, az endometriosis kialakulásában. Az elvégzett tanulmányok vagy nem találtak különbséget a betegek szérum-dioxinkoncentrációjában a kontrollokhoz viszonyítva, vagy nem szignifikáns emelkedést mutattak ki, illetve alacsony statisztikai erőt értek csak el. A kezdeti majomkísérletek alapján tett megállapítással szemben állnak az egérkísérletek eredményei, ahol együttes ösztrogén-dioxin kezelést kaptak az állatok. Genetikai összehasonlítások igazolják, hogy az ember a dioxinrezisztens fajok közé tartozik, így az átlagpopulációban kimutatható dioxinkoncentráció nem okozhat betegséget, különösen nem olyan ösztrogénfüggő elváltozást, mint az endometriosis.
Runx1Protects Hematopoietic Stem/Progenitor Cells from Oncogenic Insult
Authors: Motoda Lena , Osato Motomi , Yamashita Namiko , Jacob Bindya , Chen Lynnette Q. , Yanagida Masatoshi , Ida Hiroshi , Wee Hee-Jun , Sun Alfred X. , Taniuchi Ichiro , Littman Dan , Ito Yoshiaki
Published: September 2007

The RUNX1/AML1 gene encodes a transcription factor essential for the generation of hematopoietic stem cells and is frequently targeted in human leukemia. In human RUNX1-related leukemias, the RAS pathway is often concurrently mutated, but the mechanism of the synergism remains elusive. Here, we found that inactivation of Runx1 in mouse bone marrow cells results in an increase in the stem/progenitor cell fraction due to suppression of apoptosis and elevated expression of the polycomb gene Bmi-1, which is important for stem cell self-renewal. Introduction of oncogenic N-RAS into wild-type cells, in contrast, reduced the stem/progenitor cell fraction because of senescence, apoptosis, and differentiation. Such detrimental events presumably occurred because of the cellular fail-safe program, although hyperproliferation was initially induced by an oncogenic stimulus. Runx1 insufficiency appears to impair such a fail-safe mechanism, particularly in the stem/progenitor cells, thereby supporting the clonal maintenance of leukemia-initiating cells expressing an activated oncogene.

Disclosure of potential conflicts of interest is found at the end of this article.
Pleiotrophin Enhances Clonal Growth and Long-Term Expansion of Human Embryonic Stem Cells
Authors: Soh Boon Seng , Song Chun Meng , Vallier Ludovic , Li Pin , Choong Cleo , Yeo Boon Huat , Lim Elaine Hsuen , Pedersen Roger A. , Yang Henry He , Rao Mahendra , Lim Bing
Published: September 2007

To identify additional growth factors for optimizing propagation of human embryonic stem cells (hESCs), we mined publicly available data sets for the transcriptomes of murine and human ESCs and feeder cells, thereby generating a list of growth factors and complementary receptors. We identified the major pathways previously reported to be important, as well as several new ones. One pathway is the Pleiotrophin (PTN)-Pleiotrophin receptor (PTPRZ1) axis. Murine fibroblasts secrete Ptn, whereas hESCs expressed PTPRZ1, which is downregulated upon differentiation. Depletion of PTPRZ1 resulted in decreased colony formation and lower recovery of hESCs. Supplementation of chemically defined medium for feeder-free propagation of hESCs with PTN allowed higher recovery of hESCs without loss of pluripotency. PTN-PTPRZ1 functions here predominantly via an antiapoptotic effect mediated in part by the activation of Akt. These findings reveal the underlying importance of PTN in hESC survival and its usefulness in the clonal manipulation and large-scale propagation of hESCs.

Disclosure of potential conflicts of interest is found at the end of this article.