Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion

Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid activation genes (the first step in β-oxidation), main storage lipid formation genes, and phosphatidate phosphatase genes resulted in a constrained lipid metabolic network in which fatty acid flux was directed to a large extent toward phospholipids. This resulted in simultaneous increases of phospholipids by up to 2.8- fold and of FFAs by up to 40-fold compared with wild-type levels. Further deletion of phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and 105% increase in phospholipid levels, suggesting that phospholipid hydrolysis plays an important role in FFA production when phospholipid levels are increased. The multiple deletion mutant generated allowed for a study of fatty acid dynamics in lipid metabolism and represents a platform strain with interesting properties that provide insight into the future development of lipid-related cell factories

Integration Between Lean Manufacturing and Other Quality Tools: A Scale Development

In order to improve organization’s performance, both in quality and productivity, several quality programs were created and implemented, with recent highlight to Lean Manufacturing (LM). All these initiatives are based on the involvement of employees, managers and organizational procedures, and it is expected that there will be some interaction between them. This paper describes the development and validation of a multi-item scale, an instrument which measures how employees perceive the integration between a production system based on the principles of Lean Manufacturing with other quality tools already used in the companies. The method included analyzes related to apparent validity, content validity, total item correlations, factor analysis and reliability. A questionnaire submitted to 317 respondents from a population of 1,699 employees of a metal-mechanic company included a proposed scale of 10 items to evaluate the integration between LM and other quality tools. After the analysis of the data, two questions were excluded because they did not present relevant factor loadings and the other eight questions resulted in two factors (Structure of integration of SP with other tools and Results in integration between SP and other tools). Confirmatory factor analysis confirmed that these factors constituted a model with good fit

Optimal Timing of Insecticide Fogging to Minimize Dengue Cases: Modeling Dengue Transmission among Various Seasonalities and Transmission Intensities

Dengue virus infection is a serious infectious disease transmitted by Aedes mosquitoes in the tropics and sub-tropics. Disease control often involves the use of insecticide fogging against mosquito vectors. However, the effectiveness of this method for reducing dengue cases, in addition to appropriate application procedures, is still debated. The previous mathematical simulation study reported that insecticide fogging reduces dengue cases most effectively when applied soon after the epidemic peak; however, the model did not take into account seasonality and population immunity, which strongly affect the epidemic pattern of dengue infection. Considering these important factors, we used a mathematical simulation model to explore the most effective time for insecticide fogging and to evaluate its impact on reducing dengue cases. Simulations were conducted with various lengths of the wet season and population immunity levels. We found that insecticide fogging substantially reduces dengue cases if conducted at an appropriate time. In contrast to the previously suggested application time during the peak of disease prevalence, the optimal timing is relatively early: between the beginning of the dengue season and the prevalence peak

Risk factors for hospital admission of Brazilian children with non-rotavirus diarrhoea: a case control-study

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-04-13T18:38:29Z No. of bitstreams: 1 Ichihara MYT Risk factors....pdf: 373112 bytes, checksum: 42869149bc783f5c4b6e3660f4b87911 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-04-13T18:51:08Z (GMT) No. of bitstreams: 1 Ichihara MYT Risk factors....pdf: 373112 bytes, checksum: 42869149bc783f5c4b6e3660f4b87911 (MD5)Made available in DSpace on 2016-04-13T18:51:09Z (GMT). No. of bitstreams: 1 Ichihara MYT Risk factors....pdf: 373112 bytes, checksum: 42869149bc783f5c4b6e3660f4b87911 (MD5) Previous issue date: 2015Universidade Federal da Bahia. Instituto da Saúde Coletiva. Salvador, BA, BrasilLondon School of Hygiene & Tropical Medicine. London, United KingdomState University of Feira de Santana. Feira de Santana, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto da Saúde Coletiva. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilBackground: Rotavirus has been the leading cause of severe cases of acute diarrhoea (AD) among children worldwide, however, in the same areas, a large reduction in AD related to rotavirus has been observed after the introduction of the rotavirus vaccine. In Brazil, where there is a high rotavirus vaccine coverage, AD caused by pathogens other than rotavirus is still a frequent cause of outpatient visits and hospitalizations among children under 5 years. Methods: A hospital-based case-control study enrolled children aged 4 to 24 months admitted to 10 hospitals from all five Brazilian Regions. Cases (n¼1178) were children admitted with diarrhoea who tested negative for rotavirus in a stool sample. Controls (n¼2515) were children admitted without diarrhoea, frequency matched to cases by sex and age group.We estimated odds ratios using logistic regression, in a hierarchical approach according to a previously defined conceptual framework. Population-attributable fractions (PAF) were estimated for each variable, each block and for all significant variables in the latter model adjusted. Results: The factors studied accounted for 41% of the non-rotavirus AD hospital admissions and the main risk factors included lack of adequate excreta disposal (PAF¼12%), untreated drinking water (PAF¼11%) and a history of previous hospitalization due to AD (PAF¼21%). Low socio-economic conditions, no public water supply, crowding and low weight-for-age made smaller contributions. Conclusions: These findings further our knowledge of risk factors associated with severe AD in the post-rotavirus vaccination era. We recommend further increase in coverage of basic sanitation, improvements in water quality and further expansion of primary healthcare coverage to reduce the occurrence of non-rotavirus severe diarrhoea and subsequent hospitalization of Brazilian children