705 research outputs found
The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
No full textAbstract Correction to Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ: The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics 2007, 8:320.</p
Genome-wide analysis of the H-NS and Sfh regulatory networks in Salmonella Typhimurium identifies a plasmid-encoded transcription silencing mechanism
No full textThe conjugative IncHI1 plasmid pSfR27 from Shigella flexneri 2a strain 2457T encodes the Sfh protein, a paralogue of the global transcriptional repressor H-NS. Sfh allows pSfR27 to be transmitted to new bacterial hosts with minimal impact on host fitness, providing a 'stealth' function whose molecular mechanism has yet to be determined. The impact of the Sfh protein on the Salmonella enterica serovar Typhimurium transcriptome was assessed and binding sites for Sfh in the Salmonella Typhimurium genome were identified by chromatin immunoprecipitation. Sfh did not bind uniquely to any sites. Instead, it bound to a subset of the larger H-NS regulatory network. Analysis of Sfh binding in the absence of H-NS revealed a greatly expanded population of Sfh binding sites that included the majority of H-NS target genes. Furthermore, the presence of plasmid pSfR27 caused a decrease in H-NS interactions with the S. Typhimurium chromosome, suggesting that the A + T-rich DNA of this large plasmid acts to titrate H-NS, removing it from chromosomal locations. It is proposed that Sfh acts as a molecular backup for H-NS and that it provides its 'stealth' function by replacing H-NS on the chromosome, thus minimizing disturbances to the H-NS-DNA binding pattern in cells that acquire pSfR27
Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro
No full textBackground
Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. In the current study, we have analysed and compared the transcriptomes of M. bovis-infected monocyte-derived macrophages (MDM) purified from six Holstein-Friesian females with the transcriptomes of non-infected control MDM from the same animals over a 24 h period using strand-specific RNA sequencing (RNA-seq). In addition, we compare gene expression profiles generated using RNA-seq with those previously generated by us using the high-density Affymetrix? GeneChip? Bovine Genome Array platform from the same MDM-extracted RNA.
Results
A mean of 7.2 million reads from each MDM sample mapped uniquely and unambiguously to single Bos taurus reference genome locations. Analysis of these mapped reads showed 2,584 genes (1,392 upregulated; 1,192 downregulated) and 757 putative natural antisense transcripts (558 upregulated; 119 downregulated) that were differentially expressed based on sense and antisense strand data, respectively (adjusted P-value???0.05). Of the differentially expressed genes, 694 were common to both the sense and antisense data sets, with the direction of expression (i.e. up- or downregulation) positively correlated for 693 genes and negatively correlated for the remaining gene. Gene ontology analysis of the differentially expressed genes revealed an enrichment of immune, apoptotic and cell signalling genes. Notably, the number of differentially expressed genes identified from RNA-seq sense strand analysis was greater than the number of differentially expressed genes detected from microarray analysis (2,584 genes versus 2,015 genes). Furthermore, our data reveal a greater dynamic range in the detection and quantification of gene transcripts for RNA-seq compared to microarray technology.
Conclusions
This study highlights the value of RNA-seq in identifying novel immunomodulatory mechanisms that underlie host-mycobacterial pathogen interactions during infection, including possible complex post-transcriptional regulation of host gene expression involving antisense RNA
Sigmund Freud contra Helga Grebing - Kommentierende Anmerkungen zu den Beiträgen von Max Bloch, Karsten Rudolph, Meik Woyke und Walter Mühlhausen
No full textConcentrating on the contributions of Max Bloch, Karsten Rudolph, Meik Woyke and Walter Mühlhausen the author sums up the contributions of this volume in order to reflect on the current state of research in the field of the historiography of biographies of leading social democrats. He discusses remaining lacunae in research and develops perspectives for future research
Global Gene Expression and Systems Biology Analysis of Bovine Monocyte-Derived Macrophages in Response to In Vitro Challenge with Mycobacterium bovis
No full textBACKGROUND:
Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2?1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix? GeneChip? Bovine Genome Array.
RESULTS:
Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ?0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis.
CONCLUSIONS:
The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis
A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni.
No full textLeptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus
Leptospira
. More than 500,000 cases of severe leptospirosis are reported annually, with
.
10% of these being fatal.
Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically
rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when
mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans,
leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil?s)
disease and pulmonary haemorrhage. Currently, little is known about how
Leptospira
persist within a reservoir host. Prior
in
vitro
studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental
signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a
mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived
signals, we used RNA-Seq to compare the transcriptome of
L. interrogans
cultivated within dialysis membrane chambers
(DMCs) implanted into the peritoneal cavities of rats with that of organisms grown
in vitro
. In addition to determining the
relative expression levels of ??core?? housekeeping genes under both growth conditions, we identified 166 genes that are
differentially-expressed by
L. interrogans in vivo
. Our analyses highlight physiological aspects of host adaptation by
leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate
small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes
associated with mammalian host-adaption, selection of targets for mutagenesis, and the identification of previously
unrecognized virulence determinant
A bioinformatics approach to (intra-) genome comparisons
No full textTHESIS 6855The analysis of large volumes of genomic data generates special computational
needs. A Beowulf-type computer cluster was set up for high-performance
computing. Improvements over existing tools for the efficient parallelisation
of similarity searches on such systems were accomplished with the program
wrapid
B --> ([rho]/[omega]) [gamma] at BaBar
No full textThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.In title on title page, "[right arrow] appears as the symbol; and "[rho]", "[omega]" and "[gamma]" appear as lower-case Greek letters.Includes bibliographical references (leaves 203-205).This document describes the measurements of the branching fractions and isospin violations of the radiative electroweak penguin decays B [right arrow] ([rho]/[omega]) [gamma] at the asymmetric energy e+e- PEP-II collider with the BABAR detector. Together with the previously measured branching fractions of the decays ... the ratio of CKM-matrix elements Vtd=Vts are extracted and the length of the far side of the unitarity triangle is determined.by Karsten Köneke.Ph.D
Enhanced flavour profiles through radicicol induced genomic variation in the lager yeasts, Saccharomyces pastorianus
No full textThe yeasts, Saccharomyces pastorianus, are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus and have acquired traits from the combined parental genomes such as ability to ferment a range of sugars at low temperatures and to produce aromatic flavour compounds, allowing for the production of lager beers with crisp, clean flavours. The polyploid strains are sterile and have reached an evolutionary bottleneck for genetic variation. Here we describe an accelerated evolution approach to obtain lager yeasts with enhanced flavour profiles. As the relative expression of orthologous alleles is a significant contributor to the transcriptome during fermentation, we aimed to induce genetic variation by altering the S. cerevisiae to S. eubayanus chromosome ratio. Aneuploidy was induced through the temporary inhibition of the cell's stress response and strains with increased production of aromatic amino acids via the Shikimate pathway were selected by resistance to amino acid analogues. Genomic changes such as gross chromosomal rearrangements, chromosome loss and chromosome gain were detected in the characterised mutants, as were single-nucleotide polymorphisms in ARO4, encoding for DAHP synthase, the catalytic enzyme in the first step of the Shikimate pathway. Transcriptome analysis confirmed the upregulation of genes encoding enzymes in the Ehrlich pathway and the concomitant increase in the production of higher alcohols and esters such as 2-phenylethanol, 2-phenylethyl acetate, tryptophol, and tyrosol. We propose that the polyploid nature of S. pastorianus genomes is an advantageous trait supporting opportunities for genetic alteration in otherwise sterile strain
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