bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural regulatory T cells and parasites: a common quest for host homeostasis
Authors: Belkaid Yasmine , Blank Rebecca B. , Suffia Isabelle
Published: July 2006

Summary:  This review discusses the roles played by natural CD4+CD25+ regulatory T cells (natural Tregs) during parasitic infections. Natural Tregs may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural Tregs also help to limit collateral tissue damage caused by vigorous antimicrobial immune responses. We discuss the hypothesis that parasites have evolved means to manipulate the host's natural Treg population, thereby generating conditions that secure survival in their vertebrate host for an extended period of time.
Transforming growth factor‐β and T‐cell‐mediated immunoregulation in the control of autoimmune diabetes
Authors: You Sylvaine , Thieblemont Nathalie , Alyanakian Marie‐Alexandra , Bach Jean‐François , Chatenoud Lucienne
Published: July 2006

Summary:  It is now well‐established that CD4+ regulatory T cells are instrumental in controlling immune responses both to self‐antigens and to non‐self‐antigens. However, the precise modalities involved in their differentiation and survival, their mode of action and their antigen specificity are only partially understood. We have been particularly interested in the study of regulatory T cells controlling autoimmune insulin‐dependent diabetes. Here, we provide evidence to support the phenotypic and functional diversity of regulatory T cells mediating transferable ‘active’ or ‘dominant’ peripheral tolerance in the non‐obese diabetic mouse model (NOD). They include natural and adaptive regulatory T cells that are operational both in unmanipulated NOD mice and in animals undergoing treatments aimed at inducing/restoring tolerance to self‐β‐cell antigens. At least in our hands, the differential cytokine‐dependency appears as a major distinctive feature of regulatory T cells subsets. Among immunoregulatory cytokines, transforming growth factor‐β(TGF‐β) appeared to play a key role. Herein we discuss these results and the working hypothesis they evoke in the context of the present literature, where the role of TGF‐β‐dependent T‐cell‐mediated immunoregulation is still debated.
Regulatory T cells in virus infections
Authors: Rouse Barry T. , Sarangi Pranita P. , Suvas Susmit
Published: July 2006

Summary:  This review discusses situations when the magnitude and function of immune responses to virus infection are influenced by regulatory T cells (Tregs). The focus is on CD4+CD25+ forkhead box protein 3+ natural Tregs (nTregs). The immune response may be limited in magnitude and efficacy when animals with normal nTreg function are infected with virus. This limitation can be observed both in vitro and in vivo. In the case of herpes simplex virus (HSV), animals depleted of nTregs prior to infection more effectively control the virus. With some virus infections, Treg responses (either nTregs or interleukin‐10‐dependent adaptive Tregs) appear to contribute to immune dysfunction, accounting for viral persistence and chronic tissue damage. This may occur with hepatitis C virus and some retrovirus infections that include human immunodeficiency virus (HIV). Under other circumstances, the nTreg response is judged to be beneficial, as it may help limit the severity of tissue damage associated with an immunoinflammatory reaction to virus infection. Such a situation occurs in HSV‐induced immunopathological lesions in the eye. With HIV, nTregs may help limit chronic immune activation that may precede collapse of the immune system. This review also discusses how virus infections become recognized by nTreg responses and how such responses might be manipulated to increase immunity or to limit virus‐induced immunopathology.
The regulation of allergy and asthma
Authors: Umetsu Dale T. , DeKruyff Rosemarie H.
Published: July 2006

Summary:  Allergic diseases and asthma are caused by exaggerated T‐helper 2 (Th2)‐biased immune responses in genetically susceptible individuals. Tolerance to allergens is a mechanism that normally prevents such responses, but the specific immunological events that mediate tolerance in this setting are poorly understood. A number of recent studies indicate that regulatory T cells (Tregs) play an important role in controlling such Th2‐biased responses. Tregs involved in regulating allergy and asthma consist of a family of related types of T cells, including natural CD25+ Tregs as well as inducible forms of antigen‐specific adaptive Tregs. Impaired expansion of natural and/or adaptive Tregs is hypothesized to lead to the development of allergy and asthma, and treatment to induce allergen‐specific Tregs could provide curative therapies for these problems.
The lifestyle of naturally occurring CD4+CD25+Foxp3+ regulatory T cells
Authors: Shevach Ethan M. , DiPaolo Richard A. , Andersson John , Zhao Dong‐Mei , Stephens Geoffrey L. , Thornton Angela M.
Published: July 2006

Summary:  Numerous studies over the past 10 years have demonstrated the importance of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in immune regulation. We analyzed the mechanism of action of nTregs in a well‐characterized model of autoimmune gastritis and demonstrated that nTregs act at an early stage of disease progression to inhibit the differentiation of naïve T cells to pathogenic T‐helper 1 effectors. The effects of nTregs in this model are not antigen‐specific but are mediated by activation of the nTregs by ubiquitous self‐peptide major histocompatibility complex class II complexes together with cytokines released by activated effector cells. Studies in vitro confirmed that some nTregs exist in an activated state in vivo and can be activated to exert non‐specific suppressor effector function by stimulation with interleukin‐2 in the absence of engagement of their T‐cell receptor. Natural Tregs can differentiate in vitro to exhibit potent granzyme B‐dependent, partially perforin‐independent cytotoxic cells that are capable of specifically killing antigen‐presenting B cells. Natural Treg‐mediated killing of antigen‐presenting cells may represent one pathway by which they can induce long‐lasting suppression of autoimmune disease.
Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease
Authors: Sakaguchi Shimon , Ono Masahiro , Setoguchi Ruka , Yagi Haruhiko , Hori Shohei , Fehervari Zoltan , Shimizu Jun , Takahashi Takeshi , Nomura Takashi
Published: July 2006

Summary:  Naturally arising CD25+CD4+ regulatory T (Treg) cells, most of which are produced by the normal thymus as a functionally mature T‐cell subpopulation, play key roles in the maintenance of immunologic self‐tolerance and negative control of a variety of physiological and pathological immune responses. Natural Tregs specifically express Foxp3, a transcription factor that plays a critical role in their development and function. Complete depletion of Foxp3‐expressing natural Tregs, whether they are CD25+ or CD25–, activates even weak or rare self‐reactive T‐cell clones, inducing severe and widespread autoimmune/inflammatory diseases. Natural Tregs are highly dependent on exogenously provided interleukin (IL)‐2 for their survival in the periphery. In addition to Foxp3 and IL‐2/IL‐2 receptor, deficiency or functional alteration of other molecules, expressed by T cells or non‐T cells, may affect the development/function of Tregs or self‐reactive T cells, or both, and consequently tip the peripheral balance between the two populations toward autoimmunity. Elucidation of the molecular and cellular basis of this Treg‐mediated active maintenance of self‐tolerance will facilitate both our understanding of the pathogenetic mechanism of autoimmune disease and the development of novel methods of autoimmune disease prevention and treatment via enhancing and re‐establishing Treg‐mediated dominant control over self‐reactive T cells.
Anaesthetization of Arctic charr Salvelinus alpinus (L.) with tricaine methanesulphonate or 2‐phenoxyethanol for immediate blood sampling
Authors: Bystriansky J. S. , LeBlanc P. J. , Ballantyne J. S.
Published: July 2006

Anaesthetization of Arctic charr Salvelinus alpinus with tricaine methanesulphonate or 2‐phenoxyethanol did not alter plasma protein, glucose, free amino acid, non‐esterified fatty acid, ion or osmolality levels, suggesting that their use allows for the normal determination of these plasma variables.
Quantitative trait loci associated with AutoFOM grading characteristics, carcass cuts and chemical body composition during growth of Sus scrofa
Authors: Mohrmann M. , Roehe R. , Knap P. W. , Looft H. , Plastow G. S. , Kalm E.
Published: July 2006

A three‐generation full‐sib resource family was constructed by crossing two commercial pig lines. Genotypes for 37 molecular markers covering chromosomes SSC1, SSC6, SSC7 and SSC13 were obtained for 315 F2 animals of 49 families and their parents and grandparents. Phenotypic records of traits including carcass characteristics measured by the AutoFOM grading system, dissected carcass cuts and meat quality characteristics were recorded at 140 kg slaughter weight. Furthermore, phenotypic records on live animals were obtained for chemical composition of the empty body, protein and lipid accretion (determined by the deuterium dilution technique), daily gain and feed intake during the course of growth from 30 to 140 kg body weight. Quantitative trait loci (QTL) detection was conducted using least‐squares regression interval mapping. Highest significance at the 0.1% chromosome‐wise level was obtained for five QTL: AutoFOM belly weight on SSC1; ham lean‐meat weight, percentage of fat of primal cuts and daily feed intake between 60 and 90 kg live weight on SSC6; and loin lean‐meat weight on SSC13. QTL affecting daily gain and protein accretion were found on SSC1 in the same region. QTL for protein and lipid content of empty body at 60 kg liveweight were located close to the ryanodine receptor 1 (RYR1) locus on SSC6. On SSC13, significant QTL for protein accretion and feed conversion ratio were detected during growth from 60 to 90 kg. In general, additive genetic effects of alleles originating from the Piétrain line were associated with lower fatness and larger muscularity as well as lower daily gain and lower protein accretion rates. Most of the QTL for carcass characteristics were found on SSC6 and were estimated after adjustment for the RYR1 gene. QTL for carcass traits, fatness and growth on SSC7 reported in the literature, mainly detected in crosses of commercial lines × obese breeds, were not obtained in the present study using crosses of only commercial lines, suggesting that these QTL are not segregating in the analysed commercial lines.
Mutations in the melanocortin 1 receptor (MC1R) gene are associated with coat colours in the domestic rabbit (Oryctolagus cuniculus)
Authors: Fontanesi L. , Tazzoli M. , Beretti F. , Russo V.
Published: July 2006

We sequenced almost the complete coding region of the MC1R gene in several domestic rabbits (Oryctolagus cuniculus) and identified four alleles: two wild‐type alleles differing by two synonymous single nucleotide polymorphisms (c.333A>G;c.555T>C), one allele with a 30‐nucleotide in‐frame deletion (c.304_333del30) and one allele with a 6‐nucleotide in‐frame deletion (c.280_285del6). A polymerase chain reaction‐based protocol was used to distinguish the wild‐type alleles from the other two alleles in 263 rabbits belonging to 37 breeds or strains. All red/fawn/yellow rabbits were homozygous for the c.304_333del30 allele. This allele represents the recessive e allele at the extension locus identified through pioneering genetic studies in this species. All Californian, Checkered, Giant White and New Zealand White rabbits were homozygous for allele c.280_285del6, which was also observed in the heterozygous condition in a few other breeds. Black coat colour is part of the standard colour in Californian and Checkered breeds, in contrast to the two albino breeds, Giant White and New Zealand White. Following the nomenclature established for the rabbit extension locus, the c.280_285del6 allele, which is dominant over c.304_333del30, may be allele ED or allele ES.
Stressors in five client populations: Neuman systems model‐based literature review
Authors: Skalski Carole Ann , DiGerolamo Louisa , Gigliotti Eileen
Published: July 2006

Aim.  This paper reports a literature review identifying and categorizing client system stressors in Neuman systems model‐based studies.

Background.  To date, literature reviews related to the Neuman systems model have focused broadly on all concepts of the model. The concept of stressors has been selected by the Neuman Systems Model Research Institute as the focus for an initial collaborative research project.

Method.  Cooper's five‐stage integrative review method was used: problem formulation, data collection, data evaluation, analysis and interpretation, and dissemination. The Neuman systems model research literature from 1983 to February 2005 was searched using Fawcett's Neuman systems model bibliography and a follow‐up review of the CINAHL database using the keywords ‘Neuman systems model’ and ‘stressors’. A total of 87 studies published as journal articles or book chapters between 1983 and 2005 were reviewed; 13 of the 87 studies met the definition of ‘stressor studies’.

Findings.  Stressors were identified in five client populations: caregivers, cancer survivors, ICU patients in intensive care units, care receivers, and parents whose children were undergoing day surgery. The most common data collection method was the interview, and investigator‐developed interview guides were most often used. Evidence of categorization of intra‐, inter‐ and extra‐personal stressors was present. The following overall stressors were identified: burden of responsibility (caregivers); awareness of vulnerability (cancer survivors); being overwhelmed (patients in intensive care units); loss of control (parents); and frustration with role changes (care receivers).

Conclusions.  These data could form the basis for nursing practice as well as future research within a collaborative environment. Given the existing body of knowledge concerning Neuman system model‐derived middle range theory concepts in the caregiver population, the middle‐range theory of caregiver role strain could be tested empirically.
The botanist effect: counties with maximal species richness tend to be home to universities and botanists
Authors: Moerman Daniel E. , Estabrook George F.
Published: July 2006

Aim  To investigate the distribution of local flowering plant species richness in areas surrounding American universities.

Methods  Species richness in university counties was compared with neighbouring counties. Data were derived from Synthesis of the North American Flora (http://www.phylosystems.com/prepublication). Probabilities of the resultant distribution were calculated, and the results were also simulated.

Results  In almost every case there were more species reported in the university county than in its neighbours. Several possible explanations were considered. We conclude that the key element is the presence of botanists in these counties who have, apparently, paid more attention to plants near at hand, and found more species of them there.

Main conclusions  Ecologists must be aware that numerical data that appear very solid, collected over many decades, may represent not only the qualities of ‘nature’ but also something of the collectors of the data.
Elevational species richness patterns for vascular plants on Mount Kinabalu, Borneo
Authors: Grytnes John Arvid , Beaman John H.
Published: July 2006

Aim  We quantify the elevational patterns of species richness for all vascular plants and some functional and taxonomic groups on a regional scale on a tropical mountain and discuss some possible causes for the observed patterns.

Location  Mount Kinabalu, Sabah, Borneo.

Methods  A data base containing elevational information on more than 28,000 specimens was analysed for vascular plant distribution, taking into account sampling effort. The total species richness pattern was estimated per 300‐m elevational interval by rarefaction analyses. The same methods were also applied to quantify species richness patterns of trees, epiphytes, and ferns.

Results  Total species richness has a humped relationship with elevation, and a maximum species richness in the interval between 900 and 1200 m. For ferns and epiphytes the maximum species richness is found at slightly higher elevations, whereas tree species did not have a statistically significant peak in richness above the lowest interval analysed.

Main conclusions  For the first time a rigorous estimate of an elevational pattern in species richness of the whole vascular plant flora of a tropical mountain has been quantified. The pattern observed depends on the group studied. We discuss the differences between the groups and compare the results with previous studies of elevational patterns of species richness from other tropical areas. We also discuss the methods used to quantify the richness pattern and conclude that rarefaction gives an appropriate estimate of the species richness pattern.
Mitochondrial DNA phylogeography of Lissotriton boscai (Caudata, Salamandridae): evidence for old, multiple refugia in an Iberian endemic
Authors: MARTÍNEZ‐SOLANO I. , TEIXEIRA J. , BUCKLEY D. , GARCÍA‐PARÍS M.
Published: July 2006

In Europe, southern peninsulas served as refugia during cold periods in the Pleistocene, acting both as centres of origin of endemisms and as sources from which formerly glaciated areas were recolonized during interglacial periods. Previous studies have revealed that within the main refugial areas, intraspecific lineages often survived in allopatric refugia. We analysed two mitochondrial markers (nad4, control region, ∼1.4 kb) in 103 individuals representing the entire distribution of Lissotriton boscai, a newt endemic to the western Iberian Peninsula. We inferred the evolutionary history of the species through phylogenetic, phylogeographic and historical demographic analyses. The results revealed unexpected, deep levels of geographically structured genetic variability. We identified two main evolutionary lineages, each containing three well‐supported clades. The first historical split involved populations from central‐southwestern coastal Portugal and the ancestor of all the remaining populations around 5.8 million years ago. Both lineages were subsequently fragmented into different population groups between 2.5 and 1.2 million years ago. According to nested clade analysis, at lower hierarchical levels the patterns suggest restricted gene flow with isolation by distance, whereas at higher levels the clades exhibit signatures of contiguous range expansion. Bayesian Skyline Plots show recent bottlenecks, followed by demographic expansions in all lineages. The significant genetic structure found is consistent with long‐term survival of populations in allopatric refugia, supporting the ‘refugia‐within‐refugia’ scenario for southern European peninsulas. The comparison of our results with other co‐distributed species highlights the generality of this hypothesis for the Iberian herpetofauna and suggests that Mediterranean refuges had more relevance for the composition and distribution of present biodiversity patterns than currently acknowledged. We briefly discuss the taxonomic and conservation implications of our results.
Sustainable Return in Post‐conflict Contexts
Authors: Black Richard , Gent Saskia
Published: July 2006

Post‐conflict return is a highly politically charged process in a number of contexts, both for returnees and those who did not migrate or flee, leading many observers to question the notion of an unproblematic return “home”. Specifically, doubts remain both about the conditions and voluntariness of return, the ability of individual returnees to reintegrate in their home countries and regions, and the wider sustainability of the return process. This paper seeks to provide an overview of recent policy interest in returns, before setting out a tentative definition of what might be considered a “sustainable” return. It is argued that it is possible to draw a distinction between narrow indicators of the “sustainability” of return, such as whether returnees subsequently reemigrate, and wider definitions, which see “sustainability” as involving both the reintegration of individual returnees in their home societies, and the wider impact of return on macroeconomic and political indicators. Based on either definition, the development of robust indicators of the sustainability of return could assist in monitoring the impact of return programmes, providing valuable insight on return policies. The broader definition suggested also draws attention to the idea that continued mobility after an initial return ‐ including circulation and the development of a “transnational” lifestyle ‐ may be more “sustainable” than a single and definitive return to the refugee's place of origin.
Transnational Returns and Reconstruction in Post‐war Bosnia and Herzegovina
Authors: Eastmond Marita
Published: July 2006

The return of refugees and displaced persons has been a strong priority in the international commitment to reverse “ethnic cleansing” in Bosnia and Herzegovina after the war. Return and reintegration of refugees as a durable solution in profoundly changed and uncertain conditions are rarely unproblematic, and in Bosnia the sustainability of such returns, especially minority returns, remains of great concern. This article examines the strategies of return which Bosnian refugees adopt given such uncertainties, and points to the transnational space in which they occur. The return strategies described are of different duration, often take place outside of established policies and programmes, and are based on the need to keep options open in different places. While policies have tended to define refugee return as a single and definitive move to the country or place of origin, the transnational perspective suggests that return be better conceptualized as a dynamic and open‐ended process, one which may extend over long periods of time, involving mobility between places and active links to people and resources in the country of asylum. Transnational strategies also include the many refugees abroad who hold on to their repossessed houses in Bosnia and visit regularly, some of them for longer periods and in preparation for returning permanently at a later date. In such a transnational dynamic, refugees and returnees are not always clear‐cut categories, as both may move between and combine resources at both ends. The transnational perspective also throws into question notions of “home” as something bound to one particular locality or national community. If home is not just a place or a physical structure, but also a site of social relations and cultural meanings, it may well extend to several places, each one of which may hold its own particular sets of relations and meanings to those concerned. This transnational dimension of home is thus a challenge to notions of “repatriation” or “return” in the simplistic mode. Instead, as this paper shows, the reconstructed home may be translocal, where each locality becomes part of a new home. Rethinking return of refugees in terms of transnational mobility and belonging also suggests new ways of conceptualizing the potential for reconstruction of a large refugee population abroad. How policies and assistance programmes may capitalize on the skills and continued transnational engagements, not least of the many young Bosnians now acquiring higher education abroad, has yet to be developed.
A multi‐process account of startle modulation during affective perception
Authors: Bradley Margaret M. , Codispoti Maurizio , Lang Peter J.
Published: July 2006

Modulation of the startle reflex by sensory, attentional, and emotional processes was explored by presenting acoustic startle probes at various delays following picture onset. Within 500 ms of onset, blinks were first greatly facilitated and then inhibited, indicating prepulse facilitation and prepulse inhibition that did not vary with affect. Attention allocation to the picture continued across the viewing interval and was most pronounced for emotional pictures, as determined by attenuation of the P3 component to the startle probe. Startle potentiation for unpleasant pictures occurred later in the viewing interval and was strongest for highly arousing pictures. Taken together, the startle reflex during picture viewing is modulated by sequential and sometimes concurrent processes of prepulse facilitation, prepulse inhibition, attentional inhibition, and affective modulation, with reflex magnitude reflecting the net effect of multiple processes.
Isolation and characterization of microsatellite loci from yellowtail Seriola dumerilii (Perciformes: Carangidae)
Authors: BABBUCCI MASSIMILIANO , ZANE LORENZO , ANDALORO FRANCO , PATARNELLO TOMASO
Published: July 2006

The Mediterranean yellowtail Seriola dumerilii (Risso, 1810) is a semi‐pelagic fish economically important to fisheries and aquaculture. We developed nine microsatellite primer pairs for this species. Microsatellites were isolated from a partial genomic library enriched for an AC motif. The developed loci proved to be polymorphic showing three to 11 alleles per locus. They can be employed for population studies as well as for parentage assessment. Cross‐species amplification was successfully tested in Seriola fasciata and Seriola rivoliana.
Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β‐adrenergic stimulation in cirrhotic rats
Authors: Ebrahimi Farzad , Tavakoli Sina , Hajrasouliha Amir Reza , Sadeghipour Hamed , Dehghani Mehdi , Ahmadi Seyed Hossein , Dehpour Ahmad Reza
Published: July 2006

It is well known that chronotropic and inotropic responses to β‐adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on β‐adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10−6 m), N(ω)‐nitro‐l‐arginine methyl ester (l‐NAME, 10−4 m), and naltrexone plus l‐NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3 × 10−4 m). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham‐operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half‐maximal effective concentrations of isoproterenol in these concentration–response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone, l‐NAME and aminoguanidine. Concurrent administration of naltrexone and l‐NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to β‐adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO‐induced hyporesponsiveness to β‐adrenergic stimulation in cirrhosis.
Testing Hypotheses for the Success of Different Conservation Strategies
Authors: BROOKS JEREMY S. , FRANZEN MARGARET A. , HOLMES CHRISTOPHER M. , GROTE MARK N. , MULDER MONIQUE BORGERHOFF
Published: July 2006

Abstract: Evaluations of the success of different conservation strategies are still in their infancy. We used four different measures of project outcomes—ecological, economic, attitudinal, and behavioral—to test hypotheses derived from the assumptions that underlie contemporary conservation solutions. Our hypotheses concerned the effects of natural resource utilization, market integration, decentralization, and community homogeneity on project success. We reviewed the conservation and development literature and used a specific protocol to extract and code the information in a sample of papers. Although our results are by no means conclusive and suffer from the paucity of high‐quality data and independent monitoring (80% of the original sample of 124 projects provided inadequate information for use in this study), they show that permitted use of natural resources, market access, and greater community involvement in the conservation project are all important factors for a successful outcome. Without better monitoring schemes in place, it is still impossible to provide a systematic evaluation of how different strategies are best suited to different conservation challenges.
Investigations into the ability of an oblique α‐helical template to provide the basis for design of an antimicrobial anionic amphiphilic peptide
Authors: Dennison Sarah R. , Morton Leslie H. G. , Brandenburg Klaus , Harris Frederick , Phoenix David A.
Published: July 2006

AP1 (GEQGALAQFGEWL) was shown by theoretical analysis to be an anionic oblique‐orientated α‐helix former. The peptide exhibited a monolayer surface area of 1.42 nm2, implying possession of α‐helical structure at an air/water interface, and Fourier transform infrared spectroscopy (FTIR) showed the peptide to be α‐helical (100%) in the presence of vesicle mimics of Escherichia coli membranes. FTIR lipid‐phase transition analysis showed the peptide to induce large decreases in the fluidity of these E. coli membrane mimics, and Langmuir–Blodgett trough analysis found the peptide to induce large surface pressure changes in monolayer mimics of E. coli membranes (4.6 mN·m−1). Analysis of compression isotherms based on mixing enthalpy (ΔH) and the Gibbs free energy of mixing (ΔGMix) predicted that these monolayers were thermodynamically stable (ΔH and ΔGMix each negative) but were destabilized by the presence of the peptide (ΔH and ΔGMix each positive). The peptide was found to have a minimum lethal concentration of 3 mm against E. coli and was seen to cause lysis of erythrocytes at 5 mm. In combination, these data clearly show that AP1 functions as an anionic α‐helical antimicrobial peptide and suggest that both its tilted peptide characteristics and the composition of its target membrane are important determinants of its efficacy of action.
Spiritual care practices of nurse practitioners in federally designated nonmetropolitan areas of North Carolina
Authors: Hubbell Sara L. , Woodard Elizabeth K. , Barksdale‐Brown Debra J. , Parker Jill S.
Published: July 2006

Purpose: The purpose of this study was to explore if and then how nurse practitioners (NPs) living in federally designated nonmetropolitan areas of North Carolina integrated spiritual care into their practices. Participants identified the frequency in which they utilize spiritual care practices, specific spiritual interventions, and their definitions of spiritual care.

Data sources: A sample of 101 NPs was chosen through systematic sampling from 507 eligible NPs. Each participant was mailed a demographic data sheet and the Nurse Practitioner Spiritual Care Perspective Survey (NPSCPS). The NPSCPS was modified from the Oncology Nurse Spiritual Care Perspective Scale developed by Taylor and colleagues. Of the 101 mailings, 65 were returned and included in the analysis.

Conclusions: Although most of the NPs in this study felt that spiritual care was an important part of nursing practice, 73% did not routinely provide spiritual care to their patients. Barriers and limitations to the provision of spiritual care must be explored.

Implications for practice: As providers of holistic care, NPs should be proficient and comfortable in providing spiritual care to their patients. Educational programs should provide NPs and NP students with knowledge and skills to provide spiritual care.
Representation of a Gaussian beam by rays
Authors: Crooker P. P. , Colson W. B. , Blau J.
Published: July 2006

Although the ray concept is a useful tool for helping students visualize the propagation of light, rays do not produce diffraction, which is described by wave theory. Nevertheless, it is possible to retain the ray picture to describe a Gaussian beam if a suitable statistical distribution of rays is used. We transform the distribution using only ray propagation techniques (no wave theory) and show how a statistical distribution of rays gives an intuitive picture of a diffracting Gaussian beam as it freely propagates or is focused by lenses.
The unreasonable effectiveness of equilibrium theory for interpreting nonequilibrium experiments
Authors: Astumian R. Dean
Published: July 2006

There has been much interest in applying the results of statistical mechanics to single molecule experiments. Recent work has highlighted nonequilibrium work-energy relations and fluctuation theorems that have an equilibriumlike (time independent) form. I give a simple heuristic example where an equilibrium result (the barometric law for colloidal particles in water) can be derived using the thermodynamically nonequilibrium behavior of a single colloidal particle falling through the water due to gravity. This description is possible because the particle, even while falling, is in mechanical equilibrium (the gravitational force equals the viscous drag force) at every instant. The results are generalized using Onsager’s thermodynamic action approach for stochastic processes to derive time independent equations that hold for thermodynamically nonequilibrium (and even nonstationary) systems. These relations offer great possibilities for the rapid determination of thermodynamic parameters from single molecule experiments.
A Pleiotropic Regulator, Frp, Affects Exopolysaccharide Synthesis, Biofilm Formation, and Competence Development in
Streptococcus mutans
Authors: Wang Bing , Kuramitsu Howard K.
Published: July 2006

Exopolysaccharide synthesis, biofilm formation, and competence are important physiologic functions and virulence factors for
Streptococcus mutans
. In this study, we report the role of Frp, a transcriptional regulator, on the regulation of these traits crucial to pathogenesis. An Frp-deficient mutant showed decreased transcription of several genes important in virulence, including those encoding fructosyltransferase (Ftf), glucosyltransferase B (GtfB), and GtfC, by reverse transcription and quantitative real-time PCR. Expression of Ftf was decreased in the
frp
mutant, as assessed by Western blotting as well as by the activity assays. Frp deficiency also inhibited the production of GtfB in the presence of glucose and sucrose as well as the production of GtfC in the presence of glucose. As a consequence of the effects on GtfB and -C, sucrose-induced biofilm formation was decreased in the
frp
mutant. The expression of competence mediated by the competence-signaling peptide (CSP) system, as assessed by
comC
gene transcription, was attenuated in the
frp
mutant. As a result, the transformation efficiency was decreased in the
frp
mutant but was partially restored by adding synthetic CSP. Transcription of the
frp
gene was significantly increased in the
frp
mutant under all conditions tested, indicating that
frp
transcription is autoregulated. Furthermore, complementation of the
frp
gene in the
frp
mutant restored transcription of the affected genes to levels similar to those in the wild-type strain. These results suggest that Frp is a novel pleiotropic effector of multiple cellular functions and is involved in the modulation of exopolysaccharide synthesis, sucrose-dependent biofilm formation, and competence development.
Lysogeny of
Streptococcus pneumoniae
with MM1 Phage: Improved Adherence and Other Phenotypic Changes
Authors: Loeffler Jutta M. , Fischetti Vincent A.
Published: July 2006

Pneumococcal prophages are extremely frequent, but no role in pathogenesis has so far been attributed to them. We isolated a variant of phage MM1, named MM1-1998, from a serotype 24 strain of
Streptococcus pneumoniae
. We created three isogenic strain pairs (serotypes 3, 4, and 24) that differed only by the lysogenic presence of the MM1-1998 phage and did a phenotypic comparison. Lysogeny led to improved adherence to inert surfaces and pharyngeal cells compared to that with the cured variants of the strains. We found that lysogeny with MM1-1998 coincided with a more transparent phenotype and phage curing with more opaque colonies in all strain pairs, and we discovered that transparency was associated with more successful and stable lysogeny. Since transparency alone was possibly responsible for the adherence difference, we further compared the TIGR4 lysogen with an equally transparent variant of TIGR4 in order to reassess the role of phage or transparency separately. The results revealed that improved adherence was independently associated with lysogeny with the MM1-1998 phage. Other phenotypic differences such as faster growth, increased autolysis, and decreased intracellular hemolytic activity were more likely due to transparency. By improving the adherence of pneumococci, this prophage may contribute to their fitness and possibly to their persistence in humans.
Virulence ofFrancisellaspp. in Chicken Embryos
Authors: Nix Eli B. , Cheung Karen K. M. , Wang Diana , Zhang Na , Burke Robert D. , Nano Francis E.
Published: July 2006

We examined the utility of infecting chicken embryos as a means of evaluating the virulence of differentFrancisellasp. strains and mutants. Infection of 7-day-old chicken embryos with a low dose ofF. novicidaorF. tularensissubsp.holarcticalive vaccine strain (LVS) resulted in sustained growth for 6 days. Different doses of these two organisms were used to inoculate chicken embryos to determine the time to death. These experiments showed that wild-typeF. novicidawas at least 10,000-fold more virulent than the LVS strain. We also examined the virulence of several attenuated mutants ofF. novicida, and they were found to have a wide range of virulence in chicken embryos. Fluorescent microscopic examination of infected chicken embryo organs revealed thatF. tularensisgrew in scattered foci of infections, and in all cases theF. tularensisappeared to be growing intracellularly. These results demonstrate that infection of 7-day-old chicken embryos can be used to evaluate the virulence of attenuatedF. tularensisstrains.
Adherent and InvasiveEscherichia coliIs Associated with Granulomatous Colitis in Boxer Dogs
Authors: Simpson Kenneth W. , Dogan Belgin , Rishniw Mark , Goldstein Richard E. , Klaessig Suzanne , McDonough Patrick L. , German Alex J. , Yates Robin M. , Russell David G. , Johnson Susan E. , Berg Douglas E. , Harel Josee , Bruant Guillaume , McDonough Sean P. , Schukken Ynte H.
Published: July 2006

The mucosa-associated microflora is increasingly considered to play a pivotal role in the pathogenesis of inflammatory bowel disease. This study explored the possibility that an abnormal mucosal flora is involved in the etiopathogenesis of granulomatous colitis of Boxer dogs (GCB). Colonic biopsy samples from affected dogs (n= 13) and controls (n= 38) were examined by fluorescent in situ hybridization (FISH) with a eubacterial 16S rRNA probe. Culture, 16S ribosomal DNA sequencing, and histochemistry were used to guide subsequent FISH. GCB-associatedEscherichia coliisolates were evaluated for their ability to invade and persist in cultured epithelial cells and macrophages as well as for serotype, phylogenetic group, genome size, overall genotype, and presence of virulence genes. Intramucosal gram-negative coccobacilli were present in 100% of GCB samples but not controls. Invasive bacteria hybridized with FISH probes toE. coli. Three of four GCB-associatedE. coliisolates adhered to, invaded, and replicated within cultured epithelial cells. Invasion triggered a“ splash”-type response, was decreased by cytochalasin D, genistein, colchicine, and wortmannin, and paralleled the behavior of the Crohn's disease-associated strainE. coliLF 82. GCBE. coliand LF 82 were diverse in serotype and overall genotype but similar in phylogeny (B2 and D), in virulence gene profiles (fyuA,irp1,irp2,chuA,fepC,ibeA,kpsMII,iss), in having a larger genome size than commensalE. coli, and in the presence of novel multilocus sequence types. We conclude that GCB is associated with selective intramucosal colonization byE. coli. E. colistrains associated with GCB and Crohn's disease have an adherent and invasive phenotype and novel multilocus sequence types and resembleE. coliassociated with extraintestinal disease in phylogeny and virulence gene profile.
Staphylococcal Enterotoxin-Like Toxins U2 and V, Two New Staphylococcal Superantigens Arising from Recombination within the Enterotoxin Gene Cluster
Authors: Thomas Damien Yann , Jarraud Sophie , Lemercier Brigitte , Cozon Gregoire , Echasserieau Klara , Etienne Jerome , Gougeon Marie-Lise , Lina Gerard , Vandenesch François
Published: July 2006

To test the hypothesis that theStaphylococcus aureusenterotoxin gene cluster (egc) can generate new enterotoxin genes by recombination, we analyzed theegclocus in a broad panel of 666 clinical isolates ofS. aureus. egcwas present in 63% of isolates, confirming its high prevalence. The archetypal organization of theegclocus, consisting of five enterotoxin genes plus two pseudogenes, was found in 409 of 421egc-positive strains. Theegclocus was incomplete in a few strains and occasionally harbored an insertion sequence and transposase genes. These strains may represent evolutionary intermediates of theegclocus. One strain with an atypicalegclocus produced two new enterotoxins, designated SElV and SElU2, generated by (i) recombination betweenselmandsei, producingselv, and (ii) a limited deletion in theφent1-φent2pseudogenes, producingselu2. Recombinant SElV and SElU2 had superantigen activity, as they specifically activated the T-cell families Vβ 6, Vβ 18, and Vβ 21 (SElV) and Vβ 13.2 and Vβ 14 (SElU2). Immunoscope analysis showed a Gaussian CDR3 size distribution of T-cell receptor Vβ chain junctional transcripts of expanded Vβ subsets in toxin-stimulated cultures, reflecting a high level of polyclonality. These data show thategcis indeed capable of generating new superantigen genes through recombination.
Murine Model of Infection by
Tropheryma whipplei
Authors: Genot Séverine , Stein Andreas , Lepidi Hubert , Ihrig Melanie , Raoult Didier , Mege Jean-Louis
Published: July 2006

We developed an animal model reproducing several aspects of Whipple's disease. Immunocompetent mice were persistently infected with
Tropheryma whipplei
, its etiological agent, and developed liver granulomas. SCID mice were infected similarly but did not develop tissue lesions. The delayed clearance of
T. whipplei
suggests a protective role for innate immunity.
Role of
Escherichia coli
O157:H7 Virulence Factors in Colonization at the Bovine Terminal Rectal Mucosa
Authors: Sheng Haiqing , Lim Ji Youn , Knecht Hannah J. , Li Jie , Hovde Carolyn J.
Published: July 2006

The human pathogen
Escherichia coli
O157:H7 causes hemorrhagic colitis and life-threatening sequelae and transiently colonizes healthy cattle at the terminal rectal mucosa. This study analyzed virulence factors important for the clinical manifestations of human
E. coli
O157:H7 infection for their contribution to the persistence of
E. coli
in cattle. The colonizing ability of
E. coli
O157:H7 was compared with those of nonpathogenic
E. coli
K-12 and isogenic deletion mutants missing Shiga toxin (Stx), the adhesin intimin, its receptor Tir, hemolysin, or the ∼92-kb pO157. Fully ruminant steers received a single rectal application of one
E. coli
strain so that effects of mucosal attachment and survival at the terminal rectum could be measured without the impact of bacterial passage through the entire gastrointestinal tract. Colonization was monitored by sensitive recto-anal junction mucosal swab culture. Nonpathogenic
E. coli
K-12 did not colonize as well as
E. coli
O157:H7 at the bovine terminal rectal mucosa. The
E. coli
O157:H7 best able to persist had intimin, Tir, and the pO157. Strains missing even one of these factors were recovered in lower numbers and were cleared faster than the wild type. In contrast,
E. coli
O157:H7 strains that were missing Stx or hemolysin colonized like the wild type. For these three strains, the number of bacteria increased between days 1 and 4 postapplication and then decreased slowly. In contrast, the numbers of noncolonizing strains (K-12, Δ
tir
, and Δ
eae
) decreased from the day of application. These patterns consistently predicted long-term colonization or clearance of the bacteria from the bovine terminal rectal mucosa.
The BarA-UvrY Two-Component System Regulates Virulence in Avian Pathogenic
Escherichia coli
O78:K80:H9
Authors: Herren Christopher D. , Mitra Arindam , Palaniyandi Senthil Kumar , Coleman Adam , Elankumaran Subbiah , Mukhopadhyay Suman
Published: July 2006

The BarA-UvrY two-component system (TCS) in
Escherichia coli
is known to regulate a number of phenotypic traits. Both in vitro and in vivo assays, including the chicken embryo lethality assay, showed that this TCS regulates virulence in avian pathogenic
E. coli
(APEC) serotype O78:K80:H9. A number of virulence determinants, such as the abilities to adhere, invade, persist within tissues, survive within macrophages, and resist bactericidal effects of serum complement, were compromised in mutants lacking either the
barA
or
uvrY
gene. The reduced virulence was attributed to down regulation of type 1 and Pap fimbriae, reduced exopolysaccharide production, and increased susceptibility to oxidative stress. Our results indicate that BarA-UvrY regulates virulence properties in APEC and that the chicken embryo lethality assay can be used as a surrogate model to determine virulence determinants and their regulation in APEC strains.