Modelling the long QT syndrome with induced pluripotent stem cells

The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death. Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.     

Demonstration of exocytosis in the sinus gland of Astacus Leptodactylus (Nordmann) under the influence of serotonin injections]

Following a serotonin injection, a rise of exocytosis in the sinus gland of the crayfish Astacus leptodactylus is observed together with an increase of the glucose level in the hemolymph. The phenomenon of exocytosis reaches a peak between 2 and 4 h after injection, wheras the highest glucose level in the hemolymph appears between 4 and 6 h after the same injection.     

Inferring the statistical interpretation of quantum mechanics from the classical limit

It is widely believed that the statistical interpretation of quantum mechanics cannot be inferred from the Schrodinger equation itself, and must be stated as an additional independent axiom. Here I propose that the situation is not so stark. For systems that have both continuous and discrete degrees of freedom (such as coordinates and spin respectively), the statistical interpretation for the discrete variables is implied by requiring that the system's gross motion can be classically described under circumstances specified by the Schrodinger equation. However, this is not a full-fledged derivation of the statistical interpretation because it does not apply to the continuous variables of classical mechanics.     

Use of Plants for Remediation, Stabilization and Restoration of Aquatic and Terrestrial Ecosystems

植物能够吸收或降解污染物来修复受污染的土壤和水体[1-2],还能固定土壤、泥沙防止侵蚀和污染物从固体介质中释放[3]。众多无机和有机污染物都能被对其有耐性且生物量大的植物有效降解。例如,凤眼莲能吸收和净化来自金矿采掘废水的氰化物,这类废水含各种氰化物以及重金属元素的浓度达到导致生物体产生毒性效应的水平。检测表明氰化物对凤眼莲的半数致死剂量(LC50)为13 mg/L,将经过高浓度氰化物废水驯化后的凤眼莲放在野外小型湿地进行试验,结果显示这类植物对氰化物的降解效率更高。放射性同位素试验发现氰化物分子中的C和N原子经过植物代谢合成天冬酰胺,从而将有毒性的氰化物转化为无毒的产物[4]。尾矿场也可以用植物来修复,一方面植物可以过滤污染物浓度很高的渗滤液,另一方面栽种植物可以固定边坡减少侵蚀。将高覆盖度植被的概念应用在一个尾矿场上,通过种植北美黄杉使其全年都维持较高的蒸腾效率来减少渗滤液。而边坡的固定首先需要在坡面安置固定、菱形的新鲜柳条编织成的笼状网格,其后覆上土壤并喷播能在生长期对固定土壤发挥作用的草本、灌木以及树木种子。这项技术同样适用于河岸侵蚀防护。     

HIP1 exhibits an early recruitment and a late stage function in the maturation of coated pits

Huntingtin interacting protein 1 (HIP1) is an accessory protein of the clathrin-mediated endocytosis (CME) pathway, yet its precise role and the step at which it becomes involved are unclear. We employed live-cell imaging techniques to focus on the early steps of CME and characterize HIP1 dynamics. We show that HIP1 is highly colocalized with clathrin at the plasma membrane and shares similar dynamics with a subpopulation of clathrin assemblies. Employing transferrin receptor fused to pHluorin, we distinguished between open pits to which HIP1 localizes and newly internalized vesicles that are devoid of HIP1. Moreover, shRNA knockdown of clathrin compromised HIP1 membranal localization, unlike the reported behavior of Sla2p. HIP1 fragment, lacking its ANTH and Talin-like domains, inhibits internalization of transferrin, but retains colocalization with membranal clathrin assemblies. These data demonstrate HIP1’s role in pits maturation and formation of the coated vesicle, and its strong dependence on clathrin for membranal localization. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.