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161.
Asma Mechakra Yohann Vincent Philippe Chevalier Gilles Millat Eckhard Ficker Marek Jastrzebski Hugo Poulin Valérie Pouliot Mohamed Chahine Georges Christé 《Gene》2014
Background
A variant of the ether-à-go-go related channel (hERG), p.Arg148Trp (R148W) was found at heterozygous state in two infants who died from sudden infant death syndrome (SIDS), one with documented prolonged QTc and Torsade de Pointes (TdP), and in an adult woman with QTc > 500 ms, atrioventricular block and TdP. This variant was previously reported in cases of severe ventricular arrhythmia but very rarely in control subjects. Its classification as mutation or polymorphism awaited electrophysiological characterization.Methods
The properties of this N-terminal, proximal domain, hERG variant were explored in Xenopus oocytes injected with the same amount of RNA encoding for either hERG/WT or hERG/R148W or their equimolar mixture. The human ventricular cell (TNNP) model was used to test the effects of changes in hERG current.Results
R148W alone produced a current similar to the WT (369 ± 76 nA (mean ± SEM), n = 13 versus 342 ± 55 nA in WT, n = 13), while the co-expression of 1/2 WT + 1/2 R148W lowered the current by 29% versus WT (243 ± 35 nA, n = 13, p < 0.05). The voltage dependencies of steady-state activation and inactivation were not changed in the variant alone or in co-expression with the WT. The time constants of fast recovery from inactivation and of fast and slow deactivation analyzed between − 120 and + 20 mV were not changed. The voltage-dependent distribution of the current amplitudes among fast-, slow- and non-deactivating fractions was unaltered. A 6.6% increase in APD90 from 323.5 ms to 345 ms was observed using the human cardiac ventricular myocyte model.Conclusions
Such a decrease in hERG current as evidenced here when co-expressing the hERG/R148W variant with the WT may have predisposed to the observed long QT syndrome and associated TdP. Therefore, the heterozygous carriers of hERG/R148W may be at risk of cardiac sudden death. 相似文献162.
Aim The global distribution of the European species of Melanelia Essl. (Lichenes: Parmeliaceae) was investigated in order to understand their distribution patterns against the background of ecogeographical and historical factors. Location The location of the study is global, with a local emphasis on Europe. Methods Geographical distribution and ecology of the species were investigated on the basis of herbarium studies and data from the literature as well as field observations. Distribution maps were created with ArcView GIS. The distribution patterns are expressed as three‐dimensional ‘areal formulas’, regarding zonal distribution, altitudinal range and oceanicity, using a previously described method. The observed distribution patterns are discussed on the basis of their analogies with vascular plants and with respect to the ecogeographical vs. historical factors reflected by them. Results With the exception of one species that is endemic to Europe, all species studied occur in both northern continents. A number of species have tropical‐alpine outposts, and two species occur also in extratropical zones of the southern hemisphere. Arctic and boreal distributions are circumpolar, while in the southern holarctic zones an affinity to the western sides of both northern continents is frequent. Main conclusions The distribution patterns appear to be mainly determined by contemporary ecogeographical factors. Most species probably have largely filled their potential distribution, at least within the Holarctic. Thus, the geographical origin and dispersal history of a species cannot reliably be reconstructed; they can be dissimilar in different species with similar distributions. 相似文献
163.
Increasing litter sizes in modern swine production have raised an urgent need for artificial rearing strategies and formula feeding. The current experiment was conducted to study the influence of formula trace element concentration according to recommendations for weaned piglets on the mRNA concentration of zinc (Zn)-related genes in the jejunum, liver and pancreas of neonatal piglets. Eight artificially reared piglets were fed a cow-milk-based formula (Group FO) containing 100 mg Zn/kg dry matter. Eight of their sow-reared littermates (Group SM) were used as control. After 14 d, all 16 piglets were killed and the jejunum, liver and pancreas were evaluated for Zn, copper, manganese (Mn) and iron (Fe) concentration and mRNA concentration of metal and Zn-specific transporters, metallothioneins (MT) and interleukin 6 (IL-6). In Group FO the Zn concentration in liver tissue was increased (p < 0.05). Furthermore, Fe and Mn concentrations in liver and jejunal tissue were higher (p < 0.05) in Group FO, whereas neither Zn transporters nor MT in jejunal and pancreatic tissue showed differences between both groups. In the liver of Group FO, MT mRNA concentration was higher (p < 0.05), whereas Zn transporter protein 1 and divalent metal-ion transporter 1 (DMT1) mRNA concentration was lower (p < 0.05). Besides Zn-induced expression of transporters and MT, the significantly increased IL-6 expression in Group FO suggests the involvement of cytokine-mediated Mn and Fe sequestration in the liver and jejunum. The results revealed that dietary trace element concentration used in the study likely exceeded the requirements of neonatal pigs as reflected by homeostatic counter-regulation in different organs. 相似文献
164.
165.
目的:本研究旨在探讨扶正化瘀组分复方的抗肝纤维化作用及其作用机制。方法:采用DMN诱导小鼠肝纤维化模型,以扶正化瘀方为阳性对照。以天狼猩红染色和羟脯氨酸含量评估肝纤维化程度;肝脏微血管成像和CD31标记微血管密度评价肝脏血管新生;western blot法检测肝组织VEGF-R2表达;通过计数转基因斑马鱼功能性节间血管数和碱性磷酸酶活性验证药物对血管的影响。结果:扶正化瘀组分复方可显著改善纤维化小鼠血清肝功能(P<0.01):减少肝组织胶原沉积(P<0.01);减少肝脏微血管数量(P<0.01);下调VEGFR2蛋白表达(P<0.01);抑制斑马鱼碱性磷酸酶活性。结论:扶正化瘀组分复方具有抑制DMN诱导小鼠肝纤维化模型肝组织纤维化的作用,其作用机制可能与抑制血管新生有关。 相似文献
166.
The results of some recent Monte Carlo simulations (Bhuiyan et al. J. Electroanal. Chem., in press) for the electric double layer formed by rigid ions of equal diameter (the solute) in a continuum dielectric (the solvent), next to a uniformly charged planar hard wall are examined. A contact value formula for the sum of the density profiles of this system has long been known (Henderson et al. J. Electroanal. Chem. 102, 315 (1979)). Here we propose a simple formula for the contact value of the charge profile in the limit of low electrode charge density. The evidence obtained from the aforementioned simulations supports this formula. 相似文献
167.
168.
为了提高白及组培过程中愈伤的增殖系数,以白及种子为外植体,利用响应面法对诱导愈伤的增殖培养基中的激素水平进行优化。在添加不同浓度的6-BA(6-苄氨基嘌呤)和2,4-D(2,4-二氯苯氧乙酸)的正交试验诱导愈伤基础上,根据Box-Benhnken(BBD)试验设计原理,采用三因素三水平的方法对3个激素的不同浓度水平进行组合实验。结果显示,通过回归模型分析获得增殖诱导的最佳培养基为MS+0.801 mg/L 6-BA(6-苄氨基嘌呤)+1.192 mg/L 2,4-D(2,4-二氯苯氧乙酸)+0.724 mg/L NAA(萘乙酸)。以优化后培养基进行愈伤组织继代发现其增殖系数为6.154 2,为理论预测值的99.74%。利用响应面法对愈伤组织增殖培养基进行优化,为以愈伤组织为研究材料的细胞悬浮培养、遗传转化、种苗快繁等研究奠定了基础。 相似文献
169.
Michael Davidson Sherry Xueyu Liu Philip Barter Eliot A. Brinton Christopher P. Cannon Antonio M. Gotto Jr. Elizabeth T. Leary Sukrut Shah Michael Stepanavage Yale Mitchel Hayes M. Dansky 《Journal of lipid research》2013,54(2):467-472
Estimation of low-density lipoprotein cholesterol (LDL-C) using the Friedewald (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle composition is altered. We hypothesized that LDL-C estimation by the FR formula and other measurement methods might also be inaccurate in individuals treated with a cholesteryl ester transfer protein (CETP) inhibitor. An assay comparison study was conducted using pre and posttreatment serum samples from 280 of the 811 patients treated with the CETP inhibitor anacetrapib in the DEFINE study (determining the ef ficacy and tolerability of CETP in hibition with anac e trapib). After 24 weeks of treatment with anacetrapib, mean LDL-C values by FR formula, Roche direct method (RDM) and Genzyme direct method (GDM) deviated from that measured by the β-quantification (BQ) reference method by –12.2 ± 7.5, –10.2 ± 6.6, –10.8 ± 8.8 mg/dl, respectively. After treatment with anacetrapib, the FR formula and detergent-based direct methods provided lower LDL-C values than those obtained by the BQ reference method. The bias by the FR formula appeared to be due to an overestimation of VLDL-C by the TG/5 component of the formula. Evaluation of the clinical significance of these findings awaits comprehensive lipid and cardiovascular outcome data from ongoing Phase III clinical studies of anacetrapib. 相似文献
170.
Fred M. Hoppe 《Journal of mathematical biology》1984,20(1):91-94
A Markov process of partitions of the natural numbers is constructed by defining a Pólya-like urn model. The marginal distributions of this process are the Ewens' sampling distributions of population genetics.Research supported in part by NSF Grant MCS-8108689 相似文献