bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II Enhances Connecting Tubule Glomerular Feedback
Authors: Ren YiLin , D'Ambrosio Martin A. , Garvin Jeffrey L. , Carretero Oscar A.
Published: August 2010

Increasing Na delivery to epithelial Na channels (ENaCs) in the connecting tubule (CNT) causes dilation of the afferent arteriole (Af-Art), a process we call CNT glomerular feedback (CTGF). Angiotensin II (Ang II) stimulates ENaC in the collecting duct via Ang II type 1 receptors. We hypothesized that Ang II in the CNT lumen enhances CTGF by activation of Ang II type 1 receptors, protein kinase C and ENaC. Rabbit afferent arterioles and their adherent CNT were microperfused and preconstricted with norepinephrine. Each experiment involved generating 2 consecutive concentration-response curves by increasing NaCl in the CNT lumen. During the control period, the maximum dilation of the afferent arteriole was 7.9±0.4 μm, and the concentration of NaCl in the CNT needed to achieve half maximal response (EC50) was 34.7±5.2 mmol/L. After adding Ang II (10−9mol/L) to the CNT lumen, the maximal response was 9.5±0.7 μm and the EC50was 11.6±1.3 mmol/L (P=0.01 versus control). Losartan, an Ang II type 1 antagonist (10−6mol/L) blocked the stimulatory effect of Ang II; PD123319, an Ang II type 2 antagonist (10−6mol/L), did not. The protein kinase C inhibitor staurosporine (10−8mol/L) added to the CNT inhibited the stimulatory effect of Ang II. The ENaC inhibitor benzamil (10−6mol/L) prevented both CTGF and its stimulation by Ang II. We concluded that Ang II in the CNT lumen enhances CTGF via activation of Ang II type 1 and that this effect requires activation of protein kinase C and ENaC. Potentiation of CTGF by Ang II could help preserve glomerular filtration rate in the presence of renal vasoconstriction.
Angiopoietin-1 Induces Migration of Monocytes in a Tie-2 and Integrin-Independent Manner
Authors: Ahmad Shakil , Cudmore Melissa J. , Wang Keqing , Hewett Peter , Potluri Rahul , Fujisawa Takeshi , Ahmed Asif
Published: August 2010

Angiopoietin-1 (Ang-1) is an angiogenic growth factor that activates Tie-2 and integrins to promote vessel wall remodeling. The recent finding of the potential proatherogenic effects of Ang-1 prompted us to investigate whether Ang-1 promotes monocyte chemotaxis, endothelial binding, and transendothelial migration, key events in the progression of atherosclerosis. Here, we show that Ang-1 induces chemotaxis of monocytes in a manner that is independent of Tie-2 and integrin binding but dependent on phosphoinositide 3-kinase and heparin. In addition, Ang-1 promoted phosphoinositide 3-kinase-dependent binding of monocytes to endothelial monolayers and stimulated transendothelial migration. Fluorescence-activated cell sorting analysis showed that exogenous Ang-1 adheres directly to monocytes as well as to human umbilical endothelial cells, but neither Tie-2 mRNA nor protein were expressed by primary monocytes. Although Ang-1 binding to human umbilical endothelial cells was partially Tie-2 and integrin dependent, Ang-1 binding to monocytes was independent of these factors. Finally, preincubation of monocytes with soluble heparin abrogated Ang-1 binding to monocytes and migration, and partially prevented Ang-1 binding to human umbilical endothelial cells. In summary, Ang-1 induces chemotaxis of monocytes by a mechanism that is dependent on phosphoinositide 3-kinase and heparin but independent of Tie-2 and integrins. The ability of Ang-1 to recruit monocytes suggests it may play a role in inflammatory angiogenesis and may promote atherosclerosis.
Extratropical Synoptic-Scale Processes and Severe Convection
Authors: Doswell Charles A. , Bosart Lance F.
Published: August 2010

No Abstract available.
The Electrification of Severe Storms
Authors: Williams Earle R.
Published: August 2010

No Abstract available.
The Response of Performance Metrics for Binary Forecasts to Hedging that Approaches Random Change
Authors: Brill Keith F. , Pyle Matthew
Published: August 2010

Critical performance ratio (CPR) expressions for the eight conditional probabilities associated with the 2 × 2 contingency table of outcomes for binary (dichotomous “yes” or “no”) forecasts are derived. Two are shown to be useful in evaluating the effects of hedging as it approaches random change. The CPR quantifies how the probability of detection (POD) must change as frequency bias changes, so that a performance measure (or conditional probability) indicates an improved forecast for a given value of frequency bias. If yes forecasts were to be increased randomly, the probability of additional correct forecasts (hits) is given by the detection failure ratio (DFR). If the DFR for a performance measure is greater than the CPR, the forecast is likely to be improved by the random increase in yes forecasts. Thus, the DFR provides a benchmark for the CPR in the case of frequency bias inflation. If yes forecasts are decreased randomly, the probability of removing a hit is given by the frequency of hits (FOH). If the FOH for a performance measure is less than the CPR, the forecast is likely to be improved by the random decrease in yes forecasts. Therefore, the FOH serves as a benchmark for the CPR if the frequency bias is decreased. The closer the FOH (DFR) is to being less (greater) than or equal to the CPR, the more likely it may be to enhance the performance measure by decreasing (increasing) the frequency bias. It is shown that randomly increasing yes forecasts for a forecast that is itself better than a randomly generated forecast can improve the threat score but is not likely to improve the equitable threat score. The equitable threat score is recommended instead of the threat score whenever possible.
Effects of Workplace Bullying on How Women Work
Authors: MacIntosh Judith , Wuest Judith , Gray Marilyn Merritt , Aldous Sarah
Published: August 2010

Work is central to well-being but working is problematic when people experience workplace bullying, which includes psychological, physical, and sexual abuse or harassment. The purpose of the present grounded theory study was to extend current understanding, from the perspective of women, of how workplace bullying affects their work and how they engage in the workforce. The study was conducted in eastern Canada with 36 English-speaking women who had been bullied in the workplace. They reported mainly psychological bullying. The central problem for women is they cannot continue working as they had before the workplace bullying. The authors named a four-stage process of how women address this problem as “Doing Work Differently.” The four stages are Being Conciliatory, Reconsidering, Reducing Interference, and Redeveloping Balance. The process is influenced by women’s support systems, the effects on their health, and financial circumstances. There are implications for public education, workplace policies, and health care workers.
Double ECMO in severe ARDS: report of an outstanding case and literature review
Authors: Litmathe Jens , Dapunt Otto
Published: August 2010

We report on a 49-year-old male patient who suffered from severe herpes simplex (HSV) pneumonia after a fall-from-height injury, causing a circumscript type B aortic dissection.The subsequent occurrence of ARDS required a veno-venous ECMO circuit that was upgraded to a veno-arterial system due to further oxygenation deficits. Following continued respiratory deterioration, the ECMO system already in place had to be complemented by a second veno-arterial line. After the onset of recovery and because of a developing of a disseminated intravasal coagulation, the double ECMO circuit was replaced by a pumpless extracorporeal lung assist system (PECLA). The patient recovered completely under systemic virostatic therapy.
A new real-time and precision capnography for human respiration carbon dioxide concentration
Authors: Jiachen Yang  , Bin Wang  , Ran Xu  , Lei Wang
Published: August 2010

This paper is a description of the designing of a new mainstream device to measure human respiration carbon dioxide concentration, based on non-dispersive infrared (NDIR) absorption technology. The device can be used to accurately monitor the cardiopulmonary status during anaesthesia and mechanical ventilation in real time. This new device can not only make up the error of real-time gas measurement of the side-stream device, but also make up the accuracy of the main-stream device. In the paper, four issues which can affect the measurement accuracy were considered: respiration gas flow, turbulence of the light source with all ranges of wavelength, temperature drift and signal noise. The experimental results showed that the device could produce a stable output signal and deviation of measurement accuracy could be achieved to within 4%.
Arabic—Arabic Courtroom Translation in Lebanon
Authors: Khachan Victor A.
Published: August 2010

In the Arab world, the comprehension gap between Colloquial and Standard Arabic has been recognized as a major force behind illiteracy and its endless negative repercussions. One adverse impact of this comprehension gap manifests itself in the courtroom. Courtroom translation in the Arab world (i.e. consecutive interpreting/reporting from Colloquial into Standard Arabic) occurs systematically and is the only means of documenting courtroom proceedings. Despite its functional importance in the light of language manoeuvrability and translation accuracy, the legal implications of the Colloquial—Standard Arabic proximity in the context of linguistic rights have not been theoretically nor empirically researched. Accordingly, this paper introduces the dynamics of language use in a hierarchical judicial system in one Arab country, Lebanon. This paper is a theoretical first brick in the wall of linguistic rights in the Lebanese courtroom, where — in the absence of a jury system — linguistic discretion in the legal decision-making process rests upon the bench judge. In addition, this paper highlights the vulnerability of illiterate people vis-à-vis the use of Standard Arabic in legal settings at the expense of their preferred first or only language, Lebanese Colloquial.
Sport events and ethnic reconciliation: Attempting to create social change between Sinhalese, Tamil and Muslim sportspeople in war-torn Sri Lanka
Authors: Schulenkorf Nico
Published: August 2010

Reconciliation is about bringing disparate communities together and creating the communication necessary to reduce intergroup barriers, generate understanding, and connect with others to achieve a peaceful togetherness. This article investigates the role of sport events in contributing to reconciliation and inclusive social change between disparate communities in ethnically divided Sri Lanka. Following an interpretive mode of enquiry, findings suggest that if strategically designed, sport events allow the establishment of interpersonal friendships and the creation of inclusive social identities along national lines, organizational lines, common interests and imagined factors. Events can create ‘momenta of togetherness’ for members of disparate ethnic groups and as such may contribute to positive social change and a sense of imagiNation. While sport events provide a starting point, booster and catalyst for positive social change and development on a community level, they need to be integrated into a larger agenda of socio-political support to make a significant contribution to reconciliation and peace in divided societies.
Critical left-realism and sport interventions in divided societies
Authors: Sugden John
Published: August 2010

What, if any, is the value of sport to processes of peace and reconciliation? After introducing the largely rhetorical arguments for and against the value of using sport as a vehicle to promote peace building in divided societies, this article makes a more detailed and forensic examination of the evidence based on: the role played by sport in South Africa before and after apartheid; and second, drawing upon the author’s own experiences garnered over more than two decades of conducting research and leading sport-based intervention initiatives in Northern Ireland and Israel. The article argues that sport is intrinsically value neutral and under carefully managed circumstances it can make a positive if modest contribution to peace building. The mobilization of an engaged sociological imagination in the context of a broader human rights agenda is central to this contribution. Drawing upon notions of pragmatism, left realism and praxis, the article concludes by presenting a ‘ripple effect’ model that illustrates the circumstances under which sport can make a difference in the promotion of social justice and human rights in deeply divided societies.
Kid Crosby or Golden Boy: Sidney Crosby, Canadian national identity, and the policing of hockey masculinity
Authors: Allain Kristi A
Published: August 2010

In this article, I will explore how Canadian national identity is constructed with regard to ice hockey. National Hockey League (NHL) star, Sidney Crosby has been positioned as an important symbol of Canadian national identity. Given Crosby’s perceived importance, particularly within the Canadian media, I will examine how he is constructed as an appropriate model of Canadian masculinity and Canadian national identity. Crosby’s expressions of masculinity are not to be left to chance and for that reason there has been constant surveillance and critique of his expressions of masculinity. Interestingly, although the media tends to construct Crosby as a model of Canadian masculine identity, fans of the game (as well as some players and others in the media) frequently challenge this construction.
Modeling Concurrent Design Method for Product Variety
Authors: Ko Yao-Tsung , Kuo Ping-Hong
Published: August 2010

This study presents a systematic method for concurrently developing the product variety. The proposed method integrates three approaches successively. First, the quality function deployment approach identifies the external driven factors of design variation. Second, the quantified design structure matrix technique is proposed to identify the internal interactions and build the hierarchy of components interactions within a product. Third, the morphology analysis approach is applied to visualize the concepts of the developing product through creating design solutions for every component and module. This approach represents the design priority and related design constrains using a structural graph for helping designers to create design solutions in a product design for variety. A case study is employed to illustrate this method and the result validates the feasibility and effectiveness.
Facilitators, Challenges, and Collaborative Activities in Faith and Health Partnerships to Address Health Disparities
Authors: Kegler Michelle C. , Hall Sarah M. , Kiser Mimi
Published: August 2010

Interest in partnering with faith-based organizations (FBOs) to address health disparities has grown in recent years. Yet relatively little is known about these types of partnerships. As part of an evaluation of the Institute for Faith and Public Health Collaborations, representatives of 34 faith—health teams ( n = 61) completed semi-structured interviews. Interviews were tape recorded, transcribed, and coded by two members of the evaluation team to identify themes. Major facilitators to faith—health collaborative work were passion and commitment, importance of FBOs in communities, favorable political climate, support from community and faith leaders, diversity of teams, and mutual trust and respect. Barriers unique to faith and health collaboration included discomfort with FBOs, distrust of either health agencies or FBOs, diversity within faith communities, different agendas, separation of church and state, and the lack of a common language. Findings suggest that faith—health partnerships face unique challenges but are capable of aligning resources to address health disparities.
Wedge-issue dynamics and party position shifts
Authors: Seo Jungkun
Published: August 2010

Even when the stakes of party-building are high, political parties often find their members divided over a key policy position. In post-Reconstruction America, the hot-button issue of excluding Chinese immigrant workers strengthened Democratic cohesion while splitting the ‘party of Lincoln’. Previous research has not completely investigated the role of party competition and cohesiveness in paving the way for passage of the Chinese exclusion laws. In this investigation of the legislative politics of banning the Chinese from 1879 to 1882, it is found that cross-pressured members sometimes facilitate party transformation. The evidence demonstrates that partisan responses to potential wedge issues are a previously unnoticed source of explanation of eventual party position changes.
Increasing physical activity in patients with arthritis: a tailored health promotion program
Authors: Ehrlich-Jones Linda , Mallinson Trudy , Fischer Heidi , Bateman Jillian , Semanik Pamela A. , Spring Bonnie , Ruderman Eric , Chang Rowland W.
Published: August 2010

Objective: Despite recent studies showing the benefit of physical activity for people with arthritis, the vast majority of persons with arthritis are not sufficiently physically active. The purpose of this report is to describe a tailored health promotion intervention aimed at increasing physical activity among persons with arthritis. The intervention is designed to be useful for health systems and insurers interested in a chronic disease management program that could be disseminated to large populations of arthritis patients.

Methods: The intervention is carried out by a clinician who is designated as the client’s physical activity advocate. The approach emphasizes motivational interviewing, individualized goal setting, tailored strategies for increasing physical activity and for monitoring progress, and a plan of 2 years of follow-up. The intervention includes a standardized assessment of barriers to and strengths supporting increased lifestyle physical activity. A randomized, controlled trial is underway to evaluate the efficacy and cost-effectiveness of this intervention.

Conclusion: This intervention is unique in that it implements a program tailored to the individual that focuses on lifestyle physical activity and long-term monitoring. The approach recognizes that persons with arthritis present with varying levels of motivation for change in physical activity and that behavior change can take a long time to become habitual.
Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer
Authors: Raman Maitreyi , Milestone Andrew N. , Walters Julian R.F. , Hart Ailsa L. , Ghosh Subrata
Published: August 2010

Over the past 5 years, there has been a rapid resurgence of interest in vitamin D outside of its traditional role in metabolic bone disease. Some nontraditional roles ascribed to vitamin D include anti-inflammatory and immune-modulating effects. These effects have led to possible implications in the pathophysiology of immune-mediated diseases including multiple sclerosis and inflammatory bowel disease (IBD). In addition, vitamin D insufficiency has been linked to higher rates of cancers including colon, prostate and breast cancers. Given these diverse associations of vitamin D and disease states, this review describes recent advances with regard to vitamin D and gastrointestinal diseases, in particular IBD and colorectal cancer.
CCR7 impairs hematopoiesis after hematopoietic stem cell transplantation increasing susceptibility to invasive aspergillosis
Authors: Hartigan Adam J. , Kallal Lara E. , Hogaboam Cory M.
Published: August 2010

Hematopoietic stem cell transplantation (HSCT) is limited by patient susceptibility to opportunistic infections. One of the most devastating infections after HSCT is invasive aspergillosis (IA), a life-threatening disease caused by Aspergillus fumigatus. Transplantation of hematopoietic stem cells (HSCs) and myeloid progenitor cells (MPCs) has been shown to mediate protection against IA, but little is known about the factors that regulate HSC and MPC cell expansion after transplantation. Herein, we investigated the role of CCR7 in a murine model of IA after combined HSC and MPC transplantation into lethally irradiated wild-type (WT) mice. Nonirradiated CCR7−/− mice had expanded populations of HSCs in the bone marrow and spleen, compared with WT mice. Irradiated WT mice reconstituted with CCR7−/− HSCs and MPCs had increased survival, decreased fungal burden, and enhanced myeloid leukocyte numbers during IA, compared with WT controls. In addition, WT mice reconstituted with WT HSCs and MPCs and treated with anti-CCR7 exhibited accelerated myeloid cell expansion similar to that observed in CCR7−/−→WT chimeras. Thus, removal of the inhibitory effects of CCR7 through genetic alteration or ligand immunoneutralization enhanced myeloid reconstitution, thereby accelerating fungal clearance in a murine model of IA.
Identification of testis-relevant genes using in silico analysis from testis ESTs and cDNA microarray in the black tiger shrimp (Penaeus monodon)
Authors: Wongsurawat Thidathip , Leelatanawit Rungnapa , Thamniemdee Natechanok , Uawisetwathana Umaporn , Karoonuthaisiri Nitsara , Menasveta Piamsak , Klinbunga Sirawut
Published: August 2010

Background

Poor reproductive maturation of the black tiger shrimp (Penaeus monodon) in captivity is one of the serious threats to sustainability of the shrimp farming industry. Understanding molecular mechanisms governing reproductive maturation processes requires the fundamental knowledge of integrated expression profiles in gonads of this economically important species. In P. monodon, a non-model species for which the genome sequence is not available, expressed sequence tag (EST) and cDNA microarray analyses can help reveal important transcripts relevant to reproduction and facilitate functional characterization of transcripts with important roles in male reproductive development and maturation.

Results

In this study, a conventional testis EST library was exploited to reveal novel transcripts. A total of 4,803 ESTs were unidirectionally sequenced and analyzed in silico using a customizable data analysis package, ESTplus. After sequence assembly, 2,702 unique sequences comprised of 424 contigs and 2,278 singletons were identified; of these, 1,133 sequences are homologous to genes with known functions. The sequences were further characterized according to gene ontology categories (41% biological process, 24% molecular function, 35% cellular component). Through comparison with EST libraries of other tissues of P. monodon, 1,579 transcripts found only in the testis cDNA library were identified. A total of 621 ESTs have not been identified in penaeid shrimp. Furthermore, cDNA microarray analysis revealed several ESTs homologous to testis-relevant genes were more preferentially expressed in testis than in ovary. Representatives of these transcripts, homologs of saposin (PmSap) and Dmc1 (PmDmc1), were further characterized by RACE-PCR. The more abundant expression levels in testis than ovary of PmSap and PmDmc1 were verified by quantitative real-time PCR in juveniles and wild broodstock of P. monodon.

Conclusions

Without a genome sequence, a combination of EST analysis and high-throughput cDNA microarray technology can be a useful integrated tool as an initial step towards the identification of transcripts with important biological functions. Identification and expression analysis of saposin and Dmc1 homologs demonstrate the power of these methods for characterizing functionally important genes in P. monodon.
Mutations in the WTX- gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers
Authors: Scheel Silvio K , Porzner Marc , Pfeiffer Sabine , Ormanns Steffen , Kirchner Thomas , Jung Andreas
Published: August 2010

Background

Genetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCsAPC(Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like theAPC-,AXIN2- orCTNNBI(β-CATENIN) gene itself. Recently in Wilms tumors,WTX(Wilms tumor gene on the X-chromosome) was discovered as another gene involved in the destruction of β-CATENIN. As theWTX-gene harbors a short T6-microsatellite in its N-terminal coding region, we hypothesized that frameshift-mutations might occur in MSI-H CRCs in theWTXgene, thus additionally contributing to the stabilization of β-CATENIN in human CRCs.

Methods

DNA was extracted from 632 formalin-fixed, paraffin-embedded metastatic CRCs (UICCIV) and analyzed for MSI-H by investigating the stability of the highly sensitive microsatellite markers BAT25 and BAT26 applying fluorescence capillary electrophoresis (FCE). Then, in the MSI-H cases, well described mutational hot spot regions from theAPC-,AXIN2- andCTNNBIgenes were analyzed for genomic alterations by didesoxy-sequencing while theWTXT6-microsatellite was analyzed by fragment analysis. Additionally, the PCR products of T5-repeats were subcloned and mutations were validated using didesoxy-sequencing. Furthermore, theKRASand theBRAFproto-oncogenes were analyzed for the most common activating mutations applying pyro-sequencing. mRNA expression ofWTXfrom MSI-H and MSS cases and a panel of colorectal cancer cell lines was investigated using reverse transcription (RT-) PCR and FCE.

Results

In our cohort of 632 metastatic CRCs (UICCIV) we identified 41 MSI-H cases (6.5%). Two of the 41 MSI-H cases (4.8%) displayed a frameshift mutation in the T6-repeat resulting in a T5sequence. Only one case, a male patient, expressed the mutatedWTXgene while being wild type for all other investigated genes.

Conclusion

Mutations in theWTX-gene might compromise the function of the β-CATENIN destruction complex in only a small fraction of MSI-H CRCs thus contributing to the process of carcinogenesis.
Association between weight perception and socioeconomic status among adults in the Seychelles
Authors: Alwan Heba , Viswanathan Bharathi , Williams Julita , Paccaud Fred , Bovet Pascal
Published: August 2010

Background

Few studies have examined the association between weight perception and socioeconomic status (SES) in sub-Saharan Africa, and none made this association based on education, occupation and income simultaneously.

Methods

Based on a population-based survey (n = 1255) in the Seychelles, weight and height were measured and self-perception of one's own body weight, education, occupation, and income were assessed by a questionnaire. Individuals were considered to have appropriate weight perception when their self-perceived weight matched their actual body weight.

Results

The prevalence of overweight and obesity was 35% and 28%, respectively. Multivariate analysis among overweight/obese persons showed that appropriate weight perception was directly associated with actual weight, education, occupation and income, and that it was more frequent among women than among men. In a model using all three SES indicators together, only education (OR = 2.5; 95% CI: 1.3-4.8) and occupation (OR = 2.3; 95% CI: 1.2-4.5) were independently associated with appropriate perception of being overweight. The OR reached 6.9 [95% CI: 3.4-14.1] when comparing the highest vs. lowest categories of SES based on a score including all SES indicators and 6.1 [95% CI: 3.0-12.1] for a score based on education and occupation.

Conclusions

Appropriately perceiving one's weight as too high was associated with different SES indicators, female sex and being actually overweight. These findings suggest means and targets for clinical and population-based interventions for weight control. Further studies should examine whether these differences in weight perception underlie differences in cognitive skills, healthy weight norms, or body size ideals.
Comparing interfacial dynamics in protein-protein complexes: an elastic network approach
Authors: Zen Andrea , Micheletti Cristian , Keskin Ozlem , Nussinov Ruth
Published: August 2010

Background

The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces.

Results

The interface dynamics was characterized by means of an elastic network model for 22 representative dimers covering three main interface types. The three groups gather dimers sharing the same interface but with good (type I) or poor (type II) similarity of the overall fold, or dimers sharing only one of the semi-interfaces (type III). The set comprises obligate dimers, which are complexes for which no structural representative of the free form(s) is available. Considerations were accordingly limited to bound and unbound forms of the monomeric subunits of the dimers. We proceeded by first computing the mobility of amino acids at the interface of the bound forms and compare it with the mobility of (i) other surface amino acids (ii) interface amino acids in the unbound forms. In both cases different dynamic patterns were observed across interface types and depending on whether the interface belongs to an obligate or non-obligate complex.

Conclusions

The comparative investigation indicated that the mobility of amino acids at the dimeric interface is generally lower than for other amino acids at the protein surface. The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex. In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones. The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.
Artemisone effective against murine cerebral malaria
Authors: Waknine-Grinberg Judith H , Hunt Nicholas , Bentura-Marciano Annael , McQuillan James A , Chan Ho-Wai , Chan Wing-Chi , Barenholz Yechezkel , Haynes Richard K , Golenser Jacob
Published: August 2010

Background

Artemisinins are the newest class of drug approved for malaria treatment. Due to their unique mechanism of action, rapid effect on Plasmodium, and high efficacy in vivo, artemisinins have become essential components of malaria treatment. Administration of artemisinin derivatives in combination with other anti-plasmodials has become the first-line treatment for uncomplicated falciparum malaria. However, their efficiency in cases of cerebral malaria (CM) remains to be determined.

Methods

The efficacy of several artemisinin derivatives for treatment of experimental CM was evaluated in ICR or C57BL/6 mice infected byPlasmodium bergheiANKA. Both mouse strains serve as murine models for CM.

Results

Artemisone was the most efficient drug tested, and could prevent death even when administered at relatively late stages of cerebral pathogenesis. No parasite resistance to artemisone was detected in recrudescence. Co-administration of artemisone together with chloroquine was more effective than monotherapy with either drug, and led to complete cure. Artemiside was even more effective than artemisone, but this substance has yet to be submitted to preclinical toxicological evaluation.

Conclusions

Altogether, the results support the use of artemisone for combined therapy of CM.
IDOMAL: an ontology for malaria
Authors: Topalis Pantelis , Mitraka Elvira , Bujila Ioana , Deligianni Elena , Dialynas Emmanuel , Siden-Kiamos Inga , Troye-Blomberg Marita , Louis Christos
Published: August 2010

Background

Ontologies are rapidly becoming a necessity for the design of efficient information technology tools, especially databases, because they permit the organization of stored data using logical rules and defined terms that are understood by both humans and machines. This has as consequence both an enhanced usage and interoperability of databases and related resources. It is hoped that IDOMAL, the ontology of malaria will prove a valuable instrument when implemented in both malaria research and control measures.

Methods

The OBOEdit2 software was used for the construction of the ontology. IDOMAL is based on the Basic Formal Ontology (BFO) and follows the rules set by the OBO Foundry consortium.

Results

The first version of the malaria ontology covers both clinical and epidemiological aspects of the disease, as well as disease and vector biology. IDOMAL is meant to later become the nucleation site for a much larger ontology of vector borne diseases, which will itself be an extension of a large ontology of infectious diseases (IDO). The latter is currently being developed in the frame of a large international collaborative effort.

Conclusions

IDOMAL, already freely available in its first version, will form part of a suite of ontologies that will be used to drive IT tools and databases specifically constructed to help control malaria and, later, other vector-borne diseases. This suite already consists of the ontology described here as well as the one on insecticide resistance that has been available for some time. Additional components are being developed and introduced into IDOMAL.
Loss, mutation and deregulation of L3MBTL4 in breast cancers
Authors: Addou-Klouche Lynda , Adélaïde José , Finetti Pascal , Cervera Nathalie , Ferrari Anthony , Bekhouche Ismahane , Sircoulomb Fabrice , Sotiriou Christos , Viens Patrice , Moulessehoul Soraya , Bertucci François , Birnbaum Daniel , Chaffanet Max
Published: August 2010

Background

Many alterations are involved in mammary oncogenesis, including amplifications of oncogenes and losses of tumor suppressor genes (TSG). Losses may affect almost all chromosome arms and many TSGs remain to be identified.

Results

We studied 307 primary breast tumors and 47 breast cancer cell lines by high resolution array comparative genomic hybridization (aCGH). We identified a region on 18p11.31 lost in about 20% of the tumors and 40% of the cell lines. The minimal common region of loss (Chr18:6,366,938-6,375,929 bp) targeted theL3MBTL4gene. This gene was also targeted by breakage in one tumor and in two cell lines. We studied the exon sequence ofL3MBTL4in 180 primary tumor samples and 47 cell lines and found six missense and one nonsense heterozygous mutations. Compared with normal breast tissue,L3MBTL4mRNA expression was downregulated in 73% of the tumors notably in luminal, ERBB2 and normal-like subtypes. Losses of the 18p11 region were associated with lowL3MBTL4expression level. Integrated analysis combining genome and gene expression profiles of the same tumors pointed to 14 other potential 18p TSG candidates. Downregulated expression ofZFP161, PPP4R1andYES1was correlated with luminal B molecular subtype. LowZFP161gene expression was associated with adverse clinical outcome.

Conclusion

We have identifiedL3MBTL4as a potential TSG of chromosome arm 18p. The gene is targeted by deletion, breakage and mutations and its mRNA is downregulated in breast tumors. Additional 18p TSG candidates might explain the aggressive phenotype associated with the loss of 18p in breast tumors.
A qualitative study of the promotion of exclusive breastfeeding by health professionals in Niamey, Niger
Authors: Moussa Abba Aïssata , De Koninck Maria , Hamelin Anne-Marie
Published: August 2010

Background

The practice of exclusive breastfeeding depends on various factors related to both mothers and their environment, including the services delivered by health professionals. It is known that support and counseling by health professionals can improve rates, early initiation and total duration of breastfeeding, particularly exclusive breastfeeding. Mothers' decisions are influenced by health professionals' advice. However, in Niger the practice of exclusive breastfeeding is almost non-existent.

The purpose of this exploratory study, of which some results are presented here, was to document health professionals' attitudes and practices with regard to exclusive breastfeeding promotion in hospital settings in the urban community of Niamey, Niger.

Methods

Fieldwork was conducted in Niamey, Niger. A qualitative approach was employed. Health professionals' practices were observed in a sample of frontline public healthcare facilities.

Results

The field observation results presented here indicate that exclusive breastfeeding is not promoted in healthcare facilities because the health professionals do not encourage it and their practices are inappropriate. Some still have limited knowledge or are misinformed about this practice or do not believe in it. They do not systematically discuss exclusive breastfeeding with mothers, or they mention it only briefly and without giving any explanation. Worse still, some encourage the use of breast milk substitutes, which are frequently promoted in healthcare facilities. Thus mothers often receive contradictory messages.

Conclusion

The results suggest the need to train or retrain health professionals with regard to exclusive breastfeeding, and regularly supervise their activities.
Assembly of the outer retina in the absence of GABA synthesis in horizontal cells
Authors: Schubert Timm , Huckfeldt Rachel M , Parker Edward , Campbell John E , Wong Rachel OL
Published: August 2010

Background

The inhibitory neurotransmitter gamma-amino-butyric acid (GABA) not only modulates excitability in the mature nervous system but also regulates neuronal differentiation and circuit development. Horizontal cells, a subset of interneurons in the outer retina, are transiently GABAergic during the period of cone photoreceptor synaptogenesis. In rodents, both horizontal cells and cone axonal terminals express GABAA receptors. To explore the possibility that transient GABA expression in mouse neonatal horizontal cells influences the structural development of synaptic connectivity in the outer retina, we examined a mutant in which expression of GAD67, the major synthesizing enzyme for GABA, is selectively knocked out in the retina.

Results

Immunocytochemistry and electron microscopy revealed that the assembly of triad synapses involving cone axonal pedicles and the dendrites of horizontal and bipolar cells is unaffected in the mutant retina. Moreover, loss of GABA synthesis in the outer retina did not perturb the spatial distributions and cell densities of cones and horizontal cells. However, there were some structural alterations at the cellular level: the average size of horizontal cell dendritic clusters was larger in the mutant, and there was also a small but significant increase in cone photoreceptor pedicle area. Moreover, metabotropic glutamate receptor 6 (mGluR6) receptors on the dendrites of ON bipolar cells occupied a slightly larger proportion of the cone pedicle in the mutant.

Conclusions

Together, our analysis shows that transient GABA synthesis in horizontal cells is not critical for synapse assembly and axonal and dendritic lamination in the outer retina. However, pre- and postsynaptic structures are somewhat enlarged in the absence of GABA in the developing outer retina, providing for a modest increase in potential contact area between cone photoreceptors and their targets. These findings differ from previous results in which pharmacological blockade of GABAA receptors in the neonatal rabbit retina caused a reduction in cone numbers and led to a grossly disorganized outer retina.
Tian Xian Liquid (TXL) induces apoptosis in HT-29 colon cancer cell in vitro and inhibits tumor growth in vivo
Authors: Liu Qing , Tong Yao , Sze Stephen ChoWing , Liu Wing Keung , Lam Lam , Chu Ellie ShihngMeir , Yow Christine MiuNgan
Published: August 2010

Background

Tian Xian Liquid (TXL) is a Chinese medicine decoction and has been used as an anticancer dietary supplement. The present study aims to investigate the effects of TXL on the apoptosis of HT-29 cells and tumor growth in vivo.

Method

HT-29 colon cancer cells were treated with gradient dilution of TXL. The mitochondrial membrane potential was measured by JC-1 assay. The release of cytochrome c from mitochondrial and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, 9 were examined by Western blot analysis. HT-29 cells were implanted in nude mice to examine the effects of TXL on tumor growth.

Result

TXL inhibited HT-29 xenografted model and showed a strong and dose-dependent inhibitory effect on the proliferation of HT-29 cells. Mitochondrial membrane potential was reduced by TXL at the concentration of 0.5% above. For Western blot analysis, an increase in Bax expression and a decrease in Bcl-2 expression were observed in TXL-treated cells. TXL treatment increased the protein level of cleaved casepase-3 and caspase-9, and the release of cytochrome c in cytoplasm was up-regulated as well.

Conclusion

TXL significantly inhibits cell proliferation in the HT-29 cells and HT-29 xenografted model via the mitochondrial cell death pathway.
Recurrent lower gastrointestinal bleeding from idiopathic ileocolonic varices: a case report
Authors: Krishna Ravula Phani , Singh Rajneesh Kumar , Ghoshal Uday C
Published: August 2010

Introduction

Varices of the colon are a rare cause of lower gastrointestinal bleeding, usually associated with portal hypertension due to liver cirrhosis or other causes of portal venous obstruction. Idiopathic colonic varices are extremely rare. Recognition of this condition is important as idiopathic colonic varices may be a cause of recurrent lower gastrointestinal bleeding.

Case presentation

We report the case of a 21-year-old Asian man from north India who presented with recurrent episodes of lower gastrointestinal bleeding. Colonoscopy revealed varices involving the terminal ileum and colon to the sigmoid. Thorough evaluation was undertaken to rule out any underlying portal hypertension. Our patient underwent subtotal colectomy including resection of involved terminal ileum and an ileorectal anastomosis.

Conclusion

Colonic varices are an uncommon cause of lower gastrointestinal bleeding. Idiopathic colonic varices are diagnosed after excluding underlying liver disease and portal hypertension. Recognition of this condition is important as prognosis is good in the absence of liver disease and is curable by resection of the involved bowel.
Benign cervical multi-nodular goiter presenting with acute airway obstruction: a case report
Authors: Sharma Anu , Naraynsingh Vijay , Teelucksingh Surujpaul
Published: August 2010

Introduction

Benign cervical goiters rarely cause acute airway obstruction.

Case presentation

We report the case of a 64-year-old woman of African descent who presented with acute shortness of breath. She required immediate intubation and later a total thyroidectomy for a benign cervical multi-nodular goiter with no retrosternal tracheal compression.

Conclusion

Benign multi-nodular goiters are commonly left untreated once euthyroid. Peak inspiratory flow rates should be measured via spirometry in all goiters to assess the degree of tracheal compression. Once tracheal compression is identified, an elective total thyroidectomy should be performed to prevent morbidity and mortality from acute airway obstruction.
Monitoring a CO2 flood with fine time steps: Salt Creek 4D
Authors: O'brien John , Moran John , Wilbourn Gerry , Morris Stan , Andersen Janel , Quezada Oscar
Published: August 2010

Time-lapse seismic is now recognized as a powerful tool for monitoring [Formula: see text] floods and provides valuable information on the advance of the flood, the area which has been swept, and in many cases identifies areas that are unswept or poorly swept. However, these programs typically include just a baseline and one or a limited number of monitor surveys recorded over a relatively long time period. As such, they do not yield the full value of which they are capable. Recording a multiplicity of monitor surveys at fine time intervals can provide significantly more complete characterization of the flood, enabling us to monitor the evolution of the flood in a true time-lapse sense.
Near-surface geophysical techniques for geohazards investigations: Some Canadian examples
Authors: Hunter J. A. , Burns R. A. , Good R. L. , Pullan S. E. , Pugin A. , Crow H.
Published: August 2010

Over the last 40 years, there has been an expansion of activity in applications of near-surface geophysical techniques for various types of geohazards investigations in Canada; numerous national and international research groups have been working with the Near Surface Geophysics Section of the Geological Survey of Canada to develop techniques for specific Canadian engineering and environmental geohazards problems. A few of the more interesting examples from widespread parts of the country are discussed in this paper.
Genomic Index of Sensitivity to Endocrine Therapy for Breast Cancer
Authors: Symmans W. Fraser , Hatzis Christos , Sotiriou Christos , Andre Fabrice , Peintinger Florentia , Regitnig Peter , Daxenbichler Guenter , Desmedt Christine , Domont Julien , Marth Christian , Delaloge Suzette , Bauernhofer Thomas , Valero Vicente , Booser Daniel J. , Hortobagyi Gabriel N. , Pusztai Lajos
Published: August 2010

Purpose

We hypothesize that measurement of gene expression related to estrogen receptor α (ER; gene name ESR1) within a breast cancer sample represents intrinsic tumoral sensitivity to adjuvant endocrine therapy.

Methods

A genomic index for sensitivity to endocrine therapy (SET) index was defined from genes coexpressed with ESR1 in 437 microarray profiles from newly diagnosed breast cancer, unrelated to treatment or outcome. The association of SET index and ESR1 levels with distant relapse risk was evaluated from microarrays of ER-positive breast cancer in two cohorts who received 5 years of tamoxifen alone as adjuvant endocrine therapy (n = 225 and 298, respectively), a cohort who received neoadjuvant chemotherapy followed by tamoxifen and/or aromatase inhibition (n = 122), and two cohorts who received no adjuvant systemic therapy (n = 208 and 133, respectively).

Results

The SET index (165 genes) was significantly associated with distant relapse or death risk in both tamoxifen-treated cohorts (hazard ratio [HR] = 0.70, 95% CI, 0.56 to 0.88, P = .002; and HR = 0.76, 95% CI, 0.63 to 0.93, P = .007) and in the chemo-endocrine–treated cohort (HR = 0.19; 95% CI, 0.05 to 0.69, P = .011) independently from pathologic response to chemotherapy, but was not prognostic in two untreated cohorts. No distant relapse or death was observed after tamoxifen alone if node-negative and high SET or after chemo-endocrine therapy if intermediate or high SET.

Conclusion

The SET index of ER-related transcription predicted survival benefit from adjuvant endocrine therapy, not inherent prognosis. Prior chemotherapy seemed to enhance the efficacy of adjuvant endocrine therapy related to SET index.