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81.
Terence Tafatatha Miriam Taegtmeyer Bagrey Ngwira Amos Phiri Mariot Kondowe Wilson Piston Anna Molesworth Ndoliwe Kayuni Olivier Koole Amelia Crampin John Horton Neil French 《PLoS neglected tropical diseases》2015,9(6)
BackgroundLymphatic filariasis (LF) and human immunodeficiency virus (HIV) are major public health problems. Individuals may be co-infected, raising the possibility of important interactions between these two pathogens with consequences for LF elimination through annual mass drug administration (MDA).Conclusions/SignificanceIn this large cross-sectional study of two distinct LF-exposed populations, there is no evidence that HIV infection has an impact on LF epidemiology that will interfere with LF control measures. A significant association of ART use with lower CFA prevalence merits further investigation to understand this apparent beneficial impact of ART. 相似文献
82.
Mariapaola Marino Flavia Scuderi Daniela Samengo Giorgia Saltelli Maria Teresa Maiuri Chengyong Shen Lin Mei Mario Sabatelli Giovambattista Pani Giovanni Antonini Amelia Evoli Emanuela Bartoccioni 《PloS one》2015,10(8)
Background
Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoantibodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4 (LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG.Methods
The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system.Results
We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals.Conclusion
Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis. 相似文献83.
84.
Alison Donnelly Olivia Crowe Eugenie Regan Sinead Begley Amelia Caffarra 《International journal of biometeorology》2014,58(6):1237-1249
Citizen science is proving to be an effective tool in tracking the rapid pace at which our environment is changing over large geographic areas. It is becoming increasingly popular, in places such as North America and some European countries, to engage members of the general public and school pupils in the collection of scientific data to support long-term environmental monitoring. Participants in such schemes are generally volunteers and are referred to as citizen scientists. The Christmas bird count in the US is one of the worlds longest running citizen science projects whereby volunteers have been collecting data on birds on a specific day since 1900. Similar volunteer networks in Ireland have been in existence since the 1960s and were established to monitor the number and diversity of birds throughout the country. More recently, initiatives such as Greenwave (2006) and Nature Watch (2009) invite school children and members of the general public respectively, to record phenology data from a range of common species of plant, insect and bird. In addition, the Irish butterfly and bumblebee monitoring schemes engage volunteers to record data on sightings of these species. The primary purpose of all of these networks is to collect data by which to monitor changes in wildlife development and diversity, and in the case of Greenwave to involve children in hands-on, inquiry-based science. Together these various networks help raise awareness of key environmental issues, such as climate change and loss of biodiversity, while at the same time promote development of scientific skills among the general population. In addition, they provide valuable scientific data by which to track environmental change. Here we examine the role of citizen science in monitoring biodiversity in Ireland and conclude that some of the data collected in these networks can be used to fulfil Ireland’s statutory obligations for nature conservation. In addition, a bee thought previously to be extinct has been rediscovered and a range expansion of a different bee has been confirmed. However, it also became apparent that some of the networks play more of an educational than a scientific role. Furthermore, we draw on experience from a range of citizen science projects to make recommendations on how best to establish new citizen science projects in Ireland and strengthen existing ones. 相似文献
85.
Ismael Bustos-Jaimes Rodrigo Mora-Lugo Mario L. Calcagno Amelia Farrés 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(12):2222-2227
Lipases are useful catalysts for a wide variety of industrial purposes. Herein we report the stability and thermal dependence of the activity of wild-type Bacillus pumilus lipase (BplA) and four site-directed mutants designed to improve its thermal stability. The Gly28:Ser mutation produces a dramatic four-fold increase in its kcat and a remarkable increase in its stability. While the increase in kcat is temperature-independent, the increase in stability shows that the resultant interactions of this mutation have a strong enthalpic component. Thermal dependence of stability, kcat, KM and kcat/KM were analysed to gain insight on the structural effects of mutations on BplA. Our results are consistent with a gain in enzyme mobility for those mutants displaying enhanced catalytic properties; the analysis of thermal dependence of kinetic parameters indicates that the mutations did not change either the catalytic mechanism or the rate-limiting step of catalysis. 相似文献
86.
Blake C. Ballif Aaron Theisen Ryan N. Traylor Devon Lamb Thrush Caroline Astbury Dennis Bartholomew Kim L. McBride Robert E. Pyatt Kate Shane Wendy E. Smith William B. Gallentine M. Katharine Rudd Julia A. Keene Jean P. Pfotenhauer Pawel Stankiewicz Bassem A. Bejjani 《American journal of human genetics》2010,86(3):454-461
87.
John C O'LearyIII Qingyou Li Paul Marinec Laura J Blair Erin E Congdon Amelia G Johnson Umesh K Jinwal John KorenIII Jeffrey R Jones Clara Kraft Melinda Peters Jose F Abisambra Karen E Duff Edwin J Weeber Jason E Gestwicki Chad A Dickey 《Molecular neurodegeneration》2010,5(1):45
Background
It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection.Results
Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember?, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced.Conclusions
Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.88.
Pilichiewicz AN Chaikomin R Brennan IM Wishart JM Rayner CK Jones KL Smout AJ Horowitz M Feinle-Bisset C 《American journal of physiology. Endocrinology and metabolism》2007,293(3):E743-E753
Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 ("G1"), 2) 2 ("G2"), and 3) 4 ("G4") kcal/min or of 4) saline ("control") were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions (P < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 (P < 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load (r > 0.82, P < 0.05). All glucose infusions suppressed antral (P < 0.05), but only G4 decreased duodenal, pressure waves (P < 0.01), resulted in a sustained stimulation of basal pyloric pressure (P < 0.01), and decreased energy intake (P < 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes. 相似文献
89.
Viral interference with antigen presentation does not alter acute or chronic CD8 T cell immunodominance in murine cytomegalovirus infection 总被引:2,自引:0,他引:2
Munks MW Pinto AK Doom CM Hill AB 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(11):7235-7241
Both human CMV and murine CMV (MCMV) elicit large CD8 T cell responses, despite the potent effects of viral genes that interfere with the MHC class I (MHC I) pathway of Ag presentation. To investigate the impact of immune evasion on CD8 T cell priming, we infected mice with wild-type (wt) MCMV or a mutant lacking its MHC I immune evasion genes, Deltam4+m6+m152 MCMV. In acute infection, the two viruses elicited a CD8 T cell response to 26 peptide epitopes that was virtually identical in total size, kinetics, and immunodominance hierarchy. This occurred despite results demonstrating that primary DCs are susceptible to the effects of MCMV's MHC I immune evasion genes. Eight months later, responses to both wt and mutant MCMV displayed the same CD8 T cell "memory inflation" and altered immunodominance that characterize the transition to chronic MCMV infection in C57BL/6 mice. Taken together, these findings suggest either that cross-priming dominates over direct CD8 T cell priming in both acute and chronic MCMV infection, or else that the MHC I immune evasion genes of MCMV are unable to alter direct CD8 T cell priming in vivo. At 2 years postinfection, differences in CD8 T cell immunodominance emerged between individual mice, but on average there were only slight differences between wt and mutant virus infections. Overall, the data indicate that the presence or absence of MHC I immune evasion genes has remarkably little impact on the size or specificity of the MCMV-specific CD8 T cell response over an entire lifetime of infection. 相似文献
90.
A genomewide association study of skin pigmentation in a South Asian population 总被引:4,自引:0,他引:4
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Stokowski RP Pant PV Dadd T Fereday A Hinds DA Jarman C Filsell W Ginger RS Green MR van der Ouderaa FJ Cox DR 《American journal of human genetics》2007,81(6):1119-1132
We have conducted a multistage genomewide association study, using 1,620,742 single-nucleotide polymorphisms to systematically investigate the genetic factors influencing intrinsic skin pigmentation in a population of South Asian descent. Polymorphisms in three genes—SLC24A5, TYR, and SLC45A2—yielded highly significant replicated associations with skin-reflectance measurements, an indirect measure of melanin content in the skin. The associations detected in these three genes, in an additive manner, collectively account for a large fraction of the natural variation of skin pigmentation in a South Asian population. Our study is the first to interrogate polymorphisms across the genome, to find genetic determinants of the natural variation of skin pigmentation within a human population. 相似文献