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171.
Zhongli Gao William J. Hurst Etienne Guillot Werngard Czechtizky Ulrike Lukasczyk Raisa Nagorny Marie-Pierre Pruniaux Lothar Schwink Juan Antonio Sanchez Siegfried Stengelin Lei Tang Irvin Winkler James A. Hendrix Pascal G. George 《Bioorganic & medicinal chemistry letters》2013,23(11):3421-3426
A novel series of histamine H3 receptor (H3R) antagonists was derived from an arylurea lead series (1) via bioisosteric replacement of the urea functionality by an amide linkage. The arylamide series was optimized through SAR studies by a broad variation of substituents in the left-hand side benzoyl residue (analogs 2a–2ag) or replacement of the benzoyl moiety by heteroarylcarbonyl residues (analogs 5a–5n). Compounds 2p and 2q were identified within the series as potent and selective H3R antagonists/inverse agonists with acceptable overall profile. Compound 2q was orally active in food intake inhibition in diet-induced obese (DIO) mice. Compound 2q represents a novel H3R antagonist template with improved in vitro potency and oral efficacy and has its merits as a new lead for further optimization. 相似文献
172.
Pauline Burger Jean-Frederic Terral Marie-Pierre Ruas Sarah Ivorra Sandrine Picq 《Vegetation History and Archaeobotany》2011,20(5):447-458
Abundant and diverse Prunus fruitstone remains from cherries, plums, sloes, peaches, etc. are frequently recovered from archaeological waterlogged contexts
such as wells, latrines, lake dwellings etc. in Europe. The distinction between most of the Prunus species, based on traditional morphological characters of the fruit stones, is usually not problematic. However the discrimination
between P. avium L., P. cerasus L. and related cherry species, based on classical criteria alone, often turns out to be ambiguous because of the increasing
number of varieties which have been bred since Roman times. By combining geometric and traditional morphometrical approaches,
the overall variation in shape and size of stones from French and Swiss excavations dating from the 1st century to the 16th
century a.d. were assessed. Among these important archaeobotanical data, the detailed examination of 100 waterlogged stones from the 16th
century H?tel-Dieu cesspit at Tours, France, revealed that the morphological diversity is structured into two distinct morphotypes
which diverge mainly according to geometrical features. Finally, the comparison between morphological features of these well-preserved
archaeological stones and modern reference material including P. avium, P. cerasus and P. × gondouinii, suggests that these two morphotypes, which have been initially attributed to P. avium (long stones) and P. avium/cerasus (rounded stones) according to traditional morphological parameters, would correspond to two different cultivated varieties,
both belonging to Prunus avium. Results presented in this work constitute new and preliminary data obtained during the development of this project that
throw light on morphological variability and biosystematic aspects. 相似文献
173.
174.
PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells 总被引:2,自引:0,他引:2
Couty JP Rampon C Leveque M Laran-Chich MP Bourdoulous S Greenwood J Couraud PO 《Journal of neurochemistry》2007,103(2):793-801
Interactions between leukocytes and vascular endothelial cells are mediated by a complex set of membrane adhesion molecules which transduce bi-directional signals in both cell types. Endothelium of the cerebral blood vessels, which constitute the blood-brain barrier, strictly controls adhesion and trafficking of leukocytes into the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells, we previously documented the role of ICAM-1 in activation of the tyrosine phosphorylation of several actin-binding proteins and subsequent rearrangements of the actin cytoskeleton. In the present study, we show that, whereas PECAM-1 is known to control positively the trans-endothelial migration of leukocytes via homophilic interactions between leukocytes and endothelial cells, PECAM-1 engagement on brain endothelial surface unexpectedly counteracts the ICAM-1-induced tyrosine phosphorylation of cortactin and rearrangements of the actin cytoskeleton. We present evidence that the PECAM-1-associated tyrosine phosphatase SHP-2 is required for ICAM-1 signaling, suggesting that its activity might crucially contribute to the regulation of ICAM-1 signaling by PECAM-1. Our findings reveal a novel activity for PECAM-1 which, by counteracting ICAM-1-induced activation, could directly contribute to limit activation and maintain integrity of brain vascular endothelium. 相似文献
175.
The induction of resistance to disease during plant development is widespread in the plant kingdom. Resistance appears at different stages of host development, varies with plant age or tissue maturity, may be specific or broad-spectrum and is driven by diverse mechanisms, depending on plantpathogen interactions. Studies of these forms of resistance may help us to evaluate more exhaustively the plethora of levels of regulation during development, the variability of the defense potential of developing hosts and may have practical applications, making it possible to reduce pesticide applications. Here, we review the various types of developmental resistance in plants and current knowledge of the molecular and cellular processes involved in their expression. We discuss the implications of these studies, which provide new knowledge from the molecular to the agrosystem level. 相似文献
176.
Redko Y Courtin P Mézange C Huard C Chapot-Chartier MP 《Applied and environmental microbiology》2007,73(18):5825-5831
YjgB is one of five peptidoglycan hydrolases previously identified in Lactococcus lactis. Analysis of its amino acid sequence revealed that YjgB contains an NlpC/P60 domain, whereas no specific cell wall binding domain or motif could be identified. The NlpC/P60 family is characterized by three conserved residues, a cysteine, a histidine, and a polar residue. In agreement with the presence of a Cys residue in the catalytic site of YjgB, its enzymatic activity was enhanced in the presence of dithiothreitol. Peptidoglycan-hydrolyzing activity of YjgB was detected in growing cells of an L. lactis strain overexpressing YjgB, as revealed by the presence of disaccharide (DS)-dipeptide in the muropeptide composition of the overexpressing strain. YjgB hydrolyzes the peptide chains of L. lactis muropeptides between gamma-D-Gln and L-Lys residues. Its hydrolytic activity was detected on DSs with tetra- and pentapeptide chains, whereas hydrolytic activity was very low on DS-tripeptides. Thus, we demonstrated that YjgB is an endopeptidase which cleaves gamma-D-Gln-L-Lys bonds in peptide chains of L. lactis peptidoglycan. 相似文献
177.
Squamanita odorata is an agaric which is parasitic on unrecognizable, previously unidentifiable sporophores of a fungal host that is transformed into galls at the bases of the parasite's sporophore. Amplification and sequencing portions of the nuclear (ITS) and mt rDNA from three samplings originating from two sites (from France and from Switzerland) demonstrate that the galls produce sequences that are identical to that of co-occurring Hebeloma mesophaeum. This demonstrates that S. odorata is a biotrophic parasite on Hebeloma mesophaeum. 相似文献
178.
Cayer MP Veillette M Pageau P Hamelin R Bergeron MJ Mériaux A Cormier Y Duchaine C 《Canadian journal of microbiology》2007,53(1):92-99
Peat moss processing plant workers are exposed to high concentrations of bioaerosols. Although mycobacteria have been cultured from peat moss, no study has examined the workers' exposure to mycobacterial bioaerosols. We evaluated the presence of mycobacteria in air samples from peat moss processing plants using molecular biology approaches (cloning-sequencing and polymerase chain reaction (PCR)) and the workers exposure using immunoglobulin G (IgG) complexes to mycobacteria. In addition, species detected in air samples and in peat moss were compared. Two peat moss processing plants were chosen among 14 previously studied. A total of 49 clones were sequenced. Real-time PCR was also performed on the same air samples to evaluate the airborne concentration of mycobacteria and estimate exposure levels. Several Mycobacterium species were present in the air samples (M. malmoense, M. smegmatis, M. graceum, M. bohemicum, and M. interjectum). Mycobacterium avium was recovered by culture in peat moss but not in the air using the molecular approach. Total airborne Mycobacterium concentration was estimated at 8.2 x 10(8)/m3. Workers had IgG against the mycobacterial mix and M. avium, suggesting significant exposure. The findings from air samples, supported by IgG measurements, demonstrate that peat moss processing plant workers are exposed to mycobacteria in addition to other biological agents. 相似文献
179.
Kellouche S Mourah S Bonnefoy A Schoëvaert D Podgorniak MP Calvo F Hoylaerts MF Legrand C Dosquet C 《Experimental cell research》2007,313(3):486-499
During cutaneous wound repair, platelets, dermal fibroblasts (DF) and endothelial cells all cooperate. We have presently investigated the regulation of endothelial cell tubulogenesis by human platelet thrombospondin-1 (TSP-1), in comparison to transforming growth factor-beta1 (TGF-beta1) and total platelet lysates (PL), in a fibrin matrix cell culture system incorporating DF. TSP-1, TGF-beta1 and PL all stimulated VEGF expression in DF dose dependently at mRNA and protein level. TSP-1- and PL-treated DF supernatants significantly stimulated capillary-like structure formation (tubulogenesis) by dermal microvascular endothelial cells (HMEC-1 and HDMEC), in part via VEGF, as confirmed with neutralizing anti-VEGF antibodies. In contrast, TGF-beta1-treated DF supernatants did not induce tubulogenesis. This apparent discrepancy could be explained by the differential expression regulation in HMEC-1 of fibrinolysis and metalloproteinase mediators by TSP-1 and TGF-beta1. TSP-1 potently reduced the expression of plasminogen activator inhibitor-1 (PAI-1) (mRNA and protein), whereas TGF-beta1 enhanced it. The crucial role of PAI-1 in tubulogenesis was confirmed via the addition of active recombinant PAI-1, which abrogated tubulogenesis. In contrast, neutralizing PAI-1 antibodies enhanced tubulogenesis. Our results suggest that platelet TSP-1 released in a wound stimulates endothelial cell tubulogenesis through an upregulation of DF VEGF expression and a downregulation of endothelial cell PAI-1 expression. 相似文献
180.
Patten AM Jourdes M Brown EE Laborie MP Davin LB Lewis NG 《American journal of botany》2007,94(6):912-925
To our knowledge, xylary reaction tissue has never been reported in a forage crop species. Here we report the discovery of reaction tissue in a transgenic line of Medicago sativa (pC3H, for the gene for p-coumarate-3-hydroxylase) with reduced lignin content and in the wild-type (WT) line. Based on microscopy and biomechanical testing of internodal alfalfa branch sections, the transgenic (pC3H-I) line, relative to the WT (1) apparently formed more reaction tissue containing gelatinous fibers with adjacent thick-walled fibers (presumed to be "intermediate" tissue) more rapidly, (2) had more xylem tissue, and (3) had comparable tensile dynamic modulus properties. These findings thus establish the (limited) ability of this perennial angiosperm to form (inducible) reaction tissue in a manner somewhat analogous to that of woody arborescent angiosperms. The potential of effectuating reductions in lignin amounts in (woody) angiosperms with increased formation of reaction (tension wood) tissue is discussed because reaction tissues are often viewed as a deleterious trait in processing for many agronomic/industrial applications, especially with the current interest in biofuels. 相似文献