21,168 research outputs found

    The role of microbial translocation and gut microbiota in HIV-1 infection

    No full text
    HIV-1 infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Translocation of microbial compounds from a leaky gut to systemic circulation, so called microbial translocation (MT), is a major driver of the immune activation. Additionally, gut microbiota dysbiosis in HIV-1 infected patients further facilitate and fuel MT. The objectives of this thesis were to study: * how different ART regimens and usage of antibiotics affect markers of MT (I, II), * the alternations of gut microbiota during HIV-1 infection and the effect of ART (III,IV).In a clinical randomized trial, HIV-1 infected subjects started ART based on efavirenz (n=37) or ritonavir-boosted lopinavir (n=34). Levels of MT markers and of enterocyte death were elevated at baseline (BL), and MT markers declined until follow up after 72 weeks, but the reduction of anti-flagellin IgG antibodies was significant only in lopinavir treated patients. Levels of Intestinal Fatty Acid Binding Protein (I-FABP) remained unchanged at 72 weeks, but were temporarily increased after one month in efavirenz treated patients. 29 subjects with concomitant use of antibiotics had superior reduction of soluble CD14 (sCD14) levels. These data show that choice of ART and antibiotics usage could affect the kinetics of some MT markers.To further explore the impact of antibiotics usage on MT, we performed a longitudinal study on HIV-1 patients initiating ART without (n=13) or with (n=13) co-trimoxazole (TMP-SMX) as prophylaxis against Pneumocystis jirovecii. Following ART, levels of LPS-binding protein (LBP) were reduced only in the TMP-SMX group, whilst levels of sCD14 declined in both groups after one year. The LBP decrease remained significant in a multivariate analysis model adjusting for co-variates including BL CD4+ T-cell count. This study confirmed that concomitant use of antibiotics and ART in severely immune deteriorated individuals may beneficially influence the kinetics of MT markers.In the third study, the composition of gut microbiota was determined by 16S rRNA sequencing in 28 HIV-1 progressors, 3 Elite controllers (EC) and 9 uninfected controls at BL, and additionally after ten months of ART in 16 subjects. Gut microbiome α-diversity was reduced in HIV-1 infected individuals as compared to controls, and further declined after introduction of ART. At BL, α-diversity was positively correlated with CD4+ T-cell counts, but in contrary several markers of MT/immune activation were inversely correlated. Microbiome of EC had the lowest interindividual variation (ß-diversity), clustering together in PCoA analysis. The bacterial composition at genus level was altered in HIV-1 progressors with higher abundance of Lactobacillus, and depletion of Lachnobacterium, Faecalibacterium and Hemophilus. Thus, this study showed that the alternations of gut microbiota during HIV-1 infection are associated with the level of immune dysfunction, and that almost one year of ART does not restore the shifts in the gut microbiome.In the last work, we studied the gut microbiome of 16 EC in relation to 32 matched ART naive HIV-1 positive individuals and 16 uninfected controls. The number of observed genera and richness indices Chao-1 and ACE were significantly higher in EC as compared to naive patients. The gut microbiota in EC was enriched in genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira, whilst Blautia and Anaerostipes were reduced. Determination of inferred bacterial functionality by PICRUSt analysis revealed that carbohydrate metabolism related genes were depleted in EC. In contrary, pathways related to fatty acid metabolism, PPAR-signaling and lipid biosynthesis proteins were more abundant in EC vs naive. The kynurenine pathway of tryptophan metabolism was altered only during progressive HIV-1 infection, and kynurenine tryptophan (K/T) ratio was inversely associated with gut microbiota richness. This study shows that EC have richer gut microbiota than untreated HIV-1 patients with progressive infection, with a unique bacterial composition and a distinct metabolic profile which may be involved in the control of HIV-1.In summary, data from the studies in my thesis reveal that MT in HIV-1 infection is reduced by ART but also that the choice of ART influences this decline. Additionally, the antibiotics usage may affect the levels of MT. The complexity, composition and functionality of gut microbiota are disturbed in HIV-1 infected individuals with progressive disease, whilst EC have a unique gut microbiota profile that eventually contributes to their control of HIV-1.List of scientific papersI. Vesterbacka Jan, Nowak Piotr, Barqasho Babilonia, Abdurahman Samir, Nyström Jessica, Nilsson Staffan, Funaoka Hiroyuki, Kanda Tatsuo, Andersson Lars-Magnus, Gisslèn Magnus, Sönnerborg Anders. Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy. PLoS One. 2013;8(1):e55038. https://doi.org/10.1371/journal.pone.0055038 II. Vesterbacka Jan, Barqasho Babilonia, Häggblom Amanda, Nowak Piotr. Effects of Co-Trimoxazole on Microbial Translocation in HIV-1-Infected Patients Initiating Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2015 Aug;31(8):830-6. https://doi.org/10.1089/AID.2014.0366 III. Nowak Piotr, Troseid Marius, Avershina Ekatarina, Barqasho Babilonia, Neogi Ujjwal, Holm Kristian, Hov Johannes R, Noyan Kajsa, Vesterbacka Jan, Svärd Jenny, Rudi Knut, Sönnerborg Anders. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS. 2015 Nov;29(18):2409-18. https://doi.org/10.1097/QAD.0000000000000869 IV. Vesterbacka Jan, Rivera Javier, Noyan Kajsa, Parera Mariona, Neogi Ujjwal, Calle Malu, Paredes Roger, Sönnerborg Anders, Noguera-Julian Marc, Nowak Piotr. Richer gut microbiota with distinct metabolic profile in HIV infected Elite Controllers. Sci Rep. 2017 Jul 24;7(1):6269. https://doi.org/10.1038/s41598-017-06675-1 </p

    Jan Kapr's contribution to contemporary music : an essay about a composer and teacher

    No full text
    This creative project is a treatise on a leading personality of Czechoslovakian musical life, the composer, Jan Kapr. The author discusses the following:1. The complicated development of Kapr's career and work, 2. Kapr's method of organization of musical material in a composition, as described in his book Constants,3. His former and current style which is demonstrated in two of his compositions, Concert Variations, for flute and string orchestra and Testimonies for four solo instruments,4. Two of his recent works, Exercises for Gydli and the Symphony No. 7, Country of Childhood.Thesis (M.A.

    Going Beyond Counting First Authors in Author Co-citation Analysis

    No full text
    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    ELEVEN FACES OF JAN GOGOL, JR.

    No full text
    Author Jan Rendl in his thesis attempts to look at the world of ideas and educator Jan Gogola ml. through the eleven chapters in which each chapter somehow characterizes itself by Jan Gogola ml. and each of them somehow determines its creative ideas of it through the metaphor of a football match when Jan Gogola, with its characters, movies himself a teammate, as well as defensively. It gives goals with their situations as well as occasionally digging his opponents ankles. Jan Gogola ml. thus embodies one stage of the Department of Documentary Film at FAMU, which often stands at the intersection between teaching activities and Karel Vachek among students who applied by them during their seminars psychological methods that work must be peculiarly associated with the author of the film

    Dr. Jan French – Faculty Author Interview

    No full text
    Dr. Jan French, Assistant Professor of Anthropology, discusses her new book, Legalizing Identities: Becoming Black or Indian in Brazil’s Northeast, which shows how law can successfully serve as the impetus for the transformation of cultural practices and collective identity

    Jan Bernátek - organ works

    No full text
    This graduation thesis provides a more detailed view on compositoins of Jan Bernátek.The aim is to present this less well-known temporary czech author,who makes use of the organ in the majority of his work

    The Theological Work of Jan Valerián Jirsík

    No full text
    Anglická anotace The theological work of Jan Valerian Jirsík Jan Hamberger This thesis deals with the theological work of the Czech 19th century author Jan Valerián Jirsík (1798-1883). Its first part consists of an introduction into the Czech historical context of the 19th century and the life of the author. Its second part presents a survey of the literary-theological work of Jirsík in three life phases: the first phase is demarked by his activity as chaplain and vicar, the second phase by his editorial activity for Casopis pro katolické duchovenstvo (trans. Magazine for catholic clergy) and the last phase by his pontifical years in the diocese of Southern Bohemia. His literary work is divided by theme into various periods, shortly described and characterized. The last and major section of this thesis deals with the most comprehensive and renown work of Jan Valerián Jirsík - Populární dogmatika (trans. Popular doctrine). This pivotal work of theologian Jirsík is discussed at large and analyzed by tractate, both apologetic and dogmatic. The conclusion expresses the prevailing character of the entire work of Jirsík and its significance. Key words: Theology Apologetic theology Dogmatic theology Theological literature Catholic Churc

    Actor Profile of Jan Vondracek

    No full text
    Divided into seven chapters, the work treats seven roles of the Czech actor Jan Vondracek (born in 1966) in Divadlo v Dlouhe Theatre from 1997-2008. The author starts from the analysis of Vondracek's performances and describes the specifics of his showmanship and generalizes the personality traits of his characters. She also ponders the meaning of Czech dramatic art based on typical characters in the context of contemporary Czech theatre

    The picture of Jan Palach in czech culture

    No full text
    This thesis deals with cultural image of Jan Palach. It focuses especially on symbols and myths contributing to construction of this image. The main emphasis is given on the concept of sacrifice - the study analyzes comparisons of Jan Palach to archetypes of Jesus Christ and young martyrs. In the second part author analyzes national dimension of Palach's cultural image. She deals with comparison of Palach to Jan Hus and analyzes Palach's funeral as a part of tradition of Czech public funerals - quiet national demonstrations. The methodology of the study is discourse analysis, which is applied not only on texts (fiction and nonfiction), but also on photographic and film footage

    Jan Maruna - the author of my region

    No full text
    Na začátku práce jsem autora blíže představila a následně analyzovala jeho tři romány: Ambra a moře v nás, Hrobník od Svatého Bartoloměje, Vlak do nebe. Při rozboru textů jsem se zaměřila na téma, prostředí a čas, charakteristiku postav, kompozici, jazyk a jeho prostředky. Práce je rozdělena do čtyř hlavních kapitol: Portrét Jana Maruny, Vybrané romány, Analýza struktury vybraných děl a Ostatní prozaická díla v kontextu Jana Maruny.Katedra českého jazyka a literaturyObhájenoAt the beginning of the thesis I introduced the author in more detail and subsequently analysed his three novels: Ambra a moře v nás, Hrobník od Svatého Bartoloměje, Vlak do nebe. When I was examining the texts I was focused on the topic, setting and time, characteristic of characters, composition, language and its devices. The Bachelor thesis is divided into 4 main chapters: Portrait of Jan Maruna, Chosen novels, Analysis of structure of chosen works and Other prosaic works in context of Jan Maruna
    corecore