Late-onset Bartter syndrome type II

Mutations in the ROMK1 potassium channel gene (KCNJ1) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero, accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities

The case: chronic kidney disease unmasked by single-subject research

We present a 42-year-old man with a BMI of 32, who was referred because of proteinuria and decreased renal function. We were impressed by his markedly muscular physique. A renal biopsy was performed, which showed focal segmental glomerular sclerosis (FSGS). Is this patient merely an obese person with FSGS or is something else going on here? We performed extensive clinical and laboratory examinations, genetic testing, and anthropometric data monitoring over time. We transferred our methodology for routine FSGS mutation screening (Sanger sequencing) to the Ion Torrent PGM platform with a new custom-targeted NGS gene panel (Ion Ampliseq FSGS panel) and tested the performance of the system in two cohorts of patients with FSGS. We discuss FSGS in bodybuilders, including possible mechanisms, and review the literature

Electrostatic actuators for misalignment compensation in multi-layered microsystem devices

AbstractElectrostatic actuation is a promising approach to compensate for misalignment of bonded, multi-layered microsystem devices. The present work discusses the performance of electrostatic actuators used for in-plane misalignment compensation in an atom chip comprising an optical cavity. Experimental investigation revealed that the central frame suspending the mirrors can be moved between 3-5 m in the in-plane direction for the applied DC voltage of 90 volts. Future work involves characterizing the mirror displacement for optical tuning function

Elementary calcium signaling in arterial smooth muscle

Vascular smooth muscle cells (VSMCs) of small peripheral arteries contribute to blood pressure control by adapting their contractile state. These adaptations depend on the VSMC cytosolic Ca(2+) concentration, regulated by complex local elementary Ca(2+) signaling pathways. Ca(2+) sparks represent local, transient, rapid calcium release events from a cluster of ryanodine receptors (RyRs) in the sarcoplasmic reticulum. In arterial SMCs, Ca(2+) sparks activate nearby calcium-dependent potassium channels, cause membrane hyperpolarization and thus decrease the global intracellular [Ca(2+)] to oppose vasoconstriction. Arterial SMC Ca(V)1.2 L-type channels regulate intracellular calcium stores content, which in turn modulates calcium efflux through RyRs. Ca(V)3.2 T-type channels contribute to a minor extend to Ca(2+) spark generation in certain types of arteries. Their localization within cell membrane caveolae is essential. We summarize present data on local elementary calcium signaling (Ca(2+) sparks) in arterial SMCs with focus on RyR isoforms, large-conductance calcium-dependent potassium (BK(Ca)) channels, and cell membrane-bound calcium channels (Ca(V)1.2 and Ca(V)3.2), particularly in caveolar microdomains

A three-dimensional electrostatic actuator with a locking mechanism for a new generation of atom chips

A micromachined three-dimensional electrostatic actuator that is optimized for aligning and tuning optical microcavities on atom chips is presented. The design of the 3D actuator is outlined in detail, and its characteristics are verified by analytical calculations and finite element modelling. Furthermore, the fabrication process of the actuation device is described and preliminary fabrication results are shown. The actuation in the chip plane which is used for mirror positioning has a working envelope of 17.5 ?m. The design incorporates a unique locking mechanism which allows the out-of-plane actuation that is used for cavity tuning to be carried out once the in-plane actuation is completed. A maximum translation of 7 ?m can be achieved in the out-of-plane direction

The effect of self-affine fractal roughness of wires on atom chips

Atom chips use current flowing in lithographically patterned wires to produce microscopic magnetic traps for atoms. The density distribution of a trapped cold atom cloud reveals disorder in the trapping potential, which results from meandering current flow in the wire. Roughness in the edges of the wire is usually the main cause of this behaviour. Here, we point out that the edges of microfabricated wires normally exhibit self-affine roughness. We investigate the consequences of this for disorder in atom traps. In particular, we consider how closely the trap can approach the wire when there is a maximum allowable strength of the disorder. We comment on the role of roughness in future atom--surface interaction experiments.Comment: 7 pages, 7 figure

Hydrogen sulfide: potent regulator of vascular tone and stimulator of angiogenesis

Hydrogen sulfide is the "third" gasotransmitter on the rise in cardiovascular research. Recent studies show that hydrogen sulfide has a great potential in the regulation of vascular tone of systemic arteries and many molecular targets are discussed. However, the complex mechanism of vascular tone regulation by hydrogen sulfide is only incompletely understood. It seems that a potent interaction of hydrogen sulfide with vascular endothelial growth factor (VEGF) becomes important in angiogenesis, in the process of wound healing, but also in tumor angiogenesis. Hydrogen sulfide exerts anti-inflammatory effects and it could be a pharmacological target in vascular dysfunction in association with obesity-related hypertension as well as in tumor development and progression. However, the underlying molecular pathways still need to be revealed. This review primarily focuses on the regulatory role of hydrogen sulfide in controlling vascular tone. We attempt to provide recent insights into mechanisms by which CSE-dependent hydrogen sulfide plays a role in the regulation of vascular tone by perivascular adipose tissue. The role of KCNQ channels and other ionic permeation pathways as key targets will be discussed. Recent findings which are summarized in this paper provide new insights into molecular mechanisms of hydrogen sulfide that are crucial for understanding vascular dysfunction in cardiovascular disease and possibly angiogenesis. Future research will be extended to investigate the therapeutic potential of hydrogen sulfide and their targets such as KCNQ channels in cardiovascular diseases, angiogenesis and tumor genesis

Ballast Water Management for European Seas - Is There a Need for a Decision Support System?

The human mediated transfer of aquatic organisms and pathogens via shipping, specifically with ballast water, is a continuing global threat to biodiversity, human health and economic values. In February 2004, as a result of long-term effort of the International Maritime Organization (IMO), the United Nations body which deals with shipping, the International Convention for the Control and Management of Ships' Ballast Water and Sediments (BWM Convention) was adopted by the international community setting global standards. In the absence of efficient Ballast Water Treatment Systems (BWTS) on existing ships, Ballast Water Exchange (BWE) is currently the only available method approved by IMO. However, BWE has serious limitations that make it biologically inefficient and often impractical under certain conditions. A key question is whether all ships should be requested to conduct BWE (i.e., blanket approach) or whether it is more appropriate that port states determine BWE requirements on a ship-to-ship basis (i.e., selective approach) supported by a decision support system based on risk assessment? In this paper BWE in the framework of the BWM Convention is discussed. The applicability and effectiveness of BWE is studied and suggestions are given for an effective ballast water management approach, including options for a decision support system, in Europe