bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward an Aboriginal Paradigm of Healing: Addressing the Legacy of Residential Schools
Authors: Degagné Michael
Published: November 2007

Objective: Trauma experienced repeatedly over generations by Aboriginal people reverberates through tight-knit community networks and has laid down layers of psychic pain and community disruption. Healing methods that touch both individuals and communities are required. The Aboriginal Healing Foundation (AHF) has sponsored and evaluated community initiatives to address the legacy of Indian residential schools over a 7-year period. The analysis contained in its final report begins to create an empirical base for healing approaches grounded in Indigenous knowledge. The AHF commissioned quantitative and qualitative research on community projects and their impacts over the 7 years of its first mandate. This article extracts key themes from the resulting analysis.

Results: Individuals and communities engaged in healing from the legacy of residential schools move through four stages that are both sequential and recurring. Data from projects and individual participants identify promising approaches to support progress. Key findings include: (i) community healing is a necessary complement to individual healing; (ii) culture is good medicine; (iii) reservoirs of resilience in individuals and communities can be tapped; (iv) it takes time to heal; (v) service infrastructure and continuity are necessary to consolidate individual healing and assist communities who are ‘hitting the wall’ in their healing journey; and (vi) as individuals and communities heal, the depth and complexity of needs become evident, generating demand for training.
Suicide and Desert Men: The Power and Protection of Kanyirninpa (Holding)
Authors: McCoy Brian
Published: November 2007

Objective: Fred Myers described kanyirninpa (holding) as a deeply embedded value for desert Aboriginal people. He explained it as authority with nurturance where older people ‘grew up’ and protected younger people. Can a cultural understanding of kanyirninpa provide any insight or response to the high rates of suicide among young Aboriginal men today?

Method: This paper draws on qualitative health research that was conducted among desert communities in the southeast Kimberley region of Western Australia between 2001 and 2004. The research was primarily with men and explored cultural understandings of the particular male expressions and praxis of kanyirninpa. The research also occurred at a time when the first suicides of young men, who had grown up within this desert region, were taking place.

Results: Research showed that the fracture of kanyirninpa over recent generations has seriously affected key social processes and generational relationships within desert society. This wounding has implications for men's health and can provide an understanding as to why young men attempt self-harm and suicide. However, the social expression of kanyirninpa can also sustain important meanings for young men as they grow up. It can protect them from high-risk behaviour and self-harm.

Conclusions: While the experience of suicide continues to deeply wound Aboriginal families and communities, desert people's efforts to sustain and express kanyirninpa offers hope. This is a social process and relationship that can help inform health policy and practice in response to self-harm, suicide ideation and behaviour, particularly for young Aboriginal men.
Intercultural Exchange: An Approach to Training from a Franco-Canadian Perspective
Authors: Parent Roger
Published: November 2007

Objective: The current challenges of cultural diversity necessitate effective methods for training professionals in health, as well as other sectors, to work with the phenomenon of culture. This paper presents an overview of a semiotic-based approach to training in this regard.

Methods: Recent publications by Anti Randviir in semiotics on the textual nature of cultural phenomena and by Annabel Levesque on the healthcare issues of Western, French-speaking Canadians provide the methodological frame and basic cultural reference for the overview.

Results: The anthropological definition of culture as a ‘semiotic’, or universe of meaning, offers interdisciplinary common ground for designing practical approaches to cultural analysis, intercultural communication and creativity training. This definition is consistent with convergent findings and research practice in social and cognitive psychology, administrative science, philosophy, ethnography, linguistics and semiotics.

Conclusions: Cultural performances such as narrative constitute an effective methodological tool for interdisciplinary data gathering and for analysis of all kinds of cultures: organizational, family, ethnic, regional, transborder, etc. When combined with a functionalist and systemic approach to the study of culture, semiotic approaches to narrative analysis provide useful principles for decoding cultural modes of communication and for designing meaningful change based on cultural specificity.
Hydrogen Peroxide‐Dependent Arteriolar Dilation in Contracting Muscle of Rats Fed Normal and High Salt Diets
Authors: Marvar Paul J. , Hammer Leah W. , Boegehold Matthew A.
Published: November 2007

Objective: High dietary salt intake decreases the arteriolar dilation associated with skeletal muscle contraction. Because hydrogen peroxide (H2O2) can be released from contracting muscle fibers, this study was designed to assess the possible contribution of H2O2 to skeletal muscle functional hyperemia and its sensitivity to dietary salt.

Methods: The authors investigated the effect of catalase treatment on arteriolar dilation and hyperemia in contracting spinotrapezius muscle of rats fed a normal salt (0.45%, NS) or high salt (4%, HS) diet for 4 weeks. Catalase‐sensitive 2′,7′‐dichlorofluorescein (DCF) fluorescence was measured as an index of H2O2 formation, and the mechanism of arteriolar dilation to H2O2 was probed in each group using pharmacological inhibitors.

Results: DCF fluorescence increased with muscle contraction, but not if catalase was present. Catalase also reduced arteriolar dilation and hyperemia during contraction in both dietary groups. Exogenous H2O2 dilated arterioles in both groups, with greater responses in HS rats. Guanylate cyclase inhibition did not affect arteriolar responses to H2O2 in either group, but KCa or KATP channel inhibition equally reduced these responses, and KATP channel inhibition equally reduced functional hyperemia in both groups.

Conclusions: These results indicate that locally produced H2O2 contributes to arteriolar dilation and hyperemia in contracting skeletal muscle, and that the effect of H2O2 on arteriolar tone in this vascular bed is mediated largely through K+ channel activation. High dietary salt intake does not reduce the contribution of H2O2 to active hyperemia, or alter the mechanism through which H2O2 relaxes arteriolar smooth muscle.
Practical wisdom and the workplace researcher
Authors: Gibbs Paul
Published: November 2007

This paper addresses the form of enquiry appropriate for the workplace researcher. The first part of the paper is used to introduce the main themes of phronesis and relies heavily on Aristotle and Heidegger. It is argued that practical wisdom developed through experience of practical
judgements offers a form of enquiry appropriate for the complexity of the workplace. The discussion is then positioned in terms of the activities of the worker researcher and suggests that workplace researchers ought to aspire toward being practically wise within their enquiry and seek to
anticipate the impact on the welfare of the community within which they dwell.
International strategies of universities in England
Authors: Toyoshima Mihoko
Published: November 2007

The 'internationalisation' of universities has recently become a keyword in many countries. With the progress of globalisation, the mobility of students and academic staff at universities has drastically increased in the past few decades. As a result, more universities are now trying
to bring an international dimension to their institutions. While some universities are focusing on internationalising their curricula to meet the needs of a globalised society, others are emphasising the establishment of new collaboration agreements with foreign universities to raise their
profiles further. These changes have made universities main players in the age of global knowledge competition, and consequently it has been important for universities to create solid international strategies in order to survive. In this context, the United Kingdom has probably been one of
the most proactive countries in this field. This paper will examine the underlying concepts of internationalisation of universities in England. The aim of the research is to examine the different attitudes towards internationalisation between pre-1992 ('old' universities) and post1992 (former
polytechnic) universities, and to explore what kind of factors influenced their international strategies. This paper will also attempt to provide a possible explanation as to why higher education institutions in England are heading for internationalisation.
Curriculum choice, flexibility and differentiation 14–19: the way forward or flawed prospectus?
Authors: Higham Jeremy , Yeomans David
Published: November 2007

This article explores the policy and practice of choice, flexibility and differentiation within the 14–19 curriculum in England. After first locating these issues within contemporary curriculum policy it adopts a historical analysis tracing perspectives and practice since 1945.
This narrative exposes complex oscillation in policy and practice in relation to curricular choice and differentiation, especially for 14–16 year olds. The paper ends by raising parallels between current and past policy and practice and suggests the need to engage in a more fundamental
and informed curriculum dialogue in relation to choice, flexibility and differentiation.
Genome-wide selection of tag SNPs using multiple-marker correlation
Authors: Hao K.
Published: November 2007

Motivations: The tag SNP approach is a valuable tool in whole genome association studies, and a variety of algorithms have been proposed to identify the optimal tag SNP set. Currently, most tag SNP selection is based on two-marker (pairwise) linkage disequilibrium (LD). Recent literature has shown that multiple-marker LD also contains useful information that can further increase the genetic coverage of the tag SNP set. Thus, tag SNP selection methods that incorporate multiple-marker LD are expected to have advantages in terms of genetic coverage and statistical power.

Results: We propose a novel algorithm to select tag SNPs in an iterative procedure. In each iteration loop, the SNP that captures the most neighboring SNPs (through pair-wise and multiple-marker LD) is selected as a tag SNP. We optimize the algorithm and computer program to make our approach feasible on today's typical workstations. Benchmarked using HapMap release 21, our algorithm outperforms standard pair-wise LD approach in several aspects. (i) It improves genetic coverage (e.g. by 7.2% for 200 K tag SNPs in HapMap CEU) compared to its conventional pair-wise counterpart, when conditioning on a fixed tag SNP number. (ii) It saves genotyping costs substantially when conditioning on fixed genetic coverage (e.g. 34.1% saving in HapMap CEU at 90% coverage). (iii) Tag SNPs identified using multiple-marker LD have good portability across closely related ethnic groups and (iv) show higher statistical power in association tests than those selected using conventional methods.

Availability: A computer software suite, multiTag, has been developed based on this novel algorithm. The program is freely available by written request to the author at ke_hao@merck.com

Contact:  ke_hao@163.com

Supplementary information: Supplementary data are available at Bioinformatics online.
MASTR: multiple alignment and structure prediction of non-coding RNAs using simulated annealing
Authors: Lindgreen Stinus , Gardner Paul P. , Krogh Anders
Published: November 2007

Motivation: As more non–coding RNAs are discovered, the importance of methods for RNA analysis increases. Since the structure of ncRNA is intimately tied to the function of the molecule, programs for RNA structure prediction are necessary tools in this growing field of research. Furthermore, it is known that RNA structure is often evolutionarily more conserved than sequence. However, few existing methods are capable of simultaneously considering multiple sequence alignment and structure prediction.

Result: We present a novel solution to the problem of simultaneous structure prediction and multiple alignment of RNA sequences. Using Markov chain Monte Carlo in a simulated annealing framework, the algorithm MASTR (Multiple Alignment of STructural RNAs) iteratively improves both sequence alignment and structure prediction for a set of RNA sequences. This is done by minimizing a combined cost function that considers sequence conservation, covariation and basepairing probabilities. The results show that the method is very competitive to similar programs available today, both in terms of accuracy and computational efficiency.

Availability: Source code available from http://mastr.binf.ku.dk/

Contact:  stinus@binf.ku.dk
Determination and validation of principal gene products
Authors: Tress Michael L. , Wesselink Jan-Jaap , Frankish Adam , López Gonzalo , Goldman Nick , Löytynoja Ari , Massingham Tim , Pardi Fabio , Whelan Simon , Harrow Jennifer , Valencia Alfonso
Published: November 2007

Motivation: Alternative splicing has the potential to generate a wide range of protein isoforms. For many computational applications and for experimental research, it is important to be able to concentrate on the isoform that retains the core biological function. For many genes this is far from clear.

Results: We have combined five methods into a pipeline that allows us to detect the principal variant for a gene. Most of the methods were based on conservation between species, at the level of both gene and protein. The five methods used were the conservation of exonic structure, the detection of non-neutral evolution, the conservation of functional residues, the existence of a known protein structure and the abundance of vertebrate orthologues. The pipeline was able to determine a principal isoform for 83% of a set of well-annotated genes with multiple variants.

Contact:  mtress@cnio.es

Supplementary information: Supplementary data are available at Bioinformatics online.
Fast protein fold estimation from NMR-derived distance restraints
Authors: Ángyán Annamária F. , Perczel András , Pongor Sándor , Gáspári Zoltán
Published: November 2007

Summary: PRIDE-NMR is a fast novel method to relate known protein folds to NMR distance restraints. It can be used to obtain a first guess about a structure being determined, as well as to estimate the completeness or verify the correctness of NOE data.

Availability: The PRIDE-NMR server is available at http://www.icgeb.org/pride

Contact:  szpari@chem.elte.hu

Supplementary information: Description of the server and details of the tests presented can be found at http://www.icgeb.org/pride
Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2–7 loading
Authors: Chen Shuyan , de Vries Milan A. , Bell Stephen P.
Published: November 2007

The origin recognition complex (ORC) nucleates DNA replication initiation in eukaryotic cells. This six-protein complex binds replication origin DNA, recruits other initiation factors, and facilitates loading of the DNA helicase. Studying the function of individual ORC subunits during pre-RC formation has been hampered by the requirement of most subunits for DNA binding. In this study, we investigate the function of the Saccharomyces cerevisiae Orc6, the only ORC subunit not required for DNA binding. In vivo, depletion of Orc6 inhibits prereplicative complex (pre-RC) assembly and maintenance. In vitro, ORC lacking Orc6 fails to interact with Cdt1 and to load the Mcm2–7 helicase onto origin DNA. We demonstrate that two regions of Orc6 bind Cdt1 directly, and that the extreme C terminus of Orc6 (Orc6-CTD) interacts tightly with the remaining five ORC subunits. Replacing Orc6 with a fusion protein linking Cdt1 to the Orc6-CTD results in an ORC complex that loads Mcm2–7 onto DNA. Interestingly, this complex can only perform a single round of Mcm2–7 loading, suggesting that a dynamic association of Cdt1 with ORC is required for multiple rounds of Mcm2–7 loading.
Modulation of mucosal immunity in a murine model of food‐induced intestinal inflammation
Authors: Cardoso C. R. , Teixeira G. , Provinciatto P. R. , Godoi D. F. , Ferreira B. R. , Milanezi C. M. , Ferraz D. B. , Rossi M. A. , Cunha F. Q. , Silva J. S.
Published: November 2007

Background
Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance.

Objective
To develop and characterize a murine model for food‐induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens.

Methods
C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses.

Results
Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of γδ+ and CD4+CD25+Foxp3+ cells in Peyer's patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA‐3, IL‐4, IL‐13 and TNF‐α in contrast to low IFN‐γ in the gut.

Conclusion
A murine model for food‐induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T‐helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food‐related enteropathies like food allergy, focusing on gut‐specific immune response.
Seed yielding ability of landraces of lucerne in Italy
Authors: Annicchiarico P. , Pecetti L. , Romani M.
Published: November 2007

Seed yield is of crucial importance for the marketing of lucerne varieties. Statistical records for farmers’ production of certified seed suggested a slightly higher seed‐yielding ability of Italian landraces over improved varieties (proportionately 0·052). The aims were to: (i) assess the variation among landraces, and compare the germplasm of landrace and improved varieties, for seed‐yielding ability; and (ii) investigate the relationships between seed yield, environment of origin and forage yield of the landraces. Thirteen farm landraces belonging to the seven commercial ecotypes of northern Italy and four improved varieties were evaluated for seed yield in the third cropping year and for herbage yield over twelve harvests. Landraces differed in seed yield and herbage yield (P < 0·05). Landrace material, compared with variety germplasm, showed a non‐significant trend towards higher seed yield (proportionately 0·047) and had similar herbage yield and plant density at the onset of the third cropping year. Seed yield of landraces was unrelated to forage yield and was associated with frequent mowing and earlier year of seed production on its farm of origin.
Seasonal productivity and nutritive value of temperate grasses found in semi‐natural pastures in Europe: responses to cutting frequency and N supply
Authors: Pontes L. S. , Carrère P. , Andueza D. , Louault F. , Soussana J. F.
Published: November 2007

Monocultures of thirteen perennial C3 grass species that co‐occur in temperate semi‐natural grassland communities in Europe were compared in a factorial field design of two levels of N supply and two levels of cutting frequency. Above‐ground yield of dry matter (DM), crude protein (CP) concentration and pepsin‐cellulase DM digestibility of herbage were measured in two successive years. Species was the largest source of variability in yield of DM and DM digestibility of herbage, while CP concentration of herbage responded more to management factors. The highest mean DM yields and values of DM digestibility of herbage were achieved in spring for Festuca arundinacea and in autumn for Phleum pratense. Poa trivialis and Festuca rubra had the lowest DM yield and DM digestibility values, respectively, regardless of seasons and treatments. For all species CP concentration in herbage increased in response to an increase in cutting frequency and N supply by an average of 46 and 34 g kg−1 DM respectively. Differences between years and seasons indicated the importance of plant phenology on nutritional variables and the influence of environmental factors on species performance. Species ranking was compared according to their annual digestible DM and CP yields. The results show that some grasses have a nutritive value which is comparable to that of forages selected for high yields.
Tissue plasminogen activator to prevent central venous access device infections: a systematic review of central venous access catheter thrombosis, infection and thromboprophylaxis
Authors: RAGNI M. V. , JOURNEYCAKE J. M. , BRAMBILLA D. J.
Published: November 2007

Summary.  The recent unequivocal demonstration that prophylaxis, three to four weekly factor infusions, is effective in preventing joint disease in children with haemophilia, has provided impetus to initiate prophylaxis early in such children. Yet, nearly a quarter (22%) of the 83% who required central venous access devices for factor infusion developed central venous access catheter (CVAD)‐related infection. This limitation of CVAD use prevents many families from initiating prophylaxis. The frequent occurrence of local thrombosis accompanying CVAD‐related infection in surgical patients and autopsy cases, the thrombogenic plastic CVAD surfaces, and local clot formation at the insertion site, suggest the potential role of thrombolytic agents in preventing these infections. Yet, correlation between CVAD‐related infection and local thrombosis in children with haemophilia are lacking, and thromboprophylaxis to prevent CVAD‐related infection is controversial. Tissue plasminogen activator (t‐PA), a recombinant serine protease glycoprotein that lyses plasmin‐bound fibrin and is safe and effective in the treatment of occluded catheters, has not been evaluated in the prevention of these infections. We performed a literature review of CVAD‐related infection, CVAD‐related thrombosis, and thromboprophylaxis studies to evaluate the role of t‐PA in the prevention of these infections in children with haemophilia. Metanalysis of published thromboprophylaxis trials demonstrate current prophylaxis regimens do not prevent CVAD infection, and further, that thrombosis and infection do not necessarily occur simultaneously. Pilot data demonstrate CVAD infection reduction in haemophilic children by monthly t‐PA in 18 haemophilic children, suggesting the potential role of t‐PA in CVAD infection prevention. Clinical trials to evaluate t‐PA in CVAD infection prevention are justified.
Inhibition of HIV‐1 transmission in trans from dendritic cells to CD4+ T lymphocytes by natural antibodies to the CRD domain of DC‐SIGN purified from breast milk and intravenous immunoglobulins
Authors: Requena Mary , Bouhlal Hicham , Nasreddine Nadine , Saidi Hela , Gody Jean‐Chrysostome , Aubry Sylvie , Grésenguet Gérard , Kazatchkine Michel D. , Sekaly Rafick‐Pierre , Bélec Laurent , Hocini Hakim
Published: November 2007

The present study demonstrates that human breast milk and normal human polyclonal immunoglobulins purified from plasma [intravenous immunoglobulins (IVIg)] contain functional natural immunoglobulin A (IgA) and IgG antibodies directed against the carbohydrate recognition domain (CRD) domain of the dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) molecule, which is involved in the binding of human immunodeficiency virus (HIV)‐1 to dendritic cells (DCs). Antibodies to DC‐SIGN CRD were affinity‐purified on a matrix to which a synthetic peptide corresponding to the N‐terminal CRD domain (amino‐acid 342–amino‐acid 371) had been coupled. The affinity‐purified antibodies bound to the DC‐SIGN peptide and to the native DC‐SIGN molecule expressed by HeLa DC‐SIGN+ cells and immature monocyte‐derived dendritic cells (iMDDCs), in a specific and dose‐dependent manner. At an optimal dose of 200 µg/ml, natural antibodies to DC‐SIGN CRD peptide purified from breast milk and IVIg stained 25 and 20% of HeLa DC‐SIGN+ cells and 32 and 12% of iMDDCs, respectively. Anti‐DC‐SIGN CRD peptide antibodies inhibited the attachment of virus to HeLa DC‐SIGN by up to 78% and the attachment to iMDDCs by only 20%. Both breast milk‐ and IVIg‐derived natural antibodies to the CRD peptide inhibited 60% of the transmission in trans of HIV‐1JRCSF, an R5‐tropic strain, from iMDDCs to CD4+ T lymphocytes. Taken together, these observations suggest that the attachment of HIV to DCs and transmission in trans to autologous CD4+ T lymphocytes occur through two independent mechanisms. Our data support a role of natural antibodies to DC‐SIGN in the modulation of postnatal HIV transmission through breast‐feeding and in the natural host defence against HIV‐1 in infected individuals.
Organizational knowledge transfer through creation, mobilization and diffusion: a case analysis ofInTouchwithin Schlumberger
Authors: Braganza Ashley , Hackney Ray , Tanudjojo Satrijo
Published: November 2007

Abstract. There is a paucity of theory for the effective management of knowledge transfer within large organizations. Practitioners continue to rely upon ‘experimental’ approaches to address the problem. This research attempts to reduce the gap between theory and application, thereby improving conceptual clarity for the transfer of knowledge. The paper, through an in‐depth case analysis conducted within Schlumberger, studies the adoption of an intranet‐based knowledge management (KM) system (calledInTouch) to support, strategically align and transfer knowledge resources. The investigation was undertaken through the adoption of a robust empirically based qualitative research methodology incorporating the role of technology as an enabler of KM application. Consequently, the study addressed the important question of translating theoretical benefits of KM into practical reality. The research formulates a set of theoretical propositions that are seen as key to the development of an effective knowledge‐based infrastructure. The findings identify 30 generic attributes that are essential to the creation, mobilization and diffusion of organizational knowledge. The research makes a significant contribution to identifying a theoretical and empirically based agenda for successful intranet‐based KM, which will be of benefit to both the academic and practitioner communities. The paper also highlights and proposes important areas for further research.
Appetite stimulants in cystic fibrosis: a systematic review
Authors: Chinuck R. S. , Fortnum H. , Baldwin D. R.
Published: November 2007

Background  The use of appetite stimulants in cystic fibrosis (CF) is controversial because of doubts concerning efficacy and side‐effects. The aim of the review was to establish whether appetite stimulants should be recommended in CF.

Materials and methods  Medline, AMED, British Nursing Index, Cinahl, Embase, The Cochrane Library, National Research Register and Google were searched. Unpublished studies, case reports and conference abstracts were sought from experts, including authors of identified published articles, and suppliers of appetite stimulants.

Results  Fifty‐four articles were located. Fifteen studies were suitable for inclusion in the review: 10 studied, megesterol acetate (MA); 1, dronabinol; 2, mirtazapine; and 2, cyproheptadine. MA showed a beneficial effect on lung function, weight, appetite, fat free and fat mass. Adverse effects for MA included adrenal suppression, abnormalities of glycaemic control, mood changes and testicular failure. There was no consistency in the dose, frequency and duration of therapy for MA.

Conclusions  The review shows MA may have a role in the management of anorexia associated with CF. It is not possible to be conclusive for the other agents given the low numbers in the studies. Larger randomized, controlled trials of MA are necessary to confirm its safety and validate efficacy in CF.
PilO of Pseudomonas aeruginosa 1244: subcellular location and domain assignment
Authors: Qutyan Mohammed , Paliotti Michael , Castric Peter
Published: November 2007

PilO of Pseudomonas aeruginosa 1244 catalyses the attachment of an O‐antigen repeating unit to the β‐carbon of the pilin C‐terminal residue, a serine. The present study was conducted to locate the regions of this enzyme important in catalysis and to establish the cellular location of the pilin glycosylation reaction. While PilO was not detectable in extracts of P. aeruginosa or Escherichia coli, even under conditions of overexpression, it was found that an intact MalE–PilO fusion protein was produced in significant amounts. This fusion complemented a P. aeruginosa 1244 mutant containing a pilO deletion and targeted to the cytoplasmic membrane of E. coli. Wzy and WaaL, enzymes that also utilize the O‐antigen repeating unit as substrate, were found to share a sequence pattern with PilO even though these proteins have little overall sequence similarity. PilO constructs in which portions of this common sequence were deleted or altered by site‐directed mutagenesis lacked pilin glycosylating activity. Deletions of segments downstream from the common region also prevented enzyme activity. Topology studies showed that the two PilO regions associated with enzyme activity were located in the periplasm. These results establish regions of this enzyme important for catalysis and present evidence that pilin glycosylation occurs in the periplasmic space of this organism.
SipC multimerization promotes actin nucleation and contributes to Salmonella‐induced inflammation
Authors: Chang JiHoon , Myeni Sebenzile K. , Lin Tsang Long , Wu Ching Ching , Staiger Chris J. , Zhou Daoguo
Published: November 2007

Actin nucleation is the rate‐limiting step in actin assembly and is regulated by actin‐binding proteins and signal transduction molecules. Salmonella enterica serovar Typhimurium exploits actin dynamics by reorganizing the host actin cytoskeleton to facilitate its own uptake. SipC is a Salmonella actin‐binding protein that nucleates actin filament formation in vitro. The molecular mechanism by which SipC nucleates actin is not known. We show here that SipC199–409 forms multimers to promote actin nucleation. We found that wild‐type SipC199–409 forms dimers and multimers while SipC199–409#1, a nucleation mutant, is less efficient in dimer and multimer formation. Biochemical analysis suggested that SipC199–409 might form parallel dimers in an extended conformation. Furthermore, a mutant Salmonella strain that was defective in forming the SipC multimer and deficient in actin nucleation failed to cause severe colitis in a mouse model. These results allow us to present a model in which SipC forms multimers to promote actin nucleation.
Vascular adhesion protein‐1 in human ischaemic stroke
Authors: Airas L. , Lindsberg P. J. , Karjalainen‐Lindsberg M.‐L. , Mononen I. , Kotisaari K. , Smith D. J. , Jalkanen S.
Published: November 2007

Aims: Leukocyte extravasation exacerbates tissue injury after ischaemic stroke. Vascular adhesion protein‐1 (VAP‐1) is an endothelial adhesion molecule with the potential capacity to guide transmigration of inflammatory cells into ischaemic brain. Moreover, VAP‐1 could worsen ischaemic brain injury due to its function as a semicarbazide‐sensitive amine oxidase (SSAO) producing toxic metabolites from primary amines. The purpose of this study was to elucidate these aspects of VAP‐1‐function in the pathogenesis of human ischaemic stroke. Methods: We studied VAP‐1 expression in infarcted and control brains post mortem using immunohistochemistry. Levels of soluble VAP‐1 (sVAP‐1) in the serum of patients with acute stroke and in control sera were determined using enzyme‐linked immunosorbent assay. Results: In the acute phase of ischaemic stroke, the frequency of VAP‐1‐stained vessels was strongly diminished in the ipsilateral hemisphere but in the contralateral hemisphere it was comparable with the expression in the control brains. In the serum of acute stroke patients with a symptom duration <6 h the level of sVAP‐1 was significantly increased (652 ± 224 ng/ml; mean ± SD) when compared with an age‐ and sex‐matched control group (542 ± 104 ng/ml; P < 0.05). Conclusions: As both cell surface and sVAP‐1 possess vasculopathy‐promoting SSAO enzymatic activity, our results imply that by inducing SSAO‐derived toxic metabolites, VAP‐1 might aggravate ischaemic vascular changes. The subsequent release of sVAP‐1 into circulation could be further examined as a potential marker of early ischaemic vasculopathy.
CD69 upregulation on T cells as an in vitro marker for delayed‐type drug hypersensitivity
Authors: Beeler A. , Zaccaria L. , Kawabata T. , Gerber B. O. , Pichler W. J.
Published: November 2007

Background:  T cells play a key role in delayed‐type drug hypersensitivity reactions. Their reactivity can be assessed by their proliferation in response to the drug in the lymphocyte transformation test (LTT). However, the LTT imposes limitations in terms of practicability, and an alternative method that is easier to implement than the LTT would be desirable.

Methods:  Four months to 12 years after acute drug hypersensitivity reactions, CD69 upregulation on T cells of 15 patients and five healthy controls was analyzed by flow cytometry.

Results:  All 15 LTT‐positive patients showed a significant increase of CD69 expression on T cells after 48 h of drug‐stimulation exclusively with the drugs incriminated in drug‐hypersensitivities. A stimulation index of 2 as cut‐off value allowed discrimination between nonreactive and reactive T cells in LTT and CD69 upregulation. T cells (0.5–3%) showed CD69 up‐regulation. The reactive cell population consisted of a minority of truly drug reactive T cells secreting cytokines and a higher number of bystander T cells activated by IL‐2 and possibly other cytokines.

Conclusions:  CD69 upregulation was observed after 2 days in all patients with a positive LTT after 6 days, thus appearing to be a promising tool to identify drug‐reactive T cells in the peripheral blood of patients with drug‐hypersensitivity reactions.
Complement receptor 1 single nucleotide polymorphisms in Czech and Dutch patients with sarcoidosis
Authors: Mrazek F. , Kvezereli M. , Garr E. , Kubistova Z. , Kriegova E. , Fillerova R. , Arakelyan A. , Ruven H. J. T. , Drabek J. , Van Den Bosch J. M. M. , Kolek V. , Welsh K. I. , Grutters J. C. , Du Bois R. M. , Petrek M.
Published: November 2007

A single nucleotide polymorphism (SNP) C5507G of the complement receptor 1 (CR1) gene has been associated with genetic susceptibility to sarcoidosis in an Italian population. In order to provide further data on the possible involvement of CR1 gene polymorphisms in sarcoidosis, CR1 SNPs C5507G and A3650G were investigated in Czech (n = 210) and Dutch (n = 116) patients with sarcoidosis with ethnically matched groups of healthy control subjects (Czech, n = 203; Dutch, n = 112). CR1 C5507G and A3650G SNPs were not associated with susceptibility to sarcoidosis or its clinical course. Further, CR1 messenger RNA expression in bronchoalveolar lavage cells investigated by quantitative reverse transcriptase–polymerase chain reaction did not differ between sarcoidosis patients and control subjects and was not associated with the presence of the CR1 5507*G allele.
Evolution of the isochore structure in the scale of chromosome: insight from the mutation bias and fixation bias
Authors: LI M.‐K. , GU L. , CHEN S.‐S. , DAI J.‐Q. , TAO S.‐H.
Published: November 2007

Following the development of reliable methods for inferring the direction of mutations of the single nucleotide polymorphism (SNP), and the revealing of the human isochore map, it has become possible to investigate the evolution of the isochore structure in a continuous region. In this study, the recent evolution of the isochore structure on human chromosome 18, as inferred from the SNP, was examined. A remarkable mutation bias was found, which was destroying the present isochore structure. However, a fixation bias contributed by the biased gene conversion (BGC) effect and a rising fixation probability of derived alleles with increasing GC content was extending the present isochore structure. Combining the two opposing processes, the old isochore structure was declining and a more homogenous isochore structure with higher GC content was being formed on the chromosome. During this process, both the CpG and genic sites, which were present in the isochore but were paid little attention to before, played an important role. In addition, the recombination was confirmed to promote the GC alleles fixed in the genome because of the BGC effect. For the first time, it was observed that with the occurrence of little recombination, AT alleles had the identical fixation probability with GC alleles in the recombination cold spots.
Bell's palsy: A guideline proposal following a review of practice
Authors: Lunan Robert , Nagarajan Lakshmi
Published: November 2007

Abstract:  Bell's palsy occurs less frequently in children than in adults. It is important to consider other diagnosis when a child presents with an unilateral rapid onset lower motor neurone Vll nerve paresis. We propose guidelines for the management of Bell's plasy in childhood.
Human (non‐severe acute respiratory syndrome) coronavirus infections in hospitalised children in France
Authors: Vabret Astrid , Dina Julia , Gouarin Stéphanie , Petitjean Joëlle , Tripey Valérie , Brouard Jacques , Freymuth François
Published: November 2007

Aim:  This study has two objectives: to study the clinical symptoms associated with the detection of the four human coronaviruses (HCoVs), 229E, OC43, NL63 and HKU1 types, in the respiratory specimens sampled from hospitalised children in France between September 2004 and May 2005; and to develop a multiplex reverse transcription polymerase chain reaction (RT‐PCR) assay allowing for the simultaneous detection of the four HCoVs.

Methods:  1002 respiratory specimens were tested for HCoVs. The clinical and epidemiological data were compared on the basis of the type HCoV infection.

Results:  A hundred coronaviruses, 33 NL63, 2229E, 27 OC43 and 38 HKU1, were detected in 97 (9.8%) of 1002 samples negative in routine tests. The clinical and epidemiological characteristics of the study children were compared in three groups, 24 OC43‐, 27 NL63‐ and 34 HKU1‐infected children. HCoVs were identified mainly in children with upper and lower respiratory tract infections (50.5% vs. 29.4%). The significant difference in clinical presentation between the three coronavirus groups was the very low association between lower respiratory tract illness and HKU1 detection.

Conclusions:  HCoV detection in hospitalised children without any other respiratory virus detection was associated with upper and a significant rate of lower respiratory tract illness. The four types of HCoVs were detected, and new types NL63 and HKU1 represented a substantial portion of detection. The multiplex RT‐PCR enabled a sensitive one‐time detection and the characterisation of all of the known HCoV types with the exception severe acute respiratory syndrome‐coronavirus.
Polypharmacy management among Australian veterans: improving prescribing through the Australian Department of Veterans’ Affairs’ prescriber feedback programme
Authors: Woodward M. C. , Streeton C. L. , Guttmann A. , Killer G. T. , Peck R. W.
Published: November 2007

Background:  Older patients are potentially at risk from the effects of polypharmacy (PP) and/or drug–drug interactions.

Aims:  To examine the effects of a targeted patient‐specific prescriber feedback programme on patients prescribed more than 19 individual medications over the 3‐month study period.

Methods:  The Commonwealth Department of Veterans’ Affairs commissioned a review of Repatriation Pharmaceutical Benefit Scheme claims data to identify patients potentially at risk of drug injury through either PP (≥20 unique medications during 3 months) or clinically significant drug interactions (DI). Dispensing information for the patient at risk, relevant clinical guidelines and a personalized covering letter were mailed to the main prescribing general practitioner of the identified veteran patient. The claims data were then re‐analysed after the programme.

Results:  There was a significant reduction in the mean number of unique medications prescribed over a 3‐month period 1 year after the prescriber feedback (mean change = −2.22; 95% confidence interval −3.54 to −0.90; P = 0.0013) for patients identified with ongoing PP. There was also a significant reduction in the number of DI pairs (mean change = −0.73; 95% confidence interval −0.77 to −0.69; P < 0.0001) for the patients identified with an ongoing DI. The number of patients dispensed one or more DI pairs decreased from 836 to 318 after the feedback.

Conclusion:  A targeted prescriber feedback programme can influence general practitioner prescribing at an individual patient level and, therefore, contribute to the quality use of medicines.
Unpredictable feeding schedules unmask a system for daily resetting of behavioural and metabolic food entrainment
Authors: Escobar Carolina , Martínez‐Merlos Ma Teresa , Angeles‐Castellanos Manuel , Del Carmen Miñana María , Buijs Ruud M.
Published: November 2007

Restricted feeding schedules (RFS) are a potent Zeitgeber that uncouples daily metabolic and clock gene oscillations in peripheral tissues from the suprachiasmatic nucleus (SCN), which remains entrained to the light–dark cycle. Under RFS, animals develop food anticipatory activity (FAA), characterized by arousal and increased locomotion. Food availability in nature is not precise, which suggests that animals need to adjust their food‐associated activity on a daily basis. This study explored the capacity of rats to adjust to variable and unpredictable feeding schedules. Rats were exposed either to RFS with fixed daily meal (RF) or to a variable meal time (VAR) during the light phase. RF and VAR rats exhibited daily metabolic oscillations driven by the last meal event; however, VAR rats were not able to show a robust adjustment in the anticipating corticosterone peak. VAR rats were unable to exhibit FAA but exhibited a daily activation pattern in phase with the previous meal. In both groups the dorsomedial nucleus of the hypothalamus and arcuate nucleus, involved in energy balance, exhibited increased c‐Fos expression 24 h after the last meal, while only RF rats exhibited low c‐Fos expression in the SCN. Data show that metabolic and behavioural food‐entrained rhythms can be reset on a daily basis; the two conditions elicit a similar hypothalamic response, while only the SCN is inhibited in rats exhibiting anticipatory activity. The variable feeding strategy uncovered a rapid (24‐h basis) resetting mechanism for metabolism and general behaviour.
Differential expression of PKC beta II in the rat organ of Corti
Authors: Ladrech S. , Wang J. , Boukhaddaoui H. , Puel J. L. , Eybalin M. , Lenoir M.
Published: November 2007

To investigate a possible involvement of protein kinase C (PKC) in cochlear efferent neurotransmission, we studied the expression of the calcium‐dependent PKC beta II isoform in the rat organ of Corti at different postnatal ages using immunofluorescence and immunoelectron microscopy. We found evidence of PKC beta II as early as postnatal day (PND) 5 in efferent axons running in the inner spiral bundle and in Hensen cells. At PND 8, we also found PKC beta II in efferents targeting outer hair cells (OHCs), and a slight detection at the synaptic pole in the first row of the basal and middle cochlear turns. At PND 12, PKC beta II expression declined in the efferent fibres contacting OHCs, whereas expression was concentrated at the postsynaptic membrane, from the basal and middle turns. The adult‐like pattern of PKC beta II distribution was observed at PND 20. Throughout the cochlea, we found PKC beta II expression in the Hensen cells, non‐sensory cells involved in potassium re‐cycling, and lateral efferent terminals of the inner spiral bundle. In addition, we observed expression in OHCs at the postsynaptic membrane facing the endings of the medial efferent system, with the exception of some OHCs located in the most apical region of the cochlea. These data therefore suggest an involvement of PKC beta II in both cochlear efferent neurotransmission and ion homeostasis. Among other functions, PKC beta II could play a role in the efferent control of OHC activity.
Differential contribution of GABAergic and glycinergic components to inhibitory synaptic transmission in lamina II and laminae III–IV of the young rat spinal cord
Authors: Inquimbert Perrine , Rodeau Jean‐Luc , Schlichter Rémy
Published: November 2007

Using whole‐cell patch‐clamp recordings from spinal cord slices of young (10–15 days old) rats, we have characterized and compared the properties of inhibitory synaptic transmission in lamina II and laminae III–IV of the dorsal horn, which are involved in the processing of nociceptive and non‐nociceptive sensory information, respectively. All (100%) of laminae III–IV neurons, but only 55% of lamina II neurons, received both γ‐aminobutyric acid (GABA)ergic and glycinergic inputs. The remaining 45% of lamina II neurons received only GABAergic synapses. Neurons receiving only glycinergic synapses were never observed. Among the 55% of lamina II neurons receiving both GABAergic and glycinergic inputs, all displayed a small proportion (∼10%) of mixed miniature inhibitory postsynaptic currents (mIPSCs), indicating the presence of a functional GABA/glycine co‐transmission at a subset of synapses. Such a co‐transmission was never observed in laminae III–IV neurons. The presence of mixed mIPSCs and the differences in decay kinetics of GABAA‐type receptor mIPSCs between lamina II and laminae III–IV were due to the endogenous tonic production of 3α5α‐reduced steroids (3α5α‐RS) in lamina II. Stimulation of the local production of 3α5α‐RS was possible in laminae III–IV after incubation of slices with progesterone, subcutaneous injection of progesterone or induction of a peripheral inflammation. This led to the prolongation of GABAergic mIPSCs, but failed to induce the appearance of mixed mIPSCs in laminae III–IV. Our results indicate that, compared with lamina II, inhibitory synaptic transmission in laminae III–IV is characterized by a dominant role of glycinergic inhibition and the absence of a functional GABA/glycine co‐transmission.