Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease

The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.     

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.     

Evaporated Te on CdTe: A vacuum-compatible approach to making back contact to CdTe solar cell devices

A commonly used process for forming low-resistance contacts to thin-film p-type CdTe involves the formation of a Te layer by etching the CdTe film in a concentrated mixture of nitric and phosphoric acids. The authors compare evaporated Te back contacts with ‘control’ back contacts formed by the usual etching process, and demonstrate that evaporating Te onto a CdTe thin film is a viable process for forming a low-resistance contact. The best efficiency achieved for a CdTe solar cell made with an evaporated Te back contact is 12.1%, whereas the efficiency of the device made with the control back contact was 11.9%. The evaporation process offers numerous advantages over acid etching, most notably vacuum compatibility amenable to large-scale production of CdTe solar cell modules.     

Macroinvertebrate assemblages of littoral habitats in the Macquarie and Mersey rivers,Tasmania: Implications for the management of regulated rivers

Littoral habitats in large rivers are influenced to varying degrees by changes in discharge. Irrigation abstractions can increase the amount of habitat that would naturally be dewatered during low flow periods and therefore it is important to have some knowledge of the potential impact this may have on riverine macroinvertebrates. The macroinvertebrate assemblages of common littoral habitats in riffles, pools and runs in two reaches each of the Macquarie and Mersey Rivers, northern Tasmania, Australia were compared from samples collected during the low flow and irrigation season, between December 1991 and April 1992. The area under water of these habitats, riffle substrata, macrophyte beds and coarse woody debris, responded differently to changes in discharge. Within a reach, the same taxonomic groups often dominated the total number of macroinvertebrates for all habitats, but there were differences in the proportions contributed by these taxa to the different habitats. In general, taxa characteristic of slow-flowing or lentic habitats, such as ostracods and amphipods, were dominant in macrophyte beds in pools and runs, whereas taxa such as larval elmid beetles and hydropsychid caddisflies were dominant in riffles. A substantial component of the fauna from each habitat within a reach was unique to that habitat, but there was always a similar number of taxa common to all habitats. Classification and ordination grouped samples from both rivers firstly by habitat and secondly by month and reach. Total density and family richness of invertebrates differed by reach, habitat and month in both rivers, except for richness in the Mersey River where habitat was not significant. Differences in densities and numbers of invertebrate families among habitats were not consistent between reaches for each river. This study has highlighted the differences in macroinvertebrate assemblages of several littoral habitats in two lowland rivers in Tasmania. Differences in taxonomic composition, density and richness among habitats within reaches strongly imply the uniqueness of these habitats in terms of the invertebrate faunas that occupy them. We suggest that if maintenance of biotic diversity is an aim of instream flow management, water allocations that address low flows should place a high priority on the maintenance of a diversity of habitats.     

Comparative X-ray scattering,microscopical, and mechanical studies on rectangular plates injection molded from different types of isotactic polypropylene

Rectangular plates were injection molded from two grades of commercial polypropylene (PP) differing in the molar mass distribution. The mold was mechanically sealed when a desired pressure p_i,max (up to 1560 bar) was reached. Samples were taken from each plate at different distances from the gate and were investigated by applying various methods. In spatially resolved wide-angle X-ray studies, the cross section of the sample was scanned with a fine X-ray beam (collimated by a Kratky small-angle camera) and the intensity of scattering was registered by a linear detector as a function of position in the cross section. The evaluation of the scattering data delivered profiles of several parameters, describing the distribution of crystallite modification β-PP and γ-PP, the degree of orientation, the size of crystallites, and interplanar spacing, depending on the distance from surface. These results and those from measurements of birefringence and elongation at break, and from polarization microscopy and transmission electron microscopy, provided details of the layered structures in the plates, at different flow lengths, and allowed far-reaching statements about the influence of molecular properties and processing conditions on the development of texture in the plates.     

在VoIP网关中实现高精度包同步

随着VoIP网关能够在POTS线或T1/E1中继器与IP网络之间进行业务的互操作,传真、MODEM和电话业务正越来越多地依靠VoIP技术,取代了传统的TDM设备.在部署VoIP网关时,发送和接收时序同步的机理经常被忽视.因而需要改进包同步以提高业务的可靠性和质量,这一点在传统的电路交换设备中是能够实现的.     

Der einfluß von faseroberflächen auf die matrixhärtung bei faserverbundwerkstoffen

The influence of extraction of reinforced fibres on surface properties and the curing reaction of epoxy resin matrix in composites were investigated. With increasing fibre surface polarity, as the result of the extraction, the resin wettability was improved and the reaction rate of curing of the epoxy resin matrix increased. The wettability and the reaction rate oppositely decreased with decreasing fibre surface polarity.     

Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?

For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells combined with GBA1 mutation analysis. The use of dried blood spot (DBS) specimens offers many advantages, including easy collection, the need for a small amount of blood, and simpler transportation. However, DBS has limitations for measuring GCase activity. In this paper, we recount our cross-sectional study and publish seven years of experience using DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1), for GD diagnosis. Of 444 screened subjects, 99 (22.3%) were diagnosed with GD at a median (range) age of 21 (1–78) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9–1340) ng/mL and 5.4 (1.5–16) ng/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9–1050), compared to GD1 and severe GBA1 variants, 447 (38–1340) ng/mL, and neuronopathic GD, 325 (116–1270) ng/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5–15.3) ng/mL, compared to wild-type GBA1, 4.9 (1.5–16), ng/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7–10.7) in heterozygous GBA1 carriers with Parkinson’s disease (PD), similar to lyso-Gb1 levels in subjects without PD. We call for a paradigm change for the diagnosis of GD based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in DBS. Lyso-Gb1 levels could not be used to differentiate between heterozygous GBA1 carriers and wild type.