Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo ceramide biosynthesis. Moreover, we exposed WT and RAGE KO mice to side-stream cigarette smoke and found reduced mitochondrial respiration in the left ventricle myocardium from WT mice, but the RAGE KO mice were protected from this effect. Finally, conditional over-expression of RAGE in the lungs of mice also elicited a robust increase in left ventricular ceramides. Altogether, these findings suggest a RAGE-ceramide axis as an important contributor to cardiomyopathy.

This thesis will be organized into three chapters discussing the mechanism underlying the onset and progression of osteoarthritis (OA) in the temporomandibular joint (TMJ). Understanding the mechanism of OA development in the TMJ helps in understanding how OA progresses and how to treat this disease. The goal of this investigation is to examine the process of cartilage degeneration and OA biomarker expression in the TMJ to understand their role in TMJ OA onset and development.Chapter one covers mechanisms that are altered in TMJ OA during disease progression. Using animal models with different stressors such as mechanical disturbances, direct injury, and changes in the extracellular matrix composition revealed the role of the different mechanisms that are up-regulated and down regulated during cartilage destruction. Chapter two will cover a paper I wrote that introduces a novel non-invasive technique applied to mice, which induces an early onset of OA in the TMJ. I developed this technique with the aim to provide a new mouse model where the onset and progression of OA more closely mimic the natural TMJ OA progression in humans. The histopathological analysis of the cartilage demonstrates that onset of OA starts at 2 weeks after treatment induction and is aggravated by week eight. This data demonstrated the effectiveness of our technique in inducing OA in the TMJ. Chapter three will cover a second paper I wrote on the association of RAGE with the progression of OA in the TMJ of mice by using mice with and without RAGE expression. RAGE has been show to contribute to the progression of OA by releasing several pro-inflammatory and catalytic cytokines. Additionally, RAGE has been shown to modulate the expression of specific OA biomarkers, including HtrA-1, Mmp-13, and Tgf-β1 in knee cartilage. The objective of this study was to study the effect of knocking out RAGE on the expression of Mmp-1 3, HtrA-1, and Tgf-β1 in the TMJ. After histophatological and quantitative analysis of biomarkers expression, the results demonstrated for the first time that absence of RAGE expression in the TMJ provides a protective effect against development of TMJ OA in mice.

The receptor for advanced glycation end-products (RAGE) is a transmembrane cell surface protein of the immunoglobulin superfamily that acts as part of both the innate and adaptive immune system. RAGE is highly expressed in lung tissue and is therefore of interest in the pulmonary immune response. Specifically, RAGE mediates several cell-signaling responses such as inflammation and apoptosis. This work sought to elucidate the role of RAGE in the setting of chronic pulmonary irritation such as that found in long-term exposure to secondhand smoke (SHS). This irritation has several shared characteristics with lung diseases such as chronic obstructive pulmonary disease (COPD) and is therefore of value in discovering potential mechanistic targets for future therapeutic treatments for exacerbations of the disease. We validated the extracellular signal-regulated kinase (ERK) pathway as a downstream RAGE cascade to activate the cellular transcription factor NF-B and excluded the protein kinase B (AKT) pathway in chronic pulmonary inflammation. We also identified several proinflammatory cytokines mediated by RAGE in long-term SHS exposure; these included increased expression of TNF-, MIP-1, IL-13, and IFN, among others. Furthermore, we identified semisynthetic glycosaminoglycan ethers (SAGEs) as effective RAGE inhibitors in acute pulmonary inflammation and the improvement of lung function. RAGE is also implicated in many other diseases such as type II diabetes mellitus, Alzheimer’s disease, atherosclerosis, and obstetric complications. We investigated its postnatal expression in pups that experienced SHS-induced intrauterine growth restriction (IUGR) antenatally. Increased expression of RAGE correlated with concomitant decreased heart and kidney weights at 4 weeks of age. By 12 weeks of age, weights had improved to age-expected measurements, and detected RAGE protein levels had decreased. These results implicate a potential role for RAGE in disease pathologies of adults who experienced antenatal IUGR due to maternal SHS exposure during pregnancy. In addition to the RAGE signaling pathways, we also investigated the Gas6/AXL pathway in the lungs of pregnant preeclamptic rodents. Gas6 is a ligand for the transmembrane AXL receptor and has been found in increased levels in the serum of pregnant women with preeclampsia (PE). Previous studies in our lab demonstrated a rodent Gas6 model of PE. Using this model, we established that the maternal lung from Gas6-induced preeclamptic rats experienced increased AXL mRNA as well as higher total cell counts, protein, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF). These findings established a connection between lung inflammation and the development of preeclampsia that was previously unknown.

In this thesis I analyzed three different literary works; A Certain Hunger by Chelsea G. Summers (2020), Bunny by Mona Awad (2019), and Dirty Weekend by Helen Zahavi (1991) through the perspective of the female killer. The aim of the thesis was to analyze the so called “female rage” and what led the women in these novels to murder men. I also discussed how the female killers were presented and if and how the women were perceived as monstrous. The method I chose to do this was close reading, and the theory I used was queer theory. I mostly used Jack Halberstam’s book Skin Shows: Gothic Horror and the Technology of Monsters to contextualize my arguments as well as Judith Butler’s Genustrubbel and Sam Holmqvist’s chapter in Litteraturvetenskap II. The analysis showed that there is a connection between the monster and queerness, and that each of the women I wrote about has both monstrous and queer aspects. The analysis also showed the importance of power and how most of the motivation behind the women killing the men was their lack of power in a patriarchal society.

The Dula Dangerous Driving Index (DDDI) was created to measure drivers' self-reported propensity to drive dangerously (Dula & Ballard, in press). In the early stages of development, the DDDI and each of its subscales (Dangerous Driving Total, Aggressive Driving, Negative Emotional Driving, and Risky Driving) were found to have strong internal reliability (alphas from .83 to .92), and there was evidence of construct validity. In Study One, the alpha coefficient of .91 for the DDDI Total scale indicated excellent internal reliability for the measure and good internal reliability was demonstrated for its subscales with coefficient alphas equal to .81 for the DDDI Risky Driving subscale, .79 for the DDDI Negative Emotional subscale, and the DDDI Aggressive Driving subscale. Additionally, convergent and divergent validity was shown for the DDDI, but evidence was weaker for the validity of the separate subscales. Factor analysis demonstrated that the DDDI seemed to measure a unitary construct. In Study Two, coefficients of stability were generated from a four-week test-retest procedure, which were .76 for the DDDI Risky Driving subscale, .68 for the DDDI Negative Emotional subscale, .55 for the DDDI Aggressive Driving subscale, and .73 for the DDDI Total. In Study Three, the percentage of variance accounted for in criterion variables by different models ranged from 13.6% to 47.7%, where the DDDI Negative Emotional and DDDI Total scales frequently accounted for large portions of variance. In Study Four, the percent of variance accounted for in criterion variables by different models ranged from 22.0% to 65.6%, where some of the DDDI scales were regularly found to account for significant variance. Thus, it was concluded that the DDDI is a measure with high levels of internal reliability and reasonable stability across time, and that face, construct, and predictive validity was demonstrated. However, the evidence in support of the present division of subscales was weak, though present. Therefore, should further data fail to produce more substantial evidence for the validity of the DDDI subscales, a singular dangerous driving measure would be warranted, and the number of items should be shortened as guided by results from factorial analysis. / Ph. D.

RAGE (receptor for advanved glycation endproducts) was identified on endothelial cells as binding partner for AGE-modified molecules. The term "Advanced glycation endproducts" involves a number of structurally diverse molecules, which derive from multiple complex rearrangements of reducing sugars with free amino-groups of proteins. They evolve during food production and also in vivo during ageing and to an accelerated degree in diabetes, where AGEs cause receptor-mediated cellular perturbations. Due to the pathological relevance the aim of this thesis was to generate a "biosensor" for AGEs. To this end, the membrane-expressed receptor (flRAGE) as well as soluble RAGE (sRAGE) were expressed in mammalian cells and investigated in numerous binding studies. These did not reveal a specific interaction of AGE-modified ligands with RAGE. In addition, the expression of RAGE on endothelial cells, as described in the literature, could not be followed neither with the help of newly generated monoclonal anti-RAGE antibodies, nor in quantitative "real time" RT-PCR analysis. These results cast doubts on the meaning of RAGE as a proinflammatory receptor in AGE-mediated pathologies and on the adequacy of RAGE for the "biosensor". At the same time the question concerning a physiological role of the receptor arose. RAGE-expression was analysed in different healthy human tissues by "real time" RT-PCR, which revealed an almost selective expression in lung tissue. An important indication for a possible physiological function of RAGE in lung provided the selective localization of RAGE on alveolar epithelial type I cells as demonstrated in frozen lung sections as well as in in vitro cultivated lung cells. RAGE could be identified as a novel, highly specific marker for the thin, expanded AT I cell, which form part of the air-blood-barrier. In the following, RAGE was found to be an interaction partner for collagen IV, a major component of the alveolar basal lamina. Membrane-expressed RAGE did not only strengthened adherence of cells but also induced cell spreading on collagen IV-coated surfaces. This preferential interaction of RAGE with collagen IV could substantially contribute to the functional morphology of AT I cells in vivo, thereby ensuring an effective bidirectional gas-exchange. The results of this thesis expose a novel, so far unnoticed aspect of the biology of RAGE, which presumably contributes to the phenotypic characteristic und function of normal human lung tissue. / RAGE (receptor for advanced glycation endproducts) wurde als Interaktionspartner auf Endothelzellen für AGE-modifizierte Moleküle identifiziert. Unter den "Advanced glycation endproducts" werden eine Vielzahl strukturell unterschiedlicher Moleküle zusammengefasst, die durch mehrstufige komplexe Umlagerungen zwischen reduzierenden Zuckern und freien Aminogruppen von Proteinen entstehen. Sie entstehen sowohl bei der Herstellung von Lebensmitteln, als auch in vivo während des Alterns und in erhöhtem Maß bei Diabetes, wobei sie Rezeptor-vermittelt Zellstörungen hervorrufen. In der vorliegenden Arbeit wurde zunächst aufgrund der pathologischen Relevanz eine Strategie zur Konzeption eines "Biosensors" für AGEs verfolgt. Hierfür wurde sowohl der membranständige Rezeptor (flRAGE) als auch löslicher RAGE (sRAGE) in Säugerzellen exprimiert und in zahlreichen Bindungs- und Funktionsanalysen getestet. Hierbei konnte keine spezifische Interaktion der AGE-modifizierten Moleküle mit RAGE nachgewiesen werden. Auch die in der Literatur beschriebene Expression von RAGE auf Endothelzellen konnte mit Hilfe neu generierter monoklonaler Antikörper, sowie in quantitativen "real time" RT-PCR-Analysen nicht nachvollzogen werden. Diese Ergebnisse warfen Zweifel an der grundlegenden Bedeutung von RAGE als proinflammatorischer Rezeptor in AGE-bedingten Krankheiten auf und stellten damit auch dessen Eignung für einen AGE-Biosensor in Frage. Gleichzeitig warf diese Skepsis die Frage nach einer möglichen physiologischen Funktion dieses Rezeptors auf. Eine vergleichende Analyse der RAGE-Expression in verschiedenen gesunden Geweben mittels "real time" RT-PCR ergab eine nahezu selektive Expression in Lungengewebe. Wichtige Anhaltspunkte für die Funktion von RAGE in der Lunge ergaben sich aus der selektiven Lokalisation des Rezeptors auf Alveolarepithelzellen Typ I (AT I) sowohl in Gefrierschnitten der Lunge als auch nach in vitro-Kultur von Lungenzellen. RAGE konnte als neuer, hoch spezifischer Marker für die lang gestreckten AT 1 Zellen, die einen Teil der Blut-Luft-Schranke bilden, definiert werden. In folgenden Funktionsanalysen konnte RAGE als spezifischer Interaktionspartner für Kollagen IV, einer Hauptkomponente der Alveolar-Basalmembran, identifiziert werden. Membranständiger RAGE verstärkte nicht nur die Adhärenz von Zellen an Kollagen IV-beschichtete Oberflächen, er induzierte auch Zell-"Spreading". Dies gab Anlass für die Vermutung, dass die beobachtete präferentielle Interaktion von RAGE mit Kollagen IV maßgeblich zu der funktionellen Morphologie der AT I Zellen in vivo beitragen könnte, die die Voraussetzung für einen effektiven bidirektionalen Gasaustausch darstellt. Durch die Ergebnisse dieser Arbeit wurde ein neuer, bisher unbeachteter Aspekt der Biologie des RAGE aufgedeckt, der vermutlich entscheidend zur phänotypischen Ausprägung und Funktion des normalen humanen Lungengewebes beiträgt.

Diabetes is a chronic disease with high prevalence and significant morbidity. Chronic changes in the wall of small and large vessels lead to main diabetes complications. Apart from long- term hyperglycemia, several factors are involved in the development of diabetes vasculopathy. The aim of this work was to describe new early biomarkers of these vascular changes, to identify risky patients. Alongside, gene polymorphisms involved in protective pathways of glucose metabolism were studied. In three human studies with Type 1 (T1D) and Type 2 (T2D) diabetes patients special biochemical parameters of receptor for advanced glycation endproducts (RAGE) and its ligands, deglycation enzyme glyoxalase 1 (GLO1) and fructosamine 3-kinase (FN3K) gene polymorphisms were analyzed. Non-invasive measurement of glycation by skin autofluorescence (SAF) was assessed in all subjects. Soluble RAGE, HMGB1 and endothelial dysfunction markers were increased in patients with diabetes as compared with controls, however the differences between T1D and T2D were not significant. For the first time, an association between FN3K (rs1056534) and (rs3848403) polymorphism and sRAGE concentration in diabetes was shown. GLO1 (rs4746) polymorphism was associated with changes in endothelial dysfunction. Patients with diabetes had higher...

RAGE (receptor for advanved glycation endproducts) was identified on endothelial cells as binding partner for AGE-modified molecules. The term "Advanced glycation endproducts" involves a number of structurally diverse molecules, which derive from multiple complex rearrangements of reducing sugars with free amino-groups of proteins. They evolve during food production and also in vivo during ageing and to an accelerated degree in diabetes, where AGEs cause receptor-mediated cellular perturbations. Due to the pathological relevance the aim of this thesis was to generate a "biosensor" for AGEs. To this end, the membrane-expressed receptor (flRAGE) as well as soluble RAGE (sRAGE) were expressed in mammalian cells and investigated in numerous binding studies. These did not reveal a specific interaction of AGE-modified ligands with RAGE. In addition, the expression of RAGE on endothelial cells, as described in the literature, could not be followed neither with the help of newly generated monoclonal anti-RAGE antibodies, nor in quantitative "real time" RT-PCR analysis. These results cast doubts on the meaning of RAGE as a proinflammatory receptor in AGE-mediated pathologies and on the adequacy of RAGE for the "biosensor". At the same time the question concerning a physiological role of the receptor arose. RAGE-expression was analysed in different healthy human tissues by "real time" RT-PCR, which revealed an almost selective expression in lung tissue. An important indication for a possible physiological function of RAGE in lung provided the selective localization of RAGE on alveolar epithelial type I cells as demonstrated in frozen lung sections as well as in in vitro cultivated lung cells. RAGE could be identified as a novel, highly specific marker for the thin, expanded AT I cell, which form part of the air-blood-barrier. In the following, RAGE was found to be an interaction partner for collagen IV, a major component of the alveolar basal lamina. Membrane-expressed RAGE did not only strengthened adherence of cells but also induced cell spreading on collagen IV-coated surfaces. This preferential interaction of RAGE with collagen IV could substantially contribute to the functional morphology of AT I cells in vivo, thereby ensuring an effective bidirectional gas-exchange. The results of this thesis expose a novel, so far unnoticed aspect of the biology of RAGE, which presumably contributes to the phenotypic characteristic und function of normal human lung tissue. / RAGE (receptor for advanced glycation endproducts) wurde als Interaktionspartner auf Endothelzellen für AGE-modifizierte Moleküle identifiziert. Unter den "Advanced glycation endproducts" werden eine Vielzahl strukturell unterschiedlicher Moleküle zusammengefasst, die durch mehrstufige komplexe Umlagerungen zwischen reduzierenden Zuckern und freien Aminogruppen von Proteinen entstehen. Sie entstehen sowohl bei der Herstellung von Lebensmitteln, als auch in vivo während des Alterns und in erhöhtem Maß bei Diabetes, wobei sie Rezeptor-vermittelt Zellstörungen hervorrufen. In der vorliegenden Arbeit wurde zunächst aufgrund der pathologischen Relevanz eine Strategie zur Konzeption eines "Biosensors" für AGEs verfolgt. Hierfür wurde sowohl der membranständige Rezeptor (flRAGE) als auch löslicher RAGE (sRAGE) in Säugerzellen exprimiert und in zahlreichen Bindungs- und Funktionsanalysen getestet. Hierbei konnte keine spezifische Interaktion der AGE-modifizierten Moleküle mit RAGE nachgewiesen werden. Auch die in der Literatur beschriebene Expression von RAGE auf Endothelzellen konnte mit Hilfe neu generierter monoklonaler Antikörper, sowie in quantitativen "real time" RT-PCR-Analysen nicht nachvollzogen werden. Diese Ergebnisse warfen Zweifel an der grundlegenden Bedeutung von RAGE als proinflammatorischer Rezeptor in AGE-bedingten Krankheiten auf und stellten damit auch dessen Eignung für einen AGE-Biosensor in Frage. Gleichzeitig warf diese Skepsis die Frage nach einer möglichen physiologischen Funktion dieses Rezeptors auf. Eine vergleichende Analyse der RAGE-Expression in verschiedenen gesunden Geweben mittels "real time" RT-PCR ergab eine nahezu selektive Expression in Lungengewebe. Wichtige Anhaltspunkte für die Funktion von RAGE in der Lunge ergaben sich aus der selektiven Lokalisation des Rezeptors auf Alveolarepithelzellen Typ I (AT I) sowohl in Gefrierschnitten der Lunge als auch nach in vitro-Kultur von Lungenzellen. RAGE konnte als neuer, hoch spezifischer Marker für die lang gestreckten AT 1 Zellen, die einen Teil der Blut-Luft-Schranke bilden, definiert werden. In folgenden Funktionsanalysen konnte RAGE als spezifischer Interaktionspartner für Kollagen IV, einer Hauptkomponente der Alveolar-Basalmembran, identifiziert werden. Membranständiger RAGE verstärkte nicht nur die Adhärenz von Zellen an Kollagen IV-beschichtete Oberflächen, er induzierte auch Zell-"Spreading". Dies gab Anlass für die Vermutung, dass die beobachtete präferentielle Interaktion von RAGE mit Kollagen IV maßgeblich zu der funktionellen Morphologie der AT I Zellen in vivo beitragen könnte, die die Voraussetzung für einen effektiven bidirektionalen Gasaustausch darstellt. Durch die Ergebnisse dieser Arbeit wurde ein neuer, bisher unbeachteter Aspekt der Biologie des RAGE aufgedeckt, der vermutlich entscheidend zur phänotypischen Ausprägung und Funktion des normalen humanen Lungengewebes beiträgt.

Denna kandidatuppsats består av en egen översättning från engelska till svenska av första kapitlet från författaren Jesse Lee Petersons verk From Rage to Responsibility: Black Conservative Jesse Lee Peterson and America Today. Uppsatsen består dessutom av en källtextanalys samt översättningskommentarer som exemplifierar och diskuterar översättarens tillvägagångssätt i att åstadkomma en översättning som uppnår dess syfte. Syftet har primärt varit att överföra källtextinnehållet till måltexten och den djupare förståelse som förmedlas relaterat till ilska, självinsikt, förlåtelse och ansvar, på ett sätt som samtidigt bevarar författarstilen i möjligaste mån. Detta inkluderar en överföring av författarens lättsamma stil och användning av verbala och talspråkliga drag, idiom och kulturreferenser, samt en anpassning av syntax. För att åstadkomma detta har framförallt översättningsteorier och begrepp från Benjamin Walter och Theo Hermans tillämpats under översättningsprocessen och i översättningskommentarerna. / This essay is based on my own translation of the first chapter of author Jesse Lee Peterson’s work From Rage to Responsibility: Black Conservative Jesse Lee Peterson and America Today, in the language pair English to Swedish. The essay also includes a source text analysis, as well as a commentary on my own translation, where the translator’s approach in achieving a target text that accomplishes its aim is discussed and exemplified. The aim has primarily been to transfer the source text’s ideational core to the target text and the deeper understanding that is being conveyed, regarding rage, insight, forgiveness and responsibility, in an equivalent manner which stays faithful to the style of the author, to the extent that is considered possible. This includes the transference of the author’s cultural references, easy going and simple stylistic approach, along with the informal and colloquial language use, as well as a syntactic target language adaptation. To achieve this, the ideas and terms from the translation theorists Benjamin Walter and Theo Hermans have been applied during the translation process and in the commentary.

La rage est une zoonose mortelle, susceptible d’atteindre autant les mammifères sauvages et domestiques que l’Homme. Elle est à l’origine d’environ 70 000 décès humain déclarés par an, majoritairement des enfants dans les pays en développement. Le chien, réservoir majeur de l’espèce RABV, est à l’origine de 98-99% de ces décès. Quatorze espèces de Lyssavirus, circulant majoritairement chez les chiroptères sont actuellement reconnues. La vaccination, associée à des mesures sanitaires, reste le meilleur outil de prévention et de maîtrise de la maladie. A l’heure actuelle, seule la sérologie permet de contrôler l’efficacité de la vaccination antirabique, le développement des anticorps neutralisants étant le premier témoin d’une immunité protectrice. Les travaux s’appuyant sur la séroneutralisation virale, et notamment ceux auxquels j’ai participé, ont mis en évidence l’influence de différents facteurs dont certains ont conduit à préconiser des modifications de protocoles vaccinaux. Ils ont également permis d’assurer le suivi de l’efficacité de la vaccination individuelle ou de groupe sur le terrain et de contribuer à son amélioration. Les tests de séroneutralisation sont également utilisés dans le cadre de l’épidémiosurveillance de populations animales non vaccinées. La mise en œuvre de ces tests chez les chiroptères en France, après leur adaptation au Lyssavirus d’intérêt que j’ai menée à bien, a permis d’obtenir des informations sur la circulation des espèces virales EBLV-1 et EBLV-2, sur une base uniquement sérologique pour ce dernier. D’autre part, elle a permis de mettre en évidence au sein d’une même colonie des phénomènes de transition sérologique au cours du temps, dont l’étude mériterait d’être approfondie. Les tests de séroneutralisation sont cependant difficilement transférables aux pays où la rage est très présente, du fait de ressources limitées. Mes travaux, proposant l’utilisation d’un test ELISA comme méthode alternative, ont contribué à remettre en cause le dogme du recours nécessaire à la séroneutralisation. Ce test, couplé à un système de collecte d’échantillons sanguins adapté au terrain, devrait améliorer le suivi de l’efficacité des campagnes de vaccination de la faune sauvage comme des animaux domestiques, y compris dans les pays d’enzootie où la qualité des prélèvements de sang ne peut être assurée. Ainsi, les outils d’évaluation de la réponse immunitaire humorale sont des outils très précieux au service de la lutte et de la surveillance de la rage animale dans le monde. Mes travaux, complémentaires à ceux réalisés par d’autres équipes, ont contribué à rendre envisageable l’objectif prioritaire des organisations internationales : l’éradication de la rage canine dans le monde à l’horizon 2030. Il est cependant nécessaire de les poursuivre pour améliorer les outils disponibles et d’en proposer de plus adaptés, afin d’atteindre l’ensemble des objectifs d’éradication, de la rage canine comme de la rage selvatique / Rabies is a deadly zoonosis that can affect wild and domestic mammals as much as humans. About 70,000 human deaths are reported each year, mostly in children from developing countries. Dogs, which are the major reservoir and source of the RABV species, account for 98-99% of these deaths. Currently, fourteen species of Lyssavirus, mainly circulating in chiroptera, are officially recognized. Vaccination, combined with sanitary measures, remains the best tool for preventing and controlling the disease. To date, only serology has allowed to control the effectiveness of rabies vaccination, as the production of neutralizing antibodies is the first evidence of protective immunity. Studies based on viral seroneutralisation, including my own studies, have highlighted the influence of various factors. Some of them have led to recommend modifications of vaccine protocols. They also contributed to monitor the effectiveness of individual or group vaccination field programmes and to improve these programmes. Seroneutralisation tests are also used in the context of the epidemiological surveillance of unvaccinated animal populations. I first successfully adapted these tests to lyssaviruses of interest in France. In a second step, their implementation in chiropters in France provided information on the circulation of EBLV-1 and EBLV-2 species, (only on a serological basis for the latter). This survey also allowed to highlight, within a specific colony, a phenomenon of serological transition over time, which should deserve to be studied further. However, seroneutralisation tests are difficult to be implemented in countries where rabies is very prevalent, mainly because of limited resources. My work, which recommends the use of an ELISA test as an alternative method, contributed to questioning the dogma of the necessary use of seroneutralisation tests. This test, coupled with a blood sampling system adapted to the field, should improve the monitoring of the effectiveness of vaccination campaigns for both wildlife and domestic animals, including in enzootic countries, where the quality of the blood samples cannot be guaranteed. Humoral immune response assessment tools are very valuable tools for the control and surveillance of animal rabies all around the world. My work, complementary to those carried out by other teams, has helped to make the priority objective of international organizations possible, i.e. the eradication of canine rabies in the world by 2030. However, further works are needed to improve the available tools and to propose more adapted ones, in order to achieve all the goals of eradication, for both canine and sylvatic rabies