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101.
Parag Kundu Teo Wei Ling Agata Korecka Yinghui Li Rossana D'Arienzo Ralph M. Bunte Thorsten Berger Velmurugesan Arulampalam Pierre Chambon Tak Wah Mak Walter Wahli Sven Pettersson 《PLoS pathogens》2014,10(1)
To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. 相似文献
102.
Olga Zamudio-Prieto Claudia Benítez-Cardoza Rossana Arroyo Jaime Ortega-López 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(7):1299-1306
EhCP-B9, a cysteine protease (CP) involved in Entamoeba histolytica virulence, is a potential target for disease diagnosis and drug design. After purification from inclusion bodies produced in Escherichia coli, the recombinant EhCP-B9 precursor (ppEhCP-B9) can be refolded using detergents as artificial chaperones. However, the conformational changes that occur during ppEhCP-B9 refolding remain unknown. Here, we comprehensively describe conformational changes of ppEhCP-B9 that are induced by various chemical detergents acting as chaperones, including non-ionic, zwitterionic, cationic and anionic surfactants. We monitored the effect of detergent concentration and incubation time on the secondary and tertiary structures of ppEhCP-B9 using fluorescence and circular dichroism (CD) spectroscopy. In the presence of non-ionic and zwitterionic detergents, ppEhCP-B9 adopted a β-enriched structure (ppEhCP-B9β1) without proteolytic activity at all detergent concentrations and incubation times evaluated. ppEhCP-B9 also exhibits a β-rich structure in low concentrations of ionic detergents, but at concentrations above the critical micelle concentration (CMC), the protein acquires an α + β structure, similar to that of papain but without proteolytic activity (ppEhCP-B9α + β1). Interestingly, only within a narrow range of experimental conditions in which SDS concentrations were below the CMC, ppEhCP-B9 refolded into a β-sheet rich structure (ppEhCP-B9β2) that slowly transforms into a different type of α + β conformation that exhibited proteolytic activity (ppEhCP-B9α + β2) suggesting that enzymatic activity is gained as slow transformation occurs. 相似文献
103.
Caroline Tanski Bueno Cláudia Maria Dornelles da Silva Regina Bones Barcellos Juliana da Silva Carla Rossana dos Santos Jo?o Evangelista Sampaio Menezes Honório Sampaio Menezes Maria Lucia Rosa Rossetti 《Genetics and molecular biology》2014,37(3):496-499
The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal. 相似文献
104.
Katherine A. Mattos Viviane C. G. Oliveira Marcia Berrêdo‐Pinho Julio J. Amaral Luis Caetano M. Antunes Rossana C. N. Melo Chyntia C. D. Acosta Danielle F. Moura Roberta Olmo Jun Han Patricia S. Rosa Patrícia E. Almeida B. Brett Finlay Christoph H. Borchers Euzenir N. Sarno Patricia T. Bozza Georgia C. Atella Maria Cristina V. Pessolani 《Cellular microbiology》2014,16(6):797-815
105.
Federico Ambrogi Marco Fornili Patrizia Boracchi Marco Trerotola Valeria Relli Pasquale Simeone Rossana La Sorda Rossano Lattanzio Patrizia Querzoli Massimo Pedriali Mauro Piantelli Elia Biganzoli Saverio Alberti 《PloS one》2014,9(5)
Trop-2 is a calcium signal transducer that drives tumor growth. Anti-Trop-2 antibodies with selective reactivity versus Trop-2 maturation stages allowed to identify two different pools of Trop-2, one localized in the cell membrane and one in the cytoplasm. Of note, membrane-localized/functional Trop-2 was found to be differentially associated with determinants of tumor aggressiveness and distinct breast cancer subgroups. These findings candidated Trop-2 states to having an impact on cancer progression. We tested this model in breast cancer. A large, consecutive human breast cancer case series (702 cases; 8 years median follow-up) was analyzed by immunohistochemistry with anti-Trop-2 antibodies with selective reactivity for cytoplasmic-retained versus functional, membrane-associated Trop-2. We show that membrane localization of Trop-2 is an unfavorable prognostic factor for overall survival (1+ versus 0 for all deaths: hazard ratio, 1.63; P = 0.04), whereas intracellular Trop-2 has a favorable impact on prognosis, with an adjusted hazard ratio for all deaths of 0.48 (high versus low; P = 0.003). A corresponding impact of intracellular Trop-2 was found on disease relapse (high versus low: hazard ratio, 0.51; P = 0.004). Altogether, we demonstrate that the Trop-2 activation states are critical determinants of tumor progression and are powerful indicators of breast cancer patients survival. 相似文献
106.
107.
David Charles Boettiger Stephen Kerr Rossana Ditangco Tuti Parwati Merati Thuy Thi Thanh Pham Romanee Chaiwarith Sasisopin Kiertiburanakul Chung Ki Patrick Li Nagalingeswaran Kumarasamy Saphonn Vonthanak Christopher Lee Nguyen Van Kinh Sanjay Pujari Wing Wai Wong Adeeba Kamarulzaman Fujie Zhang Evy Yunihastuti Jun Yong Choi Shinichi Oka Oon Tek Ng Pacharee Kantipong Mahiran Mustafa Winai Ratanasuwan Annette Sohn Matthew Law 《PloS one》2014,9(9)
Background
Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.Methods
Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed.Results
Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).Conclusions
The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure. 相似文献108.
109.
110.
Bahareh M Schweiger Janet K Snell-Bergeon Rossana Roman Kim McFann Georgeanna J Klingensmith 《Reproductive biology and endocrinology : RB&E》2011,9(1):61