Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy

ADAM17 is a disintegrin and metalloproteinase capable of cleaving the ectodomains of a diverse variety of molecules including TNF-α, TGF-α, L-selectin, and ACE2. We have previously demonstrated that renal ADAM17 is upregulated in diabetic mice. The role of endothelial (eAdam17) and proximal tubular (tAdam17) Adam17 deletion in renal histology, modulation of the renin angiotensin system (RAS), renal inflammation, and fibrosis was studied in a mouse model of type 1 Diabetes Mellitus. Moreover, the effect of Adam17 deletion in an in vitro 3D cell culture from human proximal tubular cells under high glucose conditions was evaluated. eAdam17 deletion attenuates renal fibrosis and inflammation, whereas tAdam17 deletion decreases podocyte loss, attenuates the RAS, and decreases macrophage infiltration, α-SMA and collagen accumulation. The 3D in vitro cell culture reinforced the findings obtained in tAdam17KO mice with decreased fibrosis in the Adam17 knockout spheroids. In conclusion, Adam17 deletion either in the endothelial or the tubular cells mitigates kidney injury in the diabetic mice by targeting different pathways. The manipulation of Adam17 should be considered as a therapeutic strategy for treating DN.     

Measuring the concentrations of drinking water disinfection by-products using capillary membrane sampling-flow injection analysis

A capillary membrane sampling-flow injection analysis method is presented for selectively measuring the concentrations of total trihalomethanes (THMs) and total haloacetic acids (HAAs) in drinking water. The method is based on the reaction between nicotinamide and THM or HAA species to yield a fluorescent product. Two configurations are presented, one selective for total THMs and another selective for total HAAs. The construction of a capillary membrane sampler is described, and the results of method detection limit, accuracy and precision studies are reported for each method. Interference, selectivity and linearity studies are reported as well as the effect of temperature and ionic strength changes. Drinking water samples were analyzed by each proposed method and the results were compared to USEPA methods 502.2 and 552.3.     

A New Method for Testing Re-Programmable PLAs

We present a method for obtaining a minimal set of test configurations and their associated set of test patterns that completely tests re-programmable Programmable Logic Arrays (PLAs) including EEPROM, UV-EPROM, and SRAM based re-programmable PLAs typically found in Complex Programmable Logic Devices (CPLDs). The resultant set of test configurations and vectors detect all single and multiple stuck-at faults (including line and transistor faults) as well as all bridging faults in the PLA. Previously proposed test methods proposed for EEPROM based PLAs (IEEE Trans. on CAD, Vol. 13, No. 7, pp.935–939, 1994;Proc. IEEE International Symposium on Defect and Fault Tolerance in VLSI Systems, 1998, pp. 146–154) require additional test hardware as well as a large number of test configurations and vectors for complete testing. Our approach requires no modification to the PLA and only two or four test configurations, depending on the ratio of PLA product terms to inputs.     

Oligomer formation in the chemical degradation of dextran

Summary The production of oligomers — to a degree of polymerization 5 — during acid hydrolization of polymer dextrans was estimated quantitatively by a combined aqueous SEC and adsorption separation. It was found that the molar concentrations of the oligomers were higher for those with lower DP. This experimental result is in agreement with a degradation model, in which the molecular weight decreases with the power of 2/3 versus time, which has been proposed earlier.Extracted from a thesis submitted by J. Emmert to the University of Heidelberg in partial fulfillment of the requirements for the Ph.D. degree     

Limiting order of amino acids in a low-protein corn-soybean meal-whey-based diet for nursery pigs

Three trials were carried out with pigs between 5 and 8 wk of age to determine the limiting order of amino acids in a 13.5% CP corn-soybean meal-based diet containing 8% dried whey. The positive-control diet was a 19.2% CP corn-soybean meal-based diet (1.15% lysine), also with 8% dried whey. Amino acid additions to the low-protein, negative-control diet were based on levels needed to accomplish 110% of ideal ratios (to lysine, set at 1.15%). In Exp. 1, the addition of an amino acid mixture containing Lys, Trp, Thr, Met, Ile, and Val to the low-protein diet increased (P<.05) gain and gain: feed ratio, and these response traits were not different from those of pigs fed the 19.2% CP positive-control diet. Single deletion of Lys from the supplemental amino acid mixture depressed performance to a greater (P<.05) extent than single deletion of any of the other amino acids. Single deletions of Trp, Thr, Met, or Val decreased (P<.05) performance in a similar but lesser magnitude than the decrease caused by Lys deletion, whereas Ile deletion was without effect. Experiments 2 and 3 were designed to evaluate the limiting order of AA beyond Lys in the low-protein diet. Neither His nor Glu were found to be deficient, and, as in Exp. 1, deletion of Trp, Thr, Met, or Val from the supplemental amino acid mixture resulted in performance depressions (P<.05) that were similar. The results suggest that Lys is first-limiting and Trp, Thr, Met, and Val are equally second-limiting in a reduced protein (13.5% CP) corn-soybean meal-based diet with 8% whey for 10-kg pigs.     

Europäische und nationale Regulierungen

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