Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.info:eu-repo/semantics/publishedVersio

Metabolic drivers of IC-BEVS productivity: Tackling the production of enveloped viral particles

The Insect Cell-Baculovirus Expression System (IC-BEVS) has a major track record for the production of recombinant proteins and vaccines. Although its widespread use, the physiological aspects that contribute to systems productivity are still to be fully disclosed. In the present work, the metabolic features of the two main insect host cell lines, Sf9 and High Five, were analyzed during cellular growth and after baculovirus infection for the production of enveloped Influenza VLPs (Inf-VLPs). The gathered data were contextualized in a metabolic network representative of central carbon and nitrogen metabolism. Metabolic Flux Analysis (MFA) was performed to have a quantitative overview of the cellular fluxome dynamics that followed infection. In addition, the main carbon sources that contributed most to flux activity were identified. The impact of baculovirus infection on the physiology of High Five and Sf9 host cell lines was assessed by metabolomics, aiming at the identification of metabolic markers of productivity. The information herein generated was used to design tailored supplementation schemes that could boost IC-BEVS production yields of two enveloped viral particles: influenza VLPs (Inf-VLP) as a vaccine candidate and the recombinant baculovirus (BV). The strong correlation observed between the metabolic state of the host cell and baculovirus infection highlights the capacity of this virus to act as a metabolic engineer, re-directing the cellular fluxome to support virus replication and production. The results also show that the viral load influence the cellular responsiveness to the supplements, with lower MOIs retrieving higher improvements in specific productivity. The careful selection of the MOI, along with the supplementation of culture medium with compounds altering cellular redox state and cholesterol metabolism, yielded a 6-fold improvement of specific productivity. These results pave the way to deepen our knowledge on the relationship between host cell and virus, contributing to the disclosure of the metabolic determinants that contribute to productivity

Avaliação de Impacto de Programas de Incentivos Fiscais à Inovação - Um Estudo sobre os Efeitos do PDTI no Brasil

A prática de incentivos fiscais à inovação é comumente adotada por diversos países com objetivo de estimular as formas na realização de atividades tecnológicas, sendo especialmente dirigidos as atividades de Pesquisa e Desenvolvimento (P&D). O uso generalizado desses incentivos culminou em uma ampla discussão internacional questionando-se sua efetiva capacidade de estimular (ou não) as formas beneficiárias a ampliarem seus investimentos em atividades tecnológicas, e assim, acelerar o ritmo de inovação no país. Dentro dessa discussão, o presente trabalho tem como objetivo realizar um exercício empírico de avaliação de um programa brasileiro de incentivos fiscais às atividades tecnológicas, o Programa de Desenvolvimento Tecnológico Industrial (PDTI). Para capturar os efeitos desse programa no comportamento das forrmas beneficiarias em relação as não-beneciarias, quanto a decisão de gasto em atividades tecnológicas, será aplicado o método Propensity Score Matching entendido como uma técnica para determinação de quase-experimentos, baseada em algoritmos de pareamento de indivíduos pertencentes a grupos distintos, cujo objetivo é julgar os efeitos de um determinado tratamento.Incentivos Fiscais, Inovação, Propensity Score Matching

Epifluorescence microscope methods for bacterial enumeration in a 4-chlorophenol degrading consortium

Epifluorescence microscope methods, namely BacLight, direct epifluorescence filter technique and Rhodamine 123, consistently underestimated plate bacterial counts in a 4-chlorophenol degrading consortium. Cells capable of passing through 0.2 mgrm filters, referred as `ultramicrocells', were found. Although cell counts were higher when traditional methods were used, BacLight and direct epifluorescence filter technique were convenient techniques for the systematic monitoring of bacteria involved in biodegradation processes, as results were consistent and available within a short time

Process intensification combined with Adaptive Laboratory Evolution enhance VLP- based vaccine candidates production in insect cells

Please click Additional Files below to see the full abstract

GeoloGIS-BH: An Information System for Using the Built Heritage for Geological Teaching

There are examples of using stones of the cultural heritage for teaching purposes. Information systems have found several potential uses in the promotion and preservation of cultural heritage. In this paper is considered the conceptual framework of an information system concerning features of geological interest (FGI) in the built heritage (without any consideration in terms of its software implementation). This FGI concept is used here in a very wide sense to encompass characteristics of geological materials that can be recognized with the naked eye and analogies of geological processes in the built environment. Two perspectives are considered for information organization: occurrences of FGIs in the built heritage (more suitable for Earth Sciences teaching) and FGIs as components of built heritage elements (more suitable for humanities teaching). The main issue that arises from the ensuing discussion was found to be the findability of a given FGI, depending on its visual contrast and the characteristics of the built heritage element. It is argued that, in this way, geological concepts can contribute to the promotion and conservation of the built heritageThis work is included in the activities of the project Lab2PT - Landscapes, Heritage and Territory laboratory - AUR/04509, which has financial support of the Portuguese Fundação para a Ciência e a Tecnologia through national funds and when applicable of the FEDER co-financing, in the aim of the new partnership agreement PT2020 and COMPETE2020 - POCI 01 0145 FEDER 007528.info:eu-repo/semantics/publishedVersio

A Comprehensive Metabolic Profile of Cultured Astrocytes Using Isotopic Transient Metabolic Flux Analysis and 13C-Labeled Glucose

Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA) to estimate intracellular fluxes in primary cultures of astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C-labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time points were then analyzed by mass spectrometry and/or high performance liquid chromatography. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase [PC; PC/pyruvate dehydrogenase (PDH) ratio = 0.5], malic enzyme (5% of the total pyruvate production), and catabolism of branched-chained amino acids (contributing with ∼40% to total acetyl-CoA produced) confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate–aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (∼0.7 μmol mg prot−1 h−1) was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of isotopic transient MFA for a comprehensive analysis of energy metabolism

Personalising outcome measurement in substance misuse treatment: the feasibility and psychometrics of two individualised outcome measures

Individualised information in substance misuse treatment complements standardised outcome measures. However, few studies investigate the use of individualised measures and their robustness in terms of quantifying outcomes. In this study, we analysed the psychometrics and feasibility of two individualised outcome measures (PQ and PSYCHLOPS). We followed a cross-sectional methodology, administering the individualised measures and three additional standardised measures (TOP, a measure of psychological health within addiction services; PHQ-9; CORE-OM) to a sample of 93 patients entering substance misuse treatment in four clinical services. The results showed high levels of patient acceptability of the two individualised measures (response rates > 95%). The internal reliability was good for both PQ and PSYCHLOPS (Cronbach’s alpha, .79 and .72, respectively). Convergent validity of PQ with standardised measures was weak: Pearson’s r values for TOP (psychological health), PHQ-9 and CORE-OM were .21, .22 and .27, respectively. In contrast, convergent validity of PSYCHLOPS was moderate: r = .40, .39 and .50, respectively. Convergence between PQ and PSYCHLOPS was weak (r = .28). Experience of previous treatment episodes was associated with higher PQ and PSYCHLOPS scores; PSYCHLOPS but not PQ scores were higher among those opting to complete the questionnaires in written rather than verbal format. Our findings demonstrated that PQ and PSYCHLOPS are reliable and feasible individualised outcome measures for use in substance misuse treatment units, although the lack of strong convergent validity indicates that they may be measuring different underlying constructs. Optimal outcome measurement may involve combining individualised and standardised measures.EU FEDER COMPETE: POCI-01-0145-FEDER- 007294info:eu-repo/semantics/publishedVersio