<Emphasis Type="Italic">In vitro</Emphasis> Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K _p), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K _p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.     

Software Replica of Minimal Living Processes

There is a long tradition of software simulations in theoretical biology to complement pure analytical mathematics which are often limited to reproduce and understand the self-organization phenomena resulting from the non-linear and spatially grounded interactions of the huge number of diverse biological objects. Since John Von Neumann and Alan Turing pioneering works on self-replication and morphogenesis, proponents of artificial life have chosen to resolutely neglecting a lot of materialistic and quantitative information deemed not indispensable and have focused on the rule-based mechanisms making life possible, supposedly neutral with respect to their underlying material embodiment. Minimal life begins at the intersection of a series of processes which need to be isolated, differentiated and duplicated as such in computers. Only software developments and running make possible to understand the way these processes are intimately interconnected in order for life to appear at the crossroad. In this paper, I will attempt to set out the history of life as the disciples of artificial life understand it, by placing these different lessons on a temporal and causal axis, showing which one is indispensable to the appearance of the next and how does it connect to the next. I will discuss the task of artificial life as setting up experimental software platforms where these different lessons, whether taken in isolation or together, are tested, simulated, and, more systematically, analyzed. I will sketch some of these existing software platforms: chemical reaction networks, Varela’s autopoietic cellular automata, Ganti’s chemoton model, whose running delivers interesting take home messages to open-minded biologists.     

Skipper impoverishment on large West Mediterranean islands (Lepidoptera Hesperioidea): deterministic,historical and stochastic factors

Biogeographical analyses are applied to skipper (Hesperioidea) presence/absence data from the Western Mediterranean mainland and the three largest islands (Sardinia, Corsica and Sicily) in order to identify potential conservation issues. The analyses performed on species, both collectively and individually, indicate that regional species richness and occurrence in the Mediterranean zone are largely predicted by latitude and area but that islands have impoverished faunas. Several species, predicted to be present on these islands from logistic regression of their continental distributions, are actually absent. The number of species predicted to be present from logistic regression analyses for each island, closely matched the number of species predicted to occur in regional-focused multiple regression analysis. This suggests that missing species have been identified. When compared with species that occur in Sicily and Corsica, the missing species are shown to differ for ecological traits, mainly those linked to altitudinal tolerance. No ecological distinctions were disclosed for Sardinian skippers suggesting a mainly stochastic colonisation. These results, and those from an analogous study carried out on Papilionoidea, point to Hesperioidea having (i) overall more impoverished faunas on islands and (ii) being subject to stochastic or historical colonisation events more than Papilionoidea. Species not predicted to occur on islands based on their mainland distributions and ecological traits, are foci for conservation attention. However, as many species becoming extinct on the islands may be irreplaceable, all species, in particular the Sardinian ones, deserve to be conserved.     

Heat stress in the presence of low RNA polymerase activity increases chromosome copy number of Escherichia coli

Summary A temperature shift-up accompanied by a reduction in RNA polymerase activity in Escherichia coli causes an increased rate of initiation leading to a 1.7- to 2.2-fold increase in chromosome copy number. A temperature shift-up without a reduction in polymerase activity induces only a transient non-scheduled initiation of chromosome replication caused by heat shock with no detectable effect on chromosome copy number.     

The 30-Base-Pair Deletion in Chinese Variants of the Epstein-Barr Virus LMP1 Gene Is Not the Major Effector of Functional Differences between Variant LMP1 Genes in Human Lymphocytes

One group of sequence variants of Epstein-Barr virus is characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this deletion upon LMP1 function in four human lymphoid cell lines by using three natural variants of LMP1: the prototype B95.8 gene and the CAO and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted. These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8-LMP1 in two lines and was only slightly impaired in the other two lines. Activation of NF-κB by CAO-LMP1 was not impaired in any of the lines; rather, activation of an NF-κB reporter by CAO-LMP1 was consistently about twofold greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes, the 10-amino-acid deletion appears not to be directly responsible. This conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the distinct functional characteristics of CAO-LMP1 in human lymphoid cells.     

Analysis of Flow Phenomena in Gastric Contents Induced by Human Gastric Peristalsis Using CFD

This paper uses computational fluid dynamics to simulate and analyze intragastric fluid motions induced by human peristalsis. We created a two-dimensional computational domain of the distal stomach where peristalsis occurs. The motion of the gastric walls induced by an antral contraction wave (ACW) on the wall of the computational domain was well simulated using a function defined in this study. Retropulsive flow caused by ACW was observed near the occluded region, reaching its highest velocity of approximately 12 mm/s in the narrowest region. The viscosity of the model gastric contents applied in this study hardly affected the highest velocity, but greatly affected the velocity profile in the computational domain. The shear rate due to gastric fluid motion was calculated using the numerical output data. The shear rate reached relatively high values of approximately 20 s⁻¹ in the most occluded region. The shear rate profile was almost independent of the fluid viscosity. We also simulated mass transfer of a gastric digestive enzyme (pepsin) in model gastric content when peristalsis occurs on the gastric walls. The visualized simulation results suggest that gastric peristalsis is capable of efficiently mixing pepsin secreted from the gastric walls with an intragastric fluid.     

A catalogue of <Emphasis Type="Italic">Triticum monococcum</Emphasis> genes encoding toxic and immunogenic peptides for celiac disease patients

The celiac disease (CD) is an inflammatory condition characterized by injury to the lining of the small-intestine on exposure to the gluten of wheat, barley and rye. The involvement of gluten in the CD syndrome has been studied in detail in bread wheat, where a set of “toxic” and “immunogenic” peptides has been defined. For wheat diploid species, information on CD epitopes is poor. In the present paper, we have adopted a genomic approach in order to understand the potential CD danger represented by storage proteins in diploid wheat and sequenced a sufficiently large number of cDNA clones related to storage protein genes of Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides were found. All the classes of storage proteins were shown to contain harmful sequences. The major conclusion is that einkorn has the full potential to induce the CD syndrome, as already evident for polyploid wheats. In addition, a complete overview of the storage protein gene arsenal in T. monococcum is provided, including a full-length HMW x-type sequence and two partial HMW y-type sequences. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Midsummer heat wave effects on lacustrine plankton: Variation of assemblage structure and fatty acid composition

The effects of the 2003 European heat wave on a freshwater plankton assemblage and its fatty acid (FA) composition were investigated. Composition and FA profiles of four size categories of planktonic organisms collected in 2003 were compared to those of the colder year 2002.     

Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Background  

Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.