bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ubiquitin-Interacting Motif–Containing Protein RAP80 Interacts with BRCA1 and Functions in DNA Damage Repair Response
Authors: Yan Jun , Kim Yong-Sik , Yang Xiao-Ping , Li Li-Ping , Liao Grace , Xia Fen , Jetten Anton M.
Published: July 2007

In this study, we examine the potential role of receptor-associated protein 80 (RAP80), a nuclear protein containing two ubiquitin-interacting motifs (UIM), in DNA damage response and double-strand break (DSB) repair. We show that following ionizing radiation and treatment with DNA-damaging agents, RAP80 translocates to discrete nuclear foci that colocalize with those of γ-H2AX. The UIMs and the region of amino acids 204 to 304 are critical for the relocalization of RAP80 to ionizing radiation–induced foci (IRIF). These observations suggest that RAP80 becomes part of a DNA repair complex at the sites of IRIF. We also show that RAP80 forms a complex with the tumor repressor BRCA1 and that this interaction is mediated through the BRCA1 COOH-terminal repeats of BRCA1. The UIMs are not required for the interaction of RAP80 with BRCA1. Knockdown of RAP80 in HEK293 cells significantly reduced DSB-induced homology-directed recombination (HDR). Moreover, inhibition of RAP80 expression by small interfering RNA increased radiosensitivity, whereas increased radioresistance was observed in human breast cancer MCF-7 cells with overexpression of RAP80. Taken together, our data suggest that RAP80 plays an important role in DNA damage response signaling and HDR-mediated DSB repair. We further show that RAP80 can function as a substrate of the ataxia-telangiectasia mutated protein kinase in vitro, which phosphorylates RAP80 at Ser205 and Ser402. We show that this phosphorylation is not required for the migration of RAP80 to IRIF. [Cancer Res 2007;67(14):6647–56]
β
1
-Adrenergic Receptor Autoantibodies Mediate Dilated Cardiomyopathy by Agonistically Inducing Cardiomyocyte Apoptosis
Authors: Jane-wit Daniel , Altuntas Cengiz Z. , Johnson Justin M. , Yong Sandro , Wickley Peter J. , Clark Pamela , Wang Qing , Popović Zoran B. , Penn Marc S. , Damron Derek S. , Perez Dianne M. , Tuohy Vincent K.
Published: July 2007

Background—

Antibodies to the β
1
-adrenergic receptor (β
1
AR) are detected in a substantial number of patients with idiopathic dilated cardiomyopathy (DCM). The mechanism whereby these autoantibodies exert their pathogenic effect is unknown. Here, we define a causal mechanism whereby β
1
AR-specific autoantibodies mediate noninflammatory cardiomyocyte cell death during murine DCM.

Methods and Results—

We used the β
1
AR protein as an immunogen in SWXJ mice and generated a polyclonal battery of autoantibodies that showed selective binding to the β
1
AR. After transfer into naive male hosts, β
1
AR antibodies elicited fulminant DCM at high frequency. DCM was attenuated after immunoadsorption of β
1
AR IgG before transfer and by selective pharmacological antagonism of host β
1
AR but not β
2
AR. We found that β
1
AR autoantibodies shifted the β
1
AR into the agonist-coupled high-affinity state and activated the canonical cAMP-dependent protein kinase A signaling pathway in cardiomyocytes. These events led to functional alterations in intracellular calcium handling and contractile function. Sustained agonism by β
1
AR autoantibodies elicited caspase-3 activation, cardiomyocyte apoptosis, and DCM in vivo, and these processes were prevented by in vivo treatment with the pan-caspase inhibitor Z-VAD-FMK.

Conclusions—

Our data show how β
1
AR-specific autoantibodies elicit DCM by agonistically inducing cardiomyocyte apoptosis.
Maternal and Social Origins of Hypertension
Authors: Barker David J.P. , Osmond Clive , Forsen Tom J. , Kajantie Eero , Eriksson Johan G.
Published: July 2007

We previously reported that in 2003 people from the Helsinki birth cohort whose blood pressures were measured, 2 different paths of growth preceded the development of hypertension. People already diagnosed with hypertension were small at birth but of average body size at age 11 years. People newly diagnosed with hypertension grew slowly in utero and through childhood. We have now examined how the mother’s body size, placental size, and living conditions after birth, 3 influences that affect growth, affect hypertension. Diagnosed hypertension was associated with low placental weight and poor living conditions after birth. The odds ratios were 1.6 (95% CI, 1.1 to 2.3) in people with placental weights <550 g, compared with those with weights >750 g, and 2.2 (95% CI, 1.5 to 3.3) in people whose fathers were laborers compared with those in upper middle-class families. Newly diagnosed hypertension was associated with a small anteroposterior diameter of the mother’s bony pelvis, a known consequence of rickets or lesser degrees of malnutrition in infancy. The odds ratio was 2.2 (95% CI, 1.4 to 3.5) in people whose mothers’ pelvic external conjugate diameters were <18 cm when compared with people whose mothers’ diameters were ≥19 cm. We conclude that one path of growth that leads to hypertension is initiated by fetal undernutrition, which may make a baby vulnerable to postnatal stress, whereas the other originates in a functional incapacity in the mother’s metabolism, possibly protein metabolism, which she acquired through undernutrition during her infancy.
Community Influences on E/BD Student Achievement
Authors: Madyun Na'im , Lee Moosung
Published: July 2007

No Child Left Behind has mandated that all students reach proficiency by 2014. This mandate places special emphasis on the performance of special education students. The purpose of this study is to use social theory to understand the factors that explain the achievement of emotionally or behaviorally disordered (E/BD) students. Results suggest a differential effect of neighborhood composition on the development of social ties for Black and White E/BD students. The author argues for an increased awareness of the development of within-school social ties that integrate groups.
Committees as strategic practice: The role of strategic conversation in a public administration
Authors: Hoon Christina
Published: July 2007

This longitudinal qualitative study examined the role of committees as strategic practice during the implementation of personnel development in a public administration. The results show that the interaction between the management levels is not only organized in formal committees where the middle managers undertake strategic initiatives and the strategic context is set by the senior managers. Rather, the middle managers and the senior managers organize the discussion on strategic issues in informal interactions around committees. These close informal interactions can be understood as a strategic conversation that entails the micro-mechanisms of generating an understanding, aligning towards an issue and making prearrangements which give support for the flow of discussion. The findings show that the strategic conversations are beneficial within shaping strategy as they frame the committee as strategic practice and enable the strategic context to be reshaped and redefined.
Discrimination and stigmatization in work organizations: A multiple level framework for research on genetic testing
Authors: Barclay Lizabeth A. , Markel Karen S.
Published: July 2007

In this article, we examine how genetic testing may be the basis of a new form of exclusion in organizations. Testing reveals the genetic composition of an individual and can identify genetically linked conditions. Discrimination, related to genetic composition, may occur through either the stigmatization or categorization of individuals or groups based on genetic test results. The potential impact of genetic testing and the associated discriminatory processes on both employees and organizations is outlined. This research discusses individual (stigmatization, perceived discrimination, and symptom timing and visibility), organizational (actual discrimination, genetic testing use and accommodation) and environmental (regulatory agencies, genetic testing laboratories, insurance providers and genetic advocacy groups) factors that impact genetic testing. Lastly, we propose research questions linked to these factors to guide future organizational study.
Four Criteria to Evaluate Providers' Service-Delivery Response to New Contraceptive Introduction
Authors: León Federico R. , Arévalo Marcos , Lundgren Rebecka , Jennings Victoria , Huapaya Ana , Panfichi Rosario
Published: July 2007

This article presents an evaluation framework developed to assess the first-level effects of introducing the Standard Days Method (SDM) in Peru Ministry of Health clinics. Four questions are asked: 1) To what extent do providers routinely achieve SDM service delivery standards? 2) Is the time invested in SDM delivery consistent with program norms? 3) How does SDM delivery compare with delivery of established methods? and 4) How does SDM introduction affect delivery of established methods? A study at 62 clinics demonstrated the framework's usefulness. The Standard Days Method introduction had positive overall effects on the quality of care but provider training needed adjustments.
Cytogenetic outcomes of adjuvant chemotherapy in non-target cells of breast cancer patients
Authors: Kopjar Nevenka , Milas Ivan , Garaj-Vrhovac Verica , Gamulin Marija
Published: July 2007

Spontaneous and chemotherapy-induced sister chromatid exchanges (SCES) and lymphocyte proliferation rate index (PRI) in cultured peripheral lymphocytes were evaluated in 30 patients with diagnosed breast cancer before and after adjuvant chemotherapy and in 30 healthy women with no known familial history of breast cancer. Before chemotherapy, the breast cancer patients had a significantly increased background level of SCE, and lowered PRI as compared with the healthy women. Marked inter-individual variations were observed in both endpoints among the patients. Significantly elevated frequency of SCE and depressed PRI were recorded in blood samples collected after the first cycle of chemotherapy, with high inter-individual variations in the responses to the chemotherapy. FAC (5-fluorouracil, adriamycin and cyclophosphamide) protocol was the most genotoxic of the protocols studied, but also AC (adriamycin, cyclophosphamide) and CMF (cyclophosphamide, methotrexate and 5-fluorouracil) clearly increased SCE. All protocols significantly retarded lymphocyte proliferation in vitro. Our findings indicate that both SCE and PRI may serve as sensitive biomarkers for the routine detection of critical lesions produced by the administration of antineoplastic drugs in the clinical setting, as well as for possible screening of high-risk individuals among patients who have successfully completed chemotherapy. Human & Experimental Toxicology (2007) 26 , 391—399
Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats
Authors: de Lima Leite Aline , Ferreira Santiago Junior Joel , Mauad Levy Flavia , Gutierrez Maria Andrea , da Silva Fernandes Mileni , Favero Salvadori Daisy Maria , Araki Ribeiro Daniel , Afonso Rabelo Buzalaf Marilia
Published: July 2007

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure. Human & Experimental Toxicology ( 2007) 26, 435—440
Physical Activity Belief Scales for Diabetes Risk: Development and Psychometric Testing
Authors: Blue Carolyn L. , Marrero David G. , Black David R.
Published: July 2007

This article describes the development and psychometric evaluation of behavioral belief, normative belief, and control belief scales, derived from the theory of planned behavior to predict physical activity intentions of persons at risk for diabetes. In Study 1, belief statements from interviews were categorized, ranked, and evaluated for item construction. Content validity was established by 96.1% agreement among a five-member expert panel. In Study 2, items developed from the belief statements were administered to 106 adults at risk for diabetes. Psychometric analyses provided evidence of construct validity and reliability of the three scales. Internal consistency was sufficient (α = .76-.95), and test-retest evaluations indicated scale stability ( r = .79-.91). Factor analyses and confirmatory factor analysis using structural equation modeling provided evidence that the items were appropriately grouped under each construct. Researchers and practitioners can use these measures to assess behavioral, normative, and control beliefs about physical activity among persons at risk for diabetes.
Cognitions About Smoking and Not Smoking in Adolescence
Authors: ter Doest Laura , Dijkstra Arie , Gebhardt Winifred A. , Vitale Salvatore
Published: July 2007

The theory of planned behavior identifies important proximal determinants of behavior, including attitude toward the behavior, perception of subjective norms exerted by significant others, and perception of perceived control over performance of the behavior. Because research in the planned behavior tradition has focused on desirable target behaviors, it is not clear how these determinants can best be conceptualized to account for adolescents' acquisition of health risk behaviors such as smoking. This cross-sectional study compared the explanatory power of planned behavior constructs assessed in relation to “smoking” and “not smoking” in a sample of 248 Dutch secondary students (aged 12 to 17 years; 56% girls). The results indicated that four variables—attitude toward smoking, perceived subjective norm, and perceived behavioral control over both smoking and not smoking—best explained the adolescents' smoking intentions and smoking behavior. Methodological and practical implications for smoking interventions are discussed.
Are We There Yet? An Examination of Online Tailored Health Communication
Authors: Suggs L. Suzanne , McIntyre Chris
Published: July 2007

Increasingly, the Internet is playing an important role in consumer health and patient—provider communication. Seventy-three percent of American adults are now online, and 79% have searched for health information on the Internet. This study provides a baseline understanding of the extent to which health consumers are able to find tailored communication online. It describes the current behavioral focus, the channels being used to deliver the tailored content, and the level of tailoring in online-tailored communication. A content analysis of 497 health Web sites found few examples of personalized, targeted, or tailored health sites freely available online. Tailored content was provided in 13 Web sites, although 15 collected individual data. More health risk assessment (HRA) sites included tailored feedback than other topics. The patterns that emerged from the analysis demonstrate that online health users can access a number of Web sites with communication tailored to their needs.
Tramps and nomads
Authors: SKOTT-MYHRE HANS , FRIJTERS JAN C
Published: July 2007

The film Modern Times was singular in its historical moment as a work that considered youth as a creative and social force in itself. Indeed, while there are many ways to read the major themes in a film such as Modern Times, this article, following Gilles Deleuze and Félix Guattari, engages Charlie Chaplin's film as a vehicle for exploring a certain kind of becoming-youth as a question of force. The kind of force that is explored here is the production of youth as a specific kind of radical social subjectivity; that is to say, as a subjectivity comprising multiple collisions, contestations and struggles between sets of proscribed social roles. The article investigates how the film engages the question of youth-adult identity as a social binary that can be collapsed into a relation that flees the social containment of both youth and adult.
Watching the young use illicit drugs
Authors: MINNEBO JURGEN , EGGERMONT STEVEN
Published: July 2007

The study examines whether more television viewing contributes to negative perceptions of young people's behaviour with regard to substance use. This hypothesis is tested among middle-aged and elderly people, for whom television might be the primary source of information about youth. In addition, the study explores whether this relationship may be dependent upon respondents' direct experience and educational level. Correlational analyses and analyses of covariance performed on a sample of 246 people aged over 30 indicate that the relationship between television exposure and drug use estimations is curvilinear. It also showed to be moderated by respondents' educational level but not by their direct experience with adolescents. The interrelated impact of television viewing and education is discussed.
Young people's presentations of relationships in a Swedish Internet community
Authors: ELM MALIN SVENINGSSON
Published: July 2007

One of the most popular Swedish online meeting places is Lunarstorm, which is visited weekly by 85 per cent of all Swedes aged 15–20. This study aims at looking at young men's and women's presentations of self at Lunarstorm, focusing specifically on how personal relationships are represented. This is done by quantitative content analyses of 500 users’ personal pages. Results show that in many respects, the presentations follow a gender stereotypical pattern. More women than men emphasize their relationships and express stronger feelings about them. However, one exception was the way romantic relationships are addressed, where both men and women express strong feelings towards their relationships and partners.
Hans Haacke's eArth Samplings for the Bundestag
Authors: Wagner Monika
Published: July 2007

An art work consisting of deposits of earth from each of the constituencies represented in the German Bundestag has been conceived by the New York based artist Hans Haacke for the courtyard of the former Reichstag building in Berlin. Growing plants from seeds of each region symbolizes the unity of Germany after its reunification. Assembling natural materials from different regions of a country or an empire belongs to an enduring tradition of political symbolism. Though often more precious and durable material have been deployed, there are political rituals which focus on lowly earth which represents the country's population. Haacke's art work for the Bundestag seems to actualize the material's political iconography.
Hijab in London
Authors: Tarlo Emma
Published: July 2007

This article is about the significance of dress as a visible indicator of difference in multicultural London. It focuses in particular on the hijab (Muslim woman's headscarf), suggesting that its adoption by middle-class Muslim women is often a product, not so much of their cultural backgrounds as of the trans-cultural encounters they experience in a cosmopolitan urban environment. The article explores the transformative potential of hijab, demonstrating how its adoption not only acts as a moment of metamorphosis in the lives of wearers, but also has significant effects on the perceptions and actions of others. These themes of metamorphosis, visibility and agency are explored in relation to the complex conflicting resonance of hijab in the West, and how that resonance is constantly being reshaped both through contemporary political events and their media coverage as well as through the actions and campaigns of hijab wearers.
Mobility and Modernity in Arnhem Land
Authors: Altman Jon , Hinkson Melinda
Published: July 2007

This article explores the central role played by vehicles in a contradictory set of social processes that have unfolded in western Arnhem Land, north Australia, over the last five decades. Motor vehicles have mediated much of humanity's experience of the world over the past century. Kuninjku people's interaction with motor vehicles, we argue, provides one revealing lens through which to explore a distinctive and ambiguous experience of modernity. This article explores the role vehicles play in mediating Kuninjku interaction across diverse arenas — their customary lands, an expanding regional social universe occupied by kin, the Australian nation-state, and finally an increasingly globalized world. Briefly exploring the process by which vehicles were introduced into Kuninjku country, we then track key transformations in Kuninjku life through a series of historical phases. The distinctive Kuninjku values that govern use of vehicles are explored. In conclusion the article reflects on the paradoxical nature of Kuninjku experience of late modernity and the fragility of their apparent success in realizing their aspirations.
Unmasking delivery
Authors: Lennan Anne Mc
Published: July 2007

The challenges of poverty worldwide have led to a growing focus on public delivery. When delivery fails, it is assumed that the key strategy for improvement is manipulation of existing processes, better institutions or more efficient management. This is partly because the dominant model for understanding delivery assumes that given a number of inputs, a specific output can be expected. This article explores how delivery came to be understood as a politically neutral process and the impact these understandings have had in post-apartheid South Africa. It argues that a different, more contextual and political, conceptualisation of delivery, which learns from and builds off what works, is needed in contexts that are unequal and underdeveloped.
Parish pump politics
Authors: Muller Mike
Published: July 2007

An understanding of the politics of the water sector during the first decade of South Africa's democracy requires an engagement with a series of parallel debates. There is a technical debate about the nature of the water supply challenge. There is an institutional politics around budget allocation, between and within spheres or levels of government. There is a tension between a rights-based approach to service provision and the politics of sustainability and conservation. The interplay between these parallel dynamics is about the politics of the South African transition to democracy. But South Africa is not an island. So, finally, there is the global water debate, with its human rights, economic, anti-privatisation/imperialism and environmental dimensions. The focus of this paper is on how these different politics are playing out and how they impact on South Africans, particularly the poor who have perhaps the most to gain or lose.
Liver cirrhosis and alcohol consumption in the U.K.
Authors: Mills Terence C
Published: July 2007

The temporal relationship between cirrhosis mortality and alcohol consumption in the U.K. is examined using time series techniques that, although widespread in the analysis of economic and financial data, have only been considered sporadically in addiction research. The recent acceleration in cirrhosis mortality in the U.K. over the last decade is found to be primarily related to increases in wine consumption, with beer and spirits playing very much a minor role.
The Performative "I"
Authors: Pollock Della
Published: July 2007

Although claims to revive the first person in scholarly writing remain compelling, efforts to fulfill them have been less so. Few have survived the problems of authenticity, authority, and advocacy identified by Joan Scott and Linda Kauffman, among others. Following the model of "stunting" offered by the feminist theorist, Mary Russo, this article proposes a view toward a "performative `I'" that invites error, disorder, and difference into the world of citationality or compulsive reiteration. The article builds its proposal on readings of two live performances and three short passages from selected texts. At their intersection, it imagines the displacement of a modernist "I" by a subjectivity defined by an ethics of sensuous coalition and a politics of errant possibility.
Dismantling the Face: Toward a Phenomenology of Boxing
Authors: Rutter Jon D.
Published: July 2007

This article provides a critical study of violence in the intersubjective encounter through the sport of boxing. Employing a hauntological method first developed by Jacques Derrida, it uses the phenomenological work of Emmanuel Levinas and the poetically philosophical work of Guilles Deleuze and Félix Guattari to focus on the facial dimension of pugilism. Written as a series of aphorisms, alternating between theoretical reflection and personal recollection, this article examines the face of boxing as it uncovers an ethical understanding of the sport and how that understanding affects the larger culture.
Automatic extraction of gene ontology annotation and its correlation with clusters in protein networks
Authors: Daraselia Nikolai , Yuryev Anton , Egorov Sergei , Mazo Ilya , Ispolatov Iaroslav
Published: July 2007

Background

Uncovering cellular roles of a protein is a task of tremendous importance and complexity that requires dedicated experimental work as well as often sophisticated data mining and processing tools. Protein functions, often referred to as its annotations, are believed to manifest themselves through topology of the networks of inter-proteins interactions. In particular, there is a growing body of evidence that proteins performing the same function are more likely to interact with each other than with proteins with other functions. However, since functional annotation and protein network topology are often studied separately, the direct relationship between them has not been comprehensively demonstrated. In addition to having the general biological significance, such demonstration would further validate the data extraction and processing methods used to compose protein annotation and protein-protein interactions datasets.

Results

We developed a method for automatic extraction of protein functional annotation from scientific text based on the Natural Language Processing (NLP) technology. For the protein annotation extracted from the entire PubMed, we evaluated the precision and recall rates, and compared the performance of the automatic extraction technology to that of manual curation used in public Gene Ontology (GO) annotation. In the second part of our presentation, we reported a large-scale investigation into the correspondence between communities in the literature-based protein networks and GO annotation groups of functionally related proteins. We found a comprehensive two-way match: proteins within biological annotation groups form significantly denser linked network clusters than expected by chance and, conversely, densely linked network communities exhibit a pronounced non-random overlap with GO groups. We also expanded the publicly available GO biological process annotation using the relations extracted by our NLP technology. An increase in the number and size of GO groups without any noticeable decrease of the link density within the groups indicated that this expansion significantly broadens the public GO annotation without diluting its quality. We revealed that functional GO annotation correlates mostly with clustering in a physical interaction protein network, while its overlap with indirect regulatory network communities is two to three times smaller.

Conclusion

Protein functional annotations extracted by the NLP technology expand and enrich the existing GO annotation system. The GO functional modularity correlates mostly with the clustering in the physical interaction network, suggesting that the essential role of structural organization maintained by these interactions. Reciprocally, clustering of proteins in physical interaction networks can serve as an evidence for their functional similarity.
Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways
Authors: Dybkaer Karen , Iqbal Javeed , Zhou Guimei , Geng Huimin , Xiao Li , Schmitz Alexander , d'Amore Francesco , Chan Wing C
Published: July 2007

Background

Human natural killer (NK) cells are the key contributors of innate immune response and the effector functions of these cells are enhanced by cytokines such as interleukine 2 (IL2). We utilized genome-wide transcriptional profiling to identify gene expression signatures and pathways in resting and IL2 activated NK cell isolated from peripheral blood of healthy donors.

Results

Gene expression profiling of resting NK cells showed high expression of a number of cytotoxic factors, cytokines, chemokines and inhibitory and activating surface NK receptors. Resting NK cells expressed many genes associated with cellular quiescence and also appeared to have an active TGFβ (TGFB1) signaling pathway. IL2 stimulation induced rapid downregulation of quiescence associated genes and upregulation of genes associated with cell cycle progression and proliferation. Numerous genes that may enhance immune function and responsiveness including activating receptors (DNAM1, KLRC1andKLRC3), death receptor ligand (TNFSF6 (FASL) andTRAIL), chemokine receptors (CX3CR1, CCR5andCCR7), interleukin receptors (IL2RG, IL18RABandIL27RA) and members of secretory pathways (DEGS1, FKBP11, SSR3, SEC61GandSLC3A2) were upregulated. The expression profile suggested PI3K/AKT activation and NF-κB activation through multiple pathways (TLR/IL1R, TNF receptor induced and TCR-like possibly involving BCL10). Activation of NFAT signaling was supported by increased expression of many pathway members and downstream target genes. The transcription factorGATA3was expressed in resting cells whileT-BETwas upregulated on activation concurrent with the change in cytokine expression profile. The importance of NK cells in innate immune response was also reflected by late increased expression of inflammatory chemotactic factors and receptors and molecules involved in adhesion and lymphocyte trafficking or migration.

Conclusion

This analysis allowed us to identify genes implicated in cellular quiescence and the cytokines and cytotoxic factors ready for immediate immune response. It also allowed us to observe the sequential immunostimulatory effects of IL2 on NK cells improving our understanding of the biology and molecular mediators behind NK cell activation.
Secretory granule neuroendocrine protein 1 (SGNE1) genetic variation and glucose intolerance in severe childhood and adult obesity
Authors: Bouatia-Naji Nabila , Vatin Vincent , Lecoeur Cécile , Heude Barbara , Proença Christine , Veslot Jacques , Jouret Béatrice , Tichet Jean , Charpentier Guillaume , Marre Michel , Balkau Beverley , Froguel Philippe , Meyre David
Published: July 2007

Background

7B2 is a regulator/activator of the prohormone convertase 2 which is involved in the processing of numerous neuropeptides, including insulin, glucagon and pro-opiomelanocortin. We have previously described a suggestive genetic linkage peak with childhood obesity on chr15q12-q14, where the 7B2 encoding gene, SGNE1 is located. The aim of this study is to analyze associations of SGNE1 genetic variation with obesity and metabolism related quantitative traits.

Methods

We screened SGNE1 for genetic variants in obese children and genotyped 12 frequent single nucleotide polymorphisms (SNPs). Case control analyses were performed in 1,229 obese (534 children and 695 adults), 1,535 individuals with type 2 diabetes and 1,363 controls, all French Caucasians. We also studied 4,922 participants from the D.E.S.I.R prospective population-based cohort.

Results

We did not find any association between SGNE1 SNPs and childhood or adult obesity. However, the 5' region SNP -1,701A>G associated with higher area under glucose curve after oral glucose tolerance test (p = 0.0005), higher HOMA-IR (p = 0.005) and lower insulinogenic index (p = 0.0003) in obese children. Similar trends were found in obese adults. SNP -1,701A>G did not associate with risk of T2D but tends to associate with incidence of type 2 diabetes (HR = 0.75 95%CI [0.55–1.01]; p = 0.06) in the prospective cohort.

Conclusion

SGNE1 genetic variation does not contribute to obesity and common forms of T2D but may worsen glucose intolerance and insulin resistance, especially in the background of severe and early onset obesity. Further molecular studies are required to understand the molecular bases involved in this process.
The structure of quality systems is important to the process and outcome, an empirical study of 386 hospital departments in Sweden
Authors: Kunkel Stefan , Rosenqvist Urban , Westerling Ragnar
Published: July 2007

Background

Clinicians, nurses, and managers in hospitals are continuously confronted by new technologies and methods that require changes to working practice. Quality systems can help to manage change while maintaining a high quality of care. A new model of quality systems inspired by the works of Donabedian has three factors: structure (resources and administration), process (culture and professional co-operation), and outcome (competence development and goal achievement). The objectives of this study were to analyse whether structure, process, and outcome can be used to describe quality systems, to analyse whether these components are related, and to discuss implications.

Methods

A questionnaire was developed and sent to a random sample of 600 hospital departments in Sweden. The adjusted response rate was 75%. The data were analysed with confirmatory factor analysis and structural equation modeling in LISREL. This is to our knowledge the first large quantitative study that applies Donabedian's model to quality systems.

Results

The model with relationships between structure, process, and outcome was found to be a reasonable representation of quality systems at hospital departments (p = 0.095, indicating no significant differences between the model and the data set). Structure correlated strongly with process (0.72) and outcome (0.60). Given structure, process also correlated with outcome (0.20).

Conclusion

The model could be used to describe and evaluate single quality systems or to compare different quality systems. It could also be an aid to implement a systematic and evidence-based system for working with quality improvements in hospital departments.
DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets
Authors: Wu Qinghua , Lothe Ragnhild A , Ahlquist Terje , Silins Ilvars , Tropé Claes G , Micci Francesca , Nesland Jahn M , Suo Zhenhe , Lind Guro E
Published: July 2007

Background

The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and theirin vitromodels (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features.

Results

Eight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation ofHOXA9,RASSF1A,APC,CDH13,HOXB5,SCGB3A1 (HIN-1),CRABP1, andMLH1was found in 51% (26/51), 49% (23/47), 24% (12/51), 20% (10/51), 12% (6/52), 10% (5/52), 4% (2/48), and 2% (1/51) of the carcinomas, respectively, whereasADAMTS1,MGMT,NR3C1,p14ARF, andp16INK4awere unmethylated in all samples. The methylation frequencies ofHOXA9andSCGB3A1were higher among relatively early-stage carcinomas (FIGO I-II) than among carcinomas of later stages (FIGO III-IV;P= 0.002,P= 0.020, respectively). The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally,HOXA9hypermethylation was more common in tumours from patients older than 60 years of age (15/21) than among those of younger age (11/30;P= 0.023). Finally, there was a significant difference inHOXA9methylation frequency among the histological types (P= 0.007).

Conclusion

DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis andHOXA9,HOXB5,SCGB3A1, andCRABP1are identified as novel hypermethylated target genes in this tumour type.
Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs
Authors: Takahama Kazuo , Shirasaki Tetsuya
Published: July 2007

Narcotic antitussives such as codeine reveal the antitussive effect primarily via the μ-opioid receptor in the central nervous system (CNS). The κ-opioid receptor also seems to contribute partly to the production of the antitussive effect of the drugs. There is controversy as to whether δ-receptors are involved in promoting an antitussive effect. Peripheral opioid receptors seem to have certain limited roles. Although narcotic antitussives are the most potent antitussives at present, certain types of coughs, such as chronic cough, are particularly difficult to suppress even with codeine. In guinea pigs, coughs elicited by mechanical stimulation of the bifurcation of the trachea were not able to be suppressed by codeine. In gupigs with sub-acute bronchitis caused by SO2gas exposure, coughing is difficult to inhibit with centrally acting antitussives such as codeine. Some studies suggest that neurokinins are involved in the development of codeine-resistant coughs. However, evidence supporting this claim is still insufficient. It is very important to characterize opiate-resistant coughs in experimental animals, and to determine which experimentally induced coughs correspond to which types of cough in humans. In this review, we describe the mechanisms of antitussive effects of narcotic antitussives, addressing codeine-sensitive and -resistant coughs, and including our own results.
Trunk rotational strength asymmetry in adolescents with idiopathic scoliosis: an observational study
Authors: McIntire Kevin L , Asher Marc A , Burton Douglas C , Liu Wen
Published: July 2007

Background

Recent reports have suggested a rotational strength weakness in rotations to the concave side in patients with idiopathic scoliosis. There have been no studies presenting normative values of female adolescent trunk rotational strength to which a comparison of female adolescents with idiopathic scoliosis could be made. The purpose of this study was to determine trunk rotational strength asymmetry in a group of female adolescents with AIS and a comparison group of healthy female adolescents without scoliosis.

Methods

Twenty-six healthy adolescent females served as the healthy group (HG) (average age 14 years) and fourteen otherwise healthy adolescent females with idiopathic scoliosis served as the idiopathic scoliosis group (ISG) (average age 13.5 years, average Cobb 28°). Participant's isometric trunk rotational strength was measured in five randomly ordered trunk positions: neutral, 18° and 36° of right and left pre-rotation. Rotational strength asymmetry was compared within each group and between the two groups using several different measures.

Results

The HG showed strength asymmetry in the 36° pre-rotated trunk positions when rotating towards the midline (p < 0.05). The ISG showed strength asymmetry when rotating towards the concavity of their primary curve from the neutral position (p < 0.05) and when rotating towards the concavity from the 18° (p < 0.05) and 36° (p < 0.05) concave pre-rotated positions. The ISG is significantly weaker than the HG when rotating away from the midline toward the concave (ISG)-left (HG) side from the concave/left pre-rotated 18° (p < 0.05) and 36° (p < 0.05) positions.

Conclusion

The AIS females were found to be significantly weaker when contracting toward their main curve concavity in the neutral and concave pre-rotated positions compared to contractions toward the convexity. These weaknesses were also demonstrated when compared to the group of healthy female adolescent controls. Possible mechanisms for the strength asymmetry in ISG are discussed.
ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity
Authors: Fuentealba Rodrigo A , Barría Maria Ines , Lee Jiyeon , Cam Judy , Araya Claudia , Escudero Claudia A , Inestrosa Nibaldo C , Bronfman Francisca C , Bu Guojun , Marzolo Maria-Paz
Published: July 2007

Background

The generation of the amyloid-β peptide (Aβ) through the proteolytic processing of the amyloid precursor protein (APP) is a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies highlight APP endocytosis and localization to lipid rafts as important events favoring amyloidogenic processing. However, the precise mechanisms underlying these events are poorly understood. ApoER2 is a member of the low density lipoprotein receptor (LDL-R) family exhibiting slow endocytosis rate and a significant association with lipid rafts. Despite the important neurophysiological roles described for ApoER2, little is known regarding how ApoER2 regulates APP trafficking and processing.

Results

Here, we demonstrate that ApoER2 physically interacts and co-localizes with APP. Remarkably, we found that ApoER2 increases cell surface APP levels and APP association with lipid rafts. The increase of cell surface APP requires the presence of ApoER2 cytoplasmic domain and is a result of decreased APP internalization rate. Unexpectedly, ApoER2 expression correlated with a significant increase in Aβ production and reduced levels of APP-CTFs. The increased Aβ production was dependent on the integrity of the NPxY endocytosis motif of ApoER2. We also found that expression of ApoER2 increased APP association with lipid rafts and increased γ-secretase activity, both of which might contribute to increased Aβ production.

Conclusion

These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase.
A survey of Canadian intensivists' resuscitation practices in early septic shock
Authors: McIntyre Lauralyn A , Hébert Paul C , Fergusson Dean , Cook Deborah J , Aziz Ashique ,   the Canadian Critical Care Trials Group
Published: July 2007

Introduction

Recent evidence suggests that early, aggressive resuscitation in patients with septic shock reduces mortality. The objective of this survey was to characterize reported resuscitation practices of Canadian physicians caring for adult critically ill patients with early septic shock.

Methods

A scenario-based self-administered national survey was sent out to Canadian critical care physicians. One hypothetical scenario was developed to obtain information on several aspects of resuscitation in early septic shock, including monitoring and resuscitation end-points, fluid administration, red blood cell transfusion triggers, and use of inotropes. The sampling frame was physician members of Canadian national and provincial critical care societies.

Results

The survey response rate was 232 out of 355 (65.3%). Medicine was the most common primary specialty (60.0%), most respondents had practiced for 6 to 10 years (30.0%), and 82.0% were male. The following monitoring devices/parameters were reported as used/measured 'often' or 'always' by at least 89% of respondents: oxygen saturation (100%), Foley catheters (100%), arterial blood pressure lines (96.6%), telemetry (94.3%), and central venous pressure (89.2%). Continuous monitoring of central venous oxygen saturation was employed 'often' or 'always' by 9.8% of respondents. The two most commonly cited resuscitation end-points were urine output (96.5%) and blood pressure (91.8%). Over half of respondents used normal saline (84.5%), Ringers lactate (52.2%), and pentastarch (51.3%) 'often' or 'always' for early fluid resuscitation. In contrast, 5% and 25% albumin solutions were cited as used 'often' or 'always' by 3.9% and 1.3% of respondents, respectively. Compared with internists, surgeons and anesthesiologists (odds ratio (95% confidence interval): 9.8 (2.9 to 32.7) and 3.8 (1.7 to 8.7), respectively) reported greater use of Ringers lactate. In the setting of a low central venous oxygen saturation, 52.5% of respondents reported use of inotropic support 'often' or 'always'. Only 7.6% of physicians stated they would use a red blood cell transfusion trigger of 100 g/l to optimize oxygen delivery further.

Conclusion

Our survey results suggest that there is substantial practice variation in the resuscitation of adult patients with early septic shock. More randomized trials are needed to determine the optimal approach.
Novel experimental approach for longitudinal-radial stiffness characterisation of clear wood by a single test
Authors: Xavier José , Avril Stéphane , Pierron Fabrice , Morais José
Published: July 2007

Experimental results obtained from maritime pine (Pinus pinaster Ait.) wood are presented for the characterisation of all LR=(1,2) orthotropic stiffness parameters of clear wood specimens by a single test. The approach relies on application of the virtual field method (VFM) to a rectangular specimen loaded in the Iosipescu fixture. The displacement field over the gauge surface of the specimen is measured by the grid method. Two configurations are investigated: (1) with grain aligned along the specimen length (0° configuration) and (2) with grain at 45°. For the 0° configuration, only the parameters Q
11 and Q
66 are correctly identified, with coefficients of variation of the same order of magnitude as those obtained from reference tensile and shear tests. Better identification is obtained for the 45° configuration, for which only the parameter Q
12 exhibits large scatter. This improvement results from a more balanced influence of all stiffness parameters on the response of the 45° specimen. However, all stiffness parameters identified were systematically underestimated by approximately 30% in comparison to reference values. This deviation is due to the vertical spatial variation of the mechanical properties of wood within the stem. Literature data confirm this interpretation.
Annual weight variation and reproductive cycle of the wood mouse (Apodemus sylvaticus) in a Mediterranean environment
Authors: Rosário Ines T. , Mathias Maria L.
Published: July 2007

This paper describes the weight variation and reproductive seasonal patterns
of the wood mouse in a Mediterranean scrubland in southern Portugal. A
total of 156 individuals were marked and followed up to 242 days. Summer
corresponded to the non-breeding period in the study area, instead of winter,
such as in other areas of central and northern Europe. As a consequence, a
displacement of the annual density and weight cycles were observed. The
higher densities, usually recorded before the non-reproductive period, were
recorded during spring instead of summer. In addition, the typical weight
depression of the non-reproductive period was reported in summer.
Reproductive individuals were consistently heavier than non-reproductive,
except in summer when a significant weight decrease was observed and in
autumn when there were few subadults in the population. Juvenile males
grew faster than juvenile females. However, there was little evidence of differences
on growth of juveniles born at different times of the year.