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Combined Series (combined + series)

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Life Sciences	50%

Selected Abstracts

Capillary electrophoresis analysis of glucooligosaccharide regioisomers

ELECTROPHORESIS, Issue 6 2004
Gilles Joucla
Abstract Complex gluco-oligosaccharide mixtures of two regioisomer series were successfully separated by CE. The gluco-oligosaccharide series were synthesized, employing a dextransucrase from Leuconostoc mesenteroides NRRL B-512F, by successive glucopyranosyl transfers from sucrose to the acceptor glucose or maltose. The glucosyl transfer to both acceptors, occurring through the formation of ,1,6 linkages, differed for the two series only in the glucosidic bond to the reducing end namely ,1,6 or ,1,4 bond for glucose or maltose acceptor, respectively. Thus, the combination of the two series results in mixed pairs of gluco-oligosaccharide regioisomers with different degrees of polymerization (DP). These regioisomer series were first derivatized by reductive amination with 9-aminopyrene-1,4,6-trisulfonate (APTS). Under acidic conditions using triethyl ammonium acetate as electrolyte, the APTS-gluco-oligosaccharides of each series were separated enabling unambiguous size determination by coupling CE to electrospray-mass spectrometry. However, neither these acidic conditions nor alkaline buffer systems could be adapted for the separation of the gluco-oligosaccharide regioisomers arising from the two combined series. By contrast, increased resolution was observed in an alkaline borate buffer, using differential complexation of the regioisomers with the borate anions. Such conditions were also successfully applied to the separation of glucodisaccharide regioisomers composed of ,1,2, ,1,3, ,1,4, and ,1,6 linkages commonly synthesized by glucansucrase enzymes. [source]

Calbindin-1 association and Parkinson's disease

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2010
A. I. Soto-Ortolaza
Background and purpose:, Calcium levels have been proposed to play an important role in the selective vulnerability of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Recently, an association was reported between the calcium buffer, calbindin (rs1805874) and risk of PD in a Japanese patient,control series. Methods:, We genotyped rs1805874 in four independent Caucasian patient,control series (1543 PD patients, 1771 controls). Results:, There was no evidence of an association between rs1805874 and disease risk in individual populations or in the combined series (odds ratio: 1.04, 95% CI: 0.82,1.31, P = 0.74). Discussion:, Our study shows there is no association between rs1805874 and risk for PD in four Caucasian populations. This suggests the effect of calbindin on PD risk displays population specificity. [source]

QSAR Analysis of 2,3-Diaryl Benzopyrans/Pyrans as Selective COX-2 Inhibitors Based on Semiempirical AM1 Calculations

MOLECULAR INFORMATICS, Issue 8 2004
Sivaprakasam Prasanna
Abstract Quantitative structure-activity relationship (QSAR) analysis was performed on a combined series of 2,3 diaryl benzopyrans and pyrans for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations based on semiempirical, Austin Model-1 (AM1) calculations reveal that electronic and hydophobic interactions are primarily responsible for COX-2 enzyme-ligand interaction. The derived QSAR model aided by residual analysis demonstrated that the COX-2 inhibitory activity is highly correlated with the electronic descriptors, lowest unoccupied molecular orbital (ELUMO), Dipole-Z and hydrophobicity of the molecules. The conclusion can be drawn that more hydrophobic, electron-withdrawing substituents at 3rd aromatic ring of the lead structure improves activity. The lesser the Z component the ligand has, the more correct its orientation towards the COX-2 binding site. The derived QSAR model shows good internal (exemplified through leave one out-q2=0.786) and external (r=0.5737) predictive ability for a test set and can be used in designing better selective COX-2 inhibitors among these congeners in future. [source]

Maternal serum biochemistry at 11,13+6 weeks in relation to the presence or absence of the fetal nasal bone on ultrasonography in chromosomally abnormal fetuses: an updated analysis of integrated ultrasound and biochemical screening

PRENATAL DIAGNOSIS, Issue 11 2005
Simona Cicero
Abstract Background Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free ,-hCG and pregnancy associated plasma protein-A (PAPP-A) at 11,13+6 weeks of gestation is associated with a detection rate of 90%, for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21 the nasal bone is not visible at the 11,13+6 week scan and that the frequency of absence of nasal bone differs in different ethnic groups. In addition, there is a relationship between absent nasal bone and nuchal translucency thickness. In a preliminary study we showed that while PAPP-A levels were lower and free ,-hCG levels were higher in trisomy 21 fetuses with an absent nasal bone, this difference was not statistically different. In fetuses with trisomy 13 and trisomy 18, there is also a high (57 and 67%) incidence of an absent nasal bone. The aim of this present study was to extend our examination of whether the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone in cases with trisomy 21 and to ascertain if any differences exist in cases with trisomies 13 and 18. Methods This study data comprised 100 trisomy 21 singleton pregnancies at 11,13+6 weeks of gestation from our previous study and an additional 42 cases analysed as part of routine OSCAR screening. A total of 34 cases with trisomy 18 and 12 cases with trisomy 13 were also available. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free ,-hCG and PAPP-A were measured using the Kryptor rapid random access immunoassay analyser (Brahms Diagnostica AG, Berlin). The distribution of maternal serum free ,-hCG and PAPP-A in chromosomally abnormal fetuses with absent and present nasal bone was examined. Results The nasal bone was absent in 29 and present in 13 of the new trisomy 21 cases and in 98 (69%) and 44 respectively in the combined series. For the trisomy 18 cases, the nasal bone was absent in 19 (55.9%) cases and in 3 (25%) of cases of trisomy 13. There were no significant differences in median maternal age, median gestational age, NT delta, free ,-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone, and similarly for those with trisomies 13 or 18. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 96% of cases with trisomy 21. For a false-positive rate of 0.5%, the detection rate was 88%. Conclusions There is no relationship between an absent fetal nasal bone and the levels of maternal serum PAPP-A or free ,-hCG in cases with trisomies 13, 18 or 21. An integrated sonographic and biochemical test at 11,13+6 weeks can potentially identify about 88% of trisomy 21 fetuses for a false-positive rate of 0.5%. Copyright © 2005 John Wiley & Sons, Ltd. [source]