Relevant bibliographies by topics / Mutations de sites de clivage

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Academic literature on the topic 'Mutations de sites de clivage'

Author: Grafiati
Published: 4 June 2021
Last updated: 17 February 2022

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Journal articles on the topic "Mutations de sites de clivage"

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Larrouy, L., F. Brun-Vézinet, and D. Descamps. "Sites de clivage de gag et résistance du VIH aux inhibiteurs de la protéase." Antibiotiques 12, no. 2 (2010): 100–106. http://dx.doi.org/10.1016/j.antib.2010.02.004.

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Khosravi, Azar Dokht, Hossein Meghdadi, Ata A. Ghadiri, Ameneh Alami, Amir Hossein Sina, and Mehdi Mirsaeidi. "rpoBgene mutations amongMycobacterium tuberculosisisolates from extrapulmonary sites." APMIS 126, no. 3 (2018): 241–47. http://dx.doi.org/10.1111/apm.12804.

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Deveuve, Quentin, Valérie Gouilleux-Gruart, Gilles Thibault, and Laurie Lajoie. "La région charnière des anticorps thérapeutiques." médecine/sciences 35, no. 12 (2019): 1098–105. http://dx.doi.org/10.1051/medsci/2019218.

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La région charnière est une courte séquence des chaînes lourdes (H) d’anticorps liant le Fab (fragment antigen binding) au Fc (fragment crystallisable). Les propriétés fonctionnelles des quatre sous-classes d’immunoglobulines d’isotype G (IgG) résultent en partie des différences de séquence de leurs régions charnières. En effet, certains acides aminés de la partie C-terminale de ces régions charnières (« partie basse ») sont situés au sein ou à proximité des sites de liaison de la molécule C1q de la voie classique du complément et des récepteurs pour la région Fc des IgG (RFcγ) sur les chaînes H d’IgG. Les régions charnières sont également sensibles au clivage protéolytique par de nombreuses protéases du microenvironnement tumoral et/ou inflammatoire pouvant altérer les réponses fonctionnelles. Le format optimal de la charnière reste donc un défi majeur pour le développement de nouveaux anticorps thérapeutiques.
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Koch, Nathalie, Nouara Yahi, Jacques Fantini, and Catherine Tamalet. "Mutations in HIV-1 gag cleavage sites and their association with protease mutations." AIDS 15, no. 4 (2001): 526–28. http://dx.doi.org/10.1097/00002030-200103090-00013.

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Yazicioglu, Mustafa N., Daryl L. Goad, Aarati Ranganathan, Angelique W. Whitehurst, Elizabeth J. Goldsmith, and Melanie H. Cobb. "Mutations in ERK2 Binding Sites Affect Nuclear Entry." Journal of Biological Chemistry 282, no. 39 (2007): 28759–67. http://dx.doi.org/10.1074/jbc.m703460200.

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Murphy, Brent P., and Patrick J. Tranel. "Target-Site Mutations Conferring Herbicide Resistance." Plants 8, no. 10 (2019): 382. http://dx.doi.org/10.3390/plants8100382.

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Mutations conferring evolved herbicide resistance in weeds are known in nine different herbicide sites of action. This review summarizes recently reported resistance-conferring mutations for each of these nine target sites. One emerging trend is an increase in reports of multiple mutations, including multiple amino acid changes at the glyphosate target site, as well as mutations involving two nucleotide changes at a single amino acid codon. Standard reference sequences are suggested for target sites for which standards do not already exist. We also discuss experimental approaches for investigating cross-resistance patterns and for investigating fitness costs of specific target-site mutations.
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Hahn, Michael A., Julie McDonnell, and Deborah J. Marsh. "The effect of disease-associated HRPT2 mutations on splicing." Journal of Endocrinology 201, no. 3 (2009): 387–96. http://dx.doi.org/10.1677/joe-09-0038.

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Mutations in the tumour suppressor HRPT2 occur in patients with parathyroid carcinoma, kidney tumours and Hyperparathyroidism–Jaw Tumour syndrome. Disruption of exonic splicing through mutation of donor/acceptor splice sites or exonic splice enhancer (ESE) sites leads to loss of function of a number of major tumour suppressors including BRCA1, APC and MLH1. Given that the effect of HRPT2 mutations on splicing has not been widely studied, we used an in vitro splicing assay to determine whether 17 HRPT2 mutations located in hot-spot and other exons predicted to disrupt ESE consensus sites led to aberrant splicing. Using two independent web-based prediction programs, the majority of these mutations were predicted to disrupt ESE consensus sites; however, aberrant splicing of HRPT2 transcripts was not observed. Canonical donor or acceptor splice site mutations were also investigated using this splicing assay and transcripts assessed from tumour tissue. Splice site mutations were shown to lead to either exon skipping or retention of intronic sequences through the use of cryptic splice sites comprised of non-classical splicing signals. Aberrant splicing caused by disruption of ESE sites does not appear to have a major role in HRPT2-associated disease; however, premature truncation of parafibromin as the result of canonical donor or acceptor splice site mutations is associated with pathogenicity. Functional splicing assays must be undertaken in order to confirm web-based software predictions of the modification of putative ESE sites by disease-associated mutations.
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Gitschier, J., S. Kogan, B. Levinson, and EG Tuddenham. "Mutations of factor VIII cleavage sites in hemophilia A." Blood 72, no. 3 (1988): 1022–28. http://dx.doi.org/10.1182/blood.v72.3.1022.1022.

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Abstract Hemophilia A is caused by a defect in coagulation factor VIII, a protein that undergoes extensive proteolysis during its activation and inactivation. To determine whether some cases of hemophilia are caused by mutations in important cleavage sites, we screened patient DNA samples for mutations in these sites by a two-step process. Regions of interest were amplified from genomic DNA by repeated rounds of primer- directed DNA synthesis. The amplified DNAs were then screened for mutations by discriminant hybridization using oligonucleotide probes. Two cleavage site mutations were found in a survey of 215 patients. A nonsense mutation in the activated protein C cleavage site at amino acid 336 was discovered in a patient with severe hemophilia. In another severely affected patient, a mis-sense mutation results in a substitution of cysteine for arginine in the thrombin activation site at amino acid 1689. This defect is associated with no detectable factor VIII activity, but with normal levels of factor VIII antigen. The severe hemophilia in this patient was sporadic; analysis of the mother suggested that the mutation originated in her gametes or during her embryogenesis. The results demonstrate that this approach can be used to identify factor VIII gene mutations in regions of the molecule known to be important for function.
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Gitschier, J., S. Kogan, B. Levinson, and EG Tuddenham. "Mutations of factor VIII cleavage sites in hemophilia A." Blood 72, no. 3 (1988): 1022–28. http://dx.doi.org/10.1182/blood.v72.3.1022.bloodjournal7231022.

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Hemophilia A is caused by a defect in coagulation factor VIII, a protein that undergoes extensive proteolysis during its activation and inactivation. To determine whether some cases of hemophilia are caused by mutations in important cleavage sites, we screened patient DNA samples for mutations in these sites by a two-step process. Regions of interest were amplified from genomic DNA by repeated rounds of primer- directed DNA synthesis. The amplified DNAs were then screened for mutations by discriminant hybridization using oligonucleotide probes. Two cleavage site mutations were found in a survey of 215 patients. A nonsense mutation in the activated protein C cleavage site at amino acid 336 was discovered in a patient with severe hemophilia. In another severely affected patient, a mis-sense mutation results in a substitution of cysteine for arginine in the thrombin activation site at amino acid 1689. This defect is associated with no detectable factor VIII activity, but with normal levels of factor VIII antigen. The severe hemophilia in this patient was sporadic; analysis of the mother suggested that the mutation originated in her gametes or during her embryogenesis. The results demonstrate that this approach can be used to identify factor VIII gene mutations in regions of the molecule known to be important for function.
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Ducommun, B., P. Brambilla, and G. Draetta. "Mutations at sites involved in Suc1 binding inactivate Cdc2." Molecular and Cellular Biology 11, no. 12 (1991): 6177–84. http://dx.doi.org/10.1128/mcb.11.12.6177.

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suc1+ encodes an essential cell cycle regulator of the fission yeast Schizosaccharomyces pombe. Its product, a 13-kDa protein, interacts with the Cdc2 protein kinase. Both positive and negative effects on cell cycle progression have been attributed to Suc1. To date, the exact mechanisms and the physiological role of the interaction between Suc1 and Cdc2 remain unclear. Here we have studied the molecular basis of this association. We show that Cdc2 can bind Suc1 or its mammalian homolog directly in the absence of any additional protein component. Using an alanine scanning mutagenesis method, we analyzed the interaction between Cdc2 and Suc1. We show that the integrity of several domains on the Cdc2 protein, including sites directly involved in catalytic activity, is required for binding to Suc1. Furthermore, Cdc2 mutant proteins unable to bind Suc1 (but able to bind cyclins) are nonfunctional when overexpressed in S. pombe, indicating that a specific interaction with Suc1 is required for Cdc2 function.
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Dissertations / Theses on the topic "Mutations de sites de clivage"

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Quercia, Romina. "Déterminants moléculaires de l'évolution de la résistance du VIH aux inhibiteurs de protéase et aux inhibiteurs d'intégrase." Paris 6, 2009. http://www.theses.fr/2009PA066606.

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La résistance du VIH, liée à des mutations dans la protéase entraine des défauts réplicatifs, conséquence du clivage incomplet de Gag-Pol. En utilisant des clones proviraux porteurs de séquences Gag-Pol de patients en échec d’IP, nous avons a montré que les mutations dans Gag jouent un rôle direct dans la résistance et que les seules mutations de Gag qui sont capable d’exercer cet effet sont restreintes à la région NC-SP2-P6. La maturation de la protéine NC semble constituer une étape limitant tout autant pour la résistance que pour la fitness en l’absence d’inhibiteur. Les mutations de résistance au raltegravir, le seul INI utilisé en clinique, se divisent en deux filières évolutives principales dont les mutations initiales sont N155H et Q148R/H/K, les mutants Q148H/R/K produisent une résistance plus accentuée que celles N155H. Mais la filière N155H est progressivement remplacée par Q148R/H/K. Le projet a visé à comprendre pourquoi la résistance au raltégravir est initiée par N155H en dépit de son efficacité moindre sur la résistance. Une série de mutants de l’integrase on était testés phénotypiquement pour leur niveau de résistance et pour leur fitness. Nous avons comparé la fitness de ces virus en présence d’une gamme large de raltegravir, ce qui nous a permis d’évaluer l’avantage sélectif<br>Mutations in Gag strongly and directly contributed to PI resistance besides compensating for fitness loss. This effect was essentially carried by the C-terminal region of Gag (containing NC-SP2-p6). Mutations in the NC-SP2-p6 region can be dually selected as compensatory and as direct PI resistance mutations, with cleavage at NC-SP2-p6 site behaving as a rate-limiting step in PI resistance. These results establish a second and important pathway of HIV-1 resistance to protease inhibitors in patients failing antiretroviral treatment. Emergence of HIV-1 resistance to raltegravir, an integrase strand transfer inhibitor, follows 2 genetic pathways the N155H and the Q148HKR. Progressively, mutants of the N155H pathway are replaced by Q148HKR. Selective advantages curves revealed that among single mutants, N155H had the highest and the widest selective advantage profile. Despite higher resistance levels, Q148H displayed a lower and narrower selective advantage pattern. Among double mutants, the highest and widest selective advantage profile was seen G140S+Q148H. This findings likely explains why N155H can be selected early in the course of raltegravir resistance evolution in vivo but is later replaced by genotypes that include Q148HKR
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Carron, de la Carrière Laurence. "Interaction entre les protéines enzymatiques et structurales du VIH-1 au cours du développement de la résistance aux antirétroviraux." Paris 6, 2002. http://www.theses.fr/2002PA066067.

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Derisbourg, Maxime. "Identification et caractérisation fonctionnelle de nouveaux sites de clivage de la protéine Tau." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S027.

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Tau, pour Tubulin Associated Unit, est une protéine appartenant à la famille des protéinesassociées aux microtubules. La fonction la plus connue de cette protéine est celle derégulateur de la dynamique des microtubules, structure du cytosquelette assurant lamorphologie, le fonctionnement et l’intégrité neuronale. A côté de son rôle physiologique ausein des cellules neuronales, Tau joue un rôle déterminant dans un groupe de pathologiesneurodégénératives communément appelées Tauopathies dans lesquelles Tau est retrouvéesous forme agrégée et anormalement modifiée dans les neurones en dégénérescence. Dans lamaladie d’Alzheimer (MA), la Tauopathie la plus fréquente, l’agrégation des protéines Tauanormalement modifiées constitue une lésion histologique : la dégénérescence neurofibrillaire(DNF). L’évolution spatiotemporelle de la DNF est étroitement corrélée aux signes cliniques.Actuellement, les mécanismes qui conduisent à cette agrégation des protéines Tau et à la DNFne sont pas clairement établis.Une dérégulation des modifications post-traductionnelles (MPT) de Tau est l’un desmécanismes proposés pour expliquer l’agrégation de la protéine Tau et de la formation desDNF. Parmi les MPT, la troncation de la protéine Tau jouerait un rôle central dans l’étiologiede la MA. Les analyses des tissus cérébraux de patients atteints de la MA montrent laprésence de plusieurs fragments de troncation de Tau amino- et carboxy-terminaux.L’augmentation de la quantité de certaines de ces espèces tronquées de Tau, qui sontretrouvées dans les agrégats, est étroitement corrélée à la progression de la pathologie Tau et àla sévérité des symptômes. Néanmoins, à exception de quelques sites carboxy-terminaux defragments identifiés, la nature exacte des nombreux fragments de troncation mis en évidencedans le tissu cérébral humain, de même que leur(s) rôle(s) dans le(s) processuspathologique(s) ne sont pas encore établis.C’est dans ce contexte que se place ce travail de thèse dont le premier objectif a consisté àidentifier de nouveaux sites de clivages amino-terminaux de la protéine Tau qui sont, demanière générale, moins caractérisés que les sites carboxy-terminaux. Pour cela, nous avonsmis au point une approche protéomique en utilisant un modèle cellulaire, présentant desfragments de troncation de Tau, pour ensuite appliquer cette approche sur des tissus cérébrauxprovenant d’individus atteints de la maladie d’Alzheimer et d’individus sains. Grâce audéveloppement de cette approche protéomique, nous avons précisément identifié le premieracide aminé de vingt-quatre sites de clivage de la protéine Tau. Comme les extrémités aminoterminalesde ces fragments sont distribuées sur toute la séquence de Tau, chaque clivagepourrait entraîner des conséquences fonctionnelles différentes en fonction de la position dusite. Nous avons donc débuté des analyses fonctionnelles dans des lignées cellulaires encaractérisant les propriétés de quatre fragments de Tau. Nos résultats montrent, de manièresurprenante, que la perte d'une partie du domaine amino-terminal confère une capacitésupérieure à lier et stabiliser les microtubules, en comparaison à la protéine Tau entière,suggérant que le domaine amino-terminal de Tau jouerait un rôle dans la régulation de ladynamique microtubulaire. Des études supplémentaires basées sur nos nouveaux fragments detroncation devraient améliorer nos connaissances sur l'impact de la troncation de Tau sur sabiologie et sur les processus pathologiques de la MA<br>Tau, for Tubulin Associated Unit, is a microtubule-associated protein. Tau is primarilyinvolved in the regulation of microtubule stability and dynamics. Besides its physiological role in neurons, Tau is a central player in Alzheimer’s disease (AD) and related Tauopathies,where it is found as aggregates in degenerating neurons. One of the neuropathological hall marks of AD is the neurofibrillary degeneration (NFD), characterized by aggregated Tauproteins. Studies have shown that the progression of NFD in cortical brain areas is closelycorrelated to cognitive impairment in AD, supporting a central role for Tau in AD pathology.As of now, the mechanisms leading to NFD and its progression are far from being elucidated.A deregulation of post-translational modifications (PTM) of Tau protein could be amechanism that leads to Tau aggregation and NDF formation. Among PTM, Tau truncationcould have an etiological role in Tau pathology. Indeed, the analysis of AD brains bywestern blotting and epitope mapping suggests the occurrence of cleavage sites in both theN-terminal and C-terminal parts of Tau proteins. While several N- and C-terminally truncated Tau species are observed in AD brains, only a limited number of specific Taucleavage sites have been identified so far in situ. The species generated by these cleavagesare found in neurofibrillary tangles, and their occurrence is correlated with the severity ofthe disease. However, the exact nature of the truncated fragments identified in the braintissue, as well as their role in the pathological process are not yet established.This work takes place in this context whose primary goal is to precisely identify new Tau cleavage sites, especially those at the N-terminus, which are less well characterized than thoseat the C-terminus. For this, we developed a proteomics approach by using a cellular model that displays Tau fragments and we applied this approach to identify N-terminally truncatedTau species in the human brain, from individuals with Alzheimer's disease and healthy individuals. Twenty-four amino-terminal cleavages sites have been identified with thedevelopment of this proteomic approach. As the amino-terminal ends of these fragments aredistributed throughout the Tau sequence, each cleavage could lead to different functiona lconsequences depending on the position of the site. Thus, we started functional studies bycharacterizing the properties of four fragments of Tau in cell lines. Our results interestingly show that loss of the Tau N-terminal domain allows a stronger ability to bind and stabilize microtubules, suggesting that the Tau N-terminal domain could play a direct role in the regulation of microtubule stabilization. Future studies based on our new N-terminallytruncated-Tau species should improve our knowledge of the role of truncation in Tau biologyas well as in the AD pathological process
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BORDE, VALERIE. "Sites de clivage de la topoisomerase ii dans l'adn au cours du cycle cellulaire. Le modele de physarum polycephalum." Paris 6, 1996. http://www.theses.fr/1996PA066052.

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Par son action sur l'etat topologique de l'adn, la topoisomerase ii est impliquee dans de nombreuses etapes du cycle cellulaire. Nous avons choisi le plasmode de physarum polycephalum, dont le cycle cellulaire est naturellement synchrone, comme modele pour etudier les sites d'action de la topoisomerase ii au cours du cycle cellulaire. L'approche que nous avons utilisee fait appel a des agents antitumoraux qui bloquent in vivo la topoisomerase ii sur l'adn, prolongeant la duree de vie du complexe entre l'enzyme et l'adn clive. Les coupures double-brin ainsi produites sont alors detectees par la technique de southern blot et marquage terminal indirect. Nous avons tout d'abord cartographie les sites de la topoisomerase ii induits in vivo dans les minichromosomes d'adn ribosomique. Les sites de clivage sont intimement lies a la structure chromatinienne et sont principalement situes dans l'unite de transcription et dans la region des origines de replication. Le taux de clivage diminue considerablement lors de la differenciation de physarum en spherules, en parallele avec une baisse du taux de transcription des genes de physarum. Par contre, le clivage topoisomerase ii est plus intense pendant la mitose, alors que la transcription des genes ribosomiques est arretee. Ceci suggere un role secifique de la topoisomerase ii au moment de la mitose, pour la segregation des minichromosomes. Nous avons ensuite mis en evidence le clivage par la topoisomerase ii a grande echelle dans tout le genome de physarum. La cartographie des sites topoisomerase ii dans le gene codant pour l'histone h4, dont on connait le moment de replication et de transcription au cours du cycle cellulaire, a ete entreprise. Nous avons montre que les sites de clivage induits dans cette region ont un taux maximum au moment de la mitose et au tout debut de la phase s, suggerant que la topoisomerase ii agit dans cette region a des moments precis du cycle cellulaire relies au taux d'expression du gene et a sa replication
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Pancorbo, Bruno Marco. "FUNCTIONAL STUDIES OF FERRITIN 3-FOLD AXIS: EFFECTS OF MUTATIONS NEAR SUBUNIT INTERACTION SITES." NCSU, 2000. http://www.lib.ncsu.edu/theses/available/etd-20000228-182046.

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<p>Pancorbo, Bruno Marco. Functional studies of ferritin 3-fold axis: effects of mutations near subunit interaction sites. (Under the direction of Dr. E. C. Theil)Ferritin is an iron storage protein whose metabolic importance is reflected in its ubiquitousness in living organisms. Ferritin is a multi-subunit protein (24 subunits) and one of its most interesting features is its 3-dimensional structure: a sphere-like structure with a 4-3-2 symmetry that has a hollow interior where iron is stored. This 3-dimensional structure is highly conserved among ferritins of different living organisms even when the homology of the primary structure of the different ferritins is as low as 22%. Such a degree of structural conservation can only be interpreted as the result of a near perfect balanced between ferritin's structure and function. Among the highly conserved residues are arginine 72 and aspartate 122 which form a salt bridge near the 3-fold interface. To study the importance of these residues in ferritin function, site-directed mutagenesis was used to disrupt and rescue this salt bridge. The properties of the mutants were tested and compared with those of the parent proteins.The greatest difference between mutants and parent proteins was seen in the amount of iron each released. Mutants were found to release a greater percentage of their initial iron than the parents released. Some mutants also showed an increased rate of iron release over the parent proteins, but the effect of the mutation differed depending on the type of subunits used. Another finding was that disruption of the salt bridge caused some of the ferritin subunits to have an increase in volume which seems to correlate with the difference in iron uptake rates for the different ferritin mutants.<P>
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Eyengué, Aimé. "Associations en danger, Quartiers en danger : Mutations des relations entre l'Etat et les associations de quartier : à la lumière du clivage idéologique Gauche-Droite." Paris 8, 2012. http://octaviana.fr/document/177624973#?c=0&m=0&s=0&cv=0.

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Cette thèse doctorale analyse sociologiquement le mot « danger » brandi par des collectifs d’associations locales mobilisées en France pour réclamer des subventions publiques à l’Etat, avec leur mot d’alerte « Associations en danger, Quartiers en danger ». Cette mobilisation suggère une analyse sociolinguistique des problèmes sociaux liés à la problématique des quartiers et de la vie associative, à la lumière du clivage idéologique gauche-droite. Il nous a semblé pertinent, dans ce contexte, de prendre ce clivage comme grille de lecture et d’analyse pour déceler quelque instrumentalisations de ce mot « danger ». Partant, nous avons essayé d’analyser les mutations dans les rapports de partenariat Etat-Associations, dans le cadre de la politique de la ville. Cela en s’appuyant sur les stéréotypes, les stigmates, les préjugés et les représentations sociales ou idéologiques qui sous-tendent ses rapports. Parmi les réalités sociales observées dans ce contexte, il y a la logique de professionnalisation des associations de quartier, la logique des subventions publiques de la vie associative, les polémiques et les paradoxes autour de la question des « banlieues », des « quartiers » et du financement de la vie associative<br>This doctoral thesis analyze sociologically the word "danger" brandished by a collective of local associations mobilized in France to claim public grants to the State, with their word of warning "Associations in danger, neighbourhoods in danger". This mobilization suggests a sociolinguistic analysis of the social problems associated with the problematic of neighbourhoods and community life, on the left-right ideological divide. It seemed relevant, in this context, to take this cleavage as a grid of reading and analysis to detect any instrumentalisations of the word "danger". Therefore, we have tried to analyze the changes in partnership reports State-Associations, in the policy of the city. This by relying on stereotypes, stigma, prejudice and social or ideological representations that underlie its reports. Among the social realities observed in this context, there is the logic of professionalization of neighbourhood associations, the logic of public subsidies of associative life, the controversies and paradoxes on the question of the "suburbs", "neighbourhoods" and funding of community life
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Wright, Theodore G. "Point mutations of weak lysine binding sites in apolipoprotein(a), effects on Lp(a) assembly." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ55940.pdf.

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Clifton, Katherine M. "The effect on transcriptional activity of mutations that alter possible phosphorylation sites in Drosophila melanogaster ultraspiracle (USP)." Greensboro, N.C. : University of North Carolina at Greensboro, 2007. http://libres.uncg.edu/edocs/etd/1498Clifton/umi-uncg-1498.pdf.

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Thesis (M.S.)--University of North Carolina at Greensboro, 2007.<br>Title from PDF t.p. (viewed Mar. 3, 2008). Directed by Vincent C. Henrich; submitted to the Dept. of Biology. Includes bibliographical references (p. 43-46).
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Dassah, MaryAnn. "Identifying and characterizing suppressors of intronic +1 G mutations and cryptic 5' splice sites in Caenorhabditis elegans /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2008. http://uclibs.org/PID/11984.

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BRAKCH, NOUREDDINE. "Maturation proteolytique post-traductionnelle de precurseurs d'hormones peptidiques : importance fonctionnelle de la structure en beta-turn et de certains residus au voisinage des sites de clivage." Paris 6, 1992. http://www.theses.fr/1992PA066069.

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La maturation proteolytique selective de pro-proteines retrovirales et des precurseurs de peptides et de recepteurs hormonaux au niveau de sites constitues par des residus d'acides amines basiques met en jeu des mecanismes enzymatiques encore peu etudies a ce jour. Nous avons choisi pour etudier in vitro les parametres de l'action enzymatique d'une endoprotease de conversion (appelee pro-ocytocine-neurophysine) une serie de 60 peptides reproduisant ou mimant la sequence de la proforme au voisinage du doublet de clivage (lys-arg). Les resultats nous permettent de deduire que: 1) l'integrite du doublet basique est necessaire; 2) la reactivite des paires de doublets depend de la nature de celui-ci et de ses interactions avec les sequences adjacentes; 3) le doublet basique est localise au voisinage d'une structure en beta-turn; 4) cette structure joue un role fonctionnel dans la maturation proteolytique; 5) l'exposition du doublet basique est primordiale; 6) l'acide amine en aval (p1) du doublet basique presente des caracteristiques correspondant a l'image d'un sous site enzymatique (s1). Par ailleurs, nous avons developpe une approche cellulaire qui a consiste a analyser la maturation de la pro-somatostatine native, ou apres mutagenese selective sur certains residus, ou segments, de la proforme dans des cellules de neuroblastome (neuro 2a). Celle-ci nous a permis de demontrer que les residus proline en plus de leur participation a une structure en beta-turns, grace a leur emplacement en des positions cle de la region pro du precurseur jouent un role primordial dans le maintien de l'architecture des sites de reconnaissance (un monobasique, arg et un dibasique arg-lys) par les enzymes de maturation. Les resultats de ces etudes fournissent un ensemble de donnees nous permettant d'envisager la modelisation, et la synthese, d'un inhibiteur specifique de la pro-ocytocine/neurophysine convertase en particulier, ou des convertases, en general, qui constituerait un outil pour completer l'etude de cette endoprotease et permettre peut-etre des applications therapeutiques importantes dans le domaine des pathologies mettant en uvre des dereglements neurohormonaux
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Books on the topic "Mutations de sites de clivage"

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Walsh, Bruce, and Michael Lynch. The Genetic Effective Size of a Population. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198830870.003.0003.

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The effects of genetic drift usually assume an idealized population of constant size. This chapter shows how the population size for such an idealized population can be replaced with an effective population size for populations with age structure, unequal sex ratios, a history of expansion or contraction, inbreeding, and population subdivision. These demographic features impact the entire genome more or less equally. A relatively recent understanding is that selection at a site can dramatically reduce the local effective population size experienced by nearby linked sites (the Hill-Robertson effect). This can arise from background selection to remove deleterious new mutations or from selective sweeps wherein favorable new mutations are driven toward fixation. The Hill-Robertson effect is a general way to describe the fact that selection at a site makes selection are other linked sites less efficient, and, therefore, more neutral. This chapter discusses the implications of this finding for genome structure.
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Walsh, Bruce, and Michael Lynch. Hitchhiking and Selective Sweeps. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198830870.003.0008.

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When a favorable allele increases in frequency, it alters the coalescent structure (the pattern of times back to a common ancestor) at linked sites relative to that under drift. This creates patterns of sequence polymorphism than can be used to potentially detect ongoing, or very recent, selection. This idea of a neutral allele hitchhiking up to high frequency when coupled to a favorable allele is the notion of a selective sweep, and this chapter reviews the considerable body of associated population-genetics theory on sweeps. Different types of sweeps leave different signatures, resulting in the very diverse collection of tests of selection discussed in Chapter 9. Either a history of recurrent sweeps, or of background selection, results in linked genomic regions of reduced effective population size. This implies that more mutations in sich regions are efficiently neutral, which can result in increased substitution rates and lower codon bias. Finally, the chapter examines the theory for when response is expected to start from existing variation, as opposed to waiting for the appearance of new mutations.
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Cassidy, Jim, Donald Bissett, Roy A. J. Spence OBE, Miranda Payne, Gareth Morris-Stiff, and Madhumita Bhattacharyya. Breast cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199689842.003.0014_update_001.

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Thoracic cancer examines the epidemiology, aetiology, and role of screening and prevention in the reduction of deaths from lung cancer, the majority caused by cigarette smoking. The pathology and genetics of lung cancer, with particular note of the driver mutations, are followed by the symptoms and signs of the disease. Appropriate investigations are described to stage the tumour. The optimum treatment for localised non-small cell lung cancer (NSCLC) is surgical resection, followed in some cases by adjuvant chemotherapy. However, most cases present with disease too advanced for surgery, and for these chemotherapy and radiotherapy are appropriate. Metastatic NSCLC can be treated with platinum based doublet chemotherapy with modest palliative benefits. Metastatic NSCLC with specific driver mutations are amenable to control by targeted therapy. Locally advanced NSCLC is often treated with similar chemotherapy and radiotherapy, ideally administered concurrently, to achieve symptom relief but also improved survival rates. Short course simple radiotherapy offers symptom relief in patients not fit for chemotherapy. Patients with localised NSCLC who are not fit for surgery, may benefit from radical radiotherapy, particularly stereotactic radiotherapy. Small cell lung cancer (SCLC) is characterised by almost universal systemic spread, so that surgery is rarely appropriate. Staging is similar to NSCLC, and chemotherapy is the mainstay of treatment, usually cisplatin or carboplatin combined with etoposide. When possible, this is combined with concurrent thoracic irradiation covering all radiological sites of disease. Prophylactic cranial irradiation reduces the risk of CNS disease. Malignant pleural mesothelioma is caused by occupational asbestos exposure. Symptoms and signs, investigation and staging, and management are discussed. Thymic tumours, their pathology, presenting symptoms including paraneoplastic syndromes, investigation, staging and treatment are reviewed.
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Matthew Kynes, J. Hemophilia (Presentation in Emergency Surgery). Edited by Matthew D. McEvoy and Cory M. Furse. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190226459.003.0085.

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Hemophilia is a complex disease of variable severity that affects clotting function and has significant implications in perioperative and emergency care. Hereditary or de novo mutations cause deficiencies in factor VIII or IX production, which may manifest as spontaneous bleeding into joint spaces, muscles, or other sites in severe forms of the disease. Intracranial bleeding is one of the most serious and often fatal complications. In a patient with abnormal bleeding, laboratory results indicative of hemophilia include an increased partial prothromboplastin time (PT), with normal prothrombin time/international normalized ratio (PTT/INR) and normal platelet count. The diagnosis is confirmed with specific factor assays. Advances in prophylaxis with factor replacement have improved outcomes and reduced bleeding episodes in hemophilia. However, patients with hemophilia may present emergently for operation and require factor replacement. In patients that have developed antibodies to factor replacement, clotting factor bypass agents may be required to control bleeding.
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Book chapters on the topic "Mutations de sites de clivage"

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Cosic, Irena. "Prediction of Functionally Active Sites and Functional Mutations." In The Resonant Recognition Model of Macromolecular Bioactivity. Birkhäuser Basel, 1997. http://dx.doi.org/10.1007/978-3-0348-7475-5_6.

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"Materialist Mutations of the Bilderverbot." In Sites of Vision. The MIT Press, 1999. http://dx.doi.org/10.7551/mitpress/6253.003.0012.

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Forman, Stuart A. "Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated Ion Channels." In Methods in Enzymology. Elsevier, 2018. http://dx.doi.org/10.1016/bs.mie.2018.01.014.

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Eden, Tim. "Acute lymphoblastic leukaemia." In Oxford Textbook of Medicine. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.220303.

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Genetic changes in key progenitor cells in acute lymphoblastic leukaemia (ALL) are typically either point mutations or (more frequently) translocation of proto-oncogenes to active promoter sites, with such genetic rearrangements leading to aberrant protein production. In most childhood disease the first genetic events arise in utero...
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Lucchesi, John C. "Aging, cellular senescence and cancer: epigenetic alterations and nuclear remodeling." In Epigenetics, Nuclear Organization & Gene Function. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198831204.003.0021.

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Epigenetic modifications correlated with aging and oncogenesis are changes in the pattern of DNA methylation and of histone modifications, and changes in the level of histone variants (H3.3, macroH2A, H2A.Z) and gene mutations. The sirtuins are a set of highly conserved protein deacetylases of particular significance to the aging process. Many cancer types are found to carry mutations in chromatin-modifying genes such as those encoding methyl or acetyl transferases, affecting the histone modifications of promoters and enhancers. The aging process and oncogenesis present a number of changes in the nuclear architecture. Mutations in the lamina-coding genes lead to premature aging syndromes. Mutations in remodeling complexes are found in different cancers. Modifications that affect the architectural protein binding sites at topologically associating domain (TAD) borders can cause the merging of neighboring TADs. The levels of short non-coding RNAs (sncRNAs) are altered in model organisms and are associated with cancer. Changes in the position of chromosome territories often occur in tumor cells. Nevertheless, cellular senescence, due mostly to the absence of telomerase, represents a mechanism of tumor suppression.
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Prokaeva, T., G. Doros, D. Seldin, et al. "Somatic Mutations Create Potential N-Glycosylation Sites in the Immunoglobulin Light Chain Variable Regions in Primary Amyloidosis." In XIth International Symposium on Amyloidosis. CRC Press, 2007. http://dx.doi.org/10.1201/9781420043358.ch98.

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Cutter, Asher D. "The origins of molecular diversity." In A Primer of Molecular Population Genetics. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198838944.003.0002.

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At its simplest, evolution is change in the relative abundance of alternative alleles, from one generation to the next. But where do these different alleles come from? As the ultimate origin of all genetic novelty, the input of new mutations into a population forms the critical first step for incorporating biological detail into how we conceive of genome evolution. Chapter 2, “The origins of molecular diversity,” summarizes the many mechanisms of mutation, the distribution of fitness effects, and how to characterize mutational processes themselves in conceptual models. It covers point mutations, indels, microsatellites, transposable elements, and other mutation types in the context of the genetic code and gene duplication, as well as the role of mutation accumulation experiments in understanding mutation rates and fitness effects. The infinite alleles, infinite sites, and stepwise mutation models are summarized, along with the concept of homoplasy and complexities to the mutation process in nature. These important extra pieces of biological realism connect more closely the mechanisms of evolution to show the path toward a deeper analysis of genomes.
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"Sodium Bisulfite Conversion of Human Genome for DNA Methylation Studies." In Protocols used in Molecular Biology, edited by Aastha Mishra and Qadar Pasha. BENTHAM SCIENCE PUBLISHERS, 2020. http://dx.doi.org/10.2174/9789811439315120010012.

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The regulation of transcription and translation of a gene under a given environment is dependent on several factors and epigenetics is one such factor, responsible for the differential expression of several genes in health and in various diseases. DNA methylation, an important epigenetics mechanism has been shown to play a vital role in numerous cellular processes, and the abnormal patterns of methylation have been linked to the number of human diseases. CpG islands, a short stretch of DNA enriched with CpG sites in the 5’ end of a gene, although remains unmethylated but tends to methylate aberrantly upon certain environmental exposures. The methylation of the promoter region bearing transcriptional start sites of those genes that encodes tumor suppressors such as tumor protein p53, retinoblastoma-associated protein 1, tumor protein p16, breast cancer 1 and many more result in the reduced expression of these genes and have been implicated in a large number of cancers like retinoblastoma, colon, lung and ovarian. A growing number of human diseases have been found to be associated with the aberrant DNA methylation. Hence, a deep insight into the individual’s epigenetic profile is the need of the hour. Several approaches have been developed to map DNA methylation patterns genome-wide. Some of these approaches include enzymatic digestion with methylation-sensitive restriction enzymes, the capture of 5-mC by methylated DNA-binding proteins followed by nextgeneration sequencing and methyl-DNA immunoprecipitation followed by sequencing of precipitated fragments. However, this chapter is going to describe the most recommended method for studying DNA methylation pattern, the method based on bisulfite sequencing. The bisulfite treatment of DNA converts unmethylated cytosine(s) to uracil(s), which are subsequently amplified as Ts by PCR. Hence, the bisulfitetreated DNA has mutations specifically at unmethylated Cs that can be mapped by Next-Generation sequencing.
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Mackenzie, Isla S., and Morris J. Brown. "Phaeochromocytomas, paragangliomas, and neuroblastoma." In Oxford Textbook of Endocrinology and Diabetes. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235292.003.0554.

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Phaeochromocytomas are rare neuroendocrine tumours of neural crest origin, which often produce excess catecholamines (1). Although usually arising from the chromaffin cells of the adrenal medulla, phaeochromocytomas may also arise at other sites of sympathetic or parasympathetic chromaffin tissue anywhere from the base of the skull to the pelvis. Extra-adrenal phaeochromocytomas are called paragangliomas. Some patients with phaeochromocytoma or paraganglioma present with the classical triad of symptoms of headaches, palpitations, and sweating but many others present with less specific features such as hypertension or with an unidentified mass lesion. Owing to the rarity of the condition and the relatively nonspecific symptoms with which it often presents, it is not unusual for several years to pass from symptom onset until the diagnosis of phaeochromocytoma is made. However, the consequences of not finding a phaeochromocytoma can be severe and may even result in death. In fact, in one study, around 50% of cases of phaeochromocytoma found at post mortem were unsuspected during life. Interestingly, a former US President, Dwight Eisenhower, was found to have a 1.5 cm adrenal phaeochromocytoma at post mortem, which was undiagnosed during life despite a history of severe hypertension and headaches (2). Patients with untreated phaeochromocytoma are at risk of the cardiovascular consequences of catecholamine surges, including hypertensive emergencies, intracerebral haemorrhage, and acute heart failure. Approximately 10% of phaeochromocytomas are malignant and some represent part of familial syndromes. The genetic basis of many phaeochromocytomas is becoming increasingly apparent as more mutations are found.
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Hatton, Chris. "Histiocytosis." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0521.

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The histiocytoses are disorders derived from the dendritic cell and monocyte/macrophage lineages, with the classification of this group of disorders relating to the underlying cell of origin. Dendritic cell disorders—there has been much debate about the nature of these conditions, and their status as neoplastic or primary inflammatory diseases; for Langerhans’ cell histiocytosis in particular, there is increasing evidence of their clonal nature, as manifest by recurrent BRAF mutations. Clinical features and diagnosis—these are highly variable and dependent on the sites affected by histiocytic infiltration. Symptoms and signs may include rashes, bony pain, lymphadenopathy, hepatomegaly and splenomegaly, cough and dyspnoea, features of marrow failure, and endocrine presentations (classically diabetes insipidus). Diagnosis typically follows imaging and biopsy, with the demonstration of a histiocytic infiltrate confirmed by immunostaining. Treatment and prognosis—the rarity and heterogeneity of these diseases has made it difficult to achieve a consensus on treatment. For localized disease, curettage, steroid injections, or targeted radiotherapy may be helpful. For more systemic disease, combination chemotherapy is typically used. Treatment schedules differ between adults and children. Prognosis is dependent mainly on the site(s) of involvement. Our expanding appreciation of the molecular basis of these conditions also provides some justification for the use of BRAF inhibitors and other targeted small molecule therapies. Macrophage-related disorders—these include haemophagocytic lymphohistiocytosis, a collection of macrophage-activating syndromes which may be either reactive to underlying inflammatory, infective, or neoplastic disease, or consequent upon a primary genetic lesion affecting cytotoxic T-cell killing function. Rosai–Dorfman disease is a separate macrophage proliferation syndrome, thought to be non-neoplastic, which causes massive cervical lymphadenopathy, usually in children.
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Conference papers on the topic "Mutations de sites de clivage"

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Palmisano, Alida, Suleyman Vural, Yingdong Zhao, and Dmitriy Sonkin. "Abstract 2480: MutSpliceDB: A database of splice sites mutations effects." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-2480.

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Palmisano, Alida, Suleyman Vural, Yingdong Zhao, and Dmitriy Sonkin. "Abstract 2480: MutSpliceDB: A database of splice sites mutations effects." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-2480.

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Bu, Rong, Abdul K. Siraj, Kaleem Iqbal, et al. "Abstract 1577: Telomerase reverse transcriptase (TERT) promoter mutations in cancers derived from multiple organ sites among Middle Eastern population." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-1577.

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Bu, Rong, Abdul K. Siraj, Kaleem Iqbal, et al. "Abstract 1577: Telomerase reverse transcriptase (TERT) promoter mutations in cancers derived from multiple organ sites among Middle Eastern population." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-1577.

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Cai, Wen, Dehao Wu, Li dong Wang, Shu Zheng, Hanguang Hu, and Weiting Ge. "IDDF2020-ABS-0026 Ultra-mutated patients with POLE or POLD1 mutations exhibits distinct pattern between races and primary sites in colorectal cancer (CRC)." In Abstracts of the International Digestive Disease Forum (IDDF), 22–23 November 2020, Hong Kong. BMJ Publishing Group Ltd and British Society of Gastroenterology, 2020. http://dx.doi.org/10.1136/gutjnl-2020-iddf.47.

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Rodrik-Outmezguine, Vanessa S., Zhan Yao, Radha Mukherjee, et al. "Abstract 1726: Acquired resistance to rapamycin and mTOR kinase inhibitors is mediated by non-overlapping mutations in distinct sites in the mTOR protein." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-1726.

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Rodrik-Outmezguine, V., Z. Yao, M. Berger, et al. "Abstract PD1-8: Acquired resistance to rapamycin and mTOR kinase inhibitors is mediated by non-overlapping mutations in distinct sites in the mTOR protein." In Abstracts: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium - Dec 10-14, 2013; San Antonio, TX. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/0008-5472.sabcs13-pd1-8.

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Geng, C., S. Li, S. Yang, et al. "Abstract P3-01-18:In vivoisolation of circulating tumour cells using CellCollector and detection of gene mutations in different metastasis organ sites in breast cancer." In Abstracts: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-p3-01-18.

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Kono, M., T. Fujii, N. Matsuda, et al. "Abstract P1-16-04: Somatic mutations, clinicopathologic characteristics, and survival in patients with untreated breast cancer with bone-only and non-bone sites of first metastasis." In Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, Texas. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.sabcs17-p1-16-04.

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Pittman, Debra D., Louise C. Wasley, Beth L. Murray, Jack H. Wang, and Randal J. Kaufman. "ANALYSIS OF STRUCTURAL REQUIREMENTS FOR FACTOR VIII FUNCTION USING SITE-DIRECTED MUTAGENESIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644044.

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Factor VIII (fVIII) functions in the intrinsic pathway of coagulation as the cofactor for Factor IXa proteolytic activation of Factor X. fVIII contains multiple sites which are susceptible to cleavage by thrombin, Factor Xa, and activate) protein C. Proteolytic cleavage is required for cofactor activity and may be responsible for inactivation of cofactor activity. In order to identify the role ofthe individual cleavages of fVIII in its activation and inactivation, site-directed DNA mediated mutagenesis of fVIII was performed and the altered forms of fVIII produced and characterized. Conversionof Arg residues to lie residues at amino acid positions 740, 1648, and 1721 resulted in resistance to thrombin cleavage at those siteswith no alteration of in vitro procoagulant activity. Modification of the thrombin cleavage sites at either positions 372 or 1689 resulted in loss of cofactor activity suggesting that these sites are important for activation. Modification of the postulated activated protein C cleavage site at position 336 resulted in fVIII with a higher specific activity than wild type, possibly due to resistance toproteolytic inactivation.DNA mediated mutagenesis was also used to study the role of post-translational biosynthetic modifications of fVIII. Structural characterization of recombinant fVIII suggested the presence of sulfated tyrosine residues within two acidic regions located between amino acid residues 336-372 and 1648-1689. Individual modification of theseTyr residues to Phe had negligible effect on synthesis and in vitrocofactor activity. The effect of combinations of these mutations onsecretion, cofactor activity, and vWF interaction will be presented.
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