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991.
Agnieszka Paziewska Bozena Cukrowska Michalina Dabrowska Krzysztof Goryca Magdalena Piatkowska Anna Kluska Michal Mikula Jakub Karczmarski Beata Oralewska Anna Rybak Jerzy Socha Aneta Balabas Natalia Zeber-Lubecka Filip Ambrozkiewicz Ewa Konopka Ilona Trojanowska Malgorzata Zagroba Malgorzata Szperl Jerzy Ostrowski 《PloS one》2015,10(9)
Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing. 相似文献
992.
Jiří Šponer Michal Sabat Jaroslav V. Burda Jerzy Leszczynski Pavel Hobza Bernhard Lippert 《Journal of biological inorganic chemistry》1999,4(5):537-545
Ab initio calculations have been carried out to characterize the structure and energetics of a silver(I) complex with the
cytosine-adenine DNA base pair and an aqua ligand in the coordination sphere of Ag. In addition, we have also studied analogous
complexes with Cu(I) and Au(I), and structures in which adenine has been replaced by purine in order to investigate the structural
role of the adenine amino group. The calculations revealed that all metal-modified structures are dominated by the metal-base
interactions, while the water-metal ion interaction and many-body interligand repulsion are less important contributions.
Nevertheless, the structural role of the water molecule in the complex is quite apparent and in agreement with an earlier
crystallographic study. The metal-modified base pairs exhibit large conformational flexibility toward out-of-plane motions
(propeller twist and buckle), comparable or, in some cases, even larger than that observed in the base pairs without metal
ions. All structures have been optimized within the Hartree-Fock approximation, while interaction energies were evaluated
with the inclusion of electron correlation.
Received: 25 March 1999 / Accepted: 10 June 1999 相似文献
993.
994.
Plasmodesmata ensure the continuity of cytoplasm between plant cells and play an important part in the intercellular communication and signal transduction. During the development of the suspensor of both Sedum acre L. and Sedum hispanicum L., changes in the ultrastructure of plasmodesmata and adjoining cytoplasm are observed. Numerous simple plasmodesmata are present in the inner wall of the two-celled embryo separating the basal cell from the apical cell. From the early-globular to the torpedo stage of embryo development, the part of the wall separating the basal cell from the first layer of the chalazal suspensor cells is perforated by unusual, compound plasmodesmata. The role and the sort of transport through these plasmodesmata are discussed. 相似文献
995.
996.
Sara Agnolet Jerzy W. Jaroszewski Robert Verpoorte Dan Staerk 《Metabolomics : Official journal of the Metabolomic Society》2010,6(2):292-302
Commercial preparations of Ginkgo biloba are very complex mixtures prepared from raw leaf extracts by a series of extraction and prepurification steps. The pharmacological
activity is attributed to a number of flavonoid glycosides and unique terpene trilactones (TTLs), with largely uncharacterized
pharmacological profiles on targets involved in neurological disorders. It is therefore important to complement existing targeted
analytical methods for analysis of Ginkgo biloba preparations with alternative technology platforms for their comprehensive and global characterization. In this work, 1H NMR-based metabolomics and hyphenation of high-performance liquid chromatography, photo-diode array detection, mass spectrometry,
solid-phase extraction, and nuclear magnetic resonance spectroscopy (HPLC-PDA-MS-SPE-NMR) were used for investigation of 16
commercially available preparations of Ginkgo biloba. The standardized extracts originated from Denmark, Italy, Sweden, and United Kingdom, and the results show that 1H NMR spectra allow simultaneous assessment of the content as well as identity of flavonoid glycosides and TTLs based on a
very simple sample-preparation procedure consisting of extraction, evaporation and reconstitution in acetone-d
6. Unexpected or unwanted extract constituents were also easily identified in the 1H NMR spectra, which contrasts traditional methods that depend on UV absorption or MS ionizability and usually require availability
of reference standards. Automated integration of 1H NMR spectral segments (buckets or bins of 0.02 ppm width) provides relative distribution plots of TTLs based on their H-12
resonances. The present study shows that 1H NMR-based metabolomics is an attractive method for non-selective and comprehensive analysis of Ginkgo extracts. 相似文献
997.
Gabriele M?ller Bettina Husen Dorota Kowalik Leena Hirvel? Dariusz Plewczynski Leszek Rychlewski Josef Messinger Hubert Thole Jerzy Adamski 《PloS one》2010,5(6)
Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD 1) for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17β-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17β-HSD types 1, 2, 4, 5 and 7 but also against 17β-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17β-HSDs analyzed were observed. Especially, the rodent 17β-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17β-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution. 相似文献
998.
Rost-Roszkowska MM Poprawa I Klag J Migula P Mesjasz-Przybyłowicz J Przybyłowicz W 《Folia biologica》2010,58(3-4):209-216
Differentiation of regenerative cells in the midgut epithelium of Epilachna cf nylanderi (Mulsant 1850) (Insecta, Coleoptera, Coccinellidae), a consumer of the Ni-hyperaccumulator Berkheya coddii (Asteracae) from South Africa, has been monitored and described. Adult specimens in various developmental phases were studied with the use of light microscopy and transmission electron microscopy. All degenerated epithelial cells are replaced by newly differentiated cells. They originate from regenerative cells which act as stem cells in the midgut epithelium. Just after pupal-adult transformation, the midgut epithelium of E. nylanderi is composed of columnar epithelial cells and isolated regenerative cells distributed among them. The regenerative cells proliferate intensively and form regenerative cell groups. In each regenerative cell group the majority of cells differentiate into new epithelial cells, while some of them still act as stem cells and persist as a reservoir of cells capable for proliferation and differentiation. Because this species is an obligate monophage of plants which accumulate nickel, proliferation and differentiation of midgut stem cells follow degeneration intensively and in a typical manner. 相似文献
999.
Hydrogen sulfide (H2S) is a modulator of various physiological and pathological processes in the cardiovascular and nervous system and plays an important role in the regulation of gastrointestinal tract, liver and kidney function. The effect of the pleiotropic action of the tissue specific angiotensin-converting enzyme inhibitor (ACEI), ramipril, exceeds renin-angiotensin aldosterone system (RAAS) blockade and involves different biological mechanisms. The aim of the study is to assess the influence of ramipril on H2S production in mouse liver and kidneys. Thirty mice (CBA) of both sexes were given intraperitoneal injections of ramipril solutions--0.125 mg (5 mg/kg--group D1) and 0.25 mg (10 mg/kg--group D2) for 5 consecutive days at the same time of the day (10:30 am). The control group received physiological saline in portions of the same volume--0.2 ml. The measurements of the tissue concentration of H2S were performed using the modified spectrophotometric method of Siegel. There was a significant rise in the tissue concentration of H2S [microg/g] in livers of group D1 (2.70 +/- 0.02 vs 2.81 +/- 0.06; P = 0.03) and group D2 (2.70 +/- 0.02 vs 2.98 +/- 0.03; P < 0.001) and a significant decrease of H2S kidney tissue concentration in group D1 (3.35 +/- 0.06 vs 3.15 +/- 0.07; P = 0.02) and in group D2 (3.35 +/- 0.06 vs 2.89 +/- 0.03; P < 0.001). Our results show that ACEI ramipril affects hydrogen sulfide generation in mouse liver and kidneys. 相似文献
1000.
Chitosan was characterized by Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and elemental analysis (EA). The thin chitosan films obtained by the casting method were heated in vacuum from room temperature to 600 °C. The progress of thermal degradation and carbonization process was monitored by FTIR spectroscopy in a vacuum cell, which allows the elimination of the influence of atmospheric humidity on the chitosan and carbonizate properties. The adsorption of water on the degassed chitosan and its carbonizate as well the oxidation process was also investigated by FTIR spectroscopy. The surface morphology of initial chitosan and obtained carbonaceous material was observed using atomic force microscopy (AFM). Detailed characterization of raw material and carbonization conditions is necessary for tailoring reproducible adsorbent properties. 相似文献