Individual differences in gene expression : insights from transcriptional control of the CSL gene and from human population studies

CSL is a key transcription factor, mostly acting as a repressor, which has been shown to have a highly context-dependent function. While known as the main effector of Notch signaling, it can also exert Notch-independent functions. The downstream effects of the Notch/CSL signaling pathway and its involvement in several biological processes have been intensively studied. We recently showed that CSL is important to maintain skin homeostasis, as its specific deletion in mouse dermal fibroblasts -or downmodulation in human stromal fibroblasts- creates an inducing environment for squamous cell carcinoma (SCC) development, possibly due to the conversion of stromal fibroblasts into cancer associated fibroblasts (CAFs). Despite the wide interest in CSL as a transcriptional regulator, the mechanism of its own regulation has so far been neglected. We show here that CSL expression levels differ between individuals, and correlate among others with genes involved in DNA damage response. Starting from this finding we show that in dermal fibroblasts CSL is under transcriptional control of stress inducers such as UVA irradiation and Reactive Oxygen Species (ROS) induction, and that a main player in CSL transcriptional regulation is the transcription factor p53. In a separate line of work, we focused on individual variability, studying the differences in gene expression between human populations in various cancer types, particularly focusing on the Caucasian and African populations. It is indeed widely known that these populations have different incidences and mortalities for various cancers, and response to cancer treatment may also vary between them. We show here several genes that are differentially expressed and could be of interest in the study of population differences in cancer. -- CSL est un facteur de transcription agissant essentiellement comme répresseur, et qui a une fonction hautement dépendant du contexte. C'est l'effecteur principal de la voie de signalisation de Notch, mais il peut également exercer ses fonctions dans une façon Notch- indépendante. Nous avons récemment montré que CSL est important pour maintenir l'homéostasie de la peau. Sa suppression spécifique dans les fibroblastes dermiques de la souris ou dans les fibroblastes stromales humaines crée un environnement favorable pour le développement du carcinome épidermoïde (SCC), probablement en raison de la conversion des fibroblastes en fibroblastes associé au cancer (CAF). Malgré le grand intérêt de CSL comme régulateur transcriptionnel, le mécanisme de sa propre régulation a été jusqu'ici négligée. Nous montrons ici que dans les fibroblastes dermiques CSL est sous le contrôle transcriptionnel de facteurs de stress tels que l'irradiation UVA et l'induction des ROS dont p53 est l'acteur principal de cette régulation. Nous montrons aussi que les niveaux d'expression de CSL varient selon les individus, en corrélation avec d'autres gènes impliqués dans la réponse aux dommages de l'ADN. Dans une autre axe de recherche, concernant la variabilité individuelle, nous avons étudié les différences dans l'expression des gènes dans différents types de cancer entre les populations humaines, en se concentrant particulièrement sur les populations africaines et caucasiennes. Il est en effet bien connu que ces populations montrent des variations dans l'incidence des cancers, la mortalité, ainsi que pour les réponses au traitement. Nous montrons ici plusieurs gènes qui sont exprimés différemment et pourraient être digne d'intérêt dans l'étude du cancer au sein de différentes populations.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

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Peer-reviewed

Individual Perception of Organizational Values

The objective of this master’s thesis was to examine how corporate values come true among the white-collar employees in the case organization. It was also studied if values were perceived similarly in the different departments. Impact of organizational position and education on value orientation was tested through hypotheses based on earlier values research. There are only few value scales available for measuring organizational values. The empirical study results indicate that personnel’s perception of organizational values can be measured statistically. When defining the scale it is utmost important to link the questions and claims close to the employees’ daily working environment. In this study, Work ethic appeared as the strongest organizational value reflecting respondents’ commitment to their duties. Related to corporate values, Performance was perceived as the strongest value and Emphasis on people the weakest. Value consensus between the departments varied. According to the previous research organizational position and educational level has an impact on value perceptions. In this study, employees in superior position or with higher education perceived organizational values to come true better than subordinates or employees with lower education. Empirical data (N=229) was collected by a web-based survey questionnaire among white-collar employees in the case organization in April 2008. Statistical analyses were performed by SPSS programme.

Individual Differences in True and False Memory Retrieval Are Related to White Matter Brain Microstructure

We sometimes vividly remember things that did not happen, a phenomenon with general relevance, not only in the courtroom. It is unclear to what extent individual differences in false memories are driven by anatomical differences in memory-relevant brain regions. Here we show in humans that microstructural properties of different white matter tracts as quantified using diffusion tensor imaging are strongly correlated with true and false memory retrieval. To investigate these hypotheses, we tested a large group of participants in a version of the Deese-Roediger-McDermott paradigm (recall and recognition) and subsequently obtained diffusion tensor images. A voxel-based whole-brain level linear regression analysis was performedto relatefractional anisotropyto indices oftrue andfalse memory recall and recognition. True memory was correlated to diffusion anisotropy in the inferior longitudinal fascicle, the major connective pathway of the medial temporal lobe, whereas a greater proneness to retrieve false items was related to the superior longitudinal fascicle connecting frontoparietal structures. Our results show that individual differences in white matter microstructure underlie true and false memory performance.

Individual differences in control of language interference in late bilinguals are mainly related to general executive abilities

Background: Recent research based on comparisons between bilinguals and monolinguals postulates that bilingualism enhances cognitive control functions, because the parallel activation of languages necessitates control of interference. In a novel approach we investigated two groups of bilinguals, distinguished by their susceptibility to cross-language interference, asking whether bilinguals with strong language control abilities ('non-switchers") have an advantage in executive functions (inhibition of irrelevant information, problem solving, planning efficiency, generative fluency and self-monitoring) compared to those bilinguals showing weaker language control abilities ('switchers"). Methods: 29 late bilinguals (21 women) were evaluated using various cognitive control neuropsychological tests [e.g., Tower of Hanoi, Ruff Figural Fluency Task, Divided Attention, Go/noGo] tapping executive functions as well as four subtests of the Wechsler Adult Intelligence Scale. The analysis involved t-tests (two independent samples). Non-switchers (n = 16) were distinguished from switchers (n = 13) by their performance observed in a bilingual picture-naming task. Results: The non-switcher group demonstrated a better performance on the Tower of Hanoi and Ruff Figural Fluency task, faster reaction time in a Go/noGo and Divided Attention task, and produced significantly fewer errors in the Tower of Hanoi, Go/noGo, and Divided Attention tasks when compared to the switchers. Non-switchers performed significantly better on two verbal subtests of the Wechsler Adult Intelligence Scale (Information and Similarity), but not on the Performance subtests (Picture Completion, Block Design). Conclusions: The present results suggest that bilinguals with stronger language control have indeed a cognitive advantage in the administered tests involving executive functions, in particular inhibition, self-monitoring, problem solving, and generative fluency, and in two of the intelligence tests. What remains unclear is the direction of the relationship between executive functions and language control abilities.

Prediction of individual automobile RBNS claim reserves in the context of Solvency II

Automobile bodily injury (BI) claims remain unsettled for a long time after the accident. The estimation of an accurate reserve for Reported But Not Settled (RBNS) claims is therefore vital for insurers. In accordance with the recommendation included in the Solvency II project (CEIOPS, 2007) a statistical model is here implemented for RBNS reserve estimation. Lognormality on empirical compensation cost data is observed for different levels of BI severity. The individual claim provision is estimated by allocating the expected mean compensation for the predicted severity of the victim’s injury, for which the upper bound is also computed. The BI severity is predicted by means of a heteroscedastic multiple choice model, because empirical evidence has found that the variability in the latent severity of injured individuals travelling by car is not constant. It is shown that this methodology can improve the accuracy of RBNS reserve estimation at all stages, as compared to the subjective assessment that has traditionally been made by practitioners.

Dynamic patterns of flow in the workplace: characterizing within-individual variability using a complexity science approach

As a result of the growing interest in studying employee well-being as a complex process that portrays high levels of within-individual variability and evolves over time, this present study considers the experience of flow in the workplace from a nonlinear dynamical systems approach. Our goal is to offer new ways to move the study of employee well-being beyond linear approaches. With nonlinear dynamical systems theory as the backdrop, we conducted a longitudinal study using the experience sampling method and qualitative semi-structured interviews for data collection; 6981 registers of data were collected from a sample of 60 employees. The obtained time series were analyzed using various techniques derived from the nonlinear dynamical systems theory (i.e., recurrence analysis and surrogate data) and multiple correspondence analyses. The results revealed the following: 1) flow in the workplace presents a high degree of within-individual variability; this variability is characterized as chaotic for most of the cases (75%); 2) high levels of flow are associated with chaos; and 3) different dimensions of the flow experience (e.g., merging of action and awareness) as well as individual (e.g., age) and job characteristics (e.g., job tenure) are associated with the emergence of different dynamic patterns (chaotic, linear and random).

Self-assessment of individual differences in language switching

Language switching is omnipresent in bilingual individuals. In fact, the ability to switch languages (code switching) is a very fast, efficient, and flexible process that seems to be a fundamental aspect of bilingual language processing. In this study, we aimed to characterize psychometrically self-perceived individual differences in language switching and to create a reliable measure of this behavioral pattern by introducing a bilingual switching questionnaire. As a working hypothesis based on the previous literature about code switching, we decomposed language switching into four constructs: (i) L1 switching tendencies (the tendency to switch to L1; L1-switch); (ii) L2 switching tendencies (L2-switch); (iii) contextual switch, which indexes the frequency of switches usually triggered by a particular situation, topic, or environment; and (iv) unintended switch, which measures the lack of intention and awareness of the language switches. A total of 582 SpanishCatalan bilingual university students were studied. Twelve items were selected (three for each construct). The correlation matrix was factor-analyzed using minimum rank factor analysis followed by oblique direct oblimin rotation. The overall proportion of common variance explained by the four extracted factors was 0.86. Finally, to assess the external validity of the individual differences scored with the new questionnaire, we evaluated the correlations between these measures and several psychometric (language proficiency) and behavioral measures related to cognitive and attentional control. The present study highlights the importance of evaluating individual differences in language switching using self-assessment instruments when studying the interface between cognitive control and bilingualism.

Individual Differences in Music Reward Experiences

Music is one of the most pleasant human experiences, even though it has no direct biological advantage. However little is known about individual differences in how people experience reward in music-related activities. The goal of the present study was to describe the main facets of music experience that could explain the variance observed in how people experience reward associated with music. To this end we developed the Barcelona Music Reward Questionnaire (BMRQ), which was administrated to three large samples. Our results showed that the musical reward experience can be decomposed into five reliable factors: Musical Seeking, Emotion Evocation, Mood Regulation, Social Reward, and Sensory-Motor. These factors were correlated with socio-demographic factors and measures of general sensitivity to reward and hedonic experience. We propose that the five-factor structure of musical reward experience might be very relevant in the study of psychological and neural bases of emotion and pleasure associated to music.

Gestão da qualidade total: introdução dos conceitos e a sua utilização em um curso para abordar o comportamento individual do aluno/profissional/cidadão

A introdução do assunto qualidade, segundo as necessidades de mercado abre espaço para a discussão da qualidade como necessidade pessoal, e também para a formação do cidadão/profissional, além de introduzir assuntos específicos de administração de empresas. Dessa forma, foi oferecida uma disciplina optativa para os alunos do Instituto de Química do Campus de Araraquara, abordando o tema Qualidade e foi denominada "Gestão da Qualidade" por três anos seguidos. Da avaliação geral do curso extraiu-se que ele deveria ser realizado sempre, que o tema é atual e relevante e contribui para a formação profissional/pessoal. Com relação ao comprometimento com o curso de graduação, cerca de metade dos alunos assume o seu comprometimento com os estudos e os restantes dizem estarem somente envolvidos. Conclui-se, portanto que o curso atingiu os seus objetivos propostos, introduziu os principais conceitos de qualidade segundo as normas da qualidade da série ISO 9000 e suscitou a discussão da formação do aluno/profissional/cidadão.

As ações do serviço de saúde voltadas para o âmbito individual e pouco coletivo

Este estudo avalia a compreensão sobre o modelo de atenção básica nas ações de saúde. Trata-se de uma pesquisa de natureza qualitativa exploratória, desenvolvida em Unidades de Saúde da Família (USFs) de Marília, com amostra composta por profissionais de saúde, usuários e estudantes de Medicina e Enfermagem inseridos nas unidades. Os dados foram coletados por meio de entrevistas semiestruturadas e analisados pela técnica de análise de conteúdo, modalidade temática. Pôde-se observar que, independentemente da categoria entrevistada e da área onde se encontra a USF, a compreensão dos entrevistados sobre o modelo de atenção é o modelo médico-assistencial privatista, que reflete o predomínio das ações curativas em uma relação individualista, operada diretamente pelo médico e oferecida na demanda espontânea, não sendo exclusiva do setor privado. Foi proposto utilizar o espaço de grupos organizados para educação em saúde, em que trabalhadores e usuários são participantes para uma interação com as necessidades da comunidade e participação ativa dos usuários no planejamento do serviço, além de investimento nas ações de promoção e prevenção, o que causaria adesão da população e geraria credibilidade no modelo não médico-centrado.