Anti-human immunodeficiency virus type 1 (HIV-1) antibodies whose binding to gp120 is enhanced by CD4 binding (CD4i antibodies) are generally considered nonneutralizing for primary HIV-1 isolates. However, a novel CD4i-specific Fab fragment, X5, has recently been found to neutralize a wide range of primary isolates.To investigate the precise nature of the extraordinary neutralizing ability of Fab X5, we evaluated the abilities of different forms (immunoglobulin G [IgG], Fab, and single-chain Fv) of X5 and other CD4i monoclonal antibodies to neutralize a range of primary HIV-1 isolates. Our results show that, for a number of isolates, the size of the neutralizing agent is inversely correlated with its ability to neutralize. Thus, the poor ability of CD4i-specific antibodies to neutralize primary isolates is due, at least in part, to steric factors that limit antibody access to the gp120 epitopes. Studies of temperature-regulated neutralization or fusion-arrested intermediates suggest that the steric effects are important in limiting the binding of IgG to the viral envelope glycoproteins after HIV-1 has engaged CD4 on the target cell membrane. The results identify hurdles in using CD4i epitopes as targets for antibody-mediated neutralization in vaccine design but also indicate that the CD4i regions could be efficiently targeted by small molecule entry inhibitors.Human immunodeficiency virus type 1 (HIV-1) entry into host cells is initiated by the binding of the gp120 subunit of the viral envelope glycoprotein (Env) complex to the host cell receptor (CD4) (8,20). This interaction induces conformational changes in gp120 resulting in the exposure of a conserved high-affinity binding site for the coreceptor (the chemokine receptors CCR5 or CXCR4) (46,47,54,56,59). A second obligatory binding step between the gp120-CD4 complex and the coreceptor is then thought to induce additional conformational changes that ultimately result in the fusion of viral and host cell membranes (9, 18).Neutralizing antibodies are believed to act, at least in part, by binding to the exposed Env surface and obstructing the initial interaction between a trimeric array of gp120 molecules on the virion surface and receptor molecules on the target cell (36,37,57). In response, HIV-1 has evolved a number of strategies to evade recognition by neutralizing antibodies, particularly those directed to the conserved CD4 and coreceptor binding sites of Env. The extent of protection of these sites from antibody recognition is limited by the necessity to preserve the accessibility for receptor interaction. In the case of the CD4bs this has led to the following structural features: (i) it is partially obscured from antibody recognition by the V1/V2 loop and associated carbohydrate structures; (ii) the flanking residues are variable and modified by glycosylation; (iii) it is recessed to an extent that limits direct access by an antibody variable region; (iv) clusters of residues within the CD4bs that do not directly interact with CD4 are subject to variation...
O principal objetivo deste estudo foi gerar tecnologias para a extração de óleo de pinhão manso, avaliando a quantidade e qualidade com diferentes métodos de extração. Para a extração do óleo foram utilizados dois tipos de extratores (fator A), prensa tipo expeller e prensa hidráulica, temperatura (fator B) frio (ambiente) e quente (80ºC) e diferentes níveis de descascado das sementes (fator C). Foi utilizado um delineamento inteiramente casualizado com arranjo fatorial AxBxC. As variáveis estudadas foram: quantidade e qualidade (acidez, teor de fósforo e umidade), do óleo bruto e filtrado, e a quantidade de torta. A prensa tipo expeller apresentou as maiores médias de desempenho de óleo bruto. A partir de três kg de sementes com 40% de descascado foi obtido 37,18% de óleo bruto. No índice de acidez, as menores médias foram observadas por prensa hidráulica, com 0% de cascas, com 4,11 mg KOH/g na acidez do óleo bruto e 5,17 mg KOH/g na acidez do óleo filtrado. Foram obtidos menores teores de fósforo, usando prensa hidráulica sem pré-aquecimento, com valores de 72,53 ppm no óleo bruto e 10,32 ppm no óleo filtrado. Foi alcançado maior teor de óleo com a prensa tipo expeller, mas de melhor qualidade na prensa hidráulica.Palavras Chave: bioenergia, biodiesel, teor de óleo.
In the actual mining scenario, copper bioleaching, mainly raw mined material known as run‐of‐mine (ROM) copper bioleaching, is the best alternative for the treatment of marginal resources that are not currently considered part of the profitable reserves because of the cost associated with leading technologies in copper extraction. It is foreseen that bioleaching will play acomplementary role in either concentration—as it does in Minera Escondida Ltd. (MEL)—or chloride main leaching plants. In that way, it will be possible to maximize mines with installed solvent‐extraction and electrowinning capacities that have not been operative since the depletion of their oxide ores. One of the main obstacles for widening bioleaching technology applications is thelack of knowledge about the key events and the attributes of the technology’s critical events at the industrial level and mainly in ROM copper bioleaching industrial operations. It is relevant to assess the bed environment where the bacteria–mineral interaction occurs to learn about the limiting factors determining the leaching rate. Thus, due to inability to accurately determine in‐situ key variables, their indirect assessment was evaluated by quantifying microbial metabolic‐associated responses. Several candidate marker genes were selected to represent the predominant components of the microbial community inhabiting the industrial heap and the metabolisms involved in microbial responses to changes in the heap environment that affect the process performance. The microbial community’s predominant components were Acidithiobacillus ferrooxidans, At. thiooxidans, Leptospirillum ferriphilum, and Sulfobacillus sp. Oxygen reduction, CO2 and N2 fixation/uptake, iron and sulfur oxidation, and response to osmotic stress were the metabolisms selected regarding research results previously reported in the system. After that, qPCR primers for each candidate gene were designed and validated. The expression profile of the selected genes vs. environmental key variables in pure cultures, column‐leaching tests, and the industrial bioleaching heap was defined. We presented the results obtained from the industrial validation of the marker genes selected for assessing CO2 and N2 availability, osmotic stress response, as well as ferrous iron and sulfur oxidation activity in the bioleaching heap process of MEL. We demonstrated that molecular markers are useful for assessing limiting factors like nutrients and air supply, and the impact of the quality of recycled solutions. We also learned about the attributes of variables like CO2, ammonium, and sulfate levels that affect the industrial ROM‐scale operation.
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