A novel approach to modelling water transport and drug diffusion through the stratum corneum

<p>Abstract</p> <p>Background</p> <p>The potential of using skin as an alternative path for systemically administering active drugs has attracted considerable interest, since the creation of novel drugs capable of diffusing through the skin would provide a great step towards easily applicable -and more humane- therapeutic solutions. However, for drugs to be able to diffuse, they necessarily have to cross a permeability barrier: the <it>stratum corneum </it>(SC), the uppermost set of skin layers. The precise mechanism by which drugs penetrate the skin is generally thought to be diffusion of molecules through this set of layers following a "tortuous pathway" around corneocytes, i.e. impermeable dead cells.</p> <p>Results</p> <p>In this work, we simulate water transport and drug diffusion using a three-dimensional porous media model. Our numerical simulations show that diffusion takes place through the SC regardless of the direction and magnitude of the fluid pressure gradient, while the magnitude of the concentrations calculated are consistent with experimental studies.</p> <p>Conclusions</p> <p>Our results support the possibility for designing arbitrary drugs capable of diffusing through the skin, the time-delivery of which is solely restricted by their diffusion and solubility properties.</p

Endoreplication Controls Cell Fate Maintenance

Cell-fate specification is typically thought to precede and determine cell-cycle regulation during differentiation. Here we show that endoreplication, also known as endoreduplication, a specialized cell-cycle variant often associated with cell differentiation but also frequently occurring in malignant cells, plays a role in maintaining cell fate. For our study we have used Arabidopsis trichomes as a model system and have manipulated endoreplication levels via mutants of cell-cycle regulators and overexpression of cell-cycle inhibitors under a trichome-specific promoter. Strikingly, a reduction of endoreplication resulted in reduced trichome numbers and caused trichomes to lose their identity. Live observations of young Arabidopsis leaves revealed that dedifferentiating trichomes re-entered mitosis and were re-integrated into the epidermal pavement-cell layer, acquiring the typical characteristics of the surrounding epidermal cells. Conversely, when we promoted endoreplication in glabrous patterning mutants, trichome fate could be restored, demonstrating that endoreplication is an important determinant of cell identity. Our data lead to a new model of cell-fate control and tissue integrity during development by revealing a cell-fate quality control system at the tissue level

Exploiting Malicious Node Detection for Lifetime Extension of Sensor Networks

Abstract—Wireless Sensor Networks (WSN) have attracted considerable research effort in the community during the past couple of years. One of the most challenging issues so far is the extension of network lifetime with regards to small battery capacity and self-sustained operation. Endeavors to save energy have been made on various frontiers, ranging from hardware improvements over medium access and routing protocols to network clustering and role changing strategies. In addition some authors studied failures in communication regarded as error detection. Yet, only weak attention has been paid to the detection of malicious nodes and its potential for lifetime extension. In this work, we present a short overview of detection and classification of malicious nodes in WSN and describe its potential in terms of network lifetime and reliability

Experimental superinfection of a Lesser Malayan mousedeer (Tragulus javanicus) persistently infected with bovine viral diarrhea virus

A Lesser Malayan mousedeer (Tragulus javanicus), persistently infected with noncytopathogenic bovine viral diarrhea virus (BVDV) type 1f, was experimentally superinfected with a cytopathogenic isolate of BVDV type 1c, which antigenically partially matched the endogenous strain. Within the observational period of 125 days after superinfection, the animal did not demonstrate any clinical signs of the disease and/or significant changes in blood values. Neutralizing antibodies were detected at 35 and 42 days postinfection. The isolate causing the superinfection was found in feces, nasal swabs, and saliva starting from day 29 and at various times postchallenge. Macroscopic or histologic examination did not reveal mucosal disease-like lesions, despite the detection of the cytopathogenic isolate in the salivary gland, rumen, abomasum, kidney, and superficial prescapular lymph node. Results indicate that the cytopathogenic BVDV strain, which was used in the superinfection, persisted in the viremic animal without causing disease within the observation period

Genetic variability of the Gironde population of Acipenser sturio

International audienceAcipenser sturio reproduces currently only in the Gironde basin, France, with three natural reproductions observed in 1980, 1988 and 1994. The survival of the species depends upon successful artificial reproduction and stocking. We analysed the genetic structure of the population including both, genetic variability in the entire population and degree of relatedness between single individuals. The results of the study suggest the utilization of specimens representing the largest genetic differences for artificial reproduction first

Origin and patterns of genetic diversity of German fallow deer as inferred from mitochondrial DNA

Although not native to Germany, fallow deer (Dama dama) are commonly found today, but their origin as well as the genetic structure of the founding members is still unclear. In order to address these aspects, we sequenced ~400 bp of the mitochondrial d-loop of 365 animals from 22 locations in nine German Federal States. Nine new haplotypes were detected and archived in GenBank. Our data produced evidence for a Turkish origin of the German founders. However, German fallow deer populations have complex patterns of mtDNA variation. In particular, three distinct clusters were identified: Schleswig-Holstein, Brandenburg/Hesse/Rhineland and Saxony/lower Saxony/Mecklenburg/Westphalia/Anhalt. Signatures of recent demographic expansions were found for the latter two. An overall pattern of reduced genetic variation was therefore accompanied by a relatively strong genetic structure, as highlighted by an overall Phict value of 0.74 (P < 0.001)

Gene expression profiling of single epidermal, basal and trichome cells of Arabidopsis thaliana

Samples of single epidermal, basal and trichome cells were collected by glass microcapillaries from 7-week-old Arabidopsis thaliana leaves. Transcript amplification of these single-cell samples was performed by RT PCR. For gene expression profiling, we hybridized the amplified transcriptome of each individual cell type to nylon membranes spotted with 16,000 Arabidopsis expressed sequence tags (ESTs). Initial analysis of the array filter data enabled us to functionally categorize transcripts that were present in each individual cell type. In order to confirm the filter array data, we used RT PCR. Results of this RT PCR approach confirmed the presence of 12 selected candidate genes in agreement with array filter hybridization data. Further, transcripts involved in detoxification and sulfur metabolism could be identified in epidermal cell extracts. Together, the results of our study provide the localization of approximately 1000 expressed genes to either pavement, basal or trichome cells. To cluster transcripts with similar expression levels, we developed a novel mathematical algorithm. Based on the mean and standard deviation, ratios of expression levels of a transcript were defined for pairs of the three cell types. This numerical analysis enabled subdivision into 67 categories of genes differentially expressed in epidermal, basal and trichome cells. Transcripts in each category displayed similar ratios of expression levels in the three cell types. Examples of these clusters are presented and discussed in Appendix A