Genetic Variations Strongly Influence Phenotypic Outcome in the Mouse Retina

Variation in genetic background can significantly influence the phenotypic outcome of both disease and non-disease associated traits. Additionally, differences in temporal and strain specific gene expression can also contribute to phenotypes in the mammalian retina. This is the first report of microarray based cross-strain analysis of gene expression in the retina investigating genetic background effects. Microarray analyses were performed on retinas from the following mouse strains: C57BL6/J, AKR/J, CAST/EiJ, and NOD.NON-H2-nb1 at embryonic day 18.5 (E18.5) and postnatal day 30.5 (P30.5). Over 3000 differentially expressed genes were identified between strains and developmental stages. Differential gene expression was confirmed by qRT-PCR, Western blot, and immunohistochemistry. Three major gene networks were identified that function to regulate retinal or photoreceptor development, visual perception, cellular transport, and signal transduction. Many of the genes in these networks are implicated in retinal diseases such as bradyopsia, night-blindness, and cone-rod dystrophy. Our analysis revealed strain specific variations in cone photoreceptor cell patterning and retinal function. This study highlights the substantial impact of genetic background on both development and function of the retina and the level of gene expression differences tolerated for normal retinal function. These strain specific genetic variations may also be present in other tissues. In addition, this study will provide valuable insight for the development of more accurate models for human retinal diseases

Niobium tunnel junctions with multi-layered electrodes

The current-voltage characteristics of the niobium - aluminum oxide - niobium tunnel junctions have been studied systematically and are compared with numerical simulations based on the microscopic theory of the proximity effect. The thickness of the base niobium layer is varied from 35 to 500 mn while the thickness of the aluminum layer is kept constant (about 9 mm). In a separate series of experiments the aluminum thickness is varied from 2 to 30 mn for two fixed thickness of the base electrode: 50 and 200 mn. The appropriate conditions for a full suppression of the so called "knee" structure at the gap voltage in the current-voltage characteristic are experimentally determined and theoretically interpreted in the framework of the microscopic theory. The influence of the additional aluminum layer in a composite base electrode on the properties of the tunnel junction have been studied in dependence on the aluminum thickness and distance of this layer from the barrier. The obtained results demonstrate that the current-voltage characteristics of tunnel junction can be engineering by an appropriate layer thickness of compound base electrode

Selectivity of 7-alkoxycoumarins as probe substrates for rat hepatic cytochrome P450 forms is influenced by the substitution pattern on the coumarin nucleus

1. The O-dealkylation of 7-alkoxycoumarins is widely used as an assay to characterize cytochrome P450 (CYP) activity. These substrates can also undergo oxidative attack at additional sites on the coumarin nucleus, which may influence their apparent selectivity for particular CYP forms. 2. Accordingly, the effect of blockade of these additional sites was investigated on the selectivity towards rat hepatic CYP forms, with emphasis on the CYP1A and 2B forms. 3. Blockade of the 3-/4- and 6-positions resulted in substrates for which the CYP1A1/2 selectivity of the unsubstituted 7-alkoxycoumarins was altered to a CYP2B selectivity; this was achieved with little overall change in the molecular dimensions of the substrate. Limited analysis of other inducible CYP forms indicated at most only small effects of structure modi. cation on activity. 4. The findings suggest that the sensitivity of probe substrates for CYP forms may be limited by the occurrence of competing side reactions of the substrate, and that better probes may be derived by blocking the sites of these side reactions

Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

<p>Abstract</p> <p>Background</p> <p>Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition.</p> <p>Results</p> <p>New improved extraction methods were applied on the bark of <it>Betula pendula</it> in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and ¹³C NMR spectroscopy which revealed a very high yield of betulin (over 90%). Growth inhibiting effects were measured <it>in vitro</it> on four malignant human cell lines: A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma), HeLa (cervix adenocarcinoma) and MCF7 (breast adenocarcinoma), by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice.</p> <p>Conclusions</p> <p>The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.</p