Ageing and the evolution of female resistance to remating in seed beetles

Female remating behaviour is a key mating system parameter that is predicted to evolve according to the net effect of remating on female fitness. In many taxa, females commonly resist male remating attempts because of the costs of mating. Here, we use replicated populations of the seed beetle Acanthoscelides obtectus selected for either early or late life reproduction and show that 'Early' and 'Late' females evolved different age-specific rates of remating. Early females were more likely to remate with control males as they aged, while Late females were more resistant to remating later in life. Thus, female remating rate decreases with age when direct selection on late-life fitness is operating and increases when such selection is relaxed. Our findings not only demonstrate that female resistance to remating can evolve rapidly, but also that such evolution is in accordance with the genetic interests of females.     

Evaluation of Novel Acyclic Nucleoside Phosphonates against Human and Animal Gammaherpesviruses Revealed an Altered Metabolism of Cyclic Prodrugs upon Epstein-Barr Virus Reactivation in P3HR-1 Cells

Acyclic nucleoside phosphonates (ANPs), such as (S)-1-[(3-hydroxy-2-phosphonomethoxy)propyl)]cytosine (HPMPC), are an important group of broad-spectrum antiviral agents with activity against DNA viruses. In this report, we present the in vitro potencies of novel ANPs against gammaherpesviruses, including Kaposi''s sarcoma-associated herpesvirus, Epstein-Barr virus (EBV), and three animal gammaherpesviruses. 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-3-deazaadenine (3-deaza-HPMPA), and their cyclic derivatives have emerged as highly potent antigammaherpesvirus agents. Interestingly, cyclic prodrugs of ANPs exhibited reduced activities against EBV strain P3HR-1, but not against EBV strain Akata. Cell culture metabolism studies with HPMPC and cyclic HPMPC revealed that these differences were attributable to an altered drug metabolism in P3HR-1 cells after EBV reactivation and, more specifically, to a reduced hydrolysis of cyclic HPMPC by cyclic CMP phosphodiesterase. We did not correlate this effect with phosphodiesterase downregulation, or to functional mutations. Instead, altered cyclic AMP levels in P3HR-1 cells indicated a competitive inhibition of the phosphodiesterase by this cyclic nucleotide. Finally, both HPMPC and HPMP-5-azaC emerged as highly effective inhibitors in vivo through significant inhibition of murine gammaherpesvirus replication and dissemination. With the current need for potent antigammaherpesvirus agents, our findings underline the requirement of appropriate surrogate viruses for antiviral susceptibility testing and highlight HPMP-5-azaC as a promising compound for future clinical development.     

Restoration of pool margin communities in cutover peatlands

Two experiments were conducted for developing restoration techniques for pool margin communities in cutover peatlands. We first aimed to measure the regeneration potential of a typical edge pool liverwort, Cladopodiella fluitans (Nees) H. Buch. We introduced C. fluitans in floating baskets in a restored peatland. We tested three fragment sizes (patches of 2 cm², stretched patches and shredded fine fragments of 0.1-1 mm), two introduction densities (ratio between surface of collected areas and surface of restored areas of 1:5 and 1:10) as well as the effect of a straw mulch. After two years, the percentage covers of C. fluitans were five times larger in experimental units protected with straw than in those without protection. Yet, the fragment sizes and the densities tested had no effect on the regeneration of the liverwort. The second experiment aimed to test a moss layer transfer approach to restore plant diversity around pool margins. We tested four communities, dominated by (1) Sphagnum cuspidatum Hoffman, (2) Sphagnum fallax (H. Klinggraff) H. Klinggraff, (3) Sphagnum papillosum Linberg as well as (4) a mixed community composed of equal quantities of C. fluitans, S. cuspidatum and S. papillosum. We introduced plant material in two density ratios (1:5 and 1:10). Sphagnum mosses did colonize pool margins, and showed even more than 60% cover for some treatments after three growing seasons, but the recovery of the introduced vascular plants remained below 5% for most species. The establishment of pool vascular species thus seems to be more intricate than for bryophytes and specific introduction techniques might be needed.     

Rational design of RAR-selective ligands revealed by RARbeta crystal stucture

The crystal structure of the ligand-binding domain of RARbeta, a suspect tumour suppressor, reveals important features that distinguish it from the two other RAR isotypes. The most striking difference is an extra cavity allowing RARbeta to bind more bulky agonists. Accordingly, we identified a ligand that shows RARbeta selectivity with a 100-fold higher affinity to RARbeta than to alpha or gamma isotypes. The structural differences between the three RAR ligand-binding pockets revealed a rationale explaining how a single retinoid can be at the same time an RARalpha, gamma antagonist and an RARbeta agonist. In addition, we demonstrate how to generate an RARbeta antagonist by gradually modifying the bulkiness of a single substitution. Together, our results provide structural guidelines for the synthesis of RARbeta-selective agonists and antagonists, allowing for the first time to address pharmacologically the tumour suppressor role of RARbeta in vitro and in animal models.     

Brain extracellular fluid protein changes in acute stroke patients

In vivo human brain extracellular fluids (ECF) of acute stroke patients were investigated to assess the changes in protein levels associated with ischemic damages. Microdialysates (MDs) from the infarct core (IC), the penumbra (P), and the unaffected contralateral (CT) brain regions of patients suffering an ischemic stroke (n = 6) were compared using a shotgun proteomic approach based on isobaric tagging and mass spectrometry. Quantitative analysis showed 53 proteins with increased amounts in the IC or P with respect to the CT samples. Glutathione S-transferase P (GSTP1), peroxiredoxin-1 (PRDX1), and protein S100-B (S100B) were further assessed with ELISA on the blood of unrelated control (n = 14) and stroke (n = 14) patients. Significant increases of 8- (p = 0.0002), 20- (p = 0.0001), and 11-fold (p = 0.0093) were found, respectively. This study highlights the value of ECF as an efficient source to further discover blood stroke markers.