The Interaction of the Calcium Sensitiser Levosimendan with Cardiac Troponin C

Cardiac failure is one of the leading causes of mortality in developed countries. As life expectancies of the populations of these countries grow, the number of patients suffering from cardiac insufficiency also increase. Effective treatments including the use of calcium sensitisers are being sought. They cause a positive inodilatory effect on cardio-myocytes without deleterious effects (arrhythmias) resulting from increases in intracellular calcium concentration. Levosimendan is a novel calcium sensitiser that hasbeen proved to be a welltolerated and effective treatment for patients with severe decompensated heart failure. Cardiac troponin C (cTnC) is its target protein. However, there have been controversies about the interactions between levosimendan and cTnC. Some of these controversies have been addressed in this dissertation. Furthermore, studies on the calcium sensitising mechanism based on the interactions between levosimendan and cTnC as followed by nuclear magnetic resonance(NMR) are presented and discussed. Levosimendan was found to interact with bothdomains of the calcium-saturated cTnC in the absence of cardiac troponin I (cTnI). In the presence of cTnI, the C-domain binding site was blocked and levosimendan interacted only with the regulatory domain of cTnC. This interaction may have caused the observed calcium sensitising effect by priming the N-domain for cTnI binding thereby extending the lifetime of that complex. It is suggested that this is achieved by shifting the equilibrium between open and closed conformations.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint.

BACKGROUND: This study aimed to determine 5-year efficacy of catheter ablation for persistent atrial fibrillation (AF) using AF termination as a procedural end point. METHODS AND RESULTS: One hundred fifty patients (57±10 years) underwent persistent AF ablation using a stepwise ablation approach (pulmonary vein isolation, electrogram-guided, and linear ablation) with the desired procedural end point being AF termination. Repeat ablation was performed for recurrent AF or atrial tachycardia. AF was terminated by ablation in 120 patients (80%). Arrhythmia-free survival rates after a single procedure were 35.3%±3.9%, 28.0%±3.7%, and 16.8%±3.2% at 1, 2, and 5 years, respectively. Arrhythmia-free survival rates after the last procedure (mean 2.1±1.0 procedures) were 89.7%±2.5%, 79.8%±3.4%, and 62.9%±4.5%, at 1, 2, and 5 years, respectively. During a median follow-up of 58 (interquartile range, 43-73) months after the last ablation procedure, 97 of 150 (64.7%) patients remained in sinus rhythm without antiarrhythmic drugs. Another 14 (9.3%) patients maintained sinus rhythm after reinitiation of antiarrhythmic drugs, and an additional 15 (10.0%) patients regressed to paroxysmal recurrences only. Failure to terminate AF during the index procedure (hazard ratio 3.831; 95% confidence interval, 2.070-7.143; P<0.001), left atrial diameter ≥50 mm (hazard ratio 2.083; 95% confidence interval, 1.078-4.016; P=0.03), continuous AF duration ≥18 months (hazard ratio 1.984; 95% confidence interval, 1.024-3.846; P<0.04), and structural heart disease (hazard ratio 1.874; 95% confidence interval, 1.037-3.388; P=0.04) predicted arrhythmia recurrence. CONCLUSIONS: In patients with persistent AF, an ablation strategy aiming at AF termination is associated with freedom from arrhythmia recurrence in the majority of patients over a 5-year follow-up period. Procedural AF nontermination and specific baseline factors predict long-term outcome after ablation.

Viabilidade da cultura do morangueiro no Paraná - BR

Avaliou-se a viabilidade da exploração do morangueiro, no Paraná, em duas áreas, 0,3 ha (área média cultivada pela agricultura familiar) e 1 ha, por um ano. Elaborou-se uma planilha de fluxo de caixa a partir da qual se calcularam: Período de Recuperação do Capital (PRC), Retorno sobre Investimento (RI), Valor Presente Líquido (VPL) e Taxa Interna de Retorno (TIR). Todos para Custo Operacional Efetivo (COE), Custo Operacional Total (COT) e Custo Total de Produção (CTP). Para uma situação considerada normal, os indicadores de rentabilidade calculados foram (Tipo de custo: VPL área-padrão (TIR área- padrão) / VPL área efetiva (TIR área efetiva)) COE: US$ 17.856,55 (42%) / US$ 4.795,85 (39%); COT: US$ 5.182,40 (11%) / - US$ 1.691,97 (-13%); CPT: US$ 4.846,26 (10%) / -US$ 1.792,80 (-14%). Fez-se a análise de cenários para os fatores produtividade, preço de venda e mão de obra, analisando o VPL e a TIR. Verificou-se que o tamanho da área influenciou na viabilidade econômica, mostrando a importância de se determinar anualmente a área mínima viável para a agricultura familiar. Os resultados indicaram que a cultura é viável em curto prazo, quando considerado o COE como parâmetro de análise, mas pode não se sustentar em prazos maiores quando se consideram o COT, o CTP e a variação de alguns fatores de produção. Pela análise de cenários definidos pelos fatores de produção analisados, o VPL e a TIR alteram-se para níveis que oferecem risco à exploração.

β1 integrin regulation

Integrins are heterodimeric adhesion receptors mediating adhesion to extracellular matrix proteins and to other cells. Integrins are important in embryonic development, structural integrity of connective tissue, blood thrombus formation, and immune defense system. Integrins are transmembrane proteins whose ligand binding capacity (activity) is regulated by large conformational changes. Extracellular ligand binding or intracellular effector binding to integrin cytoplasmic face regulate integrin activity. Integrins are thus able to mediate bi-directional signaling. Integrin function is also regulated by intracellular location. Integrins are constantly recycled from endocytic vesicles to plasma membrane, and this has been shown to be important for cell migration and invasion as well. Deregulation of integrin functionality can lead to deleterious illnesses, such as bleeding or inflammatory disorders. It is also evident that integrin deregulation is associated with cancer progression. In this study, a novel Beta1 integrin associating protein, Rab21, was characterized. Rab21 binding to integrin cytoplasmic tail was shown to be important for Beta1 integrin endo- and exocytosis – intracellular trafficking. It was furher shown that this interaction has an important role in cell adhesion, migration, as well as in the final step of cell division, cytokinesis. This work showed that abrogation of Rab21 function or β1 integrin endocytic traffic, can lead to defects in cell division and results in formation of multinucleated cells. Multinucleation and especially tetraploidy can be a transient pathway to aneuploidy and tumorigenesis. This work characterized chromosomal deletions in rab21 locus in ovarian and prostate cancer samples and showed that a cell line with rab21 deletion also had impairment in cell division, which could be rescued by Rab21 re-expression. The work demonstrates an important role for Rab21 and Beta1 integrin traffic regulation in cell adhesion and division, and suggests a probable associaton with tumorigenesis. In this study, Beta1 integrin activity regulation was also addressed. A novel cell array platform for genome-scale RNAi screenings was characterized here. More than 4500 genes were knocked-down in prostate cancer cells using siRNA-mediated silencing. The effects on Beta1 integrin activity were analyzed upon knock-downs. The screen identified more that 400 putative regulators of Beta1 integrin activity in prostate cancer. In conclusion, this work will help us to understand complex regulatory pathways involved in cancer cell adhesion and migration.

Treatment of oily wastewater by ultrafiltration: The effect of different operating and solution conditions

In many industries, such as petroleum production, and the petrochemical, metal, food and cosmetics industries, wastewaters containing an emulsion of oil in water are often produced. The emulsions consist of water (up to 90%), oils (mineral, animal, vegetable and synthetic), surfactants and other contaminates. In view of its toxic nature and its deleterious effects on the surrounding environment (soil, water) such wastewater needs to be treated before release into natural water ways. Membrane-based processes have successfully been applied in industrial applications and are considered as possible candidates for the treatment of oily wastewaters. Easy operation, lower cost, and in some cases, the ability to reduce contaminants below existing pollution limits are the main advantages of these systems. The main drawback of membranes is flux decline due tofouling and concentration polarisation. The complexity of oil-containing systems demands complementary studies on issues related to the mitigation of fouling and concentration polarisation in membranebased ultrafiltration. In this thesis the effect of different operating conditions (factors) on ultrafiltration of oily water is studied. Important factors are normally correlated and, therefore, their effect should be studied simultaneously. This work uses a novel approach to study different operating conditions, like pressure, flow velocity, and temperature, and solution properties, like oil concentration (cutting oil, diesel, kerosene), pH, and salt concentration (CaCl2 and NaCl)) in the ultrafiltration of oily water, simultaneously and in a systematic way using an experimental design approach. A hypothesis is developed to describe the interaction between the oil drops, salt and the membrane surface. The optimum conditions for ultrafiltration and the contribution of each factor in the ultrafiltration of oily water are evaluated. It is found that the effect on permeate flux of the various factors studied strongly depended on the type of oil, the type of membrane and the amount of salts. The thesis demonstrates that a system containing oil is very complex, and that fouling and flux decline can be observed even at very low pressures. This means that only the weak form of the critical flux exists for such systems. The cleaning of the fouled membranes and the influence of different parameters (flow velocity, temperature, time, pressure, and chemical concentration (SDS, NaOH)) were evaluated in this study. It was observed that fouling, and consequently cleaning, behaved differently for the studied membranes. Of the membranes studied, the membrane with the lowest propensity for fouling and the most easily cleaned was the regenerated cellulose membrane (C100H). In order to get more information about the interaction between the membrane and the components of the emulsion, a streaming potential study was performed on the membrane. The experiments were carried out at different pH and oil concentration. It was seen that oily water changed the surface charge of the membrane significantly. The surface charge and the streaming potential during different stages of filtration were measured and analysed being a new method for fouling of oil in this thesis. The surface charge varied in different stages of filtration. It was found that the surface charge of a cleaned membrane was not the same as initially; however, the permeability was equal to that of a virgin membrane. The effect of filtration mode was studied by performing the filtration in both cross-flow and deadend mode. The effect of salt on performance was considered in both studies. It was found that salt decreased the permeate flux even at low concentration. To test the effect of hydrophilicity change, the commercial membranes used in this thesis were modified by grafting (PNIPAAm) on their surfaces. A new technique (corona treatment) was used for this modification. The effect of modification on permeate flux and retention was evaluated. The modified membranes changed their pore size around 33oC resulting in different retention and permeability. The obtained results in this thesis can be applied to optimise the operation of a membrane plant under normal or shock conditions or to modify the process such that it becomes more efficient or effective.

Vaticinium Nahumi latine et fennice

Arkit: E4 F2.

De echo

Dedicatio: Carolus Joh. Jegerschiöld, Elias Nibling.

Progress of soybean charcoal rot under tillage and no-tillage systems in Brazil

The increase in incidence of charcoal rot caused by Macrophomina phaseolina on soybeans (Glycine max) was followed four seasons in conventional and no-till cropping systems. In the 1997/98 and 2000/01 seasons, total precipitation between sowing and harvest reached 876.3 and 846.9 mm, respectively. For these seasons, disease incidence did not differ significantly between the no-till and conventional systems. In 1998/99 and 1999/00 precipitation totaled 689.9 and 478.3 mm, respectively. In 1998/99, in the no-till system, the disease incidence was 43.7% and 53.1% in the conventional system. In 1999/00 the final incidence was 68.7% and 81.2% for the no-till and conventional systems, respectively. For these two seasons, precipitation was lower than that required for soybean crops (840 mm), and the averages of disease incidence were significantly higher in the conventional system. The concentration of microsclerotia in soil samples was higher in samples collected in conventional system at 0 - 10 cm depth. However, analysis of microsclerotia in roots showed that in years with adequate rain no difference was detected. In dry years, however, roots from plants developed under the conventional system had significantly more microsclerotia. Because of the wide host range of M. phaseolina and the long survival times of the microsclerotia, crop rotation would probably have little benefit in reducing charcoal rot. Under these study conditions it may be a better alternative to suppress charcoal rot by using the no-till cropping system to conserve soil moisture and reduce disease progress.

Barcarola

Soitinnus: lauluäänet, piano.

L'Univers

1869/08/25 (Numéro 846).

Análise estrutural em floresta ombrófila densa de terra firme não explorada, Amazônia Oriental

O estudo teve como objetivo analisar a composição florística e as estruturas horizontal, interna e diamétrica da floresta. A pesquisa foi conduzida na Unidade de Manejo Florestal (UMF) da Fazenda Tracajás (02º35'53"S e 47º47'10"W), Município de Paragominas, Estado do Pará, Brasil. A floresta foi estratificada em três áreas homogêneas, denominadas classes I, II e III de estoques volumétricos, empregando-se análise multivariada: análises de agrupamento e discriminante. Em cada classe de estoque foram instaladas, aleatoriamente, cinco parcelas de 100 x 100 m (1,0 ha) cada uma, para medição dos indivíduos com dap > 15 cm. No centro de cada parcela de 100 x 100 m foi instalada uma subparcela de 10 x 100 m (0,1 ha), para medição dos indivíduos com 5 cm < dap < 15 cm. Nas classes I, II e III de estoques volumétricos das árvores com dap > 15 cm (nível I de inclusão), respectivamente, estimou-se uma densidade total de 322,4; 309,0; e 313,8 indivíduos por hectare, bem como dominância total de 27,36; 27,45; e 25,88 m²/ha e volume de fuste total de 358,69; 328,33; e 308,69 m³/ha. Nas classes I, II e III de estoques volumétricos das árvores com 5 cm < dap < 15 cm (nível II de inclusão), respectivamente, estimaram-se densidade total de 846; 854; e 886 indivíduos por hectare, dominância total de 4,80; 4,93; e 5,46 m²/ha e volume de fuste total de 93,98; 91,23; e 97,61 m³/ha. As espécies de maior valor de importância relativa, Lecythis idatimon (potencial), Rinorea guianensis (não comercial) e Pouteria guianensis (potencial), ocorreram em todos os níveis de inclusão e classes de estoque. As distribuições de diâmetros de todas as espécies e das espécies comerciais com dap > 5 cm, estimadas pela equação de Meyer, confirmaram a tendência exponencial negativa ("J-invertido"). A análise da estrutura da floresta em classes de estoque permitiu melhor conhecimento da composição de espécies e da estrutura fitossociológica, sendo útil na tomada de decisões em planos de manejo de rendimento sustentável.

Dinâmica da cobertura vegetal (1980-2004) em um projeto de produção florestal, nos municípios de Bugre e Ibapa, MG

O objetivo principal do trabalho foi analisar a dinâmica da estrutura da paisagem em um projeto de produção florestal, entre os anos de 1980 e 2004, enfatizando-se as alterações ocorridas na paisagem após a implantação de talhões de eucalipto. A área de estudo compreendeu os limites do projeto de produção florestal Macedônia, localizado nos Municípios de Bugre e Ipaba, região leste do Estado de Minas Gerais. O mapeamento do uso da terra referente ao ano de 1980 foi realizado por meio da interpretação visual de um mosaico de fotografias aéreas. Para o mapeamento do uso da terra referente ao ano de 2004, foi empregada uma imagem multiespectral do satélite Quickbird. A caracterização quantitativa da estrutura da paisagem foi descrita utilizando-se índices de ecologia da paisagem. Constatou-se que os plantios de eucalipto foram implantados em áreas de pastagem arborizada (45,2 %) e pastagem limpa (46,9%). Essas duas classes foram as que mais tiveram seu uso alterado; elas deram lugar principalmente a florestas nativas (15,6%). Constatou-se que, dos 938,6 ha das florestas nativas em 1980, 846,42 ha mantiveram inalteradas as respectivas áreas. A conectividade entre as reservas florestais nativas também diminuiu, de 165,04 m de distância mínima média entre elas em 1980 para 15,86 m no ano de 2004. O manejo integrado da propriedade alterou positivamente a estrutura da paisagem, alterando também o uso predominante destinado à produção de madeira e à preservação e conservação da biodiversidade.

Triagem pré-natal para toxoplasmose e fatores associados à soropositividade de gestantes em Goiânia, Goiás

OBJETIVO: estimar a prevalência e identificar fatores associados à soropositividade pelo Toxoplasma gondii em gestantes. MÉTODOS: estudo de corte transversal retrospectivo, a partir dos registros de mulheres triadas para toxoplasmose pelo Programa de Proteção à Gestante, em 2008, residentes em Goiânia (GO). Esses registros foram vinculados aos do banco de dados do Sistema Nacional de Informações sobre Nascidos Vivos do Estado de Goiás. O processo de vinculação ocorreu em três etapas, sendo pareados 10.316 registros para análise dentre os 12.846 registros iniciais. Nesse processo foram consideradas as variáveis: nome da mulher, idade, data de nascimento, data provável do parto, data de nascimento do recém-nascido e dados referentes ao domicílio. Os anticorpos anti-Toxoplasma gondii foram detectados em amostras de sangue seco coletadas em papel filtro por meio dos testes Q-Preven Toxo para IgG e IgM. O teste do χ2 e χ2 para tendência foram utilizados para análise dos dados, e o odds ratio (OR) para estimar a chance de associação entre variáveis de exposição e desfecho. RESULTADOS: a prevalência da infecção foi de 67,7%, e 0,7% apresentou anticorpos anti-Toxoplasma gondii IgM e IgG reagentes. Dessas, apenas três não se submeteram ao teste confirmatório em sangue venoso. A mediana do intervalo entre o screening e a nova coleta de sangue venoso foi de 12,5, e entre o screening e o teste confirmatório e de avidez, 20 dias. As variáveis associadas à exposição foram: faixa etária de 20-30 anos, OR=1,6, e >31 anos, OR=1,8; cor da pele parda, OR=1,4, e preta, OR=1,6; e escolaridade de 8-11 anos, OR=0,7, e >12 anos de estudo, OR=0,6. CONCLUSÃO: estimou-se elevada prevalência da infecção entre gestantes. Os fatores associados encontrados devem ser considerados durante o acompanhamento pré-natal, juntamente com ações educativas para a prevenção da infecção e vigilância do status sorológico de gestantes soronegativas.