SGK1 in the kidney: disrupted sodium transport in diabetes and beyond

Renal complications of diabetes can be severe; however, the mechanisms that underlie the development and progression of diabetic nephropathy are poorly understood. Recent evidence suggests that the serum and glucocorticoid induced kinase-1 (SGK1) may be key to this process. SGK1 expression and function are increased in models of diabetes and polymorphisms of the SGK1 gene are associated with type 2 diabetes mellitus. A key regulator of sodium transport within the renal epithelium of the distal nephron, SGK1 was originally isolated as a glucocorticoid-sensitive gene that regulated the epithelial sodium channel (ENaC; known also as the sodium channel, nonvoltage-gated 1, SCNN1). It is now apparent that SGK1 modulates sodium re-absorption by a number of sodium transporters/channels throughout the length of the nephron including; the Na+/H+ exchange isoform 3 (NHE3), the Na+Cl- co-transporter (NCC) and the Na+/K+-ATPase. In addition, SGK1 is regulated by a diverse range of factors including; insulin, glucose, intracellular calcium, transforming growth factor-beta1, flow rate and osmolality. This brief review examines the evidence supporting an involvement of SGK1 in diabetic nephropathy and discusses how dysregulated sodium transport may account for the development of secondary hypertension associated with the condition. Furthermore, the article examines how aberrant SGK1 expression and activity may be responsible for the cellular changes seen in the damaged nephron

Functional expression of TRPV4 channels in human collecting duct cells: implications for secondary hypertension in diabetic nephropathy

Background. The Vanilloid subfamily of transient receptor potential (TRPV) ion channels has been widely implicated in detecting osmotic and mechanical stress. In the current study, we examine the functional expression of TRPV4 channels in cell volume regulation in cells of the human collecting duct. Methods. Western blot analysis, siRNA knockdown, and microfluorimetry were used to assess the expression and function of TRPV4 in mediating Ca2+-dependent mechanical stimulation within a novel system of the human collecting duct (HCD). Results. Native and siRNA knockdown of TRPV4 protein expression was confirmed by western blot analysis. Touch was used as a cell-directed surrogate for osmotic stress. Mechanical stimulation of HCD cells evoked a transient increase in [Ca2+]i that was dependent upon thapsigargin-sensitive store release and Ca2+ influx. At 48 hrs, high glucose and mannitol (25 mM) reduced TRPV4 expression by 54% and 24%, respectively. Similar treatment doubled SGK1 expression. Touch-evoked changes were negated following TRPV4 knockdown. Conclusion. Our data confirm expression of Ca2+-dependent TRPV4 channels in HCD cells and suggest that a loss of expression in response to high glucose attenuates the ability of the collecting duct to exhibit regulatory volume decreases, an effect that may contribute to the pathology of fluid and electrolyte imbalance as observed in diabetic nephropathy

Developments in steady and unsteady aerodynamics for use in aeroelastic analysis and design

A review is given of seven research projects which are aimed at improving the generality, accuracy, and computational efficiency of steady and unsteady aerodynamic theory for use in aeroelastic analysis and design. These projects indicate three major thrusts of current research efforts: (1) more realistic representation of steady and unsteady subsonic and supersonic loads on aircraft configurations of general shape with emphasis on structural-design applications, (2) unsteady aerodynamics for application in active-controls analyses, and (3) unsteady aerodynamics for the frequently critical transonic speed range. The review of each project includes theoretical background, description of capabilities, results of application, current status, and plans for further development and use

Astrophotonic micro-spectrographs in the era of ELTs

The next generation of Extremely Large Telescopes (ELT), with diameters up to 39 meters, will start opera- tion in the next decade and promises new challenges in the development of instruments. The growing field of astrophotonics (the use of photonic technologies in astronomy) can partly solve this problem by allowing mass production of fully integrated and robust instruments combining various optical functions, with the potential to reduce the size, complexity and cost of instruments. In this paper, we focus on developments in integrated micro-spectrographs and their potential for ELTs. We take an inventory of the identified technologies currently in development, and compare the performance of the different concepts. We show that in the current context of single-mode instruments, integrated spectrographs making use of, e.g., a photonic lantern can be a solution to reach the desired performance. However, in the longer term, there is a clear need to develop multimode devices to improve overall the throughput and sensitivity, while decreasing the instrument complexity.Comment: 9 pages. 2 figures. Proceeding of SPIE 9147 "Ground-based and Airborne Instrumentation for Astronomy V

Fine Structure of the Motile Cells and Flagella in a Member of the Actinoplanaceae (Actinomycetales)

The motile cells (sporangiospores) of an undescribed member of the Actinoplanaceae are studied by electron microscopy as shadowed, negatively stained, and sectioned preparations. The rod-shaped spores exhibit a typically bacterial internal structure. However, a single tubular structure (rhapidosome) is positioned just inside the site of flagellar attachment of each spore and is oriented perpendicular to the direction of the flagella. Flagella arise from basal discs and pass through the plasma membrane and the two-layered cell wall to become associated with other flagella to function as a posteriorly directed unit. Each flagellum consists of a helical band or ribbon which dissociates into 5 or 6 subfibrils. Original version published in Proceedings of the National Academy of Sciences of the United States

A Tunable Echelle Imager

We describe and evaluate a new instrument design called a Tunable Echelle Imager (TEI). In this instrument, the output from an imaging Fabry-Perot interferometer is cross-dispersed by a grism in one direction and dispersed by an echelle grating in the perpendicular direction. This forms a mosaic of different narrow-band images of the same field on a detector. It offers a distinct wavelength multiplex advantage over a traditional imaging Fabry-Perot device. Potential applications of the TEI include spectrophotometric imaging and OH-suppressed imaging by rejection.Comment: 11 pages, 12 figures, accepted by PAS

Differential torsion theory

AbstractDifferential torsion theories are introduced and it is shown that for a hereditary torsion theory τ every derivation on an R-module M has a unique extension to its module of quotients if and only if τ is a differential torsion theory. Dually, we show that when τ is cohereditary, every derivation on M can be lifed uniquely to its module of coquotients

Developing Gospel Movement Leaders

This research seeks to address the current crisis of leadership in the African American community, specifically regarding the continuation of racial hatred, discrimination, and violence by offering a solution that can be used to help address the problem. The objective of this research was accomplished through the process of reading, analyzing, and synthesizing theoretical and biographic materials to create a viable response. The research led to formulating a program involving the spiritual development of a new generation of Christian African American emerging leaders’ engaging with the leadership crisis as biblical reformers of their culture. The research indicates that the racial problem of today mirrors the same problem that existed during Frederick Douglass’ day in the eighteenth and nineteenth centuries. The difference is that Douglass developed into a biblical reformer because of his exposure to the scriptures, his engagement in a discipleship relationship, and his participation in a relational community of faith. His engagement with this process created in him the spiritual fortitude to confront the problem of race from his biblically astute and theologically motivated core beliefs. As Christian African American emerging leaders emulate Douglass as a biblical reformer, they will have the same spiritual fortitude to address the social injustice of racial hatred in their culture milieu. The research concludes with placing significant importance on the role of the scriptures in the sanctification process to refine and reshape Christian leader’s attitudes and actions towards acting justly, loving mercy, and walking humbly with God (Mic. 6:8). Also, as they engage in a discipleship relationship, they are taught by a mature believer how to access scripture to discern God’s will, make ethical choices, and live a viii life of integrity. Finally, as Christian leaders participate in a relational community of faith, it provides the training venue for applying the scriptures to biblically reform their culture