378 research outputs found
Zassenhaus conjecture for central extensions of S5
We confirm a conjecture of Zassenhaus about rational conjugacy of torsion units in
integral group rings for a covering group of the symmetric group S5 and for the general linear
group GLð2; 5Þ. The first result, together with others from the literature, settles the conjugacy
question for units of prime-power order in the integral group ring of a finite Frobenius group
Cryptic Polyketide Synthase Genes in Non-Pathogenic Clostridium SPP
Modular type I polyketide synthases (PKS) produce a vast array of bacterial metabolites with highly diverse biological functions. Notably, all known polyketides were isolated from aerobic bacteria, and yet no example has been reported for strict anaerobes. In this study we explored the diversity and distribution of PKS genes in the genus Clostridium. In addition to comparative genomic analyses combined with predictions of modular type I polyketide synthase (PKS) gene clusters in sequenced genomes of Clostridium spp., a representative selection of other species inhabiting a variety of ecological niches was investigated by PCR screening for PKS genes. Our data reveal that all studied pathogenic Clostridium spp. are devoid of putative PKS genes. In stark contrast, cryptic PKS genes are widespread in genomes of non-pathogenic Clostridium species. According to phylogenetic analyses, the Clostridium PKS genes have unusual and diverse origins. However, reverse transcription quantitative PCR demonstrates that these genes are silent under standard cultivation conditions, explaining why the related metabolites have been overlooked until now. This study presents clostridia as a putative source for novel bioactive polyketides
Time evolution, cyclic solutions and geometric phases for the generalized time-dependent harmonic oscillator
The generalized time-dependent harmonic oscillator is studied. Though several
approaches to the solution of this model have been available, yet a new
approach is presented here, which is very suitable for the study of cyclic
solutions and geometric phases. In this approach, finding the time evolution
operator for the Schr\"odinger equation is reduced to solving an ordinary
differential equation for a c-number vector which moves on a hyperboloid in a
three-dimensional space. Cyclic solutions do not exist for all time intervals.
A necessary and sufficient condition for the existence of cyclic solutions is
given. There may exist some particular time interval in which all solutions
with definite parity, or even all solutions, are cyclic. Criterions for the
appearance of such cases are given. The known relation that the nonadiabatic
geometric phase for a cyclic solution is proportional to the classical Hannay
angle is reestablished. However, this is valid only for special cyclic
solutions. For more general ones, the nonadiabatic geometric phase may contain
an extra term. Several cases with relatively simple Hamiltonians are solved and
discussed in detail. Cyclic solutions exist in most cases. The pattern of the
motion, say, finite or infinite, can not be simply determined by the nature of
the Hamiltonian (elliptic or hyperbolic, etc.). For a Hamiltonian with a
definite nature, the motion can changes from one pattern to another, that is,
some kind of phase transition may occur, if some parameter in the Hamiltonian
goes through some critical value.Comment: revtex4, 28 pages, no figur
Discovery of 3-Formyl-Tyrosine Metabolites from Pseudoalteromonas tunicata through Heterologous Expression
Genome mining and identification of natural product gene clusters typically relies on the presence of canonical nonribosomal polypeptide synthetase (NRPS) or polyketide synthase (PKS) domains. Recently, other condensation enzymes, such as the ATP-grasp ligases, have been recognized as important players in natural product biosynthesis. In this study, sequence based searching for homologues of DdaF, the ATP-grasp amide ligase from dapdiamide biosynthesis, led to the identification of a previously unannotated biosynthetic gene cluster in Pseudoalteromonas tunicata. Heterologous expression of the cluster in Escherichia coli allowed for the production and structure determination of two new 3-formyl tyrosine metabolites.Molecular and Cellular Biolog
Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-Sphinganine, (+)-spisulosine and D-ribo-phytosphingosine
Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM-ether directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, while the Overman rearrangement of chiral allylic trichloroacetimidates generated by asymmetric reduction of an alpha,beta-unsaturated methyl ketone allowed rapid access to both D-ribo-phytosphingosine and L-arabino-phytosphingosine
Revisiting German labour market reform effects—a panel data analysis for occupational labour markets
There is an ongoing discussion that centres on the German labour market reforms (2003- 2005) and the role of these reforms in boosting the German economy. Considering that one of the main objectives of the reforms was to improve the matching process on the labour market, I use rich, high-frequency, and recent administrative panel data to present new details regarding the development of job-matching performance before and after the reform years. The results show that matching productivity increased during all reform stages and slightly deteriorated in 2009 (the year of the financial crisis), even after controlling for the recession. Furthermore, increases in matching productivity have become smaller in recent years. Beyond these findings, the results show detailed differences in the changes in matching productivity on occupational labour markets.Über einen etwaigen Beitrag der deutschen Arbeitsmarktreformen (2003-2005) zur Stabilisierung der deutschen Wirtschaft wird sowohl in Wissenschaft als auch Politik nach wie vor debattiert. Dabei war die Verbesserung der Effizienz des Arbeitsmarktausgleichs eines der erklärten Hauptziele der Reformen. Zur Frage, ob dieses Ziel erreicht wurde, stelle ich präzise und neue detaillierte Befunde auf der Basis von umfangreichen administrativen Daten vor, die auch die Zeit der Wirtschafts- und Finanzkrise (2008/2009) einschließen. Die Effizienz des Arbeitsmarktausgleichs erhöhte sich während und nach den Reformjahren deutlich. Dies lässt sich nun auch für die Einführung der letzten Reformstufe im Jahr 2005 belegen. Jedoch waren die Arbeitsmarktausgleichsprozesse nicht vollständig immun gegen die Wirtschafts- und Finanzkrise; die positive Entwicklung wurde hier unterbrochen und setzte sich danach nicht in dem gleichen Maße fort. Darüber hinaus zeigen die Analysen eine unterschiedliche Entwicklung der Matchingeffizienz in beruflichen Teilarbeitsmärkten auf
Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger.
SummarySecondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA
The Natural Product Domain Seeker NaPDoS: A Phylogeny Based Bioinformatic Tool to Classify Secondary Metabolite Gene Diversity
New bioinformatic tools are needed to analyze the growing volume of DNA sequence data. This is especially true in the case of secondary metabolite biosynthesis, where the highly repetitive nature of the associated genes creates major challenges for accurate sequence assembly and analysis. Here we introduce the web tool Natural Product Domain Seeker (NaPDoS), which provides an automated method to assess the secondary metabolite biosynthetic gene diversity and novelty of strains or environments. NaPDoS analyses are based on the phylogenetic relationships of sequence tags derived from polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, respectively. The sequence tags correspond to PKS-derived ketosynthase domains and NRPS-derived condensation domains and are compared to an internal database of experimentally characterized biosynthetic genes. NaPDoS provides a rapid mechanism to extract and classify ketosynthase and condensation domains from PCR products, genomes, and metagenomic datasets. Close database matches provide a mechanism to infer the generalized structures of secondary metabolites while new phylogenetic lineages provide targets for the discovery of new enzyme architectures or mechanisms of secondary metabolite assembly. Here we outline the main features of NaPDoS and test it on four draft genome sequences and two metagenomic datasets. The results provide a rapid method to assess secondary metabolite biosynthetic gene diversity and richness in organisms or environments and a mechanism to identify genes that may be associated with uncharacterized biochemistry
Discovery of the pseudomonas polyyne protegencin by a phylogeny-guided study of polyyne biosynthetic gene cluster diversity
Natural products that possess alkyne or polyyne moieties have been
isolated from a variety of biological sources and possess a broad a range of bioactivities. In bacteria, the basic biosynthesis of polyynes is known, but their biosynthetic
gene cluster (BGC) distribution and evolutionary relationship to alkyne biosynthesis
have not been addressed. Through comprehensive genomic and phylogenetic analyses, the distribution of alkyne biosynthesis gene cassettes throughout bacteria was
explored, revealing evidence of multiple horizontal gene transfer events. After investigation of the evolutionary connection between alkyne and polyyne biosynthesis, a
monophyletic clade was identified that possessed a conserved seven-gene cassette
for polyyne biosynthesis that built upon the conserved three-gene cassette for
alkyne biosynthesis. Further diversity mapping of the conserved polyyne gene cassette revealed a phylogenetic subclade for an uncharacterized polyyne BGC present
in several Pseudomonas species, designated pgn. Pathway mutagenesis and high-resolution analytical chemistry showed the Pseudomonas protegens pgn BGC directed
the biosynthesis of a novel polyyne, protegencin. Exploration of the biosynthetic
logic behind polyyne production, through BGC mutagenesis and analytical chemistry,
highlighted the essentiality of a triad of desaturase proteins and a thioesterase in
both the P. protegens pgn and Trinickia caryophylli (formerly Burkholderia caryophylli)
caryoynencin pathways. We have unified and expanded knowledge of polyyne diversity and uniquely demonstrated that alkyne and polyyne biosynthetic gene clusters
are evolutionarily related and widely distributed within bacteria. The systematic mapping of conserved biosynthetic genes across the available bacterial genomic diversity
proved to be a fruitful method for discovering new natural products and better
understanding polyyne biosynthesis.
IMPORTANCE Natural products bearing alkyne (triple carbon bond) or polyyne (multiple alternating single and triple carbon bonds) moieties exhibit a broad range of important biological activities. Polyyne metabolites have been implicated in important
ecological roles such as cepacin mediating biological control of plant pathogens and caryoynencin protecting Lagriinae beetle eggs against pathogenic fungi. After further
phylogenetic exploration of polyyne diversity, we identified a novel gene cluster in
Pseudomonas bacteria with known biological control abilities and proved it was responsible for synthesizing a new polyyne metabolite, protegencin. The evolutionary
analysis of polyyne pathways showed that multiple biosynthetic genes were conserved, and using mutagenesis, their essentiality was demonstrated. Our research
provides a foundation for the future modification of polyyne metabolites and has
identified a novel polyyne, protegencin, with potential bioactive roles of ecological
and agricultural importance
Down-Regulation of Serum/Glucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation
Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples. Methodology/Principal Findings: We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG. Conclusions/Significance: Our results show that even though partial methylation of the promoter region of SGK1 is present
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