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41.
Richelle C. Charles Tania Sultana Mohammad Murshid Alam Yanan Yu Ying Wu-Freeman Meagan Kelly Bufano Sean M. Rollins Lillian Tsai Jason B. Harris Regina C. LaRocque Daniel T. Leung W. Abdullah Brooks Tran Vu Thieu Nga Sabina Dongol Buddha Basnyat Stephen B. Calderwood Jeremy Farrar Farhana Khanam John S. Gunn Firdausi Qadri Stephen Baker Edward T. Ryan 《PLoS neglected tropical diseases》2013,7(8)
Background
Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage.Methodology/Principal Findings
To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present.Conclusions/Significance
Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers. 相似文献42.
van Dooren SH Raijmakers R Pluk H Lokate AM Koemans TS Spanjers RE Heck AJ Boelens WC van Venrooij WJ Pruijn GJ 《Biochimie et biologie cellulaire》2011,89(6):545-553
The aminoacyl-tRNA synthetases are ubiquitously expressed enzymes that catalyze the esterification of amino acids to their cognate tRNAs. Autoantibodies against several aminoacyl-tRNA synthetases are found in autoimmune polymyositis and dermatomyositis patients. Because necrosis is often found in skeletal muscle biopsies of these patients, we hypothesized that cell-death-induced protein modifications may help in breaking immunological tolerance. Since cell death is associated with oxidative stress, the effect of oxidative stress on the main myositis-specific autoantibody target Jo-1 (histidyl-tRNA synthetase; HisRS) was studied in detail. The exposure of Jurkat cells to hydrogen peroxide resulted in the detection of several oxidized methionines and one oxidized tryptophan residue in the HisRS protein, as demonstrated by mass spectrometry. Unexpectedly, the tRNA aminoacylation activity of HisRS appeared to be increased upon oxidative modification. The analysis of myositis patient sera did not lead to the detection of autoantibodies that are specifically reactive with the modified HisRS protein. The results of this study demonstrate that the Jo-1/HisRS autoantigen is modified under oxidative stress conditions. The consequences of these modifications for the function of HisRS and its autoantigenicity are discussed. 相似文献
43.
44.
Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine,Shanchol, in Haiti
Richelle C. Charles Isabelle J. Hilaire Leslie M. Mayo-Smith Jessica E. Teng J. Gregory Jerome Molly F. Franke Amit Saha Yanan Yu Paul Ková? Stephen B. Calderwood Edward T. Ryan Regina C. LaRocque Charles P. Almazor Firdausi Qadri Louise C. Ivers Jason B. Harris 《PLoS neglected tropical diseases》2014,8(5)
Background
Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae.Methodology/Principal Findings
We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6–17 years), and 47 younger children (1–5 years) in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine.Conclusions/Significance
A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae. 相似文献45.
Alban Longchamp Florent Allagnat Xavier Berard Florian Alonso Jacques-Antoine Haefliger Sébastien Deglise Jean-Marc Corpataux 《Journal of visualized experiments : JoVE》2014,(92)
The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh. 相似文献
46.
Grégoire A Allard A Huamán E León S Silva RM Buff S Berard M Joly T 《Theriogenology》2012,78(4):842-847
The aim of this work was to look for a simple method to obtain synchronized ovulation in guinea pigs under farming conditions while respecting animal welfare. The luteolytic activity of three different prostaglandins F2alpha (PGF2α) analogs (D-cloprostenol, D,L-cloprostenol and luprostiol) and a daily treatment with oral progestagen (altrenogest) was tested successively at different stages of the estrous cycle on the same group of females during a period of 8 mo. The estrous cycle length was not modified by the administration of PGF2α analogs, whatever the stage of the estrous cycle when the treatment was initiated. Our results led us to reject the use of PGF2α analog to induce practical synchronization of the estrus in this species. In females (n = 29), given 15 days with altrenogest (0.1 mL po once a day), ovulation occurred 4.43 ± 0.13 days after the end of the treatment. Altrenogest treatment was followed by mating. No negative impacts of the treatment on the pregnancy rates, delivery rates and litter sizes were observed. This standard method of guinea-pig estrus synchronization is less stressful for the animals compared to techniques using progesterone tubing. 相似文献
47.
Christeller JT Farley PC Marshall RK Anandan A Wright MM Newcomb RD Laing WA 《Journal of molecular evolution》2006,63(6):747-757
The squash (Cucurbita maxima) phloem exudate-expressed aspartic proteinase inhibitor (SQAPI) is a novel aspartic acid proteinase inhibitor, constituting
a fifth family of aspartic proteinase inhibitors. However, a comparison of the SQAPI sequence to the phytocystatin (a cysteine
proteinase inhibitor) family sequences showed ∼30% identity. Modeling SQAPI onto the structure of oryzacystatin gave an excellent
fit; regions identified as proteinase binding loops in cystatin coincided with regions of SQAPI identified as hypervariable,
and tryptophan fluorescence changes were also consistent with a cystatin structure. We show that SQAPI exists as a small gene
family. Characterization of mRNA and clone walking of genomic DNA (gDNA) produced 10 different but highly homologous SQAPI
genes from Cucurbita maxima and the small family size was confirmed by Southern blotting, where evidence for at least five loci was obtained. Using primers
designed from squash sequences, PCR of gDNA showed the presence of SQAPI genes in other members of the Cucurbitaceae and in
representative members of Coriariaceae, Corynocarpaceae, and Begoniaceae. Thus, at least four of seven families of the order
Cucurbitales possess member species with SQAPI genes, covering ∼99% of the species in this order. A phylogenetic analysis
of these Cucurbitales SQAPI genes indicated not only that SQAPI was present in the Cucurbitales ancestor but also that gene
duplication has occurred during evolution of the order. Phytocystatins are widespread throughout the plant kingdom, suggesting
that SQAPI has evolved recently from a phytocystatin ancestor. This appears to be the first instance of a cystatin being recruited
as a proteinase inhibitor of another proteinase family.
[Reviewing Editor: Dr. Antony Dean] 相似文献
48.
Parsons AB Lopez A Givoni IE Williams DE Gray CA Porter J Chua G Sopko R Brost RL Ho CH Wang J Ketela T Brenner C Brill JA Fernandez GE Lorenz TC Payne GS Ishihara S Ohya Y Andrews B Hughes TR Frey BJ Graham TR Andersen RJ Boone C 《Cell》2006,126(3):611-625
Discovering target and off-target effects of specific compounds is critical to drug discovery and development. We generated a compendium of "chemical-genetic interaction" profiles by testing the collection of viable yeast haploid deletion mutants for hypersensitivity to 82 compounds and natural product extracts. To cluster compounds with a similar mode-of-action and to reveal insights into the cellular pathways and proteins affected, we applied both a hierarchical clustering and a factorgram method, which allows a gene or compound to be associated with more than one group. In particular, tamoxifen, a breast cancer therapeutic, was found to disrupt calcium homeostasis and phosphatidylserine (PS) was recognized as a target for papuamide B, a cytotoxic lipopeptide with anti-HIV activity. Further, the profile of crude extracts resembled that of its constituent purified natural product, enabling detailed classification of extract activity prior to purification. This compendium should serve as a valuable key for interpreting cellular effects of novel compounds with similar activities. 相似文献
49.
Jan A. Pechenik Richelle Berard Dara Daniels Timothy R. Gleason Denise Champlin 《Invertebrate Biology》2001,120(2):142-148
Abstract. It is well known that the competent larvae of many marine invertebrate species can be stimulated to metamorphose by exposing them to elevated concentrations of certain ions, neuroactive substances, and pharmacological agents. In this study we report that larvae of the euryhaline polychaete Capitella sp. I are induced to metamorphose within 24–48 h by reducing salinity from 30%‰ to 12–15%‰. At 10%‰, however, fewer larvae metamorphosed and the normal metamorphic response to sediment was inhibited; competence was restored within 3 h of transferring the larvae back to full strength seawater (30%‰). Larvae also metamorphosed within 24 h in response to increased external cadmium concentrations of 1000–2000 μg 1–1 . Further understanding of how reduced salinity and elevated cadmium stimulate (or inhibit) metamorphosis may lead to a better understanding of signal perception and transduction in this and other species. 相似文献
50.
Daniel T. Leung Taufiqur R. Bhuiyan Naoshin S. Nishat Mohammad Rubel Hoq Amena Aktar M. Arifur Rahman Taher Uddin Ashraful I. Khan Fahima Chowdhury Richelle C. Charles Jason B. Harris Stephen B. Calderwood Firdausi Qadri Edward T. Ryan 《PLoS neglected tropical diseases》2014,8(8)