Дисертації з теми "Mediated pathways"
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Raval, Raju R. "Hypoxia-mediated pathways in cancer." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433331.
Повний текст джерелаPrado, Sánchez Judith. "Regulation of neuroinflammation by cGMP-mediated pathways." Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/96910.
Повний текст джерелаIn the present work we investigated the involvement of intracellular cGMP levels in regulating different aspects of neuroinflammation. In the first chapter we observed that cultured rat astrocytes and microglial cells express the necessary machinery to synthesize cGMP in response NPs and to degrade the nucleotide. We also investigated the effects of NP stimulation in the expression of the pro-inflammatory protein iNOS. We observed that pretreatment with ANP down-regulates iNOS protein levels induced by the pro-inflammatory agent LPS by an NPR-A-PKG dependent mechanism in rat cultured microglial cells. In addition we found that this down-regulation seems to be done at translational level, without affecting transcription or protein degradation rate. Based on evidence obtained in our laboratory in cultured glial cells indicates that cGMP-mediated pathways regulate cytoskeleton dynamics, GFAP expression and motility in astrocytes, as well as inflammatory gene expression in microglia found in the first chapter, suggesting a role in the regulation of the glial reactive phenotype. In the second chapter we wanted to examine if cGMP regulates the glial inflammatory response in vivo following CNS damage caused by a focal cryolesion onto the cortex in rats and mice. We investigated the effect of 3 doses of treatment with two different cGMP-phosphodiesterase (PDE) inhibitors, zaprinast and sildenafil. We observed that the non-selective GMP-PDE inhibitor zaprinast enhances astrogliosis around the lesion while decreasing macrophage/microglial activation, oxidative stress and neuronal death in rat. We observed also that treatment with the selective PDE5 inhibitor sildenafil reproduces in mice the changes in glial reactivity and the antioxidant and antiapoptotic effects previously observed with zaprinast in rats indicating that inhibition of PDE5 is responsible for these neuroprotective actions. However, sildenafil effects were not observed in mice deficient in MT-I/II. We further show that sildenafil significantly increases MT-I/II protein levels in lesioned cortical homogenates and MT-I/II immunostaining in glial cells around the lesion, and decreases activation of the transcriptor factor STAT3, supporting the involvement of these proteins in the neuroprotective effects of sildenafil in focal brain lesion. As a result of the anti- inflammatory and neuroprotective effects observed by PDE5 inhibitors in the cryolesion model, in the third chapter we investigate if treatment with sildenafil could have beneficial effects in a MOG35-55-induced EAE model, an animal model of MS, a disease where an altered inflammatory response occurs. We show that treatment with sildenafil after disease onset markedly reduces the clinical signs of EAE by preventing axonal loss and promoting remyelination. Furthermore, sildenafil decreases CD3+-leukocyte infiltration and microglial/macrophage activation in the spinal cord, while increasing Foxp3-Tregs. In addition, sildenafil treatment decreased ICAM-1 in spinal cord infiltrated cells. The presence of reactive astrocytes forming scar-like structures around infiltrates was enhanced by sildenafil suggesting a possible mechanism for restriction of leukocyte spread into healthy parenchyma. We show also that treatment with sildenafil at the onset of clinical symptoms, when the inflammatory process is stronger, prevent disease advance and regulates peripheral adaptative immune response and PDE5 levels. Taking in account all the results obtained we evidenced that modulation of intracellular cGMP levels have beneficial effects in neuroinflammatory processes and that this benefits are related to regulation of reactive gliosis, oxidative stress, antioxidant factors, adaptative immune response and infiltration of immune cells into CNS leading to decrease neuronal damage.
Vosten, Alexander. "Mathematical modelling of scaffold-mediated signalling pathways." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/213225/1/Alexander_Vosten_Thesis.pdf.
Повний текст джерелаWong, Tsz-yeung, and 王子揚. "IBDV-mediated antiviral responses by TLR3 signaling pathways." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B41897201.
Повний текст джерелаCharlesworth, Amanda. "Signalling pathways mediated by the bombesin/GRP receptor." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244267.
Повний текст джерелаZhu, Liang. "RAP1-TRIGGERED PATHWAYS FOR TALIN-MEDIATED INTEGRIN ACTIVATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1512580363343006.
Повний текст джерелаWong, Tsz-yeung. "IBDV-mediated antiviral responses by TLR3 signaling pathways." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B41897201.
Повний текст джерелаBoyer, Robert D. (Robert Damian) 1978. "Stress-mediated reaction pathways for dislocation nucleation in copper." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39550.
Повний текст джерелаIncludes bibliographical references (p. 111-119).
The ductile behavior of metals requires dislocation nucleation, from either homogeneous or heterogeneous sources, in order to produce the large number of dislocations necessary for extensive plastic deformation. As with the majority of the defect processes that comprise deformation and failure of materials, dislocation nucleation is well described in the framework of transition state theory as a stress-mediated, thermally activated process. We have used reaction pathway sampling methods and well-fit empirical potentials to determine the stress-dependent behavior of and atomistic mechanisms for dislocation nucleation at stresses much lower than typically accessible to atomistic techniques. We have shown that a significant range of stresses exist for which homogeneous dislocation loop nucleation is feasible because the critical nucleate transitions to an in-plane shear perturbation where the shear displacement of most particles is significantly less than the Burger's vector. We have also revealed that the common structural conception of activation volume for dislocation nucleation does not apply for all stresses and in general over-predicts the stress-dependence of activation by considering only the shear displacement of the critical defect.
(cont.) Furthermore, by considering the full reaction pathway for dislocation nucleation in perfect crystals and at a vacancy, we have provided a fully atomistic description of shear localization via an expanded one-dimensional chain analysis of the wave-steepening behavior. Lastly, both breaking the local atomic symmetry and increasing the extent of heterogeneous nucleation sites are shown to lower the activation energy for dislocation nucleation. In general we have applied reaction pathway sampling to the problem of dislocation nucleation in Cu not only for a perfect crystal, but also in the presence of point defects, vacancy clusters and nanowire surfaces. As a result the strength of a variety of nucleation sites in mediating activation as well as specific atomistic mechanisms for dislocation nucleation have been discussed from both structural and energetic perspectives.
by Robert D. Boyer.
Ph.D.
Sickle, Eugene Stanford. "Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids." Doctoral thesis, University of Cape Town, 1997. http://hdl.handle.net/11427/17967.
Повний текст джерелаIncludes bibliographical references.
An efficient strategy for the synthesis of 14β-3'-oxobutyl 19-norsteroids has been developed and the intramolecular reactivity of the derived compounds has been investigated. The approach is based on cycloaddition of methyl vinyl ketone to 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate which proceeded with a high degree of regio- and stereoselectivity to give 16α-acetyl-3-methoxy-14, 17α-ethenoestra-1 ,3,5(1 O)-trien-17β-yl acetate. The cycloadduct underwent base mediated fragmentation, affording an efficient and stereocontrolled synthesis of 3-methoxy-14β-3'-oxobutylestra-1,3,5(10),15-tetraen-17-one which in turn gave 3-methoxy-5',6'-dihydro-15αH-benzo[14,15]-14β-estra-1,3,5(1O)-trien-4'(3'H), 17-dione via an intramolecular Michael reaction. Regioselective deoxygenation of the dione at C-4', followed by standard functional group modifications provided the parent 14β-perhydrobenzo[14,15]-estradiol analogues. An alternative, more expedient, route to this novel steroidal ring system was developed which relied on an anionic oxy-Cope rearrangement as the key step. Thus methylenation of the cycloadducts derived from reaction of the dienyl acetate and selected dienophiles (acrolein and methyl vinyl ketone) gave after hydrolysis of the bridgehead ester, substrates which underwent [3,3]sigmatropic rearrangement to generate a series of 14β-perhydrobenzo[14,15]-17-ketones.
Perens, Gregory S. "NMDA Receptor-mediated Synaptic Plasticity in Developing Mammalian Visual Pathways." VCU Scholars Compass, 1995. https://scholarscompass.vcu.edu/etd/5246.
Повний текст джерелаVenkateswaran, Anjli. "RET/PTC1-mediated phosphotyrosine signaling pathways involved in thyroid cell transformation." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1100117850.
Повний текст джерелаTitle from first page of PDF file. Document formatted into pages; contains xvi, 157 p.; also includes graphics (some col.) Includes bibliographical references (p. 146-157).
Sukhai, Mahadeo A. "Cytokine-mediated pathways of mdr1 gene regulation in cultured rat hepatocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58862.pdf.
Повний текст джерелаHartley, Strachan. "Prolactin mediated activation of survival pathways in human breast cancer cells." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29440.
Повний текст джерелаFosu, Stacy C. "Functionalization of Arenes, Amines, Alkenes, and Alkynes Mediated by Radical Pathways." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555514456659022.
Повний текст джерелаWallace, Erin K. "Enzyme mediated reductive chemistry in plant flavonoid and monolignol biosynthetic pathways /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3167819.
Повний текст джерелаGuerra, Jillian. "Pathways to agroecology : mediated markets and credit access in Santa Catarina, Brazil." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/58792.
Повний текст джерелаScience, Faculty of
Resources, Environment and Sustainability (IRES), Institute for
Graduate
Kennedy, Christopher R. J. "Signalling pathways of bradykinin-mediated arachidonic acid release in MDCK-D1 cells." Thesis, University of Ottawa (Canada), 1997. http://hdl.handle.net/10393/4074.
Повний текст джерелаKennedy, Chris R. J. "Signalling pathways of bradykinin-mediated arachidonic acid release in MDCK-D1 cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21003.pdf.
Повний текст джерелаHorner, Amy Jean. "Functional Roles of Crustacean Dual Antennular Chemosensory Pathways in Odor Mediated Behaviors." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/biology_diss/18.
Повний текст джерелаRoux, Philippe P. "Signaling pathways implicated in p75 neurotrophin receptor-mediated neuronal survival and death." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38267.
Повний текст джерелаNervous system injuries represent interesting models to study p75NTR because several types of injury induce p75NTR expression. In the first part of this thesis, we have used the pilocarpine model of seizure in the rat and found that this type of injury induces neuronal apoptosis and p75NTR expression. Apoptosis was tightly linked with p75NTR expression, suggesting that p75NTR may promote apoptosic cell death after seizure, and consistent with this, we have found that p75NTR can promote JNK activation and apoptosis in vitro. In the second study, we discovered that p75NTR can also facilitate survival under some cellular circumstances. The survival-promoting effect of p75NTR was accompanied with PI3-K-dependent Akt activation, and correlated with a reduction in cytosolic protein tyrosine phosphatase activity, suggesting that p75NTR may regulate a tyrosine phosphatase involved in the regulation of Akt and survival. In the last study, we have found that the related neuroprotective compounds, K252a and CEP 1347, are potent. MLK3 inhibitors, yet they simultaneously activated Akt and ERK, and survival through MLK3-independent mechanisms. These findings suggested that K252a and CEP1347 may act on a novel target responsible for their survival-promoting activities.
Taken together, the data in this thesis adds to our understanding of the physiological functions of p75NTR, and contributes to our knowledge of the cellular machinery that control neuronal cell survival and death.
Ratcliffe, Marianne Jennifer. "Intercellular junctional proteins as targets for protein kinase c-mediated signalling pathways." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300471.
Повний текст джерелаLam, Huy Hong. "Discrete Transition System Model and Verification for Mitochondrially Mediated Apoptotic Signaling Pathways." Thesis, Virginia Tech, 2007. http://hdl.handle.net/10919/33802.
Повний текст джерелаMaster of Science
Yamagishi, Kenji. "Studies on the cAMP-mediated signal transduction pathways in homobasidiomycete, Schizophyllum commune." Kyoto University, 2006. http://hdl.handle.net/2433/144347.
Повний текст джерела0048
新制・論文博士
博士(農学)
乙第11785号
論農博第2591号
新制||農||923(附属図書館)
学位論文||H18||N4113(農学部図書室)
23840
UT51-2006-C707
(主査)教授 大東 肇, 教授 吉川 正明, 教授 永尾 雅哉
学位規則第4条第2項該当
Shah, Bhavik P. "Targeting Fat-Sensitive Pathways In Enteroendocrine Cells Using Nanoparticle-Mediated Drug Delivery." DigitalCommons@USU, 2009. https://digitalcommons.usu.edu/etd/432.
Повний текст джерелаCatt, Samantha. "Light-activated nitrile imine mediated reaction pathways for the synthesis of bioinks." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/131122/1/Samantha_Catt_Thesis.pdf.
Повний текст джерелаPingguan, Belinda Bte Simon Jingking. "Calcium mediated signalling pathways for chondrocytes in 3D constructs subjected to cyclic loading." Thesis, Queen Mary, University of London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426066.
Повний текст джерелаBuchmann, Cody. "Reversal of RNA-mediated gene silencing pathways by geminivirus AL2 and L2 proteins." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1221847080.
Повний текст джерелаBuckwalter, Tara Lynne Furminger. "Phosphotyrosine-mediated signal transduction pathways essential for RET/PTC-1-induced tumor formation /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu970163275.
Повний текст джерелаTraub, Oren. "Mechanisms of shear stress-mediated ERK1/2 modulating signal transduction pathways in endothelial cells /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/6309.
Повний текст джерелаNewman, Alice Clare. "Autophagy- and TBK1-mediated regulation of TRAF2/3 in alternative NF-κB signalling". Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25842.
Повний текст джерелаMitchell, Dianne Courtenay. "Regulation and function of the Rho GTPase mediated signaling pathways in metastasis and lenticular differentiation." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/5845.
Повний текст джерелаPüschel, Gerhard, C. Kirchner, A. Schröder, and Kurt Jungermann. "Glycogenolytic and antiglycogenolytic prostaglandin E₂ actions in rat hepatocytes are mediated via different signalling pathways." Universität Potsdam, 1993. http://opus.kobv.de/ubp/volltexte/2010/4585/.
Повний текст джерелаSchilling, Ramon [Verfasser], and Viktor [Akademischer Betreuer] Umansky. "Identification of novel molecular components in Ripoptosome-mediated signaling pathways / Ramon Schilling ; Betreuer: Viktor Umansky." Heidelberg : Universitätsbibliothek Heidelberg, 2016. http://d-nb.info/1180617096/34.
Повний текст джерелаPathak, Ashutosh K. "A proteomics based approach of IgE-receptor mediated signalling pathways in a mast cell line." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427236.
Повний текст джерелаAldossary, Sara Abdulrahman M. "The sensitisation of TRPV1 mediated responses by prostaglandin and bradykinin and the signalling pathways involved." Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/33359.
Повний текст джерелаPu, Qiaoxue, and 浦峤雪. "Investigation of the regulatory pathways involved in NO- and EDHF-mediated relaxations in porcine coronary arteries." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50712652.
Повний текст джерелаpublished_or_final_version
Pharmacology and Pharmacy
Master
Master of Medical Sciences
Wilkinson, Meredyth Grace Llewellyn. "Investigating novel pathways in B cell mediated autoimmunity in the context of the disease juvenile dermatomyositis." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10048930/.
Повний текст джерелаRush, Craig Michael. "Crosstalk between the Jak-Stat and Wingless pathways is mediated by Mad in Drosophila melanogaster larval hematopoiesis." Ohio University Art and Sciences Honors Theses / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ouashonors1367508013.
Повний текст джерелаKleveman, Jan Alexander Verfasser], and Martin [Akademischer Betreuer] [Korte. "Neurotrophin mediated signaling pathways common to the immune and nervous system / Jan Alexander Kleveman ; Betreuer: Martin Korte." Braunschweig : Technische Universität Braunschweig, 2018. http://d-nb.info/1175816302/34.
Повний текст джерелаJindra, Peter Thomas. "Anti-MHC class I antibody-mediated activation of cell proliferation and survival signaling pathways in endothelial cells." Diss., Restricted to subscribing institutions, 2007. http://proquest.umi.com/pqdweb?did=1495958881&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Повний текст джерелаJessop, Lea. "Architecture of the synaptic intermediates of the site-specific recombination pathways mediated by the bacteriophage Lambda integrase /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9981973.
Повний текст джерелаSagi, Sarah Ann. "G alpha q- and G alpha 12-mediated signaling pathways activated by G protein-coupled thrombin receptors /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9992384.
Повний текст джерелаForaker, Amy Beth. "Characterization of the endocytic pathways regulating riboflavin (vitamin B2) absorption and trafficking in human epithelial cells." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1172865566.
Повний текст джерелаOliveira, Mateos Cristina. "Epigenetic regulation mediated by antisense non-coding RNAs and its impact on oncogenic pathways: the HMGA2/RPSAP52 locus." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/669259.
Повний текст джерелаLa gran mayoría del genoma humano se transcribe, dando lugar en muchos casos a RNAs no codificantes. Los transcritos antisentido son uno de los tipos más abundantes de RNAs no codificantes largos y muchos poseen importantes funciones en la regulación de los genes cercanos. Este es el caso de RPSAP52, transcrito antisentido del gen codificante HMGA2. La expresión de ambos genes es elevada en varios cánceres humanos y correlaciona positivamente como consecuencia de la regulación que RPSAP52 ejerce sobre HMGA2. RPSAP52 forma un R-loop en la región promotora de los dos genes, lo que modifica la conformación de la cromatina y favorece la transcripción de HMGA2. RPSAP52 desempeña funciones adicionales en el citoplasma gracias a su unión a la proteína IGF2BP2, cuya transcripción es regulada por HMGA2. IGF2BP2 promueve la traducción de genes relacionados con importantes rutas proliferativas, y su interacción con RPSAP52 afecta su unión a algunos RNAs mensajeros, así como su reclutamiento a polisomas. En este trabajo demostramos que LIN28B, uno de los principales reguladores negativos de la maduración del miRNA let-7, es uno de sus targets. De este modo, RPSAP52 aumenta la traducción de LIN28B y reduce los niveles del supresor tumoral let-7. La regulación mediada por RPSAP52 tiene un importante impacto en rutas génicas relacionadas con el cáncer. Su depleción afecta negativamente las características tumorigénicas de las células in vitro y disminuye la progresión tumoral in vivo. Además, RPSAP52 puede ser considerado como un biomarcador en sarcomas, ya que sus altos niveles se asocian a un peor pronóstico. En resumen, el presente trabajo propone un modelo regulador mediado por RPSAP52 con dos niveles diferentes de acción. Este transcrito antisentido promueve la activación transcripcional de HMGA2 y, a su vez, regula la función de la proteína IGF2BP2. Dado que HMGA2 e IGF2BP2 están en la misma vía proliferativa, RPSAP52 refuerza la función de HMGA2 tanto sobre IGF2BP2 como sobre sus efectores posteriores, lo que afecta la progresión del cáncer. Debido a los importantes roles desempeñados por RPSAP52 y a sus propiedades oncogénicas, podría ser una potencial diana terapéutica para el desarrollo de nuevos tratamientos contra el cáncer.
Franco, Alier J. "Functional and anatomical basis for corticotropin releasing factor mediated analgesia covergence of parallel pathways on the periaqueductal gray /." Cincinnati, Ohio : University of Cincinnati, 2005. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin.
Повний текст джерелаTitle from electronic thesis title page (viewed Mar. 6, 2006). Includes abstract. Keywords: rat, corticotropin, stress, pain, analgesia. Includes bibliographical references.
Kavuri, Megha Shyam [Verfasser]. "Molecular analysis of death receptors mediated apoptotic and non-apoptotic signalling pathways in human keratinocytes / Megha Shyam Kavuri." Magdeburg : Universitätsbibliothek, 2011. http://d-nb.info/104720276X/34.
Повний текст джерелаSeeliger, Christine. "Spatial and stochastic modeling of TrkB mediated signaling pathways involved in long term potentation in the dendritic spine." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708013.
Повний текст джерелаFRANCO, ALIER J. "FUNCTIONAL AND ANATOMICAL BASIS FOR CORTICOTROPIN RELEASING FACTOR MEDIATED ANALGESIA: COVERGENCE OF PARALLEL PATHWAYS ON THE PERIAQUEDUCTAL GRAY." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1122923847.
Повний текст джерелаKarthik, A. G. "Effect of hexadecylglycerol supplementation on protein kinase C-mediated signaling pathways in a murine macrophage-like cell line." Thesis, Boston University, 2005. https://hdl.handle.net/2144/37161.
Повний текст джерелаPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
All mammalian membranes contain ether-linked glycerolipids in which the sn-1 position of the glycerol backbone is occupied by an alkyl chain attached through either an ether, or vinyl ether linkage (plasmalogens). Plasmalogens and ether lipids have been implicated in important cellular functions such as (i) mediating membrane-fusion events, (ii) serving as endogenous antioxidants and (iii) modulating protein kinase C (PKC) and/or phosphatidylinositol-3-kinase (PI3-K)-mediated cellular responses to stimuli. sn -1-hexadecylglycerol (HG) is a simple ether lipid precursor that is able to enter cells and then enter the biosynthetic pathway for ether lipids. We have used HG and ether lipid-deficient animal cell mutants to examine ether lipids' cellular roles. We have examined three cellular events thought to be influenced by cellular ether lipid levels and mediated by both PKC and PI3-K, namely, the generation of superoxide anion (respiratory burst), the release of arachidonic acid (AA) and fragment crystallizable γ (Fcγ) receptor-mediated phagocytosis, three processes essential for neutrophil and macrophage immune functions. When the ether lipid-deficient murine macrophage-like cell line, RAW.108, was treated with HG prior to simulation, superoxide production in response to either a soluble stimulus (phorbol ester, PMA) or particulate stimulus (zymosan), was reduced by >90%. HG supplementation also inhibited PMA-induced but not zymosan-induced AA release, suggesting that two different pathways exist for the release of AA in these cells depending on the stimulus. Fcγ receptor-mediated phagocytosis was also inhibited by HG supplementation. This inhibition was not related to changes in plasmalogen levels as HG was also effective in inhibiting the respiratory burst in the mutant cell line, RAW.12, which cannot form plasmalogens even with HG supplementation. The mechanism of inhibition of these events by HG was likely due to inhibition of PKC and not PI3-K, which was verified independently using other inhibitors of these enzymes.
2031-01-01
Lemaitre, Philippe. "Early role of IL-17 and calcineurin inhibitor-mediated Th2- and Th17-polarization of chronic trachea allograft rejection pathways." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209243.
Повний текст джерелаWe first demonstrated that interleukin-17 contributes to inflammatory lesions in the early phase post-transplantation. Interleukin-17 was found to be produced by &61543;&61540;+ T cells and CD4+ T cells infiltrating the graft and interleukin-17 neutralization significantly reduced the development of epithelial lesions together with inhibition of interleukin-6 and heat-shock-protein 70 gene transcription.
We then investigated the contribution of interleukin-17 to obliterative airway disease. Although interleukin-17 did not play a dominant role in absence of immunosuppression, it was found to contribute to airway pathology in animals receiving cyclosporin A. Under this treatment, we first observed dramatic changes in the composition of the lymphocyte populations infiltrating the graft: the numbers of CD8+ T cells producing interferon-&61543; and type 1 CD4+ T cells were dramatically decreased while the numbers of type 17, and also type 2 CD4+ T cells were unaffected. The pathological relevance of these findings was first demonstrated by the prolongation of graft survival afforded by the depletion of CD4+ T cells in cyclosporin A-treated animals. Furthermore, graft rejection was also delayed in mice genetically deficient in either interleukin-17 or interleukin-4, providing evidence that type 17 and type 2 CD4+ T cells actively contribute to graft rejection in cyclosporin A-treated recipients. On the other hand, parallel experiments in interferon-&61543;-deficient mice revealed that interferon-&
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished