"Le Travailleur" et les intellectuels de la survivance franco-américaine face au déclin des communautés francophones de la Nouvelle-Angleterre (1945-1978)

Ce mémoire propose une analyse de la réaction des intellectuels faisant la promotion de la survivance intégrale du fait français en Nouvelle-Angleterre face à l'assimilation progressive des communautés franco-américaines, entre 1945 et 1978. Principal organe dédié à cette cause après la Deuxième Guerre mondiale, le contenu du journal Le Travailleur montre bien l'évolution de la perception des élites intellectuelles face à la progression du processus d'anglicisation du groupe. Du ton virulent et accusateur utilisé à la fin des années 1940 pour dénoncer les responsables de la situation qu’ils déplorent, les artisans du journal s'ouvrent progressivement aux débats et véhiculent au milieu des années 1950 des idées normalement défendues par les promoteurs d'une plus grande intégration à la société américaine. S’ils restent muets quant aux phénomènes structuraux qui affectent l'ensemble de la population américaine à mesure qu'avancent les Trente Glorieuses, les solutions mises de l’avant par les intellectuels de la survivance, centrées sur l’unité, l’identification d’un idéal à atteindre et la valorisation du passé par la commémoration, n’auront que bien peu d’impact face aux grandes tendances alors en cours. Autrement, après y avoir accordé bien peu d’attention depuis sa création en 1931, Le Travailleur dirige son regard vers un Québec en pleine effervescence au cours des années 1960, sans toutefois tirer profit du contexte favorable aux revendications des minorités culturelles américaines au cours des mêmes années. Une nouvelle élite, en marge des promoteurs traditionnels de la survivance, prendra la relève au cours des années 1970 dans l'espoir de générer une renaissance culturelle franco-américaine chez une population de laquelle Le Travailleur se sera montré, au final, complètement déconnecté

Interleukin-36γ is expressed by neutrophils and can activate microglia, but has no role in experimental autoimmune encephalomyelitis

Primers used for genotyping. (PDF 39 kb

N-Phenyl-N'-(2-chloroethyl)urea analogues of combretastatin A-4: Is the N-phenyl-N'-(2-chloroethyl)urea pharmacophore mimicking the trimethoxy phenyl moiety ?

A series of novel N-phenyl-N'-(2-chloroethyl)urea derivatives potentially mimicking the structure of combretastatin A-4 were synthesized and tested for their cell growth inhibition and their binding to the colchicine-binding site of beta-tubulin. Compounds 2a, 3a, and 3b were found to inhibit cell growth at the micromolar level on four human tumor cell lines. Flow cytometric analysis indicates that the new compounds act as antimitotics and arrest the cell cycle in G(2)/M phase. Covalent binding of 2a, 3a, and 3b to the colchicine-binding site of beta-tubulin was confirmed also using SDS-PAGE and competition assays

N-Phenyl-N’-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents. part 3 : role of carbonyl group

n the course of the development of N-phenyl-N′-(2-chloroethyl)ureas (CEUs) as potential antineoplastic agents, we investigated the effect of carbonylated substituting chains of the aromatic ring of CEU on their covalent binding to the colchicine-binding site (C-BS). In this study, we found that CEU, 5e, 5f, 8e, and 8f substituted by either a methyl ester or a methyl ketyl group at the ω-position exhibited a significant antiproliferative activity on HT-29, M21, and MCF-7 tumor cells. SDS–PAGE assays and cell cycle analysis confirmed that 5e, 5f, 8e, and 8f covalently bind to the C-BS and arrest the cell division in G2/M phase. Surprisingly, the presence of ω-carboxyl, ω-ethyl esters or ω-amides decreased significantly both the antiproliferative activity and the specificity toward β-tubulin

An integrated approach to historical population assessment of the great whales: case of the New Zealand southern right whale

Accurate estimation of historical abundance provides an essential baseline for judging the recovery of the great whales. This is particularly challenging for whales hunted prior to twentieth century modern whaling, as population-level catch records are often incomplete. Assessments of whale recovery using pre-modern exploitation indices are therefore rare, despite the intensive, global nature of nineteenth century whaling. Right whales (Eubalaena spp.) were particularly exploited: slow swimmers with strong fidelity to sheltered calving bays, the species made predictable and easy targets. Here, we present the first integrated population-level assessment of the whaling impact and pre-exploitation abundance of a right whale, the New Zealand southern right whale (E. australis). In this assessment, we use a Bayesian population dynamics model integrating multiple data sources: nineteenth century catches, genetic constraints on bottleneck size and individual sightings histories informing abundance and trend. Different catch allocation scenarios are explored to account for uncertainty in the population's offshore distribution. From a pre-exploitation abundance of 28 800–47 100 whales, nineteenth century hunting reduced the population to approximately 30–40 mature females between 1914 and 1926. Today, it stands at less than 12% of pre-exploitation abundance. Despite the challenges of reconstructing historical catches and population boundaries, conservation efforts of historically exploited species benefit from targets for ecological restoration

Microtubule disrupting N-phenyl-N’-(2-chloroethyl) ureas display anticancer activity on cell adhesion, P-glycoprotein and BCL-2-mediated drug resistance

Objective: Our research program has focused on the development of promising, soft alkylating N-phenyl-N’-(2-chloroethyl)urea (CEU) compounds which acylate the glutamic acid-198 of β-tubulin, near the binding site of colchicum alkaloids. CEUs inhibit the motility of cancerous cells in vitro and, interestingly, exhibit antiangiogenic and anticancer activity in vivo. Mitotic arrest induced by microtubule-interfering agents such as CEUs remains the major mechanism of their anticancer activity, leading to apoptosis. However, we recently demonstrated that microtubule disruption by CEUs and other common antimicrotubule agents greatly alters the integrity and organization of microtubule-associated structures, the focal adhesion contact, thereby initiating anoikis, an apoptosis-like cell death mechanism caused by the loss of cell contact with the extracellular matrix. Methods: To ascertain the activated signaling pathway profile of CEUs, flow cytometry, Western blot, immunohistochemistry and transfection experiments were performed. Wound-healing and chick embryo assays were carried out to evaluate the antiangiogenic potency of CEUs. Results: CEU-induced apoptosis involved early cell cycle arrest in G2/M and increased level of CDK1/cycline B proteins. These signaling events were followed by the specific activation of the intrinsic apoptosis pathway, involving loss of mitochondrial membrane potential (Δψm) and ROS production, cytochrome c release from mitochondria, caspase activation, AIF nuclear translocation, PARP cleavage and nuclear fragmentation. CEUs maintained their efficacy on cells plated on pro-survival extracellular matrices or exhibiting overexpression of P-glycoprotein or the anti-apoptotic protein Bcl-2. Conclusion: Our results suggest that CEUs represent a promising new class of antimicrotubule, antiangiogenic and pro-anoikis agents

Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90

Hsp90 stabilizes and prevents degradation of cytoplasmic activation-induced deaminase

Active nuclear import and cytoplasmic retention of activation-induced deaminase

The enzyme activation-induced deaminase (AID) triggers antibody diversification in B cells by catalyzing deamination and consequently mutation of immunoglobulin genes. To minimize off-target deamination, AID is restrained by several regulatory mechanisms including nuclear exclusion, thought to be mediated exclusively by active nuclear export. Here we identify two other mechanisms involved in controlling AID subcellular localization. AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. We also identify in its C terminus a determinant for AID cytoplasmic retention, which hampers diffusion to the nucleus, competes with nuclear import and is crucial for maintaining the predominantly cytoplasmic localization of AID in steady-state conditions. Blocking nuclear import alters the balance between these processes in favor of cytoplasmic retention, resulting in reduced isotype class switching.This work was supported by the Canadian Institutes of Health Research (MOP 84543) and a Canada Research Chair (to J.M.D.). A.O. was supported by a fellowship from the Canadian Institutes of Health Research Cancer Training Program at the IRCM. V.A.C. was supported in part by a Michel Saucier fellowship from the Louis-Pasteur Canadian Fund through the University of Montreal

"Le Travailleur" et les intellectuels de la survivance franco-américaine face au déclin des communautés francophones de la Nouvelle-Angleterre (1945-1978)

Ce mémoire propose une analyse de la réaction des intellectuels faisant la promotion de la survivance intégrale du fait français en Nouvelle-Angleterre face à l'assimilation progressive des communautés franco-américaines, entre 1945 et 1978. Principal organe dédié à cette cause après la Deuxième Guerre mondiale, le contenu du journal Le Travailleur montre bien l'évolution de la perception des élites intellectuelles face à la progression du processus d'anglicisation du groupe. Du ton virulent et accusateur utilisé à la fin des années 1940 pour dénoncer les responsables de la situation qu’ils déplorent, les artisans du journal s'ouvrent progressivement aux débats et véhiculent au milieu des années 1950 des idées normalement défendues par les promoteurs d'une plus grande intégration à la société américaine. S’ils restent muets quant aux phénomènes structuraux qui affectent l'ensemble de la population américaine à mesure qu'avancent les Trente Glorieuses, les solutions mises de l’avant par les intellectuels de la survivance, centrées sur l’unité, l’identification d’un idéal à atteindre et la valorisation du passé par la commémoration, n’auront que bien peu d’impact face aux grandes tendances alors en cours. Autrement, après y avoir accordé bien peu d’attention depuis sa création en 1931, Le Travailleur dirige son regard vers un Québec en pleine effervescence au cours des années 1960, sans toutefois tirer profit du contexte favorable aux revendications des minorités culturelles américaines au cours des mêmes années. Une nouvelle élite, en marge des promoteurs traditionnels de la survivance, prendra la relève au cours des années 1970 dans l'espoir de générer une renaissance culturelle franco-américaine chez une population de laquelle Le Travailleur se sera montré, au final, complètement déconnecté

N-Phenyl-N′-(2-chloroethyl)ureas (CEU) as potential antineoplastic agents. Part 2 : role of ω-hydroxyl group in the covalent binding to β-tubulin

Tubulin is the target of many anticancer drugs, including N-phenyl-N′-(2-chloroethyl)urea (CEU). Unlike most anti-β-tubulin agents, CEUs are protein monoalkylating agents binding through their N′-(2-chloroethyl)urea moiety to an amino acid nearby the colchicine-binding site on β-tubulin isoform-2. Following the previously synthesized and attractive N-(3-ω-hydroxyalkylphenyl)-N′-(2-chloroethyl)urea that exhibited growth inhibitory activity at the nanomolar level, we investigated the importance of lower alkyl and alkoxy groups to evaluate the effect of hydroxylated group and chain length on both cell growth inhibition and the mechanism of action of CEU. Here, we describe the preparation of two new series of CEU and show that the most potent CEU derivatives beside the ω-hydroxylated 1f were 2f and 3e, respectively. We have confirmed that the pentyl substituted CEUs 1f, 2f, and 3e are still covalently binding to β-tubulin and still arrest cell division in G2/M phase