961 research outputs found
Maternal Pregnancy Levels of Polychlorinated Biphenyls and Risk of Hypospadias and Cryptorchidism in Male Offspring
Role of P-selectin in platelet sequestration in pulmonary capillaries during endotoxemia
Background: There is growing evidence that platelets accumulate in the lung and contribute to the pathogenesis of acute lung injury during endotoxemia. The aims of the present study were to localize platelet sequestration in the pulmonary microcirculation and to investigate the role of P-selectin as a molecular mechanism of platelet endothelial cell interaction. Methods: We used in vivo fluorescence microscopy to quantify the kinetics of fluorescently labeled erythrocytes and platelets in alveolar capillary networks in rabbit lungs. Results: Six hours after onset of endotoxin infusion we observed a massive rolling along and firm adherence of platelets to lung capillary endothelial cells whereas under control conditions no platelet sequestration was detected. P-selectin was expressed on the surface of separated platelets which were incubated with endotoxin and in lung tissue. Pretreatment of platelets with fucoidin, a P-selectin antagonist, significantly attenuated the endotoxin-induced platelet rolling and adherence. In contrast, intravenous infusion of fucoidin in endotoxin-treated rabbits did not inhibit platelet sequestration in pulmonary capillaries. Conclusion: We conclude that platelets accumulate in alveolar capillaries following endotoxemia. P-selectin expressed on the surface of platelets seems to play an important role in mediating this platelet-endothelial cell interaction. Copyright (c) 2006 S. Karger AG, Basel
Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus
Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses
Therapeutic monoclonal antibodies for Ebola virus infection derived from vaccinated humans
We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- to pico-molar range, similar to “affinity matured” antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies
Seagrass can mitigate negative ocean acidification effects on calcifying algae
The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters
funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks
to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm
structure and experimental assistance.info:eu-repo/semantics/publishedVersio
Genome Sequence Analysis of Dengue Virus 1 Isolated in Key West, Florida
Dengue virus (DENV) is transmitted to humans through the bite of mosquitoes. In November 2010, a dengue outbreak was reported in Monroe County in southern Florida (FL), including greater than 20 confirmed human cases. The virus collected from the human cases was verified as DENV serotype 1 (DENV-1) and one isolate was provided for sequence analysis. RNA was extracted from the DENV-1 isolate and was used in reverse transcription polymerase chain reaction (RT-PCR) to amplify PCR fragments to sequence. Nucleic acid primers were designed to generate overlapping PCR fragments that covered the entire genome. The DENV-1 isolate found in Key West (KW), FL was sequenced for whole genome characterization. Sequence assembly, Genbank searches, and recombination analyses were performed to verify the identity of the genome sequences and to determine percent similarity to known DENV-1 sequences. We show that the KW DENV-1 strain is 99% identical to Nicaraguan and Mexican DENV-1 strains. Phylogenetic and recombination analyses suggest that the DENV-1 isolated in KW originated from Nicaragua (NI) and the KW strain may circulate in KW. Also, recombination analysis results detected recombination events in the KW strain compared to DENV-1 strains from Puerto Rico. We evaluate the relative growth of KW strain of DENV-1 compared to other dengue viruses to determine whether the underlying genetics of the strain is associated with a replicative advantage, an important consideration since local transmission of DENV may result because domestic tourism can spread DENVs
Experiences of Alcohol Use and Harm among Travellers, Roma, and Gypsies: A Participatory Qualitative Study
Alcohol is widely used in many cultures as part of everyday life and for special occasions. It is a leading cause of preventable death in the UK, with higher rates among socioeconomically disadvantaged people. Gypsies and Travellers are ethnic and cultural minorities who experience extreme social disadvantage but there is a lack of knowledge about their alcohol use. The study aim was to explore experiences of alcohol use and harm in these distinct groups. Taking a participatory research approach, peer researchers conducted semistructured interviews (n = 26) to explore experiences of alcohol use and harm within the following four Gypsy/Traveller communities: Irish Travellers, Boaters, Gypsies, and Slovakian Roma. Vignettes were used as a basis for interview questions. Data were analysed thematically following the framework model. Alcohol consumption was found to be fundamental to celebration in all groups and integrated within social norms. Among Gypsies, Irish Travellers and Roma, drinking was associated with masculinity and despite an increase in alcohol use among women, female drinking remains highly socially regulated. Gypsies and Irish Travellers reported being illegally excluded from public drinking venues, while Slovakian Roma experienced less discrimination towards their ethnic group in the UK. Knowledge of the risks of alcohol dependence was high in all groups, but there was little awareness of the health impact of regular heavy drinking. Shame was a barrier to help-seeking for Gypsy, Roma, and Irish Traveller men and women, while Boaters' nomadism reduced access to both primary care and alcohol treatment services. These distinct ethnic and cultural groups are aware of the health and social risks of alcohol use but experience barriers to accessing healthcare. Each community has different needs in relation to prevention of alcohol dependence, highlighting the need for targeted health promotion to accompany national strategies to reduce alcohol harm
Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer
PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken
Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis
Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1
<p><b>Background:</b> The three sub-species of <i>Trypanosoma brucei</i> are important pathogens of sub-Saharan Africa. <i>T. b. brucei</i> is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. <i>T. b. rhodesiense</i> and <i>T. b. gambiense</i> are able to resist lysis by TLF. There are two distinct sub-groups of <i>T. b. gambiense</i> that differ genetically and by human serum resistance phenotypes. Group 1 <i>T. b. gambiense</i> have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 <i>T. b. gambiense</i> are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (<i>HpHbR</i>)) gene. Here we investigate if this is also true in group 2 parasites.</p>
<p><b>Methodology:</b> Isogenic resistant and sensitive group 2 <i>T. b. gambiense</i> were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the <i>HpHbR</i> gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to <i>T. b. brucei</i>. Both resistant and sensitive group 2, as well as group 1 <i>T. b. gambiense</i>, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.</p>
<p><b>Conclusions:</b> Our data indicate that, despite group 1 <i>T. b. gambiense</i> avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 <i>T. b. gambiense</i> is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 <i>T. b. gambiense</i> variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of <i>HpHbR</i>. Thus there are differences in the mechanism of human serum resistance between <i>T. b. gambiense</i> groups 1 and 2.</p>
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