bluuebunny/crossref_metadata_2025 huggingface dataset:
Akt1 Activation Can Augment Hypoxia-Inducible Factor-1α Expression by Increasing Protein Translation through a Mammalian Target of Rapamycin–Independent Pathway
Authors: Pore Nabendu , Jiang Zibin , Shu Hui-Kuo , Bernhard Eric , Kao Gary D. , Maity Amit
Published: July 2006

The phosphoinositide 3-kinase (PI3K)/Akt pathway is commonly activated in cancer; therefore, we investigated its role in hypoxia-inducible factor-1α (HIF-1α) regulation. Inhibition of PI3K in U87MG glioblastoma cells, which have activated PI3K/Akt activity secondary to phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutation, with LY294002 blunted the induction of HIF-1α protein and its targets vascular endothelial growth factor and glut1 mRNA in response to hypoxia. Introduction of wild-type PTEN into these cells also blunted HIF-1α induction in response to hypoxia and decreased HIF-1α accumulation in the presence of the proteasomal inhibitor MG132. Akt small interfering RNA (siRNA) also decreased HIF-1α induction under hypoxia and its accumulation in normoxia in the presence of dimethyloxallyl glycine, a prolyl hydroxylase inhibitor that prevents HIF-1α degradation. Metabolic labeling studies showed that Akt siRNA decreased HIF-1α translation in normoxia in the presence of dimethyloxallyl glycine and in hypoxia. Inhibition of mammalian target of rapamycin (mTOR) with rapamycin (10-100 nmol/L) had no significant effect on HIF-1α induction in a variety of cell lines, a finding that was confirmed using mTOR siRNA. Furthermore, neither mTOR siRNA nor rapamycin decreased HIF-1α translation as determined by metabolic labeling studies. Therefore, our results indicate that Akt can augment HIF-1α expression by increasing its translation under both normoxic and hypoxic conditions; however, the pathway we are investigating seems to be rapamycin insensitive and mTOR independent. These observations, which were made on cells grown in standard tissue culture medium (10% serum), were confirmed in PC3 prostate carcinoma cells. We did find that rapamycin could decrease HIF-1α expression when cells were cultured in low serum, but this seems to represent a different pathway. (Mol Cancer Res 2006;4(7):471–9)
Tyrosines in the MUC1 Cytoplasmic Tail Modulate Transcription via the Extracellular Signal-Regulated Kinase 1/2 and Nuclear Factor-κB Pathways
Authors: Thompson Eric J. , Shanmugam Kandavel , Hattrup Christine L. , Kotlarczyk Kari L. , Gutierrez Albert , Bradley Judy M. , Mukherjee Pinku , Gendler Sandra J.
Published: July 2006

Much of the ability of the MUC1 oncoprotein to foster tumorigenesis and tumor progression likely originates from the interaction of its cytoplasmic tail with proteins involved in oncogenic signaling. Many of these interactions are regulated by phosphorylation, as the cytoplasmic tail contains seven highly conserved tyrosines and several serine/threonine phosphorylation sites. We have developed a cell line–based model system to study the effects of tyrosine phosphorylation on MUC1 signaling, with particular emphasis on its effects on gene transcription. COS-7 cells, which lack endogenous MUC1, were stably infected with wild-type MUC1 or a MUC1 construct lacking all seven tyrosines (MUC1 Y0) and analyzed for effects on transcription mediated by the extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) pathways. COS.MUC1 Y0 cells showed heightened active ERK1/2 with increased activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) transcriptional activity; there was also a simultaneous decrease in NF-κB transcriptional activity and nuclear localization. These changes altered the phenotype of COS.MUC1 Y0 cells, as this line displayed increased invasion and enhanced [3H]thymidine incorporation. Analysis of the three lines also showed significant differences in their cell cycle profile and bromodeoxyuridine incorporation when the cells were serum starved. These data support the growing evidence that MUC1 is involved in transcriptional regulation and link MUC1 for the first time to the NF-κB pathway. (Mol Cancer Res 2006;4(7):489–97)
An Autocrine Loop Involving Ret and Glial Cell–Derived Neurotrophic Factor Mediates Retinoic Acid–Induced Neuroblastoma Cell Differentiation
Authors: Cerchia Laura , D'Alessio Amelia , Amabile Giovanni , Duconge Frederic , Pestourie Carine , Tavitian Bertrand , Libri Domenico , de Franciscis Vittorio
Published: July 2006

In several neuroblastoma cell lines, retinoic acid (RA)–induced differentiation is coupled to increased expression of functional neurotrophic factor receptors, including Trk family receptors and the glial cell–derived neurotrophic factor receptor, Ret. In several cases, increased expression is dependent on signaling through TrkB. Unlike TrkA and TrkB, Ret has never been implicated as a prognostic marker for neuroblastomas. SK-N-BE(2) cells do not express any of Trk family receptors; therefore, they are a choice system to study the specific role of Ret in RA-induced differentiation. Using a 2′-fluoro-RNA aptamer and a truncated Ret protein as specific inhibitors of Ret, we show that RA-induced differentiation is mediated by a positive autocrine loop that sustains Ret downstream signaling and depends on glial cell–derived neurotrophic factor expression and release. This report shows that in SK-N-BE(2) cells, stimulation of Ret is a major upstream mechanism needed to mediate RA-induced differentiation. These results provide important insights on the molecular mechanism of RA action, which might be relevant for the development of biologically based therapeutic strategies. (Mol Cancer Res 2006;4(7):481–8)
Aldosterone Impairs Bone Marrow–Derived Progenitor Cell Formation
Authors: Marumo Takeshi , Uchimura Hideki , Hayashi Matsuhiko , Hishikawa Keiichi , Fujita Toshiro
Published: July 2006

Aldosterone has been suggested recently to cause vascular injury by directly acting on the vasculature, in addition to causing injury by raising the blood pressure. Bone marrow–derived endothelial progenitor cells (EPCs) have been shown to exert an important role in the repair of the endothelium. In addition, cell-based therapy using EPCs is emerging as a novel therapeutic strategy for myocardial and peripheral vascular diseases. However, impaired formation and function of EPCs has been observed in patients with risk factors for cardiovascular diseases. We evaluated the possible effects of aldosterone on EPCs by examining the progenitor cell formation from bone marrow mononuclear cells ex vivo. Aldosterone (10 to 1000 nmol/L) reduced the formation of progenitor cells in a concentration-dependent manner. This effect of aldosterone was attenuated by cotreatment with spironolactone. Aldosterone reduced the mRNA levels of vascular endothelial growth factor (VEGF) receptor (VEGFR) 2 without having any effect on the production of VEGF or mRNA levels of VEGF and hepatocyte growth factor in the progenitor cells. However, the expression of stromal-derived growth factor 1 mRNA was paradoxically increased. Consistent with the downregulation of VEGFR-2, VEGF-induced phosphorylation of Akt was abolished in the progenitor cells after aldosterone treatment. N-acetylcysteine, an antioxidant, attenuated the inhibitory effects of aldosterone. These data indicate that aldosterone inhibits the formation of bone marrow–derived progenitor cells, at least partly, by attenuating VEGFR-2 expression and the subsequent Akt signaling. Reduction of aldosterone levels, blockade of mineralocorticoid receptor, and/or cotreatment with antioxidants may, therefore, enhance vascular regeneration by EPCs.
Outcome of Listing for Cardiac Transplantation for Failed Fontan
Authors: Bernstein D. , Naftel D. , Chin C. , Addonizio L.J. , Gamberg P. , Blume E.D. , Hsu D. , Canter C.E. , Kirklin J.K. , Morrow W.R. ,   Pediatric Heart Transplant Study
Published: July 2006

Background—

The Fontan procedure is a successful palliation for children with single-ventricle physiology; however, many will eventually require heart transplantation. The purpose of this study was to determine risk factors for death awaiting transplantation and to examine results after transplantation in Fontan patients.

Methods and Results—

A retrospective, multi-institutional review was performed of 97 Fontan patients <18 years of age listed at 17 Pediatric Heart Transplant Study centers from 1993 to 2001. Mean age at listing was 9.7 years (0.5 to 17.9 years); 25% were <4 years old; 53% were United Network for Organ Sharing status 1; 18% required ventilator support. Pretransplantation survival was 78% at 6 months and 74% at 12 months and was similar to 243 children with other congenital heart disease (CHD) and 747 children without congenital heart disease (No-CHD), who were also awaiting transplantation. Patients who were younger, status 1, had shorter interval since Fontan, or were on a ventilator were more likely to die while waiting. At 6 months, the probability of receiving a transplant was similar for status 1 and 2 (65% versus 68%); however, the probability of death was higher for status 1 (22% versus 5%). Seventy patients underwent transplantation. Survival was 76% at 1 year, 70% at 3 years, and 68% at 5 years, slightly less than CHD and No-CHD patients. Causes of death included infection (30%), graft failure (17%), rejection (13%), sudden death (13%), and graft coronary artery disease (9%). Protein-losing enteropathy (present in 34 patients) resolved in all who survived >30 days after transplantation.

Conclusions—

Heart transplantation is an effective therapy for pediatric patients with a failed Fontan. Although early posttransplantation survival is slightly lower than other patients with CHD, long-term results are encouraging, and protein-losing enteropathy can be expected to resolve.
Lower Myocardial Perfusion Reserve Is Associated With Decreased Regional Left Ventricular Function in Asymptomatic Participants of the Multi-Ethnic Study of Atherosclerosis
Authors: Rosen Boaz D. , Lima João A.C. , Nasir Khurram , Edvardsen Thor , Folsom Aaron R. , Lai Shenghan , Bluemke David A. , Jerosch-Herold Michael
Published: July 2006

Background—

Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease.

Methods and Results—

Seventy-four participants (66±9 years, mean±SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between regional flow and function after multivariable adjustment for age, gender, body mass index, left ventricular mass, and traditional risk factors. Lower regional myocardial blood flow during hyperemia was associated with reduced regional left ventricular function expressed as lower Ecc in the RCA (
P
<0.01) and left circumflex regions (
P
<0.05) measured in the subendocardium, mid-wall, and subepicardium. In contrast, no significant association was seen in the LAD territory (
P
=0.16). In addition, segmental function in LAD and RCA regions was reduced when individuals in the lowest 10th percentile for regional myocardial flow reserve were compared with the other participants. Absolute decreases in mid-wall Ecc LAD and RCA and global Ecc were 3.0%, 3.4%, and 2.8%, respectively (
P
<0.05 for all regions).

Conclusions—

Lower myocardial flow reserve is related to reduced regional function in asymptomatic individuals.
Surgical Correction of Mitral Regurgitation in the Elderly
Authors: Detaint Delphine , Sundt Thoralf M. , Nkomo Vuyisile T. , Scott Christopher G. , Tajik A. Jamil , Schaff Hartzell V. , Enriquez-Sarano Maurice
Published: July 2006

Background—

In the elderly, mitral regurgitation (MR) is frequent, but surgery risks are considered high. Benefits and indications of MR surgery are uncertain in the elderly.

Methods and Results—

Baseline characteristics, outcome, and trends for surgical results improvement were analyzed in elderly patients (≥75 years of age; n=284) operated on for MR in 1980 to 1995 compared with younger patients (65 to 74 years of age, n=504; and <65 years of age, n=556). Preoperatively, class III to IV symptoms, atrial fibrillation, coronary disease, creatinine, and comorbidity index were more severe in elderly patients (all
P
<0.002). In the long term after surgery, observed survival stratified by age (≥75, 65 to 74, <65 years) was lower in elderly than in younger patients (at 5 years, 57±3%, 73±2%, and 85±2%, respectively;
P
<0.001), but ratios of observed to expected survival were similar (83%, 85%, and 88%, respectively). In multivariate analysis adjusted to expected survival, elderly patients showed no difference in life expectancy restoration compared with younger patients (adjusted hazard ratio, 0.89; 95% confidence interval, 0.73 to 1.30;
P
=0.54). Temporal trends showed that risk of operative mortality, although higher in elderly patients (
P
<0.001), declined markedly for all ages (27% to 5% in those ≥75 years of age,
P
<0.01; 21% to 4% in those 65 to 74 years of age,
P
<0.01; and 7% to 2% in those <65 years of age,
P
=0.06), with a parallel decline in low cardiac output and length of hospital stay. Over time, valve repair feasibility increased in all age groups (30% to 84% overall and 31% to 93% in degenerative MR;
P
<0.0001).

Conclusions—

Elderly patients undergoing MR surgery display more severe preoperative characteristics and incur higher operative risks than younger patients. However, restoration of life expectancy after surgery is similar in elderly and younger patients, and outstanding recent surgical improvements particularly benefited elderly patients. Thus, elderly patients with MR can now carefully be considered for surgery before refractory heart failure is present.
'Power' and 'the Other' in Joshua: The Brutal Birthing of a Group Identity
Authors: Prior John Mansford
Published: July 2006

In a world marked by war, terrorism and ethnic cleansing, reading violent biblical writings such as the Book of Joshua has become problematic. This study probes the phenomenology of violence in Joshua in the light of analyses of state-instigated genocide by contemporary social and political scientists. With the aid of African scholar Mahmood Mamdani the cultural, economic and political group identity of Joshua's Israelites and their stigmatization of 'the other' is investigated. Then, with the help of studies on violence in Indonesia (Colombijn & Lindblad, 2002) where the author lives, the essay outlines seven missiological questions concerning the dynamics of brutality and the issue of 'power'. The contemporary reader may not be that distant from the mind-set of Joshua and, perhaps unconsciously, is engaged in prejudicial categorizing. Only after facing uncomfortable facts and our own ingrained fear can reconciliation move forward. Reading Joshua forces us to re-assess our place in our strife-torn world.
Conflicting Visions of Jonah – or Rather Diversity?
Authors: Bachmann Mercedes García
Published: July 2006

In conversation with a proposal that the book of Jonah was written as a reaction to the two apparently contradictory wisdom sayings of Proverbs 13:21 and Psalm 25:8, this paper reviews the book of Jonah in light of the two maxims from a Latin American perspective. Noting the element of surprise throughout the book, the author gives a contextual interpretation to the change of Jonah's appearance from dove (a passive character) to wolf (an enraged character) willing to die rather than witness God's mercy. As a missionary concern, the author parallels the anger of "Christian continent" (Latin America) against God's mercy for "outsiders" and the continent's self-righteousness with Jonah's enraged character. The self-righteousness is so strong that churches and congregations would rather die than open God's grace to others (Jonah 4). The paper concludes by stating that gender studies have alerted us to the danger of employing either/or (rather than both/and) and hierarchical (rather than egalitarian) categories and interpretations that do not leave sufficient space for diversity, both in the biblical text and in congregational life today.
The Genesis of Reconciliation: The Reconciliation of Genesis
Authors: Amos Clare
Published: July 2006

The article begins by explaining the reason for the author's selection of the motif of reconciliation as a key to understanding Genesis in missional terms. She draws attention to the fact that though 'reconciliation' is often linked to mission, in reality the theological connections between mission and reconciliation are not always clearly spelt out. Additionally Robert Schreiter's seminal work on the subject has largely ignored the Old Testament.The article then identifies the key episodes in Genesis where reconciliation is explored, that between Jacob and Esau and that between Joseph and his brothers. She draws attention to the way that these two scenes are in effect the climax of a motif which has run through the entire book, the relationship between 'pairs', and particularly between brothers. The article suggests that the theme of reconciliation as it is explored in Genesis offers a significant challenge to a too ready focus on particularity.
Thinking Mission with Paul and the Romans: Romans 15:1–33
Authors: Patte Daniel
Published: July 2006

I write these notes on Romans 15:1–33 (read together with 1:1–15 and other passages of Romans) as resources for a group discussion of Romans 15 and its teaching about mission for the group's life context. I presuppose that the group will want to have three rounds of discussion. According to the size of the group these three rounds can take place in one long session – with the larger group breaking down in smaller groups and coming back together three times, for instance during an evening – or in three shorter sessions. The first round-table discussion is focused on the group members' first readings of Romans 15. The second round-table involves comparing the members' readings with those of scholars. For this purpose, since there are presently three types of scholarly readings of Romans, I present them, underscoring the different ways they conceive of Paul's teaching about mission. Throughout I also presuppose that each member of the group is committed to "read with" the other members this text of Paul as a Scripture about mission, a process that requires a third round-table.
Sexuality, Masculinity, and Taint Management Among Firefighters and Correctional Officers
Authors: Tracy Sarah J. , Scott Clifton
Published: July 2006

Based on qualitative field and interview data, this comparative analysis of dirty work by firefighters and correctional officers demonstrates that taint management and its relative utility is inextricably bound to and embedded within macro-level discourses. While firefighters labor to fulfill expectations as “America's heroes,” correctional officers work to squelch images as “professional babysitters” and the “scum of law enforcement.” The authors' analysis illustrates how discourses of occupational prestige and masculine heterosexuality allow firefighters to frame their work in preferred, privileged terms while correctional officers struggle to combat taint discursively associated with low-level feminized care work or with brutish, deviant sexuality. This study extends theoretical understandings of identity construction, dirty work, taint management, and organizational performances of masculinity and sexuality. The authors' analysis concludes with limitations, future directions, and practical applications regarding the potentially dysfunctional results of taint management.
Habermas's Discourse Ethics and Principle of Universalization as a Moral Framework for Organizational Communication
Authors: Meisenbach Rebecca J.
Published: July 2006

The author argues for the potential of discourse ethics as a framework for guiding and assessing ethical action in organizational communication. Habermas's discourse ethics offers an intersubjective procedure for developing and challenging ethical norms through reasoned public communication. After examining the development of discourse ethics and reviewing existing organizational applications of Habermas's ideas, the author then forms the principle of universalization into five steps necessary for an organization to enact a discourse ethic. These steps are used to assess the ethical problems and to identify alternative courses of action relating to the American Red Cross's Liberty Fund case.
Structural Health Monitoring for Future Space Vehicles
Authors: Mancini Simone , Tumino Giorgio , Gaudenzi Paolo
Published: July 2006

Structural health monitoring (SHM) is certainly one of the key technologies required to achieve the goal for new space vehicles of having reduced maintenance costs with increased levels of safety. For the time being, sensor technology has reached a good technology readiness level, but the integration of these technologies into the design process of a space vehicle has not received much consideration. The present article aims at giving a reference about the existing technologies on the matter and an introduction to some of the key issues for the integration of a SHM system into the design process of future space vehicles. In addition, the accident that occurred to the space shuttle Columbia is analyzed in order to show how SHM could be effective for the improvement of safety in future space vehicles. Furthermore, since important changes to aeronautical design procedures have been introduced as a consequence of catastrophic events, the evolution of aeronautical design practices in parallel with accidents has been examined.
An Active Diagnostic System for Structural Health Monitoring of Rocket Engines
Authors: Qing Xinlin P. , Chan Hian-Leng , Beard Shawn J. , Kumar Amrita
Published: July 2006

An active diagnostic system using built-in piezoelectric actuator/sensor networks was developed for monitoring crack growth in a rocket engine pipe. The diagnostic system combines a sensor network, portable diagnostic hardware and data analysis software which allows for real-time in situ monitoring and long term tracking of the structural integrity of pressure vessels. Experimental data shows that the system can detect a surface crack as small as 4 mm and a through-crack as small as 2 mm in the high pressure engine pipe made of Inconel 718. It was found that the actuator-sensor paths that are most sensitive to crack growth are the ones in which the crack is growing away from, rather than towards the path. This discovery will provide important guidelines for the design of a sensor network for crack detection. It was also observed that the bending mode (equivalent to the A0 mode in plates) is more sensitive than the longitudinal mode (equivalent to the S0 mode in plates) to crack growth.
Teamwork Orientation, Group Cohesiveness, and Student Learning: A Study of the Use of Teams in Online Distance Education
Authors: Williams Ethlyn A. , Duray Rebecca , Reddy Venkateshwar
Published: July 2006

This research examines computer-supported collaborative learning. Master’s of business administration (MBA) students in an online program were surveyed to examine the extent to which an orientation toward teamwork and the development of group cohesiveness affect overall student learning and the learning that results specifically from team interactions (team-source learning). The results indicate that both teamwork orientation and group cohesiveness predict student learning, with group cohesiveness mediating the relationship between teamwork orientation and student learning. Teamwork orientation and group cohesiveness appear to be equally important predictors of team-source learning. The implications of this research for the use of teams in online distance education are discussed.
Are Heterogeneous or Homogeneous Groups More Beneficial to Students?
Authors: Schullery Nancy M. , Schullery Stephen E.
Published: July 2006

This study investigated the relative benefits to the student of working in homogeneous versus heterogeneous classroom groups. Correlation analysis of 18 desirable outcomes versus 8 personality-based heterogeneity variables reveals that heterogeneity associates with advantages as well as disadvantages. Ways in which group composition might be customized to benefit students with particular needs or to emphasize particular goals are described, along with their potential downsides.
Can’t We Pick our Own Groups? The Influence of Group Selection Method on Group Dynamics and Outcomes
Authors: Chapman Kenneth J. , Meuter Matthew , Toy Dan , Wright Lauren
Published: July 2006

In today’s business world, the ability to work efficiently and effectively with others in a group is a mandatory skill. Many employers rank “ability to work with a group” as one of the most important attributes for business school graduates to possess. Therefore, it is important for instructors to understand the factors that influence group dynamics and outcomes and students’ attitudes toward group experiences. The objective of this research is to test whether the method of group member assignment (i.e., random or self-selected) affects the nature of group dynamics and outcomes, and students’ attitudes toward the group experience. The results indicate that the method of group member assignment does influence group dynamics, attitudes toward the group experience, and group outcomes.
Toward Fairness in Assessing Student Groupwork: A Protocol for Peer Evaluation of Individual Contributions
Authors: Fellenz Martin R.
Published: July 2006

A key challenge for management instructors using graded groupwork with students is to find ways to maximize student learning from group projects while ensuring fair and accurate assessment methods. This article presents the Groupwork Peer-Evaluation Protocol (GPEP) that enables the assessment of individual contributions to graded student groupwork. The GPEP is designed to achieve the three objectives of providing accurate and fair assessment, supporting student learning, and enabling group self-management. This article discusses instructor experiences with and student reactions to the protocol, opportunities for customization, and potential limitations of the protocol.
Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative
Authors: Randi Maria Luigia , Putti Maria Caterina , Scapin Margherita , Pacquola Enrica , Tucci Fabio , Micalizzi Concetta , Zanesco Luigi , Fabris Fabrizio
Published: July 2006

Essential thrombocythemia (ET) is rare in children, and little or no information is available about clonality or JAK2 mutations. However, the analyses in this work prove useful for the diagnosis of adult myeloproliferative disorders (MPDs). We evaluated the clonality status and V617FJAK2 mutation in 20 children affected by ET and compared them with 47 consecutive adult ET cases. Clonality was evaluated on the DNA of granulocytes and on the RNA of platelets. V617FJAK2 was analyzed by sequencing tests, allele-specific polymerase chain reaction (PCR), and digestion by BsaXI. A monoclonal pattern was found in 4 (28.5%) of 14 children and in 45% of informative adults. Heterozygous V617FJAK2 was found less frequently in children than in adults (P < .009). Only 2 girls showed both the V617FJAK2 mutation and a monoclonal pattern; one of them was the only child presenting a major thrombotic complication. In contrast to adults, most children with ET do not show either a clonal disorder or the V617FJAK2 mutation.
Simulation of microarray data with realistic characteristics
Authors: Nykter Matti , Aho Tommi , Ahdesmäki Miika , Ruusuvuori Pekka , Lehmussola Antti , Yli-Harja Olli
Published: July 2006

Background

Microarray technologies have become common tools in biological research. As a result, a need for effective computational methods for data analysis has emerged. Numerous different algorithms have been proposed for analyzing the data. However, an objective evaluation of the proposed algorithms is not possible due to the lack of biological ground truth information. To overcome this fundamental problem, the use of simulated microarray data for algorithm validation has been proposed.

Results

We present a microarray simulation model which can be used to validate different kinds of data analysis algorithms. The proposed model is unique in the sense that it includes all the steps that affect the quality of real microarray data. These steps include the simulation of biological ground truth data, applying biological and measurement technology specific error models, and finally simulating the microarray slide manufacturing and hybridization. After all these steps are taken into account, the simulated data has realistic biological and statistical characteristics. The applicability of the proposed model is demonstrated by several examples.

Conclusion

The proposed microarray simulation model is modular and can be used in different kinds of applications. It includes several error models that have been proposed earlier and it can be used with different types of input data. The model can be used to simulate both spotted two-channel and oligonucleotide based single-channel microarrays. All this makes the model a valuable tool for example in validation of data analysis algorithms.
Environmental stress and reproduction in Drosophila melanogaster: starvation resistance, ovariole numbers and early age egg production
Authors: Wayne Marta L , Soundararajan Usha , Harshman Lawrence G
Published: July 2006

Background

The Y model of resource allocation predicts a tradeoff between reproduction and survival. Environmental stress could affect a tradeoff between reproduction and survival, but the physiological mechanisms underlying environmental mediation of the tradeoff are largely unknown. One example is the tradeoff between starvation resistance and early fecundity. One goal of the present study was to determine if reduced early age fecundity was indeed a robust indirect response to selection for starvation resistance, by investigation of a set of D. melanogaster starvation selected lines which had not previously been characterized for age specific egg production. Another goal of the present study was to investigate a possible relationship between ovariole number and starvation resistance. Ovariole number is correlated with maximum daily fecundity in outbred D. melanogaster. Thus, one might expect that a negative genetic correlation between starvation resistance and early fecundity would be accompanied by a decrease in ovariole number.

Results

Selection for early age female starvation resistance favored survival under food deprivation conditions apparently at the expense of early age egg production. The total number of eggs produced by females from selected and control lines was approximately the same for the first 26 days of life, but the timing of egg production differed such that selected females produced fewer eggs early in adult life. Females from lines selected for female starvation resistance exhibited a greater number of ovarioles than did unselected lines. Moreover, maternal starvation resulted in progeny with a greater number of ovarioles in both selected and unselected lines.

Conclusion

Reduced early age egg production is a robust response to laboratory selection for starvation survival. Ovariole numbers increased in response to selection for female starvation resistance indicating that ovariole number does not account for reduced early age egg production. Further, ovariole number increased in a parallel response to maternal starvation, suggesting an evolutionary association between maternal environment and the reproductive system of female progeny.
Chest radiography practice in critically ill patients: a postal survey in the Netherlands
Authors: Graat Marleen E , Hendrikse Karin A , Spronk Peter E , Korevaar Johanna C , Stoker Jaap , Schultz Marcus J
Published: July 2006

Background

To ascertain current chest radiography practice in intensive care units (ICUs) in the Netherlands.

Methods

Postal survey: a questionnaire was sent to all ICUs with > 5 beds suitable for mechanical ventilation; pediatric ICUs were excluded. When an ICU performed daily-routine chest radiographs in any group of patients it was considered to be a "daily-routine chest radiography" ICU.

Results

From the number of ICUs responding, 63% practice a daily-routine strategy, in which chest radiographs are obtained on a daily basis without any specific reason. A daily-routine chest radiography strategy is practiced less frequently in university-affiliated ICUs (50%) as compared to other ICUs (68%), as well as in larger ICUs (> 20 beds, 50%) as compared to smaller ICUs (< 20 beds, 65%) (P> 0.05). Remarkably, physicians that practice a daily-routine strategy consider daily-routine radiographs helpful in guiding daily practice in less than 30% of all performed radiographs. Chest radiographs are considered essential for verification of the position of invasive devices (81%) and for diagnosing pneumothorax, pneumonia or acute respiratory distress syndrome (82%, 74% and 69%, respectively). On demand chest radiographs are obtained after introduction of thoracic drains, central venous lines and endotracheal tubes in 98%, 84% and 75% of responding ICUs, respectively. Chest films are also obtained in case of ventilatory deterioration (49% of responding ICUs), and after cardiopulmonary resuscitation (59%), tracheotomy (58%) and mini-tracheotomy (23%).

Conclusion

There is notable lack of consensus on chest radiography practice in the Netherlands. This survey suggests that a large number of intensivists may doubt the value of daily-routine chest radiography, but still practice a daily-routine strategy.
Observation of intermediate states of the human prion protein by high pressure NMR spectroscopy
Authors: Kachel Norman , Kremer Werner , Zahn Ralph , Kalbitzer Hans Robert
Published: July 2006

Background

Prions as causative agents of transmissible spongiform encephalopathies (TSEs) in humans and animals are composed of the infectious isomer, PrPSc, of the cellular prion protein, PrPC. The conversion and thus the propensity of PrPCto adopt alternative folds leads to the species-specific propagation of the disease. High pressure is a powerful tool to study the physico-chemical properties of proteins as well as the dynamics and structure of folding intermediates.

Results

Conformational intermediates of the human prion proteinhuPrPCwere characterized by a combination of hydrostatic pressure (up to 200 MPa) with two-dimensional NMR spectroscopy. All pressure effects showed to be reversible and there is virtually no difference in the overall pressure response between the folded core of the N-terminal truncatedhuPrPC(121–230) and the full-lengthhuPrPC(23–230). The only significant differences in the pressure response of full-length and truncated PrP suggest that E168, H187, T192, E207, E211 and Y226 are involved in a transient interaction with the unfolded N-terminus. High-pressure NMR spectroscopy indicates that the folded core of the human prion protein occurs in two structural states N1and N2in solution associated with rather small differences in free enthalpies (3.0 kJ/mol). At atmospheric pressure approximately 29% of the protein are already in the pressure favored conformation N2. There is a second process representing two possible folding intermediates I1and I2with corresponding average free enthalpies of 10.8 and 18.6 kJ/mol. They could represent preaggregation states of the protein that coexist at ambient pressure with a very small population of approximately 1.2% and less than 0.1%. Further the pressure response of the N-terminus indicates that four different regions are in a fast equilibrium with non-random structural states whose populations are shifted by pressure.

Conclusion

We identified pressure stabilized folding intermediates of the human prion protein. The regions reflecting most strongly the transition to the intermediate states are the β1/α1-loop and the solvent exposed side of α3. The most pressure-sensitive region (representing mainly intermediate I1) is the loop between β-strand 1 and α-helix 1 (residue 139–141), indicating that this region might be the first entry point for the infectious conformer to convert the cellular protein.
A general method for selection of riboflavin-overproducing food grade micro-organisms
Authors: Burgess Catherine M , Smid Eddy J , Rutten Ger , van Sinderen Douwe
Published: July 2006

Background

This study describes a strategy to select and isolate spontaneous riboflavin-overproducing strains of Lactobacillus (Lb.) plantarum, Leuconostoc (Lc.) mesenteroides and Propionibacterium (P.) freudenreichii.

Results

The toxic riboflavin analogue roseoflavin was used to isolate natural riboflavin-overproducing variants of the food grade micro-organisms Lb. plantarum, Lc. mesenteroides and P. freudenreichii strains. The method was successfully employed for strains of all three species. The mutation(s) responsible for the observed overproduction of riboflavin were identified for isolates of two species.

Conclusion

Selection for spontaneous roseoflavin-resistant mutants was found to be a reliable method to obtain natural riboflavin-overproducing strains of a number of species commonly used in the food industry. This study presents a convenient method for deriving riboflavin-overproducing strains of bacterial starter cultures, which are currently used in the food industry, by a non-recombinant methodology. Use of such starter strains can be exploited to increase the vitamin content in certain food products.
The positive impact of red palm oil in school meals on vitamin A status: study in Burkina Faso
Authors: Zeba Augustin N , Prével Yves Martin , Somé Issa T , Delisle Hélène F
Published: July 2006

Background

Vitamin A (VA) deficiency is widespread in sub-Saharan Africa and school-age children are a vulnerable group. In Burkina Faso, the production and consumption of red palm oil (RPO) is being promoted as a food supplement for VA. The objective of the study was to assess the impact on serum retinol of adding RPO to school lunch in two test zones of Burkina Faso.

Methods

Over one school year, 15 ml RPO was added to individual meals 3 times a week in selected primary schools in two sites. Serum retinol was measured with HPLC at baseline and exactly 12 months later to take account of seasonality. A simple pre-post test design was used in the Kaya area (north-central Burkina), where 239 pupils from 15 intervention schools were randomly selected for the evaluation. In Bogandé (eastern Burkina), 24 schools were randomised for the controlled intervention trial: 8 negative controls (G1) with only the regular school lunch; 8 positive controls (G2) where the pupils received a single VA capsule (60 mg) at the end of the school year; and 8 schools with RPO through the school year (G3). A random sample of 128 pupils in each school group took part in the evaluation.

Results

In Kaya, serum retinol went from 0.77 ± 0.37 μmol/L at baseline to 1.07 ± 0.40 μmol/L one year later (p < 0.001). The rate of low serum retinol (<0.7 μmol/L) declined from 47.2% to 13.1%. In Bogandé, serum retinol increased significantly (p < 0.001) only in the capsule and RPO groups, going from 0.77 ± 0.28 to 0.98 ± 0.33 μmol/L in the former, and from 0.82 ± 0.3 to 0.98 ± 0.33 μmol/L in the latter. The rate of low serum retinol went from 46.1 to 17.1% in the VA capsule group and from 40.4% to 14.9% in the RPO group. VA-deficient children benefited the most from the capsule or RPO. Female sex, age and height-for-age were positively associated with the response to VA capsules or RPO.

Conclusion

RPO given regularly in small amounts appears highly effective in the reduction of VA deficiency. RPO deserves more attention as a food supplement for VA and as a potential source of rural income in Sahelian countries.
Combining partial liver resection and local ablation of liver tumours: a preliminary Dutch experience
Authors: Fioole Bram , Jansen Maarten C , van Duijnhoven Frederieke H , van Hillegersberg Richard , van Gulik Thomas M , Borel Rinkes Inne H M
Published: July 2006

Background

The combination of partial liver resection and radiofrequency ablation (RFA) is a novel concept in the treatment of unresectable liver malignancies. The aim of this study is to evaluate the results of this combined strategy in the Netherlands.

Methods

Thirty-five patients treated with a combination of partial liver resection and RFA were identified from a prospectively registered pooled multicentre database. All patients were operated between June 1999 and November 2003 in 8 medical centres in the Netherlands. Main outcome parameters were morbidity, mortality, local success rate, and survival.

Results

Thirty-seven operations were performed in 35 patients. The group consisted of 20 male and 15 female patients with a median age of 59 years (range 41–76). Seventy-six lesions were resected and RFA was performed to ablate 82 unresectable liver tumours. Twelve patients developed a total of 24 complications, resulting in an overall perioperative morbidity rate of 32%. In two patients major complications resulted in postoperative death (postoperative mortality rate 5.4%). Local success rate after RFA was 88% and the estimated 1-, 2- and 3-year overall survival rates were 84%, 70% and 43%, respectively.

Conclusion

This strategy should only be performed following strict patient selection and within the context of prospective clinical trials.
A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles
Authors: Kitayama Tomoya , Kinoshita Ayako , Sugimoto Masahiro , Nakayama Yoichi , Tomita Masaru
Published: July 2006

Background

In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems.

Results

The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations.

Conclusion

The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.
The prenatal ultrasonographic detection of myelomeningocele in patients referred to Children's Hospital Medical Center: a cross sectional study
Authors: Kazmi Syed Shuja , Nejat Farideh , Tajik Parvin , Roozbeh Hadi
Published: July 2006

Background

To find out about the prenatal diagnosis rate of myelomeningocele (MMC) by ultrasound scan in patients referred to the Children's Hospital Medical Center in Tehran, Iran from July 2004 to July 2005.

Methods

We included 140 children born with MMC and who were referred for management, surgery and treatment of complications associated with it. The ultrasound reports were examined. Data on sex, age, location of MMC, time of prenatal ultrasound and the trimester in which the diagnosis was made along with the results of the diagnosis (MMC, hydrocephalus, or both), were collected.

Results

Among the studied patients, 136 (97.1%) cases had prenatal ultrasound, amongst those, 58 (42.6%) sonographic evaluations were diagnostic for hydrocephalus and/or MMC. The prenatal ultrasound was positive for MMC in 16 (11.8%), hydrocephalus in 25 (18.4%) and both MMC and hydrocephalus in 17 (12.5%) cases. Among all cases with prenatal diagnosis of MMC, 3.4% were detected in the first, 31% in the second and 65.5% in the third trimester. Thoracic/thoracolumbar lesions were found prenatally in 40% of cases, which is significantly higher than the detection rate of other locations including cervical/cervicothoracic and lumbar/lumbosacral/sacral regions diagnosed only in 0% and 21% of cases respectively.

Conclusion

There is a large difference between the detection rate of our population (24.3%) compared to others (68%). Pregnant women should have an ultrasound at 20–22 week for detection of congenital anomalies including MMC.
Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats: response
Authors: Preuss Harry G , Bagchi Manashi , Bagchi Debasis
Published: July 2006

A response to Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG: Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats. Nutr Metabol 2005, 2:23
Differential effects of curcumin on vasoactive factors in the diabetic rat heart
Authors: Farhangkhoee Hana , Khan Zia A , Chen Shali , Chakrabarti Subrata
Published: July 2006

Background

Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications, including cardiomyopathy. Recent studies indicate that curcumin, a potent antioxidant, may be beneficial in preventing diabetes-induced oxidative stress and subsequent secondary complications. We have investigated the effects of curcumin on the nitric oxide (NO) pathway in cardiac tissues and cultured cells.

Methods

Streptozotocin-induced diabetic rats were treated with curcumin for a period of one month. Heart tissues were then analyzed for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression. Oxidative protein and DNA damage were assessed by immunohistochemical analysis of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Heart tissues were further subjected to endothelin-1 (ET-1) mRNA expression. In order to further characterize the effects of curcumin, we assayed microvascular endothelial cells (MVECs). Cultured MVECs, exposed either to glucose or glucose and varying concentrations of curcumin, were assessed for alterations of NOS expression and activation of nuclear factor-κB (NF-κB) and activating protein-1 (AP-1). Oxidative stress and ET-1 expression levels were also assayed.

Results

Our results indicate that one month of diabetes causes an upregulation of both eNOS and iNOS mRNA levels, and nitrotyrosine and 8-OHdG immunoreactivity in the heart. Treatment of diabetic rats with curcumin reduced eNOS and iNOS levels in association with reduced oxidative DNA and protein damage. Interestingly, curcumin further increased vasoconstrictor ET-1 in the heart. Exposure of MVECs to high glucose increased both eNOS and iNOS levels and oxidative stress. Curcumin prevented NOS alteration and oxidative stress in a dose-dependent manner which was mediated by nuclear factor-κB and activating protein-1. Exposure to curcumin also increased ET-1 levels in the MVECs.

Conclusion

Our studies indicate the differential effects of curcumin in vasoactive factor expression in the heart and indicate the importance of tissue microenvironment in the treatment of diabetic complications.