bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leishmania pifanoiProteoglycolipid Complex P8 Induces Macrophage Cytokine Production through Toll-Like Receptor 4
Authors: Whitaker Shanta M. , Colmenares Maria , Pestana Karen Goldsmith , McMahon-Pratt Diane 
Published: February 2008

ABSTRACTThe P8 proteoglycolipid complex (P8 PGLC) is a glyconjugate expressed byLeishmania mexicanacomplex parasites. We previously have shown that vaccination with P8 PGLC provides protection against cutaneous leishmaniasis in susceptible BALB/c mice. However, the biological importance of this complex remains unknown. Here we show that P8 PGLC localizes to the surface ofLeishmania pifanoiamastigotes and that upon exposure to macrophages, P8 PGLC binds and induces inflammatory cytokine and chemokine mRNAs such as tumor necrosis factor alpha and RANTES early after stimulation. Our studies indicate that cytokine and chemokine induction is dependent upon Toll-like receptor 4 (TLR4). Interestingly, key inflammatory cytokines and chemokines (such as interleukin-6 [IL-6], macrophage inflammatory protein 1β, and beta interferon [IFN-β]) that can be induced through TLR4 activation were not induced or only slightly upregulated by P8 PGLC. Activation by P8 PGLC does not occur in the presence of TLR4 alone and requires both CD14 and myeloid differentiation protein 2 for signaling; this requirement may be responsible for the limited TLR4 response. This is the first characterization of a TLR4 ligand forLeishmania. In vitro experiments indicate thatL. pifanoiamastigotes induce lower levels of cytokines in macrophages in the absence of TLR4; however, notably higher IL-10/IFN-γ ratios were found for TLR4-deficient mice than for BALB/c mice. Further, increased levels of parasites persist in BALB/c mice deficient in TLR4. Taken together, these results suggest that TLR4 recognition ofLeishmania pifanoiamastigotes is important for the control of infection and that this is mediated, in part, through the P8 PGLC.
Tobacco industry targeting youth in Argentina
Authors: Braun S , Mejia R , Ling P M , Pérez-Stable E J 
Published: February 2008

Background/aim:Argentina has one of the highest cigarette smoking rates among both men and women in the Americas and no legislated restrictions on tobacco industry advertising. The tobacco industry has traditionally expanded markets by targeting adolescents and young adults. The objective of this study was to determine whether and how the tobacco industry promotes cigarettes to adolescents in Argentina.Methods:We conducted a systematic search of tobacco industry documents available through the internet dated between 1995 and 2004 using standard search terms to identify marketing strategies in Argentina. A selected review of the four leading newspapers and nine magazines with reported high readership among adolescents was completed. The selected print media were searched for tobacco images and these were classified as advertisements if associated with a commercial product or as a story if not.Results:The tobacco industry used market segmentation as a strategy to target Argentinean consumers. British American Tobacco (BAT) undertook a young adult psychographic study and classified them as “progressives”, “Jurassics” or “conservatives” and “crudos” or “spoiled brats”. BAT marketed Lucky Strike to the “progressives” using Hollywood movies as a vehicle. The tobacco industry also targeted their national brands to the conservatives and linked these brands with “nationalistic values” in advertising campaigns. Philip Morris promoted Marlboro by sponsoring activities directed at young people and they launched the 10 cigarettes packet as a starter vehicle.Conclusions:The tobacco industry used psychographic segmentation of the population and developed advertising strategies focused on youth. Tobacco control researchers and advocates must be able to address these strategies in counter-marketing interventions.
Epigenetic Down-Regulation and Suppressive Role of DCBLD2 in Gastric Cancer Cell Proliferation and Invasion
Authors: Kim Mirang , Lee Kyung-Tae , Jang Hay-Ran , Kim Jeong-Hwan , Noh Seung-Moo , Song Kyu-Sang , Cho June-Sik , Jeong Hyun-Yong , Kim Seon-Young , Yoo Hyang-Sook , Kim Yong Sung 
Published: February 2008

Abstract
The promoter region of Discoidin, CUB and LCCL domain containing 2 (DCBLD2) was found to be aberrantly methylated in gastric cancer cell lines and in primary gastric cancers, as determined by restriction landmark genomic scanning. DCBLD2 expression was inversely correlated with DCBLD2 methylation in gastric cancer cell lines. Treatment with 5-aza-2′-deoxycytidine and trichostatin A partially reversed DCBLD2 methylation and restored gene expression in DCBLD2-silenced cell lines. In an independent series of 82 paired gastric cancers and adjacent normal tissues, DCBLD2 expression was down-regulated in 79% of gastric cancers as compared with normal tissues as measured by real-time reverse transcription-PCR. Pyrosequencing analysis of the DCBLD2 promoter region revealed abnormal hypermethylation in gastric cancers, and this hypermethylation was significantly correlated with down-regulation of DCBLD2 expression. Furthermore, ectopic expression of DCBLD2 in gastric cancer cell lines inhibited colony formation in both anchorage-dependent and anchorage-independent cultures and also inhibited invasion through the collagen matrix. These data suggest that down-regulation of DCBLD2, often associated with promoter hypermethylation, is a frequent event that may be related to the development of gastric cancer. (Mol Cancer Res 2008;6(2):222–30)
Monomeric Recombinant Peptide Aptamers Are Required for Efficient Intracellular Uptake and Target Inhibition
Authors: Borghouts Corina , Kunz Christian , Delis Natalia , Groner Bernd 
Published: February 2008

Abstract
Signal transduction events often involve the assembly of protein complexes dependent on modular interactions. The inappropriate assembly of modular components plays a role in oncogenic transformation and can be exploited for therapeutic purposes. Selected peptides embedded in the context of a scaffold protein can serve as competitive inhibitors of intracellular protein functions in cancer cells. Therapeutic application depends on binding specificities and affinities, as well as on the production and purification characteristics of the peptide aptamers and their delivery into cells. We carried out experiments to improve the properties of the scaffold. We found that the commonly used bacterial thioredoxin scaffold is suboptimal for therapeutic purposes because it aggregates during purification and is most likely immunogenic in humans. We compared the properties of peptide aptamers embedded in three alternative scaffold structures: a coiled-coil stem-loop structure, a dimerization domain, and human thioredoxin (hTrx). We found that only the hTrx molecule can be efficiently produced in bacteria and purified with high yield. We removed five internal cysteines of hTrx to circumvent aggregation during purification, which is a prerequisite for efficient transduction. Insertion of our previously characterized peptide aptamers [e.g., specifically binding signal transducer and activator of transcription 3 (Stat3)] into the modified hTrx scaffold retained their target binding properties. Addition of a protein transduction domain, consisting of nine arginines, results in a fusion protein, which is taken up by cultured cells. We show that treatment of glioblastoma cells, expressing constitutively activated Stat3, with the purified peptide aptamers strongly inhibits Stat3 signaling, causing cell growth arrest and inducing apoptosis. (Mol Cancer Res 2008;6(2):267–81)
Angiotensin II Induces Oxidative Stress in Prostate Cancer
Authors: Uemura Hiroji , Ishiguro Hitoshi , Ishiguro Yukari , Hoshino Kouji , Takahashi Satoru , Kubota Yoshinobu 
Published: February 2008

Abstract
Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2′-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O2−) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2′-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O2− radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed. (Mol Cancer Res 2008;6(2):250–8)
Poly(ADP-Ribose) Polymerase 1 Promotes Tumor Cell Survival by Coactivating Hypoxia-Inducible Factor-1–Dependent Gene Expression
Authors: Elser Michael , Borsig Lubor , Hassa Paul O. , Erener Suheda , Messner Simon , Valovka Taras , Keller Stephan , Gassmann Max , Hottiger Michael O. 
Published: February 2008

AbstractHypoxia-inducible factor 1 (HIF-1) is the key transcription factor regulating hypoxia-dependent gene expression. Lack of oxygen stabilizes HIF-1, which in turn modulates the gene expression pattern to adapt cells to the hypoxic environment. Activation of HIF-1 is also detected in most solid tumors and supports tumor growth through the expression of target genes that are involved in processes like cell proliferation, energy metabolism, and oxygen delivery. Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated protein, which was shown to regulate transcription. Here we report that chronic myelogenous leukemia cells expressing small interfering RNA against PARP1, which were injected into wild-type mice expressing PARP1, showed tumor growth with increased levels of necrosis, limited vascularization, and reduced expression of GLUT-1. Of note, PARP1-deficient cells showed a reduced HIF-1 transcriptional activation that was dependent on PARP1 enzymatic activity. PARP1 neither influenced binding of HIF-1 to its hypoxic response element nor changed HIF-1α protein levels in hypoxic cells. However, PARP1 formed a complex with HIF-1α through direct protein interaction and coactivated HIF-1α–dependent gene expression. These findings provide convincing evidence that wild-type mice expressing PARP1 cannot compensate for the loss of PARP1 in tumor cells and strengthen the importance of the role of PARP1 as a transcriptional coactivator of HIF-1–dependent gene expression during tumor progression. (Mol Cancer Res 2008;6(2):282–90)
Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression
Authors: Ricciardi Annamaria , Elia Angela Rita , Cappello Paola , Puppo Maura , Vanni Cristina , Fardin Paolo , Eva Alessandra , Munroe David , Wu Xiaolin , Giovarelli Mirella , Varesio Luigi 
Published: February 2008

Abstract
Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues. Dendritic cells (DC) are professional antigen-presenting cells whose differentiation, migration, and activities are intrinsically linked to the microenvironment. DCs will home and migrate through pathologic tissues before reaching their final destination in the lymph node. We studied the differentiation of human monocytes into immature DCs (iDCs) in a hypoxic microenvironment. We generated iDC in vitro under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and examined the hypoxia-responsive element in the promoter, gene expression, and biochemical KEGG pathways. Hi-DCs had an interesting phenotype represented by up-regulation of genes associated with cell movement/migration. In addition, the Hi-DC cytokine/receptor pathway showed a dichotomy between down-regulated chemokines and up-regulated chemokine receptor mRNA expression. We showed that CCR3, CX3CR1, and CCR2 are hypoxia-inducible genes and that CCL18, CCL23, CCL26, CCL24, and CCL14 are inhibited by hypoxia. A strong chemotactic response to CCR2 and CXCR4 agonists distinguished Hi-DCs from iDCs at a functional level. The hypoxic microenvironment promotes the differentiation of Hi-DCs, which differs from iDCs for gene expression profile and function. The most prominent characteristic of Hi-DCs is the expression of a mobility/migratory rather than inflammatory phenotype. We speculate that Hi-DCs have the tendency to leave the hypoxic tissue and follow the chemokine gradient toward normoxic areas where they can mature and contribute to the inflammatory process. (Mol Cancer Res 2008;6(2):175–85)
Legal Pluralism and the Study of Shari'a Courts
Authors: Shahar Ido 
Published: February 2008

AbstractLegal pluralism has emerged in the last few decades as a prominent theoretical perspective in socio-legal research. Recently, scholars of Islamic law have begun to employ analytical concepts and theoretical insights drawn from this theoretical framework in their studies of Islamic law and shari'a courts. In this article I argue that the time has come for a systematic assessment of the relevancy of a legal-pluralist perspective for the study of shari'a courts. Specifically, I discuss its potential contribution for understanding relations between shari'a courts and other tribunals, and between qadis affiliated with different madhhabs.
Bifurcation of the Subtropical South Equatorial Current against New Caledonia in December 2004 from a Hydrographic Inverse Box Model*
Authors: Ganachaud Alexandre , Gourdeau Lionel , Kessler William 
Published: February 2008

Abstract
The South Equatorial Current (SEC), the westward branch of the South Pacific subtropical gyre, extends from the equator to 30°S at depth. Linear ocean dynamics predict that the SEC forms boundary currents on the eastern coasts of the South Pacific islands it encounters. Those currents would then detach at the northern and southern tips of the islands, and cross the Coral Sea in the form of jets. The Fiji Islands, the Vanuatu archipelago, and New Caledonia are the major topographic obstacles on the SEC pathway to the Australian coast. Large-scale numerical studies, as well as climatologies, suggest the formation of three jets in their lee: the north Vanuatu jet (NVJ), the north Caledonian jet (NCJ), and the south Caledonian jet (SCJ), implying a bifurcation against the east coast of each island. The flow observed during the SECALIS-2 cruise in December 2004 between Vanuatu and New Caledonia is presented herein. An inverse box model is used to provide quantitative transport estimates with uncertainties and to infer the pathways and boundary current formation. For that particular month, the 0–2000-m SEC inflow was found to be 20 ± 4 Sv (1 Sv ≡ 106 m3 s−1) between Vanuatu and New Caledonia. Of that, 6 ± 2 Sv bifurcated to the south in a boundary current against the New Caledonia coast (the Vauban Current), and the remainder exited north of New Caledonia, feeding the NCJ. The flow is comparable both above and below the thermocline, while complex topography, associated with oceanic eddy generation, introduces several recirculation features. To the north, the NCJ, which extends down to 1500 m, was fed not only by the SEC inflow, but also by waters coming from the north, which have possibly been recirculated. To the south, a westward current rounds the tip of New Caledonia. A numerical simulation suggests a partial continuity with the deep extension of the Vauban Current (this current would then be the SCJ) while the hydrographic sections are too distant to confirm such continuity.
Research Versus Problem Solving for the Education Leadership Doctoral Thesis: Implications for Form and Function
Authors: Archbald Doug 
Published: February 2008

Background: A growing literature is questioning the appropriateness of a research dissertation for practitioners in education doctoral programs. Although this literature persuasively critiques the prevailing theory-research orientation of most programs and theses, it goes little beyond exhorting change and describing extant alternatives in a few programs. There is little attention in this literature to the powerful structures and values holding in place the traditional research dissertation. This literature has not examined in-depth distinctions between research and organizational problem solving and the implications for an alternative thesis design for education leadership doctorates. Findings: This article presents four “qualities of acceptability” that alternatives to the traditional research thesis must address: (a) developmental efficacy, (b) community benefit, (c) stewardship of doctoral values, and (d) distinctiveness of design. The author comments on existing proposals from the standpoint of this framework, noting their strengths and shortcomings; elaborates on five key distinctions between research and organizational problem solving; presents theory and research supporting a thesis based on organizational problem solving; and proposes a specific and distinctive thesis design.
The development of a minimum dataset audit tool for Scotland's NHS Hand Hygiene Campaign
Authors: Kilpatrick Claire 
Published: February 2008

Hand hygiene compliance is considered to be an essential element in the prevention and control of healthcare associated infections (HCAI). The options for promoting and evaluating compliance have been debated and a range of approaches are both recommended and used in practice. Audit is commonly used for monitoring compliance and a number of hand hygiene audit tools are available. From these, varying compliance rates have been widely published. A tool for mandatory auditing in Scotland, as part of their national Hand Hygiene Campaign, was deemed appropriate. The involvement of the Nurse Consultant Infection Control from the Health Protection Scotland's (HPS) infection control team (ICT) as clinical lead in the Scottish Hand Hygiene Campaign meant that the team had responsibility for developing a tool that would meet the needs of both national and local data collection and reporting. After a review of available tools and a consultation period with identified stakeholders, both an electronic and paper audit tool have been developed and made available to Scottish NHS boards. Evaluation of this tool will be carried out after completion of the planned Hand Hygiene Campaign in March 2008.
Quality of life in patients with chronic obstructive pulmonary disease: the predictive validity of the BODE index
Authors: Medinas-Amorós M. , Alorda C. , Renom F. , Rubí M. , Centeno J. , Ferrer V. , Gorriz T. , Mas-Tous C. , Ramis F. 
Published: February 2008

Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth cause of mortality and morbility in the developed world. Patients with COPD experience a progressive deterioration of health-related quality of life (HRQOL). A new model of severity classification, the body mass index, bronchial obstruction, dyspnoea, exercise (BODE) index, has recently been proposed. Objective: To evaluate the relationship between HRQOL and the BODE index, and the predictive ability of BODE on HRQOL measurements. Methods: Two HRQOL questionnaires were administered, namely the Nottingham Health Profile (NHP) and St George's Respiratory Questionnaire (SGRQ), in a sample of 67 patients with severe COPD. Results: Pearsonś correlation coefficient analysis shows a positive correlation between the BODE index and the total scores of the specific ( P < 0.001), and general HRQOL ( P < 0.001); the analysis shows a significant correlation between the BODE index and the subscales of symptoms, activity and impact of SGRQ ( P < 0.001) and the subscales energy and physical mobility of the NHP ( P < 0.001). The regression analysis shows that the BODE index is a significant predictor of HRQOL, explaining 46,1% of the total score of the SGRQ ( P < 0.001) and 14.8% of the total score of the NHP ( P < 0.001). Conclusions: The BODE index is good at predicting the worsening of HRQOL in patients with severe COPD. Chronic Respiratory Disease 2008; 5: 7—11
Risk factors for increased need for intravenous antibiotics for pulmonary exacerbations in adult patients with cystic fibrosis
Authors: Jarad N. A. , Giles K. 
Published: February 2008

Background: Pulmonary exacerbations (P Exs) are important in cystic fibrosis (CF). They are very common, and are associated with poor quality of life. P Exs are regarded as an important end point in clinical trials. Risk factors associated with increase in P Exs have not been examined at a large scale. This study investigates factors associated with P Exs in a large cohort of adolescent and adult patients. Patients and methods: This is a cross-sectional study on data collected in the South and West Regions in England in 2002. Patients aged 16 years and over were included. Data on age, gender, FEV1, body mass index (BMI), infection with Pseudomonas aeruginosa (Pa) and on CF-related diabetes were included in the analysis. P Ex was defined as an episode treated with IV antibiotics. Forward stepwise multiple regression analysis was performed with the number of P Exs being the independent variable. The rest of the variables were considered to be the dependent variables. Results: Data from 341 patients (194 female), mean age (SD), 24.9 (8.9) years were available. In 2002, a total of 599 P Exs were reported, median 1.00 range 0—16 P Exs. Using stepwise multiple regression analysis factors associated with increased number of P Exs were: infection with Pa ( t-value —5.0, P < 0.0001), FEV1, ( t-value —4.9, P < 0.0001) and diabetes mellitus, ( t-value —2.1, P = 0.04). Age, gender and BMI did not influence the annual number of exacerbations. Conclusions: In this study, risk factors for P Exs were found to be as follows: growth of Pa in the sputum, reduced FEV1 and CF-related diabetes mellitus. Chronic Respiratory Disease 2008; 5: 29—33