RESUMO
Ethanolic fermentation is frequently performed under conditions of low nitrogen. In Saccharomyces cerevisiae, nitrogen limitation induces macroautophagy, including the selective removal of mitochondria, also called mitophagy. Previous research showed that blocking mitophagy by deletion of the mitophagy-specific gene ATG32 increased the fermentation performance during the brewing of Ginjo sake. In this study, we tested if a similar strategy could enhance alcoholic fermentation in the context of fuel ethanol production from sugarcane in Brazilian biorefineries. Conditions that mimic the industrial fermentation process indeed induce Atg32-dependent mitophagy in cells of S. cerevisiae PE-2, a strain frequently used in the industry. However, after blocking mitophagy, no significant differences in CO2 production, final ethanol titers, or cell viability were observed after five rounds of ethanol fermentation, cell recycling, and acid treatment, which is commonly performed in sugarcane biorefineries. To test if S. cerevisiae's strain background influenced this outcome, cultivations were carried out in a synthetic medium with strains PE-2, Ethanol Red (industrial), and BY (laboratory) with and without a functional ATG32 gene and under oxic and oxygen restricted conditions. Despite the clear differences in sugar consumption, cell viability, and ethanol titers, among the three strains, we did not observe any significant improvement in fermentation performance related to the blocking of mitophagy. We concluded, with caution, that the results obtained with Ginjo sake yeast were an exception and cannot be extrapolated to other yeast strains and that more research is needed to ascertain the role of autophagic processes during fermentation. IMPORTANCE Bioethanol is the largest (per volume) ever biobased bulk chemical produced globally. The fermentation process is well established, and industries regularly attain nearly 85% of maximum theoretical yields. However, because of the volume of fuel produced, even a small improvement will have huge economic benefits. To this end, besides already implemented process improvements, various free energy conservation strategies have been successfully exploited at least in laboratory strains to increase ethanol yields and decrease byproduct formation. Cellular housekeeping processes have been an almost unexplored territory in strain improvement. It was previously reported that blocking mitophagy by deletion of the mitophagy receptor gene ATG32 in Saccharomyces cerevisiae led to a 2.1% increase in final ethanol titers during Japanese sake fermentation. We found in two commercially used bioethanol strains (PE-2 and Ethanol Red) that ATG32 deficiency does not lead to a significant improvement in cell viability or ethanol levels during fermentation with molasses or in a synthetic complete medium. More research is required to ascertain the role of autophagic processes during fermentation conditions.
Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Bebidas Alcoólicas , Proteínas Relacionadas à Autofagia , Etanol , Fermentação , Microbiologia Industrial , Mitofagia , Receptores Citoplasmáticos e Nucleares , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
We present results from a genome-wide scan of a six generation pedigree with 28 affected members with apparently dominant bipolar I disorder from eastern Cuba. Genotypes were obtained using the early access version of the Genechip Mapping 10K Xba array from AFFYMETRIX. Parametric and non-parametric linkage analyses under dominant and recessive models were performed using GENEHUNTER v2.1r5. Two phenotypic models were included in the analyses: bipolar I disorder and recurrent depressive disorder, or bipolar I disorder only. LOD scores were calculated for the entire family combined, and for four subdivisions of the family. For the entire family a suggestive parametric LOD score was obtained under the dominant model and the broader phenotype at 14q11.2-12 (LOD = 2.05). In the same region, a non-parametric LOD score close to genome-wide significance was also obtained, based on the entire family (NPL = 7.31, P-value = 0.07). For two individual branches of the pedigree, genome-wide significance (P < 0.005) was obtained with NPL scores of 8.71 and 12.99, respectively, also in the same region on chromosome 14. Chromosome 5q21.3-22.3 also showed close to genome-wide significant linkage for the complete pedigree (NPL = 7.26, P = 0.07), also supported by significant linkage in one individual branch (NPL = 9.86, P < 0.005). In addition, genome-wide significant nonparametric results (P-values <0.005) were obtained for individual branches at 5p13.1-q12.3, 6p22.3, 8q13.3-21.13, and 10q22.3-23.32. Finally, 2p25.1-25.3, 2p13.3-14, 3p14.2, 6p22.3-24.1, 7p14.1-14.2, 8q12.2-12.3, 10q21.1-21.2, 14q13.1-21.1, 15q15.1-21.2, and 22q12.3-13.32 showed suggestive linkage in the complete family. Most of these potential susceptibility loci overlap with, or are close, to previous linkage findings. The locus on 5q may, however, represent a novel susceptibility locus.
Assuntos
Transtorno Bipolar/genética , Cromossomos Humanos/genética , Ligação Genética , Predisposição Genética para Doença , Cuba , Feminino , Testes Genéticos , Genótipo , Humanos , Escore Lod , Masculino , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , FenótipoRESUMO
Homozygosity mapping is a very powerful method for finding rare recessive disease genes in monogenic disorders and may also be useful for locating risk genes in complex disorders, late onset disorders where parents often are not available, and for rare phenotypic subgroups. In the present study, homozygosity mapping was applied to 24 persons with bipolar disorder from 22 inbred families. The families were selected irrespective of whether other affected family members were present or not. A genome wide screen using genotypes from only a single affected person in each family was performed using the AFFYMETRIX GeneChip HuSNP Mapping Assay, which contains 1,494 single nucleotide polymorphisms. At chromosome 17q24-q25 a parametric multipoint LOD score of 1.96 was found at WIAF-2407 and WIAF-2405. When analyzing 19 additional microsatellite markers on chromosome 17q the maximum parametric multipoint LOD score was 2.08, 1.5 cM proximal to D17S668. The present study replicates a recent significant linkage finding.
Assuntos
Transtorno Bipolar/genética , Mapeamento Cromossômico/métodos , Predisposição Genética para Doença/genética , Genoma Humano , Polimorfismo de Nucleotídeo Único , Alelos , Cromossomos Humanos Par 17/genética , Consanguinidade , Cuba , Saúde da Família , Feminino , Frequência do Gene , Genótipo , Homozigoto , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , LinhagemRESUMO
De início tentamos situar o problema e esclarecê-lo a partir da tradição da psicanálise. A regressão tem um caráter ambivalente: abandono da vida com o mundo, volta a um self monádico. A ameaça deste 'grandioso Self' pode causar reações precipitadas. Apresentamos então exemplos de casuística de análise de pessoas 'normais' com traços narcisistas. Comprovamos os motivos das vivências tanatóides (de tipo mortal) nas defesas da regressão ao ventre materno. Fornecemos finalmente elementos para discussão do conteúdo ambivalente da 'psicanálise pré-natal', assim, como compreendida por Graber e como é natural na continuidade da tradição e desenvolvimento psicanalíticos(AU)