The Ashbya Genome Database (AGD)—a tool for the yeast community and genome biologists

The Ashbya Genome Database (AGD) is a comprehensive online source of information covering genes from the filamentous fungus Ashbya gossypii. The database content is based upon comparative genome annotation between A.gossypii and the closely related budding yeast Saccharomyces cerevisiae taking both sequence similarity and synteny (conserved order and orientation) into account. Release 2 of AGD contains 4718 protein-encoding loci located across seven chromosomes. Information can be retrieved using systematic or standard locus names from A.gossypii as well as budding and fission yeast. Approximately 90% of the genes in the genome of A.gossypii are homologous and syntenic to loci of budding yeast. Therefore, AGD is a useful tool not only for the various yeast communities in general but also for biologists who are interested in evolutionary aspects of genome research and comparative genome annotation. The database provides scientists with a convenient graphical user interface that includes various locus search and genome browsing options, data download and export functionalities and numerous reciprocal links to external databases including SGD, MIPS, GeneDB, KEGG, GermOnline and Swiss-Prot/TrEMBL. AGD is accessible at http://agd.unibas.c

Reinvestigation of the Saccharomyces cerevisiae genome annotation by comparison to the genome of a related fungus: Ashbya gossypii

BACKGROUND: The recently sequenced genome of the filamentous fungus Ashbya gossypii revealed remarkable similarities to that of the budding yeast Saccharomyces cerevisiae both at the level of homology and synteny (conservation of gene order). Thus, it became possible to reinvestigate the S. cerevisiae genome in the syntenic regions leading to an improved annotation. RESULTS: We have identified 23 novel S. cerevisiae open reading frames (ORFs) as syntenic homologs of A. gossypii genes; for all but one, homologs are present in other eukaryotes including humans. Other comparisons identified 13 overlooked introns and suggested 69 potential sequence corrections resulting in ORF extensions or ORF fusions with improved homology to the syntenic A. gossypii homologs. Of the proposed corrections, 25 were tested and confirmed by resequencing. In addition, homologs of nearly 1,000 S. cerevisiae ORFs, presently annotated as hypothetical, were found in A. gossypii at syntenic positions and can therefore be considered as authentic genes. Finally, we suggest that over 400 S. cerevisiae ORFs that overlap other ORFs in S. cerevisiae and for which no homolog can be detected in A. gossypii should be regarded as spurious. CONCLUSIONS: Although, the S. cerevisiae genome is rightly considered as one of the most accurately sequenced and annotated eukaryotic genomes, we have shown that it still benefits substantially from comparison to the completed sequence and syntenic gene map of A. gossypii, an evolutionarily related fungus. This type of approach will strongly support the annotation of more complex genomes such as the human and murine genomes

Genetic Circuitry of Survival Motor Neuron, the Gene Underlying Spinal Muscular Atrophy

The clinical severity of the neurodegenerative disorder spinal muscular atrophy (SMA) is dependent on the levels of functional Survival Motor Neuron (SMN) protein. Consequently, current strategies for developing treatments for SMA generally focus on augmenting SMN levels. To identify additional potential therapeutic avenues and achieve a greater understanding of SMN, we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog. We identified more than 300 candidate genes that alter an Smn-dependent phenotype in vivo. Integrating the results from our genetic screens, large-scale protein interaction studies, and bioinformatic analysis, we define a unique interactome for SMN that provides a knowledge base for a better understanding of SMA.Stem Cell and Regenerative Biolog

Währungseffekte in der Planung und Kontrolle internationaler Unternehmen

Internationale Unternehmen sind im Rahmen ihrer grenzüberschreitenden Tätigkeiten von verschiedenen Währungen tangiert. Die damit einhergehenden Wechselkurse unterliegen aufgrund verschiedener Faktoren starken Volatilitäten. Im Rahmen der erfolgsorientierten Planung und Kontrolle bedarf es einer konstanten Umrechnung von Auslandsgeschäften und Ergebnissen ausländischer Tochtergesellschaften in die Konzernwährung. Aufgrund daraus resultierender Unsicherheiten sind Unternehmen einer Vielzahl von Risiken ausgesetzt, die zu Verzerrungen innerhalb der Erfolgsmessung führen. Die vorliegende Forschung zielt darauf ab, die Verfahren der Währungsumrechnung im Rahmen der operativen Planung des internationalen Controllings aufzuzeigen sowie die Bedeutung der Währungsrisiken auf den Unternehmenserfolg zu prüfen. Die Integration des Währungsmanagements in die Unternehmenspraxis wird mittels einer quantitativen Studie, in Form der standardisierten Befragung, analysiert. Die von der Literatur unterstellte Vernachlässigung von Wechselkursentwicklungen in der Planungspraxis kann von der Studie nicht bestätigt werden. Zusätzlich wird eine Wissensbasis hinsichtlich der Verwendung von Umrechnungskursen sowie dem Umgang mit Absicherungsmaßnahmen geschaffen

Contribution of Horizontal Gene Transfer to the Evolution of Saccharomyces cerevisiae

The genomes of the hemiascomycetes Saccharomyces cerevisiae and Ashbya gossypii have been completely sequenced, allowing a comparative analysis of these two genomes, which reveals that a small number of genes appear to have entered these genomes as a result of horizontal gene transfer from bacterial sources. One potential case of horizontal gene transfer in A. gossypii and 10 potential cases in S. cerevisiae were identified, of which two were investigated further. One gene, encoding the enzyme dihydroorotate dehydrogenase (DHOD), is potentially a case of horizontal gene transfer, as shown by sequencing of this gene from additional bacterial and fungal species to generate sufficient data to construct a well-supported phylogeny. The DHOD-encoding gene found in S. cerevisiae, URA1 (YKL216W), appears to have entered the Saccharomycetaceae after the divergence of the S. cerevisiae lineage from the Candida albicans lineage and possibly since the divergence from the A. gossypii lineage. This gene appears to have come from the Lactobacillales, and following its acquisition the endogenous eukaryotic DHOD gene was lost. It was also shown that the bacterially derived horizontally transferred DHOD is required for anaerobic synthesis of uracil in S. cerevisiae. The other gene discussed in detail is BDS1, an aryl- and alkyl-sulfatase gene of bacterial origin that we have shown allows utilization of sulfate from several organic sources. Among the eukaryotes, this gene is found in S. cerevisiae and Saccharomyces bayanus and appears to derive from the alpha-proteobacteria

Phosphatidylinositol-dependent phospholipases C Plc2 and Plc3 of Candida albicans are dispensable for morphogenesis and host-pathogen interaction

International audiencePhospholipases play an important role as virulence factors in human pathogens. Candida albicans, the major fungal pathogen of humans, encodes phospholipases of type A, B, C and D. Type B Plb2 and type D Pld1 phospholipases have been shown to contribute to virulence in this organism. We analyzed, in C. albicans, PLC2 and PLC3, two highly conserved genes coding for phosphatidylinositol-dependent phospholipases C with homology to the known virulence factor PlcA in the human pathogen Listeria monocytogenes. We show that expression of PLC2 and PLC3 is upregulated under different filament-inducing conditions and in the constitutive filamentous mutant tup1Δ. In order to analyze PLC2 and PLC3 function in C. albicans, we constructed strains that carry PLC2 or PLC3 under a constitutive promoter and strains that lack all four PLC2/3 alleles. These strains were not affected in their ability to produce filaments under non-inducing conditions, nor was filamentation modified under inducing conditions, suggesting that PLC2/3 are not critical determinants of the yeast-to-hypha switch. In a cell culture model for macrophage interaction, phagocytosis of C. albicans and subsequent killing were not influenced by PLC2/3. These results demonstrate that C. albicans PLC2 and PLC3 are dispensable for virulence; moreover, they underline the sharp contrast with the function of plcA in L. monocytogenes

Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration.

The marbling of skeletal muscle by ectopic adipose tissue is a hallmark of many muscle diseases, including sarcopenia and muscular dystrophies, and generally associates with impaired muscle regeneration. Although the etiology and the molecular mechanisms of ectopic adipogenesis are poorly understood, fatty regeneration can be modeled in mice using glycerol-induced muscle damage. Using comprehensive molecular and histological profiling, we compared glycerol-induced fatty regeneration to the classical cardiotoxin (CTX)-induced regeneration model previously believed to lack an adipogenic response in muscle. Surprisingly, ectopic adipogenesis was detected in both models, but was stronger and more persistent in response to glycerol. Importantly, extensive differential transcriptomic profiling demonstrated that glycerol induces a stronger inflammatory response, and promotes adipogenic regulatory networks while reducing fatty acid β-oxidation. Altogether, these results provide a comprehensive repository of gene expression changes during the time course of two muscle regeneration models, and strongly suggest that adipogenic commitment is a hallmark of muscle regeneration, which can lead to ectopic adipocyte accumulation in response to specific physiopathological challenge

A Long Non-coding RNA, LncMyoD, Regulates Skeletal Muscle Differentiation by Blocking IMP2-mediated protein translation

Long non-coding RNAs (LncRNA) constitute a new class of genes recently identified in various tissues1-8. LncRNAs play important roles in normal physiology as well as in many diseases, including embryonic stem cell maintenance, organ development and cancer progression 1,9-14. However, the various roles of LncRNAs in somatic stem cell maintenance and myogenesis remain largely unknown 15,16. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during muscle differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during early myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. RNA pull-down experiments demonstrate that LncMyoD directly binds to IGF2-mRNA-binding-proteins (IMPs), which regulate translation of particular mRNAs, and thus negatively regulates IMP-mediated translation of proliferation genes such as N-Ras and c-Myc. While the sequence of LncMyoD is not well-conserved between human and mouse, its locus and mechanism is preserved. It was largely unclear how MyoD blocks proliferation to help create a permissive state for differentiation; elucidation of the MyoD-LncMyoD-IMP2 pathway provides this mechanism

Genomic Profiling Reveals That Transient Adipogenic Activation Is a Hallmark of Mouse Models of Skeletal Muscle Regeneration

<div><p>The marbling of skeletal muscle by ectopic adipose tissue is a hallmark of many muscle diseases, including sarcopenia and muscular dystrophies, and generally associates with impaired muscle regeneration. Although the etiology and the molecular mechanisms of ectopic adipogenesis are poorly understood, fatty regeneration can be modeled in mice using glycerol-induced muscle damage. Using comprehensive molecular and histological profiling, we compared glycerol-induced fatty regeneration to the classical cardiotoxin (CTX)-induced regeneration model previously believed to lack an adipogenic response in muscle. Surprisingly, ectopic adipogenesis was detected in both models, but was stronger and more persistent in response to glycerol. Importantly, extensive differential transcriptomic profiling demonstrated that glycerol induces a stronger inflammatory response and promotes adipogenic regulatory networks while reducing fatty acid β-oxidation. Altogether, these results provide a comprehensive mapping of gene expression changes during the time course of two muscle regeneration models, and strongly suggest that adipogenic commitment is a hallmark of muscle regeneration, which can lead to ectopic adipocyte accumulation in response to specific physio-pathological challenges.</p></div