bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of Regulatory and Effector T Cells in Progressively Growing versus Rejecting Tumors of Similar Origins
Authors: Bui Jack D. , Uppaluri Ravindra , Hsieh Chyi-Song , Schreiber Robert D.
Published: July 2006

Although regulatory T cells (Tregs) have been detected in clinically apparent and experimentally induced tumors, the significance of their presence is obscured because past studies examined late-stage tumors that had formed in immunocompetent hosts and thus had evolved mechanisms to escape immunologic recognition and/or elimination. Herein, we report the first comparative analysis of the antitumor response to 3′-methylcholanthrene–induced tumors, which either grow progressively (progressor tumors) or are rejected by the immune system (regressor tumors). Surprisingly, we found that both progressor and regressor tumors harbored proliferating (i.e., activated) Foxp3+CD25+Tregs. However, progressor tumors contained a higher percentage of Tregs in the lymphocyte subset versus regressor tumors. The Tregs in progressor tumors were derived from peripheral CD25+ natural Tregs, accumulated early after tumor challenge and were actively proliferating, suggesting that progressor tumors recruited and/or activated endogenous Tregs as a mechanism of escaping immune destruction. To explore whether Tregs directly contributed to the progressive growth phenotype of progressor tumors, we monitored tumor outgrowth in naive wild-type recipients pretreated with either a control monoclonal antibody (mAb) or a depleting CD25-specific mAb. In mice predepleted of CD25+ cells, the tumors that subsequently developed displayed an increased accumulation of proliferating CD8+ T cells and were rejected. These results show that, although Tregs are activated in both regressor and progressor tumors, the ratio of regulatory to effector T cells is critical in determining whether the host successfully rejects the tumor or eventually succumbs to tumor outgrowth. (Cancer Res 2006; 66(14): 7301-9)
The Human Orthologue of Drosophila Ecdysoneless Protein Interacts with p53 and Regulates Its Function
Authors: Zhang Ying , Gurumurthy Channabasavaiah B. , Kim JunHyun , Bhat Ishfaq , Gao Qingshen , Dimri Goberdhan , Lee Sam W. , Band Hamid , Band Vimla
Published: July 2006

Biochemical mechanisms that control the levels and function of key tumor suppressor proteins are of great interest as their alterations can lead to oncogenic transformation. Here, we identify the human orthologue of Drosophila melanogaster ecdysoneless (hEcd) as a novel p53-interacting protein. Overexpression of hEcd increases the levels of p53 and enhances p53 target gene transcription whereas hEcd knockdown has the opposite effects on p53 levels and target gene expression. Furthermore, hEcd interacts with murine double minute-2 and stabilizes p53 by inhibiting murine double minute-2–mediated degradation of p53. Thus, hEcd protein represents a novel regulator of p53 stability and function. Our studies also represent the first demonstration of a biochemical function for hEcd protein and raise the possibility that altered hEcd levels and/or function may contribute to oncogenesis. (Cancer Res 2006; 66(14): 7167-75)
Papilloma Development Is Delayed in Osteopontin-Null Mice: Implicating an Antiapoptosis Role for Osteopontin
Authors: Hsieh Yu-Hua , Juliana M. Margaret , Hicks Patricia H. , Feng Gong , Elmets Craig , Liaw Lucy , Chang Pi-Ling
Published: July 2006

Osteopontin is a secreted, adhesive glycoprotein, whose expression is markedly elevated in several types of cancer and premalignant lesions, implicating its association with carcinogenesis. To test the hypothesis that induced osteopontin is involved in tumor promotion in vivo, osteopontin-null and wild-type (WT) mice were subjected to a two-stage skin chemical carcinogenesis protocol. Mice were initiated with 7,12-dimethylbenz(a)anthracene (DMBA) applied on to the dorsal skin followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 27 weeks. Osteopontin-null mice showed a marked decrease both in tumor/papilloma incidence and multiplicity compared with WT mice. Osteopontin is minimally expressed in normal epidermis, but on treatment with TPA its expression is highly induced. To determine the possible mechanism(s) by which osteopontin regulates tumor development, we examined cell proliferation and cell survival. Epidermis from osteopontin-null and WT mice treated with TPA thrice or with DMBA followed by TPA for 11 weeks showed a similar increase in epidermal hyperplasia, suggesting that osteopontin does not mediate TPA-induced cell proliferation. Bromodeoxyuridine staining of papillomas and adjacent epidermis showed no difference in cell proliferation between groups. However, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling analyses indicated a greater number of apoptotic cells in DMBA-treated skin and papillomas from osteopontin-null versus WT mice. These studies are the first to show that induction of the matricellular protein osteopontin facilitates DMBA/TPA-induced cutaneous carcinogenesis most likely through prevention of apoptosis. (Cancer Res 2006; 66(14): 7119-27)
Prohibitin Is a Novel Target Gene of Vitamin D Involved in Its Antiproliferative Action in Breast Cancer Cells
Authors: Peng Xinjian , Mehta Rajeshwari , Wang Sheng , Chellappan Srikumar , Mehta Rajendra G.
Published: July 2006

Previously, we showed that N-methyl-N-nitrosourea–transformed MCF12F breast epithelial cells exhibited differential expression of several genes, including up-regulation of prohibitin and elevated sensitivity to a relatively noncalcemic vitamin D analogue, 1α-hydroxyvitamin D5 [1α(OH)D5]. In this report, we evaluated the functional significance of prohibitin in relation to the cellular response to vitamin D. The in silico screening for putative transcription factor binding sites identified two vitamin D receptor (VDR)/retinoid X receptor binding sites in the 1-kb promoter region of prohibitin. Prohibitin up-regulation by 1α(OH)D5 treatment at both transcriptional and translational levels was confirmed by real-time reverse transcription-PCR and Western blot analysis in breast cancer cells, identifying prohibitin as a vitamin D target gene. Confocal microscopic analysis showed that prohibitin was localized in the nuclei of MCF-7 cells and a portion of prohibitin was colocalized with VDR, but direct physical interaction between VDR and prohibitin in cell lysates was not detectable. In MCF-7 cells expressing tetracycline-inducible prohibitin (Tet-On model), the overexpression of prohibitin inhibited cell proliferation and enhanced vitamin D–induced antiproliferative activity. Knockdown of prohibitin was accompanied by increased number of cells incorporating bromodeoxyuridine in the whole population and increased cell distribution in the S phase of cell cycle. In addition, prohibitin level had no significant effect on the vitamin D–induced transactivation of CYP24, a VDR target gene. This is the first report to suggest that prohibitin serves as a novel vitamin D target gene, which is involved in the antiproliferative action of vitamin D without affecting CYP24 transactivation in breast cancer cells. (Cancer Res 2006; 66(14): 7361-9)
Association with HSP90 Inhibits Cbl-Mediated Down-regulation of Mutant Epidermal Growth Factor Receptors
Authors: Yang Seungchan , Qu Shimian , Perez-Tores Marianela , Sawai Ayana , Rosen Neal , Solit David B. , Arteaga Carlos L.
Published: July 2006

Activating mutations in the epidermal growth factor receptor (EGFR), localized in the activation loop within the kinase domain, have been discovered in non–small cell lung cancers (NSCLC). Most of these mutants are exquisitely sensitive to EGFR tyrosine kinase inhibitors, suggesting that they generate receptor dependence in the cancers that express them. 32D cells stably expressing EGFR-L861Q and EGFR-L858R but not wild-type EGFR exhibited ligand-independent receptor phosphorylation and viability. Ligand-induced receptor down-regulation (LIRD) was impaired in mutant-expressing cells. The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein CIN85 on the addition of ligand. Inhibition of HSP90 activity with geldanamycin restored Cbl function as indicated by receptor ubiquitination and LIRD. These results suggest that EGFR mutants form defective endocytic complexes. In addition, HSP90 plays a role in maintaining the functional conformation of EGFR mutants and protecting activated receptors from LIRD. (Cancer Res 2006; 66(14): 6990-7)
Prevention of Hypertension and Organ Damage in 2-Kidney, 1-Clip Rats by Tetradecylthioacetic Acid
Authors: Gudbrandsen Oddrun Anita , Hultstrøm Michael , Leh Sabine , Monica Bivol Liliana , Vågnes Øyvind , Berge Rolf K. , Iversen Bjarne M.
Published: July 2006

Dietary lipids are reported to affect the blood pressure in both humans and experimental animal models with hypertension. In the present study, 2-kidney, 1-clip (2K1C) hypertensive rats were treated with the modified fatty acid tetradecylthioacetic acid (TTA) from the time of clipping or after hypertension was established. TTA treatment attenuated the development of hypertension and reduced established 2K1C hypertension. The mRNA level of renin in the clipped kidney and the plasma renin activity were markedly reduced, and the plasma angiotensin II level tended to decrease after TTA treatment. In addition, TTA reduced the mRNA level of angiotensinogen in white adipose tissue. Prevention of organ damage was demonstrated by normal urinary excretion of protein, maintained serum albumin, lower heart weight, and clearly reduced vascular, glomerular, and tubulointerstitial damage in the nonclipped kidney. Renal function was not affected as estimated by unchanged plasma creatinine. Furthermore, the serum levels of triacylglycerol and cholesterol were reduced by TTA. The serum fatty acid composition was changed, resulting in a favorable increase of oleic acid. However, the levels of all of the omega-3 fatty acids and of linoleic acid were reduced, and no change was seen in the level of arachidonic acid, but the urinary excretion of 8-iso-prostaglandin F2α was declined. In conclusion, TTA attenuated the development of hypertension, reduced established hypertension, and prevented the development of organ damage in 2K1C rats, possibly by reducing the amounts of the vasoconstrictors angiotensin II and 8-iso-prostaglandin F2α and by inducing a favorable increase of oleic acid in serum.
Increase in Vascular Permeability and Vasodilation Are Critical for Proangiogenic Effects of Stem Cell Therapy
Authors: You Dong , Waeckel Ludovic , Ebrahimian Téni G. , Blanc-Brude Olivier , Foubert Philippe , Barateau Véronique , Duriez Micheline , LeRicousse-Roussanne Sophie , Vilar José , Dejana Elisabetta , Tobelem Gérard , Lévy Bernard I. , Silvestre Jean-Sébastien
Published: July 2006

Background—

Proangiogenic cell therapy based on administration of bone marrow–derived mononuclear cells (BMCs) or endothelial progenitor cells (EPCs) is now under investigation in humans for the treatment of ischemic diseases. However, mechanisms leading to the beneficial effects of BMCs and EPCs remain unclear.

Methods and Results—

BMC- and CD34
+
-derived progenitor cells interacted with ischemic femoral arteries through SDF-1 and CXCR4 signaling and released nitric oxide (NO) via an endothelial nitric oxide synthase (eNOS)–dependent pathway. BMC-induced NO production promoted a marked vasodilation and disrupted vascular endothelial–cadherin/β-catenin complexes, leading to increased vascular permeability. NO-dependent vasodilation and hyperpermeability were critical for BMC infiltration in ischemic tissues and their proangiogenic potential in a model of hindlimb ischemia in mice.

Conclusions—

Our results propose a new concept that proangiogenic progenitor cell activity does not rely only on their ability to differentiate into endothelial cells but rather on their capacity to modulate the function of preexisting vessels.
MEF2 Activates a Genetic Program Promoting Chamber Dilation and Contractile Dysfunction in Calcineurin-Induced Heart Failure
Authors: van Oort Ralph J. , van Rooij Eva , Bourajjaj Meriem , Schimmel Joost , Jansen Maurits A. , van der Nagel Roel , Doevendans Pieter A. , Schneider Michael D. , van Echteld Cees J.A. , De Windt Leon J.
Published: July 2006

Background—

Hypertrophic growth, a risk factor for mortality in heart disease, is driven by reprogramming of cardiac gene expression. Although the transcription factor myocyte enhancer factor-2 (MEF2) is a common end point for several hypertrophic pathways, its precise cardiac gene targets and function in cardiac remodeling remain to be elucidated.

Methods and Results—

We report the existence of synergistic interactions between the nuclear factor of activated T cells and MEF2 transcription factors triggered by calcineurin signaling. To circumvent the embryonic lethality and mitochondrial deficiency associated with germ-line null mutations for MEF2C and MEF2A respectively, we used conditional transgenesis to express a dominant-negative form of MEF2 in the murine postnatal heart and combined this with magnetic resonance imaging to assess MEF2 transcriptional function in Ca
2+
/calcineurin-induced cardiac remodeling. Surprisingly, end-diastolic and end-systolic ventricular dimensions and contractility were normalized in the presence of severely hypertrophied left ventricular walls on MEF2 inhibition in calcineurin transgenic mice. In line, we generated lines of transgenic mice expressing MEF2A in the heart, which displayed primarily chamber dilation. Microarray profiling indicated that MEF2 promotes a gene profile functioning primarily to or at the nucleus, cytoskeletal and microtubular networks, and mitochondria.

Conclusions—

These findings assign a novel function to MEF2 transcription factors in the postnatal heart, where they activate a genetic program that minimally affects cardiac growth yet promotes chamber dilation, mechanical dysfunction, and dilated cardiomyopathy.
Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial
Authors: Morrow David A. , de Lemos James A. , Sabatine Marc S. , Wiviott Stephen D. , Blazing Michael A. , Shui Amy , Rifai Nader , Califf Robert M. , Braunwald Eugene
Published: July 2006

Background—

Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain.

Methods and Results—

We measured the serum concentration of hsCRP at 30 days (n=3813) and 4 months in patients with non–ST-elevation or ST-elevation acute coronary syndrome randomly assigned to an early intensive versus delayed conservative simvastatin strategy in the Aggrastat-to-Zocor Trial. Patients with hsCRP >3 mg/L at 30 days had significantly higher 2-year mortality rates than those with hsCRP 1 to 3 mg/L or hsCRP <1 mg/L (6.1% versus 3.7% versus 1.6%,
P
<0.0001). Results were similar with hsCRP measured at 4 months. After adjusting for age, gender, diabetes, smoking, cardiovascular history, index event, lipid levels, and randomly assigned treatment, patients with hsCRP >3 mg/L were at more than 3-fold higher risk of death (HR, 3.7; 95% CI, 1.9 to 7.2) compared with those with hsCRP <1 mg/L. “Average” levels of hsCRP (1 to 3 mg/L) were also associated with increased risk compared with those with hsCRP <1 mg/L (HR, 2.3; 95% CI, 1.2 to 4.6). Patients allocated to early intensive statin therapy were more likely to achieve hsCRP levels <1 mg/L at 30 days (
P
=0.028) and 4 months (
P
<0.0001).

Conclusions—

Achieved levels of hsCRP at 30 days and 4 months after acute coronary syndrome are independently associated with long-term survival. Patients treated with more aggressive statin therapy are more likely to achieve lower levels of hsCRP.
"The Ministry of Reconciliation" (2 Cor 5:14–21): Paul's Key to the Problem of "the Other" in Corinth
Authors: Okure Teresa
Published: July 2006

Locating the theme of reconciliation in the complex world of diversity, this article affirms and revisits reconciliation as a theological key to deal with the complex reality of our world. Recognizing the possibility of deep diversity of the first century Corinth, the author states that Paul's main purpose in writing to the Corinthians was to help them relate with "the other" within the Christian community and with him. The author then went on to draw what can be learned from Paul's plea to reconcile with God and with each other in 2 Corinthians 5:14–21. In his ministry of reconciliation, the former Pharisee of Pharisees crossed new boundaries as evident, for instance, in his affirmation of women as his co-ministers. Secondly, Paul tried to persuade others to join him in reflecting the meaning of their call to be ministers of reconciliation in concrete situations. Did Paul succeed in his ministry of reconciliation? It is clear from his letters that he was not successful. We will also encounter obstacles and difficulties, but we must hold on to God's reconciling ministry given to us as a gift, plead the author.
My Job Sucks
Authors: Gossett Loril M. , Kilker Julian
Published: July 2006

Counterinstitutional Web sites are often portrayed as publicizing the outbursts of disgruntled employees and customers. However, they also enable participants to take part in discussions normally discouraged within traditional work environments. These sites permit individuals to publicly and anonymously voice their concerns and frustrations with particular institutions with reduced fear of retribution or termination. A close examination of one of these counterinstitutional Web sites (RadioShackSucks.com) illustrates the dissent and resistance functions that such sites provide to a wide variety of stakeholders. The authors' analysis of 1,095 site postings during a 1-month period finds that participants use these sites to engage in voice and resistance efforts outside formal organizational boundaries. Theoretical and practical implications of the findings are discussed.
Performance Characteristics of Electro–chemically Driven Polyacrylonitrile Fiber Bundle Actuators
Authors: Choe Kiyoung , Kim Kwang J. , Kim Doyeon , Manford Chris , Heo Soek , Shahinpoor Moshen
Published: July 2006

Polyacrylonitrile (PAN) gel is known for its large volume change when subjected to environmental stimuli. In particular, PAN fiber contracts when exposed to a low pH environment and expands when exposed to a high pH environment. Due to this phenomenon, PAN fibers can create effective actuation forces and displacements through muscle–like contractile behavior during the volume change. An alternative way to manage contraction/elongation is to generate a local pH gradient, which can be achieved through an electrochemical cell and is more convenient than using a pH changing solution. The main objective of this study is to investigate the chemo–mechanical (i.e., pH response) and electro–chemo–mechanical behavior of PAN bundle actuators in order to characterize the performance capability of PAN fiber gel as an effective soft actuator for new engineering applications. In order to do this, the shrinking and swelling properties of PAN gel fiber bundles under the influence of various stimuli, such as pH difference and electric field, are investigated and characterized, while a capability map has been suggested and compared with other conventional actuators. Pre–oxidized PAN fibers are annealed for 5 h at 220 C and then placed in a bundle configuration. Fibers of 30 strands, 150 mm in length, are bound as a soft actuator, with a ring gripper epoxied to each end of the bundle. After significant efforts were made to properly address the corrosive behavior of the electrode, performance characteristics of PAN actuators have been experimentally obtained and compared to other conventional actuator technologies. It was found that the actuation stress of PAN bundle actuators is in the range of a moving coil transducer, and the actuation strain is also better than a solenoid, as well as similar to natural muscle. The power, density, and frequency of a PAN actuator are within the range of other polymer gel actuators. The obtained maximum actuation stress and linear actuation strain are generally in the range of 2 10 3 –1 100 MPa and 20–100% for both chemically induced and electro–chemically induced PAN bundle actuators, respectively. Finally, suggestions for the practical application ranges of PAN actuation systems are given.
Nonlinear Response of the Macro Fiber Composite Actuator to Monotonically Increasing Excitation Voltage
Authors: Williams R. Brett , Inman Daniel J. , Wilkie W. Keats
Published: July 2006

A nonlinear model for a piezoelectric continuum subjected to a monotonic increase in electric field under constant mechanical load is investigated. A general model is derived and then specialized for a piezoceramic-based material with anisotropic actuation and mechanical properties, for example, the Macro Fiber Composite (MFC) actuator. This formulation includes the linear-elastic mechanical response, as well as linear and second-order piezoelectric behavior and a second-order electromechanical cross-term. Using previously published work by the same authors (Williams, R.B., Inman, D.J. and Wilkie, W.K. 2004. “Tensile and Shear Behavior of Macro Fiber Composite Actuators,” Journal of Composite Materials, 38(10):855—870) dealing with the mechanical response of the MFC, this set of material properties is determined experimentally in order to characterize the response of this device to given external loading conditions.
Self-Diagnosis of Hybrid CFRP Rods and As-Strengthened Concrete Structures
Authors: Yang C. Q. , Wu Z. S. , Ye L. P.
Published: July 2006

A literature survey reveals that extensive studies have been published on the hybridization of composite and self-diagnosis of carbon fiber reinforced polymer (CFRP) composites. In these researches, not more than one type of carbon fibers or powders is used as active materials. This article addresses a new class of smart hybrid CFRP (HCFRP) rods consisting of at least two types of carbon fibers of different strength and moduli as active materials and their applications to concrete structures. The carbon fibers function as both structural and sensing materials by virtue of their good mechanical properties, electrical conductivity, and piezoresistivity. The hybridization focuses on two aspects: to better the electrical behavior of the HCFRP rods in order to obtain a stage-based sensing function, and to upgrade their mechanical properties. The self-diagnosis and damage detection functions of the HCFRP rods and/or the as-strengthened concrete structures are realized through measuring the change in electrical resistance. The sensing principles are based on the electrical resistance change with the strain change and sudden jumps in electrical resistance due to the gradual fractures of different types of carbon fibers. The results show that the electrical resistance of the HCFRP rods changes with strain in a stepwise manner. The sudden jumps in electrical resistance at different strain amplitudes are associated with the ruptures of different types of carbon fibers. Thus, the step-based sensing of HCFRP rods-selves or strengthened structures is realized. Moreover, the initiation and propagation of cracks in the HCFRP rod-strengthened concrete beams are also measured by means of clip gages and distributed fiber optic sensors (FOS).
Damage Bounding Structural Health Monitoring
Authors: Elwasia Nazar , Sundaresan Mannur J. , Schulz Mark J. , Ghoshal Anindya , Pai P. Frank , Tu Peter K. C.
Published: July 2006

The accuracy of locating damage using vibration measurements depends on the number and locations of sensors on the structure. In practical applications, only a limited number of on-board sensors will be available. The limited number of sensors causes spatial aliasing when solving an underdetermined inverse problem to locate damage. In this study, instead of trying to exactly locate damage, a method is developed that bounds the damage in-between the closest sensors on bar and beam structures. The method is based on current and predamage measurement of all the degrees of freedom (dofs) of vibration at a small number of sensor locations on the structure, and the excitation must be applied at the points where the response is measured. No model of the structure is needed. The technique bounds the damage location between the closest sensors, and it can compensate for a uniform change in temperature that would otherwise be interpreted as damage. The damage force is also approximated. A limitation of the technique is that rotational vibration must be measured if bending occurs. A finite-element method (FEM) model of an axial bar was used to demonstrate the technique using full and partial measurements. A simulation verified that the damage is always bounded between the closest sensors. Experiments were then performed in which reversible damage was put in an axial bar. The damage was detectable, but the damage location was found to be sensitive to errors in the experimental measurements. Suggestions for improving the experimental technique and for extending the method to plate and frame structures are given. The damage bounding method may also be useful as an FEM model verification tool. In this case, the technique might tell in what region of a structure there is a modeling problem. Existing model updating methods, or model-based damage detection methods, could then be used with more confidence to correct the model.
Permanent or Temporary Classroom Groups: A Field Study
Authors: Zeff Lawrence E. , Higby Mary A. , Bossman Larry J.
Published: July 2006

Interviews of graduate and undergraduate students and faculty members at several urban universities were conducted during a 3-year period. The results suggest differences in satisfaction and performance with respect to temporary versus permanent groups and groups versus teams. Possible explanations for these differences are provided. The article discusses types of projects for which permanent and temporary groups will be effective. Findings also suggest the need for increased training of faculty in creating appropriate classroom environments and projects. Areas of additional training necessary for students include group dynamics and leadership requirements to supplement course concepts.
Creativity and Team Environment: An Exercise Illustrating How Much One Member Can Matter
Authors: Zimmerman D. Kent , Gallagher Scott R.
Published: July 2006

This experiential exercise is designed to explore the effects of positive and negative group environments on creativity. It asks students to undertake a creative activity (i.e., draw a picture) in groups with a member predesignated to offer either positive or negative comments. Students in the two different types of group environment produced dramatically different drawings. The exercise can be used to discuss the role of positive and negative work environments on teams and how students can use their skills to effectively handle negative environments.
BBP: Brucella genome annotation with literature mining and curation
Authors: Xiang Zuoshuang , Zheng Wenjie , He Yongqun
Published: July 2006

Background

Brucella species are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and animals. Sequences of four Brucella genomes have been published, and various Brucella gene and genome data and analysis resources exist. A web gateway to integrate these resources will greatly facilitate Brucella research. Brucella genome data in current databases is largely derived from computational analysis without experimental validation typically found in peer-reviewed publications. It is partially due to the lack of a literature mining and curation system able to efficiently incorporate the large amount of literature data into genome annotation. It is further hypothesized that literature-based Brucella gene annotation would increase understanding of complicated Brucella pathogenesis mechanisms.

Results

The Brucella Bioinformatics Portal (BBP) is developed to integrate existing Brucella genome data and analysis tools with literature mining and curation. The BBP InterBru database and Brucella Genome Browser allow users to search and analyze genes of 4 currently available Brucella genomes and link to more than 20 existing databases and analysis programs. Brucella literature publications in PubMed are extracted and can be searched by a TextPresso-powered natural language processing method, a MeSH browser, a keywords search, and an automatic literature update service. To efficiently annotate Brucella genes using the large amount of literature publications, a literature mining and curation system coined Limix is developed to integrate computational literature mining methods with a PubSearch-powered manual curation and management system. The Limix system is used to quickly find and confirm 107 Brucella gene mutations including 75 genes shown to be essential for Brucella virulence. The 75 genes are further clustered using COG. In addition, 62 Brucella genetic interactions are extracted from literature publications. These results make possible more comprehensive investigation of Brucella pathogenesis. Other BBP features include publication email alert service, Brucella researchers' contact database, and discussion forum.

Conclusion

BBP is a gateway for Brucella researchers to search, analyze, and curate Brucella genome data originated from public databases and literature. Brucella gene mutations and genetic interactions are annotated using Limix leading to better understanding of Brucella pathogenesis.
Expression patterns of plexins and neuropilins are consistent with cooperative and separate functions during neural development
Authors: Mauti Olivier , Sadhu Rejina , Gemayel Joelle , Gesemann Matthias , Stoeckli Esther T
Published: July 2006

Background

Plexins are a family of transmembrane proteins that were shown to act as receptors for Semaphorins either alone or in a complex together with Neuropilins. Based on structural criteria Plexins were subdivided into 4 classes, A through D. PlexinAs are mainly thought to act as mediators of repulsive signals in cell migration and axon guidance. Their functional role in vertebrates has been studied almost exclusively in the context of Semaphorin signaling, i.e. as co-receptors for class 3 Semaphorins. Much less is known about Plexins of the other three classes. Despite the fact that Plexins are involved in the formation of neuronal circuits, the temporal changes of their expression patterns during development of the nervous system have not been analyzed in detail.

Results

Only seven plexins are found in the chicken genome in contrast to mammals, where nine plexins have been identified. Here, we describe the dynamic expression patterns of all known plexin family members in comparison to the neuropilins in the developing chicken spinal cord.

Conclusion

Our in situ hybridization study revealed that the expression patterns of plexins and neuropilins are only partially overlapping, especially during early and intermediate stages of spinal cord development, supporting both cooperative and separate functions of plexins and neuropilins in neural circuit formation.
The yfhQ gene of Escherichia coli encodes a tRNA:Cm32/Um32 methyltransferase
Authors: Purta Elzbieta , van Vliet Françoise , Tkaczuk Karolina L , Dunin-Horkawicz Stanislaw , Mori Hirotada , Droogmans Louis , Bujnicki Janusz M
Published: July 2006

Background

Naturally occurring tRNAs contain numerous modified nucleosides. They are formed by enzymatic modification of the primary transcripts during the complex RNA maturation process. In model organisms Escherichia coli and Saccharomyces cerevisiae most enzymes involved in this process have been identified. Interestingly, it was found that tRNA methylation, one of the most common modifications, can be introduced by S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases (MTases) that belong to two structurally and phylogenetically unrelated protein superfamilies: RFM and SPOUT.

Results

As a part of a large-scale project aiming at characterization of a complete set of RNA modification enzymes of model organisms, we have studied the Escherichia coli proteins YibK, LasT, YfhQ, and YbeA for their ability to introduce the last unassigned methylations of ribose at positions 32 and 34 of the tRNA anticodon loop. We found that YfhQ catalyzes the AdoMet-dependent formation of Cm32 or Um32 in tRNASer1 and tRNAGln2 and that an E. coli strain with a disrupted yfhQ gene lacks the tRNA:Cm32/Um32 methyltransferase activity. Thus, we propose to rename YfhQ as TrMet(Xm32) according to the recently proposed, uniform nomenclature for all RNA modification enzymes, or TrmJ, according to the traditional nomenclature for bacterial tRNA MTases.

Conclusion

Our results reveal that methylation at position 32 is carried out by completely unrelated TrMet(Xm32) enzymes in eukaryota and prokaryota (RFM superfamily member Trm7 and SPOUT superfamily member TrmJ, respectively), mirroring the scenario observed in the case of the m1G37 modification (introduced by the RFM member Trm5 in eukaryota and archaea, and by the SPOUT member TrmD in bacteria).
Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole
Authors: Schaars CF , Meintjes GA , Morroni C , Post FA , Maartens G
Published: July 2006

Background

AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period.

Methods

Retrospective chart review of adult patients before and after the fluconazole donation.

Results

205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively.

Conclusion

Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.
Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission
Authors: Lietzau Susanne , Raum Elke , von Baum Heike , Marre Reinhard , Brenner Hermann
Published: July 2006

Background

Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse.

Methods

Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002–2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained.

Results

Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1–15.5) and 3.3 (1.5–18.0), respectively.

Conclusion

Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts.
Changes in the incidence of occupational disability as a result of back and neck pain in the Netherlands
Authors: Steenstra Ivan A , Verbeek Jos H , Prinsze Femmeke J , Knol Dirk L
Published: July 2006

Background

Back pain (including neck pain) is one of the most prevalent health problems for which physicians are consulted. Back pain can decrease the quality of life considerably during a great part of the lives of those who suffer from it. At the same time it has an enormous economic impact, mainly through sickness absence and long-term disability. The objective of this paper is to compare the incidence of occupational disability as a result of back and neck pain in 1980–1985 to 1999–2000 and to explain the findings.

Methods

A descriptive study was performed at population level of changes in incidence of occupational disability as a result of back and neck pain. Statistics from the National Institute of Social Insurance in the Netherlands are used to calculate age and gender specific incidence rates for back pain diagnoses based on the ICD-classification. Incidence rate ratios stratified according to gender and adjusted for age were calculated to indicate changes over time.

Results

The incidence of occupational disability as a result of back pain decreased significantly by 37% (95% CI 37%–38%) in men and with 21% (95% CI 20%–24%) in women, after adjustment for age. For overall occupational disability as a result of all diagnoses this was 18% (95% CI 18%–19%) and 34% (95% CI 33%–35%) respectively. Changes were not homogeneous over diagnostic subcategories and age groups. Spondylosis decreased most in men by 59% (95% CI 57%–61%). The incidence of non-specific back pain and neck pain increased most by 196% (95% CI 164%–215%). Post-laminectomy syndrome increased over all age categories both for men (85%, 95% CI 61%–113%) and women (113%, 95% CI 65%–179%).

Conclusion

The decrease in occupational disability as a result of back pain was larger than the decrease in occupational disability over all diagnoses. However, time trends were not homogeneous over age-, nor over sex- nor back pain categories. Most of this decrease was due to general changes such as legal and economic changes. One of several additional explanations for a decrease is the changed view on management of back pain.
Using a conceptual framework during learning attenuates the loss of expert-type knowledge structure
Authors: Novak Kerry , Mandin Henry , Wilcox Elizabeth , McLaughlin Kevin
Published: July 2006

Background

During evolution from novice to expert, knowledge structure develops into an abridged network organized around pathophysiological concepts. The objectives of this study were to examine the change in knowledge structure in medical students in one year and to investigate the association between the use of a conceptual framework (diagnostic scheme) and long-term knowledge structure.

Methods

Medical students' knowledge structure of metabolic alkalosis was studied after instruction and one year later using concept-sorting. Knowledge structure was labeled 'expert-type' if students shared ≥ 2 concepts with experts and 'novice-type' if they shared < 2 concepts. Conditional logistic regression was used to study the association between short-term knowledge structure, the use of a diagnostic scheme and long-term knowledge structure.

Results

Thirty-four medical students completed the concept-sorting task on both occasions. Twenty-four used a diagnostic scheme for metabolic alkalosis. Short-term knowledge structure was not a correlate of long-term knowledge structure, whereas use of a diagnostic scheme was associated with increased odds of expert-type long-term knowledge structure (odds ratio 12.6 [1.4, 116.0], p = 0.02). There was an interaction between short-term knowledge structure and the use of a diagnostic scheme. In the group who did not use a diagnostic scheme the number of students changing from expert-type to novice-type was greater than vice versa (p = 0.046). There was no significant change in the group that used the diagnostic scheme (p = 0.6).

Conclusion

The use of a diagnostic scheme by students may attenuate the loss of expert-type knowledge structure.
The cost of health professionals' brain drain in Kenya
Authors: Kirigia Joses Muthuri , Gbary Akpa Raphael , Muthuri Lenity Kainyu , Nyoni Jennifer , Seddoh Anthony
Published: July 2006

Background

Past attempts to estimate the cost of migration were limited to education costs only and did not include the lost returns from investment. The objectives of this study were: (i) to estimate the financial cost of emigration of Kenyan doctors to the United Kingdom (UK) and the United States of America (USA); (ii) to estimate the financial cost of emigration of nurses to seven OECD countries (Canada, Denmark, Finland, Ireland, Portugal, UK, USA); and (iii) to describe other losses from brain drain.

Methods

The costs of primary, secondary, medical and nursing schools were estimated in 2005. The cost information used in this study was obtained from one non-profit primary and secondary school and one public university in Kenya. The cost estimates represent unsubsidized cost. The loss incurred by Kenya through emigration was obtained by compounding the cost of educating a medical doctor and a nurse over the period between the average age of emigration (30 years) and the age of retirement (62 years) in recipient countries.

Results

The total cost of educating a single medical doctor from primary school to university is US$ 65,997; and for every doctor who emigrates, a country loses about US$ 517,931 worth of returns from investment. The total cost of educating one nurse from primary school to college of health sciences is US$ 43,180; and for every nurse that emigrates, a country loses about US$ 338,868 worth of returns from investment.

Conclusion

Developed countries continue to deprive Kenya of millions of dollars worth of investments embodied in her human resources for health. If the current trend of poaching of scarce human resources for health (and other professionals) from Kenya is not curtailed, the chances of achieving the Millennium Development Goals would remain bleak. Such continued plunder of investments embodied in human resources contributes to further underdevelopment of Kenya and to keeping a majority of her people in the vicious circle of ill-health and poverty. Therefore, both developed and developing countries need to urgently develop and implement strategies for addressing the health human resource crisis.
Detection of estrogen receptors ER-alpha and ER-beta in human ejaculated immature spermatozoa with excess residual cytoplasm
Authors: Rago Vittoria , Siciliano Laura , Aquila Saveria , Carpino Amalia
Published: July 2006

Background

A key role of estrogens in human sperm biology has been recently suggested by aromatase and estrogen receptor detection in human testicular germ cells and ejaculated spermatozoa. However, the involvement of these hormones in the sperm maturation process is still not defined. The aim of this work was to investigate the expression of estrogen receptors, ER-alpha and ER-beta, in human ejaculated immature spermatozoa with excess residual cytoplasm.

Methods

Immunofluorescence labelling has been used to localize ER-alpha and ER-beta proteins in immature spermatozoa isolated by Percoll gradient, while Western blot analysis was carried out on sperm protein extracts.

Results

Both estrogen receptors were localized in excess residual cytoplasm of immature sperm, while sperm tails showed only ER-beta. Furthermore, in the same cells, immunoblots detected the presence of the full-length (~67 kDa) ER-alpha and (~59 kDa) ER-beta proteins, together with a ~50 kDa ER-beta species, lacking in mature sperm.

Conclusion

The present investigation demonstrated ER-alpha and ER-beta presence in excess residual cytoplasm of human abnormal sperm cells, suggesting the hypothesis that both the 'classical' ERs could be able to mediate estrogen action in spermatogenetic cells. Furthermore, the presence of the short ER-beta form in abnormal germ cells and its disappearance in mature sperm, support estrogen modulation via different ER forms during sperm maturation.
Haemostasis, inflammation and renal function following exercise in patients with intermittent claudication on statin and aspirin therapy
Authors: Collins Patrick , Ford Isobel , Croal Bernard , Ball Derek , Greaves Michael , Macaulay Ewan , Brittenden Julie
Published: July 2006

Background

Previous studies have suggested that exercise in patients with intermittent claudication (IC) may induce a systemic thrombo-inflammatory response. The effect of secondary prevention therapy on this response is unknown. This study aimed to investigate the effects of treadmill exercise on markers of coagulation activation, inflammation and renal function in patients with IC, receiving aspirin and statin therapy compared to healthy controls.

Methods

Samples were taken before, immediately and 1 hour after exercising on a treadmill in 20 patients with IC and 20 healthy volunteers. Interleukin-6 (IL-6), thrombin-anti-thrombin complex (TAT) and fibrin D-dimer were measured by ELISA. High sensitivity CRP (HsCRP) and urinary albumin were measured via a nephelometric technique, urinary protein via a turbidometric assay and N-acetyl-β-D-glucosaminidase (NAG) via a colorimetric assay.

Results

Elevated baseline levels of Hs-CRP, IL-6, white cell counts, D-dimer and urinary NAG occurred in patients with IC compared to volunteers (p > 0.05). Following exercise there was no increase in Hs CRP or IL-6. D-dimer levels significantly increased following exercise in the patients and volunteers. TAT levels increased immediately after exercise in the patient group only and were significantly increased at 1 hour in both patients and volunteers. A transient rise in the protein creatinine ratio occurred in both groups (p < 0.007), and in albumin creatinine ratio in the patient group. There was no change in urinary NAG.

Conclusion

Elevated markers of inflammation occurred in patients with IC on statin and aspirin therapy but these did not increase following exercise. However, acute exercise resulted in a prothrombotic state evident in both groups, although this was more prolonged in patient with IC. The clinical significance of these findings in patients who are known to be at an increased risk of cardiac and other thrombotic event are unclear.