Docking and molecular dynamics studies of peripheral site ligand–oximes as reactivators of sarin-inhibited human acetylcholinesterase

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.     

ON THE EVOLUTION OF MIGRATION IN HETEROGENEOUS ENVIRONMENTS

Populations often experience variable conditions, both in time and space. Here we develop a novel theoretical framework to study the evolution of migration under the influence of spatially and temporally variable selection and genetic drift. First, we examine when polymorphism is maintained at a locus under heterogeneous selection, as a function of the pattern of spatial heterogeneity and the migration rate. In a second step, we study how levels of migration evolve under the joint action of kin competition and local adaptation at a polymorphic locus. This analysis reveals the existence of evolutionary bistability, whereby a low or a high migration rate may evolve depending on the initial conditions. Last, we relax several assumptions regarding selection heterogeneity commonly made in previous studies and explore the consequences of more complex spatial and temporal patterns of variability in selection on the evolution of migration. We found that small modifications in the pattern of environmental heterogeneity may have dramatic effects on the evolution of migration. This work highlights the importance of considering more general scenarios of environmental heterogeneity when studying the evolution of life‐history traits in ecologically complex settings.     

HOLOKINETIC DRIVE: CENTROMERE DRIVE IN CHROMOSOMES WITHOUT CENTROMERES

Similar to how the model of centromere drive explains the size and complexity of centromeres in monocentrics (organisms with localized centromeres), our model of holokinetic drive is consistent with the divergent evolution of chromosomal size and number in holocentrics (organisms with nonlocalized centromeres) exhibiting holokinetic meiosis (holokinetics). Holokinetic drive is proposed to facilitate chromosomal fission and/or repetitive DNA removal (or any segmental deletion) when smaller homologous chromosomes are preferentially inherited or chromosomal fusion and/or repetitive DNA proliferation (or any segmental duplication) when larger homologs are preferred. The hypothesis of holokinetic drive is supported primarily by the negative correlation between chromosome number and genome size that is documented in holokinetic lineages. The supporting value of two older cross‐experiments on holokinetic structural heterozygotes (the rush Luzula elegans and butterflies of the genus Antheraea) that indicate the presence of size‐preferential homolog transmission via female meiosis for holokinetic drive is discussed, along with the further potential consequences of holokinetic drive in comparison with centromere drive.     

Understanding the Role of Dicer in Astrocyte Development

The Dicer1 allele is used to show that microRNAs (miRNAs) play important roles in astrocyte development and functions. While it is known that astrocytes that lack miRNAs are dysregulated, the in vivo phenotypes of these astrocytes are not well understood. In this study, we use Aldh1l1-EGFP transgene, a marker of astrocytes, to characterize mouse models with conditional Dicer1 ablation (via either human or mouse GFAP-Cre). This transgene revealed novel features of the defective astrocytes from the absence of miRNA. Although astrocyte miRNAs were depleted in both lines, we found histological and molecular differences in the Aldh1l1-EGFP cells between the two Cre lines. Aldh1l1-EGFP cells from hGFAP-Cre mutant lines displayed up-regulation of Aldh1l1-EGFP with increased proliferation and a genomic profile that acquired many features of wildtype primary astrocyte cultures. In the young mGFAP-Cre mutant lines we found that Aldh1l1-EGFP cells were disorganized and hyperproliferative in the developing cerebellum. Using the Aldh1l1-EGFP transgene, our work provides new insights into the roles of miRNAs in astrocyte development and the features of astrocytes in these two mouse models.     

Prise en charge des troubles de la reproduction chez l’adolescent

Adolescence is a period marked by the search for sexual identity. How do paraplegic or quadriplegic teenagers develop their sexual identity? How can the nursing team help them in this process? The authors study erection and the quality of sexual relations and then examine the problem of procreation. Early, practical information adapted to the neurological definition of the spinal cord injury is essential, with preservation of sperm prior to the development of urological and infectious complications. The authors report their experience of 24 paraplegic or tetraplegic teenagers at the CMPA in Neufmoutiers and the CECOS at Cochin Hospital in Paris.