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81.
In vitro and in vivo characterization of an interleukin‐15 antagonist peptide by metabolic stability, 99mTc‐labeling,and biological activity assays 下载免费PDF全文
Yunier Rodríguez‐Álvarez Ania Cabrales‐Rico Alejandro Perera‐Pintado Anais Prats‐Capote Hilda E. Garay‐Pérez Osvaldo Reyes‐Acosta Erik Pérez‐García Araceli Chico‐Capote Alicia Santos‐Savio 《Journal of peptide science》2018,24(4-5)
Interleukin (IL)–15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL‐15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with 99mTc to investigate its stability in human plasma and its biodistribution pattern in healthy rats. The biological activity of [K6T]P8 peptide and its dimer was evaluated in CTLL‐2 cells, using 3 different additives to improve the solubility of these peptides. The half‐life of [K6T]P8 in human synovial fluid was 5.88 ± 1.73 minutes, and the major chemical modifications included peptide dimerization, cysteinylation, and methionine oxidation. Radiolabeling of [K6T]P8 with 99mTc showed a yield of approximately 99.8%. The 99mTc‐labeled peptide was stable in a 30‐fold molar excess of cysteine and in human plasma, displaying a low affinity to plasma proteins. Preliminary biodistribution studies in healthy Wistar rats suggested a slow elimination of the peptide through the renal and hepatic pathways. Although citric acid, sucrose, and Tween 80 enhanced the solubility of [K6T]P8 peptide and its dimer, only the sucrose did not interfere with the in vitro proliferation assay used to assess their biological activity. The results here presented, reinforce nonclinical characterization of the [K6T]P8 peptide, a potential agent for the treatment of RA and other diseases associated with IL‐15 overexpression. 相似文献
82.
Allister EM Pal S Thomson AM Helmerhorst E Mamo JC 《Journal of biomedical science》2004,11(6):789-798
We compared the acute effect of insulin on the human colonic intestinal epithelial cell line CaCo-2 and the transformed human hepatic cell line HepG2. Over 24 h, 100 nM and 10 µM insulin significantly inhibited the secretion of apolipoprotein (apo) B-100 from HepG2 cells to 63 and 49% of control, respectively. Insulin had no effect on the secretion of apoB-48 from CaCo-2 cells. There was no effect of insulin on the cholesterol ester or free cholesterol concentrations in HepG2 or CaCo-2 cells. HepG2 and CaCo-2 cells bound insulin with high affinity, leading to similar stimulation of insulin receptor protein tyrosine kinase activation. Protein kinase C or mitogen-activated protein kinase activity in the presence or absence of insulin was not correlated with apoB-48 production in CaCo-2 cells. Therefore, insulin acutely decreases the secretion of apoB-100 in hepatic HepG2 cells, but does not acutely modulate the production or secretion of apoB-48 from CaCo-2 intestinal cells. 相似文献
83.
1,1,2,2‐Tetrachloroethane (TeCA) as a Solvent Additive for Organic Hole Transport Materials and Its Application in Highly Efficient Solid‐State Dye‐Sensitized Solar Cells 下载免费PDF全文
84.
Among the three main categories of small silencing RNAs in insects and mammals-siRNAs, miRNAs, and piRNAs-siRNAs were thought to arise primarily from exogenous sources, whereas miRNAs and piRNAs arise from endogenous loci. Recent work in flies and mice reveals several classes of endogenous siRNAs (endo-siRNAs) that contribute to functions previously reserved for miRNAs and piRNAs, including gene regulation and transposon suppression. 相似文献
85.
Fian R Grasser E Treiber F Schmidt R Niederl P Rosker C 《Journal of receptor and signal transduction research》2007,27(2-3):113-124
A large variety of cation transport systems are involved in the regulation of calcium homeostasis in endothelial cells. The focus of the present study is to determine the contribution of nonselective cation channels from the TRP (transient receptor potential) family to cellular calcium homeostasis of porcine aortic endothelial cells (PAEC). One member of the TRPV (vanniloid) subfamily, TRPV4, has previously been shown to be involved in cation transport induced by a large variety of stimulations including osmolarity, temperature, mechanical stress, and phosphorylation. Here, we demonstrate the existence of several TRP proteins, including TRPV4, in PAEC using RT-PCR. To test whether this channel is functional, we performed FURA-2 calcium measurements and whole-cell patch-clamp experiments. We observed the induction of large calcium signals following mechanical stress, altered extracellular temperature, and the selective TRPV4 activator 4-alpha -PDD. These effects were diminished in the presence of the TRPV4 inhibitor miconazole, suggesting the involvement of this channel in mediating endothelial calcium signals. The large amounts of transported calcium and the short signaling ways suggest a potentially important role of this channel in many physiological processes. 相似文献
86.
Chi Zhang Hanqin Tian Shufen Pan Mingliang Liu Graeme Lockaby Erik B. Schilling John Stanturf 《Ecosystems》2008,11(8):1211-1222
Forest regrowth after cropland abandonment and urban sprawl are two counteracting processes that have influenced carbon (C)
sequestration in the southeastern United States in recent decades. In this study, we examined patterns of land-use/land-cover
change and their effect on ecosystem C storage in three west Georgia counties (Muscogee, Harris, and Meriwether) that form
a rural–urban gradient. Using time series Landsat imagery data including MSS for 1974, TM for 1983 and 1991, and ETM for 2002,
we estimate that from 1974 to 2002, urban land use in the area has increased more than 380% (that is, 184 km2). Most newly urbanized land (63%) has been converted from forestland. Conversely, cropland and pasture area has decreased
by over 59% (that is, 380 km2). Most of the cropland area was converted to forest. As a result, the net change in forest area was small over the past 29
years. Based on Landsat imagery and agricultural census records, we reconstructed an annual gridded data set of land-cover
change for the three counties for the period 1850 to 2002. These data sets were then used as input to the Terrestrial Ecosystem
Model (TEM) to simulate land-use effects on C fluxes and storage for the study area. Simulated results suggest that C uptake
by forest regrowth (approximately 23.0 g C m−2 y−1) was slightly greater than the amount of C released due to deforestation (approximately 18.4 g C m−2 y−1), thus making the three counties a weak C sink. However, the relative importance of different deforestation processes in
this area changed significantly through time. Although agricultural deforestation was generally the most important C-release
process, the amount of C release attributable to urbanization has increased over time. Since 1990, urbanization has accounted
for 29% of total C loss from the study area. We conclude that balancing urban development and forest protection is critically
important for C management and policy making in the southeastern United States. 相似文献
87.
Philip K. Frykman Erik H. Lindsley Mark Gaon Daniel L. Farkas 《Journal of biophotonics》2008,1(2):97-103
We used advanced spectral imaging for intrasurgical decision making in a preclinical study, on a mouse model of Hirschsprung's Disease. Our imaging device sampled areas from normal and abnormal (aganglionic) colon in these animals. Spectral segmentation and classification of the resulting images showed a clear distinction between the normal and aganglionic regions, as confirmed by pathological analysis and use of mutant mice. We developed a simple algorithm that could distinguish normal from aganglionic colon with high spatial resolution and reproducibility, and the following statistics: sensitivity = 97%, specificity = 94%, positive predictive value = 92%, negative predictive value = 98%. These studies showed translational proof of concept that spectral imaging could be used during operations, in real time, to help surgeons precisely distinguish normal from abnormal tissue without requiring traditional biopsy. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
88.
Letter: Preliminary x-ray data from well-ordered crystals of a human immunoglobulin G molecule 总被引:1,自引:0,他引:1
Crystals of an intact immunoglobulin G molecule, which are suitable for high resolution X-ray analysis, have been grown. The space group is P3121 (or enantiomorph) and the crystallographic diad relates the two halves of one molecule. 相似文献
89.
Recent studies have suggested that ribosomal protein S12 modulates 16S rRNA function and susceptibility to 2-deoxystreptamine aminoglycosides. To study whether the non-restrictive K42R mutation in RpsL affects 2-deoxystreptamine susceptibility in Mycobacterium smegmatis, we studied the drug susceptibility pattern of various mutants with genetic alterations in the 16S rRNA decoding A-site in the context of wild-type and mutant protein S12. RpsL K42R substitution was found not to affect the drug resistance pattern associated with mutational alterations in 16S rRNA H44. 相似文献
90.
The molecular structure of a dimer composed of the variable portions of the Bence-Jones protein REI refined at 2.0-A resolution. 总被引:13,自引:0,他引:13
The structure of the variable portions of a K-type Bence-Jones protein REI forming a dimer has been determined by X-ray diffraction to a resolution of 2.0 A. The structure has been refined using a constrained crystallographic refinement procedure. The final R value is 0.24 for 15000 significantly measured reflections; the estimated standard deviation of atomic positions is 0.09 A. A more objective assessment of the error in the atomic positions is possible by comparing the two independently refined monomers. The mean deviation of main-chain atoms of the two chains in internal segments in 0.22 A, of main-chain dihedral angles 6.3 degrees for these segments. The unrefined molecular structure of the VREI dimer has been published (Epp, O., Colman, P., Fehlhammer, H., Bode, W., Schiffer, M., Huber, R., and Palm, W. (1974), Eur. J. Biochem. 45, 513). Now a detailed analysis is presented in terms of hydrogen bonds and conformational angles. Secondary structural elements (antiparallel beta structure, reverse turns) are defined. A more precise atomic arrangement of the amino acid residues forming the contact region and the hapten binding site is given as well as the localization of solvent molecules. Two cis-prolines (Pro-8 and Pro-95) were detected. The intrachain disulfide bridge (Cys-23-Cys-88) occurs statistically in two alternative conformations. The structure suggests reasons for strong conservation of several amino acid residues. The knowledge of the refined molecular structure enables crystal structure analyses of related molecules to be made by Patterson search techniques. The calculated phases based on the refined structure are much improved compared to isomorphous phases. Therefore the effects of hapten binding on the molecular structure can be analyzed by the difference Fourier technique with more reliability. Hapten binding studies have been started. 相似文献