Tandemly arrayed non-coding sequences or satellite DNAs (satDNAs) are rapidly evolving segments of eukaryotic genomes, including the centromere, and may raise a genetic barrier that leads to speciation. However, determinants and mechanisms of satDNA sequence dynamics are only partially understood. Sequence analyses of a library of five satDNAs common to the root-knot nematodes Meloidogyne chitwoodi and M. fallax together with a satDNA, which is specific for M. chitwoodi only revealed low sequence identity (32–64%) among them. However, despite sequence differences, two conserved motifs were recovered. One of them turned out to be highly similar to the CENP-B box of human alpha satDNA, identical in 10–12 out of 17 nucleotides. In addition, organization of nematode satDNAs was comparable to that found in alpha satDNA of human and primates, characterized by monomers concurrently arranged in simple and higher-order repeat (HOR) arrays. In contrast to alpha satDNA, phylogenetic clustering of nematode satDNA monomers extracted either from simple or from HOR array indicated frequent shuffling between these two organizational forms. Comparison of homogeneous simple arrays and complex HORs composed of different satDNAs, enabled, for the first time, the identification of conserved motifs as obligatory components of monomer junctions. This observation highlights the role of short motifs in rearrangements, even among highly divergent sequences. Two mechanisms are proposed to be involved in this process, i.e., putative transposition-related cut-and-paste insertions and/or illegitimate recombination. Possibility for involvement of the nematode CENP-B box-like sequence in the transposition-related mechanism and together with previously established similarity of the human CENP-B protein and pogo-like transposases implicate a novel role of the CENP-B box and related sequence motifs in addition to the known function in centromere protein binding. 相似文献
In this review, we address the regulatory and toxic role of ·NO along several pathways, from the gut to the brain. Initially, we address the role on ·NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson’s disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by ·NO, it became clear the potential for toxic ·NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins. Accordingly, we have proposed a novel mechanism potentially leading to dopaminergic cell death, providing evidence that NO synergistically interact with DOPAC in promoting cell death via mechanisms that involve GSH depletion. The modulatory role of NO will be then briefly discussed as a master regulator on brain energy metabolism. The energy metabolism in the brain is central to the understanding of brain function and disease. The core role of ·NO in the regulation of brain metabolism and vascular responses is further substantiated by discussing its role as a mediator of neurovascular coupling, the increase in local microvessels blood flow in response to spatially restricted increase of neuronal activity. The many facets of NO as intracellular and intercellular messenger, conveying information associated with its spatial and temporal concentration dynamics, involve not only the discussion of its reactions and potential targets on a defined biological environment but also the regulation of its synthesis by the family of nitric oxide synthases. More recently, a novel pathway, out of control of NOS, has been the subject of a great deal of controversy, the nitrate:nitrite:NO pathway, adding new perspectives to ·NO biology. Thus, finally, this novel pathway will be addressed in connection with nitrate consumption in the diet and the beneficial effects of protein nitration by reactive nitrogen species.
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 (Kp), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for Kp 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. 相似文献
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. 相似文献
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. 相似文献
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. 相似文献
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. 相似文献
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. 相似文献
In heterogeneous environments, sex-biased dispersal could lead to environmental adaptive parental effects, with offspring
selected to perform in the same way as the parent dispersing least, because this parent is more likely to be locally adapted.
We investigate this hypothesis by simulating varying levels of sex-biased dispersal in a patchy environment. The relative
advantage of a strategy involving pure maternal (or paternal) inheritance is then compared with a strategy involving classical
biparental inheritance in plants and in animals. 相似文献