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1.
均衡的体成分构成对维持机体的健康状态具有重要作用,体成分受遗传与环境因素的共同影响。多巴胺参与摄食、运动及认知等活动的调节,多巴胺D3受体(DRD3)对多巴胺神经通路起关键调节作用,进而对摄食功能发挥作用,从而可能对体成分产生影响。为了解遗传与环境因素对双生子儿童体成分的影响,并探讨DRD3基因单核苷酸多态性(SNP)与体成分的相关性,对160对4-12岁双生子肱三头肌皮褶厚度( d1)、肩胛下皮褶厚度( d2)、髂前上棘位皮褶厚度( d3)和体质量( m)进行了测量,计算 d4( d1+ d2)、 d5( d2/ d1),体脂率( Pf)、瘦体质量( ml);从口腔拭子中提取全基因组DNA;通过Amp FISTR Sino filerPlus试剂盒分析确定卵型;采用SNaPshot技术对DRD3基因4个SNP位点进行检测;使用Mx软件估算各指标遗传度;运用广义估计方程模型分析各指标与DRD3基因SNP的相关性。校正年龄效应后,除个别指标( d3, ml)外,男女生指标遗传度( h)学龄前期总体偏低,且某些指标( d2, d4, Pf, ml)的遗传度存在一定的性别差异。 d2分别与rs324029、rs226082存在相关( P<0.05); d3分别与rs2134655、rs226082存在相关( P<0.05); d5分别与rs2134655、rs167771存在相关( P<0.05); Pf分别与rs226082、rs167771存在相关( P<0.05); ml分别与rs2134655、rs226082、rs167771存在相关( P<0.05)。本研究结果表明,遗传和环境因素对儿童体成分发育均有影响,但遗传效应可能存在一定的发育阶段和性别差异;DRD3基因SNPs与儿童的体成分可能存在一定的相关性。 相似文献
2.
Complexes of type A 4[VO(tart)] 2· nH 2O, where A = Rb or Cs and tart = d, l-tartrate(4−) ( n = 2) or d,d-tartrate(4−) ( n = 2 for Rb and n = 3 for Cs), were prepared from an aqueous mixture of V 2O 5, AOH and H 4tart. These complexes were studied by single-crystal X-ray diffraction methods: Rb 4[VO( d, l-tart)] 2·2H 2O, space group P1 with a = 8.156(1), b = 8.246(1), c = 8.719(1)Å, = 66.09(1)°, β = 65.07(1)°, γ = 82.40(1)°, Z = 2, 1917 observed reflections, and final Rw = 0.035; Cs 4[VO( d, l-tart)] 2·2H 2O, space group P21/ c with a = 9.350(1), b = 13.728(2), c = 8.479(1)Å, β = 106.77(1)°, Z = 4, 2235 observed reflections, and final Rw = 0.054; Rb 4[VO( d, d-tart)] 2·2H 2O, space group P4122 with a = 8.072(1), c = 32.006(3)Å, Z = 8, 1014 observed reflections and final Rw = 0.038; Cs 4[VO( d, d-tart)] 2·3H 2O, space group P122 with a = 8.184(1), c = 33.680(5)Å, Z = 8, 1310 observed reflections, and final Rw = 0.063. Bulk magnetic susceptibility data (1.5–300 K) for these compounds and A 4[VO l, l-tart)] 2· nH 2O (A = Rb, Cs) were obtained on polycrystalline samples. These data were analyzed in terms of a Van Vleck exchange coupled S = 1/2 model which was modified to include an interdimer exchange parameters Θ. Analysis of the low-temperature (1.5–20 K) susceptibility data gave 2 J = +1.30 cm −1 and Θ = −1.86 K for Rb 4[VO( d, l-tart)] 2·2H 2O, 2 J = +1.16 cm −1 and Θ = −1.69 K for Cs 4[VO( d, l-tart)] 2·2H 2O, 2 J = +1.90 cm −1 and Θ = −0.82 K for Rb 4[VO( d, d-tart)] 2·2H 2O, 2 J = +2.04 cm −1 and Θ = −0.80 K for Rb 4[VO( l, l-tart)] 2·2H 2O, 2 J = +1.52 cm −1 and Θ = −0.25 K for Cs 4[VO( d, d-tart)] 2·3H 2O, and 2 J = +1.64 cm −1 and Θ = −0.31 K for Cs 4[VO( l, l-tart)] 2·3H 2O. These results suggest the magnitudes of intradimer (ferromagnetic and interdimer (antiferromagnetic) exchange interactions are similar in these complexes, as observed for the analogous Na salts. 相似文献
3.
The shear piezoelectricity was observed in oriented films of poly-β-hydroxybutyrate (PHB) and copolymers of β-hydroxybutyrate (HB) and β-hydroxyvalerate (HV). The piezoelectric stress constant 3 14 = e′ 14 − ie″ 14 (polarization/strain), the piezoelectric strain constant d14 = d′ 14 − id″ 14 (polarization/stress), the elastic constant c = c′ + ic″ and the dielectric constant = ′ − i″ were determined at a frequency of 10 Hz over a temperature range from −150° to +150°C. Piezoelectric relaxations as well as elastic and dielectric relaxations were clearly observed at the glass transition temperature of about 15°C. In order to evaluate the piezoelectric constants ( e2 and d2) for the piezoelectric phase which consists of the crystalline region and the oriented non-crystalline region, a spherical dispersion two phase model was utilized. Assuming the appropriate fixed values for the elastic and dielectric constants in the piezoelectric phase, d2 and d2 were calculated as a function of temperature. For a PHB and a copolymer (17 HV/83 HB), e2 and d2 showed relaxations, leading to a conclusion that the instantaneous piezoelectric constant in the crystalline phase is constant independent of temperature but the piezoelectric constant in the oriented non-crystalline phase is relaxational and has the opposite sign. For a copolymer (25 HV/75 HB) and a chloroform treated copolymer (17 HV/83 HB), e2 and d2 were constant independent of temperature, indicating that the oriented non-crystalline phase has disappeared owing to the increased molecular flexibility due to copolymerization or annealing in chloroform vapour. 相似文献
4.
Growth-promoting effects of gibberellins and their glucosides isolated from immature seeds of Japanese morning glory ( Pharbitis nil) were compared in six bioassay systems. GA 3 glucoside exhibited much less activity than GA 3 in the dwarf rice (under aseptic conditions), dwarf maize ( d1, d2 and d5), cucumber and dwarf pea assays. GA 8, GA 26, GA 27 and GA 29 showed low activities in all the bioassay systems, while their glucosides were even less active. Thus gibberellin glucosides do not appear to be active in growth regulation. 相似文献
5.
1. Cyanide causes a slow disappearance of the oxidized band (648 nm) of cytochrome d in particles of Azotobacter vinelandii and inhibits the appearance of the reduced band (631 nm). No effect of cyanide is found on the reduced band of cytochrome d. 2. The kinetics of the disappearance of the 648-nm band of cytochrome d with excess cyanide deviates from first-order kinetics at lower temperatures (22 °C) indicating that at least two conformations of the enzyme are involved. At higher temperatures (32 °C) the observed kinetics of the cyanide reaction are first order with a kon = 0.7 M−1·s−1 and with an estimated koff of approximately 5·10−5 s−1. 3. The value of the koff (7·10−4−14·10−4 s−1 at 32 °C) determined from the rate of reduction of cyanocytochrome d by Na2S2O4 or NADH is one order of magnitude larger than the koff value found when the enzyme is in its oxidized state. 4. No effect of cyanide is found on the spectrum of cytochrome a1. 相似文献
6.
Two novel complexes Co(N 3) 2(PNN) 4 (I) and Mn(N 3) 2(PNN) 2(CH 3OH)(C 2H 5OH) (II) (PNN=2-( p-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3–oxide) were synthesized and characterized by infrared spectra, elemental analyses and UV–Vis techniques. The crystal structures of both complexes have been determined by X-ray diffraction analysis. Complex I is a neutral five-spin system and adopts a centrosymmetric tetragonally compressed octahedral coordination geometry in which Co(II) ion is coordinated to four radicals through the nitrogen atoms of the pyridine rings and two azide anions occupying the axial positions. Complex II is a neutral three-spin system in which Mn(II) ion is bound to two azide anions, two alcohol molecules and two radicals through the nitrogen atom of pyridine rings, and shows one-dimensional chain structure via hydrogen bonds ( dON=2.78 Å). The magnetic properties for complexes I and II have been investigated in the temperature range 2–300 K. A theoretical model has been developed for complex I and the magnetic behaviors for both complexes have been discussed in detail. 相似文献
7.
The 2-isopropyl thiazolyl group is a highly optimized P 3 ligand for C2 symmetry-based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we report that incorporation of this P 3 ligand into a piperazine hydroxyethylamine series also yielded novel, highly potent inhibitors. In tissue culture assays, the presence of human serum was less deleterious to the activity of these inhibitors than to that of ritonavir. Furthermore, potent activity against ritonavir resistant HIV was observed. 相似文献
8.
A set of HIV protease inhibitors represented by compound 2 has previously been described. Structural and conformational analysis of this compound suggested that conformational restriction of the P 1/P 2 portion of the molecule could lead to a novel set of potent protease inhibitors. Thus, probe compounds 3–7 were designed, synthesized, and found to be potent inhibitors of HIV protease. 相似文献
9.
Factor Xa (FXa) is a serine protease which plays a pivotal role in the coagulation cascade. The inhibition of FXa has received great interest as a potential target for the development of new antithrombotic drug. Herein we describe a series of novel 7-amidino-2-naphthoanilide and 7-amidino-2-naphthalensulfonanilide derivatives which are potent FXa inhibitors. These scaffolds are rigid and are allowed to adopt an L-shape conformation which was estimated as the active conformation based on a docking study of YM-60828 with FXa. Optimization of the side chain at the central aniline nitrogen of 7-amidino-2-naphthoanilide has led to several potent and orally active FXa inhibitors. 5h (YM-169964), the best compound of these series, showed potent FXa inhibitory activity (IC(50)=3.9nM) and effectively prolonged prothrombin time by 9.6-fold ex vivo at an oral dose of 3mg/kg in squirrel monkeys. 相似文献
10.
Factor Xa (FXa) is a trypsin-like serine protease involved in the coagulation cascade and has received great interest as a potential target for the development of new antithrombotic agents. Most of amidine-type FXa inhibitors reported have been found to show extremely poor oral bioavailability. Compound 1 is one of the first reported non-amidine type FXa inhibitors. To discover novel and orally active FXa inhibitors, we investigated flexible linear linkers between the 6-chloronaphthalene ring and the 1-(pyridin-4-yl)piperidine moiety of 1 and found the orally active sulfonylalkylamide 2f with an FXa IC(50) of 0.05 microM, comparable with that of 1. Further modification to reduce the CYP3A4 inhibitory activity of 2f resulted in the potent, selective, and orally active 2-methylpyridine analogue 2s (FXa IC(50) of 0.061 microM), for which the liability of CYP3A4 inhibition was significantly weakened compared to 2f. Compound 2s also showed long lasting anticoagulant activity in cynomolgus monkeys. 相似文献
11.
Photosystem I (PSI) is a large protein supercomplex that catalyzes the light-dependent oxidation of plastocyanin (or cytochrome c6) and the reduction of ferredoxin. This catalytic reaction is realized by a transmembrane electron transfer chain consisting of primary electron donor (a special chlorophyll (Chl) pair) and electron acceptors A 0, A 1, and three Fe 4S 4 clusters, F X, F A, and F B. Here we report the PSI structure from a Chl d-dominated cyanobacterium Acaryochloris marina at 3.3 Å resolution obtained by single-particle cryo-electron microscopy. The A. marina PSI exists as a trimer with three identical monomers. Surprisingly, the structure reveals a unique composition of electron transfer chain in which the primary electron acceptor A 0 is composed of two pheophytin a rather than Chl a found in any other well-known PSI structures. A novel subunit Psa27 is observed in the A. marina PSI structure. In addition, 77 Chls, 13 α-carotenes, two phylloquinones, three Fe-S clusters, two phosphatidyl glycerols, and one monogalactosyl-diglyceride were identified in each PSI monomer. Our results provide a structural basis for deciphering the mechanism of photosynthesis in a PSI complex with Chl d as the dominating pigments and absorbing far-red light. 相似文献
12.
Renin inhibitors containing a 4,5- or a 3,5-dihydroxy-2-substituted-6-phenylhexanamide fragment at the P 2---P 3 sites have been prepared and evaluated. The four possible diastereomeric diols of the two series of inhibitors were synthesized to determine the optimal configuration of the carbinol centers for these replacements. The most potent inhibitors of each series, 1a and 2c have a molecular weight of only 503 and IC 50 values of 23 and 20 nM in a human plasma renin assay at pH 6.0. Their very low aqueous solubility limited their further evaluation. The efficacy of these P 2---P 3 replacements is a result of their ability to maintain the important hydrogen-bonds with the enzyme. Due to conformational differences with the dipeptide, adjustment at the P 2 side chain was required. These 4,5- and 3,5-dihydroxyhexanamide segments could be seen as novel N-terminal dipeptide replacements. 相似文献
13.
Possible mechanisms for the silylformylation of 1-alkynes catalyzed by Rh 2Co 2(CO) 12 are investigated. Novel Rh-Co mixed metal complexes, (PhMe 2Si) 2Rh(CO)nCo(CO) 4 ( n = 2 or 3) (3) and RhCo(HC≡CBu n)(CO) 5 (5), are found to play important roles in this catalysis. The reaction of 3 with 1-hexyne and HSiMe 2Ph at ambient temperature and pressure of CO gives n-BuC(CHO)=CHSiMe 2Ph (1a, Z/E = 95/5), (PhMe 2Si) 2Rh(CO) 3Co(CO) 4 (3-B) and an Rh-Co mixed metal butterfly complex, h 2Co 2(HC≡CBu n)(CO) 10 (4). The reaction of 5 with 1-hexyne and HSiMe 2Ph under the same ambient conditions affords 1a (100% Z) very cleanly as the sole reaction product. The crossover experiments u sing RhCo(DC≡CBu n)(CO) 5(5- d), 1-hexyne-1 d and DSiMe 2Ph strongly support the mixed metal bimetallic catalysis and involvement of bis(alkyne)-Rh-Co species. The most plausible catalytic cycle of silylformylation which can accommodate all the observed results is proposed. 相似文献
14.
A novel class of substrate-based β-secretase (BACE1) inhibitors containing a hydroxymethylcarbonyl (HMC) isostere was designed and synthesized. Phenylnorstatine [(2 R,3 S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] was an effective transition-state mimic at the P 1 position. Structure–activity relationships (SARs) of the P 3–P 3′ positions of BACE1 inhibitors were studied. 相似文献
15.
We have recently reported the discovery of orally active sulfonylalkylamide Factor Xa (FXa) inhibitors, as typified by compound 1 (FXa IC(50)=0.061 microM). Since the pyridylpiperidine moiety was not investigated in our previous study, we conducted detailed structure-activity relationship studies on this S4 binding element. This investigation led to the discovery of piperazinylimidazo[1,2-a]pyridine 2b as a novel and potent FXa inhibitor (FXa IC(50)=0.021 microM). Further modification resulted in the discovery of 2-hydroxymethylimidazo[1,2-a]pyridine 2e (FXa IC(50)=0.0090 microM), which was found to be a selective and orally bioavailable FXa inhibitor with reduced CYP3A4 inhibition. 相似文献
16.
The toxicity of cinnamon, Cinnamomum zeylanicum, bark essential oil compounds against eggs and adult females of human head louse, Pediculus humanus capitis, was examined using direct contact and vapour phase toxicity bioassays and compared with the lethal activity of their related compounds, benzyl alcohol, cinnamic acid, cinnamyl acetate, 4-hydroxybenzaldehyde and salicylaldehyde, as well as two widely used pediculicides, d-phenothrin and pyrethrum. In a filter-paper contact toxicity bioassay with female lice at 0.25 mg/cm 2, benzaldehyde was 29- and 27-fold more toxic than pyrethrum and d-phenothrin, respectively, as judged by median lethal time (LT 50) values. Salicylaldehyde was nine and eight times more active than pyrethrum and d-phenothrin, respectively. Pediculicidal activity of linalool was comparable with that of d-phenothrin and pyrethrum. Cinnamomum bark essential oil was slightly less effective than either d-phenothrin or pyrethrum. Benzyl alcohol and ( E)-cinnamaldehyde exhibited moderate pediculicidal activity. After 24 h of exposure, no hatching was observed with 0.063 mg/cm 2 salicylaldehyde, 0.125 mg/cm 2 benzaldehyde, 0.5 mg/cm 2 Cinnamomum bark essential oil, 1.0 mg/cm 2 ( E)-cinnamaldehyde, and 1.0 mg/cm 2 benzyl cinnamate. Little or no ovicidal activity was observed with d-phenothrin or pyrethrum. In vapour phase toxicity tests with female lice, benzaldehyde and salicylaldehyde were much more effective in closed containers than in open ones, indicating that the mode of delivery of these compounds was largely due to action in the vapour phase. Neither d-phenothrin nor pyrethrum exhibited fumigant toxicity. Cinnamomum bark essential oil and test compounds described merit further study as potential pediculicides or ovicides for the control of P. h. capitis. 相似文献
17.
The reaction between a cytochrome oxidase from Pseudomonas aeruginosa and oxygen has been studied by a rapid mixing technique. The data indicate that the heme d1 moiety of the ascorbate-reduced enzyme is oxidized faster than the heme c component. The oxidation of heme d1 is accurately second order with respect to oxygen and has a rate constant of 5.7 · 10 4 M −1 · s −1 at 20 °C. The oxidation of the heme c has a first-order rate constant of about 8 s −1 at infinite concentration of O 2. The results indicate that the rate-limiting step is the internal transfer of electrons from heme c to heme d1. These more rapid reactions are followed by more complicated but smaller absorbance changes whose origin is still not clear. The reaction of ascorbate-reduced oxidase with CO has also been studied and is second order with a rate constant of 1.8 · 104 M−1 · s−1. The initial reaction with CO is followed by a slower reaction of significantly less magnitude. The equilibrium constant for the reaction with CO, calculated as a dissociation constant from titrimetric experiments with dithionite-reduced oxidase, is about 2.3 · 10−6 M. From these data a rate constant of 0.041 s−1 can be calculated for the dissociation of CO from the enzyme. 相似文献
18.
A series of electrophilic glutamine analogues based on 6-diazo-5-oxo-norleucine has been prepared, using novel synthetic routes, and evaluated as inhibitors of Escherichia coli. glucosamine synthetase. The γ-dimethylsulphonium salt analogue of glutamine was found to be one of the most potent inactivators of this enzyme yet reported, with an apparent second order rate constant ( k2/ Ki) of 3.5×10 5 M −1 min −1. 相似文献
19.
Crystal structure and evolving SAR considerations of potent, selective benzylsulfonamide lactam thrombin inhibitors and related serine protease inhibitors have led to the design of novel thrombin inhibitors 1a-g, featuring hydrophobic, basic, P 4-alkylaminolactam scaffolds that serve as novel types of P 3---P 4 dipeptide mimics. The design, synthesis, and biological activity of these targets is presented. 相似文献
20.
Efficient syntheses of structurally novel 4-substituted benzo[ b]thiophene-2-carboxamidmes 1–3, which selectively inhibit urokinase-type plasminogen activator (uPA) with IC 50 values of 70–320 nM, are described. The key intermediate, methyl 4-iodobenzo[ b]thiophene-2-carboxylate (7), is prepared from 3-fluoroiodobenzene in two steps in 70% overall yield via fluorine-directed metalation/formylation and subsequent thiophene annulation. Amidination of ester 7 gives the 320 nM inhibitor 1. Palladium-catalyzed arylacetylene and vinyl stannane couplings with ester 7 or 4-iodobenzo[ b]thiophene-2-carbonitrile (16, derived from 7), respectively, followed by amidination leads to the more potent inhibitors 2 (IC 50 = 133 nM) and 3 (IC 50 = 70 nM). These compounds represent an important new class of synthetic uPA inhibitors, with carboxamidine 3 being the most potent selective inhibitor currently described in the literature. 相似文献
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