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L’un des enjeux de la lutte contre le cancer réside dans la compréhension de l’hétérogénéité de la maladie. Le but de notre travail a été d’explorer l’hétérogénéité des cellules cancéreuses du point de vue de la séquence d’ARN messager. Les ESTs (ou Expressed Sequence Tags) d’origine humaine ont été alignées aux séquences de référence ARNm. Les alignements ont été exploités de manière à mesurer les variations de séquence des ESTs issues de tissus tumoraux ou non tumoraux à chaque position de chaque transcrit. L’analyse statistique mise en place a consisté à identifier les positions pour lesquelles les variations de séquence, i.e. substitutions, insertions et délétions, sont différentes entre les ESTs d’origine tumorale et les ESTs d’origine non tumorale. L’étude bioinformatique s’est d’abord concentrée sur 17 transcrits abondamment exprimés avant d’être étendue à l’ensemble du transcriptome. Elle a ensuite été réalisée sur les ESTs murines. Les résultats montrent que l’hétérogénéité des transcrits cancéreux est plus grande que celle des tissus sains. Ainsi, l’infidélité de transcription est augmentée au cours de la carcinogénèse. Ce résultat bioinformatique a été validé par différentes approches biologiques. Tout d’abord, le clonage puis le séquençage d’un ARN provenant d’une tumeur pulmonaire humaine et présentant une délétion prédite de manière bioinformatique ont été réalisés, et ce, en l’absence de mutation somatique. Ensuite, l’identification par spectrométrie de masse d’un variant protéique issu de la traduction d’un ARN dont le codon stop est substitué en triplet codant a été possible. Enfin, l’intérêt de rechercher dans le sérum de patients cancéreux la présence d’anticorps dirigés contre des protéines issues de la traduction d’ARNm infidèles a été démontré. Ainsi, l’infidélité de transcription est un phénomène augmenté dans le cancer et responsable d’une partie de l’hétérogénéité des cellules cancéreuses. L’intérêt de cette découverte réside dans les perspectives nouvelles qu’elle offre en termes de compréhension des mécanismes de carcinogénèse et en termes de diagnostic de la maladie / One of the aim of the fight against cancer is to understand the heterogeneity of cancer cells. The goal of our work has been to explore cancer cell mRNA heterogeneity. ESTs (Expressed Sequence Tags) extracted from normal and cancer tissues have been aligned to mRNA reference sequences. This allowed identification of non-random sequence variations that occurred at statistically significant increased rates in cancer compared to normal libraries. This analysis first focused on 17 abundant transcripts and was next extended to whole human genome, as well as to that of Mus musculus. The results show an increase of transcription infidelity events in cancer tissues. Three types of events occur, i.e. base substitutions, deletions and insertions. Bioinformatics results have been validated through different biological methods. First, the cloning and sequencing of mRNA from lung cancer human with a deletion occurring at bioinformatically predicted position in absence of somatic mutation has been achieved. Then, mass spectrometry analysis confirmed the existence of protein variants resulting from translation of mRNA bypassing stop codon. Finally, we showed that transcription infidelity peptides contain specific epitopes of immunoglobulins ; detection of changes in immunoglobulins in patients with cancers opens a novel path toward early stage cancer diagnosis. This increased transcription infidelity in cancer contributes to the heterogeneity of cancer cells. This finding opens novel perspectives and strategies toward understanding carcinogenesis and diagnostic of the disease

A principal concern in crop agriculture is yield, and a key factor for crop growth is the availability of nitrogen. The large amount of nitrogen fertilizer required by plants is a major cost to farmers. Moreover, environmental issues such as groundwater pollution arise from the utilization of nitrogen fertilizers. Therefore, improvement in the nitrogen use efficiency (NUE) of plants is of urgent importance for sustainable and efficient agriculture. Although hybrid varieties have increased crop yields in low N conditions, the molecular mechanism of plant adaptation to N stress is not completely understood. Herein, the study of responses to N limitations in the natural signalling pathways of model plants facilitates the understanding of complex responses in plants to N stress, and this information can be used to further improve NUE. In this research, the transcriptomes of three model plants Arabidopsis, maize, and rice were compared under diverse N growth conditions. An evaluation of the response of the three plants to varying N levels was also conducted. From a statistical point of view, three distinct methods of detecting differential expression were utilized to reduce the likelihood of false positives due to the tens of thousands of genes simultaneously studied. Furthermore, the performance of three statistical approaches was compared during detection of the N-responsive genes. Finally, a clustering analysis (agglomerative hierarchical clustering) was performed on the genes that significantly responded to N levels as identified by a more biologically intuitive method called Rank Products (RP).

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Background: This study examined whether levels of parental reflective function (RF), parental expressed emotion (EE) and children’s attachment styles are significantly related in a sample of children with high levels of conduct disorder (CD) symptoms. Method: The sample (n = 143) consisted of children aged 5-7 years at risk of behaviour problems. Participants were recruited from a borough of London and a unitary authority in the south west of England. Data for the three main variables and confounders were collected using semi-structured interview, direct observation and questionnaires from both parents and children. The Parent Development Interview (PDI) was used to assess RF; the Five-Minute Speech Sample to assess EE and the Manchester Child Attachment Story Task (MCAST) to assess child attachment. Results: Global levels of maternal RF did not significantly differ between the securely and insecurely attached groups of children. Mothers of securely attached children, however, had higher RF ratings on the negative interactions and anger subscales of the PDI compared to mothers of insecurely attached children. No significant difference was found in parental EE between secure and insecurely attached children. High EE-warmth was associated with high global RF, but there was no significant relationship between EE-criticism and RF. Multiple logistic regression found no significant relationships between parental RF, parental EE and child attachment. Conclusions: These findings may suggest that attachment classification influences the levels of maternal RF in specific negative situations. Conversely it is possible that high maternal RF in such situations enables mothers to respond more sensitively to their child, leading to more secure attachment. The finding that maternal RF and EE were not associated with child attachment may suggest these variables are not strongly related, the sample is too small to detect any effect or that the specific sample lacks variability in scores. To the author’s knowledge this is the first study to test for these relationships with confounders included in the model, which may explain the null findings.