bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer
Authors: Wilcox Cathy B , Feddes Grace O , Willett-Brozick Joan E , Hsu Lih-Ching , DeLoia Julie A , Baysal Bora E 
Published: December 2007

Abstract

Background
Ovarian cancer (OvCa) most often derives from ovarian surface epithelial (OSE) cells. Several lines of evidence strongly suggest that increased exposure to progesterone (P4) protects women against developing OvCa. However, the underlying mechanisms of this protection are incompletely understood.

Methods
To determine downstream gene targets of P4, we established short term in vitro cultures of non-neoplastic OSE cells from six subjects, exposed the cells to P4 (10-6 M) for five days and performed transcriptional profiling with oligonucleotide microarrays containing over 22,000 transcripts.

Results
We identified concordant but modest gene expression changes in cholesterol/lipid homeostasis genes in three of six samples (responders), whereas the other three samples (non-responders) showed no expressional response to P4. The most up-regulated gene was TMEM97 which encodes a transmembrane protein of unknown function (MAC30). Analyses of outlier transcripts, whose expression levels changed most significantly upon P4 exposure, uncovered coordinate up-regulation of 14 cholesterol biosynthesis enzymes, insulin-induced gene 1, low density lipoprotein receptor, ABCG1, endothelial lipase, stearoyl- CoA and fatty acid desaturases, long-chain fatty-acyl elongase, and down-regulation of steroidogenic acute regulatory protein and ABCC6. Highly correlated tissue-specific expression patterns of TMEM97 and the cholesterol biosynthesis genes were confirmed by analysis of the GNF Atlas 2 universal gene expression database. Real-time quantitative RT-PCR analyses revealed 2.4-fold suppression of the TMEM97 gene expression in short-term cultures of OvCa relative to the normal OSE cells.

Conclusion
These findings suggest that a co-regulated transcript network of cholesterol/lipid homeostasis genes and TMEM97 are downstream targets of P4 in normal OSE cells and that TMEM97 plays a role in cholesterol and lipid metabolism. The P4-induced alterations in cholesterol and lipid metabolism in OSE cells might play a role in conferring protection against OvCa.
Group cognitive behavior therapy for Japanese patients with social anxiety disorder: preliminary outcomes and their predictors
Authors: Chen Junwen , Nakano Yumi , Ietzugu Tetsuji , Ogawa Sei , Funayama Tadashi , Watanabe Norio , Noda Yumiko , Furukawa Toshi A 
Published: December 2007

Abstract

Background
A number of studies have provided strong evidence for the use of cognitive behavior therapy (CBT) in the treatment of social anxiety disorder (SAD). However, all of the previous reports were from Europe and North America and it is unknown whether Western psychological therapies are effective for SAD in non-Western cultures. The present pilot study aimed to evaluate CBT program for SAD which was originally developed for Western patients, among Japanese patients.

Methods
Fifty-seven outpatients who participated in group CBT for SAD were evaluated using eight self-reported and one clinician-administered questionnaires to measure various aspects of SAD symptomatology at the beginning and at the end of the program. Pre- and post-treatment scores were compared and the magnitude of treatment effect was quantified as well based once on the intention-to-treat (ITT) and once among the completers only. We also examined baseline predictors of the CBT outcomes.

Results
Seven patients (12%) did not complete the program. For the ITT sample, the percentage of reduction was 20% to 30% and the pre to post treatment effect sizes ranged from 0.37 to 1.01. Among the completers, the respective figures were 20% to 33% and 0.41 to 1.19. We found no significant pretreatment predictor of the outcomes.

Conclusion
Group CBT for SAD is acceptable and can bring about a similar degree of symptom reduction among Japanese patients with SAD as among Western patients.
GADD153 expression does not necessarily correlate with changes in culture behavior of hybridoma cells
Authors: Mallory Matthew , Chartrand Kevin , Gauthier Eric R 
Published: December 2007

Abstract

Background
The acute sensitivity of some hybridoma cell lines to culture-related stresses severely limits their productivity. Recent developments in the characterization of the stress signals modulating the cellular phenotype revealed that the pro-apoptotic transcription factor Gadd153 could be used as a marker to facilitate the optimization of mammalian cell cultures. In this report, we analyzed the expression of Gadd153 in Sp2/0-Ag14 murine hybridoma cells grown in stationary batch culture and subjected to two different culture optimization paradigms: L-glutamine supplementation and ectopic expression of Bcl-xL, an anti-apoptotic gene.

Results
The expression of Gadd153 was found to increase in Sp2/0-Ag14 cells in a manner which coincided with the decline in cell viability. L-glutamine supplementation prolonged Sp2/0-Ag14 cell survival and greatly suppressed Gadd153 expression both at the mRNA and protein level. However, Gadd153 levels remained low after L-glutamine supplementation even as cell viability declined. Bcl-xL overexpression also extended Sp2/0-Ag14 cell viability, initially delayed the induction of Gadd153, but did not prevent the increase in Gadd153 protein levels during the later phase of the culture, when cell viability was declining. Interestingly, L-glutamine supplementation prevented Gadd153 up-regulation in cells ectopically expressing Bcl-xL, but had no effect on cell viability.

Conclusion
This study highlights important limitations to the use of Gadd153 as an indicator of cell stress in hybridoma cells.
Physicians' migration in Europe: an overview of the current situation
Authors: García-Pérez Miguel A , Amaya Carlos , Otero Ángel 
Published: December 2007

Abstract
Background
The migration of medical professionals as a result of the expansion of the European Union is cause for concern. But there is a significant lack of information available about this phenomenon.

Methods
Search of secondary databases about the presence of european doctors working abroad, through two search engines in the Internet (Google and Pubmed) and a survey of professional organisations and regulators in countries of the European Union.

Results
The United Kingdom has more foreign doctors than all other European countries for which figures are available (Ireland, France, Germany, Norway, Portugal, Italy, Austria and Poland). Some 74,031 foreign doctors are registered in the UK, 30.94% of the total. European countries with the highest percentage of doctors working abroad are Ireland (47.5%, or 10,065 doctors) and Malta (23.1%, 376 doctors). The data obtained from Norway, France and Germany do not indicate an increase in the migration of professionals from countries recently incorporated into the EU.

Conclusion
There is significant mobility and heterogeneous distribution of doctors within the EEA and it should be cause for concern among health care authorities. However, there is no evidence about a possible increase in this phenomenon after the recent expansion of the EU.
Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi)
Authors: Kobbe Robin , Adjei Samuel , Kreuzberg Christina , Kreuels Benno , Thompson Benedicta , Thompson Peter A , Marks Florian , Busch Wibke , Tosun Meral , Schreiber Nadine , Opoku Ernest , Adjei Ohene , Meyer Christian G , May Juergen 
Published: December 2007

Abstract

Background
Intermittent preventive antimalarial treatment in infants (IPTi) is currently evaluated as a malaria control strategy. Among the factors influencing the extent of protection that is provided by IPTi are the transmission intensity, seasonality, drug resistance patterns, and the schedule of IPTi administrations. The aim of this study was to determine how far the protective efficacy of IPTi depends on spatio-temporal variations of the prevailing incidence of malaria.

Methods
One thousand seventy infants were enrolled in a registered controlled trial on the efficacy of IPTi with sulphadoxine-pyrimethamine (SP) in the Ashanti Region, Ghana, West Africa (ClinicalTrial.gov: NCT00206739). Stratification for the village of residence and the month of birth of study participants demonstrated that the malaria incidence was dependent on spatial (range of incidence rates in different villages 0.6–2.0 episodes/year) and temporal (range of incidence rates in children of different birth months 0.8–1.2 episodes/year) factors. The range of spatio-temporal variation allowed ecological analyses of the correlation between malaria incidence rates, anti-Plasmodium falciparum lysate IgG antibody levels and protective efficacies provided by IPTi.

Results
Protective efficacy of the first SP administration was positively correlated with malaria incidences in children living in a distinct village or born in a distinct month (R2 0.48, p < 0.04 and R2 0.63, p < 0.003, respectively). Corresponding trends were seen after the second and third study drug administration. Accordingly, IgG levels against parasite lysate increased with malaria incidence. This correlation was stronger in children who received IPTi, indicating an effect modification of the intervention.

Conclusion
The spatial and temporal variations of malaria incidences in a geographically and meteorologically homogeneous study area exemplify the need for close monitoring of local incidence rates in all types of intervention studies. The increase of the protective efficacy of IPTi with malaria incidences may be relevant for IPTi implementation strategies and, possibly, for other malaria control measures.
Rapid, widespread transduction of the murine myocardium using self-complementary Adeno-associated virus
Authors: Andino Lourdes M , Conlon Thomas J , Porvasnik Stacy L , Boye Sanford L , Hauswirth William W , Lewin Alfred S 
Published: December 2007

Abstract
Adeno-associated virus (AAV) has shown great promise as a gene transfer vector. However, the incubation time needed to attain significant levels of gene expression is often too long for some clinical applications. Self-complementary AAV (scAAV) enters the cell as double stranded DNA, eliminating the step of second-strand synthesis, proven to be the rate-limiting step for gene expression of single-stranded AAV (ssAAV). The aim of this study was to compare the efficiency of these two types of AAV vectors in the murine myocardium. Four day old CD-1 mice were injected with either of the two AAV constructs, both expressing GFP and packaged into the AAV1 capsid. The animals were held for 4, 6, 11 or 21 days, after which they were euthanized and their hearts were excised. Serial sections of the myocardial tissue were used for real-time PCR quantification of AAV genome copies and for confocal microscopy. Although we observed similar numbers of AAV genomes at each of the different time points present in both the scAAV and the ssAAV infected hearts, microscopic analysis showed expression of GFP as early as 4 days in animals injected with the scAAV, while little or no expression was observed with the ssAAV constructs until day 11. AAV transduction of murine myocardium is therefore significantly enhanced using scAAV constructs.
An epigenetic vaccine model active in the prevention and treatment of melanoma
Authors: Khan A Nazmul H , Magner William J , Tomasi Thomas B 
Published: December 2007

Abstract

Background
Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity.

Methods
HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity.

Results
HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-γ-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity.

Conclusion
The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.
Agreement between physicians and parents in rating functional ability of children with juvenile idiopathic arthritis
Authors: Palmisani Elena , Solari Nicoletta , Pistorio Angela , Ruperto Nicolino , Malattia Clara , Viola Stefania , Buoncompagni Antonella , Loy Anna , Martini Alberto , Ravelli Angelo 
Published: December 2007

Abstract

Objective
To investigate concordance between physicians and parents in rating the degree of functional ability of children with juvenile idiopathic arthritis (JIA).

Methods
The attending physician and a parent were asked to rate independently the level of physical functioning of 155 patients with disease duration ≥ 5 years on a 6-point scale ranging from 1 = no disability (i.e. the child can do without difficulty all activities that children of his/her age can do) to 6 = severe disability (i.e. all activities are difficult for the child). At study visit, measures of JIA activity and damage were assessed. Agreement was evaluated with weighted kappa (<0.40 = poor agreement; 0.41–0.60 = moderate agreement; 0.61–0.80 = substantial agreement; >0.80 excellent agreement). Physician/parent evaluations were divided in 3 groups: 1) concordance; 2) parent over-rating = parent assessment over-rated relative to physician assessment; 3) physician over-rating = physician assessment over-rated relative to parent assessment. Factors affecting concordance/discordance were evaluated by means of Kruskal-Wallis or Chi-square/Fisher exact test.

Results
Concordance, parent over-rating and physician over-rating were observed in 107 (69%), 29 (18.7%) and 19 (12.3%) evaluations, respectively. Kappa value was 0.69. Parent over-rating was associated with greater intensity of pain (p = 0.01) and higher Childhood Health Assessment Questionnaire (C-HAQ) score (p = 0.004), whereas physician over-rating was associated with more severe joint disease (p = 0.04 to <0.001), higher C-reactive protein (p = 0.03) higher frequency of Steinbrocker functional class = II (p < 0.001), and greater articular damage, as measured with the Juvenile Arthritis Damage Index (p < 0.001).

Conclusion
Physicians and parents revealed fair concordance in rating functional ability of children with JIA. Parent over-rating was associated with greater child's pain and worse C-HAQ score, whereas physician over-rating was associated with greater severity of joint inflammation and damage.
Regulator of G-protein signalling 2 mRNA is differentially expressed in mammary epithelial subpopulations and over-expressed in the majority of breast cancers
Authors: Smalley Matthew J , Iravani Marjan , Leao Maria , Grigoriadis Anita , Kendrick Howard , Dexter Tim , Fenwick Kerry , Regan Joseph L , Britt Kara , McDonald Sarah , Lord Christopher J , MacKay Alan , Ashworth Alan 
Published: December 2007

Abstract
Introduction
To understand which signalling pathways become deregulated in breast cancer, it is necessary to identify functionally significant gene expression patterns in the stem, progenitor, transit amplifying and differentiated cells of the mammary epithelium. We have previously used the markers 33A10, CD24 and Sca-1 to identify mouse mammary epithelial cell subpopulations. We now investigate the relationship between cells expressing these markers and use gene expression microarray analysis to identify genes differentially expressed in the cell populations.

Methods
Freshly isolated primary mouse mammary epithelial cells were separated on the basis of staining with the 33A10 antibody and an α-Sca-1 antibody. The populations identified were profiled using gene expression microarray analysis. Gene expression patterns were confirmed on normal mouse and human mammary epithelial subpopulations and were examined in a panel of breast cancer samples and cell lines.

Results
Analysis of the separated populations demonstrated that Sca-1- 33A10High stained cells were estrogen receptor α (Esr1)- luminal epithelial cells, whereas Sca-1+ 33A10Low/- stained cells were a mix of nonepithelial cells and Esr1+ epithelial cells. Analysis of the gene expression data identified the gene Rgs2 (regulator of G-protein signalling 2) as being highly expressed in the Sca-1- 33A10Low/- population, which included myoepithelial/basal cells. RGS2 has previously been described as a regulator of angiotensin II receptor signalling. Gene expression analysis by quantitative real-time RT-PCR of cells separated on the basis of CD24 and Sca-1 expression confirmed that Rgs2 was more highly expressed in mouse myoepithelial/basal mammary cells than luminal cells. This expression pattern was conserved in normal human breast cells. Functional analysis demonstrated RGS2 to be a modulator of oxytocin receptor signalling. The potential significance of RGS2 expression in breast cancer was demonstrated by semi-quantitative RT-PCR analysis, data mining and quantitative real-time RT-PCR approaches, which showed that RGS2 was expressed in the majority of solid breast cancers at much higher levels than in normal human mammary cells.

Conclusion
Molecular analysis of prospectively isolated mammary epithelial cells identified RGS2 as a modulator of oxytocin receptor signalling, which is highly expressed in the myoepithelial cells. The RGS2 gene, but not the oxytocin receptor, was also shown to be over-expressed in the majority of breast cancers, identifying the product of this gene, or the pathway(s) it regulates, as potentially significant therapeutic targets.
Determining promoter location based on DNA structure first-principles calculations
Authors: Goñi J Ramon , Pérez Alberto , Torrents David , Orozco Modesto 
Published: December 2007

AbstractA new method for the prediction of promoter regions based on atomic molecular dynamics simulations of small oligonucleotides has been developed. The method works independently of gene structure conservation and orthology and of the presence of detectable sequence features. Results obtained with our method confirm the existence of a hidden physical code that modulates genome expression.
Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress
Authors: Ralser Markus , Wamelink Mirjam M , Kowald Axel , Gerisch Birgit , Heeren Gino , Struys Eduard A , Klipp Edda , Jakobs Cornelis , Breitenbach Michael , Lehrach Hans , Krobitsch Sylvia 
Published: December 2007

Abstract
Background
Eukaryotic cells have evolved various response mechanisms to counteract the deleterious consequences of oxidative stress. Among these processes, metabolic alterations seem to play an important role.

Results
We recently discovered that yeast cells with reduced activity of the key glycolytic enzyme triosephosphate isomerase exhibit an increased resistance to the thiol-oxidizing reagent diamide. Here we show that this phenotype is conserved in Caenorhabditis elegans and that the underlying mechanism is based on a redirection of the metabolic flux from glycolysis to the pentose phosphate pathway, altering the redox equilibrium of the cytoplasmic NADP(H) pool. Remarkably, another key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is known to be inactivated in response to various oxidant treatments, and we show that this provokes a similar redirection of the metabolic flux.

Conclusion
The naturally occurring inactivation of GAPDH functions as a metabolic switch for rerouting the carbohydrate flux to counteract oxidative stress. As a consequence, altering the homoeostasis of cytoplasmic metabolites is a fundamental mechanism for balancing the redox state of eukaryotic cells under stress conditions.
Performance Contracting in After-Sales Service Supply Chains
Authors: Kim Sang-Hyun , Cohen Morris A. , Netessine Serguei 
Published: December 2007

Performance-based contracting is reshaping service support supply chains in capital-intensive industries such as aerospace and defense. Known as “power by the hour” in the private sector and as “performance-based logistics” (PBL) in defense contracting, it aims to replace traditionally used fixed-price and cost-plus contracts to improve product availability and reduce the cost of ownership by tying a supplier's compensation to the output value of the product generated by the customer (buyer). To analyze implications of performance-based relationships, we introduce a multitask principal-agent model to support resource allocation and use it to analyze commonly observed contracts. In our model the customer (principal) faces a product availability requirement for the “uptime” of the end product. The customer then offers contracts contingent on availability to n suppliers (agents) of the key subsystems used in the product, who in turn exert cost reduction efforts and set spare-parts inventory investment levels. We show that the first-best solution can be achieved if channel members are risk neutral. When channel members are risk averse, we find that the second-best contract combines a fixed payment, a cost-sharing incentive, and a performance incentive. Furthermore, we study how these contracts evolve over the product deployment life cycle as uncertainty in support cost changes. Finally, we illustrate the application of our model to a problem based on aircraft maintenance data and show how the allocation of performance requirements and contractual terms change under various environmental assumptions.
Internet Use and Well-Being Among College Students: Beyond Frequency of Use
Authors: Gordon Cheryl F , Juang Linda P. (Linda Pailiang) , Syed Moin 
Published: December 2007

The purpose of the study was to gather descriptive information about college students' Internet use and to explore the relationship between types of Internet use and well-being. The sample consisted of 312 college students (67% female; age range 18-49 years; M = 21.34 years, SD = 5.05). Self-report questionnaires were administered in a large undergraduate psychology course. Exploratory factor analyses suggested 5 specific types of use: Meeting People, Information Seeking, Distraction, Coping, and E-mail. Confirmatory factor analyses on a new sample from the same university (N = 169) verified the 5-factor structure. Using the Internet for coping purposes related to depression, social anxiety, and family cohesion more so than frequency of use. This study highlights the importance of examining types of Internet use in relation to well-being.