Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Relationships between students' conceptions of constructivist learning and their regulation and processing strategies

The present study investigated relationships between students' conceptions of constructivist learning on the one hand, and their regulation and processing strategies on the other hand. Students in a constructivist, problem-based learning curriculum were questioned about their conceptions of knowledge construction and self-regulated learning, as well as their beliefs regarding their own (in)ability to learn and motivation to learn. Two hypothesized models were tested within 98 psychology students, using a structural equation modelling approach: The first model implemented regulation and processing variables of the Inventory of Learning Styles [ILS, Vermunt (Learning styles and regulation of learning in higher education - towards process-oriented instruction in autonomous thinking, 1992)], the second model of the Motivated Strategies for Learning Questionnaire [MSLQ, Pintrich and de Groot (Journal of Educational Psychology, 82, 33-40, 1990)]. Results showed that structural relations exist between conceptions of constructivist learning and regulation and processing strategies. Furthermore, students who express doubt with regard to their own learning capacities are at risk for adopting an inadequate regulation strategy. A three-tiered structure of conceptual, controlling, and operational level appeared valid for the MSLQ variables, but not entirely for those of the ILS

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Genetic diversity and structure of Iberian Peninsula cowpeas compared to world-wide cowpea accessions using high density SNP markers

Cowpea (Vigna unguiculata L. Walp) is an important legume crop due to its high protein content, adaptation to heat and drought and capacity to fix nitrogen. Europe has a deficit of cowpea production. Knowledge of genetic diversity among cowpea landraces is important for the preservation of local varieties and is the basis to obtain improved varieties. The aims of this study were to explore diversity and the genetic structure of a set of Iberian Peninsula cowpea accessions in comparison to a worldwide collection and to infer possible dispersion routes of cultivated cowpea.This study was supported by EUROLEGUME project. This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 613781. European Investment Funds by FEDER/COMPETE/ POCI – Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT – Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. MMA was partially supported by the Feed the Future Innovation Lab for Climate Resilient Cowpea (USAID Cooperative Agreement AID-OAA-A-13-00070), which is directed by TJC. The funding entities had no role in the design of the study, collection, analysis and interpretation of data, or in writing the manuscript.info:eu-repo/semantics/publishedVersio

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans

Extraction of pharmacokinetic evidence of drug-drug interactions from the literature

Drug-drug interaction (DDI) is a major cause of morbidity and mortality and a subject of intense scientific interest. Biomedical literature mining can aid DDI research by extracting evidence for large numbers of potential interactions from published literature and clinical databases. Though DDI is investigated in domains ranging in scale from intracellular biochemistry to human populations, literature mining has not been used to extract specific types of experimental evidence, which are reported differently for distinct experimental goals. We focus on pharmacokinetic evidence for DDI, essential for identifying causal mechanisms of putative interactions and as input for further pharmacological and pharmacoepidemiology investigations. We used manually curated corpora of PubMed abstracts and annotated sentences to evaluate the efficacy of literature mining on two tasks: first, identifying PubMed abstracts containing pharmacokinetic evidence of DDIs; second, extracting sentences containing such evidence from abstracts. We implemented a text mining pipeline and evaluated it using several linear classifiers and a variety of feature transforms. The most important textual features in the abstract and sentence classification tasks were analyzed. We also investigated the performance benefits of using features derived from PubMed metadata fields, various publicly available named entity recognizers, and pharmacokinetic dictionaries. Several classifiers performed very well in distinguishing relevant and irrelevant abstracts (reaching F10.93, MCC0.74, iAUC0.99) and sentences (F10.76, MCC0.65, iAUC0.83). We found that word bigram features were important for achieving optimal classifier performance and that features derived from Medical Subject Headings (MeSH) terms significantly improved abstract classification. We also found that some drug-related named entity recognition tools and dictionaries led to slight but significant improvements, especially in classification of evidence sentences. Based on our thorough analysis of classifiers and feature transforms and the high classification performance achieved, we demonstrate that literature mining can aid DDI discovery by supporting automatic extraction of specific types of experimental evidence.National Institutes of Health, National Library of Medicine Program, grant 01LM011945-01 "BLR: Evidence-based Drug-Interaction Discovery: In-Vivo, In-Vitro and Clinical," a grant from the Indiana University Collaborative Research Program 2013, "Drug-Drug Interaction Prediction from Large-scale Mining of Literature and Patient Records," as well as a grant from the joint program between the Fundação Luso-Americana para o Desenvolvimento (Portugal) and National Science Foundation (USA), 2012-2014, "Network Mining For Gene Regulation And Biochemical Signaling.

Queen Elizabeth’s Leadership Abroad: The Netherlands in the 1570s

In 1576, after Edmund Grindal, archbishop of Canterbury, presumed to lecture Queen Elizabeth on the importance of preaching and on her duty to listen to such lectures, his influence diminished precipitously, and leadership of the established English church fell to Bishop Aylmer. Grindal’s friends on the queen’s Privy Council, “forward” Calvinists (or ultra-Protestants), were powerless to save him from the consequences of his indiscretion, which damaged the ultras’ other initiatives’ chances of success. This paper concerns one of those initiatives. From the late 1560s, they urged their queen “actively” to intervene in the Dutch wars. They collaborated with Calvinists on the Continent who befriended Prince William of Orange and who hoped to help him hold together a coalition of religiously reformed and Roman Catholic insurgents in the seventeen provinces of the Low Countries. The English ultra-Protestants would have their government send money, munitions, and men in arms to the Netherlands, to tip the balance against viceroys sent by King Philip II of Spain. Grindal’s setback undermined the English Calvinists’ efforts to form an Anglo-Dutch alliance which, they assumed, would boost the prospects for an international Protestant league. Yet Elizabeth did assist the Dutch as they wrestled with decisions forced on them by developments in the Netherlands during the 1570s, and she did so more consistently and more cleverly than many historians of Tudor diplomacy have thought. Two competing assessments determine the way questions are formulated in the study of the queen’s and regime’s Dutch diplomacy. The general consensus is that she was indecisive and inconsistent. Paul Hammer characterizes Elizabeth’s responses to the crises in the Low Countries as a “zigzag of different” (“even contradictory”) maneuvers. Wallace McCaffrey and R. B. Wernham agree that England’s “hesitations and gyrations” do not pass as coherent, creditable policy. Charles Wilson scolds Elizabeth for being timid and tepid--incapable of enthusiasm for “a great cause.” But David J.B. Trim’s striking counterthrust depicts the queen’s overtures to Netherlanders as part of her courageous – and “confessionally driven” – foreign policy; Trim replaces “hesitation” and “zigzag” with a coherent “Protestant programme of action prioritized by the Elizabethan government” with the aim of improving prospects for “Calvinist internationalism.” What follows is an alternative to all these characterizations, one that, as noted, finds evidence for greater consistency and coherence in Elizabeth’s leadership and less confessional “drive.” That she would have been uneasy around religious extremists ought not to astonish us; her father’s, step-brother’s, and step-sister’s reigns as well as the start of her own were disturbed by zealous subjects, who were bent on shoring up or dismantling the realm’s religious settlements

Interaction of 8-Hydroxyquinoline with Soil Environment Mediates Its Ecological Function

Background: Allelopathic functions of plant-released chemicals are often studied through growth bioassays assuming that these chemicals will directly impact plant growth. This overlooks the role of soil factors in mediating allelopathic activities of chemicals, particularly non-volatiles. Here we examined the allelopathic potential of 8-hydroxyquinoline (HQ), a chemical reported to be exuded from the roots of Centaurea diffusa. Methodology/Principal Findings: Growth bioassays and HQ recovery experiments were performed in HQ-treated soils (non-sterile, sterile, organic matter-enriched and glucose-amended) and untreated control soil. Root growth of either Brassica campestris or Phalaris minor was not affected in HQ-treated non-sterile soil. Soil modifications (organic matter and glucose amendments) could not enhance the recovery of HQ in soil, which further supports the observation that HQ is not likely to be an allelopathic compound. Hydroxyquinoline-treated soil had lower values for the CO2 release compared to untreated non-sterile soil. Soil sterilization significantly influenced the organic matter content, PO 4-P and total organic nitrogen levels. Conclusion/Significance: Here, we concluded that evaluation of the effect of a chemical on plant growth is not enough in evaluating the ecological role of a chemical in plant-plant interactions. Interaction of the chemical with soil factors largel

Changes in Seizure Frequency and Test-Retest Scores on the Wechsler Adult Intelligence Scale

Test-retest performance on the Wechsler Adult Intelligence Scale (WAIS) of two groups of adult epilepsy patients are presented and compared. In one group, Seizures Improved (SI) group, seizure frequency had decreased during the test-retest interval, and in the other group, Seizures Unimproved (SU) group, the number of seizures had either increased or stayed the same over the test-retest interval. The SI group showed a significant test-retest improvement on WAIS Verbal IQ, Performance 1Q, and Full Scale IQ, as well as on eight of 11 WAIS subtests. In comparison, the SU group showed significant increases only on the Performance IQ and Object Assembly subtest. Furthermore, differences between the two groups were observed in the pattern of test-retest changes seen on the Performance measures relative to the Verbal measures. The results suggest that change in seizure frequency is one of the factors associated with test-retest changes in the intellectual functioning of epilepsy patients. RÉSUMÉ Les rÉsultats obtenus À I‘Échelle de WAIS (Wechsler Adults Intelligence Scale) a partir d'une passation I (test) et d'une passation II (retest) chez deux groupes d'Épileptiques adultes sont prÉsentÉs et compares: (a) Dans un groupe la frequence des crises a diminue dur-ant I'intervalle “test-retest” (c'est a dire dans I'inter-valle separant la passation I (test) de la passation II (retest): Groupe des crises ameliorees (SI: seizures improved), (b) Dans l'autre groupe le nombre des crises au contraire a augmente ou bien est reste iden-tique au cours de I'intervalle “test-retest”: Groupe des crises non ameliorees (SU: seizures unimproved). Le groupe des “crises ameliorees” montre une amelioration significative tant sur le plan du QIV (quotient de I'echelle verbale), que du QIP (quotient de I'echelle performance) et du QIG (quotient global), ainsi que de 8 des subtests parmi les onze que contien I'echelle. En comparaison le groupe des “crises non ameliorees” ne montre une amelioration significative qu'au niveau du QIP et en particulier sur le subtest d'assemblage d'ob-jets (celui-ci faisant partie de I'echelle performance). De plus, on observe entre les deux groupes des differences du “type” des modifications entrainees par la situation “test-retest”, sur les rÉsultats obtenus a I'echelle performance et ceux obtensus a I'echelle verbale. Ces rÉsultats permettent de suggerer que, dans le fonctionnement intellectuel des sujets epileptiques, les changements dans la frequence des crises sont un des facteurs a mettre en correlation avec les changements observes a partir de la situation “test-retest”. RESUMEN Se compararon dos grupos de adultos con epilepsia por medio del rendimiento en dos tests de WAIS. En un grupo, la frecuencia de los ataques habia disminuido en el intervalo entre el primer test y el segundo [grupo con mejoria (SI)], mientras que en el otro el mimero de crisis no habia variado o habia au-mentado [grupo sin mejoria (SU)]. El grupo SI mostro una mejoria en laescala verbal CI, en la realizacion CI, en la escala total de CI y en los subtests WAIS. En comparacion, el grupo SU solo mostro un aumento significativo en la realizacion CI y en el subtest de Reunion de Objetos. Ademas, se observaron diferen-cias entre los dos grupos en lo que respecta a la prim-era y a la segunda prueba en la realizacion de las medidas verbales. Los resultados sugieren que los cambios en la frecuencia de los ataques juegan un papel en lo que respecta a funciÓn intelectual cuando se compara el primer WAIS con el segundo. ZUSAMMENFASSUNG Test und Retest Ergebnisse im WAIS von 2 Gruppen erwachsener Epileptiker werden dargestellt und ver-glichen. In einer Gruppe hatte die Anfallshaufigkeit wahrend des Test-Retest-Intervalls abgenommen– verbesserte Gruppe (SI)–und in einer anderen Gruppe war die Anfallshaufigkeit entweder gestiegen oder gleich geblieben wahrend des Test-Retest-Intervalls– unveranderte Gruppe (SU). Die SI-Gruppe zeigte signifikante Verbesserung zwischen Test und Retest im Verbal-IQ des WAIS, im Handlungsteil und im Gesamt-IQ ebenso wie in 8 von 11 WAIS Subtests. Im Vergleich hierzu zeigte die SU-Gruppe signifikante Verbesserung nur im Handlungs-IQ und im Objekte-zuordnungs-Subtest. Weiterhin wurden Unterschiede zwischen den beiden Gruppen im Muster der Test-Retest-Veranderungen im Verhaltnis des Handlung-steils zum Verbalteil bemerkt. Die Ergebnisse lassen vermuten, dalJ die Veranderung der Anfallshaufigkeit einer der Faktoren ist, der hinsichtlich der in-tellektuellen Funktion anfallskranker Patienten Bezie-hungen zu den Veranderungen des Test-Retest-Ergeb-nis aufweist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65457/1/j.1528-1157.1981.tb04334.x.pd