MicroARN (miARN) ont récemment émergé comme un acteur central du gène réseau de régulation impliqués dans la prise du destin cellulaire. L'apoptose, un actif processus, par lequel des cellules déclenchent leur auto-destruction en réponse à un signal, peut être contrôlé par les miARN. Il a également été impliqué dans une variété de maladies humaines, comme les maladies du cœur, et a été pensé comme une cible pour le traitement de la maladie. Tanshinone IIA (TIIA), un monomère de phenanthrenequinones utilisé pour traiter maladies cardiovasculaires, est connu pour exercer des effets cardioprotecteurs de l'infarctus du myocarde en ciblant l'apoptose par le renforcement de Bcl-2 expression. Pour explorer les liens potentiels entre le miARN et l'action anti-apoptotique de TIIA, nous étudié l'implication possible des miARN. Nous avons constaté que l'expression de tous les trois membres de la famille miR-34, miR-34a, miR-34b et miR-34c ont été fortement régulée à la hausse après l'exposition soit à la doxorubicine, un agent endommageant l'ADN ou de pro-oxydant H2O2 pendant 24 heures. Cette régulation à la hausse causé significativement la mort cellulaire par apoptose, comme déterminé par fragmentation de l'ADN, et les effets ont été renversés par les ARNs antisens de ces miARN. Le prétraitement des cellules avec TIIA avant l'incubation avec la doxorubicine ou H2O2 a empêché surexpression de miR-34 et a réduit des apoptose. Nous avons ensuite établi BCL2L2, API5 et TCL1, en plus de BCL2, comme les gènes nouveaux cibles pour miR-34. Nous avons également élucidé que la répression des ces gènes par MiR-34 explique l'effet proapoptotique dans les cardiomyocytes. Ce que la régulation positive de ces gènes par TIIA realisée par la répression de l'expression de miR-34 est probable le mécanisme moléculaire de son effet bénéfique contre ischémique lésions cardiaques. / MiRNAs (miRNAs) have recently emerged as a central player of gene regulatory network involved in decision of cell fate. Apoptosis, an active process that leads to cell death, has been shown to be controlled by miRNAs. It has also been implicated in a variety of human disease, such as heart disease, and established as a target process for disease therapy. Tanshinone IIA (TIIA), a monomer of phenanthrenequinones used to treat cardiovascular diseases, is known to exert cardioprotective effects in myocardial infarction by targeting apoptosis through enhancing Bcl-2 expression. To explore the potential link between miRNAs and the anti-apoptotic action of TIIA, we studied the possible involvement of miRNAs. We found that expression of all three members of the miR-34 family, miR-34a, miR-34b and miR-34c that have been known to mediate the apoptotic effect of p53 in cancer cells, were robustly upregulated after exposure to either the DNA-damaging agent doxorubicin or pro-oxidant H2O2 for 24 hr in cultured neonatal rat ventricular myocytes. This upregulation caused significant apoptotic cell death, as determined by DNA fragmentation, and the effects were reversed by the antisense to these miRNAs. Pretreatment of cells with TIIA prior to incubation with doxorubicin or H2O2 prevented upregulation of miR-34 and reduced apoptosis. We then established BCL2L2, API5 and TCL1, in addition to BCL2, as the novel target genes for miR-34. We further unraveled that repression of these genes by miR-34 accounts for its proapoptotic effect in cardiomyocytes whereas upregulation of these genes by TIIA through downregulating miR-34 is likely the molecular mechanism for its beneficial effect against ischemic myocardial injuries.

In the present project we study compactifications of type IIA/IIB string theories on toroidal orbifolds. We present the moduli space for N=1 four-dimensional reductions and its topological properties. To fix the value of all moduli, we will construct the most general holomorphic superpotential W using a set of T-dual iterations for the fluxes. Using a 3-torus toy-model, we will give an introductory description to the background of these generalised fluxes.

O parvovírus canino (CPV-2) e o coronavírus canino (CCoV-II) são considerados os principais patógenos responsáveis pela gastroenterite viral aguda em cães filhotes, causando, em alguns casos a alta morbidade e mortalidade, sobretudo em função da capacidade de potencializar infecções por outros agentes. Esses vírus estão distribuídos mundialmente na população canina, sendo responsáveis por diversos surtos em muitos países, sobretudo onde ocorre grande concentração de animais, como em abrigos e canis. O CPV-2 e o CCoV-II foram identificados a partir da década de 1970 e desde então, têm sido detectados em animais clinicamente saudáveis, assim como em cães que apresentam vômitos e diarreia severa. A presente tese tem como objetivo a identificação desses agentes na população canina do Brasil, sendo constituída de dois capítulos distintos: Capítulo 1- Caracterização de cepas de parvovírus canino circulantes no Brasil entre 2008 e 2010 e o Capítulo 2 - Caracterização do coronavírus canino pantrópico no Brasil. No Capítulo 1, foram analisadas amostras de fezes de 144 cães pela reação em cadeia da polimerase (PCR) para CPV-2, 29,2% (42/144) das amostras foram positivos. Das 42 amostras positivas, 71,4% (30) dos cães tinham sinais de gastroenterite hemorrágica. O sequenciamento de 583 pb do gene VP2 das amostras positivas, identificaram 78,6% (33/42) como CPV-2c, 19% (8/42) como CPV-2b e 2,4% (1/42) como tipo de 2a. A análise filogenética dos CPV-2 encontrados nas amostras brasileiras mostrou que elas são muito semelhantes às de outros países e o CPV-2c tornou-se predominante no Brasil. No Capítulo 2, foram analisadas amostras de órgãos de cinco cães jovens pela transcrição reversa (RT-PCR) para os genes M e S de CCoV-II, sendo que três cães foram positivos para CCoV-II e CPV-2, um foi positivo apenas para CCoV-II e um para o CPV-2 e o outro foi negativo para todos os agentes pesquisados. O sequenciamento dos produtos de amplificação identificou que eles eram CPV-2c e CCoV-IIa. A análise filogenética dos CCoV-IIa circulantes na população canina da região Sul do Brasil mostrou que são semelhantes aos encontrados em outros países. No entanto, os espécimes brasileiros tendem a agrupar-se em um único clado, sugerindo um ancestral comum. Os sinais clínicos e lesões causados pela nova variante de CPV-2 e do subtipo pantrópico CCoV-II foram muito semelhantes entre si, sendo de grande importância a inclusão do diagnóstico diferencial entre esses dois agente virais. Esta foi a primeira caracterização do subtipo CCoV-IIa em cães no Brasil. A detecção e caracterização do CPV-2 e do CCoV-II, que estão circulando atualmente, são essenciais para o entendimento da evolução viral e para o desenvolvimento de medidas de controle e prevenção. / Canine parvovirus (CPV-2) and canine coronavirus (CCoV-II) are considered the major pathogens causing acute viral gastroenteritis in puppies, in some cases with high morbidity and mortality, especially in terms of ability to potentiate infections by other agents. These viruses are distributed worldwide being responsible for outbreaks in many countries, especially where there is high concentration of animals, such as shelters and kennels. The CPV-2 and CCoV-II were identified from the late 1970 and since then have been detected in clinically healthy animals, as well as in dogs with vomiting and severe diarrhea. This work aims the identification of these agents in the canine population of Brazil, comprised by two distinct chapters: Chapter 1- Typing of canine parvovirus strains circulating in Brazil between 2008 and 2010, and Chapter 2- Characterization of pantropic canine coronavirus in Brazil. In chapter 1, stool samples of 144 dogs were analyzed by polymerase chain reaction (PCR) for CPV-2, 29,2% (42/144) of them were positive. Of the 42 positive samples, 7,4% (30) of the dogs had signs of hemorrhagic gastroenteritis. The sequencing of 583 bp VP2 gene of the positive samples identified 78,6% (33/42) as CPV-2c, 19% (8/42) as CPV-2b and 2,4% (1/42) as type 2a. Phylogenetic analysis of CPV-2 found in the canine population of Brazil, has shown that they are very similar to those of other countries and CPV-2c has become prevalent in Brazil. In Chapter 2 organ samples of five puppies were analyzed by reverse transcription (RT-PCR) for CCoV-II M and S genes, of wich three dogs were positive to CCoV-II and CPV-2, one was positive only to CCoV-II and one for CPV-2 and the other was negative for all the agents searched. The sequencing of the amplification products identified that they were CPV-2c and CCoV-IIa. Phylogenetic analysis of circulating CCoV-IIa in canine population in southern Brazil showed that they are similar to those found in other countries. However, the Brazilian specimens tend to group together in a single clade, suggesting a common ancestor. Clinical signs and injuries caused by the new CPV-2 variant and of pantropic subtype of CCoV-II are very similar to each other, being of great importance for the diagnosis including the differential diagnosis of these two viral agents. This was the first characterization of subtype CCoV-IIa in dogs in Brazil. The detection and characterization of CPV-2 and CCoV-II, that are currently circulating, are essential to understanding the viral evolution and to the development of more effective control and prevention measures.

<p>Audit is a common concept in Sweden. This occurs in many contexts and situations and may intend a wide spectrum of areas. It might consider environment audit, amateur audit, internal auditing, external audit etc. In the business community external audit and the associated external auditor is possibly, from the general public's side, the most recognized. The external audits purposes in big features are checking limited companies economic accounting along with the board and CEO: s management. In connection with increased requirements from the market, the own ranks and a row scandals where companies consistently created misled accounting which the external audit never detected, the internal auditing has grown himself stronger as well international as in Sweden. The internal auditing will according to their instruction from the company’s management in the specific company se to that nothing of the above occurs. Instead, this function will contribute to that the company is govern in better ways with fewer mistakes and a more reliable accounting as well financial as general. A big difference between the external audit and the internal audit which this thesis basically builds on is the theoretical knowledge that one is required to posses in order to conduct external opposite internal audit. In order to conduct external audit, the auditor need to, as described in Swedish legislation, hold a certain number academic points in specified subjects. The internal auditor however doesn´t have this kind of rules to follow. So how is quality in a function is that alone works with quality assurance assured? Well, through its own world extensive interest association, IIA, The Institute of Internal Auditors agency. This association provides a certification that persons that work with internal auditing can undergo. This certification which is standardized around in the entire world, is suitable to give the internal auditor fundamental knowledge of its intention and also to seem as a quality assurance for the internal auditing around in the globe. This certification is however rather extensive and requiring for the student. In Sweden only a minority of the internal auditors has undergone it. This thesis, which examine possible factors to why internal auditors choose to undergo this certification intend to answer this fact and the result that arrives is as follows:</p><ul><li>The employer requires this. </li><li>The employee wants to market her/him on the labor market, often on an international such. </li><li>The employee is on the verge to start up and the lead the organization in a new internal auditing department. </li></ul> / <p>Revision är ett vanligt förekommande begrepp i Sverige. Den förekommer i många sammanhang och situationer och kan avse ett vitt spektra av områden. Det kan handla om miljörevision, lekmannarevision, internrevision, externrevision etc. I den ekonomiska sfären av näringslivet är externrevision och den därtill hörande externrevisorn möjligen den, från allmänhetens sida, mest igenkända. Externrevisionen går i stora drag ut på att granska aktiebolags ekonomiska redovisning samt styrelse och VD:s löpande förvaltning av detsamma. Med anledning av höjda krav från marknaden, de egna leden samt en rad skandaler där företag konsekvent skapat vilseledande bokföring vilken revisionen inte upptäckt, har internrevisionen vuxit sig allt starkare såväl internationellt som i Sverige. Internrevisionen skall på uppdrag av företagsledningen i det specifika bolaget tillse att inget av ovanstående inträffar. Istället ska funktionen bidra till att företaget leds på ett bättre sätt med färre misstag och en mer pålitlig redovisning såväl finansiell som allmän. En skillnad mellan externrevisionen och internrevisionen vilken uppsatsen i stort bygger på är de teoretiska förkunskaper som krävs för att utöva dem. För att utöva externrevision finns det stadgat i lag och förordning att personen ska inneha ett visst antal akademiska poäng i på förhand specificerade ämnen. Internrevisorn har emellertid inte detta av lag stödda kravet. Hur kvalitetssäkras då en funktion som själva arbetar med kvalitetssäkring? Jo genom sin egen världsomfattande intresseförening, IIA, The<strong> </strong>Institute of Internal Auditors försorg. Förening tillhandahåller en certifiering vilken personer som arbetar med internrevision kan genomgå. Certifieringen är standardiserad runt om i världen och är avsedd att ge internrevisorn grundläggande kunskaper men avser även att verka som en kvalitetssäkring för internrevisionen runt om i världen. Certifieringen är emellertid tämligen omfattande och krävande för studenten och i Sverige är det endast en minoritet av internrevisorerna som genomgått den. I uppsatsen undersöks en rad tänkbara faktorer till varför internrevisorer väljer att genomå certifieringen och resultatet som framkommer är att:</p><ul><li>Arbetsgivaren ställer det som krav </li><li>Arbetstagaren vill marknadsföra sig själv på arbetsmarknaden, ofta på en internationell sådan.</li><li>Arbetsagaren ska starta upp och leda arbetet på en nystartad internrevisionsavdelning. </li><p> </p></ul>

Audit is a common concept in Sweden. This occurs in many contexts and situations and may intend a wide spectrum of areas. It might consider environment audit, amateur audit, internal auditing, external audit etc. In the business community external audit and the associated external auditor is possibly, from the general public's side, the most recognized. The external audits purposes in big features are checking limited companies economic accounting along with the board and CEO: s management. In connection with increased requirements from the market, the own ranks and a row scandals where companies consistently created misled accounting which the external audit never detected, the internal auditing has grown himself stronger as well international as in Sweden. The internal auditing will according to their instruction from the company’s management in the specific company se to that nothing of the above occurs. Instead, this function will contribute to that the company is govern in better ways with fewer mistakes and a more reliable accounting as well financial as general. A big difference between the external audit and the internal audit which this thesis basically builds on is the theoretical knowledge that one is required to posses in order to conduct external opposite internal audit. In order to conduct external audit, the auditor need to, as described in Swedish legislation, hold a certain number academic points in specified subjects. The internal auditor however doesn´t have this kind of rules to follow. So how is quality in a function is that alone works with quality assurance assured? Well, through its own world extensive interest association, IIA, The Institute of Internal Auditors agency. This association provides a certification that persons that work with internal auditing can undergo. This certification which is standardized around in the entire world, is suitable to give the internal auditor fundamental knowledge of its intention and also to seem as a quality assurance for the internal auditing around in the globe. This certification is however rather extensive and requiring for the student. In Sweden only a minority of the internal auditors has undergone it. This thesis, which examine possible factors to why internal auditors choose to undergo this certification intend to answer this fact and the result that arrives is as follows: The employer requires this. The employee wants to market her/him on the labor market, often on an international such. The employee is on the verge to start up and the lead the organization in a new internal auditing department. / Revision är ett vanligt förekommande begrepp i Sverige. Den förekommer i många sammanhang och situationer och kan avse ett vitt spektra av områden. Det kan handla om miljörevision, lekmannarevision, internrevision, externrevision etc. I den ekonomiska sfären av näringslivet är externrevision och den därtill hörande externrevisorn möjligen den, från allmänhetens sida, mest igenkända. Externrevisionen går i stora drag ut på att granska aktiebolags ekonomiska redovisning samt styrelse och VD:s löpande förvaltning av detsamma. Med anledning av höjda krav från marknaden, de egna leden samt en rad skandaler där företag konsekvent skapat vilseledande bokföring vilken revisionen inte upptäckt, har internrevisionen vuxit sig allt starkare såväl internationellt som i Sverige. Internrevisionen skall på uppdrag av företagsledningen i det specifika bolaget tillse att inget av ovanstående inträffar. Istället ska funktionen bidra till att företaget leds på ett bättre sätt med färre misstag och en mer pålitlig redovisning såväl finansiell som allmän. En skillnad mellan externrevisionen och internrevisionen vilken uppsatsen i stort bygger på är de teoretiska förkunskaper som krävs för att utöva dem. För att utöva externrevision finns det stadgat i lag och förordning att personen ska inneha ett visst antal akademiska poäng i på förhand specificerade ämnen. Internrevisorn har emellertid inte detta av lag stödda kravet. Hur kvalitetssäkras då en funktion som själva arbetar med kvalitetssäkring? Jo genom sin egen världsomfattande intresseförening, IIA, The Institute of Internal Auditors försorg. Förening tillhandahåller en certifiering vilken personer som arbetar med internrevision kan genomgå. Certifieringen är standardiserad runt om i världen och är avsedd att ge internrevisorn grundläggande kunskaper men avser även att verka som en kvalitetssäkring för internrevisionen runt om i världen. Certifieringen är emellertid tämligen omfattande och krävande för studenten och i Sverige är det endast en minoritet av internrevisorerna som genomgått den. I uppsatsen undersöks en rad tänkbara faktorer till varför internrevisorer väljer att genomå certifieringen och resultatet som framkommer är att: Arbetsgivaren ställer det som krav  Arbetstagaren vill marknadsföra sig själv på arbetsmarknaden, ofta på en internationell sådan. Arbetsagaren ska starta upp och leda arbetet på en nystartad internrevisionsavdelning.

This dissertation analyses the implications of international investment law on host states’ legal ability to protect the environment, regulate sustainable use of natural resources, and develop new approaches to manage environmental risks and uncertainties. ‘Environmental policy space’ is found to be a useful term when exploring the regulatory autonomy in this context. On one hand, investment law aims to ensure stability of the investment environment. On the other hand, environmental law needs flexibility to react to the degradation of the environment. It is found that those different aims do not have to be in conflict. There are useful mechanisms in national environmental law which provide for accessible, transparent and predictable decisions for the private actor. These mechanisms can fulfill the aim of stability in investment law. It is, however, concluded that core provisions of international investment treaties risk to put constraints to environmental law in a variety of ways. To diminish these risks, states, when concluding investment treaties, should make clear that constraining environmental regulation is not compatible with the overarching aim of sustainable development. Furthermore, the interpretation of provisions of investment protection must respect principles and instruments of environmental law not to continue being unbalanced towards investor interests. It is also concluded that allowing for investor – state arbitration, without the investor exhausting local remedies, will ignore the important national administrative review system of public environmental measures.

MicroARN (miARN) ont récemment émergé comme un acteur central du gène réseau de régulation impliqués dans la prise du destin cellulaire. L'apoptose, un actif processus, par lequel des cellules déclenchent leur auto-destruction en réponse à un signal, peut être contrôlé par les miARN. Il a également été impliqué dans une variété de maladies humaines, comme les maladies du cœur, et a été pensé comme une cible pour le traitement de la maladie. Tanshinone IIA (TIIA), un monomère de phenanthrenequinones utilisé pour traiter maladies cardiovasculaires, est connu pour exercer des effets cardioprotecteurs de l'infarctus du myocarde en ciblant l'apoptose par le renforcement de Bcl-2 expression. Pour explorer les liens potentiels entre le miARN et l'action anti-apoptotique de TIIA, nous étudié l'implication possible des miARN. Nous avons constaté que l'expression de tous les trois membres de la famille miR-34, miR-34a, miR-34b et miR-34c ont été fortement régulée à la hausse après l'exposition soit à la doxorubicine, un agent endommageant l'ADN ou de pro-oxydant H2O2 pendant 24 heures. Cette régulation à la hausse causé significativement la mort cellulaire par apoptose, comme déterminé par fragmentation de l'ADN, et les effets ont été renversés par les ARNs antisens de ces miARN. Le prétraitement des cellules avec TIIA avant l'incubation avec la doxorubicine ou H2O2 a empêché surexpression de miR-34 et a réduit des apoptose. Nous avons ensuite établi BCL2L2, API5 et TCL1, en plus de BCL2, comme les gènes nouveaux cibles pour miR-34. Nous avons également élucidé que la répression des ces gènes par MiR-34 explique l'effet proapoptotique dans les cardiomyocytes. Ce que la régulation positive de ces gènes par TIIA realisée par la répression de l'expression de miR-34 est probable le mécanisme moléculaire de son effet bénéfique contre ischémique lésions cardiaques. / MiRNAs (miRNAs) have recently emerged as a central player of gene regulatory network involved in decision of cell fate. Apoptosis, an active process that leads to cell death, has been shown to be controlled by miRNAs. It has also been implicated in a variety of human disease, such as heart disease, and established as a target process for disease therapy. Tanshinone IIA (TIIA), a monomer of phenanthrenequinones used to treat cardiovascular diseases, is known to exert cardioprotective effects in myocardial infarction by targeting apoptosis through enhancing Bcl-2 expression. To explore the potential link between miRNAs and the anti-apoptotic action of TIIA, we studied the possible involvement of miRNAs. We found that expression of all three members of the miR-34 family, miR-34a, miR-34b and miR-34c that have been known to mediate the apoptotic effect of p53 in cancer cells, were robustly upregulated after exposure to either the DNA-damaging agent doxorubicin or pro-oxidant H2O2 for 24 hr in cultured neonatal rat ventricular myocytes. This upregulation caused significant apoptotic cell death, as determined by DNA fragmentation, and the effects were reversed by the antisense to these miRNAs. Pretreatment of cells with TIIA prior to incubation with doxorubicin or H2O2 prevented upregulation of miR-34 and reduced apoptosis. We then established BCL2L2, API5 and TCL1, in addition to BCL2, as the novel target genes for miR-34. We further unraveled that repression of these genes by miR-34 accounts for its proapoptotic effect in cardiomyocytes whereas upregulation of these genes by TIIA through downregulating miR-34 is likely the molecular mechanism for its beneficial effect against ischemic myocardial injuries.

O parvovírus canino (CPV-2) e o coronavírus canino (CCoV-II) são considerados os principais patógenos responsáveis pela gastroenterite viral aguda em cães filhotes, causando, em alguns casos a alta morbidade e mortalidade, sobretudo em função da capacidade de potencializar infecções por outros agentes. Esses vírus estão distribuídos mundialmente na população canina, sendo responsáveis por diversos surtos em muitos países, sobretudo onde ocorre grande concentração de animais, como em abrigos e canis. O CPV-2 e o CCoV-II foram identificados a partir da década de 1970 e desde então, têm sido detectados em animais clinicamente saudáveis, assim como em cães que apresentam vômitos e diarreia severa. A presente tese tem como objetivo a identificação desses agentes na população canina do Brasil, sendo constituída de dois capítulos distintos: Capítulo 1- Caracterização de cepas de parvovírus canino circulantes no Brasil entre 2008 e 2010 e o Capítulo 2 - Caracterização do coronavírus canino pantrópico no Brasil. No Capítulo 1, foram analisadas amostras de fezes de 144 cães pela reação em cadeia da polimerase (PCR) para CPV-2, 29,2% (42/144) das amostras foram positivos. Das 42 amostras positivas, 71,4% (30) dos cães tinham sinais de gastroenterite hemorrágica. O sequenciamento de 583 pb do gene VP2 das amostras positivas, identificaram 78,6% (33/42) como CPV-2c, 19% (8/42) como CPV-2b e 2,4% (1/42) como tipo de 2a. A análise filogenética dos CPV-2 encontrados nas amostras brasileiras mostrou que elas são muito semelhantes às de outros países e o CPV-2c tornou-se predominante no Brasil. No Capítulo 2, foram analisadas amostras de órgãos de cinco cães jovens pela transcrição reversa (RT-PCR) para os genes M e S de CCoV-II, sendo que três cães foram positivos para CCoV-II e CPV-2, um foi positivo apenas para CCoV-II e um para o CPV-2 e o outro foi negativo para todos os agentes pesquisados. O sequenciamento dos produtos de amplificação identificou que eles eram CPV-2c e CCoV-IIa. A análise filogenética dos CCoV-IIa circulantes na população canina da região Sul do Brasil mostrou que são semelhantes aos encontrados em outros países. No entanto, os espécimes brasileiros tendem a agrupar-se em um único clado, sugerindo um ancestral comum. Os sinais clínicos e lesões causados pela nova variante de CPV-2 e do subtipo pantrópico CCoV-II foram muito semelhantes entre si, sendo de grande importância a inclusão do diagnóstico diferencial entre esses dois agente virais. Esta foi a primeira caracterização do subtipo CCoV-IIa em cães no Brasil. A detecção e caracterização do CPV-2 e do CCoV-II, que estão circulando atualmente, são essenciais para o entendimento da evolução viral e para o desenvolvimento de medidas de controle e prevenção. / Canine parvovirus (CPV-2) and canine coronavirus (CCoV-II) are considered the major pathogens causing acute viral gastroenteritis in puppies, in some cases with high morbidity and mortality, especially in terms of ability to potentiate infections by other agents. These viruses are distributed worldwide being responsible for outbreaks in many countries, especially where there is high concentration of animals, such as shelters and kennels. The CPV-2 and CCoV-II were identified from the late 1970 and since then have been detected in clinically healthy animals, as well as in dogs with vomiting and severe diarrhea. This work aims the identification of these agents in the canine population of Brazil, comprised by two distinct chapters: Chapter 1- Typing of canine parvovirus strains circulating in Brazil between 2008 and 2010, and Chapter 2- Characterization of pantropic canine coronavirus in Brazil. In chapter 1, stool samples of 144 dogs were analyzed by polymerase chain reaction (PCR) for CPV-2, 29,2% (42/144) of them were positive. Of the 42 positive samples, 7,4% (30) of the dogs had signs of hemorrhagic gastroenteritis. The sequencing of 583 bp VP2 gene of the positive samples identified 78,6% (33/42) as CPV-2c, 19% (8/42) as CPV-2b and 2,4% (1/42) as type 2a. Phylogenetic analysis of CPV-2 found in the canine population of Brazil, has shown that they are very similar to those of other countries and CPV-2c has become prevalent in Brazil. In Chapter 2 organ samples of five puppies were analyzed by reverse transcription (RT-PCR) for CCoV-II M and S genes, of wich three dogs were positive to CCoV-II and CPV-2, one was positive only to CCoV-II and one for CPV-2 and the other was negative for all the agents searched. The sequencing of the amplification products identified that they were CPV-2c and CCoV-IIa. Phylogenetic analysis of circulating CCoV-IIa in canine population in southern Brazil showed that they are similar to those found in other countries. However, the Brazilian specimens tend to group together in a single clade, suggesting a common ancestor. Clinical signs and injuries caused by the new CPV-2 variant and of pantropic subtype of CCoV-II are very similar to each other, being of great importance for the diagnosis including the differential diagnosis of these two viral agents. This was the first characterization of subtype CCoV-IIa in dogs in Brazil. The detection and characterization of CPV-2 and CCoV-II, that are currently circulating, are essential to understanding the viral evolution and to the development of more effective control and prevention measures.

O parvovírus canino (CPV-2) e o coronavírus canino (CCoV-II) são considerados os principais patógenos responsáveis pela gastroenterite viral aguda em cães filhotes, causando, em alguns casos a alta morbidade e mortalidade, sobretudo em função da capacidade de potencializar infecções por outros agentes. Esses vírus estão distribuídos mundialmente na população canina, sendo responsáveis por diversos surtos em muitos países, sobretudo onde ocorre grande concentração de animais, como em abrigos e canis. O CPV-2 e o CCoV-II foram identificados a partir da década de 1970 e desde então, têm sido detectados em animais clinicamente saudáveis, assim como em cães que apresentam vômitos e diarreia severa. A presente tese tem como objetivo a identificação desses agentes na população canina do Brasil, sendo constituída de dois capítulos distintos: Capítulo 1- Caracterização de cepas de parvovírus canino circulantes no Brasil entre 2008 e 2010 e o Capítulo 2 - Caracterização do coronavírus canino pantrópico no Brasil. No Capítulo 1, foram analisadas amostras de fezes de 144 cães pela reação em cadeia da polimerase (PCR) para CPV-2, 29,2% (42/144) das amostras foram positivos. Das 42 amostras positivas, 71,4% (30) dos cães tinham sinais de gastroenterite hemorrágica. O sequenciamento de 583 pb do gene VP2 das amostras positivas, identificaram 78,6% (33/42) como CPV-2c, 19% (8/42) como CPV-2b e 2,4% (1/42) como tipo de 2a. A análise filogenética dos CPV-2 encontrados nas amostras brasileiras mostrou que elas são muito semelhantes às de outros países e o CPV-2c tornou-se predominante no Brasil. No Capítulo 2, foram analisadas amostras de órgãos de cinco cães jovens pela transcrição reversa (RT-PCR) para os genes M e S de CCoV-II, sendo que três cães foram positivos para CCoV-II e CPV-2, um foi positivo apenas para CCoV-II e um para o CPV-2 e o outro foi negativo para todos os agentes pesquisados. O sequenciamento dos produtos de amplificação identificou que eles eram CPV-2c e CCoV-IIa. A análise filogenética dos CCoV-IIa circulantes na população canina da região Sul do Brasil mostrou que são semelhantes aos encontrados em outros países. No entanto, os espécimes brasileiros tendem a agrupar-se em um único clado, sugerindo um ancestral comum. Os sinais clínicos e lesões causados pela nova variante de CPV-2 e do subtipo pantrópico CCoV-II foram muito semelhantes entre si, sendo de grande importância a inclusão do diagnóstico diferencial entre esses dois agente virais. Esta foi a primeira caracterização do subtipo CCoV-IIa em cães no Brasil. A detecção e caracterização do CPV-2 e do CCoV-II, que estão circulando atualmente, são essenciais para o entendimento da evolução viral e para o desenvolvimento de medidas de controle e prevenção. / Canine parvovirus (CPV-2) and canine coronavirus (CCoV-II) are considered the major pathogens causing acute viral gastroenteritis in puppies, in some cases with high morbidity and mortality, especially in terms of ability to potentiate infections by other agents. These viruses are distributed worldwide being responsible for outbreaks in many countries, especially where there is high concentration of animals, such as shelters and kennels. The CPV-2 and CCoV-II were identified from the late 1970 and since then have been detected in clinically healthy animals, as well as in dogs with vomiting and severe diarrhea. This work aims the identification of these agents in the canine population of Brazil, comprised by two distinct chapters: Chapter 1- Typing of canine parvovirus strains circulating in Brazil between 2008 and 2010, and Chapter 2- Characterization of pantropic canine coronavirus in Brazil. In chapter 1, stool samples of 144 dogs were analyzed by polymerase chain reaction (PCR) for CPV-2, 29,2% (42/144) of them were positive. Of the 42 positive samples, 7,4% (30) of the dogs had signs of hemorrhagic gastroenteritis. The sequencing of 583 bp VP2 gene of the positive samples identified 78,6% (33/42) as CPV-2c, 19% (8/42) as CPV-2b and 2,4% (1/42) as type 2a. Phylogenetic analysis of CPV-2 found in the canine population of Brazil, has shown that they are very similar to those of other countries and CPV-2c has become prevalent in Brazil. In Chapter 2 organ samples of five puppies were analyzed by reverse transcription (RT-PCR) for CCoV-II M and S genes, of wich three dogs were positive to CCoV-II and CPV-2, one was positive only to CCoV-II and one for CPV-2 and the other was negative for all the agents searched. The sequencing of the amplification products identified that they were CPV-2c and CCoV-IIa. Phylogenetic analysis of circulating CCoV-IIa in canine population in southern Brazil showed that they are similar to those found in other countries. However, the Brazilian specimens tend to group together in a single clade, suggesting a common ancestor. Clinical signs and injuries caused by the new CPV-2 variant and of pantropic subtype of CCoV-II are very similar to each other, being of great importance for the diagnosis including the differential diagnosis of these two viral agents. This was the first characterization of subtype CCoV-IIa in dogs in Brazil. The detection and characterization of CPV-2 and CCoV-II, that are currently circulating, are essential to understanding the viral evolution and to the development of more effective control and prevention measures.

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