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21.
Rutendo B. L. Zinyama-Gutsire Charles Chasela Hans O. Madsen Simbarashe Rusakaniko Per Kallestrup Michael Christiansen Exnevia Gomo Henrik Ullum Christian Erikstrup Shungu Munyati Edith N. Kurewa Babill Stray-Pedersen Peter Garred Takafira Mduluza 《PloS one》2015,10(4)
Background
Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort).Methods
HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR. We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54A>G), C (codon 57A>G), and D (codon 52T>C) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test.Results
We assessed 379 adults, 80% females, median age (IQR) 30 (17–41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800μg/L (192-1936μg/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57G>A) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912μg/L) and HIV positive (688μg/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20μg/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection.Conclusion
Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S. haematobium infection. 相似文献22.
?ivind ?rstavik Ornella Manfra Kjetil Wessel Andressen Geir ?ystein Andersen Tor Skomedal Jan-Bj?rn Osnes Finn Olav Levy Kurt Allen Krobert 《PloS one》2015,10(3)
Aims
We recently published that the positive inotropic response (PIR) to levosimendan can be fully accounted for by phosphodiesterase (PDE) inhibition in both failing human heart and normal rat heart. To determine if the PIR of the active metabolite OR-1896, an important mediator of the long-term clinical effects of levosimendan, also results from PDE3 inhibition, we compared the effects of OR-1896, a representative Ca2+ sensitizer EMD57033 (EMD), levosimendan and other PDE inhibitors.Methods
Contractile force was measured in rat ventricular strips. PDE assay was conducted on rat ventricular homogenate. cAMP was measured using RII_epac FRET-based sensors.Results
OR-1896 evoked a maximum PIR of 33±10% above basal at 1 μM. This response was amplified in the presence of the PDE4 inhibitor rolipram (89±14%) and absent in the presence of the PDE3 inhibitors cilostamide (0.5±5.3%) or milrinone (3.2±4.4%). The PIR was accompanied by a lusitropic response, and both were reversed by muscarinic receptor stimulation with carbachol and absent in the presence of β-AR blockade with timolol. OR-1896 inhibited PDE activity and increased cAMP levels at concentrations giving PIRs. OR-1896 did not sensitize the concentration-response relationship to extracellular Ca2+. Levosimendan, OR-1896 and EMD all increased the sensitivity to β-AR stimulation. The combination of either EMD and levosimendan or EMD and OR-1896 further sensitized the response, indicating at least two different mechanisms responsible for the sensitization. Only EMD sensitized the α1-AR response.Conclusion
The observed PIR to OR-1896 in rat ventricular strips is mediated through PDE3 inhibition, enhancing cAMP-mediated effects. These results further reinforce our previous finding that Ca2+ sensitization does not play a significant role in the inotropic (and lusitropic) effect of levosimendan, nor of its main metabolite OR-1896. 相似文献23.
Elizabeth Peacock Sarah A. Sonsthagen Martyn E. Obbard Andrei Boltunov Eric V. Regehr Nikita Ovsyanikov Jon Aars Stephen N. Atkinson George K. Sage Andrew G. Hope Eve Zeyl Lutz Bachmann Dorothee Ehrich Kim T. Scribner Steven C. Amstrup Stanislav Belikov Erik W. Born Andrew E. Derocher Ian Stirling Mitchell K. Taylor ?ystein Wiig David Paetkau Sandra L. Talbo 《PloS one》2015,10(8)
24.
Bacillus anthracis, the causative agent of anthrax, is known as one of the most genetically monomorphic species. Canonical single-nucleotide polymorphism (SNP) typing and whole-genome sequencing were used to investigate the molecular diversity of eleven B. anthracis strains isolated from cattle in Denmark between 1935 and 1988. Danish strains were assigned into five canSNP groups or lineages, i.e. A.Br.001/002 (n = 4), A.Br.Ames (n = 2), A.Br.008/011 (n = 2), A.Br.005/006 (n = 2) and A.Br.Aust94 (n = 1). The match with the A.Br.Ames lineage is of particular interest as the occurrence of such lineage in Europe is demonstrated for the first time, filling an historical gap within the phylogeography of the lineage. Comparative genome analyses of these strains with 41 isolates from other parts of the world revealed that the two Danish A.Br.008/011 strains were related to the heroin-associated strains responsible for outbreaks of injection anthrax in drug users in Europe. Eight novel diagnostic SNPs that specifically discriminate the different sub-groups of Danish strains were identified and developed into PCR-based genotyping assays. 相似文献
25.
Gunilla Veslem?y Schmidt Anders Mellerup Lasse Engbo Christiansen Marie St?hl John Elmerdahl Olsen ?ystein Angen 《PloS one》2015,10(6)
The aim of this article was to define the sampling level and method combination that captures antibiotic resistance at pig herd level utilizing qPCR antibiotic resistance gene quantification and culture-based quantification of antibiotic resistant coliform indicator bacteria. Fourteen qPCR assays for commonly detected antibiotic resistance genes were developed, and used to quantify antibiotic resistance genes in total DNA from swine fecal samples that were obtained using different sampling and pooling methods. In parallel, the number of antibiotic resistant coliform indicator bacteria was determined in the same swine fecal samples. The results showed that the qPCR assays were capable of detecting differences in antibiotic resistance levels in individual animals that the coliform bacteria colony forming units (CFU) could not. Also, the qPCR assays more accurately quantified antibiotic resistance genes when comparing individual sampling and pooling methods. qPCR on pooled samples was found to be a good representative for the general resistance level in a pig herd compared to the coliform CFU counts. It had significantly reduced relative standard deviations compared to coliform CFU counts in the same samples, and therefore differences in antibiotic resistance levels between samples were more readily detected. To our knowledge, this is the first study to describe sampling and pooling methods for qPCR quantification of antibiotic resistance genes in total DNA extracted from swine feces. 相似文献
26.
PGE2 plays an important role in a broad spectrum of physiological and pathological processes mediated through a membrane-bound G protein-coupled receptor (GPCR) called EP receptor. In mammals, four subtypes of EP receptor (EP 1-4) are identified and each of them functions through different signal transduction pathways. Orthologous EP receptors have also been identified in other non-mammalian species, such as chicken and zebrafish. EP4 is the only identified PGE2 receptor to date in Atlantic salmon but its tissue distribution and function have not been studied in any detail. In this study, we first sequenced EP4 receptor in different tissues and found that the presence of the 3nt deletion in the 5’ untranslated region was accompanied by silent mutation at nt 668. While attempting to amplify the same sequence in TO cells (an Atlantic salmon macrophage-like cell line), we failed to obtain the full-length product. Further investigation revealed different isoform of EP4 receptor in TO cells and we subsequently documented its presence in different Atlantic salmon tissues. These two isoforms of EP4 receptor share high homology in their first half of sequence but differ in the second half part with several deletion segments though the final length of coding sequence is the same for two isoforms. We further studied the immunomodulation effect of PGE2 in TO cells and found that PGE2 inhibited the induction of CXCL-10, CCL-4, IL-8 and IL-1β genes expression in a time dependent manner and without cAMP upregulation. 相似文献
27.
Pradip K. Sasmal Sanjita Sasmal P. Tirumala Rao B. Venkatesham M. Roshaiah Chandrasekhar Abbineni Ish Khanna Vikram P. Jadhav J. Suresh Rashmi Talwar Syed Muzeeb Jean-Marie Receveur Thomas M. Frimurer Øystein Rist Lisbeth Elster Thomas Högberg 《Bioorganic & medicinal chemistry letters》2010,20(18):5443-5448
Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays role in several disorders such as obesity, stress, depression and anxiety. The synthesis and biological evaluation of novel benzimidazole derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. 相似文献
28.
Tore Skrøppa Mari Mette Tollefsrud Christoph Sperisen Øystein Johnsen 《Tree Genetics & Genomes》2010,6(1):93-99
Seedlings of open-pollinated Picea abies families from Norwegian and Central European parent trees standing at three sites in Norway were tested for timing of bud
set at the end of the first growth season together with seedlings from control provenances producing seeds at their geographical
origin. The parental origins were confirmed with a maternally inherited mitochondrial marker that distinguishes trees of the
Northern European range from those of the Central European range. The seedlings from the families of Central European mother
trees producing seeds in Norway had on average a bud set more similar to the families of local Norwegian origin producing
seeds at the same site than the provenance of the same Central European origin. It is argued that the rapid change in this
adaptive trait from one generation to the next can be explained by recent research results demonstrating that day length and
temperature conditions during embryo formation and maturation can influence the phenotypic performance of seedlings in Norway
spruce. This effect may influence the fitness of naturally regenerated plants produced in plantations of Central European
trees in Norway. 相似文献
29.
Ersvaer E Skavland J Ulvestad E Gjertsen BT Bruserud Ø 《Cancer immunology, immunotherapy : CII》2007,56(1):13-24
T cell targeting immunotherapy is now considered a possible strategy in acute myelogenous leukaemia (AML), and IFNγ release may then contribute to the antileukaemic effects. We investigated the effects of IFNγ on native human AML cells. Normal T cells could be activated to release IFNγ in the presence of AML cells. Furthermore, high levels of CD119 (IFNγ receptor α chain) expression were observed for all 39 patients examined. Receptor expression was decreased after exposure to exogenous IFNγ, and receptor ligation caused Stat1 phosphorylation but no phosphorylation of the alternative messengers Erk1/2. The effect of exogenous IFNγ on AML blast proliferation was dependent on the local cytokine network and IFNγ (1) inhibited proliferation in the presence of exogenous IL1β, GM-CSF, G-CSF and SCF; (2) had divergent effects in the presence of IL3 and Flt3 (65 patients examined); (3) inhibited proliferation in the presence of endothelial cells but had divergent effects in the presence of fibroblasts, osteoblasts and normal stromal cells (65 patients examined). IFNγ increased stress-induced (spontaneous) in vitro apoptosis as well as cytarabine-induced apoptosis only for a subset of patients. Furthermore, IFNγ decreased the release of proangiogenic CXCL8 and increased the release of antiangiogenic CXCL9–11. We conclude that IFNγ can be released in the presence of native human AML cells and affect AML cell proliferation, regulation of apoptosis and the balance between pro- and antiangiogenic chemokine release. 相似文献
30.
In winter 2000–2001, there was a serious outbreak of Gremmeniella abietina Morelet in southeastern Norway. During the outbreak, we noted that injured Scots pine trees (Pinus sylvestris L.) developed secondary buds in response to the fungus attack, and we decided to study the relationship between injury, appearance
of secondary buds and recovery of the trees thereafter. For this purpose, 143 trees from 10 to 50 years of age were chosen
and grouped into crown density classes. Injury was assessed in detail, and buds were counted before bud burst in the spring
of 2002. In addition, a subset of 15 trees was followed through the summer of 2002 to assess recovery. All injured trees developed
secondary buds, with a clear overweight of dormant winter buds in proportion to interfoliar buds. Healthy control trees did
not develop secondary buds at all. The secondary buds appeared predominantly on the injured parts of the tree; interfoliar
buds in particular developed just beneath the damaged tissue. Most of the secondary buds died during the winter of 2001–2002,
mainly because the fungus continued to spread after the first outbreak. Many of the remaining buds developed shoots with abnormal
growth during the summer. Secondary buds may help trees to recover from Gremmeniella attacks, but this strategy may fail when the fungus continues to grow and injure the newly formed buds and shoots. 相似文献