Submitted by Edineia Teixeira (edineia.teixeira@unioeste.br) on 2018-09-28T18:12:13Z No. of bitstreams: 2 Marilia_Favalesso_2018.pdf: 1901703 bytes, checksum: 0d9b6ae60903ec7aa858792cf86a51f2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-09-28T18:12:13Z (GMT). No. of bitstreams: 2 Marilia_Favalesso_2018.pdf: 1901703 bytes, checksum: 0d9b6ae60903ec7aa858792cf86a51f2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-02-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Lonomia obliqua Walker 1855 (Saturniidae: Hemileucinae) is a species of moth of sanitary interest in Brazil. Their larvae are etiological agents of lonomism, a form of erucism caused by the contact of the human beings with the stinging structures of the species. The most worrying symptoms of lonomism are the systemic hemorrhagic conditions that can lead to several outcomes, including death. The first official notifications of accidents with the species date back to the end of the 80s, in the state of Rio Grande do Sul. Since then, several accidents have been documented in Brazil, mainly in the south and southeast regions of the country. With the increase in the number of victims, health authorities in the state of São Paulo, represented by the “Instituto Butantã”, developed an anti-lonomic serum, which is distributed by the Ministry of Health in places with a higher prevalence of accidents. Hypotheses have been raised on the relation between the growth of the cases of lonomismo and the human occupation; however, little is known about the spatial distribution and ecological aspects of the species to enable the testing of these hypotheses. In view of the above, the present study aimed to produce a map for the potential geographical distribution of L. obliqua in Brazil, based on the combination of different ENM (Ecological Niche Modeling) algorithms. A total of 38 occurrence points were distributed across the geographic area of Brazil and Misiones, Argentina, which were partitioned for calibration and evaluation of the distribution model. Eight continuous climatic variables and only 16 previously considered variables were selected. Different ENM methodologies were tested and compared to TSS (True Skill Statistic) index values. The final model-map was composed of a combination of four algorithms (Gower, Mahalanobis, Maxent and SVM), with pseudo-absences outside a bioclimatic envelope and a number of pseudo-absences equal to that of presences. This model map was binarized from the Low Presence Threshold (LPT) and cut only for Brazil. According to this model map, the areas predicted as suitable for L. obliqua would be restricted to latitudes ~12° and ~32°, and longitudes ~39° and ~57°. When evaluating new sites of occurrence of the specie in Rio Grande do Sul, it was possible to verify that all the municipalities were in areas predicted by the model-map. A characterization of the abiotic variables related to the niche of the specie was also carried out, being these extracted from the area predicted as adequate the presence of the specie in the model map. To help characterize these variables, we also extract categorical descriptors of climate, soil and vegetation (in %). The percentage of land use classes was also extracted in order to contribute to the hypothesis that condition the increase of accidents due to human occupation. In this question, we find a large part of the area predicted within classes of agricultural soils in Brazil, which leads us to ratify the current hypotheses. Thus, the loss of habitat of the species for the agricultural enterprises increases the human contact with the specie, which should increase the number of notifications of the lonomism, generating greater epidemiological concern and habitat conservation for this specie. / Lonomia obliqua Walker 1855 (Saturniidae: Hemileucinae) é uma espécie de mariposa de interesse sanitário no Brasil. Suas larvas são agentes etiológicos do lonomismo, uma forma de erucismo causado pelo contato dos seres humanos com as estruturas urticantes da espécie. Os sintomas mais preocupantes do lonomismo são os quadros hemorrágicos sistêmicos que podem conduzir a diversos desfechos, inclusive o óbito. As primeiras notificações oficiais de acidentes com a espécie datam do final da década de 80, no estado do Rio Grande do Sul. A partir de então, diversos acidentes têm sido documentados no Brasil, principalmente nas regiões sul e sudeste do país. Com o aumento do número de vítimas, autoridades sanitárias do estado de São Paulo, representadas pelo do Instituto Butantã, desenvolveram um soro antilonômico, o qual é distribuído pelo Ministério da Saúde em localidades com maior prevalência de acidentes. Hipóteses têm sido levantadas sobre a relação entre o crescimento dos casos de lonomismo e a ocupação humana; contudo, pouco se conhece sobre a distribuição espacial e aspectos ecológicos da espécie para possibilitar os testes destas hipóteses. Diante do exposto, o presente estudo objetivou produzir um mapa para a distribuição geográfica potencial de L. obliqua no Brasil, baseando-se na combinação de diferentes algoritmos ENM (Ecological Niche Modeling). Foram utilizados 38 pontos de ocorrência distribuídos pela área geográfica do Brasil e região de Misiones, na Argentina, os quais foram particionados para calibração e avaliação do modelo de distribuição. Foram selecionadas oito variáveis contínuas climáticas e de solo entre 16 previamente cogitadas. Diferentes metodologias ENM foram testadas e confrontados quanto a valores de índice TSS (True Skill Statistic). O mapa-modelo final foi composto por uma combinação de quatro algoritmos (Gower, Mahalanobis, Maxent e SVM), com amostragens de pseudo-ausências fora de um envelope bioclimático e número de pseudo-ausências igual ao de presenças. Esse mapa-modelo foi binarizado a partir do limiar LPT (Lowest Presence Threshold) e recortado somente para o Brasil. Segundo este mapa-modelo, as áreas preditas como adequáveis a L. obliqua estariam restritas as latitudes ~12º e ~32º, e as longitudes ~39º e ~57º. Também foi realizada uma caracterização das variáveis abióticas relacionadas ao nicho da espécie, sendo essas extraídas da área predita como adequada a presença da espécie no mapa-modelo. O percentual de classes de uso da terra também foi extraído, a fim de contribuir com as hipóteses que condicionam o aumento de acidentes em função da ocupação humana. Neste quesito, encontramos grande parte da área predita dentro de classes de solos agrícolas no Brasil, o que nos leva a ratificar as hipóteses atuais. Assim, a perda de habitat da espécie para os empreendimentos agrícolas aumenta o contato humano com a espécie, o que deve aumentar o número de notificações do lonomismo, gerando maior preocupação a nível epidemiológico e de conservação de habitat para essa espécie.

Hemólise intravascular, causada pelo envenenamento por aranhas Loxosceles, é dependente da ação da esfingomielinase D, toxina do veneno que se liga à membrana dos eritrócitos e ativa proteases responsáveis pela clivagem de glicoforinas, tornando as células sensíveis à ação lítica do Sistema Complemento autólogo. O objetivo do estudo foi identificar possíveis proteases envolvidas nesse processo. A toxina foi expressa, purificada e apresentou suas funções biológicas ativas. O tratamento de eritrócitos humanos com a toxina removeu glicoforinas da membrana, não teve ação sobre Kell, CD59, DAF e CR1 e induziu a deposição de C1q, C3, C4, C5b-9, fator B e properdina. O pré-tratamento das células com os inibidores galardina, bestatina e fenantrolina reduziu a hemólise dependente de complemento autólogo. A ativação de proteases das membranas sobre o substrato fluorescente Abz-FRSSR-EDDnp, induzida pela toxina, foi prevenida por PMSF, simvastatina e fenantrolina, sugerindo o envolvimento de metalo- e serinoproteases no modelo de hemólise dependente de complemento estudado. / Intravascular hemolysis caused by poisoning by spiders Loxosceles, is dependent on the sphingomyelinase D action, a toxin that binds to the erythrocytes membrane and activates proteases responsible for the glycophorins cleavage, rendering the cells sensitive to the lytic action of the autologous complement system. This study aimed to identify possible membrane proteases involved in this process. The toxin was expressed, purified and showed to be functionally active. Treatment of human erythrocytes with the toxin caused the removal of the membrane glycophorins, but did not act on Kell, CD59, DAF and CR1 and induced deposition of C1q, C3, C4, C5b-9, factor B and properdin. Pretreatment of cells with inhibitors galardin, phenanthroline and bestatin reduced the complement-dependent hemolysis. The action of membrane proteases upon the fluorescent substrate Abz-FRSSR-EDDnp, induced by the toxin, was prevented by PMSF, simvastatin, and phenanthroline, suggesting the involvement of metallo- and serine proteases in this complement-dependent hemolysis model.

Im Fokus dieser Dissertation steht die Zerstörung des Lebensraumes von Schlangen durch anthropogene Einflüsse im Zusammenhang mit dem Auftreten von Schlangenbissen bei Menschen. Zum Schutz der Schlangen und dem Problem der Schlangenbisse wurden vier wesentliche Anforderungen erarbeitet. Mit Hilfe eines Artenverteilungsmodells wurden die ökologischen Nischen von 29 Giftschlangenarten aus Bangladesch und von zehn Kobraarten (Naja) aus Asien ermittelt. Auf lokaler Ebene wurde festgestellt, dass Überschwemmungen, Waldtypen, Ökosysteme und klimatische Parameter das Verbreitungsgebiet der Schlangenarten in Bangladesch beeinflussen. Auf regionaler Ebene sind anthropogene Faktoren wie die Zerstörung von Schlangenlebensräumen, Handel, Ausbeutung und Tötung von Schlangen wahrscheinlich die Hauptursachen für den Rückgang der Populationen der asiatischen Naja. Auf beiden Ebenen führt der Klimawandel zu einer Verkleinerung der ökologischen Nischen von Schlangenarten in Bangladesch und Asien. In Bangladesch könnten die untersuchten Arten innerhalb der nächsten 50 Jahre mehr als 90 % ihren derzeitigen Lebensraum verlieren (Asiatische Naja durchschnittlich 56 % (12 bis 100 %)). Wenn günstige Nischen nicht erhalten werden können, könnten viele Schlangenarten in einigen Ländern Asiens, darunter Bangladesch, in wenigen Jahrzehnten aussterben. Darüber hinaus wurde in der vorliegenden Studie geschätzt, dass die Zahl der jährlichen Schlangenbisse in Bangladesch mehr als doppelt so hoch sein könnte wie bisher angenommen. Da der Klimawandel zu einer geografischen Verschiebung günstiger Nischen führen kann, kann sich diese Veränderung auch auf die Häufigkeit von Schlangenbissen auswirken. Bei der Analyse von Giftvariationen und der Wirksamkeit von Antivenomen wurde festgestellt, dass isolierte Populationen deutliche intraspezifischere Giftvariationen zeigen. / Snakes are threatened by habitat degradation and anthropogenic impacts, while accidental encounters between humans and snakes may result in snakebite incidents. Thus, the conservation of snakes snakebite problem, a global public health emergency, are interconnected. I found four primary needs for a combined solution to satisfy both above causes. A species distribution model was employed to identify the ecological niches of 29 venomous snake species from Bangladesh and of ten cobra species (Naja) from Asia. At the local scale, flood events, forest types, ecosystems, and climatic parameters were found to shape the range of snake species in Bangladesh. At the regional scale, anthropogenic factors, like snake habitat destruction, trade, exploitation, and snake killings are likely to be the main causes for the decrease in populations of Asian Naja. At both levels, climate change causes shrinking and fragmenting the ecological niches of snake species in Bangladesh and Asia. In Bangladesh, the studied species may lose more than 90% of their current climatic niche within the next 50 years. In the same timeframe, Asiatic Naja may lose an average of 56% (12- 100%) of the area of suitable climatic niches. If favourable niches cannot be preserved, many snake species might go extinct from several countries in Asia in a few decades, including Bangladesh. In addition, the present study estimated that there might be more than double the amount of annual snakebite incidents in Bangladesh than previously estimated. As climate change may cause geographical shifting of favourable niches, this change may also have consequences for the frequency of snakebites, so snakebite should be considered a climate driven dynamic public health problem. While analysing venom variations and the efficacy of antivenom, I found that venom should be sampled from geographically or ecologically isolated populations of each venomous snake, because isolated populations have shown distinct intraspecific venom variations.

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