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101.
102.
Giulia Fregni Meriem Messaoudene Emmanuelle Fourmentraux-Neves Sarra Mazouz-Dorval Johan Chanal Eve Maubec Eduardo Marinho Isabelle Scheer-Senyarich Isabelle Cremer Marie-Fran?oise Avril Anne Caignard 《PloS one》2013,8(10)
Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III–IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients. 相似文献
103.
Toward High‐Temperature Stability of PTB7‐Based Bulk Heterojunction Solar Cells: Impact of Fullerene Size and Solvent Additive 下载免费PDF全文
Sadok Ben Dkhil Martin Pfannmöller Maria Ilenia Saba Meriem Gaceur Hamed Heidari Christine Videlot‐Ackermann Olivier Margeat Antonio Guerrero Juan Bisquert Germa Garcia‐Belmonte Alessandro Mattoni Sara Bals Jörg Ackermann 《Liver Transplantation》2017,7(4)
The use of fullerene as acceptor limits the thermal stability of organic solar cells at high temperatures as their diffusion inside the donor leads to phase separation via Ostwald ripening. Here it is reported that fullerene diffusion is fully suppressed at temperatures up to 140 °C in bulk heterojunctions based on the benzodithiophene‐based polymer (the poly[[4,8‐bis[(2‐ethylhexyl)oxy]‐benzo[1,2‐b:4,5‐b′]dithiophene‐2,6‐diyl][3‐fluoro‐2‐[(2‐ethylhexyl)carbonyl]‐thieno[3,4‐b]thiophenediyl]], (PTB7) in combination with the fullerene derivative [6,6]‐phenyl‐C71‐butyric acid methyl ester (PC70BM). The blend stability is found independently of the presence of diiodooctane (DIO) used to optimize nanostructuration and in contrast to PTB7 blends using the smaller fullerene derivative PC70BM. The unprecedented thermal stability of PTB7:PC70BM layers is addressed to local minima in the mixing enthalpy of the blend forming stable phases that inhibit fullerene diffusion. Importantly, although the nanoscale morphology of DIO processed blends is thermally stable, corresponding devices show strong performance losses under thermal stress. Only by the use of a high temperature annealing step removing residual DIO from the device, remarkably stable high efficiency solar cells with performance losses less than 10% after a continuous annealing at 140 °C over 3 days are obtained. These results pave the way toward high temperature stable polymer solar cells using fullerene acceptors. 相似文献
104.
Meriem Khairoun Mieke van den Heuvel Bernard M. van den Berg Oana Sorop Rients de Boer Nienke S. van Ditzhuijzen Ingeborg M. Bajema Hans J. Baelde Malu Zandbergen Dirk J. Duncker Ton J. Rabelink Marlies E. J. Reinders Wim J. van der Giessen Joris I. Rotmans 《PloS one》2015,10(4)
Background
Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage.Methods
Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF).Results
Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/ Angpt1balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05).Conclusion
In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of systemic microvascular damage. Concomitantly, a dysbalance in renal angiopoietins was correlated with the development of diabetic nephropathy. As such, our studies strongly suggest that defects in the systemic microvasculature mirror the accumulation of microvascular damage in the kidney. 相似文献105.
Abouzahr-Rifai S Hasmim M Boukerche H Hamelin J Janji B Jalil A Kieda C Mami-Chouaib F Bertoglio J Chouaib S 《The Journal of biological chemistry》2008,283(46):31665-31672
Tumor cells evade adaptive immunity by a variety of mechanisms, including selection of variants that are resistant to specific cytotoxic T lymphocyte (CTL) pressure. Recently, we have reported that the reorganization of the actin cytoskeleton can be used by tumor cells as a strategy to promote their resistance to CTL-mediated lysis. In this study, we further examined the functional features of a CTL-resistant tumor variant and investigated the relationship between cytoskeleton alteration, the acquisition of tumor resistance to CTL-induced cell death, Rho-GTPases, and focal adhesion kinase (FAK) pathways. Our data indicate that although the resistant cells do not display an increased migratory potential, an alteration of adhesion to the extracellular matrix was observed. When Rho-GTPases were activated in cells by the bacterial CNF1 (cytotoxic necrotizing factor 1), striking changes in the cell morphology, including actin cytoskeleton, focal adhesions, and membrane extensions, were observed. More importantly, such activation also resulted in a significant attenuation of resistance to CTL-induced cell death. Furthermore, we demonstrate that FAK signaling pathways were constitutively defective in the resistant cells. Silencing of FAK in the sensitive target cells resulted in the inhibition of immune synapse formation with specific CTLs and their subsequent lysis. Expression of the FAK mutant (Y397F) resulted in an inhibition of IGR-Heu cell adhesion and of their susceptibility to specific lysis. These results suggest that FAK activation plays a role in the control of tumor cell susceptibility to CTL-mediated lysis. 相似文献
106.
The twin-arginine translocation (Tat) machinery of the Escherichia coli inner membrane is dedicated to the export of proteins harboring a conserved SRRxFLK motif in their signal sequence. TatA, TatB, and TatC are the functionally essential constituents of the Tat machinery, but their precise function is unknown. Using site-specific crosslinking, we have analyzed interactions of the twin-arginine precursor preSufI with the Tat proteins upon targeting to inner membrane vesicles. TatA association is observed only in the presence of a transmembrane H(+) gradient. TatB is found in contact with the entire signal sequence and adjacent parts of mature SufI. Interaction of TatC with preSufI is, however, restricted to a discrete area around the consensus motif. The results reveal a hierarchy in targeting of a Tat substrate such that for the primary interaction, TatC is both necessary and sufficient while a subsequent association with TatB likely mediates transfer from TatC to the actual Tat pore. 相似文献
107.
Julia C. Marxen P. Eckhard Witten Doreen Finke Oliver Reelsen Meriem Rezgaoui Wilhelm Becker 《Invertebrate Biology》2003,122(4):313-325
Abstract. The mode of formation of the molluscan exoskeleton is still poorly understood, but studies on adult snails indicate that enzymes involved in vertebrate bone formation also participate in mollusc shell formation. The enzymes peroxidase, alkaline phosphatase, and acid phosphatase are expressed in a constant pattern and help to identify the different zones of the adult shell-forming tissue. The present study evaluates whether the expression of these enzymes is also a tool for the identification of the developing zones of the embryonic shell-forming tissue. Thus, we analyzed the temporal and spatial activity of the above-mentioned enzymes and of tartrate-resistant acid phosphatase in the shell forming tissues in Biomphalaria glabrata. Embryos of different age groups and adults were studied; alkaline phosphatase activity was seen in very young embryos in the shell field invagination prior to the secretion of any shell material, while peroxidase activity was present from the start of the periostracum production. Acid phosphatase, found in considerable amounts in yolk granules and albumen cells, appeared in the embryonic shell-forming tissue in relatively few Golgi stacks. Tartrate-resistant phosphatase was not present in embryos, but was found in adults in the same zone of the mantle edge as acid phosphatase. Using the enzymes as cell markers, the differentiation of the embryonic shell-forming tissue to the different zones of the adult mantle edge could clearly be followed. 相似文献
108.
Baouendi M Cognet JA Ferreira CS Missailidis S Coutant J Piotto M Hantz E Hervé du Penhoat C 《The FEBS journal》2012,279(3):479-490
Mucin 1 is a well-established target for the early diagnosis of epithelial cancers. The nucleotides of the S1.3/S2.2 DNA aptamer involved in binding to variable number tandem repeat mucin 1 peptides have been identified using footprinting experiments. The majority of these binding nucleotides are located in the 25-nucleotide variable region of the total aptamer. Imino proton and 2D NMR spectra of truncated and total aptamers in supercooled water reveal common hydrogen-bonding networks and point to a similar secondary structure for this 25-mer sequence alone or embedded within the total aptamer. NMR titration experiments confirm that the TTT triloop structure is the primary binding site and show that the initial structure of the truncated aptamers is conserved upon interaction with variable number tandem repeat peptides. The thermal dependence of the NMR chemical shift data shows that the base-paired nucleotides melt cooperatively at 47 ±?4°C. The structure of the 25-mer oligonucleotide was determined using a new combined mesoscale molecular modeling, molecular dynamics and NMR spectroscopy investigation. It contains three Watson-Crick pairs, three consecutive mispairs and four Watson-Crick pairs capped by a TTT triloop motif. The 3D model structures (PDB 2L5K) and biopolymer chain elasticity molecular models are consistent with both NMR and long unconstrained molecular dynamics (10 ns) in explicit water, respectively. Database Structural data are available in the Protein Data Bank and BioMagResBank databases under the accession numbers 2L5K and 17129, respectively. 相似文献
109.
Meriem Bennabi Richard Delorme José Oliveira Catherine Fortier Mohamed Lajnef Wahid Boukouaci Jean-Paul Feugeas Fran?ois Marzais Alexandru Gaman Dominique Charron Bijan Ghaleh Rajagopal Krishnamoorthy Marion Leboyer Ryad Tamouza 《PloS one》2015,10(9)
Introduction
In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro-intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin-1.Material and methods
DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). Differences in the distribution of allele, genotype and haplotype by Chi-square testing and nonparametric analysis by Kruskal-Wallis/Mann–Whitney tests, where appropriate, were performed. The free statistical package R.2.13 software was used for the statistical analysis.Results
We found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in HC as compared to ASD but failed to reach statistical significance for the latter (pc = 0.01, 0.06 respectively). However, after phenotype-based stratification, the CLEC7A rs2078178 G allele and GG genotype were found to be significantly more frequent in the Asperger group as compared to other ASD subsets (pc = 0.02, 0.01), a finding reinforced by haplotype analysis (rs2078178/rs16910631 G-G/G-G) (pc = 0.002). Further, intellectual quotient (IQ)-based stratification of ASD patients revealed that IQ values increase linearly along the CLEC7A rs2078178 AA, AG and GG genotypes (p = 0.05) and in a recessive manner (GG vs. AA+AG p = 0.02), further confirmed by haplotype distribution (CLEC7A rs2078178-16910631; A-G/A-G, A-G/G-G and G-G/G-G, p = 0.02, G-G/G-G vs. others, p = 0.01).Conclusion
Our data suggest that the genetic diversity of CLEC7A gene influences the ASD phenotype by behaving as a disease specifier and imply that the genetic control of innate immune response could determine the ASD phenotype. 相似文献110.
Etienne Simon-Loriere Roman Galetto Meriem Hamoudi John Archer Pierre Lefeuvre Darren P. Martin David L. Robertson Matteo Negroni 《PLoS pathogens》2009,5(5)
The ability of pathogens to escape the host''s immune response is crucial for the establishment of persistent infections and can influence virulence. Recombination has been observed to contribute to this process by generating novel genetic variants. Although distinctive recombination patterns have been described in many viral pathogens, little is known about the influence of biases in the recombination process itself relative to selective forces acting on newly formed recombinants. Understanding these influences is important for determining how recombination contributes to pathogen genome and proteome evolution. Most previous research on recombination-driven protein evolution has focused on relatively simple proteins, usually in the context of directed evolution experiments. Here, we study recombination in the envelope gene of HIV-1 between primary isolates belonging to subtypes that recombine naturally in the HIV/AIDS pandemic. By characterizing the early steps in the generation of recombinants, we provide novel insights into the evolutionary forces that shape recombination patterns within viral populations. Specifically, we show that the combined effects of mechanistic processes that determine the locations of recombination breakpoints across the HIV-1 envelope gene, and purifying selection acting against dysfunctional recombinants, can explain almost the entire distribution of breakpoints found within this gene in nature. These constraints account for the surprising paucity of recombination breakpoints found in infected individuals within this highly variable gene. Thus, the apparent randomness of HIV evolution via recombination may in fact be relatively more predictable than anticipated. In addition, the dominance of purifying selection in localized areas of the HIV genome defines regions where functional constraints on recombinants appear particularly strong, pointing to vulnerable aspects of HIV biology. 相似文献