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3.
J Am Board Fam Med ; 33(3): 456-459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32430379

RESUMO

OBJECTIVES: Investigation is scare on job satisfaction among general practitioners (GPs) in China. This study aimed to investigate job satisfaction of GPs in China and explore its determinants. METHODS: A multistage-stratified random sampling method was used to collect data with a structured self-administered questionnaire from 3236 GPs (response rate, 99.8%) working in community health institutions in China between October 2017 and February 2018. Multiple linear stepwise regression analysis was used to analyze the associated factors with job satisfaction among GPs. RESULTS: Among these respondents, 1215 (37.5%), 352 (10.9%), and 1669 (51.6%) GPs were dissatisfied, moderate, and satisfied for their current job, respectively. Male GPs, a higher education level, at a higher professional title, at a lower level of income, and those with heavy work stress had a lower job satisfaction. In addition, GPs who often worked overtime, who were at a higher level of emotional exhaustion, at a higher level of depersonalization, at a lower level of personal accomplishment, and who had less occupational development opportunities reported a lower level of job satisfaction. CONCLUSION: These findings suggest that job satisfaction among Chinese GPs is at a moderate level. Region, sex, professional title, education level, working overtime, income level, emotional exhaustion, depersonalization, personal accomplishment, work stress, and occupational development opportunities were significant predictors of job satisfaction.


Assuntos
Esgotamento Profissional , Clínicos Gerais , Satisfação no Emprego , Esgotamento Profissional/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Clínicos Gerais/psicologia , Humanos , Masculino , Fatores Sexuais , Inquéritos e Questionários
4.
BMC Fam Pract ; 21(1): 80, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375674

RESUMO

BACKGROUND: Studies on professional identity and related factors among Chinese general practitioners (GPs) are unavailable. The objective of this study was to investigate the professional identity level of GPs in China and explore factors associated with GPs' perceptions of their professional identity. METHODS: A multistage stratified random sampling method was used to collect data with a structured self-administered questionnaire from 3236 GPs working in community health service institutions (CHIs) in China between October, 2017 and February, 2018. Professional identity was measured by the 13 items scale. Descriptive statistics were calculated and groups' differences were estimated using nonparametric tests. Multiple linear stepwise regression analysis was used to analyze factors associated with professional identity among GPs. RESULTS: Based on a total score of 65 on the professional identity scale, the average score for GPs' professional identity was 51.23 (SD = 6.56). Multiple linear stepwise regression analysis showed that GPs who practiced in Central China, with an administrative responsibility, at a moderate or higher income level, who frequently worked overtime, had more occupational development opportunities, with a higher level of job satisfaction and older GPs had higher levels of professional identity. CONCLUSIONS: Professional identity level among GPs in China is high. Region, administrative responsibility, income level, working overtime, occupational development opportunities, age, and job satisfaction were significant predictors of professional identity.


Assuntos
Atitude do Pessoal de Saúde , Clínicos Gerais , Identificação Social , China , Estudos Transversais , Feminino , Clínicos Gerais/estatística & dados numéricos , Humanos , Renda , Satisfação no Emprego , Modelos Lineares , Masculino , Papel Profissional
5.
Obes Rev ; 21(3): e12977, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31814253

RESUMO

The relationship between long working hours and body weight outcomes remains inconclusive; thus, we conducted a meta-analysis to assess the effect of long working hours on weight-related outcomes. PubMed and Embase databases were searched from their inception to June 2019. A random-effects model was used to assess the pooled odds ratio (OR) and corresponding confidence interval (CI). Subgroup analyses and sensitivity analyses were conducted to explore sources of heterogeneity. Publication bias was evaluated by the Begg's and Egger's tests. A total of 29 articles involving 374 863 participants were included. The pooled OR of long working hours on weight-related outcomes was 1.13 (95% CI, 1.07-1.19). In subgroup analysis stratified by definition of outcomes, the pooled ORs of long working hours on "weight gain/BMI increase," "BMI ≥ 25 kg/m2 ," and "BMI ≥ 30 kg/m2 " were 1.19 (95% CI, 1.02-1.40), 1.07 (95% CI, 1.00-1.14), and 1.23 (95% CI, 1.09-1.39), respectively. We found evidence of publication bias, but correction for this bias using the trim-and-fill method did not alter the combined OR substantially. There was evidence to suggest that long working hours are associated with adverse weight-related outcomes. Preventative interventions such as improved flexibility and healthy working schedules should be established for employees.


Assuntos
Sobrepeso/epidemiologia , Trabalho/estatística & dados numéricos , Peso Corporal , Humanos , Estudos Observacionais como Assunto , Fatores de Risco , Tempo , Aumento de Peso
6.
Int J Health Plann Manage ; 35(2): 482-493, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31775176

RESUMO

Studies on turnover intention among Chinese general practitioners (GPs) at the national level are limited. This study aimed to assess intention to leave and its associated factors among a nationally representative sample of GPs. The participants were selected using a multistage stratified random sampling method. A self-administered structured questionnaire was used to collect data from 3236 GPs in China between October 2017 and February 2018. A multiple linear stepwise regression analysis was used to identify factors associated with turnover intention. Over 70.0% GPs had a moderate or high turnover intention. GPs who were male, were younger, had a higher education level, had a lower professional title, had a lower income level, and had a temporal work contract had higher turnover intention. In addition, GPs who worked night shifts, had low job satisfaction, and had few opportunities for professional development reported higher turnover intention. Substantial gender and regional differences in predictors of turnover intention among GPs were observed. The study showed that turnover intention in Chinese GPs is high, and the factors influencing turnover intention were low professional title and income level, high education level, having a temporary work contract, working night shifts, and limited opportunities for professional development.


Assuntos
Clínicos Gerais/psicologia , Intenção , Reorganização de Recursos Humanos , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
7.
BMC Public Health ; 19(1): 1607, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791282

RESUMO

BACKGROUND: High occupational burnout among general practitioners (GPs) is an important challenge to China's efforts to strengthen its primary healthcare delivery; however, data to help understand this issue are unavailable. This study aimed to investigate the prevalence of burnout and associated factors among GPs. METHODS: A cross-sectional design was used to collect data from December 12, 2014, to March 10, 2015, with a self-administered structured questionnaire from 1015 GPs (response rate, 85.6%) in Hubei Province, Central China. Burnout was measured using a 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS). MBI-HSS scores and frequency were analyzed by the three dimensions of emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Factors associated with burnout among GPs were estimated using a multiple linear regression model. RESULTS: Of the respondents, 2.46% had a high level of burnout in all three dimensions, 24.83% reported high levels of EE, 6.21% scored high on DP, and 33.99% were at high risk of PA. GPs who were unmarried, had lower levels of job satisfaction, and had been exposed to workplace violence experienced higher levels of burnout. Intriguingly, no statistically significant associations were found between burnout and the duration of GP practice, age, sex, income, practice setting, and professional level. CONCLUSION: This is the first study of occupational burnout in Chinese general practice. Burnout is prevalent among GPs in Hubei, China. Interventions aimed at increasing job satisfaction, improving doctor-patient relationships and providing safer workplace environments may be promising strategies to reduce burnout among GPs in Hubei, China.


Assuntos
Esgotamento Profissional/epidemiologia , Clínicos Gerais/psicologia , Adulto , Esgotamento Profissional/psicologia , China/epidemiologia , Estudos Transversais , Emoções , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Prevalência , Atenção Primária à Saúde , Fatores de Risco , Inquéritos e Questionários , Local de Trabalho/psicologia , Violência no Trabalho/psicologia
8.
Glob Chall ; 3(9): 1900004, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31565396

RESUMO

Solar-driven vapor generation is a promising method to mitigate freshwater shortage and water contamination. However, most of the current highly efficient solar evaporators suffer from low robustness, tedious preparation procedures, and high cost. In this study, an easy-to-manufacture, low-cost, and high-reliability solar-driven evaporator is designed using a black cotton towel with a hollow conical shape. The reactive dye molecules diffuse into the cotton and form strong covalent bonds with the fiber after dyeing, which firmly fixes light-absorbing materials on the substrate. The looped pile structure of towels and hierarchical structure of yarns enable the evaporator enlarged surface area. The hollow conical shape of the cotton towel can effectively suppress the heat loss to the environment without compromising light absorption. The 3D vapor generator exhibits an evaporation rate of 1.40 and 1.27 kg m-2 h-1 for pure water and saline water, respectively. Meanwhile, this towel-based solar-driven evaporator exhibits a promising antifouling property as well as superior reusability and provides a reliable pathway in dealing with realistic waters, such as seawater and dyeing sewage. Therefore, the low-cost, solar-driven water evaporation system offers a complementary approach for high-efficiency vapor generation and water purification in practical application.

9.
Occup Environ Med ; 76(12): 927-937, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31611310

RESUMO

We aim to quantitatively synthesise available epidemiological evidence on the prevalence rates of workplace violence (WPV) by patients and visitors against healthcare workers. We systematically searched PubMed, Embase and Web of Science from their inception to October 2018, as well as the reference lists of all included studies. Two authors independently assessed studies for inclusion. Data were double-extracted and discrepancies were resolved by discussion. The overall percentage of healthcare worker encounters resulting in the experience of WPV was estimated using random-effects meta-analysis. The heterogeneity was assessed using the I2 statistic. Differences by study-level characteristics were estimated using subgroup analysis and meta-regression. We included 253 eligible studies (with a total of 331 544 participants). Of these participants, 61.9% (95% CI 56.1% to 67.6%) reported exposure to any form of WPV, 42.5% (95% CI 38.9% to 46.0%) reported exposure to non-physical violence, and 24.4% (95% CI 22.4% to 26.4%) reported experiencing physical violence in the past year. Verbal abuse (57.6%; 95% CI 51.8% to 63.4%) was the most common form of non-physical violence, followed by threats (33.2%; 95% CI 27.5% to 38.9%) and sexual harassment (12.4%; 95% CI 10.6% to 14.2%). The proportion of WPV exposure differed greatly across countries, study location, practice settings, work schedules and occupation. In this systematic review, the prevalence of WPV against healthcare workers is high, especially in Asian and North American countries, psychiatric and emergency department settings, and among nurses and physicians. There is a need for governments, policymakers and health institutions to take actions to address WPV towards healthcare professionals globally.


Assuntos
Pessoal de Saúde , Violência no Trabalho/estatística & dados numéricos , Humanos , Prevalência
10.
Acta Ophthalmol ; 97(4): 353-363, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30402966

RESUMO

The effect of maternal smoking during pregnancy on strabismus in offspring remains unclear. We conducted a meta-analysis to summarize epidemiological evidences on the association between maternal smoking during pregnancy and the risk of offspring strabismus. Eligible studies were searched from the PubMed, Ovid, Embase and CNKI databases up to May 2018. The qualities of included articles were assessed with the Newcastle-Ottawa Scale and the assessment scale recommended by the Agency for Healthcare Research and Quality. Odds ratios (ORs) corresponding with its 95% confidence intervals (CIs) were pooled to estimate the effects of maternal cigarette smoking on the risk of offspring strabismus. Subgroup analyses and meta-regression were performed to explore the potential sources of heterogeneity. The Begg's test and Egger's test were used to assess the publication bias. Eleven articles involving 4,833 patients with strabismus were included. The pooled OR showed that maternal smoking during pregnancy was significantly associated with strabismus in offspring (OR = 1.46, 95% CI = 1.32-1.60). Compared with less than 10 cigarettes per day (OR = 1.17, 95% CI = 1.06-1.29), maternal smoking 10 cigarettes or more per day during pregnancy significantly increased the risk of offspring strabismus (OR = 1.79, 95% CI = 1.39-2.31). The risk of developing esotropia and exotropia for smoking pregnant women, respectively, increased by 65% (OR = 1.65, 95% CI = 1.31-2.09 and OR = 1.65, 95% CI = 1.24-2.19) than those who did not smoke during pregnancy. Additionally, the increased risk of maternity smoking associated with offspring strabismus was stable across all subgroup analyses. Overall, maternal smoking during pregnancy was associated with a significantly increased risk of offspring strabismus and the result was persistent in subgroup analyses, suggesting the importance in changing smoking habit or smoking cessation for women who are pregnant or preparing to.


Assuntos
Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Estrabismo/etiologia , Feminino , Saúde Global , Humanos , Incidência , Recém-Nascido , Gravidez , Fatores de Risco , Estrabismo/epidemiologia
11.
Am J Public Health ; 108(9): 1223-1226, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30024800

RESUMO

OBJECTIVES: To assess the prevalence and factors associated with physical and nonphysical violence in a sample of general practitioners (GPs). METHODS: We used a cross-sectional design to collect data from December 2014 to March 2015 with a structured self-administered questionnaire from 1015 GPs in Hubei Province, Central China (response rate, 85.6%). We used a multivariable logistic regression model to identify the predictors associated with workplace violence toward GPs. RESULTS: Of the respondents, 62.2% of respondents reported exposure to workplace violence in the preceding year, including 18.9% and 61.4% who encountered physical and nonphysical violence, respectively. Multivariable logistic regression analysis suggested that GPs who were male, at a higher professional level, and who had a lower average monthly income were more likely to experience physical violence. Male GPs, less-experienced GPs, and those with administrative responsibility were more likely than their counterparts to encounter nonphysical violence. CONCLUSIONS: This study shows that the prevalence of workplace violence against GPs is high in Hubei, China. Creating a prevention strategy and providing safer workplace environments for GPs should be urgently prioritized.


Assuntos
Clínicos Gerais , Violência no Trabalho/tendências , Adulto , China , Estudos Transversais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários
12.
Nat Commun ; 8(1): 397, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855501

RESUMO

Ubiquitin conjugation signals for selective protein degradation by the proteasome. In eukaryotes, ubiquitin is encoded both as a monomeric ubiquitin unit fused to a ribosomal gene and as multiple ubiquitin units in tandem. The polyubiquitin gene is a unique, highly conserved open reading frame composed solely of tandem repeats, yet it is still unclear why cells utilize this unusual gene structure. Using the Saccharomyces cerevisiae UBI4 gene, we show that this multi-unit structure allows cells to rapidly produce large amounts of ubiquitin needed to respond to sudden stress. The number of ubiquitin units encoded by UBI4 influences cellular survival and the rate of ubiquitin-proteasome system (UPS)-mediated proteolysis following heat stress. Interestingly, the optimal number of repeats varies under different types of stress indicating that natural variation in repeat numbers may optimize the chance for survival. Our results demonstrate how a variable polycistronic transcript provides an evolutionary alternative for gene copy number variation.Eukaryotic cells rely on the ubiquitin-proteasome system for selective degradation of proteins, a process vital to organismal fitness. Here the authors show that the number of repeats in the polyubiquitin gene is evolutionarily unstable within and between yeast species, and that this variability may tune the cell's capacity to respond to sudden environmental perturbations.


Assuntos
Poliubiquitina/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Ubiquitina C/genética , Evolução Biológica , Clonagem Molecular , Variações do Número de Cópias de DNA , Dosagem de Genes , Genes Fúngicos , Proteínas de Fluorescência Verde/metabolismo , Temperatura Alta , Poliubiquitina/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteostase , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Ubiquitina C/metabolismo
13.
PLoS Genet ; 11(11): e1005635, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26545090

RESUMO

Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.


Assuntos
Adaptação Fisiológica , Etanol/farmacologia , Aneuploidia , Haploidia
14.
ACS Appl Mater Interfaces ; 7(31): 17112-21, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26181359

RESUMO

In this study, AgCuZn sulfide is fabricated on the surface of AgCuZn alloys by hydrothermal sulfuration. This ternary metal sulfide is equipped with enhanced activity toward oxygen evolution reaction (OER) in an alkaline electrolyte. Through comparison of the alloys with diverse compositions, we find out the best electrochemical property of a particular alloy sulfide forming on a AgCuZn substrate (Ag:Cu:Zn=43:49:8). The alloy sulfide exhibits an onset overpotential (η) of 0.27 V with a Tafel slope of 95±2 mV dec(-1) and a current density of 130 mA cm(-2) at η of 0.57 V. Moreover, the obtained AgCuZn sulfide displays excellent stability, where the current density can increase to 130% of the initial value after a water electrolysis test for 100,000 s (27.7 h). Through investigating the electrode before and after the electrocatalysis, we find a remarkable activated process during which self-supported copper-silver oxide nanowire (CuO-Ag2O NW) arrays in situ form on the surface of the electrode. This work provides a feasible strategy for synthesis of high performance nonprecious metal electrocatalysts for water splitting.

15.
PLoS Genet ; 9(8): e1003693, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23966873

RESUMO

Revealing QTLs with a minor effect in complex traits remains difficult. Initial strategies had limited success because of interference by major QTLs and epistasis. New strategies focused on eliminating major QTLs in subsequent mapping experiments. Since genetic analysis of superior segregants from natural diploid strains usually also reveals QTLs linked to the inferior parent, we have extended this strategy for minor QTL identification by eliminating QTLs in both parent strains and repeating the QTL mapping with pooled-segregant whole-genome sequence analysis. We first mapped multiple QTLs responsible for high thermotolerance in a natural yeast strain, MUCL28177, compared to the laboratory strain, BY4742. Using single and bulk reciprocal hemizygosity analysis we identified MKT1 and PRP42 as causative genes in QTLs linked to the superior and inferior parent, respectively. We subsequently downgraded both parents by replacing their superior allele with the inferior allele of the other parent. QTL mapping using pooled-segregant whole-genome sequence analysis with the segregants from the cross of the downgraded parents, revealed several new QTLs. We validated the two most-strongly linked new QTLs by identifying NCS2 and SMD2 as causative genes linked to the superior downgraded parent and we found an allele-specific epistatic interaction between PRP42 and SMD2. Interestingly, the related function of PRP42 and SMD2 suggests an important role for RNA processing in high thermotolerance and underscores the relevance of analyzing minor QTLs. Our results show that identification of minor QTLs involved in complex traits can be successfully accomplished by crossing parent strains that have both been downgraded for a single QTL. This novel approach has the advantage of maintaining all relevant genetic diversity as well as enough phenotypic difference between the parent strains for the trait-of-interest and thus maximizes the chances of successfully identifying additional minor QTLs that are relevant for the phenotypic difference between the original parents.


Assuntos
Proteínas de Ciclo Celular/genética , Locos de Características Quantitativas/genética , Processamento Pós-Transcricional do RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Alelos , Mapeamento Cromossômico , Ligação Genética , Variação Genética , Temperatura Alta , RNA/genética
16.
PLoS Genet ; 9(6): e1003548, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23754966

RESUMO

The yeast Saccharomyces cerevisiae is able to accumulate ≥17% ethanol (v/v) by fermentation in the absence of cell proliferation. The genetic basis of this unique capacity is unknown. Up to now, all research has focused on tolerance of yeast cell proliferation to high ethanol levels. Comparison of maximal ethanol accumulation capacity and ethanol tolerance of cell proliferation in 68 yeast strains showed a poor correlation, but higher ethanol tolerance of cell proliferation clearly increased the likelihood of superior maximal ethanol accumulation capacity. We have applied pooled-segregant whole-genome sequence analysis to identify the polygenic basis of these two complex traits using segregants from a cross of a haploid derivative of the sake strain CBS1585 and the lab strain BY. From a total of 301 segregants, 22 superior segregants accumulating ≥17% ethanol in small-scale fermentations and 32 superior segregants growing in the presence of 18% ethanol, were separately pooled and sequenced. Plotting SNP variant frequency against chromosomal position revealed eleven and eight Quantitative Trait Loci (QTLs) for the two traits, respectively, and showed that the genetic basis of the two traits is partially different. Fine-mapping and Reciprocal Hemizygosity Analysis identified ADE1, URA3, and KIN3, encoding a protein kinase involved in DNA damage repair, as specific causative genes for maximal ethanol accumulation capacity. These genes, as well as the previously identified MKT1 gene, were not linked in this genetic background to tolerance of cell proliferation to high ethanol levels. The superior KIN3 allele contained two SNPs, which are absent in all yeast strains sequenced up to now. This work provides the first insight in the genetic basis of maximal ethanol accumulation capacity in yeast and reveals for the first time the importance of DNA damage repair in yeast ethanol tolerance.


Assuntos
Proliferação de Células , Etanol/metabolismo , Locos de Características Quantitativas/genética , Saccharomyces cerevisiae/genética , Bebidas Alcoólicas/microbiologia , Alelos , Mapeamento Cromossômico , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Tolerância a Medicamentos/genética , Etanol/farmacologia , Genoma , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética
17.
Genome Res ; 22(5): 975-84, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22399573

RESUMO

High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces cerevisiae, which enables this microorganism to dominate in natural and industrial fermentations. Up to now, ethanol tolerance has only been analyzed in laboratory yeast strains with moderate ethanol tolerance. The genetic basis of the much higher ethanol tolerance in natural and industrial yeast strains is unknown. We have applied pooled-segregant whole-genome sequence analysis to map all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants, we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of DNA from the two pools and parents revealed three major loci and additional minor loci. The latter were more pronounced or only present in the 17% pool compared to the 16% pool. In the locus with the strongest linkage, we identified three closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with SWS2 being a negative allele located in between two positive alleles. SWS2 and APJ1 probably contained significant polymorphisms only outside the ORF, and lower expression of APJ1 may be linked to higher ethanol tolerance. This work has identified the first causative genes involved in high ethanol tolerance of yeast. It also reveals the strong potential of pooled-segregant sequence analysis using relatively small numbers of selected segregants for identifying QTL on a genome-wide scale.


Assuntos
Etanol/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Mapeamento Cromossômico , Técnicas de Inativação de Genes , Genes Fúngicos , Estudos de Associação Genética , Ligação Genética , Genoma Fúngico , Viabilidade Microbiana , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Análise de Sequência de DNA
18.
Bioinformatics ; 23(9): 1049-52, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17341495

RESUMO

MOTIVATION: Elementary modes (EMs) analysis has been well established. The existing methodologies for assigning weights to EMs cannot be directly applied for large-scale metabolic networks, since the tremendous number of modes would make the computation a time-consuming or even an impossible mission. Therefore, developing more efficient methods to deal with large set of EMs is urgent. RESULT: We develop a method to evaluate the performance of employing a subset of the elementary modes to reconstruct a real flux distribution by using the relative error between the real flux vector and the reconstructed one as an indicator. We have found a power function relationship between the decrease of relative error and the increase of the number of the selecting EMs, and a logarithmic relationship between the increases of the number of non-zero weighted EMs and that of the number of the selecting EMs. Our discoveries show that it is possible to reconstruct a given flux distribution by a selected subset of EMs from a large metabolic network and furthermore, they help us identify the 'governing modes' to represent the cellular metabolism for such a condition.


Assuntos
Algoritmos , Metabolismo Energético/fisiologia , Modelos Biológicos , Proteoma/metabolismo , Transdução de Sinais/fisiologia , Simulação por Computador
19.
Appl Microbiol Biotechnol ; 73(4): 887-94, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16927085

RESUMO

In the post-genome era, it is one challenge to understand the cellular metabolism at the systematic levels. Mathematical modeling of microorganisms and subsequent computer simulation are effective tools for systems biology. In this paper, based on the genome-scale Escherichia coli stoichiometric model iJR904, through the GAMS linear programming package, the in silico maximal succinate yield was estimated to be 1.714 mol/mol glucose. When another two constraints were added, the maximal succinate yield dropped to 1.60 mol/mol glucose. Further analysis substantiated the uniqueness of the flux distribution under such constraints. After comparisons with the metabolic flux analysis (MFA) results computed from the wet experimental data of the three kinds of E. coli, three potential improvement target sites, the glucose phosphotransferase transport system, the pyruvate carboxylase, and the glyoxylate shunt, were identified and selected for the genetic modifications. All the three genetic modified strains showed increased succinate yield. The final strain TUQ19/pQZ6 had a high yield of 1.29 mol succinate/mol glucose and high productivity. The success of the above experiments proved that this in silico optimal succinate production pathway is reasonable and practical. This method may also be used as a general strategy to help enhance the yields of other favorable metabolites in E. coli.


Assuntos
Simulação por Computador , Escherichia coli/genética , Escherichia coli/metabolismo , Genoma Bacteriano , Redes e Vias Metabólicas/genética , Ácido Succínico/metabolismo , Anaerobiose , Biologia Computacional , Proteínas de Escherichia coli/genética , Deleção de Genes , Glucose/metabolismo , Glioxilatos/metabolismo , Redes e Vias Metabólicas/fisiologia , Modelos Biológicos , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/genética , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/metabolismo , Piruvato Carboxilase/genética , Piruvato Carboxilase/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição/genética
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