L’équité et le droit : étude herméneutique d’une notion fondamentale du raisonnement judiciaire et de son intégration dans l’éthos du juge

L’équité est un concept large dont la signification et la richesse conceptuelle ont évolué temporellement au sein de la théorie du droit et de la théorie politique. Au travers d’une histoire de l’équité, partant de la conception d’Aristote jusqu’aux juristes réalistes américains, ce mémoire analyse et explique la transformation graduelle de ce concept dans le droit, dont la place fut tantôt au centre des réflexions autour de la justice, tantôt minimisée, voire écartée, mais jamais complètement supprimée. Nous fondant sur cette riche histoire de l’équité, nous reconnectons ce concept phare de la théorie du droit à une réception de celui-ci au sein de la théorie politique. Pour ce faire, nous mobilisons la théorie de la liberté comme non-domination de Philip Pettit comme le cadre d’une pratique contemporaine de l’équité, au travers de la jurisprudence de la Cour suprême du Canada sur l’équité procédurale.The concept of “equity” is vast, and its meaning and depth have dramatically evolved over time within the political and legal theory fields. This thesis offers a history of the concept of equity, starting from Aristotle’s conception of justice and equity to the American legal realist movement. On that basis, this thesis analyzes and explains the reasons why such a gradual transformation of this concept happened and, therefore, how the role of equity changed from being at the centre of theories of justice and law to being minimized, almost excluded from the sphere of legal theory, but never completely suppressed. Drawing on this rich history of equity, we reconnect this key concept of legal theory with its reception in political theory. In that regard, we offer an account of Philip Pettit’s theory of freedom as non-domination understood as the framework for the contemporary practice of equity, notably through the example of the case law of the Supreme Court of Canada on procedural fairness

Health and Pleasure in Consumers' Dietary Food Choices: Individual Differences in the Brain's Value System

Taking into account how people value the healthiness and tastiness of food at both the behavioral and brain levels may help to better understand and address overweight and obesity-related issues. Here, we investigate whether brain activity in those areas involved in self-control may increase significantly when individuals with a high body-mass index (BMI) focus their attention on the taste rather than on the health benefits related to healthy food choices. Under such conditions, BMI is positively correlated with both the neural responses to healthy food choices in those brain areas associated with gustation (insula), reward value (orbitofrontal cortex), and self-control (inferior frontal gyrus), and with the percent of healthy food choices. By contrast, when attention is directed towards health benefits, BMI is negatively correlated with neural activity in gustatory and reward-related brain areas (insula, inferior frontal operculum). Taken together, these findings suggest that those individuals with a high BMI do not necessarily have reduced capacities for self-control but that they may be facilitated by external cues that direct their attention toward the tastiness of healthy food. Thus, promoting the taste of healthy food in communication campaigns and/or food packaging may lead to more successful self-control and healthy food behaviors for consumers with a higher BMI, an issue which needs to be further researched

DNA Methylation Is the Primary Silencing Mechanism for a Set of Germ Line- and Tumor-Specific Genes with a CpG-Rich Promoter

A subset of male germ line-specific genes, the MAGE-type genes, are activated in many human tumors, where they produce tumor-specific antigens recognized by cytolytic T lymphocytes. Previous studies on gene MAGE-A1 indicated that transcription factors regulating its expression are present in all tumor cell lines whether or not they express the gene. The analysis of two CpG sites located in the promoter showed a strong correlation between expression and demethylation. It was also shown that MAGE-A1 transcription was induced in cell cultures treated with demethylating agent 5′-aza-2′-deoxycytidine. We have now analyzed all of the CpG sites within the 5′ region of MAGE-A1 and show that for all of them, demethylation correlates with the transcription of the gene. We also show that the induction of MAGE-A1 with 5′-aza-2′-deoxycytidine is stable and that in all the cell clones it correlates with demethylation, indicating that demethylation is necessary and sufficient to produce expression. Conversely, transfection experiments with in vitro-methylated MAGE-A1 sequences indicated that heavy methylation suffices to stably repress the gene in cells containing the transcription factors required for expression. Most MAGE-type genes were found to have promoters with a high CpG content. Remarkably, although CpG-rich promoters are classically unmethylated in all normal tissues, those of MAGE-A1 and LAGE-1 were highly methylated in somatic tissues. In contrast, they were largely unmethylated in male germ cells. We conclude that MAGE-type genes belong to a unique subset of germ line-specific genes that use DNA methylation as a primary silencing mechanism

Identification on a human sarcoma of two new genes with tumor-specific expression.

Genes MAGE, BAGE, GAGE, and LAGE-1/NY-ESO-1 code for antigens that are recognized on melanoma cells by autologous CTLs. Because the pattern of expression of these genes results in the presence of antigens on many tumors of various histological types and not on normal tissues, these antigens qualify for cancer immunotherapy. To identify new genes with tumor-specific expression, we applied a cDNA subtraction approach, ie., representational difference analysis, to a human sarcoma cell line. We obtained two cDNA clones that appeared to be tumor specific. The corresponding genes were named SAGE and HAGE because they have the same pattern of expression as genes of the MAGE family. SAGE encodes a putative protein of 904 amino acids and shows no homology to any recorded gene. Like the MAGE-A genes, it is located in the q28 region of chromosome X. Expression of gene SAGE was observed mainly in bladder carcinoma, lung carcinoma, and head and neck carcinoma but not in normal tissues, with the exception of testis. Gene HAGE, which is located on chromosome 6, encodes a putative protein of 648 amino acids. This protein is a new member of the DEAD-box family of ATP-dependent RNA helicases. Gene HAGE is expressed in many tumors of various histological types at a level that is 100-fold higher than the level observed in normal tissues except testis. Because of this tumor-specific expression, genes SAGE and HAGE ought to encode antigens that could be useful for antitumoral therapeutic vaccination

Hypomethylation in human cancers is causally related to transcriptional activation of MAGE-type genes

MAGE-type genes comprise several unrelated families of X-linked genes that code for tumor-specific antigens recognized by cytolytic T lymphocytes. These genes are normally expressed exclusively in testicular germ cells, but become aberrantly activated in many tumors. Interestingly, MAGE-type genes were found to be expressed in tumor cell lines that show a decrease in the overall DNA methylation level, suggesting that their activation may be a consequence of the genome-wide demethylation that frequently occurs in cancer cells. MAGE-type genes are indeed methylated in all normal adult somatic tissues from either male or female origin, but are demethylated in expressing tumor cells. They are also unmethylated in spermatogenic cells. Detailed analysis of the methylation status of gene MAGEA1 in expressing cells indicated that demethylation is restricted to a region of less than 3 Kb centered around the transcription initiation site. Interestingly, promoters of MAGE-type genes have an intermediate density of CpGs and may constitute a unique class of promoters which fall between the constitutively unmethylated CpG island-promoter and the conditionally methylated CpG poor-promoter. Treatment with the demethylating agent 5'-aza-deoxycytidine suffices to induce stable expression of MAGE-type genes, and this induction was shown to correlate with promoter demethylation. Unmethylated MAGEA1 promoter constructs exert transcriptional activity after transfection in cells that do not express the gene. Conversely, in vitro methylated promoter constructs are completely and stably repressed in cells that normally express gene MAGEA1. Our data indicate that MAGE-type genes have promoters that are driven by ubiquitous transcription factors. DNA methylation appears therefore to be an essential repression mechanism ensuring the germ-cell specific expression of these genes. Hence, MAGE-type genes constitue targets for gene activation consequently to genome-wide hypomethylation in cancer cells

Identification of human testis-specific transcripts and analysis of their expression in tumor cells

Tumor-specific antigens recognized by autologous T lymphocytes are encoded by genes, including those of the MAGE, BAGE, and GAGE gene families, that are expressed in a significant fraction of tumors of various types, but not in normal adult tissues, except for testis where they appear to be expressed in germ cells. Because male germ cells are known to express many genes that are not expressed in other normal adult tissues, we wished to determine whether most of these genes are occasionally activated in tumor cells. Representational difference analysis was used to obtain testis-specific transcripts. The expression of 15 testis-specific cDNA sequences was tested by RT-PCR in a series of tumor cell lines. Only one cDNA sequence showed a significant level of expression in some tumor cell lines. Remarkably, this cDNA clone proved to be a new gene of the MAGE family. These results suggest that MAGE, BAGE, and GAGE genes belong to a minor subset of testis-specific genes that is often activated in tumors of various types, whereas most testis-specific genes are either never or very rarely activated in tumors. (C) 1997 Academic Press

Identification of a new MAGE gene with tumor-specific expression by representational difference analysis

Human genes expressed exclusively in tumors and male germ line cells, such as those of the MAGE, BAGE, and GAGE families, encode antigens recognized by T lymphocytes, which are potentially useful for antitumor immunotherapy. To identify new genes of this type, we generated cDNA populations enriched in sequences expressed only in testis and melanoma, using the representational difference analysis approach, A testis cDNA Library enriched by subtraction with cDNA from four other normal tissues was hybridized with radiolabeled melanoma cDNA enriched by subtraction with normal skin cDNA, A cDNA fragment sharing significant homology with MAGE genes was identified, and a cosmid containing this new gene, named MAGE-C1, was isolated, MAGE-C1 is composed of four exons and encodes a putative protein of 1142 amino acids, It is about 800 residues longer than the other MAGE proteins due to the insertion of a large number of short repetitive sequences in front of the MAGE-homologous sequence, The MAGE-C1 gene appears to be located on band Xq26, whereas the MAGE-A and MAGE-B genes are located on Xq28 and Xp21, respectively. Like other IMAGE genes, MAGE-C1 is expressed in a significant proportion of tumors of various histological types, whereas it is silent in normal tissues except testis, It is probable, therefore, that like other MAGE genes, MAGE-C1 encodes antigens that may constitute useful targets for cancer immunotherapy because of their strict tumoral specificity

Involvement of 2 Ets Binding-sites in the Transcriptional Activation of the Mage1 Gene

The MAGE1 gene codes for an antigen recognized on melanoma cell line MZ2-MEL by autologous cytolytic T lymphocytes. It is expressed in a number of tumors of different histological origins, but not in normal tissues except in testis. The MAGE1 promoter region was analyzed by performing transient transfections in MZ2-MEL cells with luciferase reporter plasmids. A fragment extending from nucleotide -792 to +118 exhibited high transcriptional activity. By deletional analysis of this fragment, we identified five activating regions designated C, A, B', B, and D. The activity of region A depends on the presence of region B' and vice versa. Two inverted Ets motifs contained in regions B' and B were found to drive 90% of the activity of the MAGE1 promoter in MZ2-MEL cells. Electrophoretic mobility shift assays performed with a nuclear extract from MZ2-MEL cells and with competitor oligonucleotides containing an Ets consensus site showed that nuclear proteins bind to the Ets motif of regions B' and B. Similar experiments suggested that region A binds transcription factors of the Sp1 family. The MAGE1 promoter was found to exert transcriptional activity in tumor cells where the MAGE1 gene is not expressed, suggesting that other mechanisms, such as demethylation, may contribute to the tumor-specific expression of the gene

Sequence and Expression Pattern of the Human Mage2 Gene

We reported previously identification of the human MAGE1 gene, which encodes an antigen recognized on human melanoma MZ2-MEL by autologous cytolytic T lymphocytes. In addition to MAGE1, melanoma MZ2-MEL expresses several closely related genes, one of which has been named MAGE2. The complete MAGE2 sequence was obtained and it comprises 3 exons homologous to those of MAGE1 and an additional exon homologous to a region of the first MAGE1 intron. Like the open reading frame of MAGE1, that of MAGE2 is entirely encoded by the last exon. The MAGE1 and MAGE2 sequences of this exon show 82% identity and the putative proteins show 67% identity. The MAGE2 gene is expressed in a higher proportion of melanoma tumors than MAGE1. It is also expressed in many small-cell lung carcinomas and other lung tumors, laryngeal tumors, and sarcomas. No MAGE1 and MAGE2 gene expression was found in a large panel of healthy adult tissues, with the exception of testis