Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout

Background: The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor alpha (TNF alpha) and other immune factors, are produced and act on the reproductive system. However, TNF alpha is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNF alpha in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta). Methods: To determine the in vivo regulation of TNF alpha expression in the ovary, preovulatory brook trout (Salvelinus fontinalis) were injected intraperitoneally with either saline or bacterial lipopolysaccharide (LPS). In control and recombinant trout TNF alpha (rtTNF alpha)-treated brown trout granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI) staining. Furthermore, we determined the in vitro effects of rtTNF alpha on follicle contraction and testosterone production in preovulatory brown trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNF alpha-treated ovarian tissue by microarray and real-time PCR (qPCR) analyses. Results: LPS administration in vivo causes a significant induction of the ovarian expression of TNF alpha. Treatment with rtTNF alpha induces granulosa cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNF alpha causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNF alpha induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. Furthermore, the expression of kallikrein, TOP-2, serine protease 23 and ADAM 22, genes that have been postulated to be involved in proteolytic and tissue remodeling processes during ovulation in trout, increases in follicles incubated in the presence of rtTNF alpha. Conclusions In view of these results, we propose that TNF alpha could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction.

A simple score for estimating ischemic heart disease in patients with non-traumatic chest pain in primary care

Background: Modelling epidemiological knowledge in validated clinical scores is a practical mean of integrating EBM to usual care. Existing scores about cardiovascular disease have been largely developed in emergency settings, but few in primary care. Such a toll is needed for general practitioners (GP) to evaluate the probability of ischemic heart disease (IHD) in patients with non-traumatic chest pain. Objective: To develop a predictive model to use as a clinical score for detecting IHD in patients with non-traumatic chest-pain in primary care. Methods: A post-hoc secondary analysis on data from an observational study including 672 patients with chest pain of which 85 had IHD diagnosed by their GP during the year following their inclusion. Best subset method was used to select 8 predictive variables from univariate analysis and fitted in a multivariate logistic regression model to define the score. Reliability of the model was assessed using split-group method. Results: Significant predictors were: age (0-3 points), gender (1 point), having at least one cardiovascular risks factor (hypertension, dyslipidemia, diabetes, smoking, family history of CVD; 3 points), personal history of cardiovascular disease (1 point), duration of chest pain from 1 to 60 minutes (2 points), substernal chest pain (1 point), pain increasing with exertion (1 point) and absence of tenderness at palpation (1 point). Area under the ROC curve for the score was of 0.95 (IC95% 0.93; 0.97). Patients were categorised in three groups, low risk of IHD (score under 6; n = 360), moderate risk of IHD (score from 6 to 8; n = 187) and high risk of IHD (score from 9-13; n = 125). Prevalence of IHD in each group was respectively of 0%, 6.7%, 58.5%. Reliability of the model seems satisfactory as the model developed from the derivation set predicted perfectly (p = 0.948) the number of patients in each group in the validation set. Conclusion: This clinical score based only on history and physical exams can be an important tool in the practice of the general physician for the prediction of ischemic heart disease in patients complaining of chest pain. The score below 6 points (in more than half of our population) can avoid demanding complementary exams for selected patients (ECG, laboratory tests) because of the very low risk of IHD. Score above 6 points needs investigation to detect or rule out IHD. Further external validation is required in ambulatory settings.

An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.

Il dialetto in poesia : studio metrico sulla poesia novecentesca del Nord-Italia

Cette thèse de doctorat a comme sujet la poésie dialectale contemporaine du Nord de l'Italie. Il s'agit d'une étude métrique de poésies écrites dans divers dialectes sélectionnés sur la base d'un système linguistique unitaire tel que le galloitalico que l'on trouve au Piémont, en Lombardie, en Ligurie et en Emilie-Romagne. Plus précisément, le corpus soumis à examen prend en considération les formes poétiques qui, au cours de la deuxième moitié du XXème siècle, confèrent au vers libre une certaine régularité comme les structures « simples » presque archétypiques des quatrains, des huitains et de toutes les formes métriques qui optent pour une strophe unique avec un nombre de vers multiple de quatre. Ces dernières sont particulièrement intéressantes car elles peuvent cacher une structure en quatrain souvent dévoilée par la disposition des rimes, de la syntaxe et parfois également du rythme. Ces choix qui pourraient sembler arbitraires sont en réalité liés aux tentatives des poètes de reprendre des formes de la tradition pour les innover ou simplement pour les reproposer avec ou sans modification. Les liens avec la tradition et la notion de libertà nella chiusura ont été étudiés en fonction des composantes fondamentales de l'organisme métrique, c'est-à-dire la forme, les rimes, la syllabation et le rythme. Pour citer Raboni, il s'agit de comprendre la manière dont "la dissonanza può essere usata per «salvare» l'ipotesi tonale" et la manière dont "la trasgressione metrica finisce col prolungare la vita della regola alla quale, derivandone, si oppone" (Giovanni RABONI, L'opera poetica, a cura di Rodolfo Zucco, Milano, Mondadori, i Meridiani, 2006, p.403). L'objectif de cette recherche est donc d'explorer et d'expliquer l'ambiguïté métrique de la poésie dialectale du XXème siècle tout en se référant à un article fondamental pour ce genre d'étude écrit par Pier Vincenzo Mengaldo et intitulé Questioni metriche novecentesche. L'ambition de cette thèse ne se limite pas à prolonger une réflexion encore à ses débuts dans le cas de la poésie régionale contemporaine, mais elle réalise également un panorama essentiel, bien que sommaire, qui met au premier plan les aspects innovateurs, et parfois conservateurs de la poésie dialectale contemporaine de certaines régions du Nord de l'Italie.

Sagor : af Z. Topelius - [Bilder] - Första samlingen (0001)

1 Helsingfors : A. W. Gröndahl 1847

Al-Bīrūnī's Kitāb Sānk and Kitāb Pātanğal:A Historical and Textual Study

The historical pole of this research distinguishes differing historical and cultural contexts in which the scholar al-Bïrûnî evolved. Between the years 973 and 1017, he lived in Khwarezm (Kät and JürjänTya), Ray, and Jürjän. He also dwelt in Kabul and Ghazna, both situated on a passage between Persia and India, and travelled to some parts of early medieval India between the years 1017 and 1030. Evidence pointing to him having made actual direct observations beyond the abode of Islam remains scanty. According to his writings, only five locales emerge as having been visited by him, all situated in today's Afghanistan and Pakistan. When al-BTrunl visited these places, he encountered the society of the Indian Shähis, who followed a form of Brahmanism. Al-Bïrûnï's knowledge of Sanskrit was the result of a long process that lasted at least 30 years (1000-1030). In order to reach the level of Sanskrit that enabled him to translate several works from Sanskrit into Arabic, he needed to work with literate people well-versed in Sanskrit, who may also have had some comprehension of Arabic, and/or Persian. The textual pole of this dissertation examines the question of the relationship between al- Bïrûnï's Arabic Kitab Sank and Kitäb Pätangal - two works related to Sämkhya-Yoga - and their possible Sanskrit sources. A philological survey based on these Arabic translations and on Sämkhya-Yoga Sanskrit literature highlights that al-Bïrûnï's translations, both, are related to the classical phase in the development of these two Indian philosophical systems. Despite the early spread of Yoga and Sämkhya ideas through Sanskrit literature, it seems that between the early 11th and 16th centuries they lost vitality amongst Indian scholars. Therefore, al-Bïrûnï's translation of works related to these specific Indian philosophies in the early 11th century CE deserves attention. The second pole of this study also demonstrates that al-BTrünl's hermeneutics played an important part in his transmission of these two Indian schools of thought, as he highly transformed his source in both form and substance. This dissertation considers the question of the relationship between al-Bïrûnï's Arabic translations and their possible Sanskrit sources from the viewpoint of Translation Studies; which makes it possible to point out potential candidates for being al-Bïrûnï's original Sanskrit sources with some confidence. Overall, the Kitäb Sank and the Kitäb Pätangal represent original works of Sämkhya and Yoga, as viewed and transmitted by a Perso-Muslim scholar, rather than pure translations of Sanskrit work.

Nanoantenna enhanced emission of lightharvesting complex 2: the role of resonance, polarization, and radiative and non-radiative rates

Nanoantennae show potential for photosynthesis research for two reasons; first by spatially confining light for experiments which require high spatial resolution, and second by enhancing the photon emission of single light-harvesting complexes. For effective use of nanoantennae a detailed understanding of the interaction between the nanoantenna and the light-harvesting complex is required. Here we report how the excitation and emission of multiple purple bacterial LH2s (light-harvesting complex 2) are controlled by single gold nanorod antennae. LH2 complexes were chemically attached to such antennae, and the antenna length was systematically varied to tune the resonance with respect to the LH2 absorption and emission. There are three main findings. (i) The polarization of the LH2 emission is fully controlled by the resonant nanoantenna. (ii) The largest fluorescence enhancement, of 23 times, is reached for excitation with light at λ = 850 nm, polarized along the long antenna-axis of the resonant antenna. The excitation enhancement is found to be 6 times, while the emission efficiency is increased 3.6 times. (iii) The fluorescence lifetime of LH2 depends strongly on the antenna length, with shortest lifetimes of [similar]40 ps for the resonant antenna. The lifetime shortening arises from an 11 times resonant enhancement of the radiative rate, together with a 2–3 times increase of the non-radiative rate, compared to the off-resonant antenna. The observed length dependence of radiative and non-radiative rate enhancement is in good agreement with simulations. Overall this work gives a complete picture of how the excitation and emission of multi-pigment light-harvesting complexes are influenced by a dipole nanoantenna.

PET-Saúde: uma experiência prática de integração ensino-serviço-comunidade

Este trabalho relata a experiência de integração ensino-serviço-comunidade vivenciada por membros de equipes de Saúde da Família e graduandos de Medicina e Enfermagem participantes do PET-Saúde da Universidade Estadual de Santa Cruz. A referida integração contextualizou-se com o desenvolvimento do projeto "Unidos contra a dengue", mobilização conjunta da instituição de ensino com o serviço de saúde e a comunidade no combate à dengue no bairro Nossa Senhora da Vitória, Ilhéus-Bahia. O foco das ações desse projeto foram as atividades de educação em saúde, nas quais se empregou preferencialmente metodologias ativas de ensino e aprendizagem. A mobilização contou com a participação expressiva da população das mais diversas faixas etárias. O sucesso do projeto ressalta a importância da implantação de programas como o PET-Saúde, que fortalecem a interação entre ensino-serviço-comunidade - importante para construção de serviços de saúde mais qualificados, capazes de inter-relacionar promoção, prevenção e assistência à saúde, possibilitando ações nessa área mais próximas das reais necessidades do SUS. Com esta experiência, espera-se ter contribuído para a formação de graduandos em saúde e qualificação em serviço de profissionais dessa área mais dispostos a trabalhar de forma integrada e integradora com a comunidade.

Pikku Ellin sunnuntaikirja - I

Tekijä: Emilie Karolina (Emmi) Ljungberg.

Pikku Ellin sunnuntaikirja - II

Tekijä: Emilie Karolina (Emmi) Ljungberg.