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共188条结果
  • 1.

    【2hr】The Saccharomyces SUN gene, UTH1, is Involved in Cell Wall Biogenesis

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    机译 酵母SUN基因，UTH1，参与细胞壁生物发生。
    摘要：Deletion of the Saccharomyces gene, UTH1, a founding member of the SUN family of fungal genes, has pleiotropic effects. Several phenotypes of Δuth1 cells including their decreased levels of mitochondrial proteins, their impaired autophagic degradation of mitochondria, and their increased viability in the presence of mammalian BAX, a pro-apoptotic regulator localized to the mitochondria, have prompted others to propose that the Uth1p functions primarily at the mitochondria. In this report, we show that cells lacking UTH1 have more robust cell walls with higher levels of β-d-glucan that allows them to grow in the presence of calcofluor white (CFW) or sodium dodecyl sulfate (SDS), two reagents known to perturb the yeast cell wall. Moreover, these Δuth1 cells are also significantly more resistant to spheroplast formation induced by zymolyase treatment than their wildtype counterparts. Surprisingly, our data suggests that several of the enhanced growth phenotypes of Δuth1 cells, including their resistance to BAX-mediated toxicity, arise from a strengthened cell wall. Therefore, we propose that Uth1p's role at the cell wall and not at the mitochondria may better explain many of its effects on yeast physiology and programmed cell death.
  • 2.

    【2hr】Prion amyloid structure explains templating: how proteins can be genes

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    机译 Prion淀粉样蛋白结构解释了模板：蛋白质如何成为基因
    摘要：The yeast and fungal prions determine heritable and infectious traits, and are thus genes composed of protein. Most prions are inactive forms of a normal protein as it forms a self-propagating filamentous β – sheet - rich polymer structure called amyloid. Remarkably, a single prion protein sequence can form two or more faithfully inherited prion variants, in effect alleles of these genes. What protein structure explains this protein-based inheritance? Using solid-state NMR, we showed that the infectious amyloids of the prion domains of Ure2p, Sup35p and Rnq1p have an in-register parallel architecture. This structure explains how the amyloid filament ends can template the structure of a new protein as it joins the filament.The yeast prions [PSI+] and [URE3] are not found in wild strains, indicating they are a disadvantage to the cell. Moreover, the prion domains of Ure2p and Sup35p have functions unrelated to prion formation, indicating that these domains are not present for the purpose of forming prions. Indeed, prion forming ability is not conserved, even within S. cerevisiae, suggesting that the rare formation of prions is a disease. The prion domain sequences generally vary more rapidly in evolution than does the remainder of the molecule, producing a barrier to prion transmission, perhaps selected in evolution by this protection.
  • 3.

    【2hr】The JmjC domain of Gis1 is dispensable for transcriptional activation

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    机译 Gis1的JmjC结构域可用于转录激活
    摘要：Yeast Gis1 protein functions as a transcription factor after nutrient limitation and oxidative stress. In this report, we show that Gis1 also regulates the induction of several genes involved in spore wall synthesis during sporulation. Gis1 contains a JmjC domain near its N-terminus. In many proteins JmjC domains provide histone demethylase activity. Whether the JmjC domain of Gis1 contributes to its transcriptional activation is still unknown. Here we show that gis1 point mutations that abolish Fe (II) and α-ketoglutarate binding, known co-factors in other JmjC proteins, are still able to induce transcription normally during glucose starvation and sporulation. Even deletion of the whole JmjC domain does not affect transcriptional activation by Gis1. Moreover, the JmjC domain is not required for the toxicity associated with Gis1 overexpression. The data demonstrate that the JmjC domain is dispensable for transcriptional activation by Gis1 during nutrient stress and sporulation.
  • 4.

    【2hr】Schizosaccharomyces cryophilus sp. nov., a new species of fission yeast

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    机译 嗜酒裂殖酵母十一月，裂变酵母的新品种
    摘要：The genus Schizosaccharomyces is presently comprised of three species, namely S. pombe, S. octosporus and S. japonicus. Here we describe a hitherto unknown species, Schizosaccharomyces cryophilus, named for its preference for growth at lower temperatures than the other fission yeast species. Although morphologically similar to S. octosporus, analysis of several rapidly evolving sequences, including the D1/D2 divergent domain of the large subunit (LSU) rRNA gene, the RNA subunit of Ribonuclease P (RNase P) and the internal transcribed spacer (ITS) elements, revealed significant divergence from any previously characterized Schizosaccharomyces strain. Based on phylogenetic analysis of the D1/D2 domain of the LSU rRNA gene S. octosporus is the closest known relative of S. cryophilus with the sequences of the two species differing by 25 nucleotide substitutions (> 4%). Sequencing of the S. cryophilus genome and phylogenetic analysis of all 1:1 protein orthologs confirmed this observation, and together with morphological and physiological characterization supports the assignment of S. cryophilus as a new species within the genus Schizosaccharomyces. The type strain of the new species is NRRL Y-48691T (=NBRC 106824T = CBS 11777T).
  • 5.

    【2hr】Antimicrobial peptide MUC7 12-mer activates calcium/calcineurin pathway in Candida albicans

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    机译 抗菌肽MUC7 12-mer激活白色念珠菌中的钙/钙调神经磷酸途径
    摘要：MUC7 12-mer is a cationic antimicrobial peptide derived from the N-terminal region of human low molecular weight salivary mucin. In order to gain new insights into the modes of action of the 12-mer against opportunistic fungal pathogen Candida albicans, we examined changes in the gene expression profile of C. albicans upon exposure to this peptide. Cells at an early logarithmic phase were exposed to 6 μM peptide and grown until an OD600 of approximately 0.4 was reached. Changes in gene expression were determined by microarray analysis and showed that 19 out of the total of 531 genes, whose expression was elevated in response to the peptide, are regulated by the calcium/calcineurin signalling pathway. Inactivation of this pathway by deletions, or by FK506, caused hypersensitivity to the peptide, demonstrating the importance of this pathway to the defence of C. albicans against the MUC7 peptide. Other differentially expressed genes that were detected include those encoding subunits of proteasome, and genes involved in cell stress, iron metabolism, cell wall maintenance, and small molecule transport. The presented results suggest that the calcium/calcineurin signalling pathway plays a role in the adaptation of C. albicans to the MUC7 antimicrobial peptide.
  • 6.

    【2hr】Protection of the Oral Mucosa by Salivary Histatin-5 against Candida albicans in an Ex Vivo Murine Model of Oral Infection

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    机译 唾液中的Histatin-5对白色念珠菌的口腔粘膜的保护作用。
    摘要：The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy oral tissue have been lacking. To that end in this study, an ex vivo murine model of infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anti-candidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide.
  • 7.

    【2hr】Evolutionary aspects of urea utilization by fungi

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    机译 真菌对尿素利用的进化方面
    摘要：The higher fungi exhibit a dichotomy with regard to urea utilization. The hemiascomycetes use urea amidolyase (DUR1,2) whereas all other higher fungi use the nickel-containing urease. Urea amidolyase is an energy dependent biotin-containing enzyme. It likely arose prior to the Euascomycete/Hemiascomycete divergence ca. 350 million years ago by insertion of an unknown gene into one copy of a duplicated methylcrotonyl CoA carboxylase (MccA). The dichotomy between urease and urea amidolyase coincides precisely with that for the Ni/Co transporter (Nic1p) which is present in the higher fungi that use urease and absent in those that do not. We suggest that the selective advantage for urea amidolyase is that it allowed the hemiascomycetes to jettison all Ni2+ and Co2+ dependent metabolism and thus to have two fewer transition metals whose concentrations need to be regulated. Also, the absence of MccA in the hemiascomycetes coincides with and may explain their production of fusel alcohols.
  • 8.

    【2hr】Transcriptional regulation of nonfermentable carbon utilization in budding yeast

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    机译 转录调控酵母中不可发酵碳的利用
    摘要：Saccharomyces cerevisiae preferentially uses glucose as a carbon source, but following its depletion, it can utilize a wide variety of other carbons including nonfermentable compounds such as ethanol. A shift to a nonfermentable carbon source results in massive reprogramming of gene expression including genes involved in gluconeogenesis, the glyoxylate cycle, and the tricarboxylic acid cycle. This review is aimed at describing the recent progress made toward understanding the mechanism of transcriptional regulation of genes responsible for utilization of nonfermentable carbon sources. A central player for the use of nonfermentable carbons is the Snf1 kinase, which becomes activated under low glucose levels. Snf1 phosphorylates various targets including the transcriptional repressor Mig1, resulting in its inactivation allowing derepression of gene expression. For example, the expression of CAT8, encoding a member of the zinc cluster family of transcriptional regulators, is then no longer repressed by Mig1. Cat8 becomes activated through phosphorylation by Snf1, allowing upregulation of the zinc cluster gene SIP4. These regulators control the expression of various genes including those involved in gluconeogenesis. Recent data show that another zinc cluster protein, Rds2, plays a key role in regulating genes involved in gluconeogenesis and the glyoxylate pathway. Finally, the role of additional regulators such as Adr1, Ert1, Oaf1, and Pip2 is also discussed.
  • 9.

    【2hr】Vaccines based on whole recombinant Saccharomyces cerevisiae cells

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    机译 基于完整的酿酒酵母细胞的疫苗
    摘要：
  • 10.

    【2hr】Massive induction of innate immune response to Candida albicans in the kidney in a murine intravenous challenge model

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    机译 在小鼠静脉内攻击模型中大规模诱导肾脏对白色念珠菌的先天免疫应答
    摘要：In the experimental Candida albicans intravenous challenge model, the kidney is one of the main organs involved in disease. In progressive infection, fungal burdens are found to increase over time, with rapid increases occurring from 24 h postinfection. Renal transcriptional responses were analyzed at this time in the kidneys of mice infected by either a virulent or an attenuated C. albicans strain, allowing comparison of host responses in progressive and nonprogressive infection. The results of this study demonstrate that both infections share a common transcriptional response, consisting of functions associated with the acute-phase reaction. In addition, challenge with the virulent strain led to a massively increased expression of cytokine genes, other innate response genes and genes suggestive of initiation of the adaptive immune response. This immune response to C. albicans infection, which occurs only in progressive infection, may contribute to development of sepsis and, ultimately, host death.
  • 11.

    【2hr】Widespread occurrence of chromosomal aneuploidy following the routine production of Candida albicans mutants

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    机译 常规生产白色念珠菌突变体后染色体非整倍性的广泛发生
    摘要：It has come to our attention that approximately 35% of >100 published microarray datasets, where transcript levels were compared between two different strains, exhibit some form of chromosome-specific bias. While some of these arose from the use of strains whose aneuploidies were not known at the time, in a worrisome number of cases the recombinant strains have acquired additional aneuploidies that were not initially present in the parental strain. The aneuploidies often affected a different chromosome than the one harboring the insertion site. The affected strains originated from either CAI-4, RM1000, BWP17 or SN95 and were produced through a variety of strategies. These observations suggest that aneuploidies frequently occur during the production of recombinant strains and have an effect on global transcript profiles outside of the afflicted chromosome(s), thus raising the possibility of unintended phenotypic consequences. Thus, we propose that all Candida albicans mutants and strains should be tested for aneuploidy before being used in further studies. To this end, we describe a new rapid testing method, based on a multiplex quantitative PCR assay, that produces eight bands of distinct sizes from either the left or right arms of each C. albicans chromosome.
  • 12.

    【2hr】Avoiding unscheduled transcription in shared promoters: Saccharomyces cerevisiae Sum1p represses the divergent gene pair SPS18-SPS19 through a midsporulation element (MSE)

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    机译 避免共享启动子中的非计划转录：酿酒酵母Sum1p通过中孢子形成元件（MSE）抑制发散基因对SPS18-SPS19。
    摘要：The sporulation-specific gene SPS18 shares a common promoter region with the oleic acid-inducible gene SPS19. Both genes are transcribed in sporulating diploid cells, albeit unevenly in favour of SPS18, whereas in haploid cells grown on fatty acids only SPS19 is highly activated. Here, SPS19 oleate-response element (ORE) conferred activation on a basal CYC1-lacZ reporter gene equally in both orientations, but promoter analysis using SPS18-lacZ reporter constructs with deletions identified a repressing fragment containing a midsporulation element (MSE) that could be involved in imposing directionality towards SPS19 in oleic acid-induced cells. In sporulating diploids, MSEs recruit the Ndt80p transcription factor for activation, whereas under vegetative conditions, certain MSEs are targeted by the Sum1p repressor in association with Hst1p and Rfm1p. Quantitative real-time PCR demonstrated that in haploid sum1Δ, hst1Δ, or rfm1Δ cells, oleic acid-dependent expression of SPS18 was higher compared with the situation in wild-type cells, but in the sum1Δ mutant, this effect was diminished in the absence of Oaf1p or Pip2p. We conclude that SPS18 MSE is a functional element repressing the expression of both SPS18 and SPS19, and is a component of a stricture mechanism shielding SPS18 from the dramatic increase in ORE-dependent transcription of SPS19 in oleic acid-grown cells.
  • 13.

    【2hr】Dissecting the Pleiotropic Consequences of a Quantitative Trait Nucleotide

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    机译 解剖定量性状核苷酸的多效性后果
    摘要：The downstream consequences of a single quantitative trait polymorphism can provide important insight into the molecular basis of a trait. However, the molecular consequences of a polymorphism may be complex and only a subset of these may influence the trait of interest. In natural isolates of Saccharomyces cerevisiae, a nonsynonymous polymorphism in cystathione beta-synthase (CYS4) causes a deficiency in both cysteine and glutathione that results in rust-colored colonies and drug-dependent growth defects. Using a single nucleotide allele-replacement, we characterized the effects of this polymorphism on gene expression levels across the genome. To determine whether any of the differentially expressed genes are necessary for the production of rust-colored colonies, we screened the yeast deletion collection for genes that enhance or suppress rust coloration. We found that genes in the sulfur assimilation pathway are required for the production of rust color but not the drug-sensitivity phenotype. Our results show that a single quantitative trait polymorphism can generate a complex set of downstream changes, providing a molecular basis for pleiotropy.
  • 14.

    【2hr】Centaurin-Like Protein Cnt5 Contributes Arsenic and Cadmium Resistance in Fission Yeast

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    机译 类半胱氨酸蛋白Cnt5促进裂殖酵母中的砷和镉抗性
    摘要：Arsenic (As) and Cadmium (Cd) are two of the most hazardous substances in the environment and have been implicated in number of human diseases including cancer. Their mechanisms of toxicity and subsequent carcinogenesis are not understood. To identify genes involved in As/Cd detoxification we screened a random insertional mutagenesis library of Schizosaccharomyces pombe for mutants that are hypersensitive to As/Cd. Mutations were mapped to spc1+ (sty1+) and SPBC17G9.08c. Spc1 is a stress-activated protein kinase orthologous to human p38. A fragment of SPBC17G9.08c was previously identified as csx2, a high-copy suppressor of cut6 that encodes an acetyl-CoA carboxylase involved in fatty acid biosynthesis. SPBC17G9.08c is a member of the Centaurin Arf GAP protein family found in a variety of fungi, plants and metazoans, but not in Saccharomyces cerevisiae. Cnt5, so named because its closest human homolog is Centaurin beta-5, binds to phosphatidic acid and phosphatidyl serine in vitro. Microscopic localization of Cnt5-GFP indicates significant redistribution of Cnt5 from the cytoplasm to cell membranes in response to arsenic stress. These data suggest a model in which Cnt5 contributes to As/Cd resistance by maintaining membrane integrity or by modulating membrane trafficking.
  • 15.

    【2hr】Pichia stipitis genomics, transcriptomics, and gene clusters

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    机译 毕赤酵母基因组学，转录组学和基因簇
    摘要：Genome sequencing and subsequent global gene expression studies have advanced our understanding of the lignocellulose-fermenting yeast Pichia stipitis. These studies have provided an insight into its central carbon metabolism, and analysis of its genome has revealed numerous functional gene clusters and tandem repeats. Specialized physiological traits are often the result of several gene products acting together. When coinheritance is necessary for the overall physiological function, recombination and selection favor colocation of these genes in a cluster. These are particularly evident in strongly conserved and idiomatic traits. In some cases, the functional clusters consist of multiple gene families. Phylogenetic analyses of the members in each family show that once formed, functional clusters undergo duplication and differentiation. Genome-wide expression analysis reveals that regulatory patterns of clusters are similar after they have duplicated and that the expression profiles evolve along with functional differentiation of the clusters. Orthologous gene families appear to arise through tandem gene duplication, followed by differentiation in the regulatory and coding regions of the gene. Genome-wide expression analysis combined with cross-species comparisons of functional gene clusters should reveal many more aspects of eukaryotic physiology.
  • 16.

    【2hr】Efficient and Rapid identification of Candida albicans allelic status using SNP-RFLP

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    机译 使用SNP-RFLP快速有效地鉴定白色念珠菌等位基因状态
    摘要：Candida albicans is the most prevalent opportunistic fungal pathogen in the clinical setting, causing a wide spectrum of diseases ranging from superficial mucosal lesions to life-threatening deep-tissue infections. Recent studies provide strong evidence that C. albicans possesses an arsenal of genetic mechanisms promoting genome plasticity and that it uses these mechanisms under conditions of nutritional or antifungal drug stress. Two microarray-based methods, SNP (Single nucleotide polymorphism) and CGH (comparative genome hybridization) arrays, have been developed to study genome changes in C. albicans. However, array technologies can be relatively expensive and are not available to every laboratory. In addition, they often generate more data than needed to analyze specific genomic loci or regions. Here we have developed a set of SNP-RFLP (or PCR-RFLP) (restriction fragment length polymorphism) markers, two per chromosome arm, for C. albicans. These markers can be used to rapidly and accurately detect large-scale changes in the C. albicans genome including loss of heterozygosity (LOH) at single loci, across chromosome arms or across whole chromosomes. Furthermore, skewed SNP-RFLP allelic ratios are indicative of trisomy at heterozygous loci. While less comprehensive than array-based approaches, we propose SNP-RFLP as an inexpensive, rapid, reliable method to screen strains of interest for possible genome changes.
  • 17.

    【2hr】A multi-species based taxonomic microarray reveals interspecies hybridization and introgression in Saccharomyces cerevisiae

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    机译 基于多物种的分类芯片揭示了酿酒酵母中的种间杂交和基因渗入。
    摘要：A multi-species based taxonomic microarray targeting coding sequences of diverged orthologous genes in Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. bayanus, S. kudriavzevii, Naumovia castellii, Lachancea kluyveri and Candida glabrata was designed to allow identification of isolates of these species and their interspecies hybrids. Analysis of isolates of several Saccharomyces species and interspecies hybrids demonstrated the ability of the microarray to differentiate these yeasts on the basis of their specific hybridization patterns. Subsequent analysis of 183 supposed S. cerevisiae isolates of various ecological and geographical backgrounds revealed one misclassified S. bayanus or S. uvarum isolate and four aneuploid interspecies hybrids, one between S. cerevisiae and S. bayanus and three between S. cerevisiae and S. kudriavzevii. Furthermore, this microarray design allowed the detection of multiple introgressed S. paradoxus DNA fragments in the genomes of three different S. cerevisiae isolates. These results show the power of multi-species based microarrays as taxonomic tools for the identification of species and interspecies hybrids, and their ability to provide a more detailed characterization of interspecies hybrids and recombinants.
  • 18.

    【2hr】In silico evidence for functional specialization after genome duplication in yeast

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    机译 酵母中基因组复制后功能专业化的计算机证据
    摘要：A fairly recent whole-genome duplication (WGD) event in yeast enables the effects of gene duplication and subsequent functional divergence to be characterized. We examined 15 ohnolog pairs (i.e. paralogs from a WGD) out of c. 500 Saccharomyces cerevisiae ohnolog pairs that have persisted over an estimated 100 million years of evolution. These 15 pairs were chosen for their high levels of asymmetry, i.e. within the pair, one ohnolog had evolved much faster than the other. Sequence comparisons of the 15 pairs revealed that the faster evolving duplicated genes typically appear to have experienced partially – but not fully – relaxed negative selection as evidenced by an average nonsynonymous/synonymous substitution ratio (dN/dSavg=0.44) that is higher than the slow-evolving genes' ratio (dN/dSavg=0.14) but still <1. Increased number of insertions and deletions in the fast-evolving genes also indicated loosened structural constraints. Sequence and structural comparisons indicated that a subset of these pairs had significant differences in their catalytically important residues and active or cofactor-binding sites. A literature survey revealed that several of the fast-evolving genes have gained a specialized function. Our results indicate that subfunctionalization and even neofunctionalization has occurred along with degenerative evolution, in which unneeded functions were destroyed by mutations.
  • 19.

    【2hr】Formalin Can Alter the Intracellular Localization of Some Transcription Factors in Saccharomyces cerevisiae

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    机译 福尔马林可以改变酿酒酵母中某些转录因子的细胞内定位
    摘要：Indirect immunofluorescence (IF) microscopy is one of the most frequently employed methods to determine intracellular protein localization in yeast. It is especially useful for low abundance proteins, eg., the GATA-factors (Gln3, Gat1) which activate NCR-sensitive transcription. Limiting the nitrogen supply or treating cells with the Tor pathway inhibitor, rapamycin, elicits nuclear GATA-factor localization and increased NCR-sensitive transcription, whereas excess nitrogen restricts these proteins to the cytoplasm and decreases transcription. The initial step of the IF procedure is formalin-fixation that quenches cellular activity and fixes protein locations via cross-linking. Indeed, it is on the success of this immobilization step that the assay depends. We have found that under some conditions, formalin itself can influence GATA-factor localization. With low concentrations of formalin (1.6%), Gat1-Myc13 became more nuclear, and with higher concentrations (5.6%), it became more cytoplasmic. Gln3-Myc13 localization, on the other hand, did not respond to low formalin, but became more cytoplasmic at the higher concentration. Interestingly, the high concentration of formalin had no demonstrable effect when the GATA-factors were completely nuclear, i.e., after rapamycin-(Gat1-Myc13) or Msx-(Gln3-Myc13) treatment. Our data indicate that these effects are most likely elicited by methylene and polyoxymethylene glycols, which account for more than 99% of the formaldehyde in formalin. These compounds greatly increased the osmolarity of the medium (0.5–2) and leads us to suggest that varying degrees of osmotic stress, to which both Gln3 and Gat1 are known to respond, and protein movement in response to it can occur after the beginning of fixation but before proteins become immobilized. Therefore, precautions are required to minimize the problem if possible or to account for it during interpretation of IF or other experimental data derived from cells treated with formalin when it cannot be avoided.
  • 20.

    【2hr】Mixed Candida albicans strain populations in colonized and infected mucosal tissues

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    机译 殖民化和感染的黏膜组织中的白色念珠菌混合菌株种群
    摘要：Multilocus sequence typing of six Candida albicans colonies from primary isolation plates revealed instances of colony-to-colony microvariation and carriage of two strain types in single oropharyngeal and vaginal samples. Higher rates of colony variation in commensal samples suggest selection of types from mixed populations either in the shift to pathogenicity or the response to antifungal treatment.
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