A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet–Biedl syndrome in a Pakistani family

Bardet–Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet–Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet–Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet–Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet–Biedl Syndrome in this family.     

海马脑片盲法膜片钳全细胞记录技术

本文较为详细地介绍了海马脑片盲法膜片钳全细胞记录技术,对其关键步骤和需要注意的问题进行了重点说明,同时对CA1区锥体神经元突触活动的特点,电压门控性Ca^2 通道以及谷氨酸（glutamate,Glu)γ－氨基丁酸（GABA）受体通道电流性质等进行了观察和分析,实验结果为采用海马脑片盲法膜片钳全细胞记录技术研究海马神经元离子通道动力学性质和中枢神经系统药物对突触活动的影响提供了可靠的依据。     

芦苇型湿地生态系统的潜水水质状态研究

以白洋淀芦苇滩地为实验地,研究了湿地生态系统中潜水的水质状况.苇地潜水运动受到芦苇根孔的强烈影响.受芦苇根区生物呼吸作用的影响,潜水pH值(6.94士0.14)显著低于淀水(9.17).潜水中CO2分压约为淀水的85～1039倍.潜水水质类型在离淀2.7至6.7m发生变化,逐渐由ClN3转变为CCa.自苇地边缘至中央,HT(总硬度),Ar(总碱度)与∑C(主要离子总量)逐渐升高.潜水中Mg2+/Ca2+的平均摩尔比值为0.60,明显低于淀水(1.31).淀水和潜水Cl-,SO2-,Na++K+含量无显著差异,平均值分别是176,116和112mg/L.苇地濒水区为一过渡带,对磷氮污染物具备首先的过滤作用.在离淀0.7m处TN,TP和活性磷酸盐的减少量分别为63.3%,84.6%,80.8%.     

Persistent tetrodotoxin-resistant Na+ currents are activated by prostaglandin E2 via cyclic AMP-dependent pathway in C-type nodose neurons of adult rats

It has been documented that nodose neurons express TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na(+) channels. However, wheteher nodose neurons functionally express persistent TTX-R Na(+) currents has not been reported. The present study first demonstrated persistent TTX-R Na(+) channel activities in 7/19 C-type nodose neurons in the presence of PGE(2) using whole-cell patch. Voltage-dependent property showed that persistent TTX-R Na(+) currents were activated at near -60mV and channels were maintained open. The average peak was approximately 300-500pA. The mid-point of activation exhibited a greater shift to a more hyperpolarized potential in the neurons co-expressing TTX-R and persistent TTX-R Na(+) currents than those expressing TTX-R only. This effect of PGE(2) was also mimicked by Forskolin. The fact that persistent TTX-R Na(+) currents were only activated by PGE(2) suggested that the modulatory effects of PGE(2) on persistent TTX-R Na(+) currents are crucial in PGE(2)-mediated neuronal excitability, and may have a great impact on specifically physiological significance.     

噬菌体phi29 DNA包装马达磷脂膜嵌合体在单分子检测及纳米医学领域的应用

生命系统包含了具有不同功能的纳米机器和高度有序的大分子结构。所有的双链线性DNA病毒使用由ATP驱动的纳米分子马达将其基因包装在蛋白质外壳内。噬菌体phi29 DNA包装马达的核心组成部分连接器已被成功嵌入到脂双层中,极为稳定且可用于离子和DNA转运的精确测量。它在包装DNA时具有单向通行的阀门机制,同时其关闭和打开可由人工控制。这对于详细研究分子马达的操作机制及未来医药应用中DNA的包装、测序、采样和投递都具有重要意义。     

电压门控性钠离子通道与伤害性感受

伤害性感受器激活引起疼痛的概念,现已广泛被人们接受,大量实验表明,伤害性感受器兴奋性的变化与一些离子通道有关,对河豚毒素不敏感的电压依赖性钠离子通道（TTXr)选择性地分布于与伤害性感受有关的初级感受神经元,炎症反应和神经损伤诱发的慢性疼痛可诱发这种TTXr功能及基因表达的变化,TTXr通道蛋白的反义寡核苷酸（antisense ODN)处理可对抗炎症或神经损伤引起的痛觉过敏或超敏,提示TTXr在伤害性感受中起重要作用,有望成为特异性镇痛药物的药理作用靶点。     

线虫区系分析指示土壤食物网结构和功能研究进展

土壤食物网结构复杂,功能众多,直接测定土壤食物网各功能群生物量并结合数学模型来推断土壤食物网结构和功能,工作量大且分析过程繁琐。线虫生态学的发展为土壤食物网的研究开辟了一条新的思路,即利用线虫区系分析来定性推断食物网的结构和功能。线虫作为土壤中数量最丰富的后生动物,占据着土壤食物网的中心位置,其物种多样性、食性多样性、生活史策略多样性、功能团多样性奠定了其作为土壤食物网结构和功能指示生物的生态学基础。线虫区系分析根据发展历史可以分为个体分类、生活史策略分类、功能团分类和代谢足迹分类四个时期,其中后两个时期主要用于推断土壤食物网结构和功能。基于功能团的线虫区系分析将线虫的食性和生活史策略结合起来,发展出一系列指数来判断土壤食物网的连通性、食物网链长度、外界养分投入情况、分解途径及对外界干扰的响应等。基于代谢足迹的线虫区系分析在功能团分析基础上,加入线虫能流分析,从而定性反映了土壤食物网功能的大小。两者在指示土壤食物网自下而上调节及对植物线虫控制等方面起着重要的作用。     

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Confers Glibenclamide Sensitivity to Outwardly Rectifying Chloride Channel (ORCC) in Hi-5 Insect Cells

Increasing evidence is now accumulating for the involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) in the control of the outwardly rectifying chloride channel (ORCC). We have examined the sensitivity of ORCC to the sulfonylurea drug glibenclamide in Hi-5 (Trichoplusia ni) insect cells infected with recombinant baculovirus expressing either wild-type CFTR, ΔF508-CFTR or E. coliβ galactosidase cDNA and in control cells either infected with virus alone or uninfected. Iodide efflux and single channel patch-clamp experiments confirmed that forskolin and 1-methyl-3-isobutyl xanthine (IBMX) or 7-methyl-1,3 dipropyl xanthine (DPMX) activate CFTR channels (unitary conductance: 9.1 ± 1.6 pS) only in cells expressing CFTR. In contrast, we identified 4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid (SITS)-sensitive ORCC in excised membrane patches in any of the cells studied, with similar conductance (22 ± 2.5 pS at −80 mV; 55 ± 4.1 pS at +80 mV) and properties. In the presence of 500 μm SITS, channel open probability (P _o ) of ORCC was reversibly reduced to 0.05 ± 0.01 in CFTR-cells, to 0.07 ± 0.02 in non-CFTR expressing cells and to 0.05 ± 0.02 in ΔF508-cells. In Hi-5 cells that did not express CFTR, glibenclamide failed to inhibit ORCC activity even at high concentrations (100 μm), whereas 500 μm SITS reversibly inhibited ORCC. In contrast in cells expressing CFTR or ΔF508, glibenclamide dose dependently (IC₅₀= 17 μm, Hill coefficient 1.2) and reversibly inhibited ORCC. Cytoplasmic application of 100 μm glibenclamide reversibly reduced P _o from 0.88 ± 0.03 to 0.09 ± 0.02 (wash: P _o = 0.85 ± 0.1) in CFTR cells and from 0.89 ± 0.05 to 0.08 ± 0.05 (wash: P _o = 0.87 ± 0.1) in ΔF508 cells. In non-CFTR expressing cells, glibenclamide (100 μm) was without effect on P _o (control: P _o = 0.89 ± 0.09, glib.: P _o = 0.86 ± 0.02; wash: P _o = 0.87 ± 0.05). These data strongly suggest that the expression of CFTR confers glibenclamide sensitivity to the ORCC in Hi-5 cells. Received: 23 October 1998/Revised: 29 December 1998     

T淋巴细胞上的离子通道

近年的研究证明,淋巴细胞上的离子通道,在免疫功能调节中具有重要的作用。T淋巴细胞上主要有三类离子通道,即Ca2 、K 和C1-通道。Ca2 通过T淋巴细胞膜上的Ca2 通道(CRAC)进入细胞内,可作为第二信使激活T淋巴细胞。通过K 通道的K 外流是T淋巴细胞膜电位形成的基础。由于膜电位水平可以影响钙离子的内流,因此,K 通道可以间接调节T淋巴细胞的活化和功能。T淋巴细胞上的Cl-通道是新近发现的一种离子通道,可能与细胞的体积调节有关。本文扼要总结了T淋巴细胞上离子通道的新近进展。