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15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Macrophage Colonization by Salmonella enterica Serovar Typhimurium
Michelle M. C. Buckner, L. Caetano M Antunes, Navkiran Gill, Shannon L. Russell, Stephanie R. Shames, B. Brett Finlay
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069759
Abstract: 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an anti-inflammatory downstream product of the cyclooxygenase enzymes. It has been implicated to play a protective role in a variety of inflammatory mediated diseases, including rheumatoid arthritis, neural damage, and myocardial infarctions. Here we show that 15d-PGJ2 also plays a role in Salmonella infection. Salmonella enterica Typhimurium is a Gram-negative facultative intracellular pathogen that is able to survive and replicate inside phagocytic immune cells, allowing for bacterial dissemination to systemic sites. Salmonella species cause a wide range of morbidity and mortality due to gastroenteritis and typhoid fever. Previously we have shown that in mouse models of typhoid fever, Salmonella infection causes a major perturbation in the prostaglandin pathway. Specifically, we saw that 15d-PGJ2 production was significantly increased in both liver and feces. In this work we show that 15d-PGJ2 production is also significantly increased in macrophages infected with Salmonella. Furthermore, we show that the addition of 15d-PGJ2 to Salmonella infected RAW264.7, J774, and bone marrow derived macrophages is sufficient to significantly reduce bacterial colonization. We also show evidence that 15d-PGJ2 is reducing bacterial uptake by macrophages. 15d-PGJ2 reduces the inflammatory response of these infected macrophages, as evidenced by a reduction in the production of cytokines and reactive nitrogen species. The inflammatory response of the macrophage is important for full Salmonella virulence, as it can give the bacteria cues for virulence. The reduction in bacterial colonization is independent of the expression of Salmonella virulence genes SPI1 and SPI2, and is independent of the 15d-PGJ2 ligand PPAR-γ. 15d-PGJ2 also causes an increase in ERK1/2 phosphorylation in infected macrophages. In conclusion, we show here that 15d-PGJ2 mediates the outcome of bacterial infection, a previously unidentified role for this prostaglandin.
Neutrophil Elastase Alters the Murine Gut Microbiota Resulting in Enhanced Salmonella Colonization
Navkiran Gill, Rosana B. R. Ferreira, L. Caetano M. Antunes, Benjamin P. Willing, Inna Sekirov, Fatimah Al-Zahrani, Martin Hartmann, B. Brett Finlay
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049646
Abstract: The intestinal microbiota has been found to play a central role in the colonization of Salmonella enterica serovar Typhimurium in the gastrointestinal tract. In this study, we present a novel process through which Salmonella benefit from inflammatory induced changes in the microbiota in order to facilitate disease. We show that Salmonella infection in mice causes recruitment of neutrophils to the gut lumen, resulting in significant changes in the composition of the intestinal microbiota. This occurs through the production of the enzyme elastase by neutrophils. Administration of recombinant neutrophil elastase to infected animals under conditions that do not elicit neutrophil recruitment caused shifts in microbiota composition that favored Salmonella colonization, while inhibition of neutrophil elastase reduced colonization. This study reveals a new relationship between the microbiota and the host during infection.
The Intestinal Microbiota Plays a Role in Salmonella-Induced Colitis Independent of Pathogen Colonization
Rosana B. R. Ferreira,Navkiran Gill,Benjamin P. Willing,L. Caetano M. Antunes,Shannon L. Russell,Matthew A. Croxen,B. Brett Finlay
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020338
Abstract: The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and preventative measures against enteric pathogens.
Genital HSV-2 Infection Induces Short-Term NK Cell Memory
Mohamed F. Abdul-Careem, Amanda J. Lee, Elishka A. Pek, Navkiran Gill, Amy E. Gillgrass, Marianne V. Chew, Sarah Reid, Ali A. Ashkar
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032821
Abstract: NK cells are known as innate immune cells that lack immunological memory. Recently, it has been shown that NK cells remember encounters with chemical haptens that induce contact hypersensitivity and cytomegalovirus infection. Here, we show the existence of NK cell memory following HSV-2 infection. Stimulation with HSV-2 Ags led to higher IFNγ production in NK cells that were exposed 30 days previously to HSV-2, compared to NK cells from na?ve mice. More importantly, this increased production of IFNγ in NK cells was independent of B- and T- lymphocytes and specific for the HSV-2 Ags. We also showed that previously exposed NK cells in a B- and T-lymphocyte free environment mediate protection against HSV-2 infection and they are necessary for the protection of mice against HSV-2 infection. Collectively, NK cells remember prior HSV-2 encounters independent of B- and T- lymphocytes leading to protection against HSV-2 mediated morbidity and mortality upon re-exposure.
A Research on Eurozone Bond Market and Determinants of Sovereign Bond Yields  [PDF]
Navjeet Gill
Journal of Financial Risk Management (JFRM) , 2018, DOI: 10.4236/jfrm.2018.72012
Abstract: This empirical research uses an OLS regression framework to examine the effect of the overall debt crisis on European sovereign bonds by conducting an overview of the bond market. It identifies the determinants which affect the generation of the indebtedness of sovereign bonds and play a major role in the determination of their solvency and hence, the spreads. These results reveal that Interest Rate, Inflation, Debt to GDP, Deficit to GDP, Gross Domestic Product rate of growth, and VSTOXX index are the most significant determinants of the sovereign bond spreads in the 6 sample countries, i.e. France, Germany, United Kingdom, Greece, Italy and Spain. To summarize, the main factors which affected bond spreads before the crisis, were not the country-specific fundamentals but rather the convergence of bond yields in the euro-zone countries due to and following the launch of the monetary union but during the crisis, increased risk aversion and lack of lender of last resort, shifted the focus to country specific factors and the bond spreads began to diverge according to the determinants highlighted in this study.
Relationship between Metabolic Syndrome and History of Cervical Cancer among a US National Population
Eribeth K. Penaranda,Navkiran Shokar,Melchor Ortiz
ISRN Oncology , 2013, DOI: 10.1155/2013/840964
Relationship between Metabolic Syndrome and History of Cervical Cancer among a US National Population
Eribeth K. Penaranda,Navkiran Shokar,Melchor Ortiz
ISRN Oncology , 2013, DOI: 10.1155/2013/840964
Abstract: The metabolic changes present in the metabolic syndrome (MetS) have been associated with increased risk of pancreatic and colon cancers; however, there is little information about the association between MetS and cervical cancer risk. We performed a case-control study using data from the National Health and Nutrition Examination Survey (NHANES) between 1999–2010. We identified women 21 years of age and older, of which an estimated 585,924 (2.3% of the sample) self-reported a history of cervical cancer (cases). About half (48.6%) of cases and 33.2% of controls met criteria for MetS. Logistic regression analysis showed increased odds of history of cervical cancer among women with MetS ( ; 95% CI 1.06, 3.42; value ≤ 0.05) for the risk of history of cervical cancer among women with MetS while adjusting for other known risk factors (high number of lifetime sexual partners, multiparty, history of hormonal contraceptive use, and history of smoking) ( ; 95% CI 1.02, 3.26; value ≤ 0.05). In this US surveyed population we found increased odds of history of cervical cancer among subjects with MetS. 1. Introduction Cervical cancer is the second most common cancer in women worldwide, killing approximately 274,000 women in 2008, most of them in developing countries [1]. In the USA, cervical cancer cases are declining [2], but every year there continue to be about 12,000 incident cases and 4,000 deaths from this disease [3]. The causal relationship between infection with the human Papilloma Virus (HPV) and the development of cervical cancer has been established in the last two decades [4]. Out of the approximately 150 identified genotypes of HPV, 12 have been classified as category 1 carcinogens, meaning that there is sufficient evidence to determine that they cause cancer in humans [5]. Some of those types are linked to cancers other than cervical, namely, vulvar, vaginal, perianal, penis, and oropharyngeal [5]. Serotypes 16 and 18 are responsible for about 70% of all the cervical cancer cases [6, 7], but HPV 16 alone causes at least half of all cervical cancers [8]. HPV 16 is also less associated with adenocarcinoma than with squamous cell carcinoma of the cervix, which makes up more than 95% of all cervical cancers [9, 10]. HPV infection is highly prevalent among sexually active young women [6, 11], but the large majority (more than 90%) of HPV infections will clear over a few years [12]. The transition from infection with one of the oncogenic types of HPV to the immediate precursor of cervical cancer (cervical intraepithelial neoplasia 3 (CIN 3)), to invasive
Exploring the Factors that Affect the Choice of Destination for Medical Tourism  [PDF]
Neha Singh, Harsimran Gill
Journal of Service Science and Management (JSSM) , 2011, DOI: 10.4236/jssm.2011.43037
Abstract: Medical Tourism has become one of the latest trends in the tourism industry which has been and has the potential to continue growing exponentially every year. More travelers than ever before are now travelling abroad to get high quality medical treatments for less cost. The purpose of my study is to explore the interest in US travelers in medical tourism. Results from the survey indicated that “competent doctors”, “high quality medical treatment facility”, and “prompt medical treatment when needed” where the top three factors before deciding whether or not to take a trip abroad. The results will be useful to businesses that are either directly or indirectly involved with this industry, such as insurance companies, credit card companies, travel agencies, hotels, food and beverage companies, medical facilities and services, and spas.
Signed Tilings by Ribbon L n-Ominoes, n Even, via Gr?bner Bases  [PDF]
Kenneth Gill, Viorel Nitica
Open Journal of Discrete Mathematics (OJDM) , 2016, DOI: 10.4236/ojdm.2016.63017
Abstract: Let Tn be the set of ribbon L-shaped n-ominoes for some n4 even, and let T+n be Tn with an extra 2 x 2 square. We investigate signed tilings of rectangles by Tn and T+n . We show that a rectangle has a signed tiling by Tn if and only if both sides of the rectangle are even and one of them is divisible by n, or if one of the sides is odd and the other side is divisible by \"\". We also show that a rectangle has a signed tiling by T+n, n≥6 even, if and only if both sides of the rectangle are even, or if one of the sides is odd and the other side is divisible by \"\". Our proofs are based on the exhibition of explicit GrÖbner bases for the ideals generated by polynomials associated to the tiling sets. In particular, we show that some of the regular tiling results in Nitica, V. (2015) Every tiling of the first quadrant by ribbon L n-ominoes follows the rectangular pattern. Open Journal of Discrete Mathematics, 5, 11-25, cannot be obtained from coloring invariants.
Identification and Quantitation of Cashmere (Pashmina) Fiber and Wool Using Novel Microchip Based Real-Time PCR Technology  [PDF]
Rajwant Gill, Sikander Gill, Maxim Slyadnev, Alexander Stroganov
Journal of Textile Science and Technology (JTST) , 2018, DOI: 10.4236/jtst.2018.44010
Abstract: The textile industrial chain all over the world is facing a challenge of differentiating cashmere fiber from mixture of wool and other fibers in case cashmere stocks are adulterated with wool or other fibers. For identification of cashmere in such mixtures, the development of microchip based real-time PCR technology offers a very sensitive, specific, and accurate solution. The technology has been validated with cashmere and wool samples procured from distant farms, and from cashmere goats and sheep of different age and sex. Model samples with incremental raw cashmere or wool content were tested. The experimentally determined content was found to be comparable to the weighed content of the respective fibers in the samples. This technology may prove a cost cutter since it needs only 1.2 μl of the PCR reagent mix. It is substantially faster than traditional real-time PCR systems for being carried as miniature reaction volume in metal microchip. These features allow faster thermal equilibrium and thermal uniformity over the entire array of microreactors. For routine tests or in commercial set up, the microchips are available as ready-to-run with lyophilized reagents in its microreactors to which only 1 μl of the 10-fold diluted isolated DNA sample is added. The lyophilized microchips offer user-friendly handling in testing laboratories and help minimize human error.
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