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61.
Aspects which need to be considered when calculating pollen influx values in three sedimentary environments (pollen traps, peats and lake sediments) are reviewed. Examples of influx values (grains cm-2 year-1) in northern Fennoscandia for two arboreal taxa Betula and Pinus, calculated from these three different environments are presented. Such long term average pollen influx values can be used to indicate the presence/absence and density of the species within the vicinity of the sampling site. Contrary to expectations, conditions do exist in which numerically comparable values are obtained from all three environments. Using these pollen influx values to interpret forest and woodland history in tree-line situations, from both peats and lake sediments, a higher degree of precision can be obtained than through the more classical pollen percentage method alone. 相似文献
62.
Gerco den Hartog Ranajoy Chattopadhyay Amber Ablack Emily H. Hall Lindsay D. Butcher Asima Bhattacharyya Lars Eckmann Paul R. Harris Soumita Das Peter B. Ernst Sheila E. Crowe 《PLoS pathogens》2016,12(1)
Generation of reactive oxygen species (ROS) during infection is an immediate host defense leading to microbial killing. APE1 is a multifunctional protein induced by ROS and after induction, protects against ROS-mediated DNA damage. Rac1 and NAPDH oxidase (Nox1) are important contributors of ROS generation following infection and associated with gastrointestinal epithelial injury. The purpose of this study was to determine if APE1 regulates the function of Rac1 and Nox1 during oxidative stress. Gastric or colonic epithelial cells (wild-type or with suppressed APE1) were infected with Helicobacter pylori or Salmonella enterica and assessed for Rac1 and NADPH oxidase-dependent superoxide production. Rac1 and APE1 interactions were measured by co-immunoprecipitation, confocal microscopy and proximity ligation assay (PLA) in cell lines or in biopsy specimens. Significantly greater levels of ROS were produced by APE1-deficient human gastric and colonic cell lines and primary gastric epithelial cells compared to control cells after infection with either gastric or enteric pathogens. H. pylori activated Rac1 and Nox1 in all cell types, but activation was higher in APE1 suppressed cells. APE1 overexpression decreased H. pylori-induced ROS generation, Rac1 activation, and Nox1 expression. We determined that the effects of APE1 were mediated through its N-terminal lysine residues interacting with Rac1, leading to inhibition of Nox1 expression and ROS generation. APE1 is a negative regulator of oxidative stress in the gastrointestinal epithelium during bacterial infection by modulating Rac1 and Nox1. Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections. 相似文献
63.
64.
Sheila N. Balinda Pascale Ondoa Ekwaro A. Obuku Aletta Kliphuis Isaac Egau Michelle Bronze Lordwin Kasambula Rob Schuurman Nicole Spieker Tobias F. Rinke de Wit Cissy Kityo ART–A consortium 《PloS one》2016,11(1)
Background
WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low–cost, qualitative viral–failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda.Methods
We conducted a cross–sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV–1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml).Results
496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%–87.1%), 93% specificity (95% CI: 89.7%–96.4%), 89.3% accuracy (95% CI: 85%–92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively.Conclusions
VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second–line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV–1 treatment in RLS. 相似文献65.
Effects of canola and high‐oleic‐acid canola oils on abdominal fat mass in individuals with central obesity 下载免费PDF全文
66.
Decker Helena Piermartiri Tetsade C. B. Nedel Cláudia B. Romão Luciana F. Francisco Sheila S. Dal-Cim Tharine Boeck Carina R. Moura-Neto Vivaldo Tasca Carla I. 《Purinergic signalling》2019,15(4):439-450
Purinergic Signalling - The guanine-based purines (GBPs) have essential extracellular functions such as modulation of glutamatergic transmission and trophic effects on neurons and astrocytes. We... 相似文献
67.
Sheila Ommeh Wei Zhang Ali Zohaib Jing Chen Huajun Zhang Ben Hu Xing-Yi Ge Xing-Lou Yang Moses Masika Vincent Obanda Yun Luo Shan Li Cecilia Waruhiu Bei Li Yan Zhu Desterio Ouma Vincent Odendo Lin-Fa Wang Danielle E. Anderson Jacqueline Lichoti Erick Mungube Francis Gakuya Peng Zhou Kisa-Juma Ngeiywa Bing Yan Bernard Agwanda Zheng-Li Shi 《中国病毒学》2019,34(1):115-115
68.
Robert B. Lochhead David Ordoez Sheila L. Arvikar John M. Aversa Luke S. Oh Benton Heyworth Ruslan Sadreyev Allen C. Steere Klemen Strle 《Cellular microbiology》2019,21(2)
Lyme arthritis (LA), a late disease manifestation of Borrelia burgdorferi infection, usually resolves with antibiotic therapy. However, some patients develop proliferative synovitis lasting months to several years after spirochetal killing, called postinfectious LA. In this study, we phenotyped haematopoietic and stromal cell populations in the synovial lesion ex vivo and used these findings to generate an in vitro model of LA using patient‐derived fibroblast‐like synoviocytes (FLS). Ex vivo analysis of synovial tissue revealed high abundance of IFNγ‐producing T cells and NK cells. Similar to marked IFNγ responses in tissue, postinfectious LA synovial fluid also had high levels of IFNγ. HLA‐DR‐positive FLS were present throughout the synovial lesion, particularly in areas of inflammation. FLS stimulated in vitro with B. burgdorferi, which were similar to conditions during infection, expressed 68 genes associated primarily with innate immune activation and neutrophil recruitment. In contrast, FLS stimulated with IFNγ, which were similar to conditions in the postinfectious phase, expressed >2,000 genes associated with pathogen sensing, inflammation, and MHC Class II antigen presentation, similar to the expression profile in postinfectious synovial tissue. Furthermore, costimulation of FLS with B. burgdorferi and IFNγ induced greater expression of IL‐6 and other innate immune response proteins and genes than with IFNγ stimulation alone. These results suggest that B. burgdorferi infection, in combination with IFNγ, initiates the differentiation of FLS into a highly inflammatory phenotype. We hypothesise that overexpression of IFNγ by lymphocytes within synovia perpetuates these responses in the postinfectious period, causing proliferative synovitis and stalling appropriate repair of damaged tissue. 相似文献
69.
Kerns JA Cargill EJ Clark LA Candille SI Berryere TG Olivier M Lust G Todhunter RJ Schmutz SM Murphy KE Barsh GS 《Genetics》2007,177(3):1679-1689
Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red-yellow pheomelanin vs. black-brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador x greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (K(B)) > brindle (k(br)) > yellow (k(y)), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection. 相似文献
70.
Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia 总被引:3,自引:0,他引:3
Rydziel S Stadmeyer L Zanotti S Durant D Smerdel-Ramoya A Canalis E 《The Journal of biological chemistry》2007,282(27):19762-19772
Nephroblastoma overexpressed (Nov), a member of the Cyr 61, connective tissue growth factor, Nov (CCN) family of proteins, is expressed by osteoblasts, but its function in cells of the osteoblastic lineage is not known. We investigated the effects of Nov overexpression by transducing murine ST-2 stromal and MC3T3 osteoblastic cells with a retroviral vector where Nov is under the control of the cytomegalovirus promoter. We also examined the skeletal phenotype of transgenic mice expressing Nov under the control of the human osteocalcin promoter. Overexpression of Nov in ST-2 cells inhibited the appearance of mineralized nodules and decreased alkaline phosphatase activity and osteocalcin mRNA levels. Nov overexpression inhibited the effect of bone morphogenetic protein (BMP)-2 on the phosphorylation of Smad 1/5/8; on the transactivation of 12xSBE-Oc-pGL3, a BMP/Smad signaling reporter construct, and of Wnt 3 on cytoplasmic beta-catenin levels; and on the transactivation of the Wnt/beta-catenin signaling reporter construct 16xTCF-Luc. Nov overexpression did not activate Notch or transforming growth factor beta signaling. Glutathione S-transferase pulldown assays demonstrated direct Nov-BMP interactions. Nov transgenic mice exhibited osteopenia. In conclusion, Nov binds BMP-2 and antagonizes BMP-2 and Wnt activity, and its overexpression inhibits osteoblastogenesis and causes osteopenia. 相似文献