Dissertations / Theses on the topic 'Disease cycle'
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1
Hong, Angela M. "Cell cycle protein expression in AIDS-related and classical Kaposi's sarcoma." Connect to full text, 2004. http://hdl.handle.net/2123/583.
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Thesis (Ph. D.)--University of Sydney, 2004.Title from title screen (viewed 5 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Medicine. Includes list of published articles and presentations. Includes bibliographical references. Also available in print form.
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Uebayashi(Yoshitoshi), Elena Yukie. "Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs." Kyoto University, 2017. http://hdl.handle.net/2433/227584.
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Hamana, Katy. "An exploration of the physical activity life cycle in Huntington's disease." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/107624/.
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This study aimed to explore how living with Huntington’s disease (HD) impacts on the experience of physical activity (PA) across the stages of the disease. The research questions were: 1) What are the experiences of PA participation across the stages of HD? 2) How do the nuances of living with a neurodegenerative disease such as HD affect engagement in PA? The focus group (FG) method was used to explore the breadth of experiences of PA in the context of HD. Participants of eight FGs across the UK included people across the spectrum of HD with varying degrees of symptom manifestation, caregivers (family members/formal caregivers), and healthcare professionals. Framework analysis method (Ritchie and Spencer 1994) was used for data analyses. The process involved five stages: familiarisation, coding, indexing, charting and mapping, and interpretation of data to develop key themes. A key part of the process was development of an analytical coding framework to use in the indexing (of the data) stage. The data itself and a theoretical model (self-regulation model) were both used to develop the framework. The literature review identified a lack of theoretically underpinned qualitative research in PA and HD, therefore the self-regulation model (SRM) (Levanthal et al. 1984) was selected to explore PA in HD. Components of the SRM were used to develop a priori ‘index codes’ of the framework. Open coding of transcripts was also used to develop ‘index codes’ of the framework. The findings highlighted that over the life-span of the disease the needs and abilities of people with HD change, and this has implications such as coping responses and strategies for how PA is experienced and sustained in HD. Social context and environment are key aspects that require consideration for PA in HD, and this has implications such as consideration of familial or caregiver support and general public awareness of HD for development of management and research interventions. The SRM facilitated understanding of participant experiences, however, it appeared that self-regulation of activities becomes more collaborative with the caregiver as HD progresses. As such, a modified version of the SRM that incorporates the increasingly collaborative regulation of PA has been suggested and is presented for understanding PA in HD.
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Wilks, Mark. "Quantitative bacteriology of the vaginal flora in health and disease." Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266015.
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Raina, Arun K. "Oncogenic Parallels in Alzheimer Disease." Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1102023891.
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Smith, Maria Z. "Neuronal cell cycle regulation and the pathophysiology of Alzheimer's disease and related dementias." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393617.
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Bourgeois, Chantal G. "The impact of AIDS on the life cycle of young gay men." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0022/MQ50697.pdf.
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Chen, Lina. "Structural and functional studies of the cell cycle regulator RGC-32." Thesis, University of Sussex, 2017. http://sro.sussex.ac.uk/id/eprint/68451/.
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Boeras, Debrah I. "Chromosome missegregation in Alzheimer's disease caused by presenilin 1." [Tampa, Fla] : University of South Florida, 2005. http://purl.fcla.edu/usf/dc/et/SFE0001706.
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Dear, Graeme. "Studies on the biology, metabolism and pathogenicity of Pseudomonas Anguilliseptica." Thesis, Heriot-Watt University, 1985. http://hdl.handle.net/10399/1599.
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Bailey, Jarrod. "Analysis of the proteins involved in the life-cycle and replication of Newcastle disease virus." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264418.
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Linseman, Tara. "Functional Analysis of a Coding Variant In ZC3HC1 at 7q32.2 Associated with Protection Against Coronary Artery Disease (CAD)." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34329.
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Coronary artery disease (CAD), characterized by the narrowing of coronary
arteries through the complex manifestation and development of atherosclerosis, is a
complex disease and one of the leading causes of death worldwide. Both genetic
and environmental factors are believed to contribute equally to the risk of CAD.
Recently, a study identified a non-synonymous coding variant, rs11556924, (MAF,
0.38) in ZC3HC1 associated with protection against CAD (p= 9.8x10-18; OR= 0.90).
NIPA, encoded by ZC3HC1, is a characterized F-Box protein and regulator of cell
cycle. Since the amino acid change (Arg363His) is in a conserved region of NIPA
and is predicted to have functional effects (Polyphen-2), this study aimed at
understanding the functional implications of this amino acid change on NIPA and cell
cycle regulation. Here we are able to effectively show a) allele specific differences in
mRNA expression in whole blood, b) a slight structural difference between
NIPA363Arg and NIPA363His variants, c) proliferation rates of NIPA363Arg
expressing cells were significantly increased, and d) phosphorylation of a critical
serine residue in close proximity to aa.363 is not statistically different between the
two variants. These results suggest that rs11556924 plays a direct role in
development of CAD through its disruption of cell cycle regulation and NIPA mRNA
availability. This study is the first to identify a molecular basis for the association of
rs11556924 to CAD development.
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Varvel, Nicholas H. "The role of beta-Amyloid and inflammation in neuronal cell cycle events in Alzheimer's disease mouse models." Cleveland, Ohio : Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1226609920.
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Fiorelli, Tina N. "Proteolytic Processing of the Amyloid Precursor Protein During Apoptosis and Cell Cycle: Implications for Alzheimer's Disease." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4486.
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Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the brain, Aϐ production may also propagate through the brain in an anatomical fashion. In order to investigate this possibility, we examined two broad cellular processes induced in cells when exposed to Aϐ, p53-dependent apoptosis and cell cycle activation. We report that p53-dependent apoptosis is associated with a decrease in the Aϐ and sAPP-alpha and an increase in an alternative, caspase-cleaved fragment of APP, resulting from an apparent cleavage in the near extracellular domain of APP. Mitosis is associated with the phosphorylation of both tau and APP, and increased production of Aϐ. Our results indicate that while p53-dependent apoptosis is not associated with increased amyloidogenesis, cell cycle activation increases Aϐ production and may play a role in disease propagation. Together, these findings suggest various treatment approaches, including cell cycle inhibition and disruption of APP endocytosis, which may decrease amyloidogenic processing. Continued research into these potential approaches, coupled with earlier detection of the disease process, could lead to promising treatments for Alzheimer's disease.
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Lopes, Previdelli Renato [Verfasser]. "Novel insights on viral factors involved in the Marek's Disease virus' life cycle / Renato Lopes Previdelli." Berlin : Freie Universität Berlin, 2019. http://d-nb.info/1200409752/34.
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Van, Niekerk Elizabeth C. "Evaluation of a quality improvement cycle intervention in the provision of PMTCT at a regional hospital." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/85669.
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Thesis (MMed)-- Stellenbosch University, 2013.ENGLISH ABSTRACT: The vast majority of new Human Immunodeficiency Virus (HIV) infections in infants and young children occur through mother-to-child-transmission (MTCT), either during pregnancy, labour or delivery or by breastfeeding. Without access to perinatal MTCT (PMTCT) programmes approximately 30% of all babies born annually will be infected with HIV. OBJECTIVES The aim was to implement and audit a quality improvement cycle at the Worcester Obstetric Unit, which comprises of Worcester Hospital, a regional hospital in the Western Cape Province and its level one midwife obstetric Unit (MOU), in order to improve the quality of the PMTCT programme. The intervention included the implementation of easy changes and tools in the Antenatal Clinic, Infectious Diseases Clinic and Labour ward. METHODS The files and antenatal records of all HIV positive patients and patients with an unknown HIV status, who delivered at the Worcester Obstetric Unit during January, February and March of 2010 and 2011, were reviewed. All HIV negative patients and patients that had stillbirths and miscarriages were excluded. The pre-interventional findings of 2010 were compared with the post-interventional findings of 2011. RESULTS At the Worcester Obstetric Unit, for the study time period, there were 907 deliveries in 2010, of which 102 (11.2%) patients were HIV positive and 4 (0.4%) had an unknown HIV status compared to 2011, with 865 deliveries of which 108(12.5%) patients were HIV positive and no patients had an unknown HIV status. Significantly more patients were diagnosed with HIV before they fell pregnant than during pregnancy in the 2011 group, when compared with the 2010 group. A CD4 count was done on 94% of patients who were newly diagnosed with HIV and those with an unknown CD4 count result in the 2010 group, compared to 92% in 2011. There was a significant improvement after the intervention in the time it took from when blood was drawn for a CD4 count until the result was followed up, the median time decreased from 34 to 8 days (p=0.000001). Significantly more patients qualified for highly active antiretroviral therapy (HAART) after the guidelines were changed and the CD4 cut off was increased to 350 cells/l (p=0.001). Prior the intervention 18 patients did not receive the correct management before delivery due to preventable reasons, compared to one at the MOU. After the intervention this decreased significantly to only one patient at Worcester Hospital and none at the MOU (p=0.000001). Before the intervention adherence to the PMTCT protocol at the MOU was significantly better than at the hospital (p=0.0005) and after the intervention there was no significant difference (p=1.0). CONCLUSION Although the audit and quality improvement cycle was performed at a single hospital, with specific changes geared towards their needs, the basic principles can be applied to any Unit in the country providing a PMTCT service. Educating staff, creating awareness and reminding staff of the basic principles of PMTCT, implementing small changes and streamlining processes and setting specific goals or timelines, can lead to significant improvements in care, which ultimately will lead to a decrease in PMTCT of HIV and HIV related maternal and infant morbidity and mortality.
AFRIKAANSE OPSOMMING: Die oorgrote meerderheid (>90%) van nuwe Menslike Immuniteitsgebreksvirus (MIV) infeksies in babas en jong kinders vind plaas deur middel van moeder-na-kind-oordrag, hetsy gedurende swangerskap, die kraamproses of borsvoeding. Sonder toegang tot perinatale voorkomingsprogramme (PMTCT) sal ongeveer 30% van alle babas jaarliks met MIV geïnfekteer word. DOELWITTE Die doel van die studie was om ‘n gehalteverbeteringsiklus by die Worcester Verloskunde Eenheid, wat bestaan uit Worcester Hospitaal, 'n streekshospitaal in die Wes-Kaapprovinsie en sy vlak een vroedvrou verlossingseenheid (VVE), te implementer en daarna te oudit, om sodoende die gehalte van die PMTCT-program te verbeter. Die intervensie het bestaan uit die implementering van eenvoudige veranderinge en prosesse in die voorgeboortekliniek, infeksiesiekte-kliniek en kraamsaal. METODES Die lêers en voorgeboorte rekords van alle MIV-positiewe pasiënte en pasiënte met 'n onbekende MIV-status, wat gedurende Januarie, Februarie en Maart van 2010 en 2011 verlos het by die Worcester Verloskunde Eenheid, is nagegaan. Alle MIV-negatiewe pasiënte en pasiënte met doodgebore babas en miskrame is uitgesluit. Die pre-intervensie bevindings van 2010 is vergelyk met die post-intervensie bevindings van 2011. RESULTATE By die Worcester Verloskunde Eenheid was daar 907 geboortes gedurende die studietydperk in 2010, waarvan 102 (11,2%) pasiënte MIV-positief was en 4 (0,4%) met ‘n onbekende MIV-status. In 2011 was daar 865 geboortes waarvan 108 (12,5%) pasiënte MIV-positief was en geen met 'n onbekende MIV-status. In die 2011-groep is beduidend meer pasiënte gediagnoseer met MIV voor as tydens swangerskap. In die 2010-groep is daar 'n CD4-telling gedoen vir 94% van nuut gediagnoseerde pasiënte en diegene met 'n onbekende CD4-telling, in vergelyking met 92% in 2011. Daar was 'n beduidende verbetering na die intervensie in die tyd wat dit geneem het vandat bloed getrek is vir 'n CD4-telling totdat die resultaat opgevolg is. Die mediane tyd het verminder vanaf 34 na 8 dae (p = 0.000001). Nadat die riglyne vir kwalifisering vir hoogs aktiewe antiretrovirale terapie (HAART) verander is na ‘n CD4 telling 350 selle/l het daar beduidend meer pasiënte gekwalifiseer vir HAART. By Worcester Hospitaal het 18 pasiënte voor die intervensie nie die korrekte behandeling intrapartum ontvang nie weens voorkombare redes, in vergelyking met slegs een pasiënt by die VVE. Na die intervensie was daar ‘n beduidende afname na slegs een pasiënt by Worcester Hospitaal en geen by die MOU (p = 0.000001). Voor die intervensie was die korrekte uitvoering van die PMTCT-protokol by die MOU beduidend beter as by die hospitaal (p = 0,0005) en na die intervensie was daar geen beduidende verskil (p = 1.0). GEVOLGTREKKING Alhoewel die oudit en gehalteverbeteringsiklus uitgevoer is by 'n enkele hospitaal, met spesifieke veranderinge gerig tot hul behoeftes, kan die basiese beginsels toegepas word in enige eenheid in die land wat ‘n PMTCT diens verskaf. Opvoeding van personeel en bewusmaking rakende die basiese beginsels van PMTCT, klein veranderinge en die vaartbelyning van prosesse by die voorgeboorte klinieke en die stel van spesifieke doelwitte of tydlyne, kan lei tot aansienlike verbeteringe in pasiënte sorg. Dit sal uiteindelik lei tot 'n afname in die MIV oordrag van moeder na kind, asook MIV-verwante morbiditeit en mortaliteit in moeders en kinders.
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Varvel, Nicholas H. "THE ROLE OF BETA-AMYLOID AND INFLAMMATION IN NEURONAL CELL CYCLE EVENTS IN ALZHEIMER'S DISEASE MOUSE MODELS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1226609920.
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Teepe, Annette. "Relationship of Estrous Cycle to Herpes Simplex Virus Type 2 Susceptibility in Female Mice." Thesis, North Texas State University, 1987. https://digital.library.unt.edu/ark:/67531/metadc500408/.
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In CBA/NJ mice, splenic natural killer (NK) cell activity varies with stages of estrous. Susceptibility of ICR mice to intravaginal inoculation of herpes simplex virus type 2 (HSV-2) decreases with age. Susceptibility of female ICR and CBA/NJ mice to HSV-2 inoculated intravaginally and intraperitoneally was examined during the estrous cycle. In cycling ICR mice, greatest susceptibility to intravaginal inoculation was observed during diestrous and the least during metestrous. CBA/NJ mice were most susceptible to intravaginal inoculation of HSV-2 during diestrous. ICR mice were ovariectomized to mimic diestrous and found to be highly susceptible to intravaginal inoculation at all virus doses. No difference in susceptibility among phases of the estrous cycle was seen following intraperitoneal inoculation.
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Milani-Nejad, Nima. "Regulation of Cardiac Contraction in Health and Disease: Studies from Animal Models to Humans." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397225239.
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Serquiña, Anna Kristina. "Studies on Cellular Host Factors Involved in the HIV-1 Life Cycle: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/646.
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Human Immunodeficiency Virus Type 1 (HIV-1) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), currently the leading cause of death from infectious diseases. Since HIV-1 co-opts the host cellular machinery, the study of cellular factors involved is a rational approach in discovering novel therapeutic targets for AIDS drug development. In this thesis, we present studies on two such proteins. APOBEC3G is from the family of cytidine deaminases known to keep endogenous retroviruses and retrotransposons at bay to maintain stability of the human genome. APOBEC3G targets Vif-deficient HIV-1 particles and renders them noninfectious, partially through deaminase-dependent hypermutation of the provirus during reverse transcription. APOBEC3G largely localizes in mRNA processing (P) bodies, cytoplasmic structures involved in RNA metabolism. Here we explore the significance of APOBEC3G localization in P bodies. We found that disrupting P bodies does not affect virion incorporation of endogenous APOBEC3G, implying that the APOBEC3G fraction in P bodies is not directly involved in the production of nascent, non-infectious particles.
We also study UPF1, another host protein encapsidated by HIV-1. It is an essential protein mainly studied for its role in nonsense-mediated decay (NMD) pathway and belongs to the same helicase superfamily as MOV10, a recently identified antiviral factor. We found that UPF1 is incorporated in HIV-1 virions in a nucleocapsid-dependent manner and is required for single-cycle infectivity at an early, post-entry step of the viral life cycle. This novel function of UPF1 most likely does not involve NMD since depletion of UPF2 does not affect viral infectivity.
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Colby-Milley, Jessica. "Characterization of the sleep-wake cycle in the TgCRND8 mouse model of Alzheimer's disease: from early to advanced pathological stages." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121302.
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Individuals affected by Alzheimer's disease (AD) experience a progressive decline in cognitive function eventually leading to a debilitating loss of memory, reasoning and communication. Although AD is readily associated with such cognitive symptoms, patients can also experience behavioural and psychological symptoms, including perturbations of the sleep-wake cycle. Features of sleep-wake cycle disturbances in AD patients include increased nocturnal awakenings and a decrease in slow-wave non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). Furthermore, changes in sleep quality can also be detected, as measured by the electroencephalogram (EEG) power spectrum. To determine if the TgCRND8 mouse model of AD mimics sleep alterations observed in AD patients, TgCRND8 mice were studied at 3, 7 and 11 months of age, representing differing pathological stages as defined by amyloid plaque load and distribution, as well as by the appearance of neuritic pathology, present from 5 months of age. Polysomnographic recordings were performed and the vigilance state durations over the light and dark cycles of 3, 7, and 11-month-old TgCRND8 were measured. During the active (dark cycle) and resting (light cycle) phases, at all ages studied, TgCRND8 mice spent a significantly greater amount of time awake and a significantly lower amount of time in NREMS when compared to non-transgenic (NTG) mice. Time spent in REMS was decreased during the active phase at 3 and 7 months of age in TgCRND8, while total time spent in REMS during the resting phase was not significantly affected in TgCRND8 at 3, 7 or 11 months. Following total sleep deprivation, 3-month-old TgCRND8 showed an effective recovery response, suggesting that alterations of the homeostatic regulation of the sleep-wake cycle may not contribute to sleep deficits observed at this age. The observed profile of sleep-wake cycle alterations supports the use of TgCRND8 mice as a model to study certain features of sleep-wake cycle disturbances associated with AD, such as increased wakefulness and decreased NREMS during the resting phase. Spectral power analysis of dark phase vigilance states revealed an increase in slow gamma power (20-50 Hz) during wakefulness at all ages studied and a decrease in slow-wave power <1 Hz during NREMS at 3 and 11 months of age. Brain rhythms during REMS were not altered at 3 months of age, however 7 and 11-month-old TgCRND8 displayed a decrease in alpha power (9-14 Hz) and an increase in slow gamma power (20-50 Hz) was also detected at 7 months. The observed tendency towards an increase in the spectral power of fast rhythms (slow gamma) is consistent with the pronounced increase in wakefulness observed in TgCRND8 and may reflect early changes in neuronal activity at the network level associated with amyloid pathology in the absence of severe neurodegeneration. Given the role of noradrenergic transmission within the ascending arousal system (AAS) in the regulation of vigilance states and promotion of arousal and the evidence for compensatory increases in noradrenergic signaling in AD, prazosin, an alpha-1-adrenoreceptor antagonist was administered to 3.5-month-old NTG and TgCRND8 mice to determine if this could restore normal NREMS levels in TgCRND8 mice. At a lower dose (2 mg/kg) prazosin increased NREMS in NTG mice but not in TgCRND8. However at a higher dose (5 mg/kg) an increase in NREMS was observed in both genotypes. Given that a different response to alpha-1-adrenoreceptor blockade was observed at a lower dose between the two genotypes, it may be possible that alterations in the noradrenergic regulation of the sleep-wake cycle are present in 3.5-month-old TgCRND8 and may explain why a higher dose (5mg/kg) of prazosin is required to achieve an increase in NREMS in TgCRND8.Les individus atteints par la maladie d'Alzheimer (MA) démontrent une diminution des fonctions cognitives conduisant à une perte de la mémoire, le raisonnement, et la communication. Bien que la MA est associés à ses symptômes cognitifs, les patients peuvent aussi démontrer des symptômes non-cognitifs, tels que les troubles du sommeil. Les troubles du sommeil chez les patients atteintes de la MA incluent des éveils nocturne plus nombreux, et plus longues en duré que chez les sujets âgés sains, ainsi qu'une diminution du sommeil lent profonde, et dans les stades avancés, une diminution du sommeil paradoxal. Des changements dans la qualité du sommeil sont aussi présent, et peuvent être détecté par l'analyse des puissances spectrale des rythmes associés aux différents stades de sommeil. Pour déterminer si le modèle de la MA, la souris TgCRND8, reproduit les troubles de sommeil que l'on voit chez les patients, nous avons étudié la souris TgCRND8 a 3, 7 et 11 mois, des âges qui représentent des différentes stades pathologiques, définit par la quantité et la distribution de plaques amyloïdes ainsi que la pathologie neuritique, présent à partir de 5 mois. Durant la phase nocturne et la phase diurne, à tous les âges étudié, les souris TgCRND8 démontre une augmentation du temps passé éveillé et une diminution du sommeil lent en comparaison avec les souris non-transgénique (NTG). Une diminution du sommeil paradoxal a été observé à 3 et a 7 mois durant la phase nocturne, par contre, cet effet n'était pas présent durant la phase diurne à 3, 7 ou 11 mois. Après une dépravation total du sommeil, les souris TgCRND8 âges de 3 mois ont démontré une récupération homéostatique effective, suggèrent qu'une altération des mécanismes homéostatiques qui gèrent le sommeil ne contribue pas aux troubles de sommeil observé chez ses souris, à cette âge. L'analyse quantitative de l'électroencéphalogramme (EEG) a révèle une augmentation de la puissance spectrale dans la bande de fréquence gamma lent (20-50 Hz) durant l'éveil a 3, 7 et 11 mois et une diminution de la puissance spectrale des fréquences <1 Hz durant le sommeil lent a 3 et 11 mois. Durant le sommeil paradoxal, une diminution de la puissance spectrale dans la bande de fréquence alpha (9-14 Hz) a été observé à 7 et 11 mois et une augmentation dans la bande de fréquence gamma lent (20-50 Hz) à 7 mois. La tendance d'une augmentation de la puissance spectrale dans les bandes de fréquences rapide (gamma) est en accords avec l'augmentation prononcé du temps passe éveillé que l'on observe chez les TgCRND8 et pourraient être relié à des changements d'activité neuronale associé à l'accumulation de pathologie amyloïdes en absences de neurodégénérescence chez les souris TgCRND8. Étant donné le rôle de la transmission noradrénergiques dans la promotion de l'éveil, ainsi que les études démontrant la possibilités d'augmentation compensatoire d'activité noradrénergiques chez les patients atteints de la MA, les effets de prazosin, un antagonistes de récepteurs alpha-1-adrenergiques, ont été testé chez des souris NTG et TgCRND8 âges de 3.5 mois pour déterminé ci cela pourrait rétablir le sommeil lent chez les souris TgCRND8. A une dose de 2mg/kg, prazosin a augmenté la quantité total de sommeil lent chez les souris NTG mais pas les souris TgCRND8. A une dose plus élevé de 5 mg/kg, une augmentation de la quantité total du sommeil lent a été observé chez the souris NTG et aussi chez les souris TgCRND8. Etant donné que les souris TgCRND8 démontre une réaction différente à la dose faible de prazosin (2 mg/kg) en comparaison aux souris NTG, il est possible qu'il existe une altération dans le contrôle noradrénergique du sommeil chez les souris TgCRND8, est pourrait expliqué exigence d'une dose plus élevé (5 mg/kg) pour atteindre une augmentation du sommeil lent.
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Maurissen, Thomas Luc. "Synergistic gene editing in human iPS cells via cell cycle and DNA repair modulation." Kyoto University, 2020. http://hdl.handle.net/2433/254520.
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Mannan, Haider Rashid. "Development and use of a Monte Carlo-Markov cycle tree model for coronary heart disease incidence-mortality and health service usage with explicit recognition of coronary artery revascularization procedures (CARPs)." University of Western Australia. School of Population Health, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0101.
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[Truncated abstract] The main objective of this study was to develop and validate a demographic/epidemiologic Markov model for population modelling/forecasting of CARPs as well as CHD deaths and incidence in Western Australia using population, linked hospital morbidity and mortality data for WA over the period 1980 to 2000. A key feature of the model was the ability to count events as individuals moved from one state to another and an important aspect of model development and implementation was the method for estimation of model transition probabilities from available population data. The model was validated through comparison of model predictions with actual event numbers and through demonstration of its use in producing forecasts under standard extrapolation methods for transition probabilities as well as improving the forecasts by taking into account various possible changes to the management of CHD via surgical treatment changes. The final major objective was to demonstrate the use of model for performing sensitivity analysis of some scenarios. In particular, to explore the possible impact on future numbers of CARPs due to improvements in surgical procedures, particularly the introduction of drug eluting stents, and to explore the possible impact of change in trend of CHD incidence as might be caused by the obesity epidemic. ... When the effectiveness of PCI due to introduction of DES was increased by reducing Pr(CABG given PCI) and Pr(a repeat PCI), there was a small decline in the requirements for PCIs and the effect seemed to have a lag. Finally, in addition to these changes when other changes were incorporated which captured that a PCI was used more than a CABG due to a change in health policy after the introduction of DES, there was a small increase in the requirements for PCIs with a lag in the effect. Four incidence scenarios were developed for assessing the effect of change in secular trends of CHD incidence as might be caused by the obesity epidemic in such a way that they gradually represented an increasing effect of obesity epidemic (assuming that other risk factors changed favourably) on CHD incidence. The strategy adopted for developing the scenarios was that based on past trends the most dominant component of CHD incidence was first gradually altered and finally the remaining components were altered. iv The results showed that if the most dominant component of CHD incidence, eg, Pr(CHD - no history of CHD) levelled off and the trends in all other transition probabilities continued into future, then the projected numbers of CABGs and PCIs for 2001-2005 were insensitive to these changes. Even increasing this probability by as much as 20 percent did not alter the results much. These results implied that the short-term effect on projected numbers of CARPs caused by an increase in the most dominant component of CHD incidence, possibly due to an ?obesity epidemic, is small. In the final incidence scenario, two of the remaining CHD incidence components-Pr(CABG - no history of CHD) and Pr(CHD death - no CHD and no history of CHD) were projected to level off over 2001-2005 because these probabilities were declining over the baseline period of 1998-2000. The projected numbers of CABGs were more sensitive (compared to the previous scenarios) to these changes but PCIs were not.
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Koh, Carline, and 許上冕. "Effects of right ventricular pacing and its interruption on left ventricular torsional mechanics and diastolic function in congenitalheart block." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45167199.
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Brandano, Laura A. "Investigation of the C-Terminal Helix of HIV-1 Matrix: A Region Essential for Multiple Functions in the Viral Life Cycle: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/552.
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Since the first cases were reported over thirty years ago, great strides have been made to control disease progression in people living with HIV/AIDS. However, current estimates report that there are about 34 million individuals infected with HIV worldwide. Critical in the ongoing fight against this pandemic is the continuing development of highly active anti-retroviral therapies, ideally those with novel mechanisms of action. Currently, there are no medications approved for use that exploit the HIV-1 MA protein, despite its central role in multiple stages of the virus life cycle.
This thesis sought to examine whether a highly conserved glutamate residue at position 99 in the understudied C-terminal helix of MA is required for HIV-1 replication. I characterized a panel of mutant viruses that contain different amino acid substitutions at this position using viral infectivity studies, virus-cell fusion assays, and immunoblotting. In doing so, I found that substitution of this glutamate with either a valine (E99V) or lysine (E99K) residue disrupted Env incorporation into nascent HIV particles, and abrogated their ability to fuse with target-cell membranes. In determining that the strain of HIV could affect the magnitude of E99V-associated defects, I identified a compensatory substitution at MA residue 84 that rescued both E99V- and E99K-associated impairments.
I further characterized the MA E99V and E99K mutations by truncating HIV Env and pseudotyping with heterologous envelope proteins in an attempt to overcome the Env incorporation defect. Unexpectedly, I found that facilitating fusion at the plasma membrane was not sufficient to reverse the severe impairments in virus infectivity. Using quantitative PCR, I determined that an early post-entry step is disrupted in these particles that contain the E99V or E99K MA substitutions. However, allowing entry of mutant virus particles into cells through an endosomal route conferred a partial rescue in infectivity. As the characterization of this post-entry defect was limited by established virological methods, I designed a novel technique to analyze post-fusion events in retroviral infection. Thus, I present preliminary data regarding the development of a novel PCR-based assay that monitors trafficking of the viral reverse transcription complex (RTC) in an infected cell.
The data presented in this thesis indicate that a single residue in MA, E99, has a previously unsuspected and key role in multiple facets of HIV-1 MA function. The pleiotropic defects that arise from specific substitutions of this amino acid implicate a hydrophobic pocket in MA in Env incorporation and an early post-entry function of the protein. These findings suggest that this understudied region of MA could be an important target in the development of a novel antiretroviral therapy.
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Alvarez, Periel Elena. "Dual role of CDK5 on cognitive deficits and striatal vulnerability in Huntington’s disease." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663831.
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Huntington’s disease (HD) is a neurodegenerative disorder caused by an autosomic mutation on the Huntingtin (HTT) coding gene. HD is mainly characterized by the appearance of motor symptoms or choreas, which are associated to the selective degeneration of striatal neurons, and by the presence of cognitive disturbances, which are attributed to alterations in corticostriatal connectivity and to hippocampal dysfunction. For this reason, finding targets involved both on striatal vulnerability and cognitive disturbances, might result in therapeutic strategies able to act simultaneously on HD’s motor and cognitive symptoms. In this Thesis we have focused on Cyclin-dependent kinase 5 (Cdk5) as one of these putative targets. Cdk5 acts mainly in the central nervous system, where its activator p35 is expressed, and it plays a major role on synaptic plasticity regulation. In addition, altered Cdk5 activity has been described in several neurodegenerative disorders, including HD, where Cdk5 deregulation has been associated to increased striatal vulnerability to excitotoxicity. Moreover, alteration of Cdk5 activity and/or subcellular distribution has also been linked to neuronal cell cycle re-entry, which has been proposed as a possible mechanism leading to neuronal dysfunction and eventual death in several neurodegenerative conditions.
Therefore, on one hand, we aimed to study Cdk5 involvement in cognitive deficits and synaptic plasticity alterations in HD. To this end, we generated a new double mutant mice model which expresses one copy of mutant HTT (mHTT) (knock-in or KI), and is conditionally heterozygous for Cdk5 (Cdk5+/). We described that double mutant mice (KI:Cdk5+/-) presented restored corticostriatal and hippocampal cognitive function when compared to their KI littermates. We also observed that preserved corticostriatal function correlated with recovery of corticostriatal NR2B surface levels, which were reduced in KI mice. Moreover, recovery of NR2B surface levels was associated to normalization of NR2B total levels and of the pSrc/pNR2B pathway in the cortex of KI:Cdk5+/- mice. On the other hand, preserved hippocampal cognitive function correlated with recovery of CA1 dendritic spine density, as well as, with increased Rac1 activity in KI:Cdk5+/- mice. Restoration of dendritic spine density was also observed in layer V cortical neurons, in a Rac1-independent manner. Finally, we described that KI mice showed reduced physiological p35 plasma membrane levels in the cortex, which was recovered in KI:Cdk5+/- mice, correlating with preferential alteration of Cdk5 substrates phosphorylation levels in this brain region. In sum, our results demonstrate Cdk5 complex and brain region-specific involvement in cognitive deficits appearance and in synaptic alterations in HD.
On the other hand, we also assessed whether Cdk5 deregulation might cause cell cycle re-entry of striatal neurons in HD. Cdk5 forms a nuclear complex with p27 and E2F1 in differentiated neurons, thus preventing E2F1 from binding to its coactivator DP1 and from activating transcription of cell cycle progression genes. For this reason, we analysed nuclear levels of Cdk5 and p27, and we observed that KI mice showed reduced Cdk5 and p27 nuclear levels, which could induce neuronal cell cycle re-entry. In agreement, we also observed increased levels of CyclinD1 in the striatum of KI mice since early symptomatic stages, and increased Cdk4 levels at late disease stages. Finally, we observed that NMDA treatment of striatal primary cultures caused a general reduction of cell cycle proteins neuronal expression, and importantly, it altered their subcellular distribution, reducing nuclear localization of the cell cycle inhibitor p27 and inducing nuclear presence of cell cycle progression proteins, E2F1 and Cdk4. Our results also suggested that presence of mHTT might further potentiate NMDA-induced subcellular distribution alteration of cell cycle proteins. Therefore, we suggest that reduction of Cdk5 nuclear levels might induce cell cycle re-entry of striatal neurons, a process which could be favoured by alterations in NMDA receptors activation, present in HD.La malaltia de Huntington (MH) és un desordre neurodegeneratiu causat per una mutació al gen que codifica per la proteïna Huntingtina (HTT), i que consisteix principalment en l’aparició de dèficits motors, associats a la degeneració selectiva de l’estriat; i en l’aparició de dèficits cognitius, associats a una alteració en la connectivitat corticoestriatal i a una disfunció hipocampal. En aquesta Tesi, hem analitzat la implicació de la cinasa Cdk5, per una banda, en l’aparició dels dèficits cognitius; i per l’altre banda, en la reentrada neuronal al cicle cel·lular com a un possible mecanisme de susceptibilitat a la vulnerabilitat estriatal en la MH. Els nostres resultats han mostrat que la reducció genètica de Cdk5 en un model murí de la MH (KI), prevé l’aparició dels dèficits cognitius corticoestriatal i hipocampals. Aquesta millora cognitiva està associada a la recuperació dels nivells de membrana de NR2B a nivell corticoestriatal, i a la restauració de la densitat d’espines dendrítiques a l’hipocamp i a l’escorça, indicant una implicació de Cdk5, complexa i específica de regió cerebral, en les alteracions sinàptiques i l’aparició dels dèficits cognitius en la MH. D’altre banda, hem observat que els nivells nuclears de Cdk5 estan disminuïts a l’estriat dels ratolins KI, cosa que podria alterar la seva funció com a inhibidor de la progressió del cicle cel·lular en neurones diferenciades. En concordança amb aquesta hipòtesi, diferents proteïnes del cicle cel·lular presenten una alteració en els seus nivells proteics, tant en ratolins KI, com en mostres de pacients humans. A més, l’activació dels receptors NMDA en neurones estriatals porta a una alteració de la distribució subcel·lular de les proteïnes del cicle cel·lular prèviament analitzades, un efecte que podria ser potenciat per la presència de la HTT mutada. En conclusió, els resultats d’aquesta Tesi, mostren la complexa implicació de Cdk5 en l’aparició dels dèficits cognitius en la MH, i suggereixen que l’alteració de la localització nuclear de Cdk5 podria portar a la desregulació de diferents proteïnes del cicle cel·lular, un mecanisme que es podria veure afavorit per alteracions en l’activació dels receptors NMDA, presents en la MH.
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Seifert, Elena. "Metabolic Changes in Pulmonary Arterial Smooth Muscle Cells Exposed to Increased Mechanical Forces from an Ovine Model of Congenital Heart Disease with Increased Pulmonary Blood Flow." Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/cmc_theses/2094.
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An important cause of pulmonary arterial hypertension (PAH) in children with congenital heart disease (CHD) is increased pulmonary blood flow (PBF). To gain a better understanding of the disease process, the changes in biochemical pathways and metabolism of pulmonary arterial smooth muscle cells (PASMCs) were studied using a unique surgical ovine model of increased pulmonary blood flow. PASMCs isolated from 4-week-old lambs with increased PBF (shunt) showed lower oxygen consumption rates and lower extracellular acidification rates linked to glutamine metabolism when compared to controls. Shunt and control PASMCs both exhibited a switch into the reverse tricarboxylic acid (TCA) cycle, while only shunt cells showed a decrease of glucose being transformed into Acetyl CoA to enter the forward TCA cycle. Shunt PASMCs also demonstrated increased levels of yes-associated protein 1 (YAP1) expression in the nucleus. These results indicate changes in glutamine metabolism, glucose metabolism, and protein signaling cascades associated with increased mechanical forces in the setting of increased PBF, as seen in PAH in children with CHD.
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Evans, Heather M. "IMMUNE EVASION BY DIVISION OF LABOR: THE TROPHIC LIFE CYCLE STAGE OF PNEUMOCYSTIS MURINA SUPPRESSES INNATE IMMUNITY TO THIS OPPORTUNISTIC, FUNGAL PATHOGEN." UKnowledge, 2017. http://uknowledge.uky.edu/microbio_etds/15.
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Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts, including AIDS patients. Pneumocystis species have a biphasic life cycle consisting of single-nucleated trophic forms and ascus-like cysts. Both stages live within the host, and, thus, must contend with threats from the host immune system. The cyst cell wall β-glucans have been shown to stimulate immune responses in lung epithelial cells, dendritic cells and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with immune cells. In this study, the immune response to the life cycle stages of Pneumocystis murina was evaluated.
Here, we report differences in the immune response of immunocompetent mice to the trophic and cystic life cycle stages of P. murina. Upon infection with purified trophic forms, wild-type adult mice developed a delayed innate and adaptive immune response compared to inoculation with the normal mixture of trophic forms and cysts. Cysts, but not trophic forms, stimulated Th1-type responses in the lungs of infected mice.
Surprisingly, trophic forms are sufficient to generate protective adaptive responses, leading to clearance in immunocompetent mice. We report that CD4+ T cells primed in the presence of trophic forms are sufficient to mediate clearance of trophic forms and cysts. In addition, primary infection with trophic forms is sufficient to prime B cell memory responses capable of clearing a secondary infection with Pneumocystis following CD4+ T cell depletion. While trophic forms are sufficient for initiation of adaptive immune responses in immunocompetent mice, infection of immunocompromised RAG2-/- mice with trophic forms in the absence of cysts does not lead to the severe weight loss and infiltration of innate immune cells associated with the development of Pneumocystis pneumonia.
Dendritic cells screen the alveolar spaces for pathogens, and are in a prime position to initiate the immune response against lung pathogens, including Pneumocystis. Our data demonstrate that trophic forms broadly dampen the ability of dendritic cells to respond to pathogen-associated molecular patterns. Bone marrow-derived dendritic cells were stimulated with trophic forms, a mixture of trophic forms and cysts, and various other inflammatory materials, including β-glucan. Trophic forms inhibited multiple components involved in antigen presentation by dendritic cells, including secretion of inflammatory cytokines and expression of MHC class II and costimulatory molecules on the cell surface. Furthermore, trophic forms suppressed or failed to induce the expression of multiple genes related to activation and maturation in dendritic cells. Dendritic cells silenced by trophic forms are unable to induce CD4+ T cell responses. These data suggest that immune evasion by trophic forms is dependent on the suppression of innate responses, and the development of adaptive immunity represents a “point of no return” at which the trophic forms are no longer able to escape clearance.
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Santos, Marcus Vinicius Rezende dos. "O efeito do atraso em movimentos reversos do cotovelos : comparação entre sujeitos saudaveis e portadores da doença de Parkinson." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314247.
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Orientador: Gil Lucio AlmeidaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-06T21:23:30Z (GMT). No. of bitstreams: 1 Santos_MarcusViniciusRezendedos_M.pdf: 2514721 bytes, checksum: a7b1ab66caadf0d4fb9a3367038033d5 (MD5) Previous issue date: 2005
Resumo: Neste trabalho, foram investigados efeitos de condições especiais como o envelhecimento e a Doença de Parkinson no controle de movimentos reversos do cotovelo, realizados com um atraso variável entre a ida (Ml) e a volta (M2) do mesmo. Outro objetivo foi verificar se o ciclo de alongamento-encurtamento (CAE) age como potencializador da contração muscular nessa população. Foram recrutados 12 voluntários, sendo seis sujeitos saudáveis (três homens e três mulheres) com idades entre 51 e 71 anos (Média = 62.33 e DP = 8.95) e seis portadores da doença de Parkinson (três homens e três mulheres) com idades entre 59 e 77 anos (Média = 68.66 e DP = 7.47). Eles realizaram movimentos uni-articulares rápidos de reversão com o cotovelo, que se movia em direção à um alvo (Ml) e depois retomava à posição inicial (M2). Esses movimentos foram realizados em três diferentes distâncias (20°, 40° e 60°) e entre os dois componentes (Ml e M2) foi realizado um atraso variável (Os, 0.2s, 0.5s e ls). O deslocamento angular do cotovelo foi registrado por um sistema óptico de análise do movimento (OPTOTRAK@ 3020) e a atividade elétrica dos músculos braquiorradial (BRR) e cabeça lateral do tríceps braquial (TR) foi registrada através de um eletromiógrafo EMG DelSYS (modelo DE2.2L) com eletrodos de superficie. O envelhecimento saudável não influenciou os padrões EMG utilizados por esses indivíduos para ativar os músculos agonista e antagonista na realização de movimentos uni-articulares com reversão com diferentes atrasos. A velocidade dos movimentos executados por esses indivíduos foi mais baixa devido ao uso de um padrão semelhante aos sujeitos jovens, porém com uma menor quantidade de ativação. Os parkinsonianos moveram mais lentamente que os idosos saudáveis e indivíduos saudáveis devido a algumas alterações na modulação da atividade EMG. Apesar de apresentarem a manutenção do padrão trifásico, a atividade elétrica dos músculos ocorreu na forma de vários bursts altemantes durante toda a realização da tarefa, o que provocou uma redução na quantidade de ativida elétrica dos músculos. Os parkinsonianos não reduziram a magnitude do segundo burst agoninos movimentos sem atraso, o que trouxe uma dificuldade maior para reverter os moviment< Por fim, notou-se que os indivíduos portadores da doença de Parkinson relaxavam menos a SI musculatura e iniciavam o retomo à posição inicial necessitando de uma atividade maior do 1 para gerar uma velocidade igual à dos indivíduos saudáveis, o que não aconteceu. ( movimentos que reverteram sem atraso apresentaram um valor maior da velocidade movimento de retomo à posição inicial, mesmo nos portadores da doença de Parkinso confirmando a ação potencializadora do ciclo de alongamento-encurtamento (CAE) sobre músculo tríceps. Isso suporta a influência, tanto dos reflexos (gerados pelo estiramento muscula quanto da energia potencial armazenada pelo músculo e tendão, que têm suas origens na fa: excêntrica do CAE e são liberados no movimento de volta (fase concêntrica). Palavras-chave: Movimentos reversos, doença de Parkinson, ciclo de alongamento encurtamento, eletromiografia e cinemática
Abstract: Within this study were investigated the effects of special conditions like aging and the Parkinson's disease on the control ofreversal movements ofthe elbow joint performed with a variable delay between the two components (Ml and M2) ofreversal. Another aim was to verify if the stretch-shortening cycle exerts his potentiating effects on muscular contraction in this population. To perform these observations, 12 volunteers were recruited. Six of them (3 males and 3 females) were normal at their neurological assessment and were between 51 and 71 years of age (Mean = 62.33 e S.D.= 8.95), and the other six (3 males and 3 females) had been diagnosised with Parkinson disease and were between 59 and 77 years old (Mean = 68.66 e S.D. = 7.47). They executed fast single-joint movements with a reversal, moving towards a target (Ml) and getting back to the initial position (M2). These movements were accomplished in three different distances (20°, 40° and 60°) and between the two components ofreversal (Ml e M2) there were variable delays (Os, 0.2s, 0.5s eIs). The elbow angle was recorded using a optoelectric system of motion analysis (OPTOTRAK@ 3020) and the electrical activity of braquioradialis (BRR) and lateral head of triceps brachi (TR) muscles were recorded by a electromyograph EMG DelSYS (model DE2.2L) with surface electrodes placed over the muscles bellies. The aging did not affect the EMG patterns used by these persons in activating the agonist and antagonist muscles to accomplish single-joint movements with a delay between the movements toward the target and the return to the initial position. The velocity of movements executed by the elder1y volunteers was lower due to the fact that the same strategy applied to young hea1thy persons was used, however with less EMG activity. The volunteers with Parkinson's disease moved slower than the heaIthy elderly and young subjects due to aIterations in the modulation of EMG activity. Altough they kept the triphasic pattern, the EMG showed multiple bursts that aItemated during the task accomplishmen~ which decreased the amount of ellectricaI activity. Besides, they did not reduce the magnitude of second agonist burst in the reversaI movements without delay, what made the reversion harder. FinaIly, it was noticed that the parkinsonians showed less relaxation of his muscles during the intervaI between TI-T4, and started the return movement needing more TR activity to produce the same velocity, when compared to heaIthy persons, which was not the case. Those movements that reverted with no delay showed higher values concerning the second peak ofvelocity, even within the volunteers with Parkinson disease, sustaining the potentianting action of SSC over the triceps muscle. This effect comes from the influence of reflexes (generated by the muscle stretching), as well as the storage of elastic energy in the muscle and tendon in the eccentric phase of SSC, which are released at the movement of returning (concentric phase)
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
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Vendrame, Édina. "Efeitos da posição social da infância e da vida adulta na perda dentária, nas doenças crônicas e na qualidade de vida relacionada a saúde bucal." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/151438.
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Introdução: Dado que a trajetória socioeconômica pode influenciar na saúde individual durante a vida, nosso objetivo foi testar um modelo de efeitos socioeconômicos do curso de vida na perda dentária, doenças crônicas e qualidade de vida relacionada a saúde bucal. Método: Este estudo de base populacional (n=433) foi realizado em Porto Alegre entre 2010 e 2012 com os usuários do Sistema Único de Saúde (SUS) com 18 anos de idade ou mais. As variáveis observadas utilizadas foram: sexo, idade, fumo e número de dentes presentes. As variáveis latentes utilizadas foram Oral Health Impact Profile (OHIP), Posição Social na Infância (SESC), Posição Social na Vida Adulta (SESA) e Doença Crônica (CD). A análise estatística foi realizada utilizando-se o modelo de equações estruturais (SEM) com o software Mplus. No modelo final foram mantidas as associações significativas (p<0,30). Resultados: O modelo final apresentou um ajuste adequado: RMSA 0,039, CFI 0,972, TLI 0,969 e WRMR 1.199. O efeito da SESC na SESA foi forte β= 0,59 (p<0,01). O efeito direto da SESC na perda dentária foi β= -0,08 (p= 0,19), e nas doenças crônicas foi β= -0,14 (p= 0,10). O efeito direto da SESA na perda dentária foi β= -0,20 (p<0,01), e no OHIP foi β= -0,14 (p= 0,05). O efeito indireto de SESC na perda dentária foi β= -0,12 (p= 0,02), e no OHIP foi β= -0,14 (p= 0,01). O efeito indireto da SESA no OHIP foi β= -0,02 (p= 0.3). SESC tem um efeito indireto sobre OHIP e perda dentária via SESA, apoiando a teoria da cadeia de efeitos. SESC e SESA tem efeitos independentes na perda dentária, apoiando a teoria do acúmulo de risco. SESC tem um efeito direto nas doenças crônicas apoiando a teoria do período crítico. Conclusão: Investigações com base no curso de vida relacionada à saúde bucal usando SEM são necessárias para melhor compreender os mecanismos que ligam fatores sociais à saúde das pessoas causando inequidades.Introduction: Since the socioeconomic trajectory can influence on individual health during the life course, we aimed to test a model of life course socioeconomic effects on tooth loss, chronic disease and Oral Health Related to Quality of Life. Method: This population-based study (n = 433) was held in Porto Alegre between 2010 and 2012 with the Public Health (PH) users aged 18 or over. The observable variables were: gender, age, smoking and number of teeth. Latent variables were Oral Health Impact Profile (OHIP), Socioeconomic Status in Childhood (SESC) Socioeconomic Status in Adulthood (SESA) and Chronic Disease (CD). Statistical analysis was performed using the Structural Equation Modeling (SEM) with Mplus software. For the final model only significant associations were kept (p<0.30). Results: The final model presented an adequate fit: RMSA 0.039, CFI 0.972, TLI 0.969 and WRMR 1.199. The effect of SESC on SESA was strong β = 0.59 (p<0.01). The direct effect of SESC on tooth loss was β = -0.08 (p = 0.19), and on chronic diseases was β = -0.14 (p = 0.10). The direct effect of SESA on tooth loss was β = -0.20 (p <0.01), and on OHIP was β = -0.14 (p = 0.05). The indirect effect of SESC on tooth loss was β = -0.12 (p = 0.02), and on OHIP was β = -0.14 (p = 0.01). The indirect effect of SESA on OHIP was β = -0.02 (p = 0.3). SESC has an indirect effect on OHIP and tooth loss via SESA, supporting the chain of effects theory. SESC and SESA have independent effects on tooth loss, supporting the accumulation theory. SESC has a direct effect on chronic diseases supporting the critical period theory. Conclusion: Investigations based on the life course approach relating to the oral health using SEM are necessary to understand the mechanisms and social determinants of health, causing inequalities.
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Nassour, Ibrahim. "Depot et mobilisation des lipides corporels au cours du cycle sexuel chez la truite arc-en-ciel : effets d'une carence en acides gras essentiels sur la composition en acides gras des differents tissus." Paris 7, 1988. http://www.theses.fr/1988PA077128.
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Mielke, Sarah Rebecca. "Environmental Persistence of Foot and Mouth Disease Virus and the Impact on Transmission Cycles in Endemic Regions." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574079284530142.
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Cabanas, Magali. "Modification des activités de réseaux in vivo chez un modèle murin de la maladie de Huntington." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0345/document.
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La maladie de Huntington est une pathologie héréditaire qui se caractérise par une dégénérescence sélective des neurones striataux de la voie indirecte des ganglions de la base. Chez les patients ainsi que chez les souris modèles de la pathologie, en plus des symptômes moteurs, cognitifs et psychiatriques, des troubles du sommeil peuvent aussi apparaitre dès la phase pré-symptomatique. L’étude électrophysiologique in vivo des souris transgéniques R6/1a, en outre, révélé en début de phase symptomatique l’apparition du rythme pathologique β observé principalement durant le sommeil. Ces travaux de thèses ont donc eut pour but d’étudier le lien entre les modifications d’activités de réseaux cérébraux, les troubles du sommeil et l’émergence du rythme β ainsi que l’implication de ces anomalies dans les perturbations comportementales observées chez les souris R6/1. Notre étude de l’imagerie c-Fos a montré une hyperactivation de la voie frontostriatale chez ces souris, et ceci uniquement au stade pré-symptomatique sans aucune modification d’activation de la voie indirecte. Notre étude pharmacogénétique a démontré que la modification d’activité de ces neurones de projection striataux pouvait modifier l’alternance veille/sommeil mais ne pouvaient générer le rythme β. Enfin, notre étude pharmacologique a établit le lien entre le dysfonctionnement du système orexinergique et l’émergence du rythme β chez les souris R6/1. Ces travaux ont permis de mieux décrire des modifications d’activités de réseaux associées aux différents stades de la pathologie, en particulier au stade présymptomatique, et leurs contributions aux troubles du sommeil et l’émergence du rythme βHuntington’s disease (HD) is an inherited pathology that causes selective degeneration ofindirect striatal pathway neurons of the basal ganglia. In addition to the classic motor,cognitive and psychiatric symptoms, patients and mouse models of HD develop sleepdisorders, which can appear at as early as pre-symptomatic stage. Furthermore, in vivoelectrophysiological study of R6/1 transgenic mice revealed a unique and pathological βrhythm that appear at early symptomatic stage and which is mainly observed during sleep.The aim of this thesis work was to examine the link between changes in cerebral networkactivities, sleep disturbances and β rhythm, and to determine the contribution of theseabnormalities to the behavioral disturbances observed in R6/1 mice. Our neuroimaging study of the marker of neuronal activity c-Fos showed a hyperactivation of frontostriatal pathway at pre-symptomatic stage without any activity changes of the vulnerable indirect pathway neurons. Our pharmacogenetic study demonstrated that changes of striatal projection neuronal activity can modify sleep/wake behaviors, without inducing the pathological β rhythm. Finally, our pharmacological study established a link between orexinergic system dysfunction and β rhythm emergence in R6/1 mice. Our data, therefore, described further the natures of altered neural circuit activity associated with different disease stages, in particular pre-motor symptomatic period, and the importance of these alterations for sleep disturbances as well as β rhythm appearance in transgenic HD mice
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Dall\'Orto, Clarissa Campo. "Avaliação das interações das células endoteliais e das células musculares lisas arteriais com os inibidores do mammalian target of rapamycin (mTOR) na presença de soro rico em plaquetas." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5167/tde-05122018-115750/.
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INTRODUÇÃO: O sucesso a longo prazo da intervenção coronária percutânea, inicialmente realizada apenas com balão, era limitado pelo recolhimento elástico da artéria e pela hiperplasia neointimal. Com o advento dos stents convencionais (BMS) houve melhora nesse cenário e diminuição da reestenose, que é resultante de uma complexa cadeia de eventos iniciada após a injúria causada na parede vascular pela insuflação de balões e da aposição das hastes do stent. A proliferação excessiva de células musculares lisas (VSMC) tem papel fundamental na formação da neoíntima no contexto da reestenose intra-stent com a consequente redução da luz arterial. Com o advento dos stents farmacológicos (DES) houve diminuição importante da hiperplasia neointimal e um dos fármacos que se mostrou efetivo nesse papel é o sirolimo, que atua se ligando à proteína de ligação 12 e o heterodímero resultante se liga à mTOR impedindo sua ativação e causando parada do ciclo celular entre as fases G1 e S, desse modo inibindo a proliferação e migração de VSMC e das células endoteliais (HUVEC). Portanto a intervenção coronária acaba interferindo diretamente no endotélio, interferindo na produção das HUVEC não apenas no aspecto quantitativo, mas também na função das mesmas, e a qualidade funcional do endotélio é tão fundamental quanto à sua presença. Após o implante dos DES, principalmente os de primeira geração, ocorre disfunção endotelial cujo principal marcador é a perda da capacidade do relaxamento do vaso. Há correlação também entre cobertura das hastes incompleta e ocorrência de trombose dos stents. Consequentemente há espaço para o aprimoramento dos DES, para que se tornem dispositivos com eficácia já alcançada na prevenção da reestenose porém com um perfil de segurança maior. O presente trabalho tem como objetivo avaliar as alterações causadas pelos DES nas HUVEC e nas VSMC em cocultura na presença e na ausência do soro rico em plaquetas. MATERIAIS E MÉTODOS: Utilizamos células HUVEC e VSMC em modelos de monocultura e cocultura, na presença e na ausência de soro rico em plaquetas, tratadas com BMS ou DES. Realizamos a determinação da IC50 do inibidor da mTOR, avaliação da citotoxicidade pelo método colorimétrico do MTT, determinação da formação de peróxidos lipídicos, avaliação das fases do ciclo celular e da expressão de marcadores de controle de proliferação e inflamação. RESULTADOS: Na avaliação da citotoxicidade pelo método colorimétrico do MTT e determinação da IC50 as VSMC foram menos sensíveis ao sirolimo que as HUVEC (IC50 em 24/48 horas 14,85/10,47uM e 9,48/22,24 uM, respectivamente para HUVEC e VSMC). As plaquetas e fatores solúveis potencializam o estresse oxidativo gerado pela presença dos stents possivelmente por ampliar o ambiente inflamatório. Houve parada do ciclo celular na fase G0/G1 causada pelos DES somente com adição das plaquetas ao meio de cultura. Nos modelos de cultura celular sem as plaquetas a parada do ciclo celular foi em G2/M. Não houveaumento das células na fase DNA fragmentado (sub-G0) evidenciando que não houve indução de morte celular. CONCLUSÃO: As VSMC foram menos sensíveis ao sirolimo que as HUVEC. Nos modelos de cocultura com adição das plaquetas os DES eluídores de sirolimo causaram parada do ciclo celular na fase G0/G1 sem indução de morte celular, sugerindo que o sirolimo exerce seus efeitos anti-inflamatórios nessas populações celulares e consequentemente reduz a hiperplasia neointimal por um mecanismo citostáticoINTRODUCTION: The long-term success of percutaneous coronary intervention, initially performed only with a balloon, was limited by the elastic recoil of the artery and by neointimal hyperplasia. There was improvement in this scenario with the advent of bare metal stents (BMS), because they decrease in restenosis, that resulting from a complex network of events initiated after the injury caused in the vascular wall by insufflation of balloons and apposition of the stent struts. Excessive proliferation of smooth muscle cells (VSMC) plays a key role in neointimal hyperplasia in the context of intrastent restenosis with consequent reduction of arterial lumen. With the advent of drug-eluting stents (DES) there was a significant decrease in neointimal hyperplasia and one of the drugs that proved effective in this role is sirolimus, which acts by binding to the binding protein 12 and the resulting heterodimer binds to mTOR preventing its activation and causing cell cycle arrest between G1 and S phases and thereby inhibiting the proliferation and migration of VSMC and also inhibiting endothelial cells (HUVEC). Therefore, coronary intervention interferes directly in the endothelium, interfering in the production of endothelial cells, not only in the quantitative aspect, but also in their function, and the functional quality of the endothelium is as fundamental as its presence. After the implantation of DES, especially those of the first generation, endothelial dysfunction occurs, whose main marker is the loss of the capacity of the vessel relaxation. There is also correlation between incomplete stem coverage and stent thrombosis. Consequently, it is possible to improve of the DES, so that they become devices with already achieved effectiveness in the prevention of restenosis but with a greater safety profile. The present study aims to evaluate the changes caused by DES in human HUVEC and VSMC in co-culture in the presence and absence of platelet-rich serum. MATERIALS AND METHODS: We used HUVEC and VSMC in monoculture and co-culture models in the presence and absence of platelet rich serum treated with BMS or DES. We performed the determination of IC50 for mTOR inhibitor, cytotoxicity evaluation by the colorimetric method of MTT, determination of lipid peroxide formation, cell cycle and expression of necrosis and inflammation markers. RESULTS: In the assessment of cytotoxicity by the MTT colorimetric method and determination of the IC50, VSMC were less sensitive to sirolimus than HUVEC (IC50 in 24/48 hours 14.85 uM/10.47uM and 9.48 uM/ 22.24 uM, respectively for HUVEC and VSMC). Platelets potentiate the oxidative stress generated by the presence of stents, possibly by increasing the inflammatory environment. Drug-eluting stents arrested VSMC and HUVEC in the G0/G1 phase of the cell cycle only with the addition of platelets to the culture medium. In cell culture models without platelets the cell cycle arrest was in G2/M. There was no increase of the cells in the fragmented DNA phase (sub-G0) evidencing that there was no induction of apoptosis. CONCLUSION: Human aorta smooth muscle cells of the were less sensitive to sirolimus than HUVEC. In coculture models with platelet addition, DES with sirolimus caused cell cycle arrest in the G0/G1 phase without induction of apoptosis, suggesting that sirolimus exerts its antiinflammatory effects in these cellular populations and consequently reduces neointimal hyperplasia via a cytostatic mechanism
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Hannou, Sarah Anissa. "Rôle du régulateur du cycle cellulaire p16INK4a dans le développement du diabète de type 2 et dans les maladies métaboliques du foie gras ou NAFLD (Non-Alcoholic Fatty Liver Disease) : rôle de p16INK4a dans le contrôle de la néoglucogenèse hépatique et dans le développement de la stéatose hépatique non alcoolique." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S012/document.
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Le diabète de type 2 (T2D) est un trouble métabolique de l’homéostasie du glucose. Il est caractérisé par une hyperglycémie chronique qui résulte en partie d’une production excessive de glucose par le foie conséquence au développement d’une résistance à l’insuline. Le T2D est une pathologie multifactorielle à la fois génétique et environnementale. Récemment des études d’associations de gènes (GWAS) dans différentes cohortes ont mis en évidence une forte corrélation entre le locus CDKN2A et le risque de développement du T2D en se basant sur certains paramètres métaboliques tel que la glycémie à jeun. Le locus CDKN2A code pour des protéines régulatrices du cycle cellulaire dont la protéine p16INK4a. p16INK4a est largement décrite dans la littérature pour son rôle suppresseur de tumeurs et comme marqueur de sénescence, cependant son rôle dans le contrôle de l’homéostasie hépatique du glucose n’a jamais été rapporté. Afin de déterminer le rôle de p16INK4a dans le métabolisme hépatique du glucose, nous avons utilisé in vivo des souris sauvages (p16+/+) et déficientes pour p16INK4a (p16-/-) et in vitro des hépatocytes primaires ainsi que la lignée AML12. Nous avons montrés qu’après un jeune, les souris p16-/- présentent une hypoglycémie moins prononcée qui se traduit par une expression hépatique plus élevée de gènes de la néoglucogenèse tels que PEPCK, G6Pase et PGC1a. De plus, les hépatocytes primaires de souris p16-/- présentent une meilleur réponse au glucagon que ceux des p16+/+. Enfin, nous avons montrés que la diminution d’expression de p16INK4a par siRNA dans les AML12 suffit à induire l’expression des gènes de la néoglucogenèse et potentialise la réponse de ces cellules à différents stimuli gluconéogenique. L’effet observé dépend de l’activation de la voie PKA-CREB-PGC1A. L’ensemble de ces données montrent pour la première fois que p16INK4a pourrait jouer un rôle un cours du développement du T2DP16INK4a is a tumor suppressor protein well described as a cell cycle regulator. p16INK4a blocks cyclin D/ cyclin dependent kinase (CDK) 4 activity by binding to the catalytic subunit of CDK4, preventing retinoblastoma protein phosphorylation and subsequently the release of the E2F1 transcription factor. As a consequence; the transcription of genes required for progression to the S phase is restrained. Recently, genome-wide association studies (GWAS) associated the CDKN2A locus, encoding, amongst other genes, p16INK4A, with an increased risk of type 2 diabetes (T2D) development. However, the pathophysiological link between p16INK4a and hepatic glucose homeostasis remains unknown. In this context, we investigated the role of p16INK4a in hepatic glucose metabolism in vivo using p16+/+ and p16-/- mice and in vitro using primary hepatocytes and the AML12 hepatocyte cell line.p16-/- mice exhibited a higher response to fasting as shown by an increased hepatic gluconeogenic gene expression including phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-biphosphatase (F1,6P) and glucose-6-phosphatase (G6Pase). p16-/- mice displayed an enhanced hepatic gluconeogenic activity in vivo upon administration of pyruvate, a gluconeogenic substrate. Consistent with this, in vitro data show that p16-/- primary hepatocytes display an enhanced gluconeogenic response to glucagon. In addition, knock down of p16INK4a by siRNA in AML12 cells increased gluconeogenic gene expression. These effects were associated with an increased activity of the PKA-CREB signaling pathway which leads to increased PPARg coactivator 1 (PGC1)α expression, a key transcriptional co-activator that regulates genes involved in energy metabolism. These findings describe a new function for p16INK4a as an actor in the hepatic adaptation to metabolic stress and suggest that p16INK4a could play a role during T2D development
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Mongeon, Kevin. "The Study of Hereditary Spastic Paraplegia-Causing Gene DDHD2 Using Cell Models." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37474.
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Hereditary spastic paraplegia type 54 is a rare autosomal recessive neurological gait disorder characterized by paraplegia, muscle spasticity, and intellectual disability. This length-dependent distal axonopathy is caused by mutations in the DDHD2 gene, which encodes the intracellular phospholipase A1 DDHD2. Little is known about the molecular function of the DDHD2 protein, especially in the context of HSP54. Thus, there is a need to further investigate its molecular functions and investigate the impact of DDHD2 deficiency in disease-relevant cells. Here, lipidomic profiling of dermal fibroblasts derived from three unrelated patients has revealed 19 glycerophosphoethanolamine species at differential levels in patients relative to unaffected controls. However, patient cells appear to have an unaffected Golgi apparatus morphology and lipid droplet formation, despite DDHD2’s proposed roles in these processes. To study the gene function in neuronal cells, I transdifferentiated the fibroblasts into induced neuronal precursor cells and found all the patient cells arrested in the G0/G1 phase of upon conversion. Given that these cell lines are unsustainable, I generated a stable knockdown cell line in the highly proliferative HEK293A to study the molecular biology of DDHD2. The knockdown cells had a reduced growth, were delayed in the G2/M phase of the cell cycle, and became multinucleated. I then treated the cells with antineoplastic compounds paclitaxel and nocodazole and found more knockdown cells in G0/G1 than controls, suggesting the possible occurrence of mitotic slippage. Lastly, I report a novel subcellular localization for DDHD2 at the microtubule organization center.
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Lundberg, Martina Helena. "Role of cyclo-oxygenase and related pathways in vascular health and disease." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/14509.
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The cardioprotective hormone prostacyclin is a potent inhibitor of platelet activation and is produced in vascular endothelium by the concerted actions of cyclo-oxygenase and prostacyclin synthase. There is an ongoing, heated debate about which COX isoform (COX-1 or COX-2) regulates endothelial prostacyclin production. This is an important area of study since non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 selective inhibitors, used to treat arthritis, are associated with an increased risk of cardiovascular events, which has been linked to a reduction of urinary markers of prostacyclin. Thus, the aim of my thesis was to investigate the relative contribution of COX-1 versus COX-2 to endothelial prostacyclin production and vascular function. Using en face confocal imaging, I found that COX-1 immunoreactivity predominates over COX-2 in the endothelium of all blood vessels studied, including aortic arches from healthy wild type (WT, C57BL/6J) mice, in WT mice injected with endotoxin, ApoE-/- mice, rats with chronic heart failure and in human pulmonary artery. I have performed bioassays with blood vessels from WT versus COX-1-/- and COX-2-/- mice to show that COX-1 not COX-2 drives the majority of vascular prostacyclin production in both young (3 month old) and mature (12 month old) mice of both sexes. Phenotypic differences in the COX-1-/- and COX-2-/- mice included elevated levels of nuclear ‘primed’ NF-κB in the endothelium of both the protected (greater) and atherosclerosis-susceptible (lesser) curvature of the aortic arch. Despite COX-2-/- mice having normal endothelial prostacyclin production, more platelets adhered to the lesser curvature of the aortic arch. The techniques and validation protocols employed have shown COX-1 as the predominant endothelial COX isoform, responsible for vascular prostacyclin production. Low levels of constitutive COX-2 was found localised to susceptible areas of the vasculature where it may contribute to prostacyclin production on a local level to limit inflammation, atherosclerosis and platelet adhesion.
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Bishop-Bailey, David. "Induction of cyclo-oxygenase and nitric oxide synthase in vessels." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286016.
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CRUVINEL, Adriane Reis. "Epidemiologia da ferrugem asiática da soja em ambientes do Estado de Goiás: efeito de fungicida e época de semeadura." Universidade Federal de Goiás, 2005. http://repositorio.bc.ufg.br/tede/handle/tde/459.
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Previous issue date: 2005-02-28During the last crops, the soybean rust has been appeared as one of the most important problems in the national agriculture. The direct loses on the production and in the costs with fungicides have been increased the damages on this crop. Aiming to understand better the disease epidemiology, this work searched for answers by epidemic progress in two locations, the time of planting effect, the cycle of planting, the use of fungicide, and by different cultivars. The experiments were assembled in Experimental Stations from Agência Rural in Senador Canedo and in Anápolis. For each place were used three times of planting, six cultivars on the three crop cycles (Monsoy 6101 and BRSNina premature cycle; Emgopa 315 and BRSGO Santa Cruz middle cycle; Emgopa 313 and BRSGO Paraíso late cycle), with and without fungicide action, have been evaluated on the three parts of the plant (lower, middle and upper). Each time, to each one of the places, have been considered as an experiment with spli-split-plot. After the disease symptom observations, the split under chemical control were freaked each 21 days using pyraclostrobin+epoxiconazole on 66,5 g + 25 g a.i. ha-1. The evaluations, after the first symptom observation, have been done weekly up to the complete leaves took away. With the periodic severity data the Area Under Progress Disease Curve (AUPDC) and Relative Area Under Progress Disease Curve (RAUPDC), that is the area divided by the epidemic time duration, were calculated. The parameters were productivity, thousand-grains weight (TGW) and small grains percent (%SG). The delay on the start of the disease on Anápolis, comparing with Senador Canedo, increases the discussion on the results. The previous disease occurrence in Senador Canedo and the high level inoculate presented can be associated to the fact of experimental site in Senador Canedo has soybean cultivate all over the year. The delay on the start of the disease on Anápolis, compared to Senador Canedo has been resulted on productivity increase and fungicide effect decrease. Comparing the time of planting in both planting places, the second one presented the highest level of severity, but the highest level of productivity even. The use of fungicide decrease significantly the AUPDC, increase the productivity, the TGW and decrease the %SG. The premature cycle cultivars presented lowest disease severity. The cultivar Emgopa 315 although be a medium cycle presented results equals premature cycles cultivars. On each site the time of planting were differentiated. On high pressure inoculate condition the difference between evaluated factors was lower. On lower inoculate pressure the evaluated factors expressed better the changes. As conclusion we have: a) how early the disease appears higher is your effect on productivity; b) using premature cultivars the escape effect decrease the disease damages when compared to medium and late cycle; c) the disease decrease the soybean cycle by the defoliation; d) although all the cultivars presented susceptibility to rust, related to lower severity on partial resistance; e) the fungicide utilization pyraclostrobin+epoxiconazole on de 66,5 g + 25 g a.i. ha-1, used on first symptom and in 21 on 21 days decrease the disease progress and the effects on productivity; f) the disease progress decrease by fungicide utilization is better in late planting; g) under the fungicide effect pyraclostrobin+epoxiconazole with 66,5 g + 25 g a.i. ha-1 there s no variation time planting and site; h) under high inoculate pressure the variation between time planting on disease progress and productivity is lower; i) the time of planting must be considered but not lonely, always in association with others factors of fungus action; j) the use of RAUPDC is necessarily when there is variation the time of soybean cycle, affecting the rust epidemic duration; l) the highest disease level occurs on the part of the plant near the soil and the defoliation difficult the disease evaluation on this part of the plant; m) the most effective disease occurs on the highest parts of the plant.
Durante as últimas safras a ferrugem asiática da soja tem se apresentado como um dos maiores problemas na sojicultura nacional. Os prejuízos diretos pela queda da produção e os gastos com fungicidas têm acarretado prejuízos que vêm aumentando a cada safra. Objetivando compreender melhor a epidemiologia da doença, este estudo a buscou respostas para fatores como variação do progresso da epidemia em duas localidades, o efeito da época de semeadura, do ciclo da cultivar, do uso de fungicida e da resposta de diferentes cultivares. Os experimentos foram montados, nas Estações Experimentais da Agência Rural de Senador Canedo e de Anápolis. Para cada local foram utilizadas três épocas de semeadura, com seis cultivares nos três ciclos da cultura (Monsoy 6101 e BRSNina ciclo precoce; Emgopa 315 e BRSGO Santa Cruz ciclo médio; Emgopa 313 e BRSGO Paraíso ciclo tardio), com e sem a ação de fungicida, sendo avaliados os três terços da planta (inferior, médio e superior). Cada época, para cada um dos locais, foi considerada como um experimento com parcelas sub-sub-divididas. Após a observação dos sintomas da doença, as parcelas com controle químico foram pulverizadas a cada 21 dias com pyraclostrobin+epoxiconazole na dosagem 66,5 g + 25 g i.a. ha-1. As avaliações após o aparecimento da doença foram realizadas semanalmente até a queda completa das folhas. Com os dados de severidade periódicos calculou-se a Área Abaixo da Curva de Progresso da Doença (AACPD) e a Área Abaixo da Curva de Progresso da Doença Relativa (AACPDR), que consiste na divisão da área pelo período de duração da epidemia. As variáveis de rendimento obtidas foram: produtividade, massa de mil grãos (MMG) e porcentagem de grãos chumbinho (%CH). O atraso da entrada da doença em Anápolis, quando comparado a Senador Canedo, propiciou variações nos resultados que enriqueceram a discussão dos dados. A antecipação da ocorrência da doença em Senador Canedo e a alta pressão de inóculo apresentadas podem estar associadas ao fato da estação experimental em Senador Canedo possuir soja cultivada durante todo o ano. O atraso da entrada da doença em Anápolis, quando comparada a Senador Canedo, possibilitou um incremento na produtividade e menor efeito de fungicida. Entre as épocas avaliadas nos dois locais, a segunda apresentou os maiores índices de severidade, mas também os maiores índices de produtividade, fator relacionado às condições do ambiente. O efeito da utilização do fungicida diminuiu significativamente a AACPD, aumentou a produtividade, a MMG e diminuiu a %CH. Cultivares de ciclo precoce apresentaram menor severidade da doença, seguidos pelas cultivares de ciclo médio e tardio. A cultivar Emgopa 315 apesar de ser de ciclo médio apresentou resultados semelhantes às cultivares de ciclo precoce nas avaliações como um todo. Em cada local as épocas se comportaram de forma diferenciada. Em condições de alta pressão de inóculo a diferença entre os fatores estudados é menor. Para pressão de inóculo menor os fatores avaliados expressaram melhor suas variações. Como conclusões retiradas a partir dos resultados discutidos concluiu-se que: a) quanto mais cedo a ferrugem aparece durante o ciclo da cultura, maior é o seu efeito na produtividade da soja; b) a utilização de cultivares de soja de ciclo precoce propicia um efeito escape, que reduz os efeitos da ferrugem, quando comparado às cultivares de ciclo médio e tardio; c) a ocorrência da doença diminui o ciclo da cultura, antecipando seu término devido à desfolha prematura; d) apesar de todas as cultivares apresentarem suscetibilidade à ferrugem, algumas apresentam menor severidade relacionada a variações nos níveis de resistência parcial à doença; e) a utilização do fungicida pyraclostrobin+epoxiconazole na dosagem de 66,5 g + 25 g i.a. ha-1, aplicado a partir do aparecimento dos primeiros sintomas e posteriormente a intervalos de 21 dias diminuiu expressivamente o progresso da doença e seus efeitos nas variáveis de rendimento da soja; f) a redução do progresso da doença devido à aplicação do fungicida estudado é mais evidente com a semeadura tardia; g) sob o efeito da mistura pyraclostrobin+epoxiconazole na dosagem de 66,5 g + 25 g i.a. ha-1 não há variação entre época de semeadura e local; h) sob alta pressão de inóculo, as variações entre épocas de semeadura no progresso da ferrugem e no rendimento da cultura são menos explícitas; i) o fator época de semeadura não deve ser considerado isoladamente, mas sempre em associação a outros fatores que influenciam a ação do fungo como aplicação de fungicida, ciclo e resistência da cultivar; j) a utilização do parâmetro Área Abaixo da Curva de Progresso da Doença Relativa (AACPDR) é justificada para dados nos quais existe variação da duração do ciclo da soja, interferindo na duração da epidemia de ferrugem. Esta adequação se faz necessária para que os resultados de progresso da doença não sejam comprometidos; l) a parte da planta mais afetada pelos sintomas é o terço inferior e a desfolha dificulta a avaliação da doença nesta região; m) o controle mais efetivo da doença pelo fungicida ocorre nos terços superior e médio da planta
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Hjort, Karin. "The cell cycle of the hyperthermophilic archaeal genus Sulfolobus." Doctoral thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3010.
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The third domain of life, Archaea is one of the three main evolutionary lineages together with the Bacteria and the Eukarya domains. The archaea are, despite their prokaryotic cell organisation, more closely related to eukaryotes than to bacteria in terms of the informational pathways (DNA replication, transcription and translation). Organisms from the archaeal hyperthermophilic genus Sulfolobus thrives in a hot (80°C), acidic (pH 2-4) and sulphur-rich environment. In my thesis, I have used a variety of different approaches to study the Sulfolobus cell cycle. After dilution of a stationary phase cell culture with fresh medium, synchronous cell cycle progression was obtained. From the synchronised cell culture experiment we could conclude that the major cell cycle events (nucleoid segregation, cell division and chromosome replication) were tightly coupled to each other and to cellular mass increase. Inhibitors of the elongation stage of chromosome replication, and of cell division, as well as drugs arresting the cell cycle in the post-replicative phase, were found in an in vivo screening of a range of antibiotics. The cell cycle was found to be regulated such that the previous cell cycle step had to be successfully accomplished before the next could initiate, except for DNA replication which could occur without an intervening cell division event. The replication pattern of Sulfolobus solfataricus was analysed using a marker frequency assay. From the results, we were able to determine that a single origin is utilized in vivo, that the replication directionality is bidirectional, and also an approximate location of the replication origin within the genome. Intracellular virus production in vivo of SIRV2 (Sulfolobus islandicus rod-shaped virus2) in Sulfolobus islandicus was also analysed. The effects on the host cell were determined, including loss of cell viability, inhibited initiation of replication at virus infection and DNA degradation and loss of cell integrity at the time of virus release. Also, for the first time intracellular virus DNA was visualized with flow cytometry.
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Rilling, Klaus. "Beeinflussung der Apoptoserate und Zellzyklusprogression humaner T-Zellen durch den probiotischen E. coli Stamm Nissle 1917." Doctoral thesis, [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=978696336.
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Quinlan, Edward J. "Control of Bovine Papillomavirus E2 Function By Acetylation and the Novel E2 Interacting Protein RINT1: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/585.
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Human papillomavirus infection is the cause of more than 99% of cervical cancer cases. The current vaccine is ineffective therapeutically; highlighting the need for continued papillomavirus research. One avenue that could be explored in this regard is the function of the papillomavirus E2 regulatory proteins. HPV E2 represses expression of the viral E6 and E7 oncoproteins. Reintroduction of E2 into cervical carcinoma cells results in growth arrest and cellular senescence. Understanding the mechanism of how E2 regulates the early promoter may be key to developing new therapeutic and prophylactic vaccines. Here, we describe regulation of E2 through acetylation and possibly through direct interaction with a novel cellular interacting protein, RINT1. Histone acetyltransferase (HAT) proteins have been demonstrated to interact with Bovine Papillomavirus (BPV) and Human Papillomavirus (HPV) E2 proteins as well as enhance E2 dependant transcription luciferase reporter plasmid containing E2 binding sites. We demonstrate that HATs p300, CBP, and pCAF are limiting for E2 dependant transcriptional activation and that each protein functions independently. We have also identified that BPV-1 E2 is a substrate for acetylation by p300. Mutants of E2 that cannot be acetylated on lysines 111 or 112, display abnormal transcriptional phenotypes. Cells deficient in p300 display similar transcriptional defects that are intensified by CBP depletion. We propose that acetylation of BPV-1 E2 is necessary for transcriptional activation. Acetylation generates a binding site through which a co-factor may interact via a bromodomain. Regulation of E2 dependent transcriptional activation through a post-transcriptional modification represents a novel method through which BPV-1 controls gene expression.
We also present evidence for a direct interaction between BPV-1 E2 and the cellular factor RINT1. This interaction does not appear to be critical for transcriptional regulation; however, several other functional pathways are indicated by the cellular complexes in which RINT1 functions. Some of these, such as ER/Golgi vesicular transport and hTERT independent telomere maintenance, are pathways in which E2 has no known role. Further investigation into regulation and consequences of E2 acetylation and the biological significance of the interaction between E2 and RINT1 could prove important in understanding the complex role of E2 in papillomavirus infection.
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Wang-Rosenke, Yingrui. "Nitric oxide-cGMP signal transduction in the injury, matrix expansion and progression of anti-thy1-induced renal disease of the rat." Saarbrücken VDM Verlag Dr. Müller, 2008. http://d-nb.info/991345665/04.
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Delmas, Véronique. "Structure et proprietes biologiques du papovavirus de hamster." Paris 6, 1986. http://www.theses.fr/1986PA066550.
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Le papovavirus de hamster (hapv) possede un tropisme restreint in vivo vis a vis des keratinocytes et des lymphocytes. Il se replique dans les tumeurs cutanes qui apparaissent chez des hamsters syriens, et induit egalement des lymphomes chez le hamster. L'organisation genetique du hapv deduite de sa sequence a montre qu'il appartient a la famille des polyomavirus. Le hapv est present dans les lymphomes sous forme de multiples copies libres possedant toujours une deletion localisee dans la meme region du genome. Les signaux de transcription precoce du hapv semblent etre actives par la region precoce de ce virus
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Stemp, Melissa. "Biomarkers of disease : concentrations in the serum of women during natural and stimulated ovarian cycles and during early pregnancy." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2013. https://ro.ecu.edu.au/theses/865.
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Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In addition, the study was able to investigate the possible erroneous crossing of clinical cut‐off values associated with disease due to other biological processes rather than the disease itself.
total of 73 blood samples (10 women) taken throughout the natural menstrual cycle, 64 blood samples (11 women) during stimulated ovarian cycles and 86 blood samples (14 women) during early pregnancy monitoring were collected and all samples were analysed by batch analysis on the Roche Cobas e411. Concentrations of CA125, tPSA, CA15‐3 and CA72‐4 showed no significant difference between the natural and stimulated ovarian cycle groups (p≥0.5989). On average the mean PAPP‐A of the natural group was 2.41±0.58 mIU/L higher than the stimulated group (t = 4.10, p < 0.001). CA125 and CA15‐3 results were both significantly influenced by the stage of the cycle (p=
In conclusion, batch analysis of all samples from each of the participants was conducted to maximise the possibility that any changes seen in biomarker concentrations were due to biological fluctuations and not because of assay variability. Ovarian stimulation reduced serum PAPP‐A levels, whilst CA125 and CA15‐3 were unaffected by ovarian stimulation per se but showed cyclical changes throughout both natural and stimulated cycles. PAPP‐A, CA125, tPSA and CA15‐3 all showed consistent changes in early pregnancy, and their combined benefits as markers of different aspects of implantation, embryogenesis and placentation warrants further investigation. Only CA125 in early pregnancy crossed the cut‐off associated with disease, ie ovarian cancer, and other gynaecological and inflammatory conditions. Care must therefore be taken when using CA125 determinations to detect disease if the woman is less than 7 weeks pregnant as transient elevations during this time appear normal.
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Mahmoud, Abady Maryam. "Modulation of growth factors and cell cycle regulatory molecules in experimental cardiomyopathy." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210244.
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Background: Different types of cardiomyopathies are associated with variable hypertrophic response. A number of growth factors are thought to play a role in pathologic cardiac remodeling.
Aims: We compared the modulation of the TGF-ƒÒ superfamily and IGF-1 signaling pathways and their target genes, the cell cycle regulatory proteins in tachycardia-induced dilated cardiomyopathy, a model with no detectable hypertrophy and in ischemic cardiomyopathy, a model with a marked hypertrophic reaction.
Methods: In the first study, endomyocardial biopsies were obtained weekly in 15 dogs, during the development of tachycardiomyopaty. Genes involved in the myostatin-TGF-ƒÒ-Activin-A/Smad signaling pathway, p21 and cyclin D were quantified and correlated to echocardiographic measures of hypertrophy. In the second study, myocardial tissue samples were obtained in 8 dogs with a healed myocardial infarction, in 8 dogs with heart failure induced by overpacing and in 7 healthy dogs. We measured gene expression of IGF-1, its receptor (IGF-1R) and cyclins A, B, D1, D2, D3 and E and correlated them to the level of hypertrophy.
Results: Tachycardiomyopathy was characterized by chambers dilation with no identifiable hypertrophy. Ischemic cardiomyopathy was characterized by eccentric hypertrophy. In tachycardiomyopathy, Activin-A mRNA was 4-fold higher than at baseline. Smad7 was overexpressed in severe heart failure; p21, a direct target gene of the Smad pathway was upregulated 8-fold and cyclin D1 was down-regulated. In that model, IGF-1 was overexpressed but neither IGF-1R nor any of the cyclins studied.
In ischemic cardiomyopathy, IGF-1, IGF-R, and cyclins B, D1, D3 and E gene expression were upregulated.
In tachycardiomyopathy, Activin-A and p21 were inversely correlated to the thickness of the interventricular septum. In normal dogs and in the both models of cardiomyopathy, IGF-1R was correlated to the thickness of the interventricular septum and to cyclins.
Conclusions: Taken together, these results agree with the notion that Activin-A, IGF and cyclins are involved in the modulation of hypertrophic response observed in cardiomyopathies.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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Tunón, Ann-Marie. "The endometrium of the gynaecologically healthy mare during oestrus : a clinical, morphological, chemical and immunological study /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 1999. http://epsilon.slu.se/avh/1999/91-576-5407-7.pdf.
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Morel, Frédéric. "Etude experimentale du controle d'une famille de proteines de secretion d'un organe androgeno-dependant : l'epididyme de lezard." Clermont-Ferrand 2, 1987. http://www.theses.fr/1987CLF21074.
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Stamateris, Rachel E. "CDK4 Rescues Diabetes in IRS2-Deficient Mice: Exploring Novel Roles of a Cell Cycle Regulator in Promoting Beta Cell Differentiation." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1138.
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Strategies aimed at expanding functional beta cell mass remain a prime goal of diabetes research. Both the insulin signaling pathway, as well as the G1/S transition of the cell cycle are critically important for the maintenance of beta cell mass. We previously demonstrated in a mouse model of diabetes, insulin receptor substrate 2 (Irs2) deficient mice, that beta cell failure was attributed to reduced islet expression of Cyclin D2, and that overexpressing Cyclin D2 rescued proliferation in Irs2 deficient beta cells in vitro. Since Cyclin D2 partners with CDK4 to drive cell cycle progression, we hypothesized that an activated form of CDK4, Cdk4-R24C (resistant to inhibition by the INK4A cell cycle inhibitor p16), would rescue the in vivo proliferation defect in Irs2 deficient mice. Interestingly, Irs2 knockout mice with the active Cdk4 R24C allele, displayed rescued blood glucose, and normalized glucose tolerance, without affecting peripheral insulin resistance. I found that both and beta cell mass and proliferation were rescued in vivo, contributing to the rescue of glucose tolerance. Interestingly, the dedifferentiated phenotype of Irs2 knockout islets (ALDH1A3+ cells, nuclear FOXO1 and suppressed PDX1) was completely restored with the active Cdk4 allele, suggesting that CDK4 may play a role in promoting beta cell differentiation. Utilizing various in vitro models where FOXO1 represses Pdx1, overexpression of CDK4/CyclinD2 was consistently able to rescue the FOXO1-mediated repression of Pdx1, without significant impacts on FOXO1 subcellular localization. These results suggested that FOXO1 regulation in the beta cell is more complex than previously described, and also suggested that CDK4/Cyclin D2 may be instead modulating the acetylation status of FOXO1, impacting its transcriptional activity. To this end, inhibiting histone acetylate transferases (HATs) partially rescued FOXO1-mediated Pdx1 suppression, while inhibiting histone deacetylase enzymes (HDACs) showed the reverse effect of trending towards blocking the Cyclin D2/CDK4-mediated rescue of Pdx1. Finally, I found that CDK4/Cyclin D2 increases phosphorylation of sirtuin 1 (SIRT1), an HDAC that modulates the acetylation status, and transcriptional activity of FOXO1, and that CDK4/Cyclin D2 promotes FOXO1 degradation. In sum, we conclude that activated CDK4 rescues beta cell failure due to IRS2 deficiency through multiple mechanisms related to not only cell cycle regulation but also to beta cell differentiation status, primarily through modulation of FOXO1 transcriptional activity.
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Sturm, Andreas. "Modulation intestinaler Wundheilungsvorgänge und Erhaltung der mukosalen Immunhomöostase." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2004. http://dx.doi.org/10.18452/13916.
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Die intestinale Mukosa bildet eine biologisch wichtige Barriere zwischen dem Organismus und den schädigenden Faktoren im intestinalen Lumen. Diese komplexe Aufgabe wird durch eine hochdifferenzierte intestinale Mukosa bewältigt, die eine strukturelle sowie funktionelle intestinale Barriere bildet. Das Ziel der vorliegenden Arbeiten war, ausgewählte Aspekte der Regulations- und Reparaturmechanismen der intestinalen mukosalen Barriere weitergehend zu charakterisieren. Unsere Untersuchungen zeigen, dass das Phospholipid Lysophosphatidsäure (LPA) die intestinale epitheliale Zellmigration stimuliert, die dieser Zellen jedoch inhibiert. Die Modulation der intestinalen Wundheilung durch LPA erfolgt durch einen TGF-b-unabhängigen Mechanismus und wird über einen G-Protein-abhängigen Rezeptor vermittelt, wie wir im Rahmen umfangreicher Untersuchungen zur Signaltransduktion unter Verwendung spezifischer Modulatoren der Signaltransduktion wie Bradykinin, Phorbolester, Pertussistoxin, Suramin und neutralisierender TGF-b-Antikörper belegen konnten. In weiteren Experimenten konnten wir zeigen, dass LPA auch in-vivo einen wundheilungsfördernden Effekt besitzt. Die topische Applikation von LPA in diesem experimentellen Kolitismodell bewirkte einen geringeren Gewichtsverlust sowie ein geringeres Ausmaß an intestinaler Entzündung und Nekrose in-vivo. Diese Untersuchungen legen somit nahe, dass LPA die intestinale epitheliale Wundheilung durch eine Modulation der intestinalen epithelialen Migration und Proliferation durch TGF-b-unabhängige Mechanismen stimuliert. Weitere Untersuchungen beschäftigten sich mit der funktionellen Charakterisierung von Lamina propria T-Zellen (LPT) und peripheren Blut T-Zellen (PBT). Wir konnten zeigen, dass der Zellzyklus von LPT distinkt von PBT reguliert wird. Hierbei spielt der Zellzyklusinhibitor p53 eine zentrale Rolle in der Zellzyklusregulation von LPT. Um Autoimmunität zu verhindern, muss es nach einer Eliminierung des Antigens wieder zu einer Depletion des Pools an Effektor-T-Zellen durch die Aktivierung der Apoptose kommen. Wir konnten zeigen, dass beim Antigen-induzierten Zelltod von LPT der intrinsische Apoptoseweg aktiviert wird und Caspase-8 hierbei eine zentrale Rolle spielt. Physiologischerweise sind Zellzyklus und Apoptose eng miteinander verbunden. In weiteren Versuchen konnten wir jedoch zeigen, dass dies nicht bei LPT der Fall ist und somit die von PBT distinkte Regulation von Zellzyklus und Apoptose mukosaler T-Zellen weiter unterstreichen. Zusammengefasst konnten wir durch ausgewählte Untersuchungen zeigen, dass die intestinale Barriere und ihre funktionelle Beeinflussung eine wesentliche Rolle in der Pathogenese und Therapie intestinaler Entzündungen besitzt. Eine Beeinflussung intestinaler Reparaturprozesse und Modulation abnormer T-Zellen könnte neue Möglichkeiten in der Therapie intestinaler Entzündungen, wie z.B. chronisch entzündlichen Darmerkrankungen bewirken.The intestinal mucosa protect the host from the potential harmful content of the intestinal lumen. To accomplish this difficult goal, the highly complex mucosa forms an anatomical as well as functional barrier to protect the organism.In this work, we aimed to characterize distinct aspect of the intestinal barrier, focussing on distinct regulation and repair mechanism of the intestinal mucosa. First, we demonstrate, that the phospholipid lysophosphatidic acid (LPA) stimulate the migration of intestinal epithelial cells, but, in contrast, inhibit their proliferation. This effect is mediated by G-protein receptors and is TGF-b-independent, as we could demonstrate in further experiments using bradykinine, phorbole ester, pertussis toxin and suramine to modulate distinct signalling pathways.We then demonstrated, using a well-established animal model of colitis, that LPA enhances intestinal wound healing in-vivo. In detail, the topical application of LPA in TNBS-treated rats reduced weight loss, ameliorate intestinal inflammation and prevented necrosis in the animals. This experiments demonstrate for the first time, that LPA modulates migration and proliferation of intestinal epithelial cells by distinct TGF-b independent pathways. Further experiments aimed to explore functional differences between peripheral blood (PBT) and mucosal T-cells (LPT). We demonstrated, that the cell cycle is distinctively regulated in PBT and LPT, identifying p53 as key regulator of LPT cell cycling. To avoid auto-immunity, the pool of effector T-cells must be depleted by apoptosis, once the antigen has been cleared. We demonstrate, that intrinsic pathway of apoptosis is activated during the antigen-induced cell death in LPT and that caspase-8 activity is required to execute LPT apoptosis. Cell cycle and apoptosis are ultimately linked. However, as we show in further experiments, this is not the case in LPT, underlining the distinct regulation of LPT cell cycle and apoptosis.In conclusion, using various distinct experimental tools, we demonstrate that the intestinal barrier itself and the modulation its function plays a fundamental role in the pathogenesis mucosal inflammation. The data presented in this work may therefore open new therapeutic options in the therapy of intestinal inflammatory disorders, such as inflammatory bowel diseases.