bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of Sex Offenders About Treatment
Authors: Levenson Jill S. , Macgowan Mark J. , Morin John W. , Cotter Leo P.
Published: October 2008

Surveying the views of sex offender clients can help ensure that treatment is relevant and responsive to client needs. The purpose of this exploratory study is to elicit sex offender clients' perceptions of their experiences in treatment in order to better understand the components of treatment perceived to be helpful in preventing reoffense. Samples ( N = 338) of male sex offenders in outpatient group therapy are found to be generally satisfied with treatment services and have positive perceptions of treatment effectiveness. Offenders in treatment value the role of group therapy, and they find accountability, victim empathy, relapse prevention, and “good lives” concepts to be most helpful in managing their behavior. Their engagement in group therapy is assessed using the Group Engagement Measure, and a positive correlation is found between engagement and treatment satisfaction. Eliciting client opinions about the helpfulness of program content and process, and adjusting treatment protocols accordingly, is consistant with the principles of risk, need, and responsivity, a model recommended for therapeutic interventions with criminal offenders.
Lipid-specific immunoglobulin M in CSF predicts adverse long-term outcome in multiple sclerosis
Authors: Thangarajh M , Gomez-Rial J , Hedström AK , Hillert J , Alvarez-Cermeño JC , Masterman T , Villar LM
Published: October 2008

Background and Objective

The presence of lipid-specific immunoglobulin M bands in the cerebrospinal fluid (CSF) predicts an aggressive course in patients with relapsing–remitting multiple sclerosis (MS) during early stages of the disease. This study examined whether it is also a predictor of long-term prognosis in MS.

Methods

Eighty-one patients with MS and 22 headache controls were analyzed for anti-lipid IgM reactivity in CSF samples. The correlation between the presence of lipid-specific immunoglobulin M bands in CSF and disease progression was assessed in patients with MS who had been followed longitudinally for, on average, more than 11 years.

Results

Lipid-specific immunoglobulin M bands were detected in the CSF of 24 of 81 patients with MS and were absent in the CSF of all headache controls. Median time to conversion to a secondary progressive course was 11 years in patients with bands and 22 years in patients without bands. Median time to an Expanded Disability Status Scale score of 4 was 14 years in patients with bands and 24 years in patients without bands.

Conclusion

The presence of lipid-specific immunoglobulin M bands in CSF predicts a more adverse long-term outcome in patients with MS; it may thus define a subset of patients who might benefit from aggressive treatment during the early phase of the disease.
The silent participant in small group collaborative learning contexts
Authors: Remedios Louisa , Clarke David , Hawthorne Lesleyanne
Published: October 2008

There is an increasing acceptance in the education literature and in classroom settings for `best practice' to be linked with verbal clarification of knowledge and reasoning, ideally in collaborative contexts where students construct both group and individual knowledge. Problem-based learning (PBL) is one such classroom context in which participation is viewed as leading to learning and where the nature of `good' participation is verbal contribution. Students who choose to participate without speaking, or `silent' students, are often seen as failing to learn, and significant tutor time is devoted to encouraging verbal input. This article examines the experience of four `silent participants' (two overseas-educated and two local Australian) in a PBL context. The analysis reported in this article suggests that students' choice to be silent is a consequence of multiple constraints — personal, contextual and cultural — and that silence should not be taken to signify lack of learning.
Using action research to teach students to manage team learning and improve teamwork satisfaction
Authors: Scott-Ladd Brenda , Chan Christopher C.A.
Published: October 2008

This article reports on a study investigating strategies that students can use to develop skills in managing team learning. Two groups of second-year management students participated in a semester-long action research project over two semesters. The students were educated on team development, team processes and conflict management and how to review and enhance team development. Teaching staff supported the approach and students were regularly encouraged to reflect on and learn about how their behaviour contributed to team effectiveness. This approach encouraged student participation and ownership as well as early intervention if problems arose. Findings suggest that when students are taught to manage the processes of teamwork and take greater ownership of managing conflict and team relations they report less conflict and less social loafing and are more satisfied with their learning outcomes.
Assessing small-scale interventions in large-scale teaching
Authors: Dyson Benjamin J.
Published: October 2008

The use of lectures is ubiquitous in higher-education institutions, but also heavily criticized from an andragogical viewpoint. A current challenge for lecturers is to provide opportunities for active learning during these sessions and to evaluate their impact on student experience. Three one-minute interventions based on the lecture materials (write down one thing you have already learnt, one question you would like answering, and take a break) were introduced approximately 20, 30 and 40 minutes into the lecture and assessed with respect to engagement over a five-week period on a final-year psychology option. Students were invited to record their current level of lecture engagement every 5 minutes. Both between-and within-subject analyses revealed a significant increase in lecture engagement for the first intervention during the first intervention week relative to baseline weeks. The data show an enhancement of student engagement with certain small-scale interventions during large-scale teaching.
Immune Reconstitution Inflammatory Syndrome Presenting as Superior Vena Cava Syndrome Secondary to Coccidioides Lymphadenopathy in an HIV-Infected Patient
Authors: Mortimer Roger B. , Libke Robert , Eghbalieh Babak , Bilello John F.
Published: October 2008

A 39-year-old man living with AIDS presented with a swollen face. He was found to be HIV infected after presenting with Coccidioides pneumonia 2 years previously and was placed on daily fluconazole and then on highly active antiretroviral therapy. Computed tomography confirmed superior vena cava obstruction secondary to lymphadenopathy. Biopsy confirmed coccidioidomycosis with no evidence of malignancy. To our knowledge, this is the first description of superior vena cave syndrome secondary to coccidioidomycosis and the first description of immune reconstitution inflammatory syndrome involving Coccidioides.
Effect of Exercise Training on Walking Mobility in Multiple Sclerosis: A Meta-Analysis
Authors: Snook Erin M. , Motl Robert W.
Published: October 2008

Objective. The study used meta-analytic procedures to examine the overall effect of exercise training interventions on walking mobility among individuals with multiple sclerosis. Methods. A search was conducted for published exercise training studies from 1960 to November 2007 using MEDLINE, PsychINFO, CINAHL, and Current Contents Plus. Studies were selected if they measured walking mobility, using instruments identified as acceptable walking mobility constructs and outcome measures for individuals with neurologic disorders, before and after an intervention that included exercise training. Results. Forty-two published articles were located and reviewed, and 22 provided enough data to compute effect sizes expressed as Cohen's d. Sixty-six effect sizes were retrieved from the 22 publications with 600 multiple sclerosis participants and yielded a weighted mean effect size of g = 0.19 (95% confidence interval, 0.09-0.28). There were larger effects associated with supervised exercise training ( g = 0.32), exercise programs that were less than 3 months in duration ( g = 0.28), and mixed samples of relapsing-remitting and progressive multiple sclerosis ( g = 0.52). Conclusions. The cumulative evidence supports that exercise training is associated with a small improvement in walking mobility among individuals with multiple sclerosis.
Male and female nursing applicants' attitudes and expectations towards their future careers in nursing
Authors: Mullan Barbara , Harrison Jon
Published: October 2008

This paper investigates the assumption that men have a greater opportunity for career success in the nursing profession than women. This study investigates, through the use of a questionnaire, the attitudes and future expectations of male and female individuals attending interviews to enter a pre-registration nursing course. The results from the questionnaires were analysed using both descriptive and inferential methods of analysis, and the findings were discussed in relation to the existing research. In only two of the items, significant differences were found between male and female nursing applicants' attitudes and expectations towards their future careers. The results of this study indicate that it is unlikely to be the individual differences between males and females that determine their career progress, and instead it is more likely to be the organisational barriers within the health service or changes in expectations that are continuing to slow the career progress of female nurses. The results from this study have many implications for recruitment to nurse education programmes for men and women within nursing and the health service organisation as a whole.
Effect of social support and coping strategies on the relationship between health care-related occupational stress and health
Authors: Button Lori A
Published: October 2008

The role of social support and individual coping strategies (problem-focused, emotion-focused) in the moderation of the relationship between health care-related occupational stress and health was examined in a survey of 212 midwives and nurses. Results indicate that neither of the coping strategies was influential, whereas social support levels were either detrimental or beneficial based on the reported level of job stress. High support in conjunction with high job stress was associated with poorer health. Conversely, when support was low, high stress was associated with better health. This implied that it was the level of overall social support in conjunction with the level of job stress that was associated with psychological and physical health levels. Subsequent to the findings of this research, a call to examine specific factors that may influence the personal formation of support networks (i.e., gender, causality), as well as causality, was emphasised.
Systematic review of the uptake and design of action research in published nursing research, 2000-2005
Authors: Munn-Giddings Carol , McVicar Andrew , Smith Lesley
Published: October 2008

Action research (AR) is promoted for health care development. A systematic review was undertaken to gain insight into the uptake and designs of practice-based AR. Empirical research papers from 2000 to 2005 were extracted from CINAHL, MEDLINE and British Nursing Index, and two specialist AR journals. The initial search identified 335 papers: 38% were AR (20% were phenomenology; 32% ethnography; 10% randomised-controlled trials). Further filtering produced 62 AR papers for detailed analysis. Eighty-seven per cent of AR studies involved 'organisational/professional development', or 'educational' settings; only 13% were directly 'clinical'. Practitioners were the main participants in 90% of studies. Seventy-two per cent of all participant groups were rated 'active' in the research process, yet 70% of first (lead) authors were from an academic institution. Patients/carers were generally passive in the research process and absent from the authorship. Ninety per cent of studies used two or more methods, predominantly qualitative. Forty-four per cent of articles identified external funding sources, relatively high for nursing research. Participatory AR has a strong identity in practice-based research, with a diversity of methods. The focus reflects that of nursing research generally. A high level of participation by practitioners is evident but with little equity in authorship. Service user/carer involvement should be given more prominence by researchers.
Incidental Findings During Routine Antepartum Obstetrical Sonography
Authors: Jeanty Cerine , Ismail Lana , Turner Cheryl Delynne
Published: October 2008

The standard for performing an antepartum obstetrical sonogram primarily involves the examination of the fetus; however, both the American Institute of Ultrasound in Medicine (AIUM) and American College of Radiology (ACR) guidelines suggest the evaluation of maternal structures as well. The authors present 35 incidental findings that were discovered on routine antepartum obstetrical sonography. These include abdominal wall, gastrointestinal, reproductive, urinary, and vascular anomalies in the maternal structures. A review of the literature demonstrates that many of these findings have clinical significance, which highlights the wisdom of the AIUM and ACR guidelines, and it also stresses the importance of seeking and reporting them.
Artificial neural networks for surface modification of cobalt based tungsten cemented carbide deposits
Authors: Jean M.-D. , Lin B.-T. , Wu C.-S.
Published: October 2008

This paper presents the application of artificial neural networks (ANNs) with statistical experiments to model and characterise WC/Co deposits of the plasma sprayings. In this study, the eight control factors were designed in a L18 factorial orthogonal array, and the effects of process conditions on the surface morphology were critically reviewed in the experiments. The surface topography properties and microstructure were studied.

A gradient steepest descent algorithm in the trained ANN was used to explore the relationships between variables and responses. Artificial neural network modelling for WC/Co coatings estimation is compared by response surface methodology. The best values obtained were 2·164 and 2·871% of error percentage for the surface roughness by the best ANN and the response surface methodology model respectively. The experimental results indicate that using a statistical experiment coupled to an ANN strategy offers an effective, efficient and adaptive approach for developing a robust and highly efficient plasma sprayed process of high quality.
Prediction of hardness–depth profile from indentations at surface of materials
Authors: Lesage J. , Chicot D. , Nosei L. , Feugeas J.
Published: October 2008

Surface treatments are used to increase the resistance of the surface of mechanical parts. Unlike thin films, surface hardened materials may cover several tenths of millimetres in depth. The effectiveness of such treatments is studied by analysing the hardness–depth profile. In this paper, the authors describe a method to evaluate the hardness profile with depth based on the estimation of the contribution of deeper zones of the hardened material to the hardness of the surface through the practice of a series of indentations on the surface with increasing loads. This model allows estimating the hardness of virtual layers through a step by step calculation process at increasing depths under the surface of the material. The model was satisfactorily tested on stainless steel previously surface treated through ion nitriding with a duplex process consisting in ion nitriding followed by the irradiation with high energy short duration plasma beams of argon.
Effect of heating rate on structure of HA coating prepared by sol–gel
Authors: Wang H. , Chen C. Z. , Wang D. G.
Published: October 2008

HA coatings were deposited on Ti–6Al–4V alloy substrate using the sol–gel technique. Various heat treatments were carried out and the subsequent effect of heating rate on the resulting coatings was also investigated. The sol–gel derived coatings were studied by X-ray diffraction, electronic probe microanalysis and scratch tester. The results show that the heating rate greatly influences the morphologies, the composition and the adhesion strength of resulting coatings. Under the slow heating rate, the coatings are characterised by high phase purity, compact lamellar structure and less cracks on the surface. Moreover, the scratch test results indicate that the adhesion strength of coatings with slow heating rate is higher than that of coatings with rapid heating rate.
A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infection
Authors: Quigley Michael , Martinez Jennifer , Huang Xiaopei , Yang Yiping
Published: October 2008

Recent advances have suggested a crucial role of the innate immunity in shaping adaptive immune responses. How activation of innate immunity promotes adaptive T-cell responses to pathogens in vivo is not fully understood. It has been thought that Toll-like receptor (TLR)–mediated control of adaptive T-cell responses is mainly achieved by the engagement of TLRs on antigen-presenting cells to promote their maturation and function. In this study, we showed that direct TLR2–myeloid differentiating factor 88 (MyD88) signaling in CD8 T cells was also required for their efficient clonal expansion by promoting the survival of activated T cells on vaccinia viral infection in vivo. Effector CD8 T cells that lacked direct TLR2-MyD88 signaling did not survive the contraction phase to differentiate into long-lived memory cells. Furthermore, we observed that direct TLR2 ligation on CD8 T cells promoted CD8 T-cell proliferation and survival in vitro in a manner dependent on the phosphatidylinositol 3-kinase (PI3K)–Akt pathway activation and that activation of Akt controlled memory cell formation in vivo. These results identify a critical role for intrinsic TLR2-MyD88 signaling and PI3K-Akt pathway activation in CD8 T-cell clonal expansion and memory formation in vivo and could lead to the development of new vaccine approaches.
Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25
Authors: Chen Jing , Zhang Meili , Ju Wei , Waldmann Thomas A.
Published: October 2008

Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus I (HTLV-1) and is an aggressive malignancy of CD4, CD25-expressing leukemia, and lymphoma cells. There is no accepted curative therapy for ATL. Depsipeptide, a histone deacetylase inhibitor, has demonstrated major antitumor effects in leukemias and lymphomas. In this study, we investigated the therapeutic efficacy of depsipeptide alone and in combination with daclizumab (humanized anti-Tac) in a murine model of human ATL. The Met-1 ATL model was established by intraperitoneal injection of ex vivo leukemic cells into nonobese diabetic/severe combined immunodeficiency mice. Either depsipeptide, given at 0.5 mg/kg every other day for 2 weeks, or daclizumab, given at 100 μg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of soluble IL-2R-α (sIL-2R-α) and soluble β2-microglobulin (β2μ) (P < .001), and prolonged survival of the leukemia-bearing mice (P < .001) compared with the control group. Combination of depsipeptide with daclizumab enhanced the antitumor effect, as shown by both sIL-2R-α and β2μ levels and survival of the leukemia-bearing mice, compared with those in the depsipeptide or daclizumab alone groups (P < .001). The significantly improved therapeutic efficacy by combining depsipeptide with daclizumab supports a clinical trial of this combination in the treatment of ATL.
SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK
Authors: Okawa Yutaka , Hideshima Teru , Steed Paul , Vallet Sonia , Hall Steven , Huang Ken , Rice John , Barabasz Amy , Foley Brianna , Ikeda Hiroshi , Raje Noopur , Kiziltepe Tanyel , Yasui Hiroshi , Enatsu Sotaro , Anderson Kenneth C.
Published: October 2008

Heat-shock protein 90 (Hsp90) acts as a molecular chaperone required for maintaining the conformational stability of client proteins regulating cell proliferation, survival, and apoptosis. Here we investigate the biologic significance of Hsp90 inhibition in multiple myeloma (MM) and other hematologic tumors using an orally available novel small molecule inhibitor SNX-2112, which exhibits unique activities relative to 17-allyamino-17-demethoxy-geldanamycin (17-AAG). SNX-2112 triggers growth inhibition and is more potent than 17-AAG against MM and other malignancies. It induces apoptosis via caspase-8, -9, -3, and poly (ADP-ribose) polymerase cleavage. SNX-2112 inhibits cytokine-induced Akt and extracellular signal-related kinase (ERK) activation and also overcomes the growth advantages conferred by interleukin-6, insulin-like growth factor-1, and bone marrow stromal cells. Importantly, SNX-2112 inhibits tube formation by human umbilical vein endothelial cells via abrogation of eNOS/Akt pathway and markedly inhibits osteoclast formation via down-regulation of ERK/c-fos and PU.1. Finally, SNX-2112, delivered by its prodrug SNX-5422, inhibits MM cell growth and prolongs survival in a xenograft murine model. Our results indicate that blockade of Hsp90 by SNX-2112 not only inhibits MM cell growth but also acts in the bone marrow microenvironment to block angiogenesis and osteoclastogenesis. Taken together, our data provide the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies.
Modification of the cysteine residues in IκBα kinase and NF-κB (p65) by xanthohumol leads to suppression of NF-κB–regulated gene products and potentiation of apoptosis in leukemia cells
Authors: Harikumar Kuzhuvelil B. , Kunnumakkara Ajaikumar B. , Ahn Kwang S. , Anand Preetha , Krishnan Sunil , Guha Sushovan , Aggarwal Bharat B.
Published: October 2008

Xanthohumol (XN), a prenylated chalcone isolated from hop plant, exhibits anti-inflammatory, antiproliferative, and antiangiogenic properties through an undefined mechanism. Whether examined by intracellular esterase activity, phosphatidylserine externalization, DNA strand breaks, or caspase activation, we found that XN potentiated tumor necrosis factor–induced apoptosis in leukemia and myeloma cells. This enhancement of apoptosis correlated with down-regulation of nuclear factor-κB (NF-κB) survivin, bcl-xL, XIAP, cIAP1, cIAP2, cylin D1, and c-myc. XN down-regulated both constitutive and inducible NF-κB activation, inhibition of phosphorylation and degradation of IκBα, suppression of p65 nuclear translocation, and NF-κB–dependent reporter gene transcription. XN directly inhibited tumor necrosis factor-induced IκBα kinase (IKK) activation and a reducing agent abolished this inhibition, indicating the role of cysteine residue. XN had no effect on the IKK activity when cysteine residue 179 of IKK was mutated to alanine. XN also directly inhibited binding of p65 to DNA, a reducing agent reversed this effect, and mutation of cysteine residue 38 to serine of p65 abolished this effect. Thus, our results show that modification of cysteine residues of IKK and p65 by XN leads to inhibition of the NF-κB activation pathway, suppression of antiapoptotic gene products, and potentiation of apoptosis in leukemia cells.
Developing and validating predictive decision tree models from mining chemical structural fingerprints and high–throughput screening data in PubChem
Authors: Han Lianyi , Wang Yanli , Bryant Stephen H
Published: October 2008

Background

Recent advances in high-throughput screening (HTS) techniques and readily available compound libraries generated using combinatorial chemistry or derived from natural products enable the testing of millions of compounds in a matter of days. Due to the amount of information produced by HTS assays, it is a very challenging task to mine the HTS data for potential interest in drug development research. Computational approaches for the analysis of HTS results face great challenges due to the large quantity of information and significant amounts of erroneous data produced.

Results

In this study, Decision Trees (DT) based models were developed to discriminate compound bioactivities by using their chemical structure fingerprints provided in the PubChem systemhttp://pubchem.ncbi.nlm.nih.gov. The DT models were examined for filtering biological activity data contained in four assays deposited in the PubChem Bioassay Database including assays tested for 5HT1a agonists, antagonists, and HIV-1 RT-RNase H inhibitors. The 10-fold Cross Validation (CV) sensitivity, specificity and Matthews Correlation Coefficient (MCC) for the models are 57.2~80.5%, 97.3~99.0%, 0.4~0.5 respectively. A further evaluation was also performed for DT models built for two independent bioassays, where inhibitors for the same HIV RNase target were screened using different compound libraries, this experiment yields enrichment factor of 4.4 and 9.7.

Conclusion

Our results suggest that the designed DT models can be used as a virtual screening technique as well as a complement to traditional approaches for hits selection.
Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans
Authors: Thewes Sascha , Moran Gary P , Magee Beatrice B , Schaller Martin , Sullivan Derek J , Hube Bernhard
Published: October 2008

Background

Invasion of host tissue by the human fungal pathogen Candida albicans is an important step during the development of candidosis. However, not all C. albicans strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the in vitro phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.

Results

In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion in vitro. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an in vitro invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, in vitro transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal in vitro growth conditions.

Conclusion

Our data suggest that the reason for differential virulence of C. albicans strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.
New insights into SRY regulation through identification of 5' conserved sequences
Authors: Ross Diana GF , Bowles Josephine , Koopman Peter , Lehnert Sigrid
Published: October 2008

Background

SRY is the pivotal gene initiating male sex determination in most mammals, but how its expression is regulated is still not understood. In this study we derived novel SRY 5' flanking genomic sequence data from bovine and caprine genomic BAC clones.

Results

We identified four intervals of high homology upstream of SRY by comparison of human, bovine, pig, goat and mouse genomic sequences. These conserved regions contain putative binding sites for a large number of known transcription factor families, including several that have been implicated previously in sex determination and early gonadal development.

Conclusion

Our results reveal potentially important SRY regulatory elements, mutations in which might underlie cases of idiopathic human XY sex reversal.
An experimental in-vivo canine model for adult shunt infection
Authors: Bayston Roger , Brant Christine , Dombrowski Stephen M , Hall Geraldine , Tuohy Marion , Procop Gary , Luciano Mark G
Published: October 2008

Background

Detailed human studies of the mechanisms and development of shunt infection in real time are not possible, and we have developed a canine hydrocephalus model to overcome this. The intention of this pilot study was to show that the canine hydrocephalus model could be shunted using conventional "human" shunts, and that a shunt infection could be established so that further studies could then be planned.

Methods

Hydrocephalus was induced in seven dogs (Canis familiaris) by fourth ventricle obstruction. Four weeks later they were shunted using a Hakim Precision valve. Four of the dogs received shunts whose ventricular catheter had been inoculated with Staphylococcus epidermidis, and three were uninoculated controls. Four weeks after shunting the dogs were sacrificed and necropsy was performed. Removed shunts and tissue samples were examined microbiologically and isolates were subjected to detailed identification and genomic comparison.

Results

All the dogs remained well after shunting. Examination of removed shunt components revealed S. epidermidis in the brain and throughout the shunt system in the four inoculated animals, but in two of these Staphylococcus intermedius was also found. S. intermedius was also isolated from all three "negative" controls. There were slight differences between S. intermedius strains suggesting endogenous infection rather than cross- infection from a point source.

Conclusion

Shunt infection was established in the canine model, and had the experiment been extended beyond four weeks the typical microbiological, pathological and clinical features might have appeared. The occurrence of unplanned shunt infections in control animals due to canine normal skin flora reflects human clinical experience and underlines the usual source of bacteria causing shunt infection.
Simulating in vitro transcriptional response of zinc homeostasis system in Escherichia coli
Authors: Cui Jiangjun , Kaandorp Jaap A , Lloyd Catherine M
Published: October 2008

Background

The zinc homeostasis system in Escherichia coli is one of the most intensively studied prokaryotic zinc homeostasis systems. Its underlying regulatory machine consists of repression on zinc influx through ZnuABC by Zur (Z n2+
u ptake r egulator) and activation on zinc efflux via ZntA by ZntR (a zinc-responsive regulator). Although these transcriptional regulations seem to be well characterized, and there is an abundance of detailed in vitro experimental data available, as yet there is no mathematical model to help interpret these data. To our knowledge, the work described here is the first attempt to use a mathematical model to simulate these regulatory relations and to help explain the in vitro experimental data.

Results

We develop a unified mathematical model consisting of 14 reactions to simulate the in vitro transcriptional response of the zinc homeostasis system in E. coli. Firstly, we simulate the in vitro Zur-DNA interaction by using two of these reactions, which are expressed as 4 ordinary differential equations (ODEs). By imposing the conservation restraints and solving the relevant steady state equations, we find that the simulated sigmoidal curve matches the corresponding experimental data. Secondly, by numerically solving the ODEs for simulating the Zur and ZntR run-off transcription experiments, and depicting the simulated concentrations of zntA and znuC transcripts as a function of free zinc concentration, we find that the simulated curves fit the corresponding in vitro experimental data. Moreover, we also perform simulations, after taking into consideration the competitive effects of ZntR with the zinc buffer, and depict the simulated concentration of zntA transcripts as a function of the total ZntR concentration, both in the presence and absence of Zn(II). The obtained simulation results are in general agreement with the corresponding experimental data.

Conclusion

Simulation results show that our model can quantitatively reproduce the results of several of the in vitro experiments conducted by Outten CE and her colleagues. Our model provides a detailed insight into the dynamics of the regulatory system and also provides a general framework for simulating in vitro metal-binding and transcription experiments and interpreting the relevant experimental data.
Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases
Authors: van Gils Janine M , Zwaginga Jaap Jan , Hordijk Peter L
Published: October 2008

Platelets, monocytes, and endothelial cells are instrumental in the development and progression of cardiovascular diseases. Inflammation, a key process underlying cardiovascular disorders, is accompanied and amplified by activation of platelets and consequent binding of such platelets to the endothelium. There, platelet-derived chemokines, in conjunction with increased expression of adhesion molecules, promote the recruitment of circulating monocytes that will eventually migrate across the endothelial lining of the vessel into the tissues. Additionally, platelets may already become activated in the circulation and may form platelet-monocyte complexes, which show increased adhesive and migratory capacities themselves but also facilitate recruitment of noncomplexed leukocytes. They should therefore be considered as important mediators of inflammation. In molecular terms, these events are additionally governed by chemokines released and presented by the endothelium as well as the different classes of endothelial adhesion molecules that regulate the interactions among the various cell types. Most important in this respect are the selectins and their ligands, such as P-selectin glycoprotein (GP) ligand 1, and the integrins binding to Ig-like cell adhesion molecules as well as to GP, such as von Willebrand factor, present in the extracellular matrix or on activated endothelium. This review aims to provide an overview of these complex interactions and of their functional implications for inflammation and development of cardiovascular disease.
Spectral-decomposition response to reservoir fluids from a deepwater West Africa reservoir
Authors: Chen Ganglin , Matteucci Gianni , Fahmy Bill , Finn Chris
Published: October 2008

We study the spectral-decomposition response to reservoir fluids from a deepwater West Africa reservoir through a systematic modeling approach. Our workflow starts from selecting the seismic data (far-angle seismic images) that show more pronounced fluid effect based on amplitude-versus-offset (AVO) analysis. Synthetic seismic forward modeling performed at the control well established the quality of the seismic well tie. Reservoir wedge modeling, spectral decomposition of the field and synthetic seismic data, and theoretical analyses were conducted to understand the spectral-decomposition responses. The reservoir fluid type is a main factor controlling the spectral response. For this deepwater reservoir, the amplitude contrast between oil sand and brine sand is higher at low frequencies [Formula: see text]. In addition, synthetic modeling can help identify the possible frequency band where the amplitude contrast between hydrocarbon sand and brine sand is higher. When properly included in a comprehensive direct-hydrocarbon-indicator (DHI)–AVO evaluation, spectral decomposition can enhance the identification of hydrocarbons.
Transport of Thyroxine and 3,3′,5-Triiodothyronine in Human Umbilical Vein Endothelial Cells
Authors: Visser W. Edward , Friesema Edith C. H. , Visser Theo J.
Published: October 2008

The prerequisite for the uptake of thyroid hormone (TH) in peripheral tissues is the exit of TH from the bloodstream. The first step in this process is transport across the endothelium. Little is known about this important step in TH physiology. Therefore, we aimed to characterize the TH transport processes across the endothelium using human umbilical vein endothelial cells as a model. Transport studies showed rapid uptake of 1 nm [125I]T3 and [125I]T4 in these cells. The apparent Michaelis constant value for [125I]T3 uptake was about 1 μm, and the IC50 for T4 inhibition of T3 uptake was about 3 μm. The aromatic amino acids phenylalanine, tyrosine, and tryptophan and the L-type amino acid transporter-specific ligand 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid did not inhibit [125I]T3 or [125I]T4 uptake. Verapamil was capable of reversibly reducing transport of [125I]T3 and [125I]T4. Human umbilical vein endothelial cells incubated with the affinity label BrAcT3 resulted in a labeling of multiple proteins, which are probably protein disulfide isomerase related. Extrapolating our findings to the endothelial lining of blood vessels suggests that T3 and T4 uptake is mediated by the same transport system. Because TH transport characteristics do not correspond to known TH transporters, further studies are required to identify the TH transporter protein(s) at the molecular level. Possible candidates may be widely expressed Na+-independent transporter proteins.

The endothelium is the first barrier in the transport of thyroid hormone from plasma into tissues. Involvement of transporters is shown in this process.
Regulation of Myogenic Differentiation by Androgens: Cross Talk between Androgen Receptor/ β-Catenin and Follistatin/Transforming Growth Factor-β Signaling Pathways
Authors: Singh Rajan , Bhasin Shalender , Braga Melissa , Artaza Jorge N. , Pervin Shehla , Taylor Wayne E. , Krishnan Venkatesh , Sinha Satyesh K. , Rajavashisth Tripathi B. , Jasuja Ravi
Published: October 2008

Androgens are important regulators of body composition and promote myogenic differentiation and inhibit adipogenesis of mesenchymal, multipotent cells. Here, we investigated the mechanisms by which androgens induce myogenic differentiation of mesenchymal multipotent cells. Incubation of mesenchymal multipotent C3H 10T1/2 cells with testosterone and dihydrotestosterone promoted nuclear translocation of androgen receptor (AR)/β-catenin complex and physical interaction of AR, β-catenin, and T-cell factor-4 (TCF-4). Inhibition of β-catenin by small inhibitory RNAs significantly decreased testosterone-induced stimulation of myogenic differentiation. Overexpression of TCF-4, a molecule downstream of β-catenin in Wnt signaling cascade, in C3H 10T1/2 cells significantly up-regulated expression of myoD and myosin heavy chain II proteins and of follistatin (Fst), which binds and antagonizes native ligands of the TGF-β/Smad pathway. Gene array analysis of C3H 10T1/2 cells treated with testosterone revealed that testosterone up-regulated the expression of Fst and modified the expression of several signaling molecules involved in the TGF-β/Smad pathway, including Smad7. Lowering of testosterone levels in mice by orchidectomy led to a significant decrease in Fst and Smad7 expression; conversely, testosterone supplementation in castrated mice up-regulated Fst and Smad7 mRNA expression in androgen-responsive levator ani muscle. Testosterone-induced up-regulation of MyoD and myosin heavy chain II proteins in C3H 10T1/2 cells was abolished in cells simultaneously treated with anti-Fst antibody, suggesting an essential role of Fst during testosterone regulation of myogenic differentiation. In conclusion, our data suggest the involvement of AR, β-catenin, and TCF-4 pathway during androgen action to activate a number of Wnt target genes, including Fst, and cross communication with the Smad signaling pathway.

Androgen-induced myogenic differentiation in mouse multipotent C3H 10T1/2 cells is mediated through androgen receptor/β-catenin signaling pathway to upregulate follistatin and cross-communication with TGF-β/Smad signaling pathway.
Kisspeptin-10 Facilitates a Plasma Membrane-Driven Calcium Oscillator in Gonadotropin-Releasing Hormone-1 Neurons
Authors: Constantin Stephanie , Caligioni Claudia Simone , Stojilkovic Stanko , Wray Susan
Published: October 2008

Kisspeptins, the natural ligands of the G-protein-coupled receptor (GPR)-54, are the most potent stimulators of GnRH-1 secretion and as such are critical to reproductive function. However, the mechanism by which kisspeptins enhance calcium-regulated neuropeptide secretion is not clear. In the present study, we used GnRH-1 neurons maintained in mice nasal explants to examine the expression and signaling of GPR54. Under basal conditions, GnRH-1 cells exhibited spontaneous baseline oscillations in intracellular calcium concentration ([Ca2+]i), which were critically dependent on the operation of voltage-gated, tetrodotoxin (TTX)-sensitive sodium channels and were not coupled to calcium release from intracellular pools. Activation of native GPR54 by kisspeptin-10 initiated [Ca2+]i oscillations in quiescent GnRH-1 cells, increased the frequency of calcium spiking in oscillating cells that led to summation of individual spikes into plateau-bursting type of calcium signals in a subset of active cells. These changes predominantly reflected the stimulatory effect of GPR54 activation on the plasma membrane oscillator activity via coupling of this receptor to phospholipase C signaling pathways. Both components of this pathway, inositol 1,3,4-trisphosphate and protein kinase C, contributed to the receptor-mediated modulation of baseline [Ca2+]i oscillations. TTX and 2-aminoethyl diphenylborinate together abolished agonist-induced elevation in [Ca2+]i in almost all cells, whereas flufenamic acid was less effective. Together these results indicate that a plasma membrane calcium oscillator is spontaneously operative in the majority of prenatal GnRH-1 neurons and is facilitated by kisspeptin-10 through phosphatidyl inositol diphosphate hydrolysis and depolarization of neurons by activating TTX-sensitive sodium channels and nonselective cationic channels.

GnRH-1 neurons exhibit a spontaneously active calcium oscillator, dependent on tetrodotoxin-sensitive sodium conductance. Kisspeptin-10/GPR54, via phosphatidyl inositol diphosphate 2 hydrolysis, utilizes these channels and non-selective cationic channels.
Membrane Estrogen Receptor-α Interacts with Metabotropic Glutamate Receptor Type 1a to Mobilize Intracellular Calcium in Hypothalamic Astrocytes
Authors: Kuo John , Hariri Omid R. , Bondar Galyna , Ogi Julie , Micevych Paul
Published: October 2008

Estradiol, acting on a membrane-associated estrogen receptor-α (mERα), induces an increase in free cytoplasmic calcium concentration ([Ca2+]i) needed for progesterone synthesis in hypothalamic astrocytes. To determine whether rapid estradiol signaling involves an interaction of mERα with metabotropic glutamate receptor type 1a (mGluR1a), changes in [Ca2+]i were monitored with the calcium indicator, Fluo-4 AM, in primary cultures of female postpubertal hypothalamic astrocytes. 17β-Estradiol over a range of 1 nm to 100 nm induced a maximal increase in [Ca2+]i flux measured as a change in relative fluorescence [ΔF Ca2+ = 615 ± 36 to 641 ± 47 relative fluorescent units (RFU)], whereas 0.1 nm of estradiol stimulated a moderate [Ca2+]i increase (275 ± 16 RFU). The rapid estradiol-induced [Ca2+]i flux was blocked with 1 μm of the estrogen receptor antagonist ICI 182,780 (635 ± 24 vs. 102 ± 11 RFU, P < 0.001) and 20 nmof the mGluR1a antagonist LY 367385 (617 ± 35 vs. 133 ± 20 RFU, P < 0.001). Whereas the mGluR1a receptor agonist (RS)-3,5-dihydroxyphenyl-glycine (50 μm) also stimulated a robust [Ca2+]i flux (626 ± 23 RFU), combined treatment of estradiol (1 nm) plus (RS)-3,5-dihydroxyphenyl-glycine (50 μm) augmented the [Ca2+]i response (762 ± 17 RFU) compared with either compound alone (P < 0.001). Coimmunoprecipitation demonstrated a direct physical interaction between mERα and mGluR1a in the plasma membrane of hypothalamic astrocytes. These results indicate that mERα acts through mGluR1a, and mGluR1a activation facilitates the estradiol response, suggesting that neural activity can modify estradiol-induced membrane signaling in astrocytes.

For rapid 17β-estradiol-induced membrane signaling in hypothalamic astrocytes, mER-α must interact with mGluR1a resulting in a dramatic increase in free cytoplasmic calcium concentration within seconds.
Facilitative Glucose Transporter Type 1 Is Differentially Regulated by Progesterone and Estrogen in Murine and Human Endometrial Stromal Cells
Authors: Frolova Antonina , Flessner Lauren , Chi Maggie , Kim Sung Tae , Foyouzi-Yousefi Nastaran , Moley Kelle H.
Published: October 2008

Embryo implantation is a highly synchronized event between an activated blastocyst and a receptive endometrium. The success of this process relies on the dynamic interplay of estrogen (E2) and progesterone (P4), however, the details of this interaction are not entirely clear. Recent data implicate E2 and P4 in the regulation of glucose utilization by affecting facilitative glucose transporter (GLUT) expression. In this study we examine GLUT1 expression in murine and human endometrial stromal cells (ESCs) using a primary culture system. We show that expression of GLUT1 is increased during ESC decidualization in vitro. P4 up-regulates, whereas E2 down-regulates, GLUT1 expression. In addition, P4 increases and E2 decreases glucose uptake in ESCs, suggesting that GLUT1 may be a major player in glucose utilization in these cells. Moreover, GLUT1 expression is increased in human ESCs when decidualized in vitro with P4 and dibutyryl cAMP, suggesting a similar role for P4 in human endometrium. In conclusion, an imbalance between P4 and E2 seen in patients with polycystic ovary syndrome, luteal phase defect, and recurrent pregnancy loss may have a critical impact on glucose utilization in the endometrial stroma, and, thus, may be responsible for endometrial dysfunction and failure of embryo implantation in these patient populations.

GLUT1 expression increases during decidualization of endometrial stromal cells in vitro. Progesterone upregulates and estrogen downregulates GLUT1 expression and glucose uptake in these cells.