Differential effects of antiepileptic drugs on human bone cells

Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.     

Butterfly–host plant synchrony determines patterns of host use across years and regions

Variation in the degree of synchrony among host plants and herbivores can disrupt or intensify species interactions, alter the strength of natural selection on traits associated with phenological timing, and drive novel host plant associations. We used field observations from three regions during four seasons to examine how timing of the butterfly herbivore Anthocharis cardamines relative to six host plant species (Arabis hirsuta, Cardamine pratensis, Arabis glabra, Arabidopsis thaliana, Thlaspi caerulescens and Capsella bursa‐pastoris) influenced host species use and the choice of host plant individuals within populations. Butterflies laid a larger fraction of their eggs on species that were closer to the butterfly's preferred stage of development than on other host species. Within host plant populations, butterflies showed a stronger preference for individuals with a late phenology when plants within the population were on average more developed at the time of butterfly flight. Our results suggest that changes in synchrony between herbivores and their host plants are associated with changes in both host species use and the choice of host plant individuals differing in phenology within populations. This is likely to be an important mechanism generating variation in interaction intensities and trait selection in the wild, and therefore also relevant for understanding how anthropogenic induced changes, such as global warming, will influence natural communities.     

Competition for alfalfa nodulation under metal stress by the metal‐tolerant strain Ochrobactrum cytisi Azn6.2

Legume plants, in association with rhizobia, are gaining increasing interest for heavy metal rhizoremediation. This symbiotic interaction combines the advantages of rhizoremediation and soil nitrogen enrichment. In metal polluted soils, Ochrobactrum cytisi can elicit non‐fixing nodules on legumes, including Medicago sativa. Nodulation kinetics was much slower when M. sativa plants were inoculated with O. cytisi Azn6.2 compared with the natural symbiont Ensifer meliloti 1021 and nodules were ineffective in nitrogen fixation. A competition experiment was performed using alfalfa grown on heavy metals, and co‐inoculated with equal amounts of the metal‐sensitive E. meliloti 1021 and the metal‐resistant O. cytisi Azn6.2. When plants were inoculated in non‐polluted substrates, all nodules were formed by E. meliloti 1021. Nevertheless, under increasing metal concentrations, the number of nodules occupied by O. cytisi grew. At the highest metal concentration, all nodules were elicited by O. cytisi, suggesting that the resistant species can take the place of the natural symbiont. This fact has important ecological and environmental implications when proposing legume–rhizobia symbioses for rhizoremediation and highlights the need of selecting highly resistant rhizobia in order to be competitive in polluted soils.     

Functional integration for enrolment constrains evolutionary variation of phacopid trilobites despite developmental modularity

Modularity and integration are variational properties expressed at various levels of the biological hierarchy. Mismatches among these levels, for example developmental modules that are integrated in a functional unit, could be informative of how evolutionary processes and trade‐offs have shaped organismal morphologies as well as clade diversification. In the present study, we explored the full, integrated and modular spaces of two developmental modules in phacopid trilobites, the cephalon and the pygidium, and highlight some differences among them. Such contrasts reveal firstly that evolutionary processes operating in the modular spaces are stronger in the cephalon, probably due to a complex regime of selection related to the numerous functions ensured by this module. Secondly, we demonstrate that the same pattern of covariation is shared among species, which also differentiate along this common functional integration. This common pattern might be the result of stabilizing selection acting on the enrolment and implying a coordinate variation between the cephalon and the pygidium in a certain direction of the morphospace. Finally, we noticed that Austerops legrandi differs slightly from other species in that its integration is partly restructured in the way the two modules interact. Such a divergence can result from the involvement of the cephalon in several vital functions that may have constrained the response of the features involved in enrolment and reorganized the covariation of the pygidium with the cephalon. Therefore, it is possible that important evolutionary trade‐offs between enrolment and other functions on the cephalon might have partly shaped the diversification of trilobites.     

Great spotted cuckoo eggshell microstructure characteristics can make eggs stronger

Obligate avian brood parasites lay stronger eggs than their hosts or non‐parasitic relatives because they are rounder and have a thicker eggshell. Additionally, some other characteristics of the brood parasitic eggshells related to their microstructure such as size and orientation of calcite crystal units could also contribute to generating even stronger shells. An eggshell microstructure formed by small randomly oriented calcite crystal units can increase the robustness of the eggshells of birds. Here, the eggshell microstructure of avian brood parasites as well as their hosts have been characterized in detail, using X‐ray diffraction analyses to estimate the size and degree of orientation of calcite crystal units making the eggshell. Specifically, the brood parasitic great spotted cuckoo Clamator glandarius and two hosts (jackdaws Corvus monedula and magpie Pica pica) and one non‐host species (the pigeon, Columba livia domestica) were considered. Calcite crystal of the eggshell of the brood parasitic species was smaller and more randomly oriented than those of the eggshells of non‐parasitic species, which suggest that eggshell microstructure would contribute to explain why parasitic eggs are more resistant to breakage than those of their hosts.     

Ab initio vibrational calculations on ara-T molecule: application to analysis of IR and Raman spectra

The FTIR and FT-Raman spectra are reported for the arabinonucleoside ara-T (1-beta-D-arabinofuranosylthymine), which shows antiviral activity. The accurate knowledge of the vibrational modes is a prerequisite for the elucidation of drug-nucleotide and drug-enzyme interactions. The FTIR and FT-Raman spectra of ara-T were recorded from 4000 to 30 cm(-1). A tetradeuterated derivative (deuteration at N3, and hydroxyl groups O'2, O'3, and O'5) was synthesized and the observed isotopic shifts in its spectra were used for the vibrational analysis of ara-T. The theoretical frequencies and the potential energy distribution (PED) of the vibrational modes of ara-T were calculated using the ab initio Hartree-Fock/3-21G method. An assignment of the vibrational spectra of ara-T is proposed considering the scaled PED and the observed band shifts under deuteration. The scaled ab initio frequencies were in reasonable agreement with the experimental data.     

Expression of NAD(P)H:quinone oxidoreductase 1 in HeLa cells: role of hydrogen peroxide and growth phase

The aim of this work was to study the role of H(2)O(2) in the regulation of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase, EC ) with relation to cell density of HeLa cells cultures and the function played by NQO1 in these cells. Levels of NQO1 activity were much higher (40-fold) in confluent HeLa cells than in sparse cells, the former cells being much more resistant to H(2)O(2). Addition of sublethal concentrations of H(2)O(2) (up to 24 microm) produced a significant increase of NQO1 (up to 16-fold at 12 microm) in sparse cells but had no effect in confluent cells. When cells reached confluency in the presence of pyruvate, a H(2)O(2) scavenger, NQO1 activity was decreased compared with cultures grown to confluency without pyruvate. Inhibition of quinone reductases by dicumarol substantially decreased viability of confluent cells in serum-free medium. This is the first demonstration that regulation of NQO1 expression by H(2)O(2) is dependent on the cell density in HeLa cells and that endogenous generation of H(2)O(2) participates in the increase of NQO1 activity as cell density is higher. This enzyme is required to promote survival of confluent cells.