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101.
Yannick Delpu Hubert Lulka Flavie Sicard Nathalie Saint-Laurent Frédéric Lopez Na?ma Hanoun Louis Buscail Pierre Cordelier Jér?me Torrisani 《PloS one》2013,8(1)
MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool. 相似文献
102.
Daniel H. Lopez Maria A. Fiol-deRoque Maria A. Noguera-Salvà Silvia Terés Federica Campana Stefano Piotto José A. Castro Raheem J. Mohaibes Pablo V. Escribá Xavier Busquets 《PloS one》2013,8(8)
Background
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies.Methodology/Principal Findings
The analogue of arachidonic acid (AA), 2-hydroxy-arachidonic acid (2OAA), was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production) activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method) and iNOS (Western blot) were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the –OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo.Conclusion/Significance
These findings demonstrate the potential of 2OAA as a NSAID. 相似文献103.
Amy Lingel Haishuang Lin Yuval Gavriel Eric Weaver Pascal Polepole Virginia Lopez Yuguo Lei Thomas M. Petro Beka Solomon Chi Zhang Luwen Zhang 《The Journal of biological chemistry》2020,295(50):17114
Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer''s diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries. 相似文献
104.
Gerardo Lopez M. Hossein Behboudian Joan Girona Jordi Marsal 《Journal of Plant Growth Regulation》2013,32(2):273-280
Responses to deficit irrigation (DI) throughout the fruit-growing season were studied in ‘Conference’ pear grafted onto quince M-A rootstock and grown in large containers. The treatments were (1) full irrigation (FI), (2) DI during Stage I of fruit growth (DI-Stage I), and (3) DI during Stage II of fruit growth (DI-Stage II). Four whole trees were sampled before Stage I and from all treatments at the end of Stage I, end of Stage II (fruit harvest), and before leaf fall. There was less discrimination against 13CO2 in DI leaves, indicative of reduced photosynthetic capacity. DI treated trees had lower starch content in branches and trunks but root starch concentration was the same between DI- and FI-treated trees. Compared to FI-treated trees, leaf, shoot, branch, and trunk dry biomass was reduced by 34, 50, 37, and 32 %, respectively, in DI-Stage I and by 45, 73, 37, and 22 % in DI-Stage II. Root growth was not affected by DI. Trees had limited capacity for storing starch in roots. Recovery of the aboveground starch concentration for DI treatments occurred within 1 month after rewatering but total starch content never recovered. 相似文献
105.
Pablo Martin Lopez Luciana Beatriz Abrahan Martin Roland Ralph Verónica Sandra Valentinuzzi 《Chronobiology international》2013,30(10):1402-1412
ABSTRACTInsects express diverse behavioral rhythms synchronized to environmental cycles. While circadian entrainment to light–dark cycles is ubiquitous in living organisms, synchronization to non-photic cycles may be critical for hematophagous bugs that depend on rhythmic hosts. The purpose was to determine whether Triatoma infestans are capable of synchronizing to the circadian rhythms of potential hosts with temporally distinct activity patterns; and, if so, if this synchronization occurs through masking or entrainment. Precise synchronization with the food source may be critical for the insects’ survival due to the specific predatory or defensive nature of each host. Kissing bugs were housed in a compartment in constant dark, air-flow-connected to another compartment with a nocturnal or a diurnal host; both hosts were synchronized to a light–dark cycle. The activity rhythms of kissing bugs were modulated by the daily activity rhythms of the vertebrates. Effects were a decrease in the endogenous circadian period, independent of the host being nocturnal or diurnal; in some cases relative coordination occurred and in others synchronization was clearly achieved. Moreover, splitting and bimodality arose, phenomena that were also affected by the host presence. The results indicate that T. infestans were able to detect the non-photic cycle of their potential hosts, an ability that surely facilitates feeding and hinders predation risk. Understanding triatomines behavior is of fundamental importance to the design of population control methods. 相似文献
106.
Jose Ramon Garmendia Leiza Jesus Maria Andres de Llano Juan Bautista Lopez Messa Carlos Alberola Lopez ARIAM Study Group 《Chronobiology international》2013,30(1):129-141
The aim of this study was to determine the existence of the circadian rhythm (CR) in the onset of acute myocardial infarction (AMI) in different patient subgroups. Information was collected about 41,244 infarctions from the database of the ARIAM (Analysis of Delay in AMI) Spanish multicenter study. CR in AMI were explored in subgroups of cases categorized by age, gender, previous ischemic heart disease (PIHD), outcome in coronary care unit, infarction electrocardiograph (ECG) characteristics (Q wave or non‐Q wave), and location of AMI. Cases were classified according to these variables in the different subgroups. To verify the presence of CR, a simple test of equality of time series based on the multiple‐sinusoid (24, 12, and 8 h periods) cosinor analysis was developed. For the groups as a whole, the time of pain onset as an indicator of the AMI occurrence showed a CR (p<0.0001), with a morning peak at 10:10 h. All the analyzed subgroups also showed CR. Comparison between subgroups showed significant differences in the PIHD (p<0.01) and infarction ECG characteristics (p<0.01) groups. The CR of the subgroup with Q‐wave infarction differed from that of non‐Q wave subgroup (p<0.01) when the patients had PIHD (23% in Q wave infarction vs. 39.2% in non‐Q wave). AMI onset followed a CR pattern, which is also observed in all analyzed subgroups. Differences in the CR according to the Q/non‐Q wave infarction characteristics could be determined by PIHD. The cosinor model fit with three components (24, 12, and 8 h periods) showed a higher sensitivity than the single 24 h period analysis. 相似文献
107.
Maria Hoffmann Steven R. Monday Peter J. McCarthy Jose V. Lopez Markus Fischer Eric W. Brown 《Cladistics : the international journal of the Willi Hennig Society》2013,29(1):46-64
Vibrio represents a diverse bacterial genus found in different niches of the marine environment, including numerous genera of marine sponges (phylum Porifera), inhabiting different depths and regions of benthic seas, that are potentially important in driving adaptive change among Vibrio spp. Using 16S rRNA gene sequencing, a previous study showed that sponge‐derived (SD) vibrios clustered with their mainstream counterparts present in shallow, coastal ecosystems, suggesting a genetic relatedness between these populations. Sequences from the topA, ftsZ, mreB, rpoD, rctB and toxR genes were used to investigate the degree of relatedness existing between these two separate populations by examining their phylogenetic and genetic disparity. Phylogenies were constructed from the concatenated sequences of the six housekeeping genes using maximum‐parsimony, maximum‐likelihood and neighbour‐joining algorithms. Genetic recombination was evaluated using the incongruence length difference test, Split decomposition and measuring overall compatibility of sites. This combined technical approach provided evidence that SD Vibrio strains are largely genetically homologous to their shallow‐water counterparts. Moreover, the analyses conducted support the existence of extensive horizontal gene transfer between these two groups, supporting the idea of a single panmictic population structure among vibrios from two seemingly distinct, marine environments. 相似文献
108.
Scott R. Higgins Ryan J. Lopez Eulyn Pagaling Tao Yan Michael J. Cooney 《Enzyme and microbial technology》2013,52(6-7):344-351
An electrogenic biofilm was developed on a macroporous chitosan-carbon nanotube (CHIT-CNT) electrode under constant poised potential (?0.25 V versus Ag/AgCl reference electrode) and flow through conditions utilizing the effluent of an anaerobic digester as both the inoculant and substrate for the electrogenic biofilm. After 125 days of inoculation the bioelectrode demonstrated an open circuit potential of ?0.62 V and a current density of 9.43 μA cm?3 (at ?0.25 V). Scanning electron microscopy images indicate thorough surface coverage of the biofilm with a high density of bacterial nanowires physically connecting bacteria to bacteria and bacteria to carbon nanotube (electrode surface) suggesting the nanowires are electrically conductive. DGGE was used to identify the major bacterial and archaeal populations. 相似文献
109.
Melany N. Lopez Timothy J. Wilding James E. Huettner 《The Journal of general physiology》2013,142(3):225-239
RNA editing at the Q/R site near the apex of the pore loop of AMPA and kainate receptors controls a diverse array of channel properties, including ion selectivity and unitary conductance and susceptibility to inhibition by polyamines and cis-unsaturated fatty acids, as well as subunit assembly into tetramers and regulation by auxiliary subunits. How these different aspects of channel function are all determined by a single amino acid substitution remains poorly understood; however, several lines of evidence suggest that interaction between the pore helix (M2) and adjacent segments of the transmembrane inner (M3) and outer (M1) helices may be involved. In the present study, we have used double mutant cycle analysis to test for energetic coupling between the Q/R site residue and amino acid side chains along the M3 helix. Our results demonstrate interaction with several M3 locations and particularly strong coupling to substitution for L614 at the level of the central cavity. In this location, replacement with smaller side chains completely and selectively reverses the effect of fatty acids on gating of edited channels, converting strong inhibition of wild-type GluK2(R) to nearly 10-fold potentiation of GluK2(R) L614A. 相似文献
110.
P. Arechavala‐Lopez P. Sanchez‐Jerez D. Izquierdo‐Gomez K. Toledo‐Guedes J. T. Bayle‐Sempere 《Zeitschrift fur angewandte Ichthyologie》2013,29(2):352-357
The present study compares fin damages in gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) according to their wild, escaped or farmed origins. In addition, the potential applicability of fin condition indices (Fin Erosion Index ‘FEI’ and Fin Splitting Index ‘FSI’) as identification tools is discussed. Farmed seabream fins evidenced more erosion and splitting (FEI ± SD: 2.1 ± 0.3; FSI ± SD: 1.9 ± 0.6) than wild seabream fins (FEI: 0.8 ± 0.6; FSI: 1.2 ± 0.9), a result of farming conditions in open‐sea cages. Escaped seabream fin erosion was between that of farmed and wild seabream (FEI: 1.6 ± 0.4), which could indicate that fins in farmed fish recover over time from farming abrasions once they are in the wild. However, the fins of escaped seabream seem to be weaker than those of the wild fish, and therefore might be more susceptible to suffer other types of erosion such as splitting or nipping (FSI: 2.3 ± 0.7). No significant differences were found in seabass FEI according to their origins, although wild seabass presented significantly more split caudal fins (FSI: 3.3 ± 2.8) than the farmed seabass (FSI: 1.2 ± 1.1) and escapees (FSI: 2.5 ± 1.6). Therefore, FEI for seabream could be used as tools not only to distinguish between wild and farmed fish, but also to identify recent escapees, improving further assessments on the contribution of seabream escapees in fishery landings. However, the healing potential of damaged fins must be considered for the proper identification of escapees. Use of fin condition indices from both species could be helpful for aquaculture management, to assess fish welfare in fish farms stocks, and improve the knowledge of handling, stock densities and open‐sea cage environment conditions. 相似文献