bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Interreligious Dialogue - Some Preliminary Remarks for Discussion -1
Authors: Dornberg Ulrich 
Published: June 2008

AbstractThe context, in which Christianity in Asia is situated can be characterized2 by both the massive poverty of the Asian people and their deep adherence to (non-Christian) religions, which make the Christian Churches a tiny minority in Asia. Therefore Christians in search for a new identity in Asia have often been turning either to 'development' activities or to dialogue with other religions. The question however is, whether there is also a relationship between development and dialogue, and if so, how does it work, what are its implications.
Recent Development of Planar Cruciform Experiment on Biaxial Tensile Deformation and Failure of Unidirectional Glass/Epoxy Composite
Authors: Mailly Luis , Su Su Wang  
Published: June 2008

Inadequate experimental characterization of strength and deformation behavior of unidirectional fiber composites under planar biaxial stresses has hindered the development of complete material models. Here the recent development of a cruciform specimen with unidirectional gage section is presented, suitable to test glass/epoxy under combined high transverse and longitudinal tensile loads. The experimental program developed comprises of six different biaxial tensile load ratios. The results show significant influence of longitudinal stress on transverse nonlinearity of a glass/epoxy. Failure loci and failure modes in biaxial tensile strain and stress domains are presented, indicating a reduction of transverse strength by high longitudinal loads.
PGE2 induces angiogenesis via MT1-MMP–mediated activation of the TGFβ/Alk5 signaling pathway
Authors: Alfranca Arántzazu , López-Oliva Juan Manuel , Genís Laura , López-Maderuelo Dolores , Mirones Isabel , Salvado Dolores , Quesada Antonio J. , Arroyo Alicia G. , Redondo Juan Miguel 
Published: June 2008

Abstract
The development of a new vascular network is essential for the onset and progression of many pathophysiologic processes. Cyclooxygenase-2 displays a proangiogenic activity in in vitro and in vivo models, mediated principally through its metabolite prostaglandin E2 (PGE2). Here, we provide evidence for a novel signaling route through which PGE2 activates the Alk5-Smad3 pathway in endothelial cells. PGE2 induces Alk5-dependent Smad3 nuclear translocation and DNA binding, and the activation of this pathway involves the release of active TGFβ from its latent form through a process mediated by the metalloproteinase MT1-MMP, whose membrane clustering is promoted by PGE2. MT1-MMP–dependent transforming growth factor β (TGFβ) signaling through Alk5 is also required for PGE2-induced endothelial cord formation in vitro, and Alk5 kinase activity is required for PGE2-induced neovascularization in vivo. These findings identify a novel signaling pathway linking PGE2 and TGFβ, 2 effectors involved in tumor growth and angiogenesis, and reveal potential targets for the treatment of angiogenesis-related disorders.
Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients
Authors: Santilli Francesca , Romano Mario , Recchiuti Antonio , Dragani Alfredo , Falco Angela , Lessiani Gianfranco , Fioritoni Francesca , Lattanzio Stefano , Mattoscio Domenico , De Cristofaro Raimondo , Rocca Bianca , Davì Giovanni 
Published: June 2008

Abstract
Polycythemia vera (PV) is associated with high morbidity and mortality for thrombosis. We hypothesized that in PV altered sensitivity to aspirin might be related to dysfunction of the endothelial repair and/or of the nitric oxide (NO) system. Urinary thromboxane (TX) A2 metabolite (TXM), endothelial colony-forming cells (ECFCs), plasma asymmetric dimethylarginine (ADMA) and von Willebrand factor (VWF) were measured in 37 PV patients on low-dose aspirin and 12 healthy controls. Patients showed an approximately 2-fold increase in median TXM and plasma ADMA levels (P < .001), while ECFC numbers were reduced by approximately 7-fold (P < .001) as compared with nonaspirinated control. These differences were more pronounced in patients with previous thrombosis. An 8-week course of aspirin did not affect ECFCs in 6 controls. VWF and TXM correlated directly with ADMA, and inversely with ECFCs. By multiple regression analysis, lower ECFC quartiles (beta = −0.39; SE = 0.17; P = .028) and higher VWF levels (beta = 0.338, SE = 0.002, P = .034) were independent predictors of higher TXM quartiles (R2 = 0.39). Serum TXB2, measured in 22 patients, was approximat-ly 10-fold higher than aspirin-treated controls. PV patients appear to have an unbalanced ECFC/NO axis, and an apparent altered sensitivity of platelet TXA2 production, all potentially contributing to aspirin-insensitive TXM formation. Thus, additional antithrombotic strategies may be beneficial in PV.
Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis
Authors: Nakazawa Youya , Sato Shigeo , Naito Mikihiko , Kato Yukinari , Mishima Kazuhiko , Arai Hiroyuki , Tsuruo Takashi , Fujita Naoya 
Published: June 2008

Abstract
CD9 has been reported to play a role in tumor metastasis suppression. However, it is not fully understood how CD9 affects the hematogenous spread of tumor cells. To clarify a new mechanism (or mechanisms), we generated HT1080 cells that had been transfected with a CD9-expressing plasmid. Ectopic expression of CD9 in HT1080 cells actually reduced their metastatic ability. CD9 expression reduced lung retention and platelet ag-gregation activity of the transfectants. Because HT1080 cells express the metastasis-promoting, platelet aggregation-inducing factor Aggrus/podoplanin on their surface, we examined the relationship between CD9 and Aggrus. We discovered that CD9 formed a complex with Aggrus via transmembrane domains 1 and 2 (TM1 and TM2) of CD9. Investigation of the interaction revealed that each CD9 and Aggrus interacted homophilically, and that they colocalized in low-density membrane fractions. Deleting TM1 and TM2 attenuated the ability of CD9 to interact homophilically or to localize in low-density membrane fractions. The expression of CD9–wild-type (WT), but not CD9 lacking TM1 and TM2, attenuated the platelet aggregation and metastasis induced by forced expression of Aggrus in CHO cells. Therefore, CD9 may act as a metastasis suppressor, at least in part, by neutralizing Aggrus-mediated platelet aggregation.
Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data
Authors: Sharov Alexei A , Masui Shinji , Sharova Lioudmila V , Piao Yulan , Aiba Kazuhiro , Matoba Ryo , Xin Li , Niwa Hitoshi , Ko Minoru SH 
Published: June 2008

AbstractBackgroundTarget genes of a transcription factor (TF)Pou5f1(Oct3/4orOct4), which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES) cells, have previously been identified based on their response toPou5f1manipulation and occurrence of Chromatin-immunoprecipitation (ChIP)-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation.ResultsTo reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR) criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR < 0.2) to a compendium of published and new microarray data (3, 6, 12, and 24 hr afterPou5f1suppression) and published ChIP data, we identified 420 tentative target genes (TTGs) forPou5f1. The majority of TTGs (372) were down-regulated afterPou5f1suppression, indicating that thePou5f1functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed thatSox2andNanogalso function mostly as transcription activators in cooperation withPou5f1.ConclusionWe have identified the most reliable sets of direct target genes for key pluripotency genes –Pou5f1,Sox2, andNanog, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly.
The patatin-like lipase family in Gallus gallus
Authors: Saarela Jani , Jung Gerlinde , Hermann Marcela , Nimpf Johannes , Schneider Wolfgang J 
Published: June 2008

Abstract

Background
In oviparous species, genes encoding proteins with functions in lipid remodeling, such as specialized lipases, may have evolved to facilitate the assembly and utilization of yolk lipids by the embryo. The mammalian gene family of patatin-like phospholipases (PNPLAs) has received significant attention, but studies in other vertebrates are lacking; thus, we have begun investigations of PNPLA genes in the chicken (Gallus gallus).

Results
We scanned the draft chicken genome using human PNPLA sequences, and performed PCR to amplify and sequence orthologous cDNAs. Full-length cDNA sequences of galline PNPLA2/ATGL, PNPLA4, -7, -8, -9, and the activator protein CGI-58, as well as partial cDNA sequences of avian PNPLA1, -3, and -6 were obtained. The high degree of sequence identities (~50 to 80%) between the avian and human orthologs suggests conservation of important enzymatic functions. Quantitation by qPCR of the transcript levels of PNPLA s and CGI-58 in 21 tissues indicates that expression patterns and levels diverge greatly between species. A particularly interesting tissue in which certain PNPLAs may contribute to physiological specialization is the extraembryonic yolk sac.

Conclusion
Knowledge about the exact in-vivo functions of PNPLAs in any system is still sparse. Thus, studies about the temporal expression patterns and functions of the enzymes identified here, and of other already known extracellular lipases and co-factors, in the yolk sac and embryonic tissues during embryogenesis are called for. Based on the information obtained, further studies are anticipated to provide important insights of the roles of PNPLAs in the yolk sac and embryo development.
Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema
Authors: Bruun Camilla S , Jørgensen Claus B , Bay Lene , Cirera Susanna , Jensen Henrik E , Leifsson Páll S , Nielsen Jens , Christensen Knud , Fredholm Merete 
Published: June 2008

Abstract

Background
A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait.

Results
The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs.

Conclusion
A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular and functional analyses have excluded that the mutated phenotype is caused by structural mutations in or ablation of any of the two candidate genes.
Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii)
Authors: Jones Stephany G , Vyazovskiy Vladyslav V , Cirelli Chiara , Tononi Giulio , Benca Ruth M 
Published: June 2008

Abstract

Background
Sleep is regulated by both a circadian and a homeostatic process. The homeostatic process reflects the duration of prior wakefulness: the longer one stays awake, the longer and/or more intense is subsequent sleep. In mammals, the best marker of the homeostatic sleep drive is slow wave activity (SWA), the electroencephalographic (EEG) power spectrum in the 0.5–4 Hz frequency range during non-rapid eye movement (NREM) sleep. In mammals, NREM sleep SWA is high at sleep onset, when sleep pressure is high, and decreases progressively to reach low levels in late sleep. Moreover, SWA increases further with sleep deprivation, when sleep also becomes less fragmented (the duration of sleep episodes increases, and the number of brief awakenings decreases). Although avian and mammalian sleep share several features, the evidence of a clear homeostatic response to sleep loss has been conflicting in the few avian species studied so far. The aim of the current study was therefore to ascertain whether established markers of sleep homeostasis in mammals are also present in the white-crowned sparrow (Zonotrichia leucophrys gambelii), a migratory songbird of the order Passeriformes. To accomplish this goal, we investigated amount of sleep, sleep time course, and measures of sleep intensity in 6 birds during baseline sleep and during recovery sleep following 6 hours of sleep deprivation.

Results
Continuous (24 hours) EEG and video recordings were used to measure baseline sleep and recovery sleep following short-term sleep deprivation. Sleep stages were scored visually based on 4-sec epochs. EEG power spectra (0.5–25 Hz) were calculated on consecutive 4-sec epochs. Four vigilance states were reliably distinguished based on behavior, visual inspection of the EEG, and spectral EEG analysis: Wakefulness (W), Drowsiness (D), slow wave sleep (SWS) and rapid-eye movement (REM) sleep. During baseline, SWA during D, SWS, and NREM sleep (defined as D and SWS combined) was highest at the beginning of the major sleep period and declined thereafter. Moreover, peak SWA in both SWS and NREM sleep increased significantly immediately following sleep deprivation relative to baseline.

Conclusion
As in mammals, sleep deprivation in the white-crowned sparrow increases the intensity of sleep as measured by SWA.
Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives
Authors: Volvert Marie-Laure , Seyen Sandrine , Piette Marie , Evrard Brigitte , Gangolf Marjorie , Plumier Jean-Christophe , Bettendorff Lucien 
Published: June 2008

AbstractBackgroundLipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration.ResultsBenfotiamine that is practically insoluble in water, organic solvents or oil was solubilized in 200 mM hydroxypropyl-β-cyclodextrin and the mice received a single oral administration of 100 mg/kg. Though thiamine levels rapidly increased in blood and liver to reach a maximum after one or two hours, no significant increase was observed in the brain. When mice received a daily oral administration of benfotiamine for 14 days, thiamine derivatives were increased significantly in the liver but not in the brain, compared to control mice. In addition, incubation of cultured neuroblastoma cells with 10 μM benfotiamine did not lead to increased intracellular thiamine levels. Moreover, in thiamine-depleted neuroblastoma cells, intracellular thiamine contents increased more rapidly after addition of thiamine to the culture medium than after addition of benfotiamine for which a lag period was observed.ConclusionOur results show that, though benfotiamine strongly increases thiamine levels in blood and liver, it has no significant effect in the brain. This would explain why beneficial effects of benfotiamine have only been observed in peripheral tissues, while sulbutiamine, a lipid-soluble thiamine disulfide derivative, that increases thiamine derivatives in the brain as well as in cultured cells, acts as a central nervous system drug. We propose that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases. It then enters the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should therefore be differentiated from truly lipid-soluble thiamine disulfide derivatives (allithiamine and the synthetic sulbutiamine and fursultiamine) with a different mechanism of absorption and different pharmacological properties.
Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion
Authors: Fu Xiao-Dong , Giretti Maria Silvia , Goglia Lorenzo , Flamini Marina Ines , Sanchez Angel Matias , Baldacci Chiara , Garibaldi Silvia , Sitruk-Ware Regine , Genazzani Andrea Riccardo , Simoncini Tommaso 
Published: June 2008

Abstract

Background
Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted.

Methods
We investigated the effects of progesterone (P), medroxyprogesterone acetate (MPA), drospirenone (DRSP) and nestorone (NES) alone or with 17β-estradiol (E2) on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling.

Results
Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells.

Conclusion
These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.
Expression of hepcidin mRNA is uniformly suppressed in hepatocellular carcinoma
Authors: Kijima Hiroaki , Sawada Tokihiko , Tomosugi Naohisa , Kubota Keiichi 
Published: June 2008

Abstract

Background
The present study evaluated the expression of hepcidin mRNA in hepatocellular carcinoma (HCC).

Methods
Samples of cancerous and non-cancerous liver tissue were taken from 40 patients with HCC who underwent hepatectomy. Expression of hepcidin mRNA was evaluated by real-time PCR, and compared in tumors differing in their degree of differentiation, number of tumors, and vessel invasion. Correlations between hepcidin expression and the interval until HCC recurrence, and the serum concentration of hepcidin were evaluated, together with the expression of mRNAs for other iron metabolism molecules, ferroportin and transferrin receptor 2 (Trf2).

Results
Hepcidin mRNA expression in non-cancerous and cancerous tissues was 1891.8 (32.3–23187.4) and 53.4 (1.9–3185.8), respectively (P < 0.0001). There were no significant differences in hepcidin expression among tumors differing in their degree of differentiation, number of tumors, or vessel invasion. There was no significant correlation between hepcidin expression and the interval until HCC recurrence. The serum concentration of hepcidin-25 was not correlated with hepcidin-mRNA expression. Finally, there were no significant differences in the expression of mRNA for ferroportin and Trf2 between cancerous and non-cancerous tissues.

Conclusion
Expression of hepcidin mRNA is strikingly suppressed in cancerous, but not in non-cancerous tissues, in patients with HCC, irrespective of ferroportin or Trf2 expression. Uniform suppression of hepcidin may be linked to the development of HCC.