Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In the present study, we applied a fast diagnostic protocol to the analysis of the quality of aquatic habitats (PAR) to assess the headwaters of the Siriri River, a first-order tributary of the Japaratuba River basin, Sergipe. The main source is located at UTM (707680, 8837848) in a 100-hectare fragment of Atlantic Forest, in the coastal plateau domain. The diagnosis proposed to evaluate external and internal human pressures, impacts resulting from the use of land and the exploitation of forest resources by the local Mata do Cipó community. The environmental diagnosis of this community was based on 52 semi-structured questionnaires applied to 24 men and 28 women, used to identify local conflicts, and the use of land and water resources. Land use was characterized by an historical overview together with a description of the geomorphology and aspects of the geology, soil, topography, climate, and vegetation. The rapid assessment protocol of habitat quality (RAP), adapted from Callisto et al (2002) was applied at 13 points along the Siriri stream, where a series of physical-chemical parameters of the water (pH, DO, TDS, ORP, eH, salinity, and total N and P) were analyzed and compared with the water quality parameters recommended by CONAMA (357). The environmental diagnosis of the community indicated a strong historical dependence for more than 80 years, the intensive exploitation of forest resources for bathing, hunting, leisure activities, and religious practices (African beliefs). The principal external pressure was the use of the land for sugarcane plantations and the main internal pressure was the exploitation of water resources by the neighboring town of Capela. The RAP concluded that 25% of the aquatic habitats are altered, with a loss of environmental resistance, while pH, nitrogen, and eH all exceeded CONAMA recommendations. We conclude that (a) this fragment of Atlantic Forest is a conservation priority due to the confirmation interviewees of the local occurrence and extinction of the titi monkey, Callicebus coimbrai Kobayashi & Langguth, 1999), (b) despite a low level of impact (25%) on this headwater environment, some physical-chemical parameters of the water have been affected, and (c) the local ecosystem appears to be resilient, although the habitats that surround the headwaters of the Siriri River require restoration. / Neste estudo aplicou o diagnóstico rápido da qualidade dos habitats terrestres e aquáticos (PAR) para avaliar a nascente do Rio Siriri, um tributário de primeira ordem da Bacia do Rio Japaratuba, Sergipe. A nascente principal está localizada na coordenada UTM (707680, 8837848) que compreende um fragmento de 100 hectares de Mata Atlântica, domínio dos Tabuleiros Costeiros. O diagnóstico propôs também avaliar as pressões antrópicas externas e internas, o estado e os impactos exercidos pelo uso da terra e pela comunidade Mata Cipó. O diagnóstico socioambiental da comunidade do entorno foram aplicados 52 questionários semiestruturados entre homens (24) e mulheres (28) com a finalidade de identificar os conflitos locais, uso do solo e dos recursos hídricos. Na caracterização uso do solo foi feito um breve histórico do uso da terra e uma descrição da geomorfologia e aspectos da litologia, solo, altimetria, relevo, clima e vegetação. O protocolo de avaliação rápida da qualidade de habitat (PAR), adaptado de Callisto et al (2002) foi aplicado em 13 pontos do riacho Siriri, assim com foram feitos análise dos parâmetros físico-químico da água: pH, OD, TDS, ORP, eH, salinidade, N e P totais e confrontadas com os parâmetros de qualidade da água pela portaria do CONAMA (357). O diagnóstico socioambiental da comunidade mostrou forte dependência histórica por mais de 80 anos de uso intenso dos recursos da mata para uso da água, lazer, caça e práticas e cultos religiosos afro. As pressões externa e interna sobre a comunidade e o fragmento de mata foram identificadas como o principal a monocultura de cana de açúcar sobre o uso do solo e a prefeitura de Capela sobre os recurso hídricos. Na avaliação do PAR constatou que 25% dos habitats aquáticos estão alterados com perda da resistência ambiental, enquanto os parâmetros da qualidade da água: pH, Nitrogênio, e eH estão acima dos parâmetros do CONAMA. Concluímos que: a) o fragmento de Mata Atlântica é prioritário para fins conservacionistas uma vez que comunidade confirmou a ocorrência e a extinção local do macaco Guigó, Callicebus coimbrai Kobayashi & Langguth, 1999); b) mesmo com 25% dos habitats de nascentes os parâmetros físico-químico da água estão alterados; c) o fragmento de mata tem capacidade de resiliência ecossistêmica, todavia os habitats de nascentes alterados necessitem de intervenção de restauração.

A doença de Wilson é um distúrbio da excreção biliar de cobre devido a um defeito na proteína ATP7B. Em caráter pioneiro na América do Sul, seqüenciou-se o gene ATP7B em 60 pacientes brasileiros pertencentes a 46 famílias; os resultados foram relacionados com aspectos demográficos e fenotípicos. Detectaram-se 25 mutações, 12 das quais novas. A 3402delC (34,8%) e a L708P (14,1%) ocorreu em 58,3% das famílias de São Paulo e em 44,4% das de Minas Gerais, respectivamente. As substituições novas, pesquisadas por RFLP ou PCR alelo-específica, não ocorreram em 60 indivíduos controle; portanto, não são polimorfismos comuns. O estudo comparativo de haplótipos dos portadores da L708P da coorte atual e de Gran Canaria sugeriu um efeito-fundador comum para ambos os grupos. O fenótipo variou amplamente para genótipos idênticos / ATP7B protein. As the first study of its kind in South America, the ATP7B gene was sequenced and the results were related to demographic and phenotypic aspects of 60 Brazilian patients, from 46 distinct families. Twenty-five mutations were detected, 12 of which are novel. The 3402delC (34.8%) and the L708P (14.1%) occurred in 58.3% of the families from Sao Paulo and in 44.4% of those from Minas Gerais, respectively. The novel substitutions were shown not to be common polymorphisms by RFLP or allele-specific PCR studies performed in 60 control subjects. Haplotype analysis comparing carriers of the L708P from this cohort study with patients from Gran Canary suggests the same founder-effect for both groups. Phenotype varied widely for identic genotypes.

Les récepteurs à la vasopressine V1bR et à la sérotonine 5HT3R jouent des rôles physiologiques importants dans la détection des signaux extracellulaires, les mécanismes de transmission nerveuse et diverses pathologies dont le cancer, le diabète et des maladies des SNC et SNP. Mes études avaient pour but de générer ou trouver des modulateurs peptidiques de ces deux récepteurs. Pour le V1bR, j’ai développé plusieurs anticorps de type VHH et les ai caractérisés aux plans biochimique et fonctionnel. L’un de ces VHHs agit comme un agoniste allostérique complet et spécifique du V1bR humain (hV1bR). In vitro ce VHH est capable d’activer les voies de signalisation de l’inositol phosphate et des MAP kinases et d’induire l'internalisation du hV1bR. Dans des îlots pancréatiques surexprimant le hV1bR, il induit une augmentation du Ca2+ intracellulaire et une sécrétion d'insuline. Pour le 5HT3R, j’ai criblé par SPR 31 venins de serpents sur des récepteurs recombinants immobilisés et mis en évidence une interaction à partir d’un de ces venins. Suite à purification par chromatographie liquide et identification par spectrométrie de masse, j’ai identifié une toxine préalablement caractérisée comme une enzyme à activité Ca2+-dépendante. Cette toxine interagit avec les 5HT3R A et AB indépendamment du Ca2+ et avec des valeurs de Kd ≤ 10 nM. L’analyse fonctionnelle par électrophysiologie suggère qu’elle agit comme un PAM de l’activité canal du 5HT3R. Des images de ME en coloration négative montrent la toxine fixée sur le domaine extracellulaire du 5HT3R, à distance du site pour la 5HT. Le VHH et la toxine pourraient être utilisés comme outils pharmacologiques et/ou agents thérapeutiques. / The vasopressin V1bR and serotonin 5HT3R receptors play important physiological roles in the detection of extracellular signals, in the mechanisms for neuronal transmission, and in various pathologies including cancer, diabetes, and CNS and PNS diseases. My studies were aimed at generating or finding peptidic modulators of these two receptors. For the V1bR, I developed several antibodies of the VHH type and characterized them biochemically and functionally. One of these VHHs acts as a complete allosteric agonist specific for the human V1bR (hV1bR). In vitro this VHH is able to activate the signaling pathways of inositol phosphate and MAP kinases and to induce the internalization of hV1bR. In pancreatic islets overexpressing hV1bR, it induces an increase in intracellular Ca2+ and a secretion of insulin. For the 5HT3R, using SPR I screened 31 snake venoms on immobilized recombinant receptors and for one of these venoms, evidenced an interaction. Following purification by liquid chromatography and identification by mass spectrometry, I identified a toxin previously characterized as an enzyme with Ca2+-dependent activity. This toxin interacts with the 5HT3R A and AB independently of Ca2+ and with Kd values ≤ 10 nM. Functional analysis by electrophysiology suggests that it acts as a PAM of the 5HT3R channel activity. Images recorded by negative staining EM show that the toxin binds to the 5HT3R extracellular domain, at a distance from the 5HT binding site. Both this VHH and this toxin could be used as pharmacological tools and / or therapeutic agents.

This study examined the ideograph of <collateral damage> through an analysis of the Bush Administration's rhetoric as well as visual photographs of Iraqi civilian deaths. The project argues that the psycho-dynamic rhetoric of the Bush Administration during a time of visual censorship lead to the dehumanization of Iraqi civilian deaths during the War in Iraq. The method consisted of a textual analysis of the Bush Administration's rhetoric and continued with a content analysis of news media's photographs. The author argues that critics gain a deeper understanding of the disappearing dead phenomenon of Iraqi civilians by examining ideographic fragments of psycho-dynamic rhetoric.

No description available.

The broad focus of this study is on how, through inequalities in power in constructed human socio-political, socio-economic and legal structures, the value and dignity of human life is destroyed. The researcher as artist wished to represent these observations though visual metaphor, metonymy and synecdoche in an installation, "Follow the thread". The dissertation contextualises that work within the works of Sheila Hicks, Amita Makan, Magdalena Abakanowicz and Ana Mendieta, all of whom use organic materials related to ideas about life and death. The first three use fibres as a metaphor for life. Through the analysis of metaphors in the selected artworks, the allusiveness of these metaphors is examined to offer insights about their indirect, referential, and evocative nature. It is revealed in the study that the success of metaphors operating within the visual language is closely linked to their complexity, their range scope and multimodality, and their ability to provoke multivalent, layered interpretations of artworks. My sculptural drawings that resemble fragments of the human body in the installation are a metaphor for the abuse of human dignity and for the disregard those in power have when life is reduced to bare life, rather than life appropriate to a legal citizen. / Arts and Music / M.V.A.

Viral proteases play crucial roles in the life cycle and maturation of many viruses by processing the viral polyprotein after translation and in some cases cleaving host proteins associated with the immune response. The essential role of viral proteases makes them attractive therapeutic targets. In this thesis, I provide an introductory summary of viral proteases, their structure, mechanism, and inhibition, while the breadth of this thesis focuses on the Hepatitis C virus (HCV) NS3/4A and Zika virus (ZIKV) NS2B/NS3 viral proteases. HCV NS3/4A protease inhibitors (PIs) have become a mainstay in combination therapies. However, drug resistance remains a major problem against these PIs. In this thesis, I applied insights from the HCV substrate envelope (SE) model to develop strategies for designing PIs that are less susceptible to resistance. Also, I used the HCV NS3/4A protease as a model system to decipher the molecular mechanism and role of fluorination in HCV PIs potency and drug resistance. The drug design strategies described in this thesis have broad applications in drug design. The ZIKV is an emerging global threat, and currently, with no treatment available. In this thesis, I described the discovery, biochemical and antiviral evaluation of novel noncompetitive quinoxaline-based inhibitors of the ZIKV NS2B/NS3 protease. The inhibitors are proposed to interfere with NS2 binding to NS3, thereby preventing the protease from adopting the closed and active conformation. The inhibitors from this work will serve as lead compounds for further inhibitor development toward the goal of developing antivirals.

We report the first total synthesis of oxydimurrayafoline via nucleophilic substitution at the benzylic position at C-3 of the carbazole framework. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

No description available.

Since the advent of the environmental crisis, some writers have raised concerns with the moral influence of Christian scripture and interpretive traditions, such as the medieval book of nature, a hermeneutic in which nature and scripture are "read" in reference to one another. Scripture, they argue, has tended to stifle sacred relationships with nature as a non-human other. This thesis argues that such perspectives are reductive of the sacred quality of scripture. Environmental perspectives should be concerned with the desacralization of religious texts in addition to nature. Chapter one suggests that two questions surrounding the medieval book of nature's history can help us address ways that such perspectives reduce religious interpretation of sacred texts. The first question is the tension between manifestation and proclamation, or the question of how scripture and nature reveal sacred meanings. The second is the problem of evil, or the question of where evil and suffering come from. It also proposes that Shakespeare's As You Like It and religious philosophy, particularly Paul Ricoeur's writings, can help us address these problems and provide a contemporary religious perspective of the "book of nature." Drawing on scenes in the play in which nature is "read" as a book and Ricoeur's essay on "Manifestation and Proclamation," chapter two argues how manifestation often works interdependently with proclamation. Chapter three discusses how anthropocentric worldviews in which natural entities are exploited also distort interpretive relationships with scripture. Overcoming desacralization requires giving up desires to suppress contingencies, particularly suffering, in nature and in interpreting religious texts. Only as the characters in As You Like It accept contingencies are they able to engage hidden sources of hope, which is comparable to the need to let go of mastery in interpretation Ricoeur describes. Chapter four discusses problems with attempts to uncover the origins of the environmental crisis by discussing what Ricoeur writes about the problems with theodicy and Jean-Luc Marion's phenomenology of evil. Assumptions that specific human origins for evil can be blamed confirm deceptively human-centered worldviews and can mask valuable messages about how to morally respond to suffering that are taught in Judeo-Christian narratives.