598 research outputs found
Elevated interferon-stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus
Hepatitis C virus (HCV) can be classified into seven distinct genotypes that are associated with differing pathologies and respond differently to antiviral therapy. In the UK, genotype 1 and 3 are present in approximately equal proportions. Chronic infection with HCV genotype 3 is associated with increased liver steatosis and reduced peripheral total cholesterol levels, which potentially influences peripheral immune responses. To understand these differences, we investigated host gene transcription in peripheral blood mononuclear cells by microarray and quantitative PCR in patients with genotype 1 (n = 22) or genotype 3 infection (n = 22) and matched healthy controls (n = 15). Enrichment of genes involved in immune response and inflammatory pathways were present in patients infected with HCV genotype 1; however, no differences in genes involved in lipid or cholesterol metabolism were detected. This genotype-specific induction of genes is unrelated to IL28B genotype or previous treatment failure. Our data support the hypothesis that genotype 1 infection drives a skewed Type I interferon response and provides a foundation for future investigations into the hostâpathogen interactions that underlie the genotype-specific clinical outcomes of chronic HCV infection
Raised serum transaminases during treatment with pegylated interferon for chronic hepatiti C
Introduction : Serum transaminases rose significantly in 7 patients with chronic hepatitis C, genotypes 2 and 3, who were treated with pegylated interferon and ribavirin.
Methods : 219 patients with chronic hepatitis C, genotypes 2 and 3, were treated between 2005 and 2011 following the same protocol. For the 7 patients presented in this paper, the initial liver screen revealed chronic hepatitis C infection only. The same liver screen was repeated following the transaminase rise during the treatment period and failed to reveal additional comorbidity.
Results : 5 male and 2 female patients with chronic hepatitis C experienced a rise in serum transaminases after commencement on treatment with pegylated interferon and ribavirin. They all achieved rapid and end of treatment virological responses. 3 of the patients achieved sustained virological response and 4 relapsed. There was no evidence to suggest that steatosis, development of autoimmunity or intercurrent illness was the cause of the liver injury. In 3 out of 7 patients, the level of transaminases exhibited a downward trend after pegylated interferon was changed to non pegylated interferon. Additionally, it is evident that in those patients whose treatment was temporarily or permanently aborted, the rise in transaminases rapidly improved and returned to baseline.
Conclusion : Our experience suggests the possibility of a toxic reaction to polyethylene glycol in a small number of patients being treated with pegylated interferon, resulting in an acute hepatitic response which resolved when therapy was stopped or switched to non-pegylated interferon
Characterisation of Agaricus bisporus response genes to Verticillium fungicola infection
Resumen de la conferencia presentada al VI Meeting on Genetics and Cellular Biology of Basidiomycetes (GCBB-VI), organizado por y celebrado en la Universidad PĂșblica de Navarra el 3-6 de junio de 2005.The mycoparasite Verticillium fungicola is a persistent threat to the cultivation
of the mushroom Agaricus bisporus. Mushroom âdry bubbleâ is characterised
by an undifferentiated mass of cells and can result in major crop losses. During
the establishment of âdry bubbleâ substantial changes occur in the biochemistry
and physiology of both partners. To enable new insights to be
made into the molecular events underlying the disease, work is in progress to
identify genes expressed during pathogen infection. Subtractive Suppressive
Hybridisation (SSH) has enabled recovery of 65 expressed sequenced tags
(ESTs) differentially expressed during infection. After database searches 27
of the genes were identified as most likely from V. fungicola, 25 from A. bisporus
and 13 unknown. Bioinformatic analysis suggested that the response
genes identified were involved in a range of biological functions that included
stress, signalling, protein synthesis and cell wall structure and function.
Specific full-length genes will be recovered using cDNA library constructed
from lesions of A. bisporus infected with V. fungicola, enabling silencing
approaches to be used to further investigate the role of the identified
genes in disease. An alternative higher-throughput method of gene function
analysis, RNA interference (RNAi) using A. bisporus model genes (URA3,
CBX), is also being developed. Silencing constructs expressing RNAi hairpin
were transformed into A. bisporus using Agrobacterium tumefaciens and hygromycin
resistance. Screening of the transformants by PCR confirmed integration
of the silencing construct in 24 transformants. RT-PCR is being
used to confirm transcription of the RNAi hairpin. Quantitative PCR will be
used to analyse levels of target gene transcripts post RNAi transformation.
The role of A. bisporus genes identified, in the infection process, will be determined
through infection trails with A. bisporus silenced lines
In vivo and in vitro synthesis of CM-proteins (A-hordeins) from barley (Hordeum vulgare L.)
CM-proteins from barley endosperm (CMa, CMb, CMc, CMd), which are the main components of the A-hordein fraction, are synthesized most actively 10 to 30 d after anthesis (maximum at 15â20 d). They are synthesized by membranebound polysomes as precursors of higher apparent molecular weight (13,000â21,000) than the mature proteins (12,000â16,000). The largest in vitro product (21,000) is the putative precursor of protein CMd (16,000), as it is selected with anti-CMd monospecific IgG's, and is coded by an mRNA of greater sedimentation coefficient (9 S) than those encoding the other three proteins (7.5 S). CM-proteins always appear in the soluble fraction, following different homogenization and subcellular fractionation procedures, indicating that these proteins are transferred to the soluble fraction after processing
Rare variants in optic disc area gene CARD10 enriched in primary open-angle glaucoma
Background: Genome-wide association studies (GWAS) have identified association of common alleles with primary open-angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study aims to determine whether rare pathogenic variants in these disease-associated genes contribute to POAG. Methods: Participants fulfilled strict inclusion criteria of advanced POAG at a young age of diagnosis. Myocilin mutation carriers were excluded using direct sequencing. Whole exome sequencing was performed on 187 glaucoma cases and 103 local screened nonglaucoma controls then joint-called with exomes of 993 previously sequenced Australian controls. GWAS-associated genes were assessed for enrichment of rare predicted pathogenic variants in POAG. Significantly enriched genes were compared against Exome Aggregation Consortium (ExAC) public control. Results: Eighty-six GWAS disease or trait-associated glaucoma genes were captured and sequenced. CARD10 showed enrichment after Bonferroni correction for rare variants in glaucoma cases (OR = 13.2, P = 6.94 Ă 10â5) with mutations identified in 4.28% of our POAG cohort compared to 0.27% in controls. CARD10 was significantly associated with optic disc parameters in previous GWAS. The whole GWAS gene set showed no enrichment in POAG overall (OR = 1.12, P = 0.51). Conclusion: We report here an enrichment of rare predicted pathogenic coding variants within a GWAS-associated locus in POAG (CARD10). These findings indicate that both common and rare pathogenic coding variants in CARD10 may contribute to POAG pathogenesis.Tiger Zhou, Emmanuelle Souzeau, Shiwani Sharma, Owen M. Siggs, Ivan Goldberg, Paul R. Healey, Stuart Graham, Alex W. Hewitt, David A. Mackey, Robert J. Casson, John Landers, Richard Mills, Jonathan Ellis, Paul Leo, Matthew A. Brown, Stuart MacGregor, Kathryn P. Burdon and Jamie E. Crai
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
The Gauteng conservation plan : planning for biodiversity in a rapidly urbanising province
BACKGROUND : Gauteng, the smallest of South Africaâs nine provinces, is rich in biodiversity;
yet it is also the most densely populated province and thus faces significant development
pressures.
OBJECTIVE : A project was therefore initiated in 2001 to identify areas of biodiversity importance
in the province, using the systematic spatial biodiversity planning approach that has been
adopted in South Africa. This article reports on the final version of the provincial conservation
plan as completed in 2011.
METHOD : Vegetation types and quaternary catchments constituted the coarse filter biodiversity
features, while rare and threatened taxa constituted the fine filter features. Ecological processes
were captured by a range of landscape features, while planning for climate change primarily
involved the design of a corridor network. Planning was undertaken within the ArcView
linked C-plan decision support system, where a cost surface preferentially directed the
selection of available sites towards low-cost areas.
RESULTS : Forty-four per cent of the province is required to achieve targets. Only 8% of features
are close to having their targets met or are adequately conserved in the current protected area
network of 23 protected areas covering 2.4% of the province, while 73% of features are absent
or poorly represented.
CONCLUSION : The existing protected area network is inadequate for the conservation of
biodiversity in Gauteng. The Gauteng Conservation Plan identifies a set of areas that are
required to achieve conservation targets. It is important that identified areas currently not
in the protected area network are protected either formally or through legislated land use
management processes.http://www.abcjournal.orgam2018Zoology and Entomolog
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
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