Uncoupling Protein 2 and 3 Gene Polymorphisms and Their Association with Type 2 Diabetes in Asian Indians

Background: This study examined the association of -866G/A, Ala55Val, 45bpI/D, and -55C/T polymorphisms at the uncoupling protein (UCP) 3-2 loci with type 2 diabetes in Asian Indians. Methods: A case-control study was performed among 1,406 unrelated subjects (487 with type 2 diabetes and 919 normal glucose-tolerant NGT]), chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in Southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Haplotype frequencies were estimated using an expectation-maximization algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results: The genotype (P = 0.00006) and the allele (P = 0.00007) frequencies of Ala55Val of the UCP2 gene showed a significant protective effect against the development of type 2 diabetes. The odds ratios (adjusted for age, sex, and body mass index) for diabetes for individuals carrying Ala/Val was 0.72, and that for individuals carrying Val/Val was 0.37. Homeostasis insulin resistance model assessment and 2-h plasma glucose were significantly lower among Val-allele carriers compared to the Ala/Ala genotype within the NGT group. The genotype (P = 0.02) and the allele (P = 0.002) frequencies of -55C/T of the UCP3 gene showed a significant protective effect against the development of diabetes. The odds ratio for diabetes for individuals carrying CT was 0.79, and that for individuals carrying TT was 0.61. The haplotype analyses further confirmed the association of Ala55Val with diabetes, where the haplotypes carrying the Ala allele were significantly higher in the cases compared to controls. Conclusions: Ala55Val and -55C/T polymorphisms at the UCP3-2 loci are associated with a significantly reduced risk of developing type 2 diabetes in Asian Indians.

(2R,3R,4aS,6S,7S,8aS)-4a-Fluoro-8a-hydroxyperhydronaphthalene-2,3,6,7-te trayl tetraacetate

The title compound, C18H25FO9, exhibits a similar unit cell and packing to the alpha polymorph of axial 4a,8a-dihydroxyperhydronaphthalene-2,3,6,7-tetrayl tetraacetate. The carbonyl O atoms of two of the four acetate groups in the molecule are disordered over two sites with occupancy ratios of 0.59 (4):0.41 (4) and 0.57 (6):0.43 (6). Crystal packing is effected via intermolecular O-H center dot center dot center dot O hydrogen bonds, which link the tetraacetate molecules into tapes along the c axis.

(2E)-3-(4-Ethoxyphenyl)-1-(2-methyl-4-phenylquinolin-3-yl)prop-2-en-1-on e monohydrate

The title hydrate, C27H23NO2 center dot H2O, features an almost planar quinoline residue (r.m.s. deviation = 0.015 angstrom) with the benzene dihedral angle = 63.80 (7)degrees] and chalcone C-C-C-O torsion angle = -103.38 (18)degrees] substituents twisted significantly out of its plane. The configuration about the C=C bond 1.340 (2) angstrom] is E. In the crystal, molecules related by the 21 symmetry operation are linked along the b axis via water molecules that form O-H center dot center dot center dot O-c and O-H center dot center dot center dot N-q hydrogen bonds (c = carbonyl and q = quinoline). A C-H center dot center dot center dot O interaction also occurs.

A parametric method 3 (PM3) study of trans‐stilbene

We report a comparative modified neglect of diatomic overlap (MNDO), Austin method one (AM1), and parametric method 3 (PM3) study of trans‐stilbene (tS) in its ground, excited (singlet and triplet), and ionic (positive and negative polarons and bipolarons) states. We have also calculated the barrier for ring rotation about the backbone single bond. Our results show that PM3 geometries are superior to MNDO and AM1, at least for tS. PM3 predicts, in contrast with MNDO, AM1 and even ab initio 3‐21G, a coplanar structure for tS, in accordance with recent experimental data. Singlet and triplet energies obtained from heats of formation are in surprisingly good agreement with experimental data.

Inverse relationship of the dehydrogenase and ADP-ribosylation activities in sodium-nitroprusside-treated glyceraldehyde-3-phosphate dehydrogenase is coincidental

Incubation of glyceraldehyde-3-phosphate dehydrogenase (GAPD) with sodium nitroprusside (SNP) decreased its activity in concentration- and time-dependent fashion in the presence of a thiol compounds, with DTT being more effective than GSH. Both forward and backward reactions were effected. Coinciding with this, HgCl2-sensitive labelling of the protein by [32P]NAD+ also increased, indicating the stimulation of ADP-ribosylation. Treatment with SNP of GAPD samples from rabbit muscle, sheep brain and yeast inactivated the dehydrogenase activity of the three, but only the mammalian proteins showed ADP-ribosylation activity. The SNP-modified protein of rabbit muscle GAPD, freed from the reagent by Sephadex filtration showed a concentration-dependent restoration of the dehydrogenase activity on preincubation with DTT and GSH. Such thiol-treated preparations also gave increased ADP-ribosylation activity with DTT, and to a lesser extent with GSH. The SNP-modified protein was unable to catalyze this activity with the native yeast enzyme and native and heat-inactivated muscle enzyme. It was possible to generate the ADP-ribosylation activity in muscle GAPD, by an NO-independent mechanism, on dialysis in Tris buffer under aerobic conditions , and on incubating with NADPH, but not NADH, in muscle and brain, but not yeast, enzymes. The results suggest that the inverse relationship of the dehydrogenase and ADP-ribosylation activities is coincidental but not correlated

Irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by H2O2

A concentration-dependent inactivation of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase was found on reincubation of rat liver microsomal preparations with H2O2 and at lower concentrations in the presence of KCN which inhibited the contaminating catalase. The inactivation was not affected in the presence quenchers of hydroxyl radicals and singlet oxygen and was also obtained when H2O2 was added during the reaction. HMG-CoA, but not NADPH, partially protected the enzyme from H2O2-inactivation. Even at high concentration DTT was unable to reverse this inactivation. The soluble 50 kDa-enzyme was similarly inactivated by H2O2, and the tryptic-digest of the inactivated protein indicated the presence of a disulfide-containing peptide. The results support the view that H2O2 by directly acting on the catalytic domain possibly converts an active thiol group to an inaccessible disulfide and irreversibly HMG-CoA reductase.

Molecular structure of Lantadene-B&C, triterpenoids ofantana camara, red variety: Lantadene-B, 22β-angeloyloxy-3-oxoolean-12-en-28-oic acid; Lantadene-C, 22 β-(S)-2′-methyl butanoyloxy-3-oxoolean-12-en-28-oic acid

(I)Lantadene-B: C35H52O5,M r =552.80, MonoclinicC2,a=25.65(1),b=6.819(9),c=18.75(1) Å,beta=100.61(9),V=3223(5) Å3,Z=4,D x =1.14 g cm–3 CuKagr (lambda=1.5418A),mgr=5.5 cm–1,F(000)=1208,R=0.118,wR=0.132 for 1527 observed reflections withF o ge2sgr(F o ). (II)Lantadene-C: C35H54O5·CH3OH,Mr=586.85, Monoclinic,P21,a=9.822(3),b=10.909(3),c=16.120(8)Å,beta=99.82(4),V=1702(1)Å3,Z=2,D x =1.145 g cm–3, MoKagr (lambda=0.7107Å), mgr=0.708 cm–1 F(000)=644,R=0.098, wR=0.094 for 1073 observed reflections. The rings A, B, C, D, and E aretrans, trans, trans, cis fused and are in chair, chair, sofa, half-chair, chair conformations, respectively, in both the structures. In the unit cell the molecules are stabilized by O-HctdotO hydrogen bonds in both the structures, however an additional C-HctdotO interaction is observed in the case of Lantadene-C.

On the involvement of intramolecular protein disulfide in the irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by diallyl disulfide

Treatment with diallyl disulfide, a constituent of garlic oil, irreversibly inactivated microsomal and a soluble 50 kDa form of HMG-CoA reductase. No radioactivity was found to be protein-bound on treating the soluble enzyme with [35S]diallyl disulfide, indicating the absence of the mixed disulfide of the type allyl-S-S-protein. SDS-PAGE and Western blot analyses of the diallyl-disulfide-treated protein showed no traces of the dimer of the type protein-S-S-protein, but clearly indicated BME-reversible increased mobility, as expected of an intramolecular protein disulfide. The sulfhydryl groups, as measured by alkylation with iodo[2-14C]acetic acid, were found to decrease in the diallyl-disulfide-treated enzyme protein. Tryptic peptide analysis also gave support for the possible presence of disulfide-containing peptides in such a protein. It appears that diallyl disulfide inactivated HMG-CoA reductase by forming an internal protein disulfide that became inaccessible for reduction by DTT, and thereby retaining the inactive state of the enzyme.

Organometallic chemistry of diphosphazanes *1: VIII. Synthesis, spectroscopic studies and crystal structure of fac-[Mo(CO)3(MeCN)Ph2PN(iPr)P(Ph)(DMP)], and its reactions with tertiary phosphines

The reaction of fac-[Mo(CO)3(MeCN)3] with the unsymmetrical diphosphazane Ph2PN(iPr)P(Ph)(DMP) (L) gives the complex fac-[Mo(CO)3(MeCN)(L)] (2) in almost quantitative yield. The structure of the complex has been determined by an X-ray diffraction study. The compound reacts with PR3 (where R = Ph, OPh) to give fac-[Mo(CO)3(PR3)(L)] (3a, 4a), which undergoes an intramolecular isomerization to afford mer-[Mo(CO)3(PR3)(L)] (3b, 4b). Synthesis of cis-[Mo(CO)4(L)] (1) and fac-[MO(CO)3L] (2a) and their spectroscopic data are also reported.

Annales Societatis zoologicae-botanicae Fennicae Vanamo tom. 3

Kielet suomi ja saksa.

Insights into conformational and packing features in a series of aryl substituted ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

The supramolecular structures of eight aryl protected ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine- 5-carboxylates have been analyzed to determine the role of different functional groups on the molecular geometry, conformational characteristics and the packing of these molecules in the crystal lattice. Out of these the para fluoro substituted compound on the aryl ring exhibits conformational polymorphism, due to the different conformation of the ester moiety. This behaviour has been characterized using both powder and single-crystal X-ray diffraction, optical microscopy and differential scanning calorimetry performed on both these polymorphs. The compounds pack via the cooperative interplay of strong N-H center dot center dot center dot O=C intermolecular dimers and chains forming a sheet like structure. In addition, weak C-H center dot center dot center dot O=C and C-H center dot center dot center dot pi interactions impart additional stability to the crystal packing.

Microwave Irradiation Assisted Method for the Rapid Synthesis of fine Particles of alpha Al2O3 And alpha (Al1-XCrx)(2)O-3 And Their Coatings on Si(100)

Chromium substituted beta diketonate complexes of aluminium have been synthesized and employed as precursors for a novel soft chemistry process wherein microwave irradiation of a solution of the complex yields within minutes well crystallized needles of alpha (Al1 XCrx)(2)O-3 measuring 20 30 nm in diameter and 50 nm long By varying the microwave irradiation parameters and using a surfactant such as polyvinyl pyrrolidone the crystallite size and shape can be controlled and their agglomeration prevented These microstructural parameters as well as the polymorph of the Cr substituted Al2O3 formed may also be controlled by employing a different complex Samples of alpha (Al1 XCrx)(2)O-3 have been characterized by XRD FTIR and TEM The technique results in material of homogeneous metal composition, as shown by EDAX and can be adjusted as desired The technique has been extended to obtain coatings of alpha (Al1 XCrx)(2)O-3 on Si(100)

Purification of 3,5-Dichlorocatechol 1,2-Dioxygenase, a Nonheme Iron Dioxygenase and a Key Enzyme in the Biodegradation of a Herbicide, 2,4-Dichlorophenoxyacetic acid (2,4-D), from Pseudomonas cepacia CSV90

An enzyme which cleaves the benzene ring of 3,5-dichiorocatechol has been purified to homogeneity from Pseudomonas cepacia CSV90, grown with 2,4-dichlorophenoxyacetic acid (2,4-D) as the sole carbon source. The enzyme was a nonheme ferric dioxygenase and catalyzed the intradiol cleavage of all the examined catechol derivatives, 3,5-dichlorocatechol having the highest specificity constant of 7.3 μM−1 s−1 in an air-saturated buffer. No extradiol-cleaving activity was observed. Thus, the enzyme was designated as 3,5-dichlorocatechol 1,2-dioxygenase. The molecular weight of the native enzyme was ascertained to be 56,000 by light scattering method, while the Mr value of the enzyme denatured with 6 M guanidine-HCl or sodium dodecyl sulfate was 29,000 or 31,600, respectively, suggesting that the enzyme was a homodimer. The iron content was estimated to be 0.89 mol per mole of enzyme. The enzyme was deep red and exhibited a broad absorption spectrum with a maximum at around 425 nm, which was bleached by sodium dithionite, and shifted to 515 nm upon anaerobic 3,5-dichlorocatechol binding. The catalytic constant and the Km values for 3,5-dichlorocatechol and oxygen were 34.7 s−1 and 4.4 and 652 μM, respectively, at pH 8 and 25°C. Some heavy metal ions, chelating agents and sulfhydryl reagents inhibited the activity. The NH2-terminal sequence was determined up to 44 amino acid residues and compared with those of the other catechol dioxygenases previously reported.

Solvation and axial ligation properties of (2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetraphenylporphyrinato)zinc(II)

he solvation of (2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetraphenylporphyrinato)zinc(II)[Zn(obtpp)], in twelve different solvents results in large red shifts of the B and Q bands of the porphyrin accompanied by enhanced absorbance ratios of the Q bands. These observations are ascribed to the destabilisation of the highest occupied molecular orbital a2u of the porphyrin arising from a flow of charge from the axial ligand to the porphyrin ring through the zinc(II) ion. The binding constants of adducts of [Zn(obtpp)] with neutral bases have been found to be an order of magnitude greater than those observed for the corresponding adducts of (5,10,15,20-tetraphenylporphyrinato)-zinc and vary in the order piperidine > imidazole > pyridine > 3-methylpyridine > pyridine-3-carbaldehyde. The enhanced binding constants and large spectral shifts are interpreted in terms of the electrophilicity of [Zn(obtpp)] induced by the electron-withdrawing bromine substituents in the porphyrin core. The structure of [Zn(obtpp)(PrCN)2] has been determined; it reveals six-co-ordinated zinc(II) with two long Zn–N distance [2.51(4), 2.59(3)Å]. The porphyrin is non-planar and displays a saddle-shaped conformation.