Extraction, quantification, and biological availability of fumonisin B1 incorporated into the Oregon test diet and fed to rainbow trout

The purpose of this study was (i) to determine whether pure fumonisin B1 could be incorporated into, recovered, and detected by high-pressure liquid chromatographic analysis from the semipurified Oregon test diet (OTD) used in rainbow trout feeding studies, and (ii) to determine if the incorporated fumonisin B1 was biologically available using the change in free sphingoid bases in liver, kidney, and serum as a mechanism-based biomarker. The results indicate that fumonisin is not easily quantified in the OTD. Recoveries ranged from 12 to 81% of the calculated concentrations based on the fumonisin B1 added to the OTD. However, the fumonisin B1 in the OTD was readily absorbed and biologically active as evidenced by marked increases in free sphinganine in liver, kidney, and serum. The magnitude of the increase in free sphinganine at 100 ppm in the OTD was comparable to that known to be associated with liver toxicity in rats, pigs, and ponies.     

Computational learning reveals coiled coil-like motifs in histidine kinase linker domains

The recent rapid growth of protein sequence databases is outpacing the capacity of researchers to biochemically and structurally characterize new proteins. Accordingly, new methods for recognition of motifs and homologies in protein primary sequences may be useful in determining how these proteins might function. We have applied such a method, an iterative learning algorithm, to analyze possible coiled coil domains in histidine kinase receptors. The potential coiled coils have not yet been structurally characterized in any histidine kinase, and they appear outside previously noted kinase homology regions. The learning algorithm uses a combination of established sequence patterns in known coiled coil proteins and histidine kinase sequence data to learn to recognize efficiently this coiled coil-like motif in the histidine kinases. The common appearance of the structural motif in a functionally important part of the receptors suggests hypotheses for kinase regulation and signal transduction.     

Investigation of the N-substituent conformation governing potency and mu receptor subtype-selectivity in (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists

A study of the binding site requirements associated with the N-substituent of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken using a set of rigid vs flexible N-substituents. The study showed that compounds 7-9 bearing the trans-cinnamyl N-substituent most closely reproduced the potency at the opioid receptor of the flexible N-propylphenyl or N-propylcyclohexyl analogues previously reported. Neither the N-substituted cis-cinnamyl nor the cis-phenylcyclopropylmethyl compounds 10 and 11, respectively, showed high affinity for the opioid receptor. However, the N-trans-phenylcyclopropylmethyl compound 12 closely approximated the affinity of compounds 7-9. Additionally, we found that free rotation of the phenyl ring is necessary for high affinity binding and mu receptor subtype selectivity as the planar N-substituted thianaphthylmethyl and benzofuranylmethyl compounds 13 and 14 had significantly lower binding affinities. Altogether, these findings suggest that the high binding affinity, selectivity, and antagonist potency of N-propylphenyl or N-propylcyclohexyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) are achieved via a conformation wherein the connecting chain of the N-substituents is extended away from piperidine nitrogen with the appended ring system rotated out-of-plane relative to the connecting chain atoms. This conformation is quite similar to that observed in the solid state for 5, as determined by single crystal X-ray analysis. Additionally, it was found that, unlike naltrexone, N-substituents bearing secondary carbons attached directly to the piperidine nitrogen of 4 suffer dramatic losses of potency vs analogues not substituted in this manner. Using a functional assay which measured stimulation or inhibition of [35S]GTP-gamma-S binding, we show that the trans-cinnamyl analogues of (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) retain opioid pure antagonist activity and possess picomolar antagonist potency at the mu receptor.     

Thyroid papillary carcinoma and its variants

The authors discuss the histological features of classical thyroid papillary carcinoma, with special emphasis on pathologic indicators related to prognosis. Its different variants are described, including: microcarcinoma, encapsulated variant, pure follicular variant, solid/trabecular variant, diffuse sclerosing and the cytologic variants of tall, columnar and oncocytic cell.     

Beanspruchungsverhalten von PVD-CrN Beschichtungen auf Leichtmetallwerkstoffen

Behaviour of light metals with PVD-CrN coatings using different test methods The application of thin hard coatings on machining tools, e.g. drilling tools is state of the art. The increase of lifetime of coated Tools compared to uncoated tools is well known. [1]. In this context ?separation of functions”? is an often used phrase, by meaning the separation of functions of the volume and the surface of materials. Going one step forward, from the point of view of tribology or corrosion this means, you have ?only”? to protect the surface by using a ?good”? coating without looking at the material underneath. In the past the influence of substrate materials or the optimization of the system (substrate-coating) was not the main aim of PVD development. Looking at substrate and coating as a system is especially necessary, if the differences of the properties of substrate and coating are large (e.g. hard coating – light metals). This paper shows different aspect of the tribological and electrochemical characterization of PVD coated light metals (CrN coating).     

Interleukin-6-associated inflammatory processes in Alzheimer's disease: new therapeutic options

The cytokine interleukin-6 is consistently detected in the brains of Alzheimer's disease patients but not in the brains of nondemented elderly persons. Until recently it was unclear whether an interleukin-6-associated inflammatory mechanism is an early or late event in the pathological cascade of Alzheimer's disease. We investigated whether interleukin-6 could be detected in plaques of Alzheimer's disease patients prior to the onset of neuritic degeneration. We found interleukin-6 mostly in plaques where neuritic pathology has not yet developed. This indicates that the appearance of interleukin-6 may precede neuritic changes and is not just a consequence of neuritic degeneration. Therefore, one may hypothesize that activation of inflammatory mechanisms may cause neuritic degeneration in plaques. A suppression of interleukin-6 synthesis could, therefore, be of therapeutic value. Upon screening a number of substances, we found that a small number of nonsteroidal antiinflammatory drugs, including tenidap, were able to inhibit interleukin-6 synthesis in cultured human astrocytoma cells. These substances may be therapeutically useful in Alzheimer's disease and should be evaluated in clinical studies.     

Mode-locking of an atmospheric pressure cross-excited electrically pulsed CO2laser

Self-mode-locking of a cross-excited electrically pulsed CO2laser has been observed and studied as a function of cavity length and operating pressure. The best results are obtained at a pressure of 450 torr with cavity lengths on the order of 1m. Two-ns duration pulses have been measured, the shortest pulses observed to date at 10.6-μ wavelength. With longer cavities more axial modes are locked, resulting in a longer dead time between pulses; however, the pulsewidths increase with increasing cavity length. Mode-locking was not improved by the use of the bleachable absorber SF6.     

Berechnung der Schmiedeguttemperaturen beim Reckschmieden

Aufteilung des Schmiedevorgangs in Abkühl- und Umformvorgänge. Wärmebilanzen für den Abkühl- und den Umformvorgang. Numerisches Lösungsverfahren. Auswertungen.