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1
ESPOSITO, ALESSANDRA. "DIVERSITY IN MTORC1 SUBSTRATE RECRUITMENT ENABLES SPECIFICITY OF METABOLIC RESPONSES TO NUTRITIONAL CUES." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/793428.
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The mechanistic target of rapamycin kinase complex 1 (mTORC1) is a key signaling hub that acts as a central regulator of several cellular processes, including cell growth and metabolism. The activation of mTORC1 occurs at the lysosomal surface via a two-step mechanism that requires a) its amino acid-dependent recruitment to the lysosome via the Rag GTPases and b) its growth factor-dependent activation by Rheb.
mTORC1 senses and integrates multiple upstream signals to phosphorylate a broad number of substrates and modulate the crucial balance between cell anabolism and catabolism. However, whether mTORC1 can differentially regulate specific proteins to selectively respond to such a variety of intracellular and environmental cues is poorly understood.
Here we show that Transcription Factor EB (TFEB), a master modulator of lysosomal biogenesis and autophagy, is modulated by mTORC1 via a specific substrate recruitment mechanism that is mediated by Rag GTPases. Differently from the well-characterized mTORC1 substrates S6K and 4E-BP1, which are recruited by mTORC1 via binding to the regulatory subunit Raptor, TFEB interaction with mTORC1 relies on its physical association with active Rag C/D. Owing to this mechanism, TFEB phosphorylation is insensitive to growth factor-mediated activation of Rheb but highly sensitive to amino acid-mediated activation of Rag GTPases. Strikingly, substituting the region of TFEB responsible for its recruitment to mTORC1 with the one of S6K, inverted TFEB phosphorylation behaviour and made it similar to S6K/4E-BP1.
Thus, our findings reveal that diversity in mTORC1 substrate recruitment mechanisms enables mTORC1 to induce selective responses to specific nutritional cues.
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Lalk, Michael [Verfasser]. "Tumorregionen-abhängige Expression der Aminosäure-Sensoren MAP4K3, RagC und VPS34 in Glioblastomen / Michael Lalk." Magdeburg : Universitätsbibliothek, 2018. http://d-nb.info/1174626593/34.
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Zarrin, Ali Akbar. "Characterization of the human recombination activating gene 1 (RAG1) and RAG2 promoter regions." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0024/NQ49915.pdf.
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Zheng, Xiuzhong. "Definition of Ku-interacting domains in RAG1 and RAG2 proteins in V(D)J recombination." Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/27102.
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V(D)J recombination is a process that generates the diversity of the immune repertoire against foreign antigens. During B and T cell development, genes encoding immunoglobulins (Ig) and T cell receptors (TCR) variable region are somatically assembled by selective V (variable), D (diversity) and J (joining) segments pre-existing in the germline. Recombination-activating genes 1 and 2 (RAG1/RAG2), the lymphocyte-specific factors, initiate V(D)J recombination by nicking at the border the heptamer sequence of RSS (recombination signal sequence) and generate four DNA double stranded breaks (DSB) in the cleavage step. After cleavage, RAG1/RAG2 complex are still bound to the DNA ends. In the joining step, DNA breaks are processed and rejoined by non-homologous end joining apparatus, which includes Ku70/Ku80, DNA-PKcs, Artemis, XRCC4 and DNA ligase IV. However, how the cleavage step is linked to the joining step is not yet known.
My results suggest that a physical interaction between RAG1/2 and Ku antigen may help coordinate the cleavage stage of V(D)J with the non homologous DNA end rejoining of the mature sequences. (Abstract shortened by UMI.)
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Corneo, Barbara. "Physiopathologie de la recombinaison v(d)j : structure et fonction des proteines rag1 et rag2." Paris 5, 2001. http://www.theses.fr/2001PA05N025.
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Cayuela, Jean-Michel. "La recombinaison V-(D)-J : étude de l'expression des gènes RAG1 et RAG2 dans les cellules lymphoi͏̈des malignes humaines." Paris 5, 1991. http://www.theses.fr/1991PA05P177.
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PRETRE, PHILIPPE. "Rage et voyages." Besançon, 1991. http://www.theses.fr/1991BESA3052.
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Mengual, Nathalie. "Epidémiologie et prophylaxie de la rage en Afrique : stratégies de lutte." Paris 5, 1989. http://www.theses.fr/1989PA05P192.
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Tanner, Anne. "Human Herpesvirus 6A Infection and Immunopathogenesis in Humanized Rag2-/-γc-/- Mice and Relevance to HIV/AIDS and Autoimmunity." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6078.
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Human herpesvirus 6A (HHV-6A) has yet to be definitively linked to a specific disease. This is due in part to the ubiquitous nature of the virus. Humanized Rag2-/-γc-/- (Rag-hu) mice were tested to determine if these were a suitable animal model to study the virus. Both cell-free and cell-associated virus was used for infection and both were found to be efficient at infecting the mice. Viral DNA was found in the plasma and cellular blood fractions, bone marrow, lymph node, and thymus, indicating successful infection and propagation of the virus in vivo. The CD3+CD4- population was depleted, while the CD3-CD4+ was increased in infected animals. The CD3-CD4+CD8- and CD3+CD4+CD8- populations were depleted and the CD3+CD4+CD8+ population increased when analysis was gated upon CD4+ cells. The CD3-CD4+CD8+ population expanded and the CD3-CD4+CD8- population was reduced when analysis was gated on the CD3- population. Additional flow cytometry analysis revealed increases in CD4+CD8+ double positive cells in the peripheral blood of cell-free infected mice, which could indicate improper T cell selection and a premature departure of these cells from the thymus, possibly contributing to autoimmunity. Previous research has shown that HIV and HHV-6A may have a synergistic effect on one another and that HHV-6A may act as a cofactor in the progression to AIDS. After determining the Rag-hu mouse model was suitable for studying HHV-6A infection, a coinfection of HHV-6A and HIV-1 was performed. Coinfected mice had fewer thymocytes when compared with the HIV-1 only, mock-infected, and to a lesser extent HHV-6A only groups which could indicate increased cell death in the coinfected group as well as possible disruptions in migration of cells, either causing cells to be sequestered in the bone marrow and unable to migrate to the thymus, or causing premature egress of the cells in the thymus due in part to premature upregulation of CCR7, both of which would explain the smaller cellular populations found in the coinfected mouse thymi. Additional studies were performed to determine if a preferential targeting existed between HHV-6A and HIV-1 as these viruses are found simultaneously coinfecting the same cell. Preferential targeting was not observed by cell-associated migration assay, but increased migration of HHV-6A-infected cells was observed in a CCL21 dependent manner. These studies have provided useful information about HHV-6A and its relevance to HIV/AIDS as well as a possible mechanism of the involvement of HHV-6A in multiple sclerosis (MS) and other autoimmune diseases.
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Herwig, Nadine. "Der RAGE-Ligand S100A4." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-214035.
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Das maligne Melanom zählt zu den aggressivsten und behandlungsresistentesten aller Krebsarten. In den letzten 20 Jahren hat sich die Rate der Melanom-Erkrankungen innerhalb der weißen Bevölkerung verdreifacht.
Mittlerweile liegen eine Reihe von Untersuchungen zu den molekularbiologischen Mechanismen der Entwicklung und Progression des malignen Melanoms vor. Aktuelle Forschungsvorhaben beschäftigen sich vor allem mit der Identifizierung Melanom-spezifischer Biomarker, die diagnostische und prognostische Informationen liefern sowie die Entwicklung einer zielgerichteten, kombinierten und individualisierten Therapie des metastasierenden Melanoms ermöglichen. In diesem Kontext soll die vorliegende Arbeit einen weiteren Beitrag zum Verständnis der Metastasierungskaskade und der daran beteiligten Proteine leisten.
Aufgrund der Überexpression in einer Reihe von Tumoren und seiner geringen Molmasse von lediglich 11,5 kDa bietet sich das S100A4-Protein als Marker mit hoher prognostischer Signifikanz für verschiedene Tumorentitäten an. Jedoch ist die Beteiligung von S100A4 bei der Ausbildung des invasiven Tumorphänotyps noch nicht vollständig aufgeklärt. S100A4 besitzt zahlreiche intra- und extrazelluläre Bindungspartner, wobei die Metastasierung scheinbar ausschließlich durch das extrazelluläre Protein beeinflusst wird. S100A4 wechselwirkt extrazellulär beispielsweise mit dem Rezeptor für fortgeschrittene Glykierungsendprodukte (RAGE). Ziel dieser Arbeit war es, speziell die Bedeutung von S100A4 und seiner Interaktion mit RAGE für das prometastatische Verhalten von Melanomzellen in vitro und in vivo näher zu charakterisieren. Darüber hinaus sollte die Beteiligung von S100A4 bei der Gehirn-Metastasierung untersucht werden, wobei insbesondere die Regulierung der Endothelzell-Permeabilität und der transendothelialen Migration der Melanomzellen im Vordergrund stand.
Im Rahmen dieser Arbeit wurde gezeigt, dass S100A4 und die Interaktion mit RAGE die prometastatischen Eigenschaften der A375-Melanomzellen förderte. Zudem verringerte extrazelluläres S100A4 die Zell-Integrität von Gehirn-Endothelzellen und erleichterte somit die Durchdringung der Blut-Hirn-Schranke. Diese Erkenntnis lässt sich möglicherweise auf andere Blut-Gewebe-Schranken übertragen. Die In-vivo-Orientierungsstudie zeigte, dass S100A4- und RAGE-überexprimierende Zellen zu einer verstärkten disseminierten Metastasierung führten, wobei sich zwei unterschiedliche Verteilungsmuster ergaben. Darüber hinaus führten beide Zelllinien vereinzelt zur Bildung von Gehirnmetastasen, wodurch sich die intrakardiale Injektion durchaus als Modell für weitere Therapiestudien mit dem Augenmerk der S100A4-RAGE-stimulierten Metastasierung eignet. Die genauere Kenntnis regulativer Mechanismen bei der Synthese und Sekretion von S100A4 sowie die pathophysiologische Differenzierung der S100A4-Interaktion mit RAGE eröffnen neue Wege, die S100A4-vermittelten Effekte therapeutisch zu beeinflussen. Daraus lassen sich möglicherweise neue zielgerichtete Radionuklid-basierte Therapieansätze für das metastasierende Melanom ableiten.
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LO, LINE MEI FRANCOIS. "La rage en afrique." Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX20044.
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Fersing, Elisabeth. "La rage, maladie professionnelle." Université Louis Pasteur (Strasbourg) (1971-2008), 1985. http://www.theses.fr/1985STR1M203.
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Williamson, David. "The Iron Rage Plus One." Honors in the Major Thesis, University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/742.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucfBachelors
Arts and Sciences
English; Creative Writing
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Lefebvre, Francis. "Étude de la dynamique de population du raton laveur (Procyon lotor) dans le Parc du Mont-Orford dans le but d'éviter l'entrée de la rage." Sherbrooke : Université de Sherbrooke, 1999.
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HAMDAN, MOUNIR. "Vaccinations antirabiques et bilan d'activite du centre antirabique d'angers, de 1981 a 1987." Angers, 1988. http://www.theses.fr/1988ANGE1041.
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Ward, Khedr. "La rage en Languedoc : analyse et réalités en 1998." Montpellier 1, 2000. http://www.theses.fr/2000MON11004.
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QUENTIN, JANE-MICHELE. "Histoire de la rage avant pasteur." Besançon, 1993. http://www.theses.fr/1993BESA3042.
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GUICHARD, JEAN-PIERRE. "Bilan de vingt annees de rage en france : 1968-1988." Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX20297.
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HUPPERT, PIERRE. "Les nouveautes en vaccination antirabique." Strasbourg 1, 1991. http://www.theses.fr/1991STR15019.
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Nuernberger, Kathryn L. "Rag and Bone: Poems." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1312926732.
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Cattral, Robert. "RAGA, Rule Acquisition with a Genetic Algorithm." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ57758.pdf.
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Pajaczkowska, Claire. "Before language : the rage at the mother." Thesis, Middlesex University, 1988. http://eprints.mdx.ac.uk/13278/.
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The thesis argues that psychoanalysis is a necessary component of cultural analysis. It is argued that existing syntheses of psychoanalysis and political theories tend to limit the recognition of the relative autonomy of psychic reality by offering accounts of the social determination of subjectivity. The contemporary reappropriation of psychoanalysis by feminist theorists has formulated new explanations of the social position of women as the 'second sex'. The challenge of feminism to traditional theories of culture and society includes questions of how sexual difference informs the transformation of thought into language, how language determines theory, and how theory conceptualises the difference between subjectivity and objectivity. The contradictions within existing syntheses of structuralism, Marxism and feminism are described, and the differences between psychoanalysis and sociology are traced through the the critical reception of Freud's Totem and Taboo by anthropologists. The validity of Freud's concept of the Oedipus complex is explored, and it is suggested that despite the limited acceptance by anthropologists, Totem and Taboo contains a valid theory of the relation of the subject to society. Freud's work is relocated within the paradigm of evolutionary biology to provide a materialist analysis of psychic structure that is not based on linguistics. A study of the origins of language reveals the complexity of the historical factors determining the co-evolution of representation, the maternal function, and the structuration of psychic reality. New discoveries about the pre-Oedipal dyad that underlies the Oedipus complex have shown the effects of infantile dependence and maternal care on adult subjectivity, and it is argued that factors such as the unconscious fear of dependency and of women are of particular significance for feminist thought. It is argued that the theory of pre-Oedipal and prelinguistic subjectivity can make intelligible aspects of ideologies of racism and sexism that are not fully explained by sociological or political theory. The mechanism of projection or projective identification, it is argued, provides a specifically psychoanalytic contribution to existing theories of culture.
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Cattral, Robert (Robert David) Carleton University Dissertation Computer Science. "RAGA: rule acquisition with a genetic algorithm." Ottawa, 2000.
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Pennington, Steven Leigh. "Road rage: Where is it coming from?" CSUSB ScholarWorks, 2002. https://scholarworks.lib.csusb.edu/etd-project/2141.
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Robert, Philippe. "La rage en france : actualites epidemiologiques et prophylactiques." Reims, 1991. http://www.theses.fr/1991REIMM018.
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WERLI, PASCALE. "La vaccination du renard contre la rage en france." Strasbourg 1, 1995. http://www.theses.fr/1995STR15007.
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Verkoczy, Laurent Karl. "Regulation studies of the human recombination activating genes, RAG-1 and RAG-2." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1995. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ51544.pdf.
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Rommel, Philipp Christian [Verfasser], and Monilola [Akademischer Betreuer] Olayioye. "RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks / Philipp Christian Rommel ; Betreuer: Monilola Olayioye." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2017. http://d-nb.info/1131076249/34.
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Soria, Baltazar Roman. "Étude de l'immunité antirabique des ruminants domestiques." Nancy 1, 1989. http://www.theses.fr/1989NAN10088.
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Les relations existantes entre l'immunité et le développement de la rage chez les ruminants domestiques ont été explorées soit après l'infection par le virus rabique, soit après la vaccination contre cette injection. Après une revue bibliographique des différents aspects de la rage chez les animaux et notamment chez les ruminants, une étude expérimentale a été conduite chez 99 ovins et 15 bovins. Cette étude à d'abord consisté à comparer la résistance naturelle des ovins aux trois virus de la rage auxquels sont principalement exposés les ruminants dans le monde : ceux du Renard, de la Chauve-souris et du Chien. Cette résistance n'apparait pas significativement différente
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Silver, Daniel P. (Daniel Peter). "Studies of the structure and function of the RAG-1 and RAG-2 genes." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/12587.
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Ortillon, Jérémy. "ARAVU (AGE-RAGE et Vasculopathie Urémique) - Rôle de l’interaction AGE-RAGE dans un modèle de vieillissement vasculaire : la vasculopathie urémique." Thesis, Reims, 2017. http://www.theses.fr/2017REIMM207/document.
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Les évènements cardiovasculaires sont la première cause de mortalité chez les patients insuffisants rénaux chroniques. Ces complications font suite à des modifications structurelles et fonctionnelles de la paroi vasculaire regroupées sous le terme de vasculopathie urémique. Parallèlement à ces modifications vasculaires, l’urémie s’accompagne d’une accumulation de substances non épurées par le rein appelées toxines urémiques, telles que les produits de la glycation avancée (AGEs) ou les ligands de RAGE. Ces toxines peuvent interagir avec leur récepteur, RAGE, qui est pro- inflammatoire et impliqué dans le remodelage artériel. Cette thèse a consisté en l’étude, chez la souris, du rôle de l’accumulation des ligands de RAGE et de leur interaction avec celui-ci dans le développement de l’athérosclérose, des calcifications vasculaires et de la thrombose artérielle au cours de l’insuffisance rénale chronique (IRC). Dans un premier temps, nous avons montré que l’IRC conduisait à une accumulation des AGEs et des ligands de RAGE sériques et tissulaires, ainsi qu’une augmentation de l’expression de RAGE au sein de la paroi vasculaire participant à la formation des plaques d’athérome. Dans un second temps, nous avons démontré que RAGE participait aux calcifications vasculaires favorisant l’expression de co-transporteur de phosphate inorganique (Pit-1), induisant la différenciation des cellules musculaires lisses en cellules « osteoblast-like ». Enfin, nous avons montré que RAGE participait à la formation d’un thrombus artériel dû à une hyperactivité plaquettaire. En conclusion, cette thèse a permis de renforcer le concept que l’axe ligands de RAGE/RAGE est un acteur important dans la vasculopathie urémiqueCardiovascular events are the primary cause of morbidity and mortality in chronic kidney disease patients. These complications are due to structural and functional changes in the vascular wall named uraemic vasculopathy. Alongside these vascular changes, uremia is accompanied by the retention of various solutes that are normally excreted by the kidneys called uremic toxins, such as the products of advanced glycation (AGEs) or the ligands of RAGE. These toxins may interact with their receptor, RAGE, which is pro-inflammatory and involved in arterial remodeling. The aim of this thesis was to study, in mice, the role of the accumulation of RAGE ligands and their interaction with it in the development of atherosclerosis, vascular calcification and arterial thrombosis in chronic renal failure (CKD). Initially, we showed that CKD leads to an accumulation of serum and tissue AGEs and RAGE ligands, as well as an increase in RAGE expression in the vascular wall involved in atheroma plaque formation. Secondly, we have demonstrated that RAGE is involved in vascular calcification promoting the expression of inorganic phosphate cotransporter (Pit-1), inducing the differentiation of smooth muscle cells "osteoblast-like". Finally, we showed that RAGE participated in the formation of arterial thrombus due to platelet hyperactivity. In conclusion this thesis consolidates that RAGE-RAGE ligands axis is an important actor in uremic vasculopathy
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Troy, Michael J. "Riches to Rags: Claude Francis Poullart des Places." Congregation of the Holy Spirit, 2005. http://digital.library.duq.edu/u?/spiritanbook,8362.
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Contents -- Introduction: A Role Model for Modern Youth -- (p. 5) -- Foreword: From Riches to Rags -- (p. 8) -- Chapter 1: Family Background and Early Years, Rennes (1679-1688) -- (p. 12) -- Chapter 2: High School Days, Rennes and Caen (1688-1695) -- (p. 17) -- Chapter 3: University Studies in Law, Nantes (1695-1701) -- (p. 27) -- Chapter 4: Choosing a Path Less Travelled, Rennes (p. 1701) -- (p. 34) -- Chapter 5: Theological Studies, Paris (1701-1703) -- (p. 39) -- Chapter 6: The Long Road to the Priesthood, Paris (1702-1707) -- (p. 55) -- Chapter 7: Founder of a New Seminary, Paris (1702-1707) -- (p. 63) -- Chapter 8: Tragic Early Death of the Founder, Paris (1709) -- (p. 79) -- Epilogue: Tri-Centennial Reflections -- (p. 90) -- Appendices -- (p. 93)
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Hirschi, Budge Kelsey May. "RAGE and Gas6/Axl Signaling in Obstetric Complications." BYU ScholarsArchive, 2020. https://scholarsarchive.byu.edu/etd/8409.
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Current research spans a wide range of objectives whose diversity includes the understanding of global epidemiology and the detailing of molecular interactions leading to specific pathologies. This work aligns more closely with the goal of mechanistic clarity by elucidating several aspects of signaling pathways involved in inflammatory and obstetric pathologies. Prior research has confirmed the role of Receptors for Advanced Glycation End-Products (RAGE) activation in signaling leading to chronic inflammation such as that observed in chronic obstructive pulmonary disease (COPD). RAGE activation has also been identified in other disease states including diabetes, Alzheimer’s disease, osteoarthritis, and cancers. We examined the role of RAGE in the obstetric complication intrauterine growth restriction (IUGR) wherein fetal development is delayed and infants are born at low birthweight. Exposure to tobacco smoke is known to activate RAGE, and smoke exposure also increases risk for IUGR. We confirm a role for RAGE signaling in development of IUGR. RAGE inhibition by semi-synthetic glycosaminoglycan ethers (SAGEs) significantly improved fetal and placental weights and reduced inflammatory signaling molecules. Interactions between RAGE and other signaling pathways have been noted in several research endeavors, and we sought to further understand signaling interactions specifically in obstetric pathologies by examining relationships between RAGE and Gas6/AXL signaling. We confirm that RAGE and Gas6/AXL signaling are not independent. Using tobacco smoke as a means of inducing RAGE, we determined that total AXL is inhibited when RAGE is active, but that phosphorylated AXL is increased. Inhibition of RAGE also increased Gas6 expression. These interactions require further clarification, but provide a foundation to expand upon. We further studied interactions within the Gas6/AXL pathway independent of RAGE. High levels of Gas6 have been noted in the serum of some women with preeclampsia, and early diagnosis and treatment of preeclampsia are currently limited. We demonstrate that, in a rat model, administration of Gas6 during pregnancy is sufficient to induce symptoms of preeclampsia including high blood pressure, increased proteinuria, and decreased trophoblast invasion. This provides a novel model which will further both diagnosis and treatment of preeclampsia. We also demonstrated that trophoblast invasion is influenced in a cell-type dependent manner by Gas6 and mTOR signaling, with decreased trophoblast invasion when Gas6 is high in trophoblast cells, but increased invasion with high Gas6 in a pulmonary adenocarcinoma cell type and in oral squamous cell carcinoma cells. Our work has clarified details of both RAGE and Gas6/AXL signaling that are crucial to further study of the pathways in which they are active, and the pathologies resulting from signaling misregulation.
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Rice, Judy A. "Behind the Rage: the Neurobiology of Impulsive Aggression." Digital Commons @ East Tennessee State University, 2003. https://dc.etsu.edu/etsu-works/7615.
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Gross, Christelle. "Etude de l'implication des produits de glycation avancés et de leur récepteur RAGE dans la cicatrisation de l'épithélium cornéen." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS010.
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De par son rôle dans de nombreuses fonctions biologiques, RAGE est une récepteur membranaire crucial du développement embryonnaire jusqu’à l’âge adulte. Ce récepteur multi-ligand est capable d’activer de nombreuses cascades de signalisation, lui permettant entre autres d’être impliqué dans les processus inflammatoires et cicatriciels. Bien que décrite, son action cellulaire et moléculaire dans les processus de régénération/cicatrisation reste encore à éclaircir, malgré des études déjà menées sur les épithéliums cutanée et pulmonaire. Concernant la cicatrisation de l’épithélium cornéen, l’action de ce récepteur et de ses ligands est peu documentée et largement controversé. Ce travail a permis de tester l’effet de 2 ligands de RAGE (HMGB1 et AGEs) sur la cicatrisation de l’épithélium cornéen en utilisant un modèle in vitro de cellules épithéliales de cornée humaine (HCE). Il visait aussi à étudier les cascades de signalisation et les processus cellulaire mis en jeu suite à l’activation de ce récepteur. Les résultats obtenus ont tout d’abord permis de démontrer que l’action pro-cicatrisante du récepteur RAGE sur des cellules de l’épithélium cornéen, était ligand et dose spécifique. Ainsi seul le ligand AGEs promeut la cicatrisation indépendamment des processus de migration et de prolifération cellulaire. Dans cette étude le couple AGEs/RAGE est capable d’activer la cascade de signalisation NF-κB et la transcription d’un gène cible Connexine 43, dont le rôle a déjà été décrit durant la cicatrisation.Malgré la complexité du « signal RAGE », les premières pistes apportées par cette étude permettent d’envisager dans un futur proche la caractérisation précise de son action pro-cicatrisante au niveau de la sphère oculaire. Ceci passera non seulement par l’étude exhaustive des cascades de signalisations activées et des gènes régulés mais aussi par l’utilisation du modèle animal souris sauvage et RAGE -/-Because of its role in many biological functions, RAGE is a crucial transmembranous receptor from development to adulthood. This multiligand receptor can activate numerous signaling pathways, and it is involved in inflammatory and wound healing processes. Although already describe, molecular and cellular processes involved during wound healing still to be clarify despite some studies conducted on skin and lung epithelium. In the corneal epithelium wound healing, RAGE and its ligands effects still poorly understood and widely controversial. This work allowed the test of 2 ligands (HMGB1 and AGEs) on corneal epithelium healing using an in-vitro model of human corneal epithelial cells (HCE). It also aims to study the signaling pathways and cellular processes involved after this receptor activation. Results obtained permit to demonstrate a ligand and dose-dependent action of RAGE during this pro-healing process. Thus, only AGEs ligand promotes wound healing independently of cellular migration and proliferation processes. In this study, AGEs/RAGE couple can activate NF-kB signaling pathway and Connexin 43 target gene expression, already describe to be involved in wound healing. Despite the “RAGE signal” complexity, first tracks brought by this study allow to plan in the near future the precise elucidation of its pro-healing properties in the ocular sphere. This will pass not only by the exhaustive study of the signaling pathways activated and the regulated genes but also by the use of wild-type and RAGE - / - mouse model
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KOCHGAGARIAN, BRIGITTE. "Evolution de la rage au maghreb depuis 1980 : etude a propos d'une observation clinique." Lyon 1, 1989. http://www.theses.fr/1989LYO1M081.
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KERN, MAYEUR SOPHIE. "La rage vulpine en alsace de 1969 a 1990." Strasbourg 1, 1992. http://www.theses.fr/1992STR15073.
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Teräsvirta, Jukka. "Tendency to Aggressive Driving and Road Rage : Identifying Drivers Prone to Aggressive Driving and Road Rage in Motor Vehicle Traffic in Sweden." Thesis, Stockholms universitet, Psykologiska institutionen, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-63803.
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In the present study possible associations between driver characteristics and aggressive driving were examined. 210 participants responded to a questionnaire consisting of self-report measures of emotion regulation ability, personality traits, and attitudes towards traffic behaviours in a Swedish translation of the Propensity for Angry Driving Scale (PADS). The main results showed that females, older age, agreeableness, openness, and social desirability were negatively correlated with angry driving behaviour as measured by the PADS. Impulsivity, attention seeking, trait irritability, verbal trait aggression, positive attitude towards speeding, and a high self-reported car manoeuvring ability were positively correlated with angry driving. Partial correlations showed that social desirability, trait irritability, and a positive attitude towards speeding explained most of the unique variance. Multiple regression analysis showed that trait irritability, positive attitude towards speeding, and a high self-reported car manoeuvring ability were the most important predictors of angry driving.
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Artois, Marc. "Ecologie de la rage et comportements de transmission de virus : Contribution à l'étude des rapports entre le renard (vulpes vulpes linnaeus, 1788) et le virus rabique en Lorraine." Nancy 1, 1990. http://docnum.univ-lorraine.fr/public/SCD_T_1990_0002_ARTOIS.pdf.
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La rage est une virose apparue récemment sur plusieurs espèces de mammifères sauvages et notamment sur le renard roux en Europe. Ce mémoire examine les rapports mutuels et les influences potentielles qui s'exercent entre le virus et son hôte. Les études montrent une adaptation du virus au renard allant dans le sens d'une forte pathogenecite, qui ne se rencontre pas lorsque ce virus est inocule à d'autres espèces telles que le chat, le furet ou le raton laveur. Il est difficile, sinon impossible de démontrer que le renard s'est adapté à son virus, toutefois les études de terrain suggèrent que les populations de renards peuvent faire face à la contrainte exercée par la rage. Cette réponse est à la fois comportementale et démographique et se traduit par le fait qu'une population de renards ne peut être affectée durablement par la mortalité due à la rage. On étudie également comment les modifications comportementales provoquées par la "maladie rabique" pourraient favoriser la transmission du virus. Au total ce mémoire précise les conditions dans lesquelles des pressions sélectives s'exercent entre un parasite (au sens fonctionnel) et son hôte.
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Lovejoy, Elizabeth A. "RAGE-based strategies for the control of gene expression." Thesis, University of Edinburgh, 1999. http://hdl.handle.net/1842/26699.
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The Cre/loxP site-specific recombinase system evolved within bacteriophage PI as a mechanism to maintain correct unit copy segregation of the prophage within host cells. This thesis reports the application of this system to regulate gene expression in murine cells. To regulate gene expression via RAGE (Recombination Activated Gene Expression) a novel floxed STOP cassette was designed, constructed and tested in murine embryonic fibroblasts (EF) and embryonic stem (ES) cells. When the floxed STOP cassette was used to regulate the expression of the Enhanced Green Fluorescent Protein (EGFP) marker gene a two-fold upregulation of EGFP transcription was observed after Cre mediated excisive recombination. However, no expression of the EGFP gene could be detected at the protein level and several reasons for this observation are discussed. The floxed STOP cassette was also utilised in RAGE-based strategies to achieve conditional expression of the tumour suppressor gene p53. A complex array of biological functions has been assigned to p53. For example, p53 is known to be involved in the regulation of apoptosis, multiple cell cycle checkpoints and the onset of replicative cellular senescence. The development of new approaches to achieve conditional p53 expression should be a valuable tool and permit further investigation into the pleiotropic nature of p53 function. Therefore, the floxed STOP cassette was used to regulate the expression of a p53 cDNA in p53 null primary EF cells in vitro. The upregulation of p53 expression after Cre administration was detected, but at a low frequency, by immunohistochemistry. The response of EF cells to the expression of p53 in terms of replicative cellular senescence was also characterised, including the first description of senescence-associated β-galactosidase expression in any murine cell. The floxed STOP technology was also used in an attempt to generate tools that will allow regulated expression of the endogenous murine p53 gene.
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Gaunce, Julia. "Liquid wrench, rage, resistance, and self-inflicted symbolic violence." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ49566.pdf.
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Hudson, Michael E. J. Nodwell J. R. "The central role of RamC in Streptomyces coelicolor development /." *McMaster only, 2004.
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Desrochers, Julien. "La Rage de Louis Hamelin et le paradoxe sociocritique." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23826/23826.pdf.
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Brodersen, Rupert. "Rage, rancour and revenge : existentialist motives in international relations." Thesis, London School of Economics and Political Science (University of London), 2014. http://etheses.lse.ac.uk/3061/.
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Emotions are gaining an increasingly prominent role in the study of International Relations. As a relatively new frontier, there is still considerable work to be done in streamlining various efforts into a systematic study. These efforts have largely circled on describing the cognitive and action potential of specific emotions, such as anger, fear and trust. This thesis is concerned with an extreme emotion, the emotion of rage. I stress the action potential of revenge, as well as the cognitive elements at play here, most specifically the issue of abrupt changes to morality. I use both Greek and Nietzschean philosophy to construct a binary approach to rage that acknowledges both the violent and bloody manifestation - we still witness today - as well as the silent, non-violent rancour that searches for an opportune moment before exploding into action.
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Talbi, Chiraz. "Evolution et dynamique de la rage canine en Afrique." Paris 6, 2009. http://www.theses.fr/2009PA066558.
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La diversité génétique des lyssavirus trouve son expression dans la capacité à coloniser de nombreuses niches écologiques et de nouveaux hôtes. Pendant la diffusion épidémique, les virus à ARN capables d’évoluer rapidement, accumulent des mutations informatives au niveau de leur génome, la diffusion spatiale laisse donc son empreinte sur le génome. La reconstruction de l’histoire de la diffusion spatiale basée sur les séquences génomiques permet donc de comprendre la dynamique d’évolution de l’épidémie. Dans ce travail, on a étudié la diversité génétique des lyssavirus, par la suite, on s'est spécifiquement intéressé à étudier l’évolution et la dynamique la rage canine en Afrique. L’analyse phylogénique de 22 génomes complets confirme la séparation des lyssavirus en 7 génotypes. La comparaison basée sur la totalité du génome nous amène à proposer de nouveaux critères de définition d'un nouveau génotype. L’étude des virus rabiques canins en Afrique montre qu’ils sont associés à l’émergence récente de deux lignées: Africa 1 et Africa 2 il y a moins de 200 ans. L’analyse de la dynamique spatiale des RABV montre que le mouvement des populations virales entre les pays de l’Afrique du Nord et les régions subsahariennes est absent. Cette diffusion est plutôt caractérisée par des mouvements de migrations selon un axe est-ouest en Afrique de l’Ouest et du Nord. Ces investigations permettent de mieux comprendre la structuration génétique et géographique des populations des RABV canins ainsi que la dynamique de la rage chez les chiens domestiques ce qui est crucial pour déterminer des stratégies d’élimination efficaces de la rageGenetic diversity of lyssaviruses is reflected in the ability of lyssavirus to colonize numerous ecological niches and new hosts. During the epidemic spread, RNA viruses evolve rapidly and can accumulate informative mutations in their genome, the spatial diffusion therefore, leaves its imprint on the genome. Reconstructing the history of the spatial distribution based on genomic sequences can therefore help to understand the epidemiological dynamic evolution. In this work, we first studied the genetic diversity of lyssavirus, and then we specifically addressed the question of the evolution and dynamics of dog rabies viruses in Africa. The phylogenetic analysis of 22 complete genomes confirms the separation of lyssavirus in 7 genotypes. The comparison based on the whole genome leads us to propose new criteria for defining a new genotype. The study of dog rabies virus in Africa shows that they are associated with the emergence of tow lineages: Africa 1 and Africa 2 introduced into this region only recently (probably <200 years ago). Spatial Dynamic analysis revealed that there was no spread of rabies between the countries of northern Africa and those of the sub-Saharan region. This distribution is rather characterized by east to west spread across west and north Africa. These investigations provide insight into the genetic structure and geographical populations of dog RABV and the dynamics of rabies in domestic dogs, which is crucial to identify effective strategies for eliminating rabies
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Arbuckle, Janeen Lynnae. "Identification and characterization of domains in non-core RAG1." Oklahoma City : [s.n.], 2007.
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Felipe, Túlio Raunyr Cândido. "Novo método para a avaliação do risco de colapso progressivo em edifícios de alvenaria estrutural." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/18/18134/tde-07032017-105034/.
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O evento do colapso progressivo começou a ser estudado, principalmente, após o acidente do edifício Ronan Point, em 1968, na cidade de Londres. Esse acidente fez o meio técnico rever as considerações normativas, sobretudo de maneira a adicionar recomendações que visem minimizar os danos causados à estrutura quando sujeita a um dano acidental.Entretanto, tais recomendações não realizam a análise do risco da estrutura colapsar. Essas também não conseguem analisar medidas de robustez e vulnerabilidade, e nem determinar qual é o elemento chave para a estrutura. Desse modo, partindo desses questionamentos, o presente trabalho desenvolveu uma nova metodologia nomeada aqui de Risk Analysis of the Progressive Collapse (RAPC). Este procedimento fornece uma medida mais precisa dos riscos, através de uma abordagem que utiliza a Teoria da Confiabilidade Estrutural. Assim, é deduzida uma expressão para a determinação da probabilidade de colapso progressivo, bem como são definidos os coeficientes de importância e vulnerabilidade para identificar o(s) elemento(s) chave. O elemento chave é definido como o que apresenta a maior interseção entre vulnerabilidade e importância para o colapso estrutural. Essas formulações desenvolvidas na metodologia do RAPC são implementadas em Fortran. Para isso, a modelagem do edifício de alvenaria estrutural é feita utilizando o software DIANA®, no qual os esforços solicitantes são obtidos e utilizados como dados de entrada na análise de confiabilidade. Valores de probabilidades de falha individual por elemento, condicional e condicional dupla são calculados pelo First Order Reliability Method (FORM) e Importance Sampling Monte Carlo (ISMC) com auxílio do programa StRAnD. Um algoritmo em Fortran é implementado para acoplamento do DIANA® e StRAnD, além de mapear a probabilidade de falha dos elementos estruturais. Portanto, torna-se evidente que a identificação dos elementos mais vulneráveis, e do elemento chave em particular, é útil para abordagens diretas de concepção estrutural, tais como a melhoria da resistência local. Contudo, os coeficientes propostos também medem os efeitos dos procedimentos de projeto que conduzem à continuidade, ductilidade e redundância. Quando essas medidas trabalham para reduzir as probabilidades de propagação de dano ou colapso, isso se reflete nas vulnerabilidades de elementos eventualmente iniciando esses caminhos de falha. Sendo assim, conclui-se que a formulação do RAPC se mostra como uma ferramenta na determinação do risco do colapso progressivo nas estruturas.The progressive collapse event began to be studied, mainly, after the accident of the Ronan Point building, at 1968, in the city of London. This accident caused the engineers review their normative considerations, mainly in order to add recommendations aimed at minimizing the damage to structure when subjected to abnormal loading. However, such recommendations do not perform the risk analysis of the structure to collapse. These also fail to analyze measures of robustness and vulnerability, and either determine which is the key element of the structure. Thus, leaving of these questions, the present work to develop a new methodology named here of Risk Analysis of the Progressive Collapse (RAPC). This procedure provides a more accurate measure of risks through an approach that uses Structural Reliability Theory. Thus, an expression is deduced for the determination of the probability of progressive collapse, as well as the importance and vulnerability coefficients are defined to identify the key element (or key elements). The key element is identified as the one presenting the largest intersection between vulnerability and importance to collapse.These formulations developed in the RAPC methodology are implemented in Fortran.For this, the structural masonry building modeling is done using the DIANA® software, in which the requesting efforts are obtained and used as input data in the reliability analysis. Probabilities values individual, conditional, and double conditional are calculated by the First Order Reliability Method (FORM) and Importance Sampling Monte Carlo (ISMC) using the StRAnD software. A Fortran algorithm is implemented for DIANA® and StRAnD coupling, besides mapping the probability of failure of the structural elements. Therefore, it is clear that identification of the most vulnerable elements, and of the key element in particular, is useful for direct design approaches to structural design, such as local resistance enhancements. However, the coefficients proposed herein also measure the effects of design procedures leading to continuity, ductility or redundancy. When these measures work to reduce probabilities of damage propagation or collapse, this is reflected in the vulnerabilities of elements eventually initiating these failure paths. Therefore, it is concluded that the formulation of RAPC is shown as an tool in determining the risk of progressive collapse in structures.
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Cla, Stéphanie. "La rage dans les pays en voie de développement : à propos d'un cas." Bordeaux 2, 1999. http://www.theses.fr/1999BOR2M081.
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ZENI, FILIPPO. "Circulating levels of soluble Receptor for Advanced Glycation End-products (sRAGE) decrease with aging and may predict age-related cardiac remodeling." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/170797.
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Background: L'invecchiamento è un inevitabile fattore di rischio in età avanzata che può influenzare l'insorgenza e la progressione di diverse malattie. Infatti, l'elevata incidenza di malattie cardiovascolari negli anziani è principalmente imputabile al fisiologico rimodellamento cardiaco associato ad un invecchiamento intrinseco. RAGE è un recettore capace di legare diverse molecole e coinvolto in molte malattie legate all'età. La sua isoforma solubile (sRAGE) agisce come un recettore decoy bloccando l'attivazione del recettore legato alla membrana, e suoi livelli circolanti sono stati trovati alterati in diverse patologie croniche ed acute. Il ruolo delle isoforme di RAGE durante l’invecchiamento e, in particolare, nell’invecchiamento cardiaco, non è mai stato studiato. Inoltre, la scoperta di biomarcatori affidabili in grado di valutare lo stato di salute individuale dei soggetti ha importanti applicazioni nel campo della prevenzione, della diagnosi e della gestione della malattia. In tale contesto, lo scopo di questo studio è stato quello di verificare se sRAGE sia un biomarcatore di invecchiamento e di rimodellamento cardiaco legato all’invecchiamento, e valutare il contributo delle isoforme RAGE nell’invecchiamento cardiaco.
Risultati: È stato collezionato il siero di soggetti sani, di entrambi i sessi, di età compresa tra i 20 e i 92 anni ed i livelli di sRAGE sono stati valutati mediante ELISA. Abbiamo trovato una significativa diminuzione di sRAGE circolante nei maschi, mentre solo una tendenza nelle femmine. Di conseguenza, abbiamo osservato una forte correlazione di sRAGE con l'età cronologica nei soggetti maschi, ma non nei soggetti di sesso femminile. Topi maschi e femmine a diverse età (2.5-12-22 mesi, Giovani, adulti (MA) e Vecchi, rispettivamente) sono stati sottoposti a ecocardiografia 2D per determinare le dimensioni e la funzione del ventricolo sinistro (LV) durante l'invecchiamento. sRAGE serico diminuisce in maniera simile in entrambi i sessi tra il gruppo Giovani e il gruppo MA, e correla inversamente con le dimensioni e la funzione del LV, in particolare nei machi. Nessuna quantità rilevabile di RAGE è stata trovata nei lisati proteici del LV a tutte le età. Topi Rage-/- hanno mostrato un significativo aumento dei volumi e dei diametri del LV in diastole e in sistole, ed una concomitante diminuzione della frazione di eiezione (EF) e di accorciamento (FS), rispetto agli animali Rage+/+ di pari età durante l'invecchiamento con le più forti differenze presenti tra i gruppi MA. Inoltre, topi MA Rage-/- hanno mostrato la maggiore deposizione di collagene e l’aumento dell'espressione di geni marcatori di scompenso cardiaco (BNP e Ankrd1) rispetto alla controparte Rage+/+. Al contrario, nessuna differenza in termini di dimensioni dei cardiomiociti è stata osservata a qualsiasi età tra i due genotipi. Infine, l’analisi funzionale di annotazione del microarray, basata sull'interazione fra età-genotipo, ha rivelato che la mancanza cronica di RAGE influenza l'espressione di geni associati alla funzione contrattile, al processo di presentazione dell'antigene e dell'immunità adattativa, del pathway dell’insulina, della morte cellulare e dell’apoptosi. Abbiamo anche trovato una correlazione tra i volumi e i diametri del LV in diastole e in sistole e i geni differenzialmente espressi, i quali sono coinvolti in diversi processi come la contrazione muscolare, la fibrosi e la regolazione dell'apoptosi.
Conclusioni: I nostri risultati indicano che sRAGE è un biomarcatore serico di invecchiamento sano e di rimodellamento cardiaco legato all'età, preferenzialmente nei maschi. L'assenza di RAGE aggrava l’avverso rimodellamento cardiaco legato all'età. Proponiamo che, tra le isoforme RAGE, sRAGE possa giocare un ruolo fondamentale nell’invecchiamento cardiaco.Background: Aging is an unavoidable risk factor in later life that can influence the onset and progression of many diseases. In fact, the high incidence of cardiovascular diseases in the elderly is mainly attributable to cardiac remodelling associated to physiological intrinsic aging. RAGE is a multi-ligand receptor involved in many age-related disorders. Its soluble isoform (sRAGE) acts as a decoy receptor being able to block the activation of the membrane-bound receptor, and its circulation levels have been found altered in several chronic and acute pathologies. The role of RAGE isoforms in aging and, in particular, cardiac senescence has never been investigated. Moreover, the finding of reliable biomarkers able to assess individual health status of subjects has important applications in prevention, diagnosis, and disease management. In this context, the aim of this study was to ascertain whether sRAGE is a biomarker of aging and age-related cardiac remodelling, and evaluate the contribution of RAGE isoforms to cardiac aging. Results: Serum of male and female from 20 to 92 years old healthy subjects was collected and sRAGE levels were evaluated by ELISA. We found a significant decrease of circulating sRAGE in males while only a trend in females. Accordingly, we observed a strong correlation of sRAGE with chronological age in male but not in female subjects. Male and female mice at different age (2.5-12-22-months, Young, Middle Age (MA) and Old, respectively) undergone 2D-echocardiography to determine the left ventricle (LV) dimensions and function during aging. Serum sRAGE similarly declines from the Young to the MA group in both sexes, and inversely correlate with LV dimensions and function, preferentially in males. No detectable amount of RAGE protein was found in LV at all ages. Rage-/- mice displayed a significant increase of LV volumes and diameters in diastole and systole, and a concomitant decrease in ejection fraction (EF) and fractional shortening (FS), compared to age-matched wt animals during aging with the strongest differences present between the MA groups. Moreover, MA Rage-/- mice exhibited higher deposition of collagen and expression of heart failure marker genes (BNP and Ankrd1) in respect to the wt counterpart. Conversely, no differences in cardiomyocytes size were observed at any age between the two genotypes. Finally, microarray functional annotation analysis based on the interaction between age-genotype revealed that the chronic lack of RAGE affected the expression of genes associated to contractile fibre function, antigen presenting process and adaptive immunity, insulin pathway, cell death and apoptosis. We also found a correlation between LV volumes and diameters in diastole and systole and differentially expressed genes involved in several processes like muscle contraction, fibrosis, wound healing and regulation of apoptosis. Conclusions: Our results indicate that sRAGE is a serum biomarker of healthy aging and age-related cardiac remodeling, preferentially in males. The absence of RAGE in mice exacerbates adverse cardiac remodeling with age. We propose that, among RAGE isoforms, sRAGE may play a pivotal role in cardiac senescence.
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Umbrasas, Dainius. "Elninių žvėrių gausumo kitimas Rytinėje Lietuvos dalyje bei stirninų ir tauriųjų elnių ragų morfometrinės charakteristikos skirtingose teritorijose." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2010~D_20140625_194146-60621.
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Elninių žvėrių gausumo kitimas rytinėja Lietuvos dalyje 2004 - 2010 metais. Taip pat tauriųjų elnių bei stirninų sumedžiotų 2006 - 2009 metais morfometrinės ragų charakteristikos. Pietvakarių Lietuvoje pagal keletą požymių patikimai skyrėsi stirninų ragų morfometrija lyginant su kitomis Lietuvos dalimis.This research is made to estimate live stock of Cervidae family animals in east Lithuania territory during winter seasons of 2004 - 2010. Also evaluate 2006 - 2009 in Lithuania hunted roe deer and red deer precious antlers morphometric features of development and differences in individual parts of Lithuania.