subject:(TAT)

1. Mammadova, Nayiba. Eléments de description et documentation du tat de l'Apshéron, langue iranienne d'Azerbaïdjan : Elements of description and documentation of Absheron Tat, an Iranian language of Azerbaijan.

Degree: Docteur es, Sciences du langage : linguistique et didactique des langues, 2017, Sorbonne Paris Cité

URL: http://www.theses.fr/2017USPCF016

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Cette thèse est une grammaire descriptive du tat de l’Apshéron, une langue iranienne de la branche sud-ouest parlée en Azerbaïdjan. Il s’agit de la première… (more)

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Cette thèse est une grammaire descriptive du tat de l’Apshéron, une langue iranienne de la branche sud-ouest parlée en Azerbaïdjan. Il s’agit de la première description d’un dialecte tat musulman dans une langue occidentale. Après une introduction détaillée présentant le contexte sociolinguistique et la phonologie, le présent travail aborde les différentes parties du discours, le marquage des fonctions grammaticales, la morphologie verbale (dérivation, classes morphologiques du verbe, locutions verbales, emplois et valeurs des formes conjuguées). Les principaux faits de syntaxe de la phrase complexe sont ensuite décrits : subordonnées relatives, complétives, et adverbiales, coordination de prédicats.La description, effectuée dans une perspective typologique, s’appuie sur l’analyse de textes spontanés récoltés sur le terrain, de traductions de l’azéri vers le tat, et sur les connaissances personnelles de l’auteur, locutrice native. Elle est suivie en annexe de textes extraits du corpus, partiellement traduits, ainsi que d’un lexique recensant les lexèmes utilisés dans l’étude et dans les textes.

This thesis is a descriptive grammar of Tat (an Iranian language of the South-Western branch) as spoken on the Absheron Peninsula, east of Baku in the Republic of Azerbaijan. It is the first description of a Muslim variety of Tat in a Western European language.After a detailed introduction outlining the sociolinguistic context and the phonology, the present study discusses the parts of speech, the marking of grammatical relations and verbal morphology of Absheron Tat (verbal derivation, verb classes, complex predicates, formation and use of inflected verb forms). This is followed by a survey of complex sentences, viz. relative clauses, complement clauses, adverbial subordinates as well as coordination.The present work adopts a typological point of view and is based on the analysis of texts originating from the author’s fieldwork and tales translated from Azeri into Tat, in addition to the author’s competence as a native speaker. The appendix presents samples of the text corpus (some of them also translated) and a glossary listing items that feature in the grammatical description and the texts.

Advisors/Committee Members: Authier, Gilles (thesis director).

Subjects/Keywords: Typologie; Tat; Typology; Tat

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APA (6^th Edition):

Mammadova, N. (2017). Eléments de description et documentation du tat de l'Apshéron, langue iranienne d'Azerbaïdjan : Elements of description and documentation of Absheron Tat, an Iranian language of Azerbaijan. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2017USPCF016

Chicago Manual of Style (16^th Edition):

Mammadova, Nayiba. “Eléments de description et documentation du tat de l'Apshéron, langue iranienne d'Azerbaïdjan : Elements of description and documentation of Absheron Tat, an Iranian language of Azerbaijan.” 2017. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 19, 2021. http://www.theses.fr/2017USPCF016.

MLA Handbook (7^th Edition):

Mammadova, Nayiba. “Eléments de description et documentation du tat de l'Apshéron, langue iranienne d'Azerbaïdjan : Elements of description and documentation of Absheron Tat, an Iranian language of Azerbaijan.” 2017. Web. 19 Jan 2021.

Vancouver:

Mammadova N. Eléments de description et documentation du tat de l'Apshéron, langue iranienne d'Azerbaïdjan : Elements of description and documentation of Absheron Tat, an Iranian language of Azerbaijan. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2017. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2017USPCF016.

Council of Science Editors:

Mammadova N. Eléments de description et documentation du tat de l'Apshéron, langue iranienne d'Azerbaïdjan : Elements of description and documentation of Absheron Tat, an Iranian language of Azerbaijan. [Doctoral Dissertation]. Sorbonne Paris Cité; 2017. Available from: http://www.theses.fr/2017USPCF016

2. Wang, Na. Characterization of Translocon and Cargo Dynamics During Tat Transport Using Real-Time Kinetic Approaches.

Degree: MS, Medical Sciences, 2017, Texas A&M University

URL: http://hdl.handle.net/1969.1/165892

► Proteins must be translocated from ribosomes where they are synthesized to different cellular destinations where they perform their functions. Many different protein translocation systems carry… (more)

▼ Proteins must be translocated from ribosomes where they are synthesized to different cellular destinations where they perform their functions. Many different protein translocation systems carry out this activity like the human nuclear pore complex and the bacterial Sec and Tat machineries. In Escherichia coli, twin arginine translocation (Tat) system is used to transport fully folded proteins across the bacterial cytoplasmic membrane and the thylakoid membrane in plants without collapsing the ion gradients. A minimal Tat system consists of 3 integral membrane proteins: TatA, TatB and TatC. TatB and TatC form a receptor complex for the signal peptide of substrates. In the presence of a proton motive force and substrate, TatA is recruited to form the conducting channel allowing the mature domain of the substrate to migrate through it. After transport, TatA disassembles from the TatBC complex. Biochemical and biophysical work has provided information about the mechanism of Tat transport, however, the details of the mechanism are poorly understood. Therefore, we want to develop an in vitro transport assay at single vesicle level to characterize the sub-steps of Tat mechanism at the single vesicle level using total internal reflection fluorescence (TIRF) microscopy. In vitro bulk experiments showed that the transport assay could be conducted at room temperature, which simplifies the assay under microscope by avoiding the temperature-control device. Additionally, ATP could replace NADH to generate PMF, which could maintain a longer membrane potential. 1.5% PVP could replace BSA to avoid background fluorescence. Vesicles could be tethered on the coverslip surface by biotin-streptavidin linkage. Last, the pre-SufI with unnatural amino acid mutation in the signal peptide and cysteine mutation in the mature domain could not be labeled with Azide-Alexa647 and Alexa568 at the same time. In total, these results laid foundation for the in vitro transport assay at the single vesicle level. Advisors/Committee Members: Musser, Siegfried (advisor), Ober, Raimund (committee member), Bondos, Sarah (committee member).

Subjects/Keywords: Tat

…26 viii LIST OF FIGURES Page Fig 1. The cycle of E.coli Tat Transport of the channel… …most proteins in an unfolded state and therefore is indispensable for bacterial growth. Tat… …system transports fully-folded and assembled proteins. The absence of a functional Tat system… …in bacteria often leads to growth defects and occasionally death. For example, the Tat… …Joanis et al., 2006). Some Tat substrates are involved in the adaption of bacteria to a…

11 more images…

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APA (6^th Edition):

Wang, N. (2017). Characterization of Translocon and Cargo Dynamics During Tat Transport Using Real-Time Kinetic Approaches. (Masters Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/165892

Chicago Manual of Style (16^th Edition):

Wang, Na. “Characterization of Translocon and Cargo Dynamics During Tat Transport Using Real-Time Kinetic Approaches.” 2017. Masters Thesis, Texas A&M University. Accessed January 19, 2021. http://hdl.handle.net/1969.1/165892.

MLA Handbook (7^th Edition):

Wang, Na. “Characterization of Translocon and Cargo Dynamics During Tat Transport Using Real-Time Kinetic Approaches.” 2017. Web. 19 Jan 2021.

Vancouver:

Wang N. Characterization of Translocon and Cargo Dynamics During Tat Transport Using Real-Time Kinetic Approaches. [Internet] [Masters thesis]. Texas A&M University; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1969.1/165892.

Council of Science Editors:

Wang N. Characterization of Translocon and Cargo Dynamics During Tat Transport Using Real-Time Kinetic Approaches. [Masters Thesis]. Texas A&M University; 2017. Available from: http://hdl.handle.net/1969.1/165892

Tulane University

3. Kauffman, W. Berkeley. Synthetic molecular evolution of hybrid cell penetrating peptides that efficiently deliver peptide and peptide nucleic acid cargoes to cells.

Degree: 2017, Tulane University

URL: https://digitallibrary.tulane.edu/islandora/object/tulane:77216

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Peptides and peptide nucleic acids (PNAs) have long been recognized as promising tools and potential therapeutics. Yet the cell membrane remains a significant barrier to… (more)

Subjects/Keywords: Penetratin Tat penetrating

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APA (6^th Edition):

Kauffman, W. B. (2017). Synthetic molecular evolution of hybrid cell penetrating peptides that efficiently deliver peptide and peptide nucleic acid cargoes to cells. (Thesis). Tulane University. Retrieved from https://digitallibrary.tulane.edu/islandora/object/tulane:77216

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kauffman, W Berkeley. “Synthetic molecular evolution of hybrid cell penetrating peptides that efficiently deliver peptide and peptide nucleic acid cargoes to cells.” 2017. Thesis, Tulane University. Accessed January 19, 2021. https://digitallibrary.tulane.edu/islandora/object/tulane:77216.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kauffman, W Berkeley. “Synthetic molecular evolution of hybrid cell penetrating peptides that efficiently deliver peptide and peptide nucleic acid cargoes to cells.” 2017. Web. 19 Jan 2021.

Vancouver:

Kauffman WB. Synthetic molecular evolution of hybrid cell penetrating peptides that efficiently deliver peptide and peptide nucleic acid cargoes to cells. [Internet] [Thesis]. Tulane University; 2017. [cited 2021 Jan 19]. Available from: https://digitallibrary.tulane.edu/islandora/object/tulane:77216.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kauffman WB. Synthetic molecular evolution of hybrid cell penetrating peptides that efficiently deliver peptide and peptide nucleic acid cargoes to cells. [Thesis]. Tulane University; 2017. Available from: https://digitallibrary.tulane.edu/islandora/object/tulane:77216

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal

4. Mungwe, S'yanda Nkanyiso. Using spectral methods on HIV infection with TAT and SSU72 activation.

Degree: 2016, University of KwaZulu-Natal

URL: http://hdl.handle.net/10413/13389

► HIV dynamics within the host are complex especially when a reservoir of latently infected CD4+ T cells are present. The failure of the immune system… (more)

Subjects/Keywords: Mathematics.; TAT; SSU72

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APA (6^th Edition):

Mungwe, S. N. (2016). Using spectral methods on HIV infection with TAT and SSU72 activation. (Thesis). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/13389

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mungwe, S'yanda Nkanyiso. “Using spectral methods on HIV infection with TAT and SSU72 activation.” 2016. Thesis, University of KwaZulu-Natal. Accessed January 19, 2021. http://hdl.handle.net/10413/13389.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mungwe, S'yanda Nkanyiso. “Using spectral methods on HIV infection with TAT and SSU72 activation.” 2016. Web. 19 Jan 2021.

Vancouver:

Mungwe SN. Using spectral methods on HIV infection with TAT and SSU72 activation. [Internet] [Thesis]. University of KwaZulu-Natal; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10413/13389.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mungwe SN. Using spectral methods on HIV infection with TAT and SSU72 activation. [Thesis]. University of KwaZulu-Natal; 2016. Available from: http://hdl.handle.net/10413/13389

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Rochester

5. Silva, Jharon Nirav. Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density.

Degree: PhD, 2013, University of Rochester

URL: http://hdl.handle.net/1802/27273

► Cerebral blood flow (CBF) is dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. To test whether dysregulation of CBF might be… (more)

▼ Cerebral blood flow (CBF) is dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. To test whether dysregulation of CBF might be due to virally-induced neuroinflammation, we used a well-defined animal model (GFAP-driven, doxycycline [Dox]-inducible HIV-1 Tat transgenic [Tat-tg] mice) of HIV-associated neuroinflammation. We first studied the response to brief hypercapnia in a model for acute HIV-induced neuroinflammation (Tat-tg mice treated with Dox for 3 weeks). In control animals, brief hypercapnia induced a brisk increase in cortical flow (20.8% above baseline) and vascular dilation, as measured by laser Doppler flowmetry and in vivo two-photon microscopy. These responses were significantly attenuated in mice that were acutely exposed to Tat (11.6% above baseline), but cortical microvascular morphology and capillary density were unaltered, suggesting that the acute, Tat-induced functional pathology was not secondary to vascular remodeling. To examine the mechanistic basis for the diminished cerebrovascular response to brief hypercapnia in mice acutely exposed to Tat, animals were treated with (i) gisadenafil, a phosphodiesterase 5 (PDE5) inhibitor and (ii) tetrahydrobiopterin (BH4). Gisadenafil largely restored the normal increase in cortical flow following hypercapnia in Tat-tg mice (17.5% above baseline), whereas BH4 had little effect. Gisadenafil also restored the dilation of small (<25μm) arterioles following hypercapnia (19.1% versus 20.6% diameter increase in control and Tat-tg + gisadenafil, respectively), although it failed to restore full dilation of larger (>25μm) vessels. Taken together, these data show that acute HIV-associated neuroinflammation can cause cerebrovascular pathology, through effects on cGMP metabolism and possibly PDE5. In follow-up experiments, we examined the effects of chronic intracranial Tat exposure, by studying Tat-tg animals that were exposed to Dox for 5-7 months. These studies revealed a significant reduction in capillary density relative to age-matched control mice. These findings suggest that HIV-associated neuroinflammation may cause two distinct forms of cerebrovascular pathology: (i) loss of normal cerebrovascular reactivity due to perturbation of normal vasodilation and cGMP-mediated signaling and (ii) a chronic remodeling of the cerebral vasculature that results in a reduction in cerebral capillary density.

Subjects/Keywords: Cerebrovascular; HIV; Tat; Phosphodiesterase

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APA (6^th Edition):

Silva, J. N. (2013). Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/27273

Chicago Manual of Style (16^th Edition):

Silva, Jharon Nirav. “Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density.” 2013. Doctoral Dissertation, University of Rochester. Accessed January 19, 2021. http://hdl.handle.net/1802/27273.

MLA Handbook (7^th Edition):

Silva, Jharon Nirav. “Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density.” 2013. Web. 19 Jan 2021.

Vancouver:

Silva JN. Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density. [Internet] [Doctoral dissertation]. University of Rochester; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1802/27273.

Council of Science Editors:

Silva JN. Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density. [Doctoral Dissertation]. University of Rochester; 2013. Available from: http://hdl.handle.net/1802/27273

University of North Texas

6. Fincher, Jennie. Decentering and the Theory of Social Development.

Degree: 2012, University of North Texas

URL: https://digital.library.unt.edu/ark:/67531/metadc149590/

► The concept of decentering originated with Piaget, who defined decentering as a feature of operational thought, the ability to conceptualize multiple perspectives simultaneously. Feffer applied… (more)

▼ The concept of decentering originated with Piaget, who defined decentering as a feature of operational thought, the ability to conceptualize multiple perspectives simultaneously. Feffer applied Piaget’s concept of decentering to the cognitive maturity of social content. This study used Feffer’s Interpersonal Decentering scoring system for stories told about TAT pictures to investigate the developmental hierarchy of decentering for children and adolescents. The participants originated from the Berkeley Guidance Study, a longitudinal sample of more than 200 individuals followed for more than 60 years by the Institute of Human Development at the University of California, Berkeley. The hypotheses tested were: (1) chronological age will be positively related to Decentering as reflected in Feffer’s Interpersonal Decentering scores obtained annually between ages 10 and 13 and at 18; (2) children born into higher class homes would have higher Age 12 Decentering scores; (3) children born later in birth order will have higher Age 12 Decentering scores; (4) children whose parents were observed to have closer bonds with their children at age 21 months will have higher Age 12 Decentering scores; (5) adolescents with higher scores from the Decentering Q-sort Scale (derived from adolescent Q-sorts) will have higher Age 12 Decentering scores; and (6) participants who have higher Age 12 Decentering scores will self-report higher CPI Empathy scale scores at Age 30. A repeated measures ANOVA tested Hypothesis 1. Pearson product-moment correlation coefficients tested Hypotheses 2-6. Age and Decentering scores were unrelated, as was birth order; social class findings were mixed. Parents’ bonds with child and Age 12 Decentering were negatively correlated (closer bonds predicted higher Decentering), as were Age 12 Decentering and Age 30 Empathy (higher early Decentering predicted lower adulthood Empathy). Girls (age 12) tended to decenter more consistently and had higher Decentering scores than boys. Advisors/Committee Members: Jenkins, Sharon Rae, Callahan, Jennifer, Cox, Randall.

Subjects/Keywords: Decentering; TAT; Piaget; Feffer

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APA (6^th Edition):

Fincher, J. (2012). Decentering and the Theory of Social Development. (Thesis). University of North Texas. Retrieved from https://digital.library.unt.edu/ark:/67531/metadc149590/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fincher, Jennie. “Decentering and the Theory of Social Development.” 2012. Thesis, University of North Texas. Accessed January 19, 2021. https://digital.library.unt.edu/ark:/67531/metadc149590/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fincher, Jennie. “Decentering and the Theory of Social Development.” 2012. Web. 19 Jan 2021.

Vancouver:

Fincher J. Decentering and the Theory of Social Development. [Internet] [Thesis]. University of North Texas; 2012. [cited 2021 Jan 19]. Available from: https://digital.library.unt.edu/ark:/67531/metadc149590/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fincher J. Decentering and the Theory of Social Development. [Thesis]. University of North Texas; 2012. Available from: https://digital.library.unt.edu/ark:/67531/metadc149590/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Maryland

7. Kerwin, John Forbes. Cyclical, Cell-Penetrating, Peptide-Protein Fusions.

Degree: Chemical Engineering, 2017, University of Maryland

URL: http://hdl.handle.net/1903/20329

► The expression of recombinant proteins often exploits amino acid motifs that can provide unique properties for recognition, post-translational modification, binding capacity, and translocation potential. Implementing… (more)

▼ The expression of recombinant proteins often exploits amino acid motifs that can provide unique properties for recognition, post-translational modification, binding capacity, and translocation potential. Implementing a poly-histidine tag, for example, creates a unique binding site for efficient purification of a target protein from unwanted impurities. This tag can later be cleaved rendering the functional ‘native’ protein. Inteins are natural, “protein ligators”, facilitating the formation of a covalent bond between two flanking protein fragments (exteins) of a translated protein sequence. The intein excises itself upon ligation of the flanking exteins. Split-inteins can flank a target protein and upon an excision event, they enable a post-translational mechanism that cyclizes the protein by cleaving out the flanking intein sequences. Cell-penetrating peptides (CPPs) permit the translocation of exogenous macromolecules across the cell membrane, while maintaining membrane integrity. Nucleic acids, proteins, and small molecules can be linked to the CPPs through a covalent bond or a non-covalent interaction to facilitate their translocation into the cell. The uptake of a CPP-protein fusion is typically rapid and follows first-order transduction kinetics. CPP-mediated uptake can be rapidly measured by quenching extracellular fluorescence with trypan blue. Trypan blue will penetrate cells with compromised membranes that could transduce proteins unmediated. In this study, eGFP is expressed alongside the transactivator of transcription (TAT) peptide derived from HIV-1 that can function as a cell-penetrating peptide. The TATeGFP fusion protein is also expressed alongside an artificial split-intein system. The cyclized TATeGFP protein exhibits enhanced in vitro stability during protein expression, resistance against exopeptidase digestion, and resistance against chaotropic agent degradation. A cell-penetrating peptide-protein fusion can transduce a cell membrane to deliver an intracellular protein with low cytotoxic effects. A cyclical, cell-penetrating, peptide-protein fusion is a novel tool for fluorometric reporting studies and a backbone for the delivery of intracellular therapeutic proteins with enhanced thermal, enzymatic, and chemical stability. Advisors/Committee Members: Bentley, William E (advisor), Kelman, Zvi (advisor).

Subjects/Keywords: Chemical engineering; GFP; intein; TAT

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APA (6^th Edition):

Kerwin, J. F. (2017). Cyclical, Cell-Penetrating, Peptide-Protein Fusions. (Thesis). University of Maryland. Retrieved from http://hdl.handle.net/1903/20329

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kerwin, John Forbes. “Cyclical, Cell-Penetrating, Peptide-Protein Fusions.” 2017. Thesis, University of Maryland. Accessed January 19, 2021. http://hdl.handle.net/1903/20329.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kerwin, John Forbes. “Cyclical, Cell-Penetrating, Peptide-Protein Fusions.” 2017. Web. 19 Jan 2021.

Vancouver:

Kerwin JF. Cyclical, Cell-Penetrating, Peptide-Protein Fusions. [Internet] [Thesis]. University of Maryland; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1903/20329.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kerwin JF. Cyclical, Cell-Penetrating, Peptide-Protein Fusions. [Thesis]. University of Maryland; 2017. Available from: http://hdl.handle.net/1903/20329

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Minnesota

8. Wu, Mariah. Modulation of the Endocannabinoid System By Hiv Tat Protein.

Degree: PhD, Neuroscience, 2020, University of Minnesota

URL: http://hdl.handle.net/11299/216103

► Despite the success of combined antiretroviral therapy (cART) in extending the lifespan and enhancing the quality of life for those infected with HIV, nearly half… (more)

▼ Despite the success of combined antiretroviral therapy (cART) in extending the lifespan and enhancing the quality of life for those infected with HIV, nearly half of the 37.9 million HIV-positive individuals experience some degree of neurocognitive impairment. These impairments are collectively termed HIV-associated neurocognitive disorders (HAND). HAND symptoms range from subtle difficulties in the tasks of daily living to severe functional impairment and dementia. cART effectively suppresses viral load and improves patient survival; however, while the severity is reduced, the prevalence of HAND remains high and may be increasing due to the prolonged lifespan of HIV patients. Currently, there are no effective treatments for HAND. HIV neurotoxicity is mainly mediated by inflammatory and excitotoxic agents released from infected macrophages and microglia. The HIV trans-activator protein Tat is one such agent that plays a major role in the neuropathogenesis of HAND. While cART suppresses viral replication, it does not halt the production of Tat once HIV has integrated into the host genome. Numerous studies have demonstrated that Tat causes excitotoxicity, which leads to a loss of spine density and altered network function; this synaptic dysfunction predicts marked impairments in learning and memory paradigms in various in vitro and in vivo models of HAND. Thus, it is essential to elucidate the mechanisms that cause and exacerbate neurotoxicity, in order to find effective therapeutic targets to ultimately treat HAND symptoms. A growing body of literature indicates that components of the endocannabinoid (eCB) system may be viable therapeutic targets. Across many models of neurological disorders that share a common pathophysiological pathway including excitotoxicity and neuroinflammation, activation of the eCB system attenuates detrimental cellular processes. Recent reports show that activating the eCB system protects against HIV-induced neurotoxicity, indicating that modulation of the eCB system may be a viable therapeutic approach to suppress the neuronal damage that underlies HAND. However, one important determinant of clinical outcome is the degree to which the target biological system is functional. Exposure to excitotoxic stimuli alters the eCB system; whether eCB signaling is altered in the presence of HIV is unknown. In this dissertation, I explore the effects of HIV Tat protein on eCB signaling in vitro. Using an electrophysiological approach, I determined that Tat impaires cannabinoid type 1 receptor (CB1R) function in a subset of neurons without affecting other components of the eCB system. Taken together, these results indicate that Tat specifically impairs CB1R-mediated presynaptic inhibition of glutamate release. This observation suggests that eCB-mediated neuroprotection may be reduced in vivo, possibly exacerbating synaptodendritic injury caused by HIV. Thus, this dissertation provides new insight into processes that further contribute to HIV-induced neurotoxicity and suggests that protecting or…

Subjects/Keywords: CB1; endocannabinoid; HIV; neurotoxicity; Tat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wu, M. (2020). Modulation of the Endocannabinoid System By Hiv Tat Protein. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/216103

Chicago Manual of Style (16^th Edition):

Wu, Mariah. “Modulation of the Endocannabinoid System By Hiv Tat Protein.” 2020. Doctoral Dissertation, University of Minnesota. Accessed January 19, 2021. http://hdl.handle.net/11299/216103.

MLA Handbook (7^th Edition):

Wu, Mariah. “Modulation of the Endocannabinoid System By Hiv Tat Protein.” 2020. Web. 19 Jan 2021.

Vancouver:

Wu M. Modulation of the Endocannabinoid System By Hiv Tat Protein. [Internet] [Doctoral dissertation]. University of Minnesota; 2020. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/11299/216103.

Council of Science Editors:

Wu M. Modulation of the Endocannabinoid System By Hiv Tat Protein. [Doctoral Dissertation]. University of Minnesota; 2020. Available from: http://hdl.handle.net/11299/216103

University of Adelaide

9. Tomusange, Khamis. Novel recombinant DNA and live virus vaccines to prevent or control HIV-1 infection.

Degree: 2016, University of Adelaide

URL: http://hdl.handle.net/2440/119714

► Background Vaccination is the most cost effective and long-term solution to the global human immunodeficiency virus (HIV) pandemic. The HIV Gag and Tat proteins are… (more)

▼ Background Vaccination is the most cost effective and long-term solution to the global human immunodeficiency virus (HIV) pandemic. The HIV Gag and Tat proteins are attractive components of a HIV vaccine as immune responses targeting these proteins confer protective benefits against HIV infections in humans. This thesis has developed two innovative candidate HIV vaccines viz. a DNA vaccine encoding oligomerised and secreted Tat (pVAXsTat-IMX313), and a recombinant live human rhinovirus serotype A1 (HRV-A1)-based vaccine encoding Gag and Tat (rHRV-Gag/Tat). Methods To construct pVAX-sTat-IMX313, Tat was fused with the oligomerisation domain of IMX313 to form Tat heptamers and linked to the leader sequence of tissue plasminogen activator to ensure that the bulk of oligomerised protein is secreted. To develop the rHRVGag/Tat vaccine, initially, the full length tat gene and 5 discrete overlapping fragments corresponding to the full length gag gene were individually inserted into the junction between the HRV-A1 genes encoding structural and non-structural proteins (P1/P2 junction) to ensure that the exogenous HIV Gag or Tat proteins were separated from the recombinant polyprotein using the HRV encoded 2Aprotease enzyme. Thus, one recombinant HRV encoding Tat (rHRV-Tat) and 5 rHRVs each encoding a unique Gag fragment (rHRV-Gag1-5) were generated. The individual rHRVs were then mixed into a single cocktail vaccine (rHRVGag/Tat), purified and titrated for inoculation in mice. The immunogenicity of these vaccines was evaluated in female BALB/c mice that received up to five intradermal injections of pVAX-sTat-IMX313 (50 μg per dose) at 2 weekly intervals in one study. In another study, mice were vaccinated intranasally with 2 doses (5x106 TCID50/dose) of the rHRV-Gag/Tat followed by a single 50 μg booster dose of a cocktail DNA vaccine containing pVAX-sTat-IMX313 and pVAX-Gag-Perforin. Vaccine-induced immune responses were examined 2 weeks after the last dose by antibody ELISA, in-vitro Tat transactivation neutralization, IFN-γ ELISpot, KdGag197-205 tetramer staining and intracellular cytokine staining assays. Results Data showed that fusing Tat with IMX313 results in complete heptamerisation of Tat. Furthermore, the data suggested that pVAX-sTat-IMX313 vaccination elicited higher titers of serum neutralizing Tat-specific IgG, secretory IgA (sIgA) in the vagina and CMI responses, and showed superior control of ecotropic HIV (EcoHIV) infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other DNA vaccines tested in this study. Human rhinovirus serotype A1 (HRV-A1) was successfully engineered into a replication-competent genetically stable recombinant vector to deliver a mucosally-targeted vaccine, rHRV-Gag/Tat, by inserting exogenous HIV gag and tat sequences into the HRV-A1 genome. Finally, intranasal administration of 2 doses of rHRV-Gag/Tat followed by a single DNA booster dose induced superior poly-functional Gag-specific CD8 T cell responses in the spleen (systemic) and mesenteric lymph… Advisors/Committee Members: Gowans, Eric James (advisor), Grubor-Bauk, Branka (advisor), Adelaide Medical School (school).

Subjects/Keywords: rHRV-Gag/Tat; Tat-IMX313; EcoHIV control; HIV; vaccine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tomusange, K. (2016). Novel recombinant DNA and live virus vaccines to prevent or control HIV-1 infection. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/119714

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tomusange, Khamis. “Novel recombinant DNA and live virus vaccines to prevent or control HIV-1 infection.” 2016. Thesis, University of Adelaide. Accessed January 19, 2021. http://hdl.handle.net/2440/119714.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tomusange, Khamis. “Novel recombinant DNA and live virus vaccines to prevent or control HIV-1 infection.” 2016. Web. 19 Jan 2021.

Vancouver:

Tomusange K. Novel recombinant DNA and live virus vaccines to prevent or control HIV-1 infection. [Internet] [Thesis]. University of Adelaide; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2440/119714.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tomusange K. Novel recombinant DNA and live virus vaccines to prevent or control HIV-1 infection. [Thesis]. University of Adelaide; 2016. Available from: http://hdl.handle.net/2440/119714

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Schatz, Malvina. Mécanistique de l'incorporation de la protéine Tat du VIH-1 dans les particules virales : How HIV-1 Tat is incorporated into viral particles.

Degree: Docteur es, Biologie Santé, 2018, Montpellier

URL: http://www.theses.fr/2018MONTT075

►

La protéine Tat du VIH-1 est principalement connue pour son rôle majeur dans l’élongation de la transcription des gènes viraux. Cependant, plusieurs études ont montré… (more)

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La protéine Tat du VIH-1 est principalement connue pour son rôle majeur dans l’élongation de la transcription des gènes viraux. Cependant, plusieurs études ont montré que Tat pouvait être impliquée dans la rétrotranscription, étape précoce du cycle de réplication du VIH-1 et antérieure à l’intégration du génome viral dans la cellule hôte. Si Tat est impliquée dans la rétrotranscription, sa présence dans la particule virale pourrait procurer au virus un avantage cinétique. Pourtant, malgré une étude de protéomique l’ayant mis en évidence dans des virions purifiés, Tat n’est toujours pas considérée comme étant incorporée aux particules virales. Récemment, nous avons montré une interaction entre Tat et la cyclophiline A (CypA), une prolyl isomérase cellulaire. Cette protéine est connue pour être incorporée dans les particules virales via son interaction avec le domaine capside (CA) de la protéine Gag virale.Les données sur l’interaction de Tat avec CypA et l’implication de Tat dans l’étape précoce de rétrotranscription, nous ont conduits à formuler l’hypothèse suivante : L’interaction de Tat avec CypA permettrait son incorporation dans les particules virales et Tat serait donc présente dans les toutes premières étapes de l’infection des cellules hôtes par le VIH-1.Dans les travaux présentés, nous avons confirmés par GST pulls down et co-immunoprécipitation l’existence d’un complexe CA-CypA-Tat. Le complexe a pu être purifié par gel filtration. Puis, nous avons montré la présence de Tat dans les particules virales par deux approches complémentaires : une approche par western blot sur des particules virales purifiées, l’autre par microscopie à force atomique couplée à la microscopie à fluorescence. Grâce à un test fonctionnel, nous avons montré que Tat, associée au VIH-1, est fonctionnelle et délivrée dans le cytoplasme des cellules nouvellement infectées. Enfin, les interactions entre CA, CypA et Tat ont été caractérisées par différentes approches biochimiques faisant appel à des protéines purifiées. Les données de thermophorèse indiquent que l’affinité de Tat pour le complexe CA-CypA est plus forte que pour la CypA seule. Donc, dans une cellule infectée, Tat se fixerait préférentiellement sur la CypA déjà complexée à CA. Le complexe CA-CypA étant majoritairement retrouvé au niveau du site d’assemblage du virus, cela pourrait favoriser l’incorporation de Tat dans les virus.La mise en évidence de Tat dans les particules virales permettra sans doute d’apporter un angle de vue nouveau sur la réplication du VIH-1, en particulier sur les étapes précoces du cycle viral. Ces résultats pourraient initier le développement d’inhibiteurs de l’incorporation de Tat pour une application thérapeutique.

HIV-1 protein Tat is essentially known for its key role in the transcription elongation of the viral genes. However, several studies showed that Tat could favor reverse transcription. This early and essential step of HIV-1 replication cycle takes place before the integration of viral genome into cellular DNA and therefore prior to the…

Advisors/Committee Members: Beaumelle, Bruno (thesis director).

Subjects/Keywords: Tat; Hiv; Capside; Cyclophiline A; Tat; Hiv; Capsid; Cyclophilin A

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schatz, M. (2018). Mécanistique de l'incorporation de la protéine Tat du VIH-1 dans les particules virales : How HIV-1 Tat is incorporated into viral particles. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2018MONTT075

Chicago Manual of Style (16^th Edition):

Schatz, Malvina. “Mécanistique de l'incorporation de la protéine Tat du VIH-1 dans les particules virales : How HIV-1 Tat is incorporated into viral particles.” 2018. Doctoral Dissertation, Montpellier. Accessed January 19, 2021. http://www.theses.fr/2018MONTT075.

MLA Handbook (7^th Edition):

Schatz, Malvina. “Mécanistique de l'incorporation de la protéine Tat du VIH-1 dans les particules virales : How HIV-1 Tat is incorporated into viral particles.” 2018. Web. 19 Jan 2021.

Vancouver:

Schatz M. Mécanistique de l'incorporation de la protéine Tat du VIH-1 dans les particules virales : How HIV-1 Tat is incorporated into viral particles. [Internet] [Doctoral dissertation]. Montpellier; 2018. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2018MONTT075.

Council of Science Editors:

Schatz M. Mécanistique de l'incorporation de la protéine Tat du VIH-1 dans les particules virales : How HIV-1 Tat is incorporated into viral particles. [Doctoral Dissertation]. Montpellier; 2018. Available from: http://www.theses.fr/2018MONTT075

University of Manchester

11. Arthanari, Yamini. Study of cellular delivery of siRNA and shRNA targeting bcr-abl in chronic myeloid leukemia using Tat derived peptide.

Degree: 2011, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:119786

► Chronic Myeloid Leukemia is characterised by the formation of a fusion gene bcr-abl. The gene product BCR-ABL has deregulated tyrosine kinase activity that plays a… (more)

▼ Chronic Myeloid Leukemia is characterised by the formation of a fusion gene bcr-abl. The gene product BCR-ABL has deregulated tyrosine kinase activity that plays a direct role in the pathogenesis of the disease. Recently, use of siRNA in leukaemic cells has led to effective gene silencing of bcr-abl. Gene delivery systems like viral vectors, electroporation and lipid based vectors have showed varying efficiencies but are limited by their level of toxicity and immunogenicity. Developments in the field of Cell Penetrating Peptides have shown effective cellular uptake of nucleic acids and proteins by the CPPs in vitro and in vivo. Report from our lab has shown the use of CPP Tat along with membrane active peptide LK15 to improve the transfection efficiency of both Tat and LK15 peptides individually. Hence, this study will focus on the use of Tat-LK15 peptide to study the delivery of siRNA and shRNA plasmid in K562 cells and observe the BCR-ABL protein expression. Cellular uptake studies using Tat-LK15 based complexes of Cy5-labelled DNA and siRNA showed a concentration dependent uptake leading to increase in percentage transfected cells. Tat-LK15 based DNA complexes achieved 80% transfected cells (charge ratio of 2:1) while siRNA complexes resulted in a maximum of 60% (charge ratio of 3:1). However, Lipofectamine based DNA complexes did not show a concentration dependent increase in percentage transfected cells. Interestingly, Tat-LK15 based siRNA complexes showed a similar level of uptake and percentage transfected cells as that of Lipofectamine based siRNA complexes. Cellular uptake studies using confocal microscopy 4 hours post transfection, showed that when 1µg of DNA was transfected, the labelled DNA was primarily localised on the cell membrane. Interestingly, using 5µg of DNA led to increased intracellular localisation of the labelled DNA, but this observation was not made with Lipofectamine based complexes. The observation at 24 hours post transfection of Tat-LK15/labelled DNA complexes was of higher intensity when compared to that of Lipofectamine based DNA complexes. The reason for this is however not known. Interestingly, the cellular uptake profile using siRNA based complexes was different. At 4 hours post transfection, there was intracellular localisation of labelled siRNA. 24 hours post transfection, there was diffuse cytoplasmic localisation using lower concentration of siRNA whereas using higher concentration led to more high intensity punctate localisations within the cell. Similar observations were made for both Tat-LK15 and Lipofectamine based siRNA complexes.Gene silencing studies of Tat-LK15/shRNA plasmid complex resulted in 80% reduction in protein levels 96 hours post transfection for higher concentrations of shRNA plasmid treated. Similar level of reduction in BCR-ABL was observed with Lipofectamine based complex. Supporting evidence of reduction in mRNA levels was observed using qRT-PCR 48 hours post transfection. However, Tat-LK15/shRNA plasmid complexes led to around 80% of protein reduction… Advisors/Committee Members: AOJULA, HARMESH HS, DEMONACOS, CONSTANTINOS C, Aojula, Harmesh, Pluen, Alain, Demonacos, Constantinos.

Subjects/Keywords: Cell penetrating peptide; Tat peptide; RNA interference

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Arthanari, Y. (2011). Study of cellular delivery of siRNA and shRNA targeting bcr-abl in chronic myeloid leukemia using Tat derived peptide. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:119786

Chicago Manual of Style (16^th Edition):

Arthanari, Yamini. “Study of cellular delivery of siRNA and shRNA targeting bcr-abl in chronic myeloid leukemia using Tat derived peptide.” 2011. Doctoral Dissertation, University of Manchester. Accessed January 19, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:119786.

MLA Handbook (7^th Edition):

Arthanari, Yamini. “Study of cellular delivery of siRNA and shRNA targeting bcr-abl in chronic myeloid leukemia using Tat derived peptide.” 2011. Web. 19 Jan 2021.

Vancouver:

Arthanari Y. Study of cellular delivery of siRNA and shRNA targeting bcr-abl in chronic myeloid leukemia using Tat derived peptide. [Internet] [Doctoral dissertation]. University of Manchester; 2011. [cited 2021 Jan 19]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:119786.

Council of Science Editors:

Arthanari Y. Study of cellular delivery of siRNA and shRNA targeting bcr-abl in chronic myeloid leukemia using Tat derived peptide. [Doctoral Dissertation]. University of Manchester; 2011. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:119786

University of KwaZulu-Natal

12. Ganga, Yashica. HIV-1 transactivator of transcription (TAT) protein causes neurotoxicity via astrocyte activation.

Degree: Physiology, 2015, University of KwaZulu-Natal

URL: http://hdl.handle.net/10413/14339

► HIV is most well-known for its negative effects on the immune system and the resulting development of AIDS, however it also has severe damaging effects… (more)

▼ HIV is most well-known for its negative effects on the immune system and the resulting development of AIDS, however it also has severe damaging effects on the central nervous system. Many infected individuals exhibit neuropsychological and behavioral dysfunctions which are collectively referred to as HIV-associated dementia (HAD). One of the worrying aspects of HAD is the fact that current anti-retroviral therapy, while being effective in managing the onslaughts of HIV on the immune system, is less efficient in addressing the impact of HIV on the CNS. The HIV-1 regulatory protein, transactivator of transcription (Tat), is responsible for the transactivation of viral transcription, and has been identified as a possible etiological factor of HAD. Neurotoxicity caused by HIV-1 is an indirect effect since the virus is unable to infect neurons directly. We subsequently hypothesized that HIV-1 infects non-neuronal cells in the CNS which leads to their activation, resulting in the release of cytokines that are detrimental to neurons. The aims of this study was therefore to (i) determine whether Tat activates astrocytes, (ii) establish whether astrocytes exposed to Tat result in the release of IL-6 and TNF-α, and to (iii) assess whether these cytokines can induce apoptosis of neuronal cells. Our study has shown that Tat does activate astrocytes and that activated astrocytes do indeed release cytokines IL-6 and TNF-α into their growth medium. Tat treated cells release more than double the amount of IL-6 than the control group of untreated astrocytes. We also observed that exogenous administration of these cytokines (individually or collectively) to neurons has the ability to cause neuronal apoptosis. Interestingly in combination, these cytokines show no cooperative effect. Our data also showed that neurons, when exposed to the culture medium of astrocytes that were subjected to Tat, exhibit hallmarks of apoptosis similar to that induced by IL-6 and TNF-α. Our findings led us to conclude that in individuals with HIV-infection, the virus activates astrocytes possibly via the production and release of Tat. This causes the astrocytes to secrete pro-inflammatory cytokines (e.g. TNF- α and IL-6) that may induce apoptotic cell death of neurons. This mechanism may explain the development of HAD. Advisors/Committee Members: Daniels, William Mark Uren. (advisor), Ramsuran, Duran. (advisor).

Subjects/Keywords: Physiology.; HIV-1 transactivator of transcription (TAT).

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ganga, Y. (2015). HIV-1 transactivator of transcription (TAT) protein causes neurotoxicity via astrocyte activation. (Thesis). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/14339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ganga, Yashica. “HIV-1 transactivator of transcription (TAT) protein causes neurotoxicity via astrocyte activation.” 2015. Thesis, University of KwaZulu-Natal. Accessed January 19, 2021. http://hdl.handle.net/10413/14339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ganga, Yashica. “HIV-1 transactivator of transcription (TAT) protein causes neurotoxicity via astrocyte activation.” 2015. Web. 19 Jan 2021.

Vancouver:

Ganga Y. HIV-1 transactivator of transcription (TAT) protein causes neurotoxicity via astrocyte activation. [Internet] [Thesis]. University of KwaZulu-Natal; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10413/14339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ganga Y. HIV-1 transactivator of transcription (TAT) protein causes neurotoxicity via astrocyte activation. [Thesis]. University of KwaZulu-Natal; 2015. Available from: http://hdl.handle.net/10413/14339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. Mediouni, Sonia. Etude par des anticorps de patients VIH-1 de la protéineTAT extracellulaire et développement thérapeutique : Epidemic spreading : the role of host mobility and transportation networks.

Degree: Docteur es, Pathologie humaine, 2011, Aix-Marseille 2

URL: http://www.theses.fr/2011AIX20712

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La protéine Tat (Trans-activator of transcription) est certainement l’une des cibles présentant le plus d’intérêts dans la lutte contre le VIH-1. En effet, synthétisée précocement,… (more)

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La protéine Tat (Trans-activator of transcription) est certainement l’une des cibles présentant le plus d’intérêts dans la lutte contre le VIH-1. En effet, synthétisée précocement, elle joue un rôle central dans le cycle viral et protège les cellules infectées. Secrétée dans le milieu extracellulaire, elle participe à l’immunodéficience en inhibant certaines fonctions ou en induisant l’apoptose des cellules du système immunitaire. Elle est également impliquée directement dans de nombreuses pathologies associées au VIH-1. Dans une première étude, nous avons voulu savoir si la trithérapie était capable d’inhiber la synthèse et la sécrétion de la protéine Tat. Nous avons proposé à des patients infectés, sous trithérapie, ayant une charge virale indétectable, de nous permettre de faire cinq prélèvements sanguins (un tous les trois mois pendant un an) afin de vérifier la présence d’anticorps anti-Tat. Nous avons pu constater que 86% des patients avaient des anticorps anti-Tat mais que ces anticorps pouvaient disparaître ou apparaître chez une majorité de patients, démontrant que la protéine Tat continue d’être sécrétée malgré les antiviraux. Une deuxième étude, sur des sérums de patients, a été effectuée afin de déterminer si la protéine Tat était structurée dans le sang des patients. Il existait une polémique, dans la littérature, sur le fait que la protéine Tat soit naturellement non structurée. Nous avons démontré que la protéine Tat est structurée dans le sérum de patients. De plus, l’activité biologique de la protéine Tat est étroitement liée à l’acquisition de sa conformation. Dans le cadre du développement clinique d’un vaccin anti-Tat dans le laboratoire, nous avons effectué des vaccinations sur des souris afin de déterminer la dose, l’adjuvant, la voie d’administration et le nombre de rappels à effectuer ainsi que la vérification de la tolérance et de la toxicité du vaccin. Des essais cliniques sont en préparation dans le cadre d’un protocole thérapeutique. Le laboratoire développe également une autre approche thérapeutique avec un anticorps monoclonal de souris capable de reconnaitre et de neutraliser les variants Tat représentatifs des cinq principaux sous-types du VIH-1. Cet anticorps qui sera humanisé, servirait à une future immunothérapie en combinaison à la trithérapie pour des patients en phase précoce ou tardive ou encore pour des nouveaux nés dont le système immunitaire est peu fonctionnel.

The protein Tat (Trans-activator of transcription) is definitely one of the most interesting targets in the fight against HIV-1. Synthesized early, it plays a central role in the viral life cycle and protects infected cells. Secreted into the extracellular medium, it participates in the immunodeficiency by inhibiting some functions or inducing apoptosis of immune cells. It is also directly involved in many diseases associated with HIV-1. In a first study, we examined whether HAART was able to inhibit the synthesis and secretion of the Tat protein. We proposed to HIV-1 infected patients under HAART, with…

Advisors/Committee Members: Loret, Erwann (thesis director).

Subjects/Keywords: Tat, VIH-1; Immunodéficience; Anticorps anti-Tat; Conformation; Vaccin; Monoclonal; Immunothérapie.; Tat; Hiv-1; Immunodeficiency; Antibodies against Tat; Conformation; Vaccine; Monoclonal; Immunotherapy.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mediouni, S. (2011). Etude par des anticorps de patients VIH-1 de la protéineTAT extracellulaire et développement thérapeutique : Epidemic spreading : the role of host mobility and transportation networks. (Doctoral Dissertation). Aix-Marseille 2. Retrieved from http://www.theses.fr/2011AIX20712

Chicago Manual of Style (16^th Edition):

Mediouni, Sonia. “Etude par des anticorps de patients VIH-1 de la protéineTAT extracellulaire et développement thérapeutique : Epidemic spreading : the role of host mobility and transportation networks.” 2011. Doctoral Dissertation, Aix-Marseille 2. Accessed January 19, 2021. http://www.theses.fr/2011AIX20712.

MLA Handbook (7^th Edition):

Mediouni, Sonia. “Etude par des anticorps de patients VIH-1 de la protéineTAT extracellulaire et développement thérapeutique : Epidemic spreading : the role of host mobility and transportation networks.” 2011. Web. 19 Jan 2021.

Vancouver:

Mediouni S. Etude par des anticorps de patients VIH-1 de la protéineTAT extracellulaire et développement thérapeutique : Epidemic spreading : the role of host mobility and transportation networks. [Internet] [Doctoral dissertation]. Aix-Marseille 2; 2011. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2011AIX20712.

Council of Science Editors:

Mediouni S. Etude par des anticorps de patients VIH-1 de la protéineTAT extracellulaire et développement thérapeutique : Epidemic spreading : the role of host mobility and transportation networks. [Doctoral Dissertation]. Aix-Marseille 2; 2011. Available from: http://www.theses.fr/2011AIX20712

University of Ottawa

14. Cherid, Hafsa. Regions of the CD127 Cytoplasmic Tail Necessary for HIV-1 Tat Binding .

Degree: 2014, University of Ottawa

URL: http://hdl.handle.net/10393/31556

► Impaired cell mediated immunity is the clinical hallmark of HIV infection yet the manner in which CD8 T-cells are disabled is not yet fully understood.… (more)

Subjects/Keywords: HIV-1 Tat; IL-7 receptor; CD127

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cherid, H. (2014). Regions of the CD127 Cytoplasmic Tail Necessary for HIV-1 Tat Binding . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/31556

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cherid, Hafsa. “Regions of the CD127 Cytoplasmic Tail Necessary for HIV-1 Tat Binding .” 2014. Thesis, University of Ottawa. Accessed January 19, 2021. http://hdl.handle.net/10393/31556.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cherid, Hafsa. “Regions of the CD127 Cytoplasmic Tail Necessary for HIV-1 Tat Binding .” 2014. Web. 19 Jan 2021.

Vancouver:

Cherid H. Regions of the CD127 Cytoplasmic Tail Necessary for HIV-1 Tat Binding . [Internet] [Thesis]. University of Ottawa; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10393/31556.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cherid H. Regions of the CD127 Cytoplasmic Tail Necessary for HIV-1 Tat Binding . [Thesis]. University of Ottawa; 2014. Available from: http://hdl.handle.net/10393/31556

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Université de Neuchâtel

15. Schiely, Marc. Architectures for peer-to-peer media streaming in large scale systems.

Degree: 2009, Université de Neuchâtel

URL: http://doc.rero.ch/record/19786

► The distribution of substantial amounts of data to a large number of clients is a problem that is often tackled by peer-to-peer(P2P)architectures. Bottlenecks are alleviated… (more)

Subjects/Keywords: tit-for-tat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schiely, M. (2009). Architectures for peer-to-peer media streaming in large scale systems. (Thesis). Université de Neuchâtel. Retrieved from http://doc.rero.ch/record/19786

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Schiely, Marc. “Architectures for peer-to-peer media streaming in large scale systems.” 2009. Thesis, Université de Neuchâtel. Accessed January 19, 2021. http://doc.rero.ch/record/19786.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Schiely, Marc. “Architectures for peer-to-peer media streaming in large scale systems.” 2009. Web. 19 Jan 2021.

Vancouver:

Schiely M. Architectures for peer-to-peer media streaming in large scale systems. [Internet] [Thesis]. Université de Neuchâtel; 2009. [cited 2021 Jan 19]. Available from: http://doc.rero.ch/record/19786.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Schiely M. Architectures for peer-to-peer media streaming in large scale systems. [Thesis]. Université de Neuchâtel; 2009. Available from: http://doc.rero.ch/record/19786

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Vienna

16. Kurtovic, Azra. TAT-SMN1-mediated protein delivery into mammalian cells.

Degree: 2018, University of Vienna

URL: http://othes.univie.ac.at/52457/

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Die spinale Muskelatrophie (SMA) ist eine schwerwiegende, autosomal-rezessiv vererbte neurodegenerative Erkrankung mit einer Trägerwahrscheinlichkeit von 1:40–1:60. Die Erkrankung betrifft eine von 10.000 Lebendgeburten pro Jahr.… (more)

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Die spinale Muskelatrophie (SMA) ist eine schwerwiegende, autosomal-rezessiv vererbte neurodegenerative Erkrankung mit einer Trägerwahrscheinlichkeit von 1:40–1:60. Die Erkrankung betrifft eine von 10.000 Lebendgeburten pro Jahr. Spinale Muskelatrophie wird durch die Deletion des survival motor neuron 1 (SMN1) Gens bzw. durch eine Mutation desselben verursacht. Dadurch kommt es zur Verminderung der SMN1-Proteinmenge, der sich im Verlust von Alpha-Motorneuronen im Rückenmark äußert. Dieser Verlust führt zu einer Schwäche der Glieder- und Rumpfmuskulatur. Die Krankheit wird in vier Gruppen untergliedert, die vom Schweregrad und dem Ausbruchsalter abhängen. Unterschiedliche therapeutische Maßnahmen werden derzeit untersucht, aber bis jetzt gibt es noch keine Heilung von SMA. Einer der bedeutendsten Ansätze liegt in der Erhöhung der SMN1- Proteinmenge in den Motorneuronen, sodass diese wieder auf das Niveau eines Gesunden angeglichen wird. Es konnte gezeigt werden, dass das zellpenetrierende Peptid TAT (transactivating transcriptional activator) die Zellmembran, wie auch die Blut-Hirn-Schranke passieren kann. In dieser Forschungsarbeit wurde ein Protokoll zur Aufreinigung von TATSMN1, einem Fusionsprotein, erstellt. Wir konnten aufzeigen, dass das Protein über einen Zeitraum von 72 Stunden stabil ist und dass es keinen zytotoxischen Auswirkungen auf NIH3T3-Zellen hatte. Wir untersuchten die Fähigkeit des Proteins, die Zellmembran zu passieren und in die Zelle bzw. den Zellkern einzutreten. Dies wurde mithilfe von Westernblot-Versuchen bestätigt. Unsere Resultate bilden eine vielversprechende Basis für weitere Versuche an anderen Zelltypen bzw. für in-vivo Versuche in der Zukunft.

Spinal muscular atrophy (SMA) is a severe autosomal recessive disease with a carrier frequency of 1:40–1:60 that affects 1 in 10.000 live births. SMA is caused by either deletions or mutations within the survival motor neuron 1 (SMN1) gene. This sort of changes leads to decreased levels of full-length SMN protein, resulting in a loss of alpha-motor neurons in the spinal cord that leads to atrophy and weakness of limb and trunk muscles. The disease is categorized into four groups, depending on age of onset and severity. Currently, there is no cure for SMA. Different therapeutic strategies are under investigation. One approach involves restoring SMN to physiological concentrations in motor neurons. This should lead to a rescue of the phenotype. Trans-activating transcriptional activator (TAT) has been shown to cross the cell membrane and the blood-brain barrier (BBB). In this study, we aimed to establish a protocol for purification of a previously expressed TAT-SMN1 fusion protein. We were able to show that the protein is stable for over 72 hours and has almost no cytotoxic effect on NIH3T3 cells. We tested TAT-SMN1’s ability to cross cell membranes and enter the cytoplasm and cell nuclei. Immunodetection has indicated that upon treatment of NIH3T3 cells with TAT-SMN1, the protein can be localized within cells…

Subjects/Keywords: 42.13 Molekularbiologie; spinale Muskelatrophie / TAT-SMN1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kurtovic, A. (2018). TAT-SMN1-mediated protein delivery into mammalian cells. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/52457/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kurtovic, Azra. “TAT-SMN1-mediated protein delivery into mammalian cells.” 2018. Thesis, University of Vienna. Accessed January 19, 2021. http://othes.univie.ac.at/52457/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kurtovic, Azra. “TAT-SMN1-mediated protein delivery into mammalian cells.” 2018. Web. 19 Jan 2021.

Vancouver:

Kurtovic A. TAT-SMN1-mediated protein delivery into mammalian cells. [Internet] [Thesis]. University of Vienna; 2018. [cited 2021 Jan 19]. Available from: http://othes.univie.ac.at/52457/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kurtovic A. TAT-SMN1-mediated protein delivery into mammalian cells. [Thesis]. University of Vienna; 2018. Available from: http://othes.univie.ac.at/52457/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Minnesota

17. Brunner, Angela Haijung. Mechanisms of HIV-associated neurotoxicity: Tat-induced synapse loss and recovery.

Degree: PhD, Pharmacology, 2013, University of Minnesota

URL: http://purl.umn.edu/152561

► HIV infection is a worldwide pandemic. A debilitating neurological consequence of HIV infection is progressive cognitive decline, known as HIV-associated neurocognitive disorders (HAND). HAND afflicts… (more)

▼ HIV infection is a worldwide pandemic. A debilitating neurological consequence of HIV infection is progressive cognitive decline, known as HIV-associated neurocognitive disorders (HAND). HAND afflicts up to 50% of all HIV patients to varying degrees, and as survival of HIV patients improves with current antiretroviral therapies, the prevalence of HAND is also increasing. This, coupled with the lack of current effective HAND therapies, creates a dire need to understand the mechanisms underlying the cognitive decline associated with HIV. HAND symptoms correlate closely with processes of neuronal injury, which are early events that precede overt neuronal death. One such injurious process is synapse loss. The HIV protein transactivator of transcription (Tat) is a neurotoxic viral protein released from infected cells into the central nervous system. Tat contributes to the pathologies seen in HAND patients, and induces loss of excitatory synapses between rat hippocampal neurons in culture. Using an innovative live cell imaging assay, our laboratory has previously shown that Tat induces reversible synapse loss via a pathway that is distinct from cell death. In this dissertation, I outline three studies that stem from the current knowledge involving Tat-induced synapse loss. These studies elucidated important information regarding the mechanisms by which HIV Tat exerts its neurotoxic effects, emphasizing the importance of subunit composition when determining toxic or beneficial effects of NMDA receptor activation as well as unmasking the importance of the postsynaptic density as the central target of Tat's effects. Furthermore, these studies highlight the reversibility of synapse loss and uncover a new role for the canonical NO/cGMP/PKG pathway in modulating synapse recovery downstream of GluN2B-containing NMDA receptors. Tat-induced synapse loss and subsequent recovery can correlate to symptoms of cognitive decline seen in HAND. Targeting these mechanisms can shed new light on therapeutic strategies to treat HAND patients.

Subjects/Keywords: HIV; Neurotoxicity; NMDA; Pharmacology; Synapse; Tat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Brunner, A. H. (2013). Mechanisms of HIV-associated neurotoxicity: Tat-induced synapse loss and recovery. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/152561

Chicago Manual of Style (16^th Edition):

Brunner, Angela Haijung. “Mechanisms of HIV-associated neurotoxicity: Tat-induced synapse loss and recovery.” 2013. Doctoral Dissertation, University of Minnesota. Accessed January 19, 2021. http://purl.umn.edu/152561.

MLA Handbook (7^th Edition):

Brunner, Angela Haijung. “Mechanisms of HIV-associated neurotoxicity: Tat-induced synapse loss and recovery.” 2013. Web. 19 Jan 2021.

Vancouver:

Brunner AH. Mechanisms of HIV-associated neurotoxicity: Tat-induced synapse loss and recovery. [Internet] [Doctoral dissertation]. University of Minnesota; 2013. [cited 2021 Jan 19]. Available from: http://purl.umn.edu/152561.

Council of Science Editors:

Brunner AH. Mechanisms of HIV-associated neurotoxicity: Tat-induced synapse loss and recovery. [Doctoral Dissertation]. University of Minnesota; 2013. Available from: http://purl.umn.edu/152561

University of Edinburgh

18. Chen, Xiaochao. Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage.

Degree: PhD, 2013, University of Edinburgh

URL: http://hdl.handle.net/1842/10641

► TAT peptide is one of the best-characterised cell penetrating peptides (CPPs) derived from the transactivator of transcription protein from the human immunodeficiency virus 1 (HIV-1).… (more)

▼ TAT peptide is one of the best-characterised cell penetrating peptides (CPPs) derived from the transactivator of transcription protein from the human immunodeficiency virus 1 (HIV-1). TAT peptide is able to cross the cell membrane and deliver various biomolecules into cells with low immunogenicity and no toxicity. However, the exact mechanism of internalization still remains a subject of controversy. Lamellar neutron scattering was used to determine the location of TAT peptide in the negativelycharged phospholipids bilayers. The results reveal two locations, one in the peripheral aqueous phase between the adjacent bilayers and the second one below the glycerol backbone region of the lipid bilayer. A concentrationindependent membrane thinning above a peptide concentration threshold (1mol%) and a contiguous transbilayer water channel at the largest peptide concentration (10mol%) were also found. This evidence led to the suggestion that the toroidal pore model might be involved in the transmembrane mechanism at high peptide concentration. Another set of neutron diffraction experiments examined the interaction between the TAT peptide and neutral phospholipids showed that TAT peptide preferentially intercalated into the hydrophobic core and the glycerol backbone region of the neutral lipid bilayer at the lowest peptide concentration investigated (0.1mol%), indicating that the insertion did not require negatively-charged phospholipids. There was also clear evidence for the concentration-dependent reorientation of TAT peptide. A plasmid containing the human copper-zinc SOD gene linked with the coding sequence for a 11-aa HIV-TAT peptide (pGEX-TAT-SOD, 513bp) was constructed and used to express a recombinant fusion protein in Escherichia coli strain BL21 (DE3). High-level expression of TAT-SOD soluble protein with a GST tag (44-kDa) was achieved under optimal expression conditions and a small-scale glutathione affinity column or large-scale ion-exchange chromatography used for its purification. The potential protective effect of TAT-SOD against UV-induced cell damage was studied on UVC-irradiated MDCK epithelial cells. Before any further clinical study, the UV full-length absorption of TAT-SOD protein was measured. The results showed the potential UV protective effect of TAT-SOD was not due to the physical absorption of UV irradiation. In a preclinical study with five healthy volunteers, the penetration of TAT-SOD through human stratum corneum on the inner upper arm was identified by the tape stripping and specific SOD activity analysis. Significant increases on SOD activity were found on the outer layers of stratum corneum in TAT-SOD treated group, compared to placebo treated control, indicating that the TAT peptide assisted SOD to penetrate into the human stratum corneum . In a clinical study with ten healthy volunteers, eight showed a significant increase of minimal erythema dose (MED) with TAT-SOD pre-treatment. The median blood flow value of ten subjects at the UVB-irradiated site decreased with TAT-SOD pretreatment.…

Subjects/Keywords: 572; HIV-TAT; SOD; ultraviolet; neutron; diffraction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, X. (2013). Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/10641

Chicago Manual of Style (16^th Edition):

Chen, Xiaochao. “Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage.” 2013. Doctoral Dissertation, University of Edinburgh. Accessed January 19, 2021. http://hdl.handle.net/1842/10641.

MLA Handbook (7^th Edition):

Chen, Xiaochao. “Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage.” 2013. Web. 19 Jan 2021.

Vancouver:

Chen X. Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage. [Internet] [Doctoral dissertation]. University of Edinburgh; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1842/10641.

Council of Science Editors:

Chen X. Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage. [Doctoral Dissertation]. University of Edinburgh; 2013. Available from: http://hdl.handle.net/1842/10641

Université Montpellier II

19. Chopard, Christophe. Régulations de la sécrétion et de l’activité biologique de la protéine Tat du VIH-1 : rôles de la palmitoylation et de Gag : Regulations of HIV-1 Tat secretion and biological activity : role of palmitoylation and Gag.

Degree: Docteur es, Biologie Santé, 2014, Université Montpellier II

URL: http://www.theses.fr/2014MON20089

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La protéine du VIH-1 est une protéine essentielle à la transcription et à la réplication du virus. Elle a donc un rôle crucial dans la… (more)

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La protéine du VIH-1 est une protéine essentielle à la transcription et à la réplication du virus. Elle a donc un rôle crucial dans la cellule infectée. On sait qu'une partie de la Tat cellulaire peut être sécrétée, malgré l'absence de séquence signal. En effet, les 2/3 de la Tat cellulaire sont exportés par la cellule T-primaire infectée. Le mécanisme de sécrétion de Tat est non conventionnel et se produit directement à travers la membrane plasmique où Tat est recrutée grâce à sa très forte affinité pour le phosphatidylinositol(4,5)-biphosphate ou PI(4,5)P2 qui est exclusivement localisé à ce niveau. La Tat extracellulaire a un effet délétère sur de nombreux types cellulaires et agit donc comme une toxine virale. Elle constitue un facteur déterminant de l'évolution vers le SIDA. En accord avec cette efficacité de sécrétion par les cellules T primaires infectées, Tat est essentiellement localisée sur la membrane plasmique des T primaires infectées par le VIH-1. Une fraction importante de Tat est donc résidente à la membrane et nous avons recherché un mécanisme pouvant expliquer cette rétention et mis en évidence la palmitoylation. Nos travaux montrent que Tat est palmitoylée, dans des cellules T ainsi que dans les ‘cibles' comme les neurones et les macrophages. Cette palmitoylation, qui inhibe la sécrétion de Tat, est réalisée sur la cystéine 31 de Tat (qui possède 7 cystéines) par l'enzyme DHHC20 avec comme cofacteurs nécessaires les immunophilines (prolyl-isomérases), Cyclophiline A et FKBP12, qui interagissent avec Tat au niveau de la membrane. Nos résultats indiquent aussi qu'en présence de Gag, la palmitoylation de Tat est inhibée. Nous pensons que l'export de la CypA dû à son encapsidation diminuerait la quantité de CypA disponible pour Tat, inhibant la palmitoylation de Tat et permettant sa sécrétion efficace par les cellules infectées. En effet, le VIH-1 encapside 250 copies de CypA/virion, le taux de CypA régulant la virulence des virions produits. Dans les cellules cibles, Tat serait fortement palmitoylée ce qui induirait sa fixation quasi irréversible au PI(4,5)P2, l'empêchant de ressortir de la cellule et permet ainsi un effet cumulatif des doses reçues par la cellules. Cette accumulation de Tat perturbe des processus membranaires dépendant du PI(4,5)P2 tels que la phagocytose et la neurosécrétion. La palmitoylation de Tat est nécessaire pour ces effets. Ces actions de la Tat extracellulaire pourraient participer au développement des infections opportunistes et des troubles neurologiques observé lors du SIDA.

HIV-1 Tat is a small protein that is required for viral transcription and multiplication. It thus has a crucial role in the infected cell. It was known that Tat can be secreted despite its lack of signal sequence. In fact 2/3 of cellular Tat are exported by infected primary T-cells. The unconventional secretion of Tat relies on its interaction with phosphatidylinositol(4,5)-biphosphate or PI(4,5)P2, a lipid that is concentrated within the inner leaflet of the plasma membrane and is strictly…

Advisors/Committee Members: Beaumelle, Bruno (thesis director).

Subjects/Keywords: Vih-1; Tat; Sécrétion; Palmitylation; Gag; Immunophilines; Hiv-1; Tat; Secretion; Palmitoylation; Gag; Immunophilines

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chopard, C. (2014). Régulations de la sécrétion et de l’activité biologique de la protéine Tat du VIH-1 : rôles de la palmitoylation et de Gag : Regulations of HIV-1 Tat secretion and biological activity : role of palmitoylation and Gag. (Doctoral Dissertation). Université Montpellier II. Retrieved from http://www.theses.fr/2014MON20089

Chicago Manual of Style (16^th Edition):

Chopard, Christophe. “Régulations de la sécrétion et de l’activité biologique de la protéine Tat du VIH-1 : rôles de la palmitoylation et de Gag : Regulations of HIV-1 Tat secretion and biological activity : role of palmitoylation and Gag.” 2014. Doctoral Dissertation, Université Montpellier II. Accessed January 19, 2021. http://www.theses.fr/2014MON20089.

MLA Handbook (7^th Edition):

Chopard, Christophe. “Régulations de la sécrétion et de l’activité biologique de la protéine Tat du VIH-1 : rôles de la palmitoylation et de Gag : Regulations of HIV-1 Tat secretion and biological activity : role of palmitoylation and Gag.” 2014. Web. 19 Jan 2021.

Vancouver:

Chopard C. Régulations de la sécrétion et de l’activité biologique de la protéine Tat du VIH-1 : rôles de la palmitoylation et de Gag : Regulations of HIV-1 Tat secretion and biological activity : role of palmitoylation and Gag. [Internet] [Doctoral dissertation]. Université Montpellier II; 2014. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2014MON20089.

Council of Science Editors:

Chopard C. Régulations de la sécrétion et de l’activité biologique de la protéine Tat du VIH-1 : rôles de la palmitoylation et de Gag : Regulations of HIV-1 Tat secretion and biological activity : role of palmitoylation and Gag. [Doctoral Dissertation]. Université Montpellier II; 2014. Available from: http://www.theses.fr/2014MON20089

20. Lecigne, David. Conception et évaluation de nouveaux peptides internalisants : Design and evaluation of news cell-penetrating peptides.

Degree: Docteur es, Sciences biologiques pharmaceutiques, 2011, Université Montpellier I

URL: http://www.theses.fr/2011MON13501

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Le peptide Tat est un des "cell penetrating peptides" (CPP) les plus utilisés pour l'internalisation cellulaire de diverses molécules cargos. La molécule chimérique (Tat-cargo) induit… (more)

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Le peptide Tat est un des "cell penetrating peptides" (CPP) les plus utilisés pour l'internalisation cellulaire de diverses molécules cargos. La molécule chimérique (Tat-cargo) induit une réponse biologique plus efficace comparée au cargo seul. Cependant, en marquant le peptide Tat à l'iode 125, il a été déterminé que seulement moins de 1 % de la quantité initiale de peptide est internalisé. Il y a donc une opportunité d'augmenter l'efficacité de cette internalisation. L'étape cruciale du processus d'internalisation est le passage transmembranaire. Cette thèse présente l'évaluation de l'impact d'un groupement hydrophobe intégré en différentes positions au peptide Tat, afin de favoriser son interaction avec la membrane. Un acide aminé modifié chimiquement comportant un groupement cholestéryle a été développé dans ce sens. Cet aminoacide peut être intégré en toute position du peptide Tat. Différentes positions au sein du peptide Tat ont été cholestérylées et l'effet sur le taux d'internalisation a été étudié par cytométrie en flux et par comptage suite au radiomarquage des peptides à l'iode 125.L'ajout de cholestérol en position centrale du peptide Tat induit une efficacité d'internalisation supérieure d'un facteur 30 alors qu'une augmentation moindre est observée suite à l'ajout du groupement hydrophobe en positions latérales, N- ou C-terminale.

The Tat peptide is one of the most used cell penetrating peptides for internalizing various cargo molecules into cells. The chimaeric molecule thus triggers an efficient cellular biological response when compared with the cargo molecule alone. However, following labeling of the Tat peptide with radiolabeled iodine, less than 1% of the external peptide was internalized. Therefore, there is an opportunity to improve the level of CPP internalization. The ultimate step is the crossing through the plasma membrane. This thesis presents an evaluation of the impact of a hydrophobic group incorporated at different positions to Tat peptide, to promote its interaction with the membrane.A chemically modified amino acid comprising a cholesteryl group was developed in this direction. This amino acid can be inserted at any position within the Tat peptide. Different positions within the Tat peptide were cholesterylated and the effect on the internalization rate of Tat CPP was investigated by flow cytometry and by counting following the radiolabeling of peptides with iodine 125.The addition of cholesterol in the central position of the peptide Tat induces internalization efficiency than a factor of 30 while a smaller increase was observed after the addition of hydrophobic group in lateral positions, N-or C-terminus.

Advisors/Committee Members: Vives, Eric (thesis director).

Subjects/Keywords: Cell-Penetrating Peptide; Tat; Cholestérol; Hydrophobisation; Cell-Penetrating Peptide; Tat; Cholesterol; Hydrophobization

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lecigne, D. (2011). Conception et évaluation de nouveaux peptides internalisants : Design and evaluation of news cell-penetrating peptides. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2011MON13501

Chicago Manual of Style (16^th Edition):

Lecigne, David. “Conception et évaluation de nouveaux peptides internalisants : Design and evaluation of news cell-penetrating peptides.” 2011. Doctoral Dissertation, Université Montpellier I. Accessed January 19, 2021. http://www.theses.fr/2011MON13501.

MLA Handbook (7^th Edition):

Lecigne, David. “Conception et évaluation de nouveaux peptides internalisants : Design and evaluation of news cell-penetrating peptides.” 2011. Web. 19 Jan 2021.

Vancouver:

Lecigne D. Conception et évaluation de nouveaux peptides internalisants : Design and evaluation of news cell-penetrating peptides. [Internet] [Doctoral dissertation]. Université Montpellier I; 2011. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2011MON13501.

Council of Science Editors:

Lecigne D. Conception et évaluation de nouveaux peptides internalisants : Design and evaluation of news cell-penetrating peptides. [Doctoral Dissertation]. Université Montpellier I; 2011. Available from: http://www.theses.fr/2011MON13501

21. Docquir, Camille. Le corps éprouvé, entre désir et douleur : étude psychodynamique comparative du trouble de conversion et du trouble douloureux chez l’enfant et l’adolescent : Experiencing one’s body, between desire and pain : a comparative psychodynamic study of conversion disorder and pain disorder in children and adolescents.

Degree: Docteur es, Psychologie, 2013, Université Paris Descartes – Paris V

URL: http://www.theses.fr/2013PA05H115

► Les symptômes de conversion, que Freud a jusqu’à la fin de sa vie qualifiés de « mystérieux », continuent aujourd’hui de susciter de nombreux questionnements.… (more)

▼ Les symptômes de conversion, que Freud a jusqu’à la fin de sa vie qualifiés de « mystérieux », continuent aujourd’hui de susciter de nombreux questionnements. L’un d’entre eux concerne le rapport qu’ils entretiennent avec la douleur : si les douleurs sans étiologie médicale retrouvée sont parfois considérées comme des symptômes de conversion au même titre que les symptômes sensori-moteurs, elles semblent pouvoir correspondre à des pathogénies variées (névrose d’angoisse, hypocondrie, manifestations psychosomatiques…). À l’appui de ce constat, nous faisons l’hypothèse que là où les symptômes sensori-moteurs représenteraient le résultat d’un mécanisme de conversion pouvant être sous-tendu par des registres conflictuels divers mais impliquant nécessairement une dimension d’expression symbolique de ces conflits, les symptômes douloureux pourraient quant à eux s’inscrire le long d’un continuum allant d’un pôle conversif, marqué par cette valeur symbolique, à un pôle non conversif, porteur d’une valeur moins symbolique qu’économique – étant cependant entendu qu’il existerait des possibilités de passage d’un pôle à l’autre. Au pôle conversif, les symptômes seraient sous-tendus par de bonnes capacités d’élaboration psychique de l’excitation, des enveloppes psychiques relativement solides et souples et de bonnes capacités à s’appuyer sur un objet psychique interne ; au pôle non conversif, ils seraient sous-tendus par des difficultés d’élaboration psychique de l’excitation, des enveloppes psychiques marquées par la fragilité et des difficultés à s’appuyer sur un objet psychique interne.Afin de mettre nos hypothèses à l’épreuve, nous avons, dans le cadre d’une vaste recherche mise en place par le Dr Lisa Ouss à l’hôpital Necker-Enfants malades, rencontré 27 enfants et adolescents âgés de 8 à 15 ans et présentant un trouble de conversion ou un trouble douloureux (diagnostics DSM-IV-TR) ; 8 présentaient des symptômes exclusivement sensori-moteurs, 11 des symptômes à la fois sensori-moteurs et douloureux, et 8 des symptômes exclusivement douloureux. Nous avons recueilli et analysé les données issues des entretiens et des épreuves projectives (Rorschach et TAT) de chaque patient dans une perspective psychodynamique, puis avons procédé à des comparaisons inter-groupes.Les résultats montrent que les patients présentant des symptômes sensori-moteurs (accompagnés ou non de symptômes douloureux) disposent de capacités d’élaboration psychique et de capacités à s’appuyer sur un objet psychique interne significativement meilleures que les patients présentant des symptômes exclusivement douloureux, ce qui tend à confirmer notre hypothèse de départ ; il n’existe en revanche pas de différence significative entre les groupes en matière de qualité des enveloppes psychiques. Les résultats montrent en outre que les (pré)adolescents (11-15 ans) disposent de capacités d’élaboration psychique et de capacités à s’appuyer sur un objet psychique interne significativement meilleures que les enfants en période de latence (8-10 ans), et que les filles… Advisors/Committee Members: Emmanuelli, Michèle (thesis director).

Subjects/Keywords: Corps; Conversion; Douleur; Enfant; Adolescent; Rorschach; TAT; Body; Conversion; Pain; Child; Adolescent; Rorschach; TAT; 155.413

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Docquir, C. (2013). Le corps éprouvé, entre désir et douleur : étude psychodynamique comparative du trouble de conversion et du trouble douloureux chez l’enfant et l’adolescent : Experiencing one’s body, between desire and pain : a comparative psychodynamic study of conversion disorder and pain disorder in children and adolescents. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2013PA05H115

Chicago Manual of Style (16^th Edition):

Docquir, Camille. “Le corps éprouvé, entre désir et douleur : étude psychodynamique comparative du trouble de conversion et du trouble douloureux chez l’enfant et l’adolescent : Experiencing one’s body, between desire and pain : a comparative psychodynamic study of conversion disorder and pain disorder in children and adolescents.” 2013. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed January 19, 2021. http://www.theses.fr/2013PA05H115.

MLA Handbook (7^th Edition):

Docquir, Camille. “Le corps éprouvé, entre désir et douleur : étude psychodynamique comparative du trouble de conversion et du trouble douloureux chez l’enfant et l’adolescent : Experiencing one’s body, between desire and pain : a comparative psychodynamic study of conversion disorder and pain disorder in children and adolescents.” 2013. Web. 19 Jan 2021.

Vancouver:

Docquir C. Le corps éprouvé, entre désir et douleur : étude psychodynamique comparative du trouble de conversion et du trouble douloureux chez l’enfant et l’adolescent : Experiencing one’s body, between desire and pain : a comparative psychodynamic study of conversion disorder and pain disorder in children and adolescents. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2013. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2013PA05H115.

Council of Science Editors:

Docquir C. Le corps éprouvé, entre désir et douleur : étude psychodynamique comparative du trouble de conversion et du trouble douloureux chez l’enfant et l’adolescent : Experiencing one’s body, between desire and pain : a comparative psychodynamic study of conversion disorder and pain disorder in children and adolescents. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2013. Available from: http://www.theses.fr/2013PA05H115

22. Suleymanov, Murad. A Grammar of the Tat Dialect of Şirvan : Grammaire du dialecte tat du Şirvan.

Degree: Docteur es, Linguistique, 2019, Paris Sciences et Lettres (ComUE)

URL: http://www.theses.fr/2019PSLEP058

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Cette « Grammaire du dialecte tat du Şirvan » est une description linguistique d’un dialecte du tat, langue iranienne à tradition orale, parlée dans le… (more)

Subjects/Keywords: Tat; Caucase; Documentation linguistique; Tat; Caucasus; Language documentation; Iranian languages; Typology; Azerbaijan

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Suleymanov, M. (2019). A Grammar of the Tat Dialect of Şirvan : Grammaire du dialecte tat du Şirvan. (Doctoral Dissertation). Paris Sciences et Lettres (ComUE). Retrieved from http://www.theses.fr/2019PSLEP058

Chicago Manual of Style (16^th Edition):

Suleymanov, Murad. “A Grammar of the Tat Dialect of Şirvan : Grammaire du dialecte tat du Şirvan.” 2019. Doctoral Dissertation, Paris Sciences et Lettres (ComUE). Accessed January 19, 2021. http://www.theses.fr/2019PSLEP058.

MLA Handbook (7^th Edition):

Suleymanov, Murad. “A Grammar of the Tat Dialect of Şirvan : Grammaire du dialecte tat du Şirvan.” 2019. Web. 19 Jan 2021.

Vancouver:

Suleymanov M. A Grammar of the Tat Dialect of Şirvan : Grammaire du dialecte tat du Şirvan. [Internet] [Doctoral dissertation]. Paris Sciences et Lettres (ComUE); 2019. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2019PSLEP058.

Council of Science Editors:

Suleymanov M. A Grammar of the Tat Dialect of Şirvan : Grammaire du dialecte tat du Şirvan. [Doctoral Dissertation]. Paris Sciences et Lettres (ComUE); 2019. Available from: http://www.theses.fr/2019PSLEP058

23. Kozulic-Pirher, Alja. La visualisation de la transcription en molécules unique révèle de nouvelles caractéristiques des promoteurs cellulaires et viraux : Real time imaging of transcription reveals new features of cellular and viral promoters.

Degree: Docteur es, Biologie Santé, 2018, Montpellier

URL: http://www.theses.fr/2018MONTT080

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La transcription est une étape fondamentale dans l'expression des gènes. Cependant, elle reste incomplètement caractérisée dans les cellules vivantes. Pour mieux comprendre la dynamique de… (more)

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La transcription est une étape fondamentale dans l'expression des gènes. Cependant, elle reste incomplètement caractérisée dans les cellules vivantes. Pour mieux comprendre la dynamique de la transcription, notre laboratoire a amélioré le système de marquage d'ARN en utilisant la séquence codante pour MS2, facilement fusionnée avec le promoteur d'intérêt et inséré copie unique dans deux lignées cellulaires HeLa cellules. Cette construction permet une vue quantitative de la transcription, a l’échelle de la molécule unique, en temps réel. Nous avons trouvé que le VIH-1 est transcrit par des groupes de polymérases nominés convois. La transcription oscille de manière aléatoire avec des périodes actives (ON) et inactives (OFF) et est contrôlée indépendamment.Sur la base de cette découverte, nous avons étudié: (i) comment l'architecture de différents promoteurs de mammifères contrôle la cinétique transcriptionnelle; et (ii) le rôle du transactivateur transcriptionnel (Tat), le régulateur principal de la transcription du VIH-1, dans les cellules vivantes. Pour traiter ces questions, une nouvelle méthode de modélisation a été établi, combinant l'information des fluctuations transcriptionnelles avec différentes résolutions temporelles. Cela a donné une vue complète et précise du processus stochastique, décrit par le modèle de Markov. Cinq des six promoteurs de mammifères pourraient être définis par trois états, probablement contrôlés par des mécanismes différents. Le passage entre ces états est défini par les constantes de vitesse et l'écart entre eux pourrait potentiellement expliquer la différence dans la quantité d'ARN produit. De manière intéressante, nous avons constaté que les taux de passage entre les états inactifs et profondément silencieux sont la marque distinctive de différents promoteurs, suggérant que les événements cruciaux définissant les profils transcriptionnels sont en fait des événements pré-transcriptionnels.Pour étudier le rôle de Tat, des lignées cellulaires contenant un rapporteur du VIH-1 et une quantité différente de Tat ont été produites. Avec cette approche décrite ci-dessus, nous avons montré que Tat, précédemment caractérisé en tant qu'acteur dominant dans la libération de la polymérase en pause, agit longtemps avant que la transcription soit initiée. Ces résultats frappants apportent de nouvelles perspectives concernant la dynamique transcriptionnelle du VIH-1 contrôlée par Tat.

Transcription is a fundamental step in gene expression. However, it is incompletely characterized in single living cells. To address this question, our laboratory developed the improved RNA tagging system using MS2-binding protein that could easily be fused with the promoter of interest inserted in a single copy in HeLa cell lines. This construct allows quantitative, single molecule view of the transcription in a real time. We have found that HIV-1 is transcribed by groups of closely spaced polymerases referred as convoys. The transcription oscillates randomly between active (ON) and inactive (OFF) periods that are…

Advisors/Committee Members: Bertrand, Édouard (thesis director), Basyuk, Eugénia (thesis director).

Subjects/Keywords: Transcription; Promoters; Imagerie; Tat; Cellules vivantes; Vih; Transcription; Promoters; Live cell imaging; Tat; Hiv

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kozulic-Pirher, A. (2018). La visualisation de la transcription en molécules unique révèle de nouvelles caractéristiques des promoteurs cellulaires et viraux : Real time imaging of transcription reveals new features of cellular and viral promoters. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2018MONTT080

Chicago Manual of Style (16^th Edition):

Kozulic-Pirher, Alja. “La visualisation de la transcription en molécules unique révèle de nouvelles caractéristiques des promoteurs cellulaires et viraux : Real time imaging of transcription reveals new features of cellular and viral promoters.” 2018. Doctoral Dissertation, Montpellier. Accessed January 19, 2021. http://www.theses.fr/2018MONTT080.

MLA Handbook (7^th Edition):

Kozulic-Pirher, Alja. “La visualisation de la transcription en molécules unique révèle de nouvelles caractéristiques des promoteurs cellulaires et viraux : Real time imaging of transcription reveals new features of cellular and viral promoters.” 2018. Web. 19 Jan 2021.

Vancouver:

Kozulic-Pirher A. La visualisation de la transcription en molécules unique révèle de nouvelles caractéristiques des promoteurs cellulaires et viraux : Real time imaging of transcription reveals new features of cellular and viral promoters. [Internet] [Doctoral dissertation]. Montpellier; 2018. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2018MONTT080.

Council of Science Editors:

Kozulic-Pirher A. La visualisation de la transcription en molécules unique révèle de nouvelles caractéristiques des promoteurs cellulaires et viraux : Real time imaging of transcription reveals new features of cellular and viral promoters. [Doctoral Dissertation]. Montpellier; 2018. Available from: http://www.theses.fr/2018MONTT080

24. Scaduto, Alessandro Antonio. O tratamento de dependentes de substâncias psicoativas numa comunidade terapêutica: estudo através da avaliação psicológica.

Degree: Mestrado, Psicologia, 2010, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/59/59137/tde-03072012-110407/ ;

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Frente ao custo social dos quadros de abuso e dependência de substâncias psicoativas, diversos modelos explicativos têm sido propostos, sejam eles baseados em preceitos morais,… (more)

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Frente ao custo social dos quadros de abuso e dependência de substâncias psicoativas, diversos modelos explicativos têm sido propostos, sejam eles baseados em preceitos morais, religiosos, experiências de grupos de autoajuda ou na pesquisa científica. As Comunidades Terapêuticas (CTs) são uma modalidade de atendimento a usuários abusivos e dependentes de substâncias psicoativas que se baseiam em vários desses modelos, que se mostram bastante diversas em sua organização e nos serviços oferecidos, mas relativamente coesas em termos dos seus princípios. Diversos estudos têm tentado explicar os aspectos relacionados a esse modelo de tratamento, sugerindo sua eficácia. Apesar disso, existem poucas pesquisas compreensivas acerca das mudanças psicológicas que ocorrem nas pessoas que passam por esse tipo de instituição. No Brasil, a escassez de trabalhos acadêmicos sobre as CTs aponta para a necessidade de estudos sobre seus componentes terapêuticos, a fim de conhecer melhor os alcances e limites desse tipo de tratamento. A presente investigação visou estudar as mudanças psicológicas de pessoas que passaram por tratamento numa CT da região de Ribeirão Preto (SP), por meio de entrevistas de avaliação no início e no final de sua internação. Os participantes do estudo foram sete homens entre 21 e 35 anos de idade, nível socioeconômico médio baixo e dependentes de crack (predominantemente), cocaína e álcool. Para a realização das avaliações, foram utilizados um roteiro de entrevista semiestruturado, o Inventário Multifásico Minnesota de Personalidade, Improved Readability Form (MMPI-IRF) e cartões selecionados do Teste de Apercepção Temática (TAT). Os dados obtidos foram categorizados e analisados a partir de dimensões e domínios do processo de mudança na CT, conforme embasamento teórico de autores da área. O conjunto de dados foi interpretado a partir de teorias psicodinâmicas de personalidade. Os resultados mostram que o tratamento promoveu melhoras no funcionamento psicológico em graus diferentes para dois subgrupos de participantes, em todas as dimensões do processo de mudança. Os resultados são discutidos em termos das diferenças entre os subgrupos em aspectos como a estrutura e o nível de funcionamento da personalidade e qualidade da introjeção das experiências durante o tratamento. Ainda, são feitas considerações acerca do método de pesquisa adotado e dos alcances e limites do tratamento em CTs e sugestões para estudos futuros no Brasil.

Considering the high social cost of substance abuse and dependence, several models have been proposed, based on moral and/or religious principles, self-help groups experiences or scientific research. The Therapeutic Community (TC) is a treatment modality for substance abusers based in many of the models above, which shows a variety in terms of its organization and services offered, as well as a relatively cohesion of principles along these institutions. Several studies have been trying to explain the aspects related to such treatment modality, suggesting its efficacy. In spite of this,…

Advisors/Committee Members: Barbieri, Valeria.

Subjects/Keywords: Abuso de Substâncias; Avaliação Psicológica; Comunidades Terapêuticas; MMPI-IRF; MMPI-IRF; Psychological Assessment; Substance Abuse; TAT; TAT; Therapeutic Communities

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Scaduto, A. A. (2010). O tratamento de dependentes de substâncias psicoativas numa comunidade terapêutica: estudo através da avaliação psicológica. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/59/59137/tde-03072012-110407/ ;

Chicago Manual of Style (16^th Edition):

Scaduto, Alessandro Antonio. “O tratamento de dependentes de substâncias psicoativas numa comunidade terapêutica: estudo através da avaliação psicológica.” 2010. Masters Thesis, University of São Paulo. Accessed January 19, 2021. http://www.teses.usp.br/teses/disponiveis/59/59137/tde-03072012-110407/ ;.

MLA Handbook (7^th Edition):

Scaduto, Alessandro Antonio. “O tratamento de dependentes de substâncias psicoativas numa comunidade terapêutica: estudo através da avaliação psicológica.” 2010. Web. 19 Jan 2021.

Vancouver:

Scaduto AA. O tratamento de dependentes de substâncias psicoativas numa comunidade terapêutica: estudo através da avaliação psicológica. [Internet] [Masters thesis]. University of São Paulo; 2010. [cited 2021 Jan 19]. Available from: http://www.teses.usp.br/teses/disponiveis/59/59137/tde-03072012-110407/ ;.

Council of Science Editors:

Scaduto AA. O tratamento de dependentes de substâncias psicoativas numa comunidade terapêutica: estudo através da avaliação psicológica. [Masters Thesis]. University of São Paulo; 2010. Available from: http://www.teses.usp.br/teses/disponiveis/59/59137/tde-03072012-110407/ ;

University of KwaZulu-Natal

25. Zulu, Simo Siyanda. Effect of highly active antiretroviral therapy (HAART) on HIV-1 tat protein-induced neurotoxicity.

Degree: Physiology, 2014, University of KwaZulu-Natal

URL: http://hdl.handle.net/10413/12627

► Background: HIV-1-trans-activating (Tat) protein has been associated with development of HIVassociated neurocognitive disorder (HAND). Previous studies have demonstrated that Tat protein causes neurotoxicity through an… (more)

▼ Background: HIV-1-trans-activating (Tat) protein has been associated with development of HIVassociated neurocognitive disorder (HAND). Previous studies have demonstrated that Tat protein causes neurotoxicity through an increase in reactive oxygen species (ROS) leading to damage of proteins and other cellular components. Tat has also been shown to cause excessive production of pro-inflammatory cytokines. However the role of antiretroviral agents in the neuropathology of HIV is not known. The objective of this study was to investigate whether a combination of antiretroviral drugs (Zidovudine, Lamivudine and Efavirenz, a highly active antiretroviral therapy, HAART) is effective in reducing the toxic effects of Tat protein in the rat hippocampus. Materials and methods: Male Sprague-Dawley rats were divided into four groups (n=10 per group). Each rat received bilateral intrahippocampal injection of either Tat protein (5μg/10μL) or vehicle, followed 7 days later by a combination of antiretroviral drugs (Zidovudine 12mg/kg, Lamivudine 6mg/kg and Efavirenz 24mg/kg) or saline injected intraperitoneally, twice a day, for 7 days. After treatment, animals were sacrificed and hippocampal tissue was collected for analysis of cleaved caspase-3, 4- hydroxynonenal (NHE), tumor necrosis factor alpha (TNF-α), phosphorylated extracellular signalregulated kinase (pERK) and Synaptophysin. Results: Tat increased cleaved caspase-3 levels in the hippocampus. Antiretroviral treatment decreased the Tat-induced increase in cleaved caspase-3. Tat increased HNE, a marker of lipid peroxidation and reduced hippocampal synaptophysin. The latter Tat-induced effects were not reversed by antiretroviral treatment. The antiretroviral drug combination activated the pERK pathway and increased TNF-α levels in hippocampal tissue, independent of Tat infusion. Discussion: Our findings showed that antiretroviral drugs reversed Tat-induced cleaved caspase-3, reducing apoptosis but did not reverse Tat-induced increase in lipid peroxidation and the synaptic marker, synaptophysin. The evidence suggests that the combination of antiretroviral drugs may be toxic, elevating hippocampal pERK and TNF-α levels. However, these effects could also be beneficial to the individual, since TNF-α has been shown to inhibit viral replication. The present results provide novel insight into the mechanism of antiretroviral action. Advisors/Committee Members: Daniels, William M. U. (advisor), Mabandla, Musa Vuyisile. (advisor).

Subjects/Keywords: Physiology.; HIV-1 tat protein.; HAART.; HIV-1-trans-activating protein.; Tat.; HAART.; ERK.; TNF-α.; Synaptophysin.; HAND.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zulu, S. S. (2014). Effect of highly active antiretroviral therapy (HAART) on HIV-1 tat protein-induced neurotoxicity. (Thesis). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/12627

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zulu, Simo Siyanda. “Effect of highly active antiretroviral therapy (HAART) on HIV-1 tat protein-induced neurotoxicity.” 2014. Thesis, University of KwaZulu-Natal. Accessed January 19, 2021. http://hdl.handle.net/10413/12627.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zulu, Simo Siyanda. “Effect of highly active antiretroviral therapy (HAART) on HIV-1 tat protein-induced neurotoxicity.” 2014. Web. 19 Jan 2021.

Vancouver:

Zulu SS. Effect of highly active antiretroviral therapy (HAART) on HIV-1 tat protein-induced neurotoxicity. [Internet] [Thesis]. University of KwaZulu-Natal; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10413/12627.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zulu SS. Effect of highly active antiretroviral therapy (HAART) on HIV-1 tat protein-induced neurotoxicity. [Thesis]. University of KwaZulu-Natal; 2014. Available from: http://hdl.handle.net/10413/12627

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Université Paris-Sud – Paris XI

26. Gadzinski, Adeline. Étude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : implications dans l'immunogénicité de protéines et applications potentielles en vaccination : Study of HIV-1 Tat self-adjuvanting property and utilization of its ability to bind heparan sulfates to assess the role of ubiquitous targets in antigen presentation mechanisms.

Degree: Docteur es, Immunologie, 2011, Université Paris-Sud – Paris XI

URL: http://www.theses.fr/2011PA11T017

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Les protéines solubles sont généralement faiblement immunogènes, ce qui constitue unelimite pour le développement de vaccins sous unitaires à base de protéines. Mes travaux de… (more)

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Les protéines solubles sont généralement faiblement immunogènes, ce qui constitue unelimite pour le développement de vaccins sous unitaires à base de protéines. Mes travaux de thèseont eu pour objectif de décrypter certains mécanismes moléculaires et cellulaires qui contribuent àl’immunogénicité et d’en tirer partie pour développer des approches originales permettantd’améliorer la capacité des protéines à déclencher la réponse immunitaire. Pour cela, j’aiprincipalement utilisé le transactivateur transcriptionnel (Tat) du VIH-1. J’ai montré quel’oligomérisation de Tat permet à un mécanisme de collaboration B-TH-2 d’induire la réponseimmunitaire en absence d’adjuvant. J’ai identifié le déterminant minimal responsable de l’effet etmontré qu’il confère la propriété adjuvante à d’autres antigènes. J’ai ensuite montré que laprésentation aux cellules T restreinte aux CMH I et CMH II est accrue lorsque les protéines sontdotées de la capacité à lier des sucres sulfatés d’expression ubiquitaire: les héparanes sulfate. Cestravaux ont permis de définir de nouvelles approches pour améliorer l’immunogénicité de protéinessusceptibles d’être intégrées dans des préparations vaccinales.

Soluble proteins are usually poorly immunogenic, which is a limit to the development ofsubunit vaccines based on proteins. My thesis work aimed to decipher some molecular and cellularmechanisms that contribute to the immunogenicity and to exploit them to develop innovativeapproaches to improve the ability of proteins to trigger the immune response. For this purpose, Imainly used the transcriptional transactivator (Tat) of HIV-1. I showed that the oligomerization of Tatenables a B-TH-2 collaborative mechanism to induce the immune response in the absence ofadjuvant. I identified the minimum region determining the effect and showed that it confers the selfadjuvantingproperty to other antigens. In the second part of my work, I showed that the MHC I andMHC II restricted presentation to T cells is increased when the proteins are endowed with the abilityto bind ubiquitous sulfated polysaccharides: heparan sulfates. This work helped to define newapproaches to improve the immunogenicity of proteins that are likely to be included in vaccinepreparations.

Advisors/Committee Members: Leonetti, Michel (thesis director).

Subjects/Keywords: Tat; Effet adjuvant; Héparanes sulfate; Présentation antigénique; Immunogénicité; Vaccination; Tat; Self-adjuvanting protein; Heparan sulfate; Antigen presentation; Immunogenicity; Vaccination.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gadzinski, A. (2011). Étude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : implications dans l'immunogénicité de protéines et applications potentielles en vaccination : Study of HIV-1 Tat self-adjuvanting property and utilization of its ability to bind heparan sulfates to assess the role of ubiquitous targets in antigen presentation mechanisms. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2011PA11T017

Chicago Manual of Style (16^th Edition):

Gadzinski, Adeline. “Étude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : implications dans l'immunogénicité de protéines et applications potentielles en vaccination : Study of HIV-1 Tat self-adjuvanting property and utilization of its ability to bind heparan sulfates to assess the role of ubiquitous targets in antigen presentation mechanisms.” 2011. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed January 19, 2021. http://www.theses.fr/2011PA11T017.

MLA Handbook (7^th Edition):

Gadzinski, Adeline. “Étude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : implications dans l'immunogénicité de protéines et applications potentielles en vaccination : Study of HIV-1 Tat self-adjuvanting property and utilization of its ability to bind heparan sulfates to assess the role of ubiquitous targets in antigen presentation mechanisms.” 2011. Web. 19 Jan 2021.

Vancouver:

Gadzinski A. Étude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : implications dans l'immunogénicité de protéines et applications potentielles en vaccination : Study of HIV-1 Tat self-adjuvanting property and utilization of its ability to bind heparan sulfates to assess the role of ubiquitous targets in antigen presentation mechanisms. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2011. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2011PA11T017.

Council of Science Editors:

Gadzinski A. Étude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : implications dans l'immunogénicité de protéines et applications potentielles en vaccination : Study of HIV-1 Tat self-adjuvanting property and utilization of its ability to bind heparan sulfates to assess the role of ubiquitous targets in antigen presentation mechanisms. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2011. Available from: http://www.theses.fr/2011PA11T017

27. Peiffer, Christine-France. De la créativité et de ses expressions chez les étudiants en grandes écoles : About creativity and its expressions among students from grandes ecoles (business and engineering schools).

Degree: Docteur es, Psychologie, 2015, Sorbonne Paris Cité

URL: http://www.theses.fr/2015USPCB209

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Cette recherche en psychanalyse et psychologie projective questionne, sous l'angle de la créativité, le système des grandes écoles en France et celui des classes préparatoires,… (more)

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Cette recherche en psychanalyse et psychologie projective questionne, sous l'angle de la créativité, le système des grandes écoles en France et celui des classes préparatoires, mode de formation le plus courant pour intégrer ces écoles (établissements élitistes, principalement de commerce et d'ingénieurs). Elle s'intéresse aussi au processus adolescent activement à l'œuvre chez les élèves qui, pour la plupart, trouvent en classe prépa, manière à traiter leurs conflits. Si l'adolescence pousse à la créativité, le passage en prépa favorise la sublimation, destin pulsionnel privilégié qui peut ouvrir aux plus belles créations. A partir de ces réflexions, étayées par l'analyse métapsychologique de la créativité et de son rapprochement avec la sublimation, nous conjecturons que les étudiants en grandes écoles, issus des classes prépas, pourraient s'avérer particulièrement créatifs. Concourraient à cette disposition une pugnacité au travail, mue par le désir inextinguible d'apprendre, ainsi qu'une certaine forme de nostalgie, relative à l'enfance envolée. Notre rencontre avec vingt étudiants - qui ont accepté de se prêter aux méthodes projectives - vient vérifier cette hypothèse : la distinction entre deux groupes d'étudiants, issus des classes prépas ou bien admis par d'autres voies, confirme l'expression plus aisée du potentiel créateur chez ceux du premier groupe. La recherche s'interroge ensuite sur l'exercice de la créativité après les diplômes, notamment lorsqu'elle se déploie dans le domaine des mathématiques.

This research in psychoanalysis and projective psychology examines the French « Grandes Ecoles » and preparatory class system, from the angle of creativity. These intensive courses called « prepa classes » are the most common way to enter the « Grandes Ecoles » (French Elite Establishments, mainly Business and Engineering Schools). This research also explores how the Teen prepa students, who are going through the adolescence process at work, can find way to resolve their conflicts through the prepa way of life. If adolescence impulses creativity, the prepa class system enhances sublimation, this pulsionnal conversion leading to the most beautiful productions. These considerations, supported by a metapsychological analysis about creativity and its link with sublimation, lead us to make the assumption that the "Grandes Ecoles" students, after the prepa classes, should be particularly creative. A strong dedication to work, moved by the very utmost desire of learning, as well as a touch of nostalgia, due to the loss of childhood, could reinforce this ability. We interviewed and tested - with projective methods - twenty « Grandes Ecoles » students, belonging to two groups : the first one had joined the Engineering or Business Schools after preparatory classes, the second one had joined them by other ways. Our results confirm that students from prepa classes show more easily their creative potential than the others . The research goes on to question how creativity is expressed after graduation and in particular,…

Advisors/Committee Members: Neau, Françoise (thesis director).

Subjects/Keywords: Grandes écoles; Classes préparatoires; Étudiants; Créativité; Sublimation; Rorschach; TAT; Grandes ecoles; Preparatory classes; Students; Creativity; Sublimation; Rorschach; TAT; 153.35

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Peiffer, C. (2015). De la créativité et de ses expressions chez les étudiants en grandes écoles : About creativity and its expressions among students from grandes ecoles (business and engineering schools). (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2015USPCB209

Chicago Manual of Style (16^th Edition):

Peiffer, Christine-France. “De la créativité et de ses expressions chez les étudiants en grandes écoles : About creativity and its expressions among students from grandes ecoles (business and engineering schools).” 2015. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 19, 2021. http://www.theses.fr/2015USPCB209.

MLA Handbook (7^th Edition):

Peiffer, Christine-France. “De la créativité et de ses expressions chez les étudiants en grandes écoles : About creativity and its expressions among students from grandes ecoles (business and engineering schools).” 2015. Web. 19 Jan 2021.

Vancouver:

Peiffer C. De la créativité et de ses expressions chez les étudiants en grandes écoles : About creativity and its expressions among students from grandes ecoles (business and engineering schools). [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2015. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2015USPCB209.

Council of Science Editors:

Peiffer C. De la créativité et de ses expressions chez les étudiants en grandes écoles : About creativity and its expressions among students from grandes ecoles (business and engineering schools). [Doctoral Dissertation]. Sorbonne Paris Cité; 2015. Available from: http://www.theses.fr/2015USPCB209

28. Halley, Clara. La dynamique du traitement de l'excitation à l'adolescence : étude comparative de deux groupes d'âge : éclairage de la clinique projective : The treatment of excitation dynamic during adolescence : a comparative study of two age groups.

Degree: Docteur es, Psychologie, 2017, Sorbonne Paris Cité

URL: http://www.theses.fr/2017USPCB206

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L'adolescence, marquée par l'éclosion de la puberté et la résurgence des pulsions sexuelles et agressives, engage, un travail interne lié aux transformations psychiques et à… (more)

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L'adolescence, marquée par l'éclosion de la puberté et la résurgence des pulsions sexuelles et agressives, engage, un travail interne lié aux transformations psychiques et à l'émergence de la sexualité génitale. La puberté peut alors faire intrusion et trauma, blessant le sujet qui est plus ou moins prêt à supporter la contrainte au changement induit par le processus pubertaire. En référence au modèle théorique psychanalytique, nous nous intéressons dans cette étude à la manière dont les adolescents font face aux afflux d'excitations, tant externes qu'internes, selon un traitement psychique, par un travail de mentalisation et de symbolisation, ou bien comportemental ou somatique, par le langage du corps ou le recours à la sensorialité. En effet, quelles que soient les capacités d'élaboration mentale de l'adolescent, une vulnérabilité transitoire de l'appareil mental est attendue à cet âge de la vie. Notre travail se propose ainsi d'explorer le traitement de l'excitation à l'adolescence, mis en évidence par l'étude de la qualité de quatre mouvements psychiques : le narcissisme, le système pare-excitation, le recours au corps par la sensorialité et le langage du corps, ainsi que les processus de pensée à travers l'étude de la mentalisation et de la symbolisation. Notre objet de recherche questionne ainsi la qualité du traitement de l'excitation, à travers la mise en perspective de ces différentes dimensions conceptuelles, susceptible d'exposer une meilleure approche processuelle de l'adolescence. Partant de l'hypothèse principale selon laquelle le traitement de l'excitation est multifactoriel, l'objectif de cette étude est de dégager la manière dont l'articulation des différents concepts étudiés est à même de rendre compte, de manière plus sensible, du traitement de l'excitation à l'adolescence. La méthodologie projective a été choisie pour mettre à l'épreuve cette hypothèse à l'aide de grilles référées aux quatre dimensions précitées. Nous avons rencontré 17 adolescents tout-venants âgés de 14 à 18 ans auxquels nous avons proposé le Rorschach et le TAT. Dans une approche comparative, nous avons étudié le traitement de l'excitation auprès de deux groupes d'âge (14-16 ans et 16-18 ans). Les résultats mettent en avant des différences dans le traitement de l'excitation à l'adolescence entre les deux groupes d'âge, les plus jeunes ayant préférentiellement recours à l'inhibition, les plus âgés étant davantage en mesure de mentaliser et symboliser l'excitation. Conformément à notre hypothèse générale, l'analyse projective des quatre dimensions de notre travail permet une approche plus fine pour chaque adolescent des spécificités du traitement de l'excitation.

Adolescence, marked by the emergence of puberty and the resurgence of sexual and aggressive drives, engages an internal work linked to psychic transformations and to the emergence of genital sexuality. Puberty can therefore intrude and cause trauma, hurting the subject who is more or less ready to bear the constraint to change induced by the pubertal process. In…

Advisors/Committee Members: Azoulay, Catherine (thesis director).

Subjects/Keywords: Adolescence; Corps; Excitation; Pare-excitation; Narcissisme; Mentalisation; Symbolisation; Rorschach; Tat; Adolescence; Body; Excitation; Protective-shield; Narcissism; Mentalisation; Symbolisation; Rorschach; Tat; 155.5

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Halley, C. (2017). La dynamique du traitement de l'excitation à l'adolescence : étude comparative de deux groupes d'âge : éclairage de la clinique projective : The treatment of excitation dynamic during adolescence : a comparative study of two age groups. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2017USPCB206

Chicago Manual of Style (16^th Edition):

Halley, Clara. “La dynamique du traitement de l'excitation à l'adolescence : étude comparative de deux groupes d'âge : éclairage de la clinique projective : The treatment of excitation dynamic during adolescence : a comparative study of two age groups.” 2017. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 19, 2021. http://www.theses.fr/2017USPCB206.

MLA Handbook (7^th Edition):

Halley, Clara. “La dynamique du traitement de l'excitation à l'adolescence : étude comparative de deux groupes d'âge : éclairage de la clinique projective : The treatment of excitation dynamic during adolescence : a comparative study of two age groups.” 2017. Web. 19 Jan 2021.

Vancouver:

Halley C. La dynamique du traitement de l'excitation à l'adolescence : étude comparative de deux groupes d'âge : éclairage de la clinique projective : The treatment of excitation dynamic during adolescence : a comparative study of two age groups. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2017. [cited 2021 Jan 19]. Available from: http://www.theses.fr/2017USPCB206.

Council of Science Editors:

Halley C. La dynamique du traitement de l'excitation à l'adolescence : étude comparative de deux groupes d'âge : éclairage de la clinique projective : The treatment of excitation dynamic during adolescence : a comparative study of two age groups. [Doctoral Dissertation]. Sorbonne Paris Cité; 2017. Available from: http://www.theses.fr/2017USPCB206

Cornell University

29. Rocco, Mark. Twin-Arginine Translocase Mutations That Suppress Folding Quality Control And Permit Export Of Misfolded Substrate Proteins.

Degree: PhD, Biomedical Engineering, 2011, Cornell University

URL: http://hdl.handle.net/1813/29403

► The twin-arginine translocation (Tat) pathway is a robust protein translocation system capable of transporting cellular proteins across the bacterial cytoplasmic membrane. A hallmark of the… (more)

▼ The twin-arginine translocation (Tat) pathway is a robust protein translocation system capable of transporting cellular proteins across the bacterial cytoplasmic membrane. A hallmark of the bacterial Tat pathway is its ability to export proteins that have attained a fully-folded structure prior to export. An inbuilt feature of the Tat system is a folding quality control (QC) mechanism that discriminates between unfolded/misfolded and correctly folded proteins, allowing only the latter to pass through the inner membrane. This mechanism holds great promise for biotechnology applications because it has the potential to ensure the quality and structural integrity of exported proteins. Yet, despite the significance of the Tat system, the precise mechanism by which the TatABC protein complex delivers folded proteins into the periplasm remains poorly understood. Likewise, very little is known about the folding QC mechanism. Studies from our laboratory suggest that the QC mechanism resides within the TatABC proteins. Thus, to shed more light on this enigmatic process, we implemented a directed co-evolution strategy whereby all three components of the Tat pathway were evolved simultaneously to isolate suppressors that relaxed the QC feature. Selection of suppressors was enabled by a genetic selection comprised of a poorly folded substrate protein ([alpha]3B) fused to the selectable reporter beta-lactamase (Bla). By screening recombinant libraries of the tatABC operon, we were able to isolate variants that exported previously translocation-incompetent substrates and nonnative Tat substrates. The resulting TatABC variants represent putative suppressors of the QC mechanism. Further information gained from these suppressors should provide a detailed understanding of the molecular mechanisms involved in TatABCmediated QC. Moreover, these studies demonstrate that directed co-evolution of cellular protein machinery is a viable new strategy for dissecting complicated, poorly understood multiprotein complexes in living cells. Advisors/Committee Members: Delisa, Matthew (chair), Wilson, David B (committee member), Varner, Jeffrey D. (committee member).

Subjects/Keywords: Twin-Arginine Translocation (Tat); Folding Quality Control; Escherichia coli

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rocco, M. (2011). Twin-Arginine Translocase Mutations That Suppress Folding Quality Control And Permit Export Of Misfolded Substrate Proteins. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/29403

Chicago Manual of Style (16^th Edition):

Rocco, Mark. “Twin-Arginine Translocase Mutations That Suppress Folding Quality Control And Permit Export Of Misfolded Substrate Proteins.” 2011. Doctoral Dissertation, Cornell University. Accessed January 19, 2021. http://hdl.handle.net/1813/29403.

MLA Handbook (7^th Edition):

Rocco, Mark. “Twin-Arginine Translocase Mutations That Suppress Folding Quality Control And Permit Export Of Misfolded Substrate Proteins.” 2011. Web. 19 Jan 2021.

Vancouver:

Rocco M. Twin-Arginine Translocase Mutations That Suppress Folding Quality Control And Permit Export Of Misfolded Substrate Proteins. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1813/29403.

Council of Science Editors:

Rocco M. Twin-Arginine Translocase Mutations That Suppress Folding Quality Control And Permit Export Of Misfolded Substrate Proteins. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/29403

Universidade de Brasília

30. Melina Magalhães Ribeiro. Proteínas recombinantes ligadas a TAT e sua aplicação terapêutica na reversão de dano isquêmico de ilhotas pancreáticas : impacto em transplante.

Degree: 2007, Universidade de Brasília

URL: http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2643 ; http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2642

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O transplante de ilhotas pode ser uma opção para o tratamento do Diabetes do tipo I em função do aumento do controle metabólico e da… (more)

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O transplante de ilhotas pode ser uma opção para o tratamento do Diabetes do tipo I em função do aumento do controle metabólico e da qualidade de vida do paciente transplantado. As maiores limitações para a aplicação dessa técnica em larga escala são o alto número de ilhotas necessárias para a obtenção de um bom funcionamento do transplante e a deteriorização de ilhotas, causados por dano isquêmico por preservação a frio. Aqui propomos o uso de nova tecnologia denominada TAT- PTD como transportador de moléculas terapêuticas para o interior de ilhotas e pâncreas com a intenção de prevenir morte de ilhotas, aumentando, assim, o número e a qualidade das ilhotas para transplante de pacientes diabéticos. Resultados da Parte I: Construímos uma proteína de fusão composta por Heme oxigenase -1 (HO1) e o domínio de transdução protéica TAT- PTD (TAT)  um peptídeo viral com 11 aminoácidos provenientes do vírus da imunodeficiência humana (HIV) e com capacidade de penetrar em membrana plasmática. A transdução de TAT-PTD-HO1 em células produtoras de insulina protege contra a ação citotóxica de TNF-α. A transdução de TAT-HO1 para o interior de células produtoras de insulina não danifica a fisiologia de ilhotas como foi mostrado quando estas são transplantadas em camundongos imunodeficientes e com Diabetes quimicamente induzida. Finalmente, mostramos que transdução de ilhotas com a proteína de fusão melhora a viabilidade de ilhotas em cultura. Essa abordagem pode ter um impacto positivo no aumento da disponibilidade de ilhotas para transplante. Resultados da Parte II: A produção de proteínas de fusão ligadas a TAT-PTD pode ser obtida em larga escala e eficientemente com a expressão protéica em E. coli. No entanto, a contaminação com endotoxina representa um problema para a aplicação dessas proteínas in vitro e in vivo. Desenvolvemos várias proteínas de fusão ligadas a TAT que têm aplicação terapêuticas em ilhotas. Apresentamos aqui um novo método para a eficiente remoção de endotoxina de soluções protéicas usando tubos de polipropileno em combinação com tratamento em pH ácido, mantendo a atividade biológica da proteína com bom rendimento protéico. Resultados da Parte III: Para poder detectar possíveis moléculas que possam ser citoprotetoras e que possam ser associadas à tecnologia de TAT-PTD, estabelecemos um modelo de isquemia a frio em pâncreas de ratos. Isso nos permitiu estudar a modulação de vias ativadas por sinal de stress que levam ao impedimento da recuperação da qualidade e função de ilhotas. Observamos que JNK e p38 são proteínas kinase ativadas por stress (SAPK) que estão presentes por causa de dano causado por isquemia pancreática e isolamento de ilhotas. Um experimento preliminar usando TAT-D-JNKi, inibidor de JNK, tentou prevenir dano causado pela ativação de JNK.

Islet transplantation can become a therapeutic option for the treatment of Type I Diabetes due to increased metabolic control and quality of life for transplanted patients. The major limitations for widespread application of this technique…

Advisors/Committee Members: Marcelo Brígido, Ricardo L. Pastori, Mari Sogayar, Pérola de O. e Magalhães, Maria Sueli Soares Felipe, Fatima G. De Sá.

Subjects/Keywords: diabetes; PTD; transplante de ilhotas; isquemia; TAT; BIOLOGIA MOLECULAR; endotoxina

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ribeiro, M. M. (2007). Proteínas recombinantes ligadas a TAT e sua aplicação terapêutica na reversão de dano isquêmico de ilhotas pancreáticas : impacto em transplante. (Thesis). Universidade de Brasília. Retrieved from http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2643 ; http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2642

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ribeiro, Melina Magalhães. “Proteínas recombinantes ligadas a TAT e sua aplicação terapêutica na reversão de dano isquêmico de ilhotas pancreáticas : impacto em transplante.” 2007. Thesis, Universidade de Brasília. Accessed January 19, 2021. http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2643 ; http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2642.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ribeiro, Melina Magalhães. “Proteínas recombinantes ligadas a TAT e sua aplicação terapêutica na reversão de dano isquêmico de ilhotas pancreáticas : impacto em transplante.” 2007. Web. 19 Jan 2021.

Vancouver:

Ribeiro MM. Proteínas recombinantes ligadas a TAT e sua aplicação terapêutica na reversão de dano isquêmico de ilhotas pancreáticas : impacto em transplante. [Internet] [Thesis]. Universidade de Brasília; 2007. [cited 2021 Jan 19]. Available from: http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2643 ; http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2642.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ribeiro MM. Proteínas recombinantes ligadas a TAT e sua aplicação terapêutica na reversão de dano isquêmico de ilhotas pancreáticas : impacto em transplante. [Thesis]. Universidade de Brasília; 2007. Available from: http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2643 ; http://bdtd.bce.unb.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=2642

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations