11 research outputs found
The Proteolipid Protein Promoter Drives Expression outside of the Oligodendrocyte Lineage during Embryonic and Early Postnatal Development
The proteolipid protein (Plp) gene promoter is responsible for driving expression of one of the major components of myelin – PLP and its splice variant DM-20. Both products are classically thought to express predominantly in oligodendrocytes. However, accumulating evidence suggests Plp expression is more widespread than previously thought. In an attempt to create a mouse model for inducing oligodendrocyte-specific gene deletions, we have generated transgenic mice expressing a Cre recombinase cDNA under control of the mouse Plp promoter. We demonstrate Plp promoter driven Cre expression is restricted predominantly to mature oligodendrocytes of the central nervous system (CNS) at postnatal day 28. However, crosses into the Rosa26LacZ and mT/mG reporter mouse lines reveal robust and widespread Cre activity in neuronal tissues at E15.5 and E10.5 that is not strictly oligodendrocyte lineage specific. By P28, all CNS tissues examined displayed high levels of reporter gene expression well outside of defined white matter zones. Importantly, our study reinforces the emerging idea that Plp promoter activity is not restricted to the myelinating cell lineage, but rather, has widespread activity both during embryonic and early postnatal development in the CNS. Specificity of the promoter to the oligodendrocyte cell lineage, as shown through the use of a tamoxifen inducible Plp-CreERt line, occurs only at later postnatal stages. Understanding the temporal shift in Plp driven expression is of consequence when designing experimental models to study oligodendrocyte biology
Global human footprint on the linkage between biodiversity and ecosystem functioning in reef fishes
Copyright: © 2011 Mora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas
Synthesis of Gly-ψ[(<i>Z</i>)CFCH]-Phe, a Fluoroalkene Dipeptide Isostere, and Its Incorporation into a Leu-enkephalin Peptidomimetic
A new
Leu-enkephalin peptidomimetic designed to explore the hydrogen
bond acceptor ability of the third peptide bond has been prepared
and studied. This new analog is produced by replacing the third amide
of Leu-enkephalin with a fluoroalkene. An efficient and innovative
synthesis of the corresponding dipeptide surrogate Fmoc-Gly-ψ[(<i>Z</i>)CFCH]-Phe-OH is described. The key step involves
the alkylation of a tin dienolate from the less hindered face of its
chiral sulfonamide auxiliary derived from camphor. Once its synthesis
was complete, its incorporation into the peptidomimetic sequence was
achieved on a solid support with chlorotrityl resin following the
Fmoc strategy. The peptidomimetic was characterized using competition
binding with [<sup>125</sup>I]-deltorphin I on membrane extracts of
HEK293 cells expressing the mouse delta opioid receptor (DOPr) and
based on its abilities to inhibit the electrically induced contractions
of the mouse <i>vas deferens</i> and to activate the ERK1/2
signaling pathway in DRGF11/DOPr-GFP cells. Together with our previous
observations, our findings strongly suggest that the third amide bond
of Leu-enkephalin primarily acts as a hydrogen bond acceptor in DOPr.
Consequently, this amide bond can be successfully replaced by an ester,
a thioamide, or a fluoroalkene without greatly impacting the binding
or biological activity of the corresponding analogs. The lipophilicity
(LogD<sub>7.4</sub>) of the active analog was also measured. It appears
that fluoroalkenes are almost as efficient at increasing the lipophilicity
as normal alkenes
Preparation and Evaluation at the Delta Opioid Receptor of a Series of Linear Leu-Enkephalin Analogues Obtained by Systematic Replacement of the Amides
Leu-enkephalin
analogues, in which the amide bonds were sequentially and systematically
replaced either by ester or <i>N</i>-methyl amide bonds,
were prepared using classical organic chemistry as well as solid phase
peptide synthesis (SPPS). The peptidomimetics were characterized using
competition binding, ERK1/2 phosphorylation, receptor internalization,
and contractility assays to evaluate their pharmacological profile
over the delta opioid receptor (DOPr). The lipophilicity (LogD<sub>7.4</sub>) and plasma stability of the active analogues were also
measured. Our results revealed that the last amide bond can be successfully
replaced by either an ester or an <i>N</i>-methyl amide
bond without significantly decreasing the biological activity of the
corresponding analogues when compared to Leu-enkephalin. The peptidomimetics
with an <i>N</i>-methyl amide function between residues
Phe and Leu were found to be more lipophilic and more stable than
Leu-enkephalin. Findings from the present study further revealed that
the hydrogen-bond donor properties of the fourth amide of Leu-enkephalin
are not important for its biological activity on DOPr. Our results
show that the systematic replacement of amide bonds by isosteric functions
represents an efficient way to design and synthesize novel peptide
analogues with enhanced stability. Our findings further suggest that
such a strategy can also be useful to study the biological roles of
amide bonds
Dictionnaire
ACTION FRANÇAISE (1917-1928) / ACTION NATIONALE (1933- ) Lancée une dizaine d’années après l’affaire Dreyfus, L’Action française (AF) de Montréal existe toujours sous le titre L’Action nationale (AN). C’est dire la place de la revue pour l’histoire des intellectuels, d’autant plus qu’au-delà de La Revue canadienne (1864-1922) et des journaux nationalistes du début du siècle – Le Nationaliste (1903) d’Olivar Asselin*, L’Action (1911-1916) de Jules Fournier*, Le Devoir (1910) d’Henri Bourassa* ..
Dictionnaire des intellectuel.les au Québec
Qui connaît vraiment les intellectuel.les hors du cercle restreint des historiens et des littéraires ? Quelle mémoire avons-nous de celles et ceux qui, au Québec, eurent recours à la parole comme « mode d'action » ? Qui, comme Hubert Aquin, entreprirent et entreprennent encore de « comprendre dangereusement » la culture et la société de leur époque, remuant idées et images, bousculant pouvoirs et doxa ? Ce dictionnaire est conçu pour combler les lacunes d'une mémoire collective quelque peu défaillante, mais aussi pour donner envie de lire ou de relire les textes de ces femmes et hommes passionnés par les idées, qui ont contribué - et qui contribuent toujours - à bâtir la société québécoise. On y trouvera les noms de celles et ceux qui, depuis trois siècles, interviennent sur la place publique et soulèvent des questions d'intérêt civique et politique à propos d'enjeux collectifs importants ; de celles et ceux qui promeuvent ou incarnent la liberté de parole et la défendent contre différents pouvoirs et structures organisationnelles