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

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

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

Atom chip for BEC interferometry

We have fabricated and tested an atom chip that operates as a matter wave interferometer. In this communication we describe the fabrication of the chip by ion-beam milling of gold evaporated onto a silicon substrate. We present data on the quality of the wires, on the current density that can be reached in the wires and on the smoothness of the magnetic traps that are formed. We demonstrate the operation of the interferometer, showing that we can coherently split and recombine a Bose–Einstein condensate with good phase stability

Renal fibrosis, immune cell infiltration and changes of TRPC channel expression after unilateral ureteral obstruction in Trpc6-/- mice

Background/Aims: The transient receptor potential cation channel subfamily C member 6 (TRPC6) is a Ca-permeable nonselective cation channel and has received recent attention because of its capability to promote chronic kidney disease (CKD). The aims of this study were (i) to examine whether deletion of TRPC6 impacts on renal fibrosis and inflammatory cell infiltration in an early CKD model of unilateral ureter obstruction (UUO) in mice; and (ii) whether TRPC6-deficiency as well as UUO affect the regulation of TRPC expression in murine kidneys. Methods: Wild-type (WT), Trpc6-knockout (Trpc6) and New Zealand obese (NZO) mice underwent sham operation or unilateral ureteral obstruction (UUO). The kidneys were harvested 7 days after surgery. We examined renal fibrosis and inflammatory cell infiltration by histological and immunohistochemical staining. The mRNA expression of TRPC members and markers of fibrosis and inflammation in kidney were assessed by using real-time quantitative reverse transcription PCR. Results: Histological and immunohistochemical analyses revealed less inflammatory cell infiltration (F4/80 and CD3) in UUO kidneys of Trpc6 mice compared to UUO kidneys of WT mice as well as less fibrosis. Genomic deletion of TRPC6 also affected the expression of pro-fibrotic genes in UUO Trpc6 kidneys compared to UUO WT kidneys while the expression of pro-inflammatory genes did not differ. UUO caused marked up-regulation of Trpc6 and down-regulation of Trpc1 mRNA in kidneys of WT and NZO mice. Trpc3 mRNA expression was significantly elevated in kidneys of Trpc6 mice underwent UUO while the levels did not change in kidneys of neither WT nor in NZO mice underwent UUO. Conclusion: TRPC6 contributes to renal fibrosis and immune cell infiltration in the UUO mouse model. Therefore, inhibition of TRPC6 emerges as a promising novel therapeutic strategy for treatment of chronic kidney failure in chronic obstructive nephropathy. However, confounding genomic and non-genomic effects of other TRPC channels should be taken into consideration to fully comprehend the renoprotective potential of targeting TRPC6 therapeutically under chronic kidney damaging conditions

Pyramidal micromirrors for microsystems and atom chips

Concave pyramids are created in the (100) surface of a silicon wafer by anisotropic etching in potassium hydroxide. High quality micromirrors are then formed by sputtering gold onto the smooth silicon (111) faces of the pyramids. These mirrors show great promise as high quality optical devices suitable for integration into micro-optoelectromechanical systems and atom chips. We have shown that structures of this shape can be used to laser-cool and hold atoms in a magneto-optical trap