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91.
Vassilios Tsikaris Marie-Christine Petit Piotr Orlewski Maria Sakarellos-Daitsiotis Constantinos Sakarellos Athina Tzinia Georgia Konidou Ketty P. Soteriadou Michel Marraud Manh Thong Cung 《Letters in Peptide Science》1997,4(4-6):323-330
The I250ASRYDQL257 synthetic octapeptideof the Leishmania major surface glycoproteingp63, which efficiently inhibits parasite attachmentto the macrophage receptors and mimics antigenicallyand functionally the RGDS sequence of fibronectin, wasstudied by 2D TR-NOESY in the presence of an anti-SRYDmonoclonal antibody (mAbSRYD) that recognizes bothSRYD-containing peptides and the cognate protein onintact parasites. Molecular modeling was performedusing distance constraints obtained from TR-NOEs. Thebound structure was compared with that of the freepeptide in DMSO solution and with the crystalstructure of the RYD fragment of the OPG2 Fab, anantireceptor antibody that mimics an RGD cell adhesion site. 相似文献
92.
Constantinos Sakarellos Vassilios Tsikaris Eugenia Panou-Pomonis Charalampos Alexopoulos Maria Sakarellos-Daitsiotis Constantinos Petrovas Panayiotis G. Vlachoyiannopoulos Haralampos M. Moutsopoulos 《Letters in Peptide Science》1997,4(4-6):447-454
The PPGMRPP sequence, found in several copies in the Sm and U1RNPautoantigens, is the main target of anti-Sm and anti-U1RNP antibodies insystemic lupus erythematosus (SLE) and mixed connective tissue disease(MCTD) patient's sera. It is also recognized, to a lower extent, byanti-Ro/SSA and anti-La/SSB specificities. The PPGMRPP-NH2peptide amide and the PPGMRPP peptide, which is bound to a pentamericsequential oligopeptide carrier (SOC5), were examined by1H-NMR spectroscopy and ELISA assays, using sera from patientswith autoimmune rheumatic diseases. Among the three main conformers foundfor the free PPGMRPP, the extended one was also identified for PPGMRPP-NH2 and (PPGMRPP)5-SOC5.This can be attributed to the absence of ionic interactions between theArg-guanidinium and the carboxylate group in the amide andSOC5-bound forms of the peptide. Immunoassays using sera fromvarious specificities showed an enhanced anti-Sm and anti-U1RNP recognitionof PPGMRPP-NH2 and(PPGMRPP)5-SOC5, and lowering of the anti-Ro/SSAand anti-La/SSB reactivity. The presence of multiple conformers of freePPGMRPP may explain the unexpected cross-reactivity to the anti-Ro/Lapositive sera, while the prevalence of the extended conformation inPPGMRPP-NH2 and (PPGMRPP)5-SOC5is mainly responsible for the enhanced recognition from the anti-Sm andanti-U1RNP autoantibodies. It is concluded that the antigenic specificity ofPPGMRPP-NH2 and (PPGMRPP)5-SOC5 ismainly induced by conformational changes resulting from the conversion ofthe C-terminal carboxylate group to the amide form. 相似文献
93.
Leeyah Issop Mariano A. Ostuni Sunghoon Lee Mireille Laforge Gabriel Péranzi Pierre Rustin Jean-Fran?ois Benoist Jérome Estaquier Vassilios Papadopoulos Jean-Jacques Lacapère 《PloS one》2016,11(4)
Chronic inflammation of the gastrointestinal tract increasing the risk of cancer has been described to be linked to the high expression of the mitochondrial translocator protein (18 kDa; TSPO). Accordingly, TSPO drug ligands have been shown to regulate cytokine production and to improve tissue reconstruction. We used HT-29 human colon carcinoma cells to evaluate the role of TSPO and its drug ligands in tumor necrosis factor (TNF)-induced inflammation. TNF-induced interleukin (IL)-8 expression, coupled to reactive oxygen species (ROS) production, was followed by TSPO overexpression. TNF also destabilized mitochondrial ultrastructure, inducing cell death by apoptosis. Treatment with the TSPO drug ligand PK 11195 maintained the mitochondrial ultrastructure, reducing IL-8 and ROS production and cell death. TSPO silencing and overexpression studies demonstrated that the presence of TSPO is essential to control IL-8 and ROS production, so as to maintain mitochondrial ultrastructure and to prevent cell death. Taken together, our data indicate that inflammation results in the disruption of mitochondrial complexes containing TSPO, leading to cell death and epithelia disruption. Significance: This work implicates TSPO in the maintenance of mitochondrial membrane integrity and in the control of mitochondrial ROS production, ultimately favoring tissue regeneration. 相似文献
94.
95.
Decisions involve two fundamental problems, selecting goals and generating actions to pursue those goals. While simple decisions involve choosing a goal and pursuing it, humans evolved to survive in hostile dynamic environments where goal availability and value can change with time and previous actions, entangling goal decisions with action selection. Recent studies suggest the brain generates concurrent action-plans for competing goals, using online information to bias the competition until a single goal is pursued. This creates a challenging problem of integrating information across diverse types, including both the dynamic value of the goal and the costs of action. We model the computations underlying dynamic decision-making with disparate value types, using the probability of getting the highest pay-off with the least effort as a common currency that supports goal competition. This framework predicts many aspects of decision behavior that have eluded a common explanation. 相似文献
96.
Synthesis and Characterization of High‐Energy,High‐Power Spinel‐Layered Composite Cathode Materials for Lithium‐Ion Batteries
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Steffen Krueger Vassilios Siozios Jie Li Sascha Nowak Martin Winter 《Liver Transplantation》2015,5(5)
Spinel‐layered composites, where a high‐voltage spinel is incorporated in a layered lithium‐rich (Li‐rich) cathode material with a nominal composition x{0.6Li2MnO3 · 0.4[LiCo0.333Mn0.333Ni0.333]O2} · (1 – x) Li[Ni0.5Mn1.5]O4 (x = 0, 0.3, 0.5, 0.7, 1) are synthesized via a hydroxide assisted coprecipitation route to generate high‐energy, high‐power cathode materials for Li‐ion batteries. X‐ray diffraction patterns and the cyclic voltammetry investigations confirm the presence of both the parent components in the composites. The electrochemical investigations performed within a wide potential window show an increased structural stability of the spinel component when incorporated into the composite environment. All the composite materials exhibit initial discharge capacities >200 mAh g–1. The compositions with x = 0.5 and 0.7 show excellent cycling stability among the investigated materials. Moreover, the first cycle Coulombic efficiency achieve a dramatic improvement with the incorporation of the spinel component. More notably, the composite materials with increased spinel component exhibit superior rate capability compared with the parent Li‐rich material especially together with the highest capacity retention for x = 0.5 composition, making this as the optimal high‐energy high‐power material. The mechanisms involved in the symbiotic relationship of the spinel and layered Li‐rich components in the above composites are discussed. 相似文献
97.
Akula N Midzak A Lecanu L Papadopoulos V 《Bioorganic & medicinal chemistry letters》2012,22(12):4139-4143
A homology model of the steroidogenic acute regulatory protein (STAR)-related lipid transfer (START) domain of STARD1 was built, and the cholesterol binding site was identified. Structure-based design studies were performed to identify small molecule inhibitors of the START domain. The lead compounds were selected based on cAMP-induced, but not 22R-hydroxycholesterol-supported, inhibition of steroid synthesis by 50% at 10 μM. The results obtained by molecular docking & dynamics show a good correlation between bioactivity, docking scores and calculated binding energies of ligand-protein complexes. The best active compounds will be optimized further and used to develop potential drugs to control excessive steroid formation. 相似文献
98.
Balatsos N Vlachakis D Chatzigeorgiou V Manta S Komiotis D Vlassi M Stathopoulos C 《Biochimie》2012,94(1):214-221
Poly(A)-specific ribonuclease (PARN) is a 3′-exoribonuclease that efficiently degrades poly(A) tails and regulates, in part, mRNA turnover rates. We have previously reported that adenosine- and cytosine-based glucopyranosyl nucleoside analogues with adequate tumour-inhibitory effect could effectively inhibit PARN. In the present study we dissect the mechanism of a more drastic inhibition of PARN by novel glucopyranosyl analogues bearing uracil, 5-fluorouracil or thymine as the base moiety. Kinetic analysis showed that three of the compounds are competitive inhibitors of PARN with Ki values in the low μM concentration and significantly lower (11- to 33-fold) compared to our previous studies. Detailed kinetic analysis of the most effective inhibitor, the uracil-based nucleoside analogue (named U1), revealed slow-binding behaviour. Subsequent molecular docking experiments showed that all the compounds which inhibited PARN can efficiently bind into the active site of the enzyme through specific interactions. The present study dissects the inhibitory mechanism of this novel uracil-based compound, which prolongs its inhibitory effect through a slow-binding and slow-release mode at the active site of PARN, thus contributing to a more efficient inhibition. Such analogues could be used as leading compounds for further rationale design and synthesis of efficient and specific therapeutic agents. Moreover, our data reinforce the notion that human PARN can be established as a novel molecular target of potential anti-cancer agents through lowering mRNA turnover rates. 相似文献
99.
Irini P. Kotti Georgios D. Gikas Vassilios A. Tsihrintzis 《Ecological Engineering》2010,36(7):862-875
In order to investigate the effect of temperature, hydraulic residence time (HRT), vegetation type, substrate material and wetland shape on the performance of free-water surface (FWS) constructed wetlands treating wastewater, 5 pilot-scale units were constructed and operated continuously from December 2004 until March 2007 in parallel experiments. Four of the units (A, B, C, D) were rectangular in plan view with dimensions 3.40 m in length and 0.85 m in width, and contained substrate material at a thickness of 0.45 m. The fifth unit (E) had a trapezoidal plan view shape, with a width at the inlet of 1.15 m and at the outlet of 0.55 m, while the length and the thickness of the substrate were the same as in the other four. All units operated at a water depth of 0.10 m. Units B–E contained clay substrate and unit A contained sand. The four units with clay were planted as follows: two with cattails (B and E), one with common reeds (C), and one with giant reeds (D). Unit A, containing sand, was planted with cattails. Planting and substrate material combinations were appropriate for comparison of the effect of vegetation and material type on the function of the system. Synthetic wastewater was introduced in the units. During the operation period four HRTs (i.e., 6 days, 8 days, 14 days and 20 days) were used, while wastewater temperatures varied from about 0.0 °C to 29.1 °C. The removal performance of the five constructed wetland units was good, since it reached on the average 77.5%, 67.9%, 60.4%, 53.9%, 56.0% and 51.7% for BOD, COD, TKN, ammonia (NH4-N), ortho-phosphate (PO4-P) and total phosphorus (TP), respectively. BOD and phosphorus removal efficiencies showed dependence on temperature in most units. The 14-day HRT was found adequate for acceptable removal of organic matter, nitrogen and phosphorus for most temperatures. A 20-day HRT is recommended for acceptable removal of BOD and PO4-P in the cold season. The unit with the trapezoidal plan view shape showed the best performance, with mean removals of 80.1%, 73.5%, 70.4%, 68.6%, 64.7% and 63.5% for BOD, COD, TKN, NH4-N, PO4-P and TP, respectively. The cattail was found statistically more efficient than the other two plants in COD and PO4-P removal. The unit that contained the clay substrate was found statistically more efficient in phosphorus removal than the unit containing sand. HSF CW units were found more efficient than FWS units in removal of most pollutant. 相似文献
100.