bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin Impairs Cardiovagal Baroreflex Function at the Level of the Solitary Tract Nucleus
Authors: Arnold Amy C. , Shaltout Hossam A. , Gallagher Patricia E. , Diz Debra I.
Published: September 2009

Circulating leptin is elevated in some forms of obesity-related hypertension, associated with impaired baroreflex function. Leptin receptors are present on vagal afferent fibers and neurons within the solitary tract nucleus, providing an anatomic distribution consistent with baroreflex modulation. Although solitary tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant effect on baroreflex sensitivity for control of the heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired baroreflex sensitivity for bradycardia in response to increases in pressure (1.15±0.04 versus 0.52±0.12 ms/mm Hg;
P
<0.01). Transgenic ASrAOGEN rats with low brain angiotensinogen have an upregulation of the leptin receptor and p85 α mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with these observations, the response to leptin was enhanced in ASrAOGEN rats, because both the 144-fmol (1.46±0.08 versus 0.75±0.10 ms/mm Hg;
P
<0.001) and 500-fmol (1.36±0.32 versus 0.44±0.06 ms/mm Hg;
P
<0.05) leptin microinjections impaired baroreflex sensitivity. At these doses, leptin microinjection had no effect on resting pressure, heart rate, or the tachycardic response to decreases in pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites within the solitary tract nucleus impairs the baroreflex sensitivity for bradycardia induced by increases in arterial pressure, consistent with a permissive role in mediating increases in arterial pressure. Baroreflex inhibition was enhanced in animals with evidence of increased leptin receptor and relevant signaling pathway mRNA.
Coplanar Doppler Lidar Retrieval of Rotors from T-REX
Authors: Hill Michael , Calhoun Ron , Fernando H. J. S. , Wieser Andreas , Dörnbrack Andreas , Weissmann Martin , Mayr Georg , Newsom Robert
Published: September 2009

Dual-Doppler analysis of data from two coherent lidars during the Terrain-Induced Rotor Experiment (T-REX) allows the retrieval of flow structures, such as vortices, during mountain-wave events. The spatial and temporal resolution of this approach is sufficient to identify and track vortical motions on an elevated, cross-barrier plane in clear air. Assimilation routines or additional constraints such as two-dimensional continuity are not required. A relatively simple and quick least squares method forms the basis of the retrieval. Vortices are shown to evolve and advect in the flow field, allowing analysis of their behavior in the mountain–wave–boundary layer system. The locations, magnitudes, and evolution of the vortices can be studied through calculated fields of velocity, vorticity, streamlines, and swirl. Generally, observations suggest two classes of vortical motions: rotors and small-scale vortical structures. These two structures differ in scale and behavior. The level of coordination of the two lidars and the nature of the output (i.e., in range gates) creates inherent restrictions on the spatial and temporal resolution of retrieved fields.
Rapid Automatized Naming and Immediate Memory Functions in Chinese Mandarin—Speaking Elementary Readers
Authors: Ding Yi , Richman Lynn C. , Yang Ling-yan , Guo Jian-peng
Published: September 2009

The purpose of this study was to evaluate rapid automatized naming skills (RAN) and immediate memory processes in 243 Chinese Mandarin—speaking elementary readers (ranging from Grade 1 to Grade 5). For RAN subtests, the mean naming time decreased monotonically with grade level in good and average readers, and a similar trajectory was found in poor readers, even though they were generally slower in rapid naming. Regardless of grouping methods (counting all participants or counting good readers only), RAN Character emerged as a significant predictor of various Chinese reading measures. Different from classical findings in English readers indicating that RAN Number was a better correlate of reading than RAN Object, RAN Object outperformed RAN Number and became a significant predictor of Chinese reading speed and spelling, suggesting that the differences in predictive power of RAN tasks may be language specific. Comparison of memory profiles for good, average, and poor readers revealed that the patterns varied depending on mode of stimulus presentation or response. Poor readers performed poorly on subtests involving a visual component and did relatively better on subtests involving verbal cues only, whereas a reversed pattern was shown in the group of good readers. The findings were interpreted to suggest that good and poor Chinese readers may be essentially different in applying visual strategies and verbal mediation during visual-verbal intra- and intermodal processing, and visual skills appear to be particularly important in reading of Chinese.
Preaching, Teaching and Researching at the Periphery:Academic Management Literature in Turkey, 1970—1999
Authors: Üsdiken Behlül , Wasti S. Arzu
Published: September 2009

Internationally accessible academic literature in management has been dominated very largely by contributions originating from the USA. Although this state of imbalance has attracted some discussion, little systematic research exists on scholarly activity in a large majority of countries that have limited presence in international academic outlets. To this end, we investigated the academic literature produced in Turkey over the last three decades, as an example of a country located at the periphery of management scholarship and where the management discipline developed under strong US influence. Based on a content analysis of articles published in local and international academic journals, cluster-analytic results indicated that the predominant form of scholarly output comprised a practice-oriented, nonempirical, de-contextualized literature, which served to transport American theories and practices to domestic audiences. The limitedly adopted scientific model manifested marginally greater interest in the local context. Further analysis showed that the type of university in which scholarly activity was carried out was highly significant. Academics working in American-modeled public and private universities were more likely to base their work on the scientific model imported wholesale from the USA. The post-1980 change in the institutional regime geared towards bringing Turkish higher education closer to American models and driving international publications, however, did not appear to have altered the overall panorama of scholarly activity in management, at least over a period of 15 years.
Angelic Organization: Hierarchy and the Tyranny of Heaven
Authors: Parker Martin
Published: September 2009

This paper suggests that one of the first influential legitimations of hierarchy comes from the writings of Pseudo-Dionysius, about 1500 years ago. Despite the fact that he was ordering angels, he suggests both ontological and political reasons for accepting that organization must equal hierarchy. This is an assumption that is rarely contested even today, and the idea of hierarchy is central to theories of organization, and justifications of managerialism. However, angels have been mutable creatures, and I employ some of their various incarnations in order to open up this 5th century common sense. I conclude by suggesting that angelic obedience should be treated with suspicion, and that other sorts of angels, particularly the fallen ones, might lead us away from the tyranny of hierarchy.
Reasonable, agonistic, or good?
Authors: Fives Allyn
Published: September 2009

Postmodernists reject what they call the universalist-rationalist framework of liberalism. When they do defend liberal democracy, they do so in a contextualist manner (within a ‘form of life’) and on the basis of contestation (‘agonism’). Liberals are right to charge postmodernism with self-contradiction, relativism, and immoralism. It is also argued in this article that liberalism and postmodernism are incompatible, and therefore, they cannot be joined together in response to the hegemonic construction of democratic debate. However, liberals are caught in a bind as they insist on impartiality but also believe the exercise of virtue (reasonableness, mutual respect) is a requirement of rational dialogue. This article argues that perfectionism (objectivism) in value judgements is required both to insist that virtuousity is a requirement of rationality and to reject postmodernism. However, it must be possible to separate perfectionism from two features of Alasdair MacIntyre’s Aristotelianism: he is hostile to liberal rights and his contextualism results in relativism.
Subcutaneous and Intraperitoneal Lipogranulomas Following Subcutaneous Injection of Olive Oil in Sprague-Dawley Rats
Authors: Ramot Yuval , Ben-Eliahu Shmulik , Kagan Leonid , Ezov Nathan , Nyska Abraham
Published: September 2009

Olive oil is commonly employed as a solubilizing agent for lipophilic materials in preclinical studies in rodents. Here we report that following subcutaneous (SC) injection of olive oil to Sprague-Dawley (SD) rats, local SC lipogranulomas formed, which were associated with an unusual location of the same changes in the peritoneum. Macroscopically, multifocal white spots were found over the liver and mesentery. Histologically, lipid granulomas were seen in the SC injection site, as well as on the capsular or serosal surface of the abdominal organs. No abnormal clinical signs were noted except for swelling at the injection site. The olive oil may have reached the peritoneal cavity from the SC tissue passively via the lymphatic vessels or actively after engulfment by antigen-presenting cells via the lymphatic or blood vessels. These findings are of particular importance for drug safety assessments, as the occurrence of lipogranulomas in locations distant from the site of administration may lead to misinterpretation of histological results. We suggest that these aberrations may be induced by the administration of olive oil as a vehicle.
Sociology and positivism in 19th-century France: the vicissitudes of the Société de Sociologie (1872—4)
Authors: Heilbron Johan
Published: September 2009

Little is known about the world’s first sociological society, Émile Littré’s Société de Sociologie (1872—4). This article, based on prosopographic research, offers an interpretation of the foundation, political-intellectual orientation and early demise of the society. As indicated by recruitment and texts by its founding members, the Société de Sociologie was in fact conceived more as a political club than a learned society. Guided in this by Littré’s heterodox positivism and the redefinition of sociology he proposed around 1870, the Société de Sociologie was intended first and foremost to accompany intellectually the political changes that Littré considered imperative in the early years of the Third Republic (1870— 1940). This expectation found little echo among the members of the society, and it seems possible that Littré himself and his closest associates were the ones to interrupt the society’s meetings. Some of its members’ general studies on the status of the social sciences and their main divisions were continued in the framework of the journal La Philosophie positive (1867—83), but the authors most committed to those studies were on the margins of the Littré network. Neither the dominant positivist republicanism, centered around Littré and Dubost, nor the general sociology of the more peripheral members of the network (Mesmer, Roberty, Vitry) represented an important intellectual contribution to the formation of academic sociology in France. Given that the Société de Sociologie did contribute to diffuse the project of a sociological science and developed forms of sociology coherent enough to be rejected by the pioneers of university sociology, the group constitutes a significant case of failure in the history of the discipline.
Portfolio Assessment in Student Teaching: A Reliability Study
Authors: Draves Tami J.
Published: September 2009

The purpose of this study was to investigate the reliability of portfolio assessment in student teaching. The specific problems were (a) to determine interjudge reliability for the music student teaching portfolio assessment and (b) to determine if music student teachers rate themselves similarly to the expert panel of judges. Participants ( N = 13) were undergraduate music education majors completing their student teaching semester at a major midwestern university. The Student Teaching Portfolio (STP) was required as part of the student teaching semester.Two expert judges rated participants’ STP using the Student Teaching Portfolio Assessment Rubric (STPAR). Participants self-assessed their portfolios using STPAR as well. Interjudge reliabilities and correlations between participants’ self-assessments and judges’ ratings were calculated. Results showed that portfolios can be a reliable and valid assessment tool for student teaching. Further research on the reliability of portfolio assessment in preservice teacher education is recommended.
Where Attachment Meets Acculturation: Three Cases of International Adoption
Authors: Lancaster Chloe , Nelson Kaye W.
Published: September 2009

Three mothers of eight children adopted from China were interviewed about their experience with international adoption. A narrative phenomenological research design resulted in the identification of six themes from their stories (a) not being prepared and survival, fear, and grief; (b) attachment; (c) barriers faced in the schools; (d) burn out; (e) counseling; (f) strategies of building community and validating ethnic identity and acculturation; and (g) becoming a family takes time. Authors recommend further research and more attention to the family counseling needs of international adoption families.
The Interpersonal Relationship Resolution Scale: A Reliability and Validity Study
Authors: Beckenbach John , Schmidt Eric , Reardon Robert
Published: September 2009

This article reports the results from a study conducted to investigate the reliability and validity of the Interpersonal Relationship Resolution Scale (IRRS). The IRRS is an instrument intended to measure relational violations and forgiveness with regard to interpersonal injury. Internal consistency coefficients and discriminant validity were explored. Similar to previous studies, the findings of this study suggest that the IRRS is generally reliable and valid. Some inconsistencies in reliability results between this study and other research are discussed, and suggestions for future research to explore these inconsistencies are provided.
Rejection Elicits Emotional Reactions but Neither Causes Immediate Distress nor Lowers Self-Esteem: A Meta-Analytic Review of 192 Studies on Social Exclusion
Authors: Blackhart Ginette C. , Nelson Brian C. , Knowles Megan L. , Baumeister Roy F.
Published: September 2009

Competing predictions about the effect of social exclusion were tested by meta-analyzing findings from studies of interpersonal rejection, ostracism, and similar procedures. Rejection appears to cause a significant shift toward a more negative emotional state. Typically, however, the result was an emotionally neutral state marked by low levels of both positive and negative affect. Acceptance caused a slight increase in positive mood and a moderate increase in self-esteem. Self-esteem among rejected persons was no different from neutral controls. These findings are discussed in terms of belongingness motivation, sociometer theory, affective numbing, and self-esteem defenses.
Retelling Tales of the Field
Authors: Cunliffe Ann L.
Published: September 2009

The special issue arose from the 2008 Qualitative Research in Management and Organization Conference, held at the University of New Mexico, to celebrate the twentieth anniversary of John Van Maanen’s (1988) book Tales of the Field. The theme of the conference, Telling Tales, reflected two of the core issues in the book—the need to think about the ways in which we carry out (our methods) and write up ethnographic work. This introductory paper sets the scene for the four papers to follow by giving an overview of ethnography: what ethnographic work entails, a brief history, issues to consider when doing ethnography, and offers a range of references for potential ethnographers. In addition, it introduces the four authors and situates their ‘‘tales’’ within the broader ethnographic context.
Imitation in fragile X syndrome
Authors: Macedoni-Luksic Marta , Greiss-Hess Laura , Rogers Sally J. , Gosar David , Lemons-Chitwood Kerrie , Hagerman Randi
Published: September 2009

To address the specific impairment of imitation in autism, the imitation abilities of 22 children with fragile X syndrome (FXS) with and without autism were compared. Based on previous research, we predicted that children with FXS and autism would have significantly more difficulty with non-meaningful imitation tasks. After controlling for full-scale IQ and age, the groups did not differ in their overall imitation accuracy scores, but analysis of error patterns revealed that children with FXS and autism made more groping errors and additional movements than the comparison group. These error patterns are consistent with the hypothesis that an action production system deficit plays an important role in the overall imitation deficit in autism, at least in children with FXS.
Firearm suicide in Queensland
Authors: Tait Gordon , Carpenter Belinda
Published: September 2009

The purpose of this article is to examine firearm suicide in Queensland. In 2006, statistical data were gathered from all closed paper coronial files for the 12-month period of December 2003—December 2004. Of the 567 people who committed suicide in Queensland during this period, 48 (8.5%) used firearms. The following results emerge from this data: first, gun suicides are continuing to decrease in Queensland, most likely as a function of ongoing gun controls, a decrease accompanied by a lesser increase in other methods of suicide, thereby providing little support for substitution theory; second, men continue to be more likely to shoot themselves, particularly elderly men; third, firearms are more likely to be used in rural settings, and by those with no known history of mental illness or previous suicide attempts. Finally, in spite of otherwise very high suicide rates, Aborigines rarely employ firearms, using instead the culturally significant method of hanging.
Work life and mental well-being: single and coupled employed mothers in Southern Europe and Scandinavia
Authors: Bull Torill
Published: September 2009

Many European mothers, single and coupled, combine work outside the home and family life. The effects of this on their mental well-being may vary depending on the level of support available from the State’s welfare system, since welfare may buffer working mothers from some of the stress that can arise from trying to manage significant responsibilities on the job and at home. Welfare may be especially important for single working mothers, for whom the burden of multiple roles may be even heavier. The present study assessed levels and predictors of well-being of single and coupled employed mothers in Greece, Portugal and Spain, where welfare support is relatively limited. Results were compared to a parallel study with data from Denmark, Norway and Sweden, where welfare support is relatively comprehensive. Coupled mothers in Scandinavia had significantly lower financial hardship, longer education, higher life satisfaction, more enriching jobs, practical support, financial support and social participation than coupled mothers in the Southern European sample. On the other hand, the Scandinavian coupled mothers had higher levels of work family conflict than coupled mothers in Southern Europe. Single mothers in Scandinavia, compared to single mothers in Southern Europe, had significantly longer education, higher life satisfaction and positive affect, more enriching jobs, confidant support, practical support, financial support and social participation. Level of job stress was the same for all mother groups. All groups differed significantly from each other in level of financial hardship, with Scandinavian coupled mothers being best off, followed by Scandinavian single mothers, Southern European coupled mothers, and Southern European single mothers. The regional differences suggest that single motherhood per se need not be a risk factor for poorer well-being, and that welfare policies may have a protective effect for the mental well-being of single mothers. (Global Health Promotion, 2009; 16(3): pp. 06—16)
Accompagner les familles pour promouvoir leur participation dans la trajectoire médicale de leur enfant
Authors: Gisquet Elsa
Published: September 2009

Le sujet traité est celui de la participation des familles dans les services hospitaliers. A travers l’exemple de deux services de réanimation néonatale, il apparaît que les modalités d’accueil et d’encadrement influencent le mode de participation des parents à la trajectoire médicale de leur enfant. Ces résultats mettent en évidence qu’une forte intégration des parents dans l’univers médical leur procure une plus grande marge de manœuvre, favorise une relation égalitaire entre usagers et professionnels et diminue les différences de départ liées à la catégorie socioprofessionnelle. Il est ainsi souligné la nécessité d’une première phase d’initiation et de formation des familles pour l’installation d’une certaine parité de participation dans la décision. (Global Health Promotion, 2009; 16(3): pp. 76—84)
Evaluación de las Escuelas Promotoras de Salud en Asturias (España)
Authors: García-Vázquez Jose , Blanco Orvíz Ana Gloria , García Alas Nadia , García Almozara Manuel , Álvarez Fernández Tomasa , González Torre Laura Rodríguez-Vigil , González Rafael Martin , Valdeón Menéndez Emma , Izquierdo Gutiérrez María Luisa , López Gutiérrez Carlos , González Osorio Elena , del Río Maojo Ladislao
Published: September 2009

n: Objetivo: Evaluar la situación de las escuelas en relación a la Promoción de la Salud, sus fortalezas y debilidades, a través de la incorporación de los principios de la Red Europea de Escuelas Promotoras de Salud y de las opiniones de alumnado y profesorado. Metodología: La población de estudio fueron 29 centros educativos. Se realizó una visita a cada centro y se recogió información por observación directa y entrevistas a equipo directivo, persona coordinadora del proyecto de salud y alumnado. Los criterios evaluados fueron: experiencia, compromiso, implicación del profesorado, metodología con alumnado, participación comunitaria, mejora del entorno, democracia y equidad, y otras acciones promotoras de salud. Cada criterio se valoró con una o varias variables. A cada criterio, se le dio 1 punto, de manera que cada centro podía obtener un total de 8 puntos. Juntos con éstas se recogieron otras variables cualitativas en relación a las fortalezas y debilidades de los centros en Promoción de la Salud. Resultados: La puntuación media de los centros fue 5,19 (DE: 1,16). Mayoritariamente, los centros tenían experiencia previa, incluía la Promoción en la Programación General Anual y en el Proyecto Educativo, y contaban con profesorado implicado, organizado y formado. Aproximadamente la mitad tenía una estética agradable y realizaba incorporación curricular, acciones de coeducación, de mejora del entorno, de alimentación saludable y actividades con comunidad. La participación del alumnado, de las familias y el uso organizado de espacios se dio en un porcentaje minoritario de centros. Conclusiones: Se constató un esfuerzo importante por incorporar la Promoción de la Salud, pero numerosas dificultades para ello. La principal limitación tiene que ver con la voluntariedad de estas acciones y la ausencia de políticas públicas para transformar los centros educativos. Destacar la aportación novedosa de esta investigación, en relación a la creación de un indicador global que permite evaluar la incorporación de la Promoción de la Salud en las escuelas utilizando los criterios de la Red Europea de Escuelas Promotoras de Salud. (Global Health Promotion, 2009; 16(3): pp. 96—106)
Reports from the field: Engaging learners as interpreters for developing health messages — designing the ‘Familias Sin Plomo’ English as a Second Language curriculum project
Authors: Handley Margaret A. , Santos Maricel G. , McClelland Jeff
Published: September 2009

California has a recently documented problem of trans-national environmental lead exposures in imported foods from Mexico but there is limited health information available in immigrant communities about this problem. This report highlights collaborative work with English as a Second Language (ESL) learners to critically review research data on lead exposures and reframe prevention messages about lead contamination of imported foods. These messages are now integrated into ESL curricula for dissemination to Spanish-speaking populations that are disproportionately affected by lead poisoning. This ‘learners as interpreters’ approach is a participatory method that can be applied across a wide range of public health activities. ESL learners emerged as ideal partners in developing curriculum for lead poisoning prevention for several reasons: the parents expressed strong interest in lead poisoning prevention, several have children under age 6 when lead screenings are recommended, and many have emigrated from regions in Mexico where lead hazards were identified. (Global Health Promotion, 2009; 16(3): pp. 53—58)
The contribution of social work in promoting rural health: a case from the grassroots
Authors: Nanjunda D.C.
Published: September 2009

Promotion of rural health has become a high priority of policy makers in many third world countries. Numerous NGOs are working to improve health quality in rural India. By describing a rural health promotion project in which a social worker played a key role, this article illustrates how social work practitioners can bring their many skills to bear in efforts to promote health. This commentary seeks to share the experience of an NGO in specific health promotion project in Rural Karnataka State (India). (Global Health Promotion, 2009; 16(3): pp. 59—62)
Expanded austenite, crystallography and residual stress
Authors: Christiansen T. L. , Hummelshøj T. S. , Somers M. A. J.
Published: September 2009

The identity of expanded austenite as developing during low temperature nitriding and/or carburising of austenitic stainless steel has been under debate since the very first observation of this phase. In the present article, recent results obtained with (a) homogeneous samples of various uniform compositions and (b) unravelling of the contributions of stress–depth and composition–depth profiles in expanded austenite layers are summarised and discussed. It is shown through simulation of line profiles that the combined effects of composition gradients, stress gradients and stacking fault gradients can explain the observations in typical X-ray diffractograms.
The BH3-only protein Bim plays a critical role in leukemia cell death triggered by concomitant inhibition of the PI3K/Akt and MEK/ERK1/2 pathways
Authors: Rahmani Mohamed , Anderson Anh , Habibi Joseph Reza , Crabtree Timothy Ryan , Mayo Mandy , Harada Hisashi , Ferreira-Gonzalez Andrea , Dent Paul , Grant Steven
Published: September 2009

Mechanisms underlying apoptosis induced by concomitant interruption of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 (MEK/ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways were investigated in human leukemia cells. Inhibition of these pathways using the MEK inhibitor PD184352 or U0126 and the PI3K/Akt inhibitor perifosine strikingly induced apoptosis in multiple malignant human hematopoietic cells, and substantially reduced the colony-forming capacity of primary acute myeloblastic leukemia, but not normal CD34+ cells. These events were associated with pronounced Bim up-regulation, Mcl-1 down-regulation, marked Bak/Bax conformational change accompanied by Bax membrane translocation, and a pronounced increase in Bax/Bak association. Molecular studies using tet-inducible Akt, constitutively active MEK1, dominant-negative Akt, and MEK1 small interfering RNA revealed that inhibition of both MEK/ERK1/2 and Akt pathways plays a critical functional role in perifosine/PD184352-mediated lethality. Ectopic Mcl-1 expression potently inhibited perifosine/PD184352-induced apoptosis, as did Bak or Bax knockdown. Notably, knockdown of Bim, but not Bad, blocked Bak and Bax conformational change, inhibited Bax membrane translocation, diminished Bax/Bak binding, and sharply attenuated perifosine/PD184352-induced apoptosis. Finally, enforced expression of Bim significantly enhanced apoptosis induced by PI3K/Akt inhibitors, analogous to the effects of MEK1/2 inhibitors. Collectively, these findings suggest that Bim, and Mcl-1, but not Bad, integrate death signaling triggered by concomitant disruption of the PI3K/Akt and MEK1/2/ERK1/2 pathways in human leukemia cells.
Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease
Authors: Brewin Jennifer , Mancao Christoph , Straathof Karin , Karlsson Helen , Samarasinghe Sujith , Amrolia Persis J. , Pule Martin
Published: September 2009

Epstein-Barr virus (EBV)–driven posttransplantation lymphoproliferative disease (PTLD) is a serious complication of immunosuppression after either stem cell transplantation (SCT) or solid organ transplantation (SOT). Adoptive transfer of EBV-specific cytotoxic T lymphocytes (EBV-CTLs) is an effective prophylaxis and treatment for PTLD after SCT, but not for PTLD after SOT when pharmacologic immunosuppression cannot be discontinued. We report the generation of calcineurin (CN) mutants that render EBV-CTL resistant to the immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA): mutant CNa12 confers resistance to CsA but not FK506, and mutant CNa22 confers resistance to FK506 but not CsA, whereas mutant CNb30 renders CTLs resistant to both calcineurin inhibitors. Untransduced EBV-CTLs do not proliferate in the presence of FK506/CsA. However, EBV-CTLs transduced with a retroviral vector coding for these mutants retain the ability to both proliferate and secrete normal levels of interferon-γ in the presence therapeutic levels of FK506 (CNa12), CsA (CNa22), or both (CNb30). The cytotoxicity and phenotype of EBV-CTL lines were unaffected by expression of these mutant CNs. This approach should allow effective immunotherapy with EBV-CTLs in the SOT setting without risking the graft by reduction in immunosuppression, and represents a generic approach to improving immunotherapy in the face of immunosuppression.
Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells
Authors: Huang Yan , Dai Zhong-Quan , Ling Shu-Kuan , Zhang Hong-Yu , Wan Yu-Min , Li Ying-Hui
Published: September 2009

Background

Stem cell therapy has emerged as a potential therapeutic option for tissue engineering and regenerative medicine, but many issues remain to be resolved, such as the amount of seed cells, committed differentiation and the efficiency. Several previous studies have focused on the study of chemical inducement microenvironments. In the present study, we investigated the effects of gravity on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into force-sensitive or force-insensitive cells.

Methods and results

Rat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and β-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes).

Conclusion

Taken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells.
Inflammatory cytokines, goblet cell hyperplasia and altered lung mechanics in Lgl1 +/- mice
Authors: Lan Jie , Ribeiro Leslie , Mandeville Isabel , Nadeau Katia , Bao Tim , Cornejo Salomon , Sweezey Neil B , Kaplan Feige
Published: September 2009

Background

Neonatal lung injury, a leading cause of morbidity in prematurely born infants, has been associated with arrested alveolar development and is often accompanied by goblet cell hyperplasia. Genes that regulate alveolarization and inflammation are likely to contribute to susceptibility to neonatal lung injury. We previously clonedLgl1, a developmentally regulated secreted glycoprotein in the lung. In rat, O2toxicity caused reduced levels ofLgl1, which normalized during recovery. We report here on the generation of anLgl1knockout mouse in order to determine whether deficiency ofLgl1is associated with arrested alveolarization and contributes to neonatal lung injury.

Methods

AnLgl1knockout mouse was generated by introduction of a neomycin cassette in exon 2 of theLgl1gene. To evaluate the pulmonary phenotype ofLgl1+/-mice, we assessed lung morphology,Lgl1RNA and protein, elastin fibers and lung function. We also analyzed tracheal goblet cells, and expression of mucin, interleukin (IL)-4 and IL-13 as markers of inflammation.

Results

Absence ofLgl1was lethal prior to lung formation. PostnatalLgl1+/-lungs displayed delayed histological maturation, goblet cell hyperplasia, fragmented elastin fibers, and elevated expression of TH2 cytokines (IL-4 and IL-13). At one month of age, reduced expression ofLgl1was associated with elevated tropoelastin expression and altered pulmonary mechanics.

Conclusion

Our findings confirm thatLgl1is essential for viability and is required for developmental processes that precede lung formation.Lgl1+/-mice display a complex phenotype characterized by delayed histological maturation, features of inflammation in the post-natal period and altered lung mechanics at maturity.Lgl1haploinsufficiency may contribute to lung disease in prematurity and to increased risk for late-onset respiratory disease.
Biofilm formation as a novel phenotypic feature of adherent-invasive Escherichia coli(AIEC)
Authors: Martinez-Medina Margarita , Naves Plínio , Blanco Jorge , Aldeguer Xavier , Blanco Jesus E , Blanco Miguel , Ponte Carmen , Soriano Francisco , Darfeuille-Michaud Arlette , Garcia-Gil L Jesus
Published: September 2009

Background

Crohn's disease (CD) is a high morbidity chronic inflammatory disorder of unknown aetiology. Adherent-invasive Escherichia coli (AIEC) has been recently implicated in the origin and perpetuation of CD. Because bacterial biofilms in the gut mucosa are suspected to play a role in CD and biofilm formation is a feature of certain pathogenic E. coli strains, we compared the biofilm formation capacity of 27 AIEC and 38 non-AIEC strains isolated from the intestinal mucosa. Biofilm formation capacity was then contrasted with the AIEC phenotype, the serotype, the phylotype, and the presence of virulence genes.

Results

Specific biofilm formation (SBF) indices were higher amongst AIEC than non-AIEC strains (P = 0.012). In addition, 65.4% of moderate to strong biofilms producers were AIEC, whereas 74.4% of weak biofilm producers were non-AIEC (P = 0.002). These data indicate that AIEC strains were more efficient biofilm producers than non-AIEC strains. Moreover, adhesion (P = 0.009) and invasion (P = 0.003) indices correlated positively with higher SBF indices. Additionally, motility (100%, P < 0.001), H1 type flagellin (53.8%, P < 0.001), serogroups O83 (19.2%, P = 0.008) and O22 (26.9%, P = 0.001), the presence of virulence genes such as sfa/focDE (38.5%, P = 0.003) and ibeA (26.9%, P = 0.017), and B2 phylotype (80.8%, P < 0.001) were frequent characteristics amongst biofilm producers.

Conclusion

The principal contribution of the present work is the finding that biofilm formation capacity is a novel, complementary pathogenic feature of the recently described AIEC pathovar. Characterization of AIEC specific genetic determinants, and the regulatory pathways, involved in biofilm formation will likely bring new insights into AIEC pathogenesis.
Identifying primary care patients at risk for future diabetes and cardiovascular disease using electronic health records
Authors: Hivert Marie-France , Grant Richard W , Shrader Peter , Meigs James B
Published: September 2009

Background

Prevention of diabetes and coronary heart disease (CHD) is possible but identification of at-risk patients for targeting interventions is a challenge in primary care.

Methods

We analyzed electronic health record (EHR) data for 122,715 patients from 12 primary care practices. We defined patients with risk factor clustering using metabolic syndrome (MetS) characteristics defined by NCEP-ATPIII criteria; if missing, we used surrogate characteristics, and validated this approach by directly measuring risk factors in a subset of 154 patients. For subjects with at least 3 of 5 MetS criteria measured at baseline (2003-2004), we defined 3 categories: No MetS (0 criteria); At-risk-for MetS (1-2 criteria); and MetS (≥ 3 criteria). We examined new diabetes and CHD incidence, and resource utilization over the subsequent 3-year period (2005-2007) using age-sex-adjusted regression models to compare outcomes by MetS category.

Results

After excluding patients with diabetes/CHD at baseline, 78,293 patients were eligible for analysis. EHR-defined MetS had 73% sensitivity and 91% specificity for directly measured MetS. Diabetes incidence was 1.4% in No MetS; 4.0% in At-risk-for MetS; and 11.0% in MetS (p < 0.0001 for trend; adjusted OR MetS vs No MetS = 6.86 [6.06-7.76]); CHD incidence was 3.2%, 5.3%, and 6.4% respectively (p < 0.0001 for trend; adjusted OR = 1.42 [1.25-1.62]). Costs and resource utilization increased across categories (p < 0.0001 for trends). Results were similar analyzing individuals with all five criteria not missing, or defining MetS as ≥ 2 criteria present.

Conclusion

Risk factor clustering in EHR data identifies primary care patients at increased risk for new diabetes, CHD and higher resource utilization.
Association between leukocyte telomere shortening and exposure to traffic pollution: a cross-sectional study on traffic officers and indoor office workers
Authors: Hoxha Mirjam , Dioni Laura , Bonzini Matteo , Pesatori Angela Cecilia , Fustinoni Silvia , Cavallo Domenico , Carugno Michele , Albetti Benedetta , Marinelli Barbara , Schwartz Joel , Bertazzi Pier Alberto , Baccarelli Andrea
Published: September 2009

Background

Telomere shortening in blood leukocytes has been associated with increased morbidity and death from cardiovascular disease and cancer, but determinants of shortened telomeres, a molecular feature of biological aging, are still largely unidentified. Traffic pollution has been linked with both cardiovascular and cancer risks, particularly in older subjects. Whether exposure to traffic pollution is associated with telomere shortening has never been evaluated.

Methods

We measured leukocyte telomere length (LTL) by real-time PCR in blood DNA from 77 traffic officers exposed to high levels of traffic pollutants and 57 office workers (referents). Airborne benzene and toluene, as tracers for traffic exposure, were measured using personal passive samplers and gas-chromatography/flame-ionization detector analysis. We used covariate-adjusted multivariable models to test the effects of the exposure on LTL and obtain adjusted LTL means and 95% Confidence Intervals (CIs).

Results

Adjusted mean LTL was 1.10 (95%CI 1.04-1.16) in traffic officers and 1.27 in referents (95%CI 1.20-1.35) [p < 0.001]. LTL decreased in association with age in both traffic officers (p = 0.01) and referents (p = 0.001), but traffic officers had shorter LTL within each age category. Among traffic officers, adjusted mean relative LTL was shorter in individuals working in high (n = 45, LTL = 1.02, 95%CI 0.96-1.09) compared to low traffic intensity (n = 32, LTL = 1.22, 95%CI 1.13-1.31) [p < 0.001]. In the entire study population, LTL decreased with increasing levels of personal exposure to benzene (p = 0.004) and toluene (p = 0.008).

Conclusion

Our results indicate that leukocyte telomere length is shortened in subjects exposed to traffic pollution, suggesting evidence of early biological aging and disease risk.
Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation
Authors: Martin Maureen V , Rollins Brandi , Sequeira P Adolfo , Mesén Andrea , Byerley William , Stein Richard , Moon Emily A , Akil Huda , Jones Edward G , Watson Stanley J , Barchas Jack , DeLisi Lynn E , Myers Richard M , Schatzberg Alan , Bunney William E , Vawter Marquis P
Published: September 2009

Background

The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL) gene expression in subjects with schizophrenia compared to non-psychotic relatives.

Methods

LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis.

Results

There were a total of 122 transcripts with significant diagnosis by probeset interaction effects and 328 transcripts with glucose deprivation by probeset interaction probeset effects after corrections for multiple comparisons. There were 8 transcripts with expression significantly affected by the interaction between diagnosis and glucose deprivation and probeset after correction for multiple comparisons. The overall validation rate by qPCR of 13 diagnosis effect genes identified through microarray was 62%, and all genes tested by qPCR showed concordant up- or down-regulation by qPCR and microarray. We assessed brain gene expression of five genes found to be altered by diagnosis and glucose deprivation in LCLs and found a significant decrease in expression of one gene, glutaminase, in the dorsolateral prefrontal cortex (DLPFC). One SNP with previously identified regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5 expression was significant in LCLs (p = 0.0001), DLPFC (p = 0.007), and anterior cingulate cortex (p = 0.002).

Conclusion

Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression.
Spatially Uniform ReliefF (SURF) for computationally-efficient filtering of gene-gene interactions
Authors: Greene Casey S , Penrod Nadia M , Kiralis Jeff , Moore Jason H
Published: September 2009

Background

Genome-wide association studies are becoming the de facto standard in the genetic analysis of common human diseases. Given the complexity and robustness of biological networks such diseases are unlikely to be the result of single points of failure but instead likely arise from the joint failure of two or more interacting components. The hope in genome-wide screens is that these points of failure can be linked to single nucleotide polymorphisms (SNPs) which confer disease susceptibility. Detecting interacting variants that lead to disease in the absence of single-gene effects is difficult however, and methods to exhaustively analyze sets of these variants for interactions are combinatorial in nature thus making them computationally infeasible. Efficient algorithms which can detect interacting SNPs are needed. ReliefF is one such promising algorithm, although it has low success rate for noisy datasets when the interaction effect is small. ReliefF has been paired with an iterative approach, Tuned ReliefF (TuRF), which improves the estimation of weights in noisy data but does not fundamentally change the underlying ReliefF algorithm. To improve the sensitivity of studies using these methods to detect small effects we introduce Spatially Uniform ReliefF (SURF).

Results

SURF's ability to detect interactions in this domain is significantly greater than that of ReliefF. Similarly SURF, in combination with the TuRF strategy significantly outperforms TuRF alone for SNP selection under an epistasis model. It is important to note that this success rate increase does not require an increase in algorithmic complexity and allows for increased success rate, even with the removal of a nuisance parameter from the algorithm.

Conclusion

Researchers performing genetic association studies and aiming to discover gene-gene interactions associated with increased disease susceptibility should use SURF in place of ReliefF. For instance, SURF should be used instead of ReliefF to filter a dataset before an exhaustive MDR analysis. This change increases the ability of a study to detect gene-gene interactions. The SURF algorithm is implemented in the open source Multifactor Dimensionality Reduction (MDR) software package available from http://www.epistasis.org.
Reflection images from ambient seismic noise
Authors: Draganov Deyan , Campman Xander , Thorbecke Jan , Verdel Arie , Wapenaar Kees
Published: September 2009

One application of seismic interferometry is to retrieve the impulse response (Green’s function) from crosscorrelation of ambient seismic noise. Various researchers show results for retrieving the surface-wave part of the Green’s function. However, reflection retrieval has proven more challenging. We crosscorrelate ambient seismic noise, recorded along eight parallel lines in the Sirte basin east of Ajdabeya, Libya, to obtain shot gathers that contain reflections. We take advantage of geophone groups to suppress part of the undesired surface-wave noise and apply frequency-wavenumber filtering before crosscorrelation to suppress surface waves further. After comparing the retrieved results with data from an active seismic exploration survey along the same lines, we use the retrieved reflection data to obtain a migrated reflection image of the subsurface.