NCube/papyrus huggingface dataset:
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.

Keyphrases: Aryl chloroethylureas, Mitotic agents, Resistance, Mitochondria, Anoikis
La reconnaissance d’autrui comme prérequis à toute forme de consentement et d’assentiment : Une réponse à Verpaelst et Touyz

La médecine engage un contrat tacite de mise à disposition du corps médicalisé que le formulaire de consentement ne fait qu’officialiser. Le récit de Frank Verpaelst met en lumière la primauté du besoin de reconnaissance inhérent à la rencontre médecin-patient tant dans un cadre de formation, de recherche que de soin. Medicine creates a tacit contract of appropriation of the medicalized body that consent forms simply formalize. The story of Frank Verpaelst highlights the primacy of the need for recognition that is inherent to the doctor/patient encounter, whether in the context of teaching, research or care.

Keyphrases: consentement, théorie de la reconnaissance, médicalisation, consent, assentiment, Axel Honneth, consent, assent, theory of recognition, medicalization
Genetic diversity of Mycoplasma hyopneumoniae isolates of abattoir pigs

Mycoplasma hyopneumoniae, the causative agent of porcine enzootic pneumonia, is present in swine herds worldwide. However, there is little information on strains infecting herds in Canada. A total of 160 swine lungs with lesions suggestive of enzootic pneumonia originating from 48 different farms were recovered from two slaughterhouses and submitted for gross pathology. The pneumonic lesion scores ranged from 2% to 84%.  Eighty nine percent of the lungs (143/160) were positive for M. hyopneumoniae by real-time PCR whereas 10% (16/160) and 8.8% (14/160) were positive by PCR for M. hyorhinis and M. flocculare, respectively. By culture, only 6% of the samples were positive for M. hyopneumoniae (10/160). Among the selected M. hyopneumoniae-positive lungs (n = 25), 9 lungs were co-infected with M. hyorhinis, 9 lungs with PCV2, 2 lungs with PRRSV, 12 lungs with S. suis and 10 lungs with P. multocida. MLVA and PCR-RFLP clustering of M. hyopneumoniae revealed that analyzed strains were distributed among three and five clusters respectively, regardless of severity of lesions, indicating that no cluster is associated with virulence. However, strains missing a specific MLVA locus showed significantly less severe lesions and lower numbers of bacteria. MLVA and PCR-RFLP analyses also showed a high diversity among field isolates of M. hyopneumoniae with a greater homogeneity within the same herd. Almost half of the field isolates presented less than 55% homology with selected vaccine and reference strains.

Keyphrases: Mycoplasma hyopneumoniae, Porcine enzootic pneumonia, Genotyping, MLVA, PCR-RFLP
In vitro effect of deoxynivalenol (DON) mycotoxin on porcine reproductive and respiratory syndrome virus replication

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. Among monogastric farm animals, swine are the most susceptible to DON as it markedly reduces feed intake and decreases weight gain. DON has also been shown to increase susceptibility to viral infections; therefore the objective of this study was to investigate in vitro impact of DON on porcine reproductive and respiratory syndrome virus (PRRSV). Permissive cells were infected or not with PRRSV and were treated with increasing concentrations of DON. Cell survival and mortality were evaluated by determining the number of viable cells with a tetrazolium compound and by measuring lactate dehydrogenase (LDH) release, respectively. Virus titration and antiviral cytokines mRNA expression were evaluated by quantitative PCR. DON significantly affected the survival of noninfected cells in a dose dependent manner. However, DON concentrations between 140 and 280 significantly increased the survival of cells infected with PRRSV. These concentrations significantly decreased PRRSV replication by inducing a pro-inflammatory cytokines environment and an early activation of apoptosis, which in turn seem to interrupt viral replication. For the first time, this study showed that DON had significant effects on the survival of PRRSV infected cells and on virus replication, in a dose dependent manner.

Keyphrases: Deoxynivalenol, PRRSV, In vitro, Virus replication, Swine
Effect of deoxynivalenol (DON) mycotoxin on in vivo and in vitro porcine circovirus type 2 infections

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp and is a common contaminant of grains in North America. Among farm animals, swine are the most susceptible to DON because it markedly reduces feed intake and decreases weight gain. Porcine circovirus type 2 (PCV2) is the main causative agent of several syndromes in weaning piglets collectively known as porcine circovirus-associated disease (PCVAD). The objectives of this study were to investigate the impact of DON on PCV2 replication in NPTr permissive cell line, and to determine eventual potentiating effects of DON on PCV2 infection in pigs. Noninfected and infected cells with PCV2 were treated with increasing concentrations of DON (0, 70, 140, 280, 560, 1200 ng/mL) and cell survival and virus titer were evaluated 72 h postinfection. Thirty commercial piglets were randomly divided into 3 experimental groups of 10 animals based on DON content of served diets (0, 2.5 and 3.5 mg/kg DON). All groups were further divided into subgroups of 6 pigs and were inoculated with PCV2b virus. The remaining pigs (control) were sham-inoculated with PBS. In vitro results showed that low concentrations of DON could potentially increase PCV2 replication depending on virus genotype. In vivo results showed that even though viremia and lung viral load tend to be higher in animal ingesting DON contaminated diet at 2.5 mg/kg, DON had no significant effect on clinical manifestation of PCVAD in PCV2b infected animals. DON has neither in vitro nor in vivo clear potentiating effects in the development of porcine circovirus infection despite slight increases in viral replication.

Keyphrases: Pig, PCV2 infection, DON contamination
In vivo effect of deoxynivalenol (DON) naturally contaminated feed on porcine reproductive and respiratory syndrome virus (PRRSV) infection

Deoxynivalenol (DON), also known as vomitoxin, is the most prevalent type B trichothecene mycotoxin worldwide. Pigs show a great sensitivity to DON, and because of the high proportion of grains in their diets, they are frequently exposed to this mycotoxin. The objective of this study was to determine the impact of DON naturally contaminated feed on porcine reproductive and respiratory syndrome virus (PRRSV) infection, the most important porcine viral pathogen in swine. Experimental infections were performed with 30 animals. Piglets were randomly divided into three groups of 10 animals based on DON content of diets (0, 2.5 and 3.5 mg/kg DON). All experimental groups were further divided into subgroups of 6 pigs and were inoculated with PRRSV. The remaining pigs (control) were sham-inoculated with PBS. Pigs were daily monitored for temperature, weight and clinical signs for 21 days. Blood samples were collected and tested for PRRSV RNA and for virus specific antibodies. Results of PRRSV infection showed that ingestion of diet highly contaminated with DON greatly increases the effect of PRRSV infection on weight gain, lung lesions and mortality, without increasing significantly viral replication, for which the tendency is rather directed toward a decrease of replication. These results suggest that PRRSV infection could exacerbate anorectic effect of DON, when ingested in large doses. Results also demonstrate a DON negative effect on PRRSV-specific humoral responses. This study demonstrate that high concentrations of DON naturally contaminated feed decreased the immune response against PRRSV and influenced the course of PRRSV infection in pigs.

Keyphrases: Pig, DON mycotoxin, PRRSV, Predisposition to infection
Persistence of porcine reproductive and respiratory syndrome virus and porcine circovirus type 2 in bacterial biofilms

The aim of this pilot project was to investigate association of viruses with bacterial biofilms. Our preliminary data indicate that important viral pathogens of swine, namely, porcine reproductive and respiratory syndrome virus and porcine circovirus type 2, can associate with and persist within bacterial biofilms for several days.

Keyphrases: Swine, Porcine reproductive and respiratory syndrome virus, Porcine circovirus type 2, Persistence, Bacterial biofilms
De la confiance trahie à la faute, n’y a-t-il qu’un pas ? Une réponse à Laliberté

La prise en charge des personnes vulnérables implique des questions d’équilibre au niveau de l’organisation d’offre de soins public-privé et des questions de confiance à l’égard du patient. The management of the vulnerable persons involves questions of balance at the level of the organization providing public-private healthcare and questions about patient trust.

Keyphrases: confiance, éthique, faute, personnes vulnérables, ressource intermédiaire, résidence, trust, ethics, fault, vulnerable persons, residence, intermediate resource
Un jeu dont vous êtes le héros : «Entre idéal et réalité : en Jeu(x) éthique(s) de la recherche»

Le principe de ce jeu, qui s’adresse essentiellement aux jeunes chercheurs, est le suivant : les participants sont invités à incarner une équipe de recherche, chargée d’étudier les impacts sanitaires inhérents à la conduite d’activités minières en Bolivie. Ce jeu interactif, qui promeut la réflexion éthique et la prise de décision par un processus dialogique et réflexif, a été conçu afin de mettre en pratique l’intégration de la prise de décision, l’interaction entre les participants et la construction conjointe de sens. The principle of this game, which is primarily aimed at junior researchers, is as follows: participants are asked to embody a research team studying the health impacts associated with the conduct of mining activities in Bolivia. This interactive game, which promotes ethical reflection and decision-making through a dialogical and reflexive process, was designed to put into practice the integration of decision-making, interaction between the participants and the co-construction of meaning.

Keyphrases: bioéthique, enseignement, jeu interactif, prise de décision, éthique de la recherche, bioethics, teaching, interactive game, decision making, research ethics
Les protestants sont plus idolophobes qu’iconoclastes!

Cet article synthétise la théologie protestante des images en montrant qu’elle vise à prévenir l’idolâtrie. Il rappelle que l’iconoclasme de la Réforme a été sélectif. Il souligne l’existence de peintres protestants, de Hans Holbein le Jeune à André Bieler. Il explique comment les principaux réformateurs ont traité la question des images. Il distingue les positions luthérienne et calviniste, notamment quant à leur interprétation du commandement biblique qui interdit les idoles. Il précise enfin à quelles conditions une image peut transmettre l’Évangile. This paper synthesizes protestant theology of pictures, showing that its aim is to prevent idolatry. It reminds that the Reform was selective in its iconoclasm. It emphasizes the existence of protestant painters, from Hans Holbein the Younger to André Bieler. It explains how Reformers dealt with the question of images. It contrasts Lutheran and Calvinist positions, especially regarding their interpretation of the second commandment, which forbids idols. It specifies under which conditions a picture is able to transmit Gospel.

Keyphrases: Théologie, Protestantisme, Histoire de l'art, Images, Iconoclasme, Théologie de l'image, Images, Religion
How fast and how often: the pharmacokinetics of drug use are decisive in addiction

How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, ‘spiking’ brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.

Keyphrases: Drug addiction, Pharmacokinetics, Cocaine, Route of drug intake, Speed of drug delivery, Intermittent drug exposure
Liquid Chromatography-Electrospray Linear Ion Trap Mass Spectrometry Analysis of Targeted Neuropeptides in Tac1-/- Mouse Spinal Cords Reveal Significant Lower Concentration of Opioid Peptides

Tachykinin and opioid peptides play a central role in pain transmission, modulation and inhibition. The treatment of pain is very important in medicine and many studies using NK1 receptor antagonists failed to show significant analgesic effects in humans. Recent investigations suggest that both pronociceptive tachykinins and the analgesic opioid systems are important for normal pain sensation. The analysis of opioid peptides in Tac1-/- spinal cord tissues offers a great opportunity to verify the influence of the tachykinin system on specific opioid peptides. The objectives of this study were to develop a HPLC–MS/MRM assay to quantify targeted peptides in spinal cord tissues. Secondly, we wanted to verify if the Tac1-/- mouse endogenous opioid system is hampered and therefore affect significantly the pain modulatory pathways. Targeted neuropeptides were analyzed by high performance liquid chromatography linear ion trap mass spectrometry. Our results reveal that EM-2, Leu-Enk and Dyn A were down-regulated in Tac1-/- spinal cord tissues. Interestingly, Dyn A was almost 3 fold down-regulated (p < 0.0001). No significant concentration differences were observed in mouse Tac1-/- spinal cords for Met-Enk and CGRP. The analysis of Tac1-/- mouse spinal cords revealed noteworthy decreases of EM-2, Leu-Enk and Dyn A concentrations which strongly suggest a significant impact on the endogenous pain-relieving mechanisms. These observations may have insightful impact on future analgesic drug developments and therapeutic strategies.

Keyphrases: Neuropeptides, Pain, Mass spectrometry, High performance liquid chromatography, Biomarkers
La police et Twitter : l’utilisation des médias sociaux par les services policiers canadiens

La police nord-américaine, adoptant une philosophie dite de la police communautaire, tente d'entrer davantage en contact avec ses citoyens. Un moyen efficace pour y arriver est par l'utilisation des médias sociaux. Par contre, des études antérieures ont montré que les services de police utilisent les médias sociaux plutôt pour diffuser des informations liées au crime. La présente recherche met l'emphase sur l'utilisation de Twitter pour quatre services policiers (SPVM, VPD, CPS et TPS) et s'ils utilisent leur compte pour diffuser des informations, s’ils entrent en contact avec les citoyens ou s’ils emploient ces deux stratégies. Les traces numériques laissées par les tweets publiés par les services de police ont été recueillies et analysées. Les résultats illustrent que l'utilisation varie selon les services de police, mais ils ont tous un point commun : ils utilisent leur compte Twitter principalement pour entrer en contact avec la population, mais diffusent aussi des informations. Ceci contredit alors les études antérieures mentionnant que les services de police diffusent en grande majorité des informations liées à la criminalité.

Keyphrases: police, médias sociaux, police communautaire, social media, community policing
The Politics of Poverty in the European Union: How States Respond to the Open Method of Coordination on Social Inclusion

This article assesses the responses of EU-15 member states to the poverty reduction objectives of the Open Method of Coordination (OMC) on social inclusion between 2001 and 2006. As a flexible mechanism of information sharing between governments, the OMC could not produce strong convergence. A thorough analysis of the OMC documents indeed points to the enduring power of national institutions and partisan politics, for the three dimensions of social inclusion identified by the EU (rights, labour market policies, and participation). There was however some learning and adaptation around emerging policy ideas like activation and the participation of people experiencing poverty.

Keyphrases: Union européenne, Pauvreté
Fédéralisme d’ouverture et pouvoir de dépenser au Canada

In power since January 2006, the leader of the Canadian Conservative party, Stephen Harper, promised to break with the previous governments’ “domineering” style of governance and to put into practice a new type of “open federalism.” Specifically, this approach involved correcting the fiscal imbalance between Ottawa and the provinces, taking measures to recognize Quebec’s specificity, and limiting the federal government’s recourse to an alleged spending power. This article briefly surveys the foundations of Canadian politics and the years when the Liberal party was in power, between 1993 and 2006, to assess the measures adopted by the Harper government, particularly with respect to the spending power. This power is not attributed in the constitution nor is it founded on clear jurisprudence, but Ottawa still claims and invokes it. Despite ther promises, the Conservatives have failed to offer a satisfactory formula for limiting its usage. So, Canada remains driven by the centralising process that has prevailed since the start of the 1980’s.

Keyphrases: Canada, Fédéralisme, Québec, Stephen Harper, Déséquilibre fiscal, Pouvoir de dépenser, Union sociale, Péréquation, Constitution, Transferts
The New Global Politics of Poverty

In recent years, governments, international institutions, and a broad array of social movements have converged around what an OECD report has described as an emerging “global anti-poverty consensus.” This new global social policy agenda has changed the terms of the debate between the left and the right, and redefined the world of policy possibilities, in global but also in domestic politics. This article proposes a constructivist interpretation of this multi-scale shift in discourse, and discusses the political and policy implications of the new global politics of poverty.

Keyphrases: Pauvreté, Politiques sociales, Néoliberalisme, Institutions internationales, Constructivisme
Divided Over Internationalism : The Canadian Public and Development Assistance

This analysis of public opinion towards foreign aid shows that Canadians are divided over internationalism. First, while most citizens agree that development assistance is important, their support often remains shallow, unmatched by a commitment to undertake concrete actions. Second, the attitudes Canadians hold toward development assistance indicate that there is a clear division in the country’s public between liberal and conservative internationalists, a cleavage that is anchored in domestic ideological and partisan differences. In many ways comparable to what is found in other countries, the internationalism of Canadians does not appear as vigorous and as consensual as is often suggested.

Keyphrases: Opinion publique, Développement, Internationalisme
La pratique de la contrepartie pour les personnes exclues du marché du travail : ici et ailleurs

Les modalités et les pratiques de la contrepartie dans l’assistance sociale, dans six pays de l’OCDE sont comparés. La littérature anglo-saxonne parle plus volontiers de workfare alors que la littérature d’Europe continentale utilise la notion de conditionnalité. Les auteurs utilisent le terme de contrepartie comme concept générique incluant l’ensemble des programmes introduisant des formes de conditionnalité de l’aide par opposition à des aides ou des prestations attribuées de manière inconditionnelle. Une interprétation de ces variations est proposée en situant les résultats obtenus par rapport aux connaissances acquises en politique comparée sur l’évolution des différents types d’État-providence. The methods and practices of reciprocity in social assistance are compared in six OECD countries. The literature from English-speaking countries tends to talk about workfare while Continental European literature uses the concept of conditionality. The authors employ the term “reciprocity” as a generic concept encompassing all of the programs that include forms of conditionality for assistance, as opposed to the unconditional provision of assistance or benefits. The authors put forth an interpretation of these variations by comparing their results with the existing body of work in comparative politics on the development of the various types of welfare states. The development of reciprocity mechanisms, therefore, follows neither a single logic, nor a series of pre-mapped paths determined by existing institutions. To understand and evaluate current experiences and innovations, each case must be carefully examined, taking into account all the constraints, but also the opportunities, created by a new era in the development of the Welfare State.

Keyphrases: Assistance sociale, Workfare, Workfare