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991.
Loriga G Manca I Murineddu G Chelucci G Villa S Gessi S Toma L Cignarella G Pinna GA 《Bioorganic & medicinal chemistry》2006,14(3):676-691
In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba-i) were synthesized and their affinity and selectivity towards mu-, delta- and kappa-receptors were evaluated. The results of the current study revealed a number of compounds (3Bb, 3Bg and 3Bh) having a high affinity for mu (Ki at mu-receptors ranging from 2.7 to 7.9 nM) versus delta (Ki at delta-receptors > 2000 nM) and versus kappa (Ki at kappa-receptors > 5000 nM) receptors. Molecular modelling carried out on the pair 3Aa/3Ba and on the 3Bh was consistent with the hypothesis that the two series of compounds 3A and 3B interact with the mu-receptor in very different ways. 相似文献
992.
993.
Caroline West Alexis Bouet Isabelle Gillaizeau Gerard Coudert Michel Lafosse Eric Lesellier 《Chirality》2010,22(2):242-251
Enantiomeric separations of six amino‐acid derivatives have been studied using packed‐column supercritical fluid chromatography with two polysaccharide‐based enantioselective stationary phases: cellulose tris(3,5‐dimethylphenylcarbamate) and cellulose tris(3‐chloro‐4‐methylphenylcarbamate) (Lux Cellulose‐1 and ‐2). The effect of analyte structure on retention and separation was studied. Varied mobile phase compositions were investigated: alcohol modifier percentage was increased from 3 to 40% but smaller amounts were most effective in separating these compounds. Besides, ethanol was preferred to methanol or isopropanol as it proved to be a good compromise to achieve sufficient resolution in a reasonable analysis time. Moreover, a carbon dioxide‐ethanol mixture allows performing analyses in safe and green conditions. The effect of temperature at constant mobile phase composition was explored between 10 and 40°C. In most cases, increasing the temperature improved the chiral separation, up to an optimum temperature. The results are discussed in line with the structure variation of the racemic derivatives analyzed and the two columns are compared. The two columns were shown to provide complementary selectivities for the investigated solutes: whereas Lux 1 provided separation for five of the six racemates, Lux 2 could resolve the last racemic mixture. Finally, optimized conditions of separation are defined. Chirality, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
994.
Christopher J. Penkett Glen van Ginkel Sameer Velankar Jawahar Swaminathan Eldon L. Ulrich Steve Mading Tim J. Stevens Rasmus H. Fogh Aleksandras Gutmanas Gerard J. Kleywegt Kim Henrick Wim F. Vranken 《Journal of biomolecular NMR》2010,48(2):85-92
We present a suite of software for the complete and easy deposition of NMR data to the PDB and BMRB. This suite uses the CCPN framework and introduces a freely downloadable, graphical desktop application called CcpNmr Entry Completion Interface (ECI) for the secure editing of experimental information and associated datasets through the lifetime of an NMR project. CCPN projects can be created within the CcpNmr Analysis software or by importing existing NMR data files using the CcpNmr FormatConverter. After further data entry and checking with the ECI, the project can then be rapidly deposited to the PDBe using AutoDep, or exported as a complete deposition NMR-STAR file. In full CCPN projects created with ECI, it is straightforward to select chemical shift lists, restraint data sets, structural ensembles and all relevant associated experimental collection details, which all are or will become mandatory when depositing to the PDB. Instructions and download information for the ECI are available from the PDBe web site at http://www.ebi.ac.uk/pdbe/nmr/deposition/eci.html. 相似文献
995.
Stift M Bregman R Oostermeijer JG van Tienderen PH 《American journal of botany》2010,97(11):1858-1866
? Premise of the study: Most plants are polyploid and have more than two copies of the genome. The evolutionary success of polyploids is often attributed to their potential to harbor increased genetic variation, but it is poorly understood how polyploids can attain such variation. Because of their formation bottleneck, newly formed tetraploids start out with little variation. Tetraploids may attain genetic variation through a combination of new mutations, recurrent formation, and gene exchange with diploid ancestors or related tetraploid species. We explore the role of gene exchange and introgression in autotetraploid Rorippa amphibia, a species that harbors more genetic variation than its diploid ancestors. ? Methods: We crossed autotetraploid R. amphibia to diploid conspecifics and tetraploid R. sylvestris and backcrossed resulting F(1) hybrids. We used flow cytometry to determine the ploidy of all progeny. ? Key results: Tetraploids of R. amphibia and R. sylvestris were interfertile; F(1) hybrids were fertile and could backcross. Crosses between diploids and tetraploids yielded a small number of viable, often tetraploid progeny. This indicates that unreduced gametes can facilitate gene flow from diploids to tetraploids. We detected a frequency of unreduced gametes of around 2.7 per 1000, which was comparable between diploids and tetraploids. ? Conclusions: Introgression from tetraploid R. sylvestris provides a realistic source of variation in autotetraploid R. amphibia. Only in a scenario where other compatible partners are absent, for example immediately after tetraploidization, gene flow through unreduced gametes from diploids could be an important source of genetic variation for tetraploids. 相似文献
996.
Clive S. McKimmie Gerard J. Graham 《Biochemical and biophysical research communications》2010,394(4):1006-1011
Immune responses in the central nervous system (CNS) are carefully regulated. Despite the absence of most immune processes and a substantive blood brain barrier, potent immune responses form during infection and autoimmunity. Astrocytes are innate immune sentinels that ensheath parenchymal blood vessels and sit at the gateway to the CNS parenchyma. Viral and bacterial infections trigger the influx of distinct leukocyte subsets. We show that astrocytes alone are sufficient for distinguishing between these two main types of infection and triggers release of relevant chemokines that relate to the microbe recognised. Bacterial-associated molecules induced the preferential expression of CCL2, CXCL1, CCL20 and CCL3 whilst a virus-associated dsRNA analogue preferentially up-regulated CXCL10 and CCL5. Thus, astrocytes can respond to infection in a distinct and appropriate manner suggesting they have the capacity to attract appropriate sets of leukocytes into the brain parenchyma. Astrocytes themselves are unable to respond to these chemokines since they were devoid of most chemokine receptors but expressed CXCR4, CXCR7 and CXCR6 at rest. Stimulation with TGF-β specifically up-regulated CXCR6 expression and may explain how TGF-β/CXCL16-expressing gliomas are so effective at attracting astroglial cells. 相似文献
997.
Sean A. Gray Kris M. Weigel Keith D. Miller Joseph Ndung'u Philippe Büscher Thao Tran Cheryl Baird Gerard A. Cangelosi 《Biotechnology and bioengineering》2010,105(5):973-981
Novel methods are reported for evaluating and utilizing single chain fragment variable (scFv) antibodies derived from yeast‐display libraries. Yeast‐display was used to select scFv specific to invariant surface glycoproteins (ISG) of Trypanosoma brucei. A limiting step in the isolation of scFv from non‐immune libraries is the conversion of highly active yeast‐displayed scFv into soluble antibodies that can be used in standard immunoassays. Challenges include limited solubility or activity following secretion and purification of scFv. For this reason, few scFv derived from yeast‐display platforms have moved into development and implementation as diagnostic reagents. To address this problem, assays were developed that employ both yeast‐displayed and ‐secreted scFv as analytical reagents. The first is a competitive inhibition flow cytometry (CIFC) assay that detects secreted scFv by virtue of their ability to competitively inhibit the binding of biotinylated antigen to yeast‐displayed scFv. The second is an epitope binning assay that uses secreted scFv to identify additional yeast‐displayed scFv that bind non‐overlapping or non‐competing epitopes on an antigen. The epitope binning assay was used not only to identify sandwich assay pairs with yeast‐displayed scFv, but also to identify active soluble scFv present in low concentration in a crude expression extract. Finally, a CIFC assay was developed that bypasses entirely the need for soluble scFv expression, by using yeast‐displayed scFv to detect unlabeled antigen in samples. These methods will facilitate the continued development and practical implementation of scFv derived from yeast‐display libraries. Biotechnol. Bioeng. 2010;105: 973–981. © 2009 Wiley Periodicals, Inc. 相似文献
998.
This study formulates and implements a finite element contact algorithm for solid-fluid (biphasic) mixtures, accommodating both finite deformation and sliding. The finite element source code is made available to the general public. The algorithm uses a penalty method regularized with an augmented Lagrangian method to enforce the continuity of contact traction and normal component of fluid flux across the contact interface. The formulation addresses the need to automatically enforce free-draining conditions outside of the contact interface. The accuracy of the implementation is verified using contact problems, for which exact solutions are obtained by alternative analyses. Illustrations are also provided that demonstrate large deformations and sliding under configurations relevant to biomechanical applications such as articular contact. This study addresses an important computational need in the biomechanics of porous-permeable soft tissues. Placing the source code in the public domain provides a useful resource to the biomechanics community. 相似文献
999.
1000.
A. M. Anithakumari Jifeng Tang Herman J. van Eck Richard G. F. Visser Jack A. M. Leunissen Ben Vosman C. Gerard van der Linden 《Molecular breeding : new strategies in plant improvement》2010,26(1):65-75
Single nucleotide polymorphisms (SNPs) represent the most abundant type of genetic variation that can be used as molecular
markers. The SNPs that are hidden in sequence databases can be unlocked using bioinformatic tools. For efficient application
of these SNPs, the sequence set should be error-free as much as possible, targeting single loci and suitable for the SNP scoring
platform of choice. We have developed a pipeline to effectively mine SNPs from public EST databases with or without quality
information using QualitySNP software, select reliable SNP and prepare the loci for analysis on the Illumina GoldenGate genotyping
platform. The applicability of the pipeline was demonstrated using publicly available potato EST data, genotyping individuals
from two diploid mapping populations and subsequently mapping the SNP markers (putative genes) in both populations. Over 7000
reliable SNPs were identified that met the criteria for genotyping on the GoldenGate platform. Of the 384 SNPs on the SNP
array approximately 12% dropped out. For the two potato mapping populations 165 and 185 SNPs segregating SNP loci could be
mapped on the respective genetic maps, illustrating the effectiveness of our pipeline for SNP selection and validation. 相似文献