Replacement of renal function in uremic animals with a tissue-engineered kidney.

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.     

Mineral oil enhances the autoradiographic detection of 32P-labeled nucleic acids bound to nitrocellulose membranes

The autoradiographic signal obtained from 32P-labeled nucleic acids hybridized to nitrocellulose membrane-bound DNA or RNA can be enhanced by making the membrane translucent with mineral oil and placing it between two intensifying screens. Elution of the mineral oil after autoradiography allows the reuse of the membranes in subsequent hybridizations.     

Phthalic acid diamides activate ryanodine-sensitive Ca2+ release channels in insects

Flubendiamide represents a novel chemical family of substituted phthalic acid diamides with potent insecticidal activity. So far, the molecular target and the mechanism of action were not known. Here we present for the first time evidence that phthalic acid diamides activate ryanodine-sensitive intracellular calcium release channels (ryanodine receptors, RyR) in insects. With Ca(2+) measurements, we showed that flubendiamide and related compounds induced ryanodine-sensitive cytosolic calcium transients that were independent of the extracellular calcium concentration in isolated neurons from the pest insect Heliothis virescens as well as in transfected CHO cells expressing the ryanodine receptor from Drosophila melanogaster. Binding studies on microsomal membranes from Heliothis flight muscles revealed that flubendiamide and related compounds interacted with a site distinct from the ryanodine binding site and disrupted the calcium regulation of ryanodine binding by an allosteric mechanism. This novel insecticide mode of action seems to be restricted to specific RyR subtypes because the phthalic acid diamides reported here had almost no effect on mammalian type 1 ryanodine receptors.     

Über das Wuchsstoff-Hemmstoffsystem der haferkoleoptile und der Kartoffelknolle

Ohne ZusammenfassungMit 8 Textabbildungen.     

Tailoring the Antibody Response to Aggregated A? Using Novel Alzheimer-Vaccines

Recent evidence suggests Alzheimer-Disease (AD) to be driven by aggregated Aß. Capitalizing on the mechanism of molecular mimicry and applying several selection layers, we screened peptide libraries for moieties inducing antibodies selectively reacting with Aß-aggregates. The technology identified a pool of peptide candidates; two, AFFITOPES AD01 and AD02, were assessed as vaccination antigens and compared to Aβ1-6, the targeted epitope. When conjugated to Keyhole Limpet Hemocyanin (KLH) and adjuvanted with aluminum, all three peptides induced Aß-targeting antibodies (Abs). In contrast to Aß1-6, AD01- or AD02-induced Abs were characterized by selectivity for aggregated forms of Aß and absence of reactivity with related molecules such as Amyloid Precursor Protein (APP)/ secreted APP-alpha (sAPPa). Administration of AFFITOPE-vaccines to APP-transgenic mice was found to reduce their cerebral amyloid burden, the associated neuropathological alterations and to improve their cognitive functions. Thus, the AFFITOME-technology delivers vaccines capable of inducing a distinct Ab response. Their features may be beneficial to AD-patients, a hypothesis currently tested within a phase-II-study.     

Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process

Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young’s modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young’s modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet–steel and tablet–tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.     

Patterns of fungal diversity and composition along a salinity gradient

Estuarine salinity gradients are known to influence plant, bacterial and archaeal community structure. We sequenced 18S rRNA genes to investigate patterns in sediment fungal diversity (richness and evenness of taxa) and composition (taxonomic and phylogenetic) along an estuarine salinity gradient. We sampled three marshes—a salt, brackish and freshwater marsh—in Rhode Island. To compare the relative effect of the salinity gradient with that of plants, we sampled fungi in plots with Spartina patens and in plots from which plants were removed 2 years prior to sampling. The fungal sediment community was unique compared with previously sampled fungal communities; we detected more Ascomycota (78%), fewer Basidiomycota (6%) and more fungi from basal lineages (16%) (Chytridiomycota, Glomeromycota and four additional groups) than typically found in soil. Across marshes, fungal composition changed substantially, whereas fungal diversity differed only at the finest level of genetic resolution, and was highest in the intermediate, brackish marsh. In contrast, the presence of plants had a highly significant effect on fungal diversity at all levels of genetic resolution, but less of an effect on fungal composition. These results suggest that salinity (or other covarying parameters) selects for a distinctive fungal composition, and plants provide additional niches upon which taxa within these communities can specialize and coexist. Given the number of sequences from basal fungal lineages, the study also suggests that further sampling of estuarine sediments may help in understanding early fungal evolution.