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61.
Luciana Gabriel Nogueira Ronaldo Honorato Barros Santos Barbara Maria Ianni Alfredo Inácio Fiorelli Eliane Conti Mairena Luiz Alberto Benvenuti Amanda Frade Eduardo Donadi Fabrício Dias Bruno Saba Hui-Tzu Lin Wang Abilio Fragata Marcelo Sampaio Mario Hiroyuki Hirata Paula Buck Charles Mady Edimar Alcides Bocchi Noedir Antonio Stolf Jorge Kalil Edecio Cunha-Neto 《PLoS neglected tropical diseases》2012,6(10)
Background
Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium.Methods and Results
Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes.Conclusions
Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC. 相似文献62.
Climate driven egg and hatchling mortality threatens survival of eastern Pacific leatherback turtles 总被引:1,自引:0,他引:1
Egg-burying reptiles need relatively stable temperature and humidity in the substrate surrounding their eggs for successful development and hatchling emergence. Here we show that egg and hatchling mortality of leatherback turtles (Dermochelys coriacea) in northwest Costa Rica were affected by climatic variability (precipitation and air temperature) driven by the El Ni?o Southern Oscillation (ENSO). Drier and warmer conditions associated with El Ni?o increased egg and hatchling mortality. The fourth assessment report of the Intergovernmental Panel on Climate Change (IPCC) projects a warming and drying in Central America and other regions of the World, under the SRES A2 development scenario. Using projections from an ensemble of global climate models contributed to the IPCC report, we project that egg and hatchling survival will rapidly decline in the region over the next 100 years by ~50-60%, due to warming and drying in northwestern Costa Rica, threatening the survival of leatherback turtles. Warming and drying trends may also threaten the survival of sea turtles in other areas affected by similar climate changes. 相似文献
63.
Various methods have been used to identify cultivares of olive trees; herein we used different bioinformatics algorithms to propose new tools to classify 10 cultivares of olive based on RAPD and ISSR genetic markers datasets generated from PCR reactions. Five RAPD markers (OPA0a21, OPD16a, OP01a1, OPD16a1 and OPA0a8) and five ISSR markers (UBC841a4, UBC868a7, UBC841a14, U12BC807a and UBC810a13) selected as the most important markers by all attribute weighting models. K-Medoids unsupervised clustering run on SVM dataset was fully able to cluster each olive cultivar to the right classes. All trees (176) induced by decision tree models generated meaningful trees and UBC841a4 attribute clearly distinguished between foreign and domestic olive cultivars with 100% accuracy. Predictive machine learning algorithms (SVM and Naïve Bayes) were also able to predict the right class of olive cultivares with 100% accuracy. For the first time, our results showed data mining techniques can be effectively used to distinguish between plant cultivares and proposed machine learning based systems in this study can predict new olive cultivars with the best possible accuracy. 相似文献
64.
65.
A miRNA signature of prion induced neurodegeneration 总被引:1,自引:0,他引:1
MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion-induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified. 相似文献
66.
Simonetti O Cirioni O Goteri G Ghiselli R Kamysz W Kamysz E Silvestri C Orlando F Barucca C Scalise A Saba V Scalise G Giacometti A Offidani A 《Peptides》2008,29(4):520-528
We investigated the effect of topical temporin A in the management of methicillin-resistant strain of Staphylococcus aureus (MRSA)-infected experimental surgical wounds in mice. The wound, cut through the panniculus carnosus of BALB/c mice, was inoculated with 5x10(7) colony-forming units of MRSA. Mice were treated with Allevyn, temporin A-soaked Allevyn, Allevyn and daily intraperitoneal teicoplanin (7mg/kg), temporin A-soaked Allevyn and daily intraperitoneal teicoplanin. Main outcome measurements were: quantitative bacterial culture, histological examination with assessment of micro-vessel density and of vascular endothelial growth factor (VEGF) expression in tissue sections, and VEGF plasma levels alike. Treatment with temporin-A associated with teicoplanin injection significantly reduced bacterial load to 0.85 x 10(1)+/-0.1 x 10(1)CFU/ml. Histological examination showed that infected mice receiving temporin A-soaked Allevyn (with or without teicoplanin) had a higher degree of granulation tissue formation and collagen deposition compared to the other treated groups. A significant increase in serum VEGF expression was observed in mice receiving temporin A topically and temporin A topically associated with intraperitoneal teicoplanin. In conclusion our results demonstrated that temporin A is effective in the management of infected wounds, by a significant bacterial growth inhibition and acceleration of wound repair process. 相似文献
67.
Flaminia Cesare Marincola Mariano Casu Giuseppe Saba Adolfo Lai Pompea del Vecchio Guido Barone 《International journal of biological macromolecules》2001,29(4-5)
The 23Na NMR quadrupolar relaxation in NaDNA aqueous solutions has been investigated in the presence of
(+) and
(−) arabitol. Quite different results were produced by the enantiomers, i.e. the addition of
(+) arabitol produced a small increase of the 23Na NMR relaxation rates, while in the presence of
(−) arabitol a significant decrease was observed. These findings were analysed and discussed in terms of an effective interaction of
(−) arabitol with DNA. 相似文献
68.
We investigated the etiology of the previously documented decrease in serum prostocyclin binding during pregnancy. Addition of albumin to the serum of pregnant women failed to raise binding to non-pregnant levels. Pregnancy serum bound significantly more prostacyclin following the removal of non-esterified fatty acids and the addition of fatty acid free albumin resulted in a rise in binding to non-pregnant levels. We conclude that serum protein prostacyclin binding is affected by both albumin concentration and non-esterified fatty acids. 相似文献
69.
Jerzy Falandysz Ji Zhang Yuan-Zhong Wang Martyna Saba Gra?yna Krasińska Anna Wiejak Tao Li 《PloS one》2015,10(11)
For the first time, highly elevated levels of mercury (Hg) have been documented for several species of the edible Fungi genus Boletus growing in latosols, lateritic red earths, and red and yellow earths from the Yunnan province of China. Analysis of Hg concentrations in the genus suggests that geogenic Hg is the dominant source of Hg in the fungi, whereas anthropogenic sources accumulate largely in the organic layer of the forest soil horizon. Among the 21 species studied from 32 locations across Yunnan and 2 places in Sichuan Province, the Hg was found at elevated level in all samples from Yunnan but not in the samples from Sichuan, which is located outside the mercuriferous belt. Particularly abundant in Hg were the caps of fruiting bodies of Boletus aereus (up to 13 mg kg-1 dry matter), Boletus bicolor (up to 5.5 mg kg-1 dry matter), Boletus edulis (up to 22 mg kg-1 dry matter), Boletus luridus (up to 11 mg kg-1 dry matter), Boletus magnificus (up to 13 mg kg-1 dry matter), Boletus obscureumbrinus (up to 9.4 mg kg-1 dry matter), Boletus purpureus (up to 16 mg kg-1 dry matter), Boletus sinicus (up to 6.8 mg kg-1 dry matter), Boletus speciosus (up to 4.9mg kg-1 dry matter), Boletus tomentipes (up to 13 mg kg-1 dry matter), and Boletus umbriniporus (up to 4.9 mg kg-1 dry matter). Soil samples of the 0–10 cm topsoil layer from the widely distributed locations had mercury levels ranging between 0.034 to 3.4 mg kg-1 dry matter. In Yunnan, both the soil parent rock and fruiting bodies of Boletus spp. were enriched in Hg, whereas the same species from Sichuan, located outside the mercuriferous belt, had low Hg concentrations, suggesting that the Hg in the Yunnan samples is mainly from geogenic sources rather than anthropogenic sources. However, the contribution of anthropogenically-derived Hg sequestered within soils of Yunnan has not been quantified, so more future research is required. Our results suggest that high rates of consumption of Boletus spp. from Yunnan can deliver relatively high doses of Hg to consumers, but that rates can differ widely because of large variability in mercury concentrations between species and locations. 相似文献
70.
Saba Naz Shruti Dabral Sathya Narayanan Nagarajan Divya Arora Lakshya Veer Singh Pradeep Kumar Yogendra Singh Dhiraj Kumar Umesh Varshney Vinay Kumar Nandicoori 《PLoS pathogens》2021,17(3)
Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is a significant public health concern, exacerbated by the emergence of drug-resistant TB. To combat the host’s dynamic environment, Mtb encodes multiple DNA repair enzymes that play a critical role in maintaining genomic integrity. Mtb possesses a GC-rich genome, rendering it highly susceptible to cytosine deaminations, resulting in the occurrence of uracils in the DNA. UDGs encoded by ung and udgB initiate the repair; hence we investigated the biological impact of deleting UDGs in the adaptation of pathogen. We generated gene replacement mutants of uracil DNA glycosylases, individually (RvΔung, RvΔudgB) or together (RvΔdKO). The double KO mutant, RvΔdKO exhibited remarkably higher spontaneous mutation rate, in the presence of antibiotics. Interestingly, RvΔdKO showed higher survival rates in guinea pigs and accumulated large number of SNPs as revealed by whole-genome sequence analysis. Competition assays revealed the superior fitness of RvΔdKO over Rv, both in ex vivo and in vivo conditions. We propose that compromised DNA repair results in the accumulation of mutations, and a subset of these drives adaptation in the host. Importantly, this property allowed us to utilize RvΔdKO for the facile identification of drug targets. 相似文献