Graduate students in top science and engineering programs have potential for remarkable accomplishment in science and engineering. Yet few studies have examined how their careers develop after graduate school and what can be done to maximize their potential. In this study, students in top science, engineering, and mathematics graduate programs (367 men, 347 women) were assessed and tracked longitudinally for 16 years. Participants classified as especially accomplished and/or creative in science and engineering (56% of men and 41% of women) demonstrated profiles of cognitive abilities, vocational interests, and lifestyle preferences that differed from those of the other participants. Quantitative ability, investigative and social vocational interests, spouse's income, and parenthood all contributed uniquely to predicting noteworthy accomplishments in science and engineering, with fathers being more likely than mothers to be highly accomplished. Participants who were highly accomplishing in science and engineering were more satisfied with their careers than the remaining participants but equally satisfied with their lives. These findings reveal that there are multiple paths to attaining a fulfilling life.

Cardiovascular responses to acute stress have been examined for mediation and moderation of the stress-illness relation, but few studies of functional abdominal pain (FAP) have evaluated cardiovascular responses with none examining this factor in the relation of psychosocial stress and health outcomes. Adolescents and young adults (Mean age = 19.50, SD = 3.36) with a history of childhood FAP (n = 239) and healthy controls (n = 127) self-reported background life stress and health status (perceived general and mental health, somatic symptoms, functional disability). Cardiovascular response via blood pressure was assessed for two laboratory stressors. Results showed that individuals with a history of FAP in childhood had significantly higher background life stress and poorer health in adolescence and young adulthood. Childhood FAP demonstrated cardiovascular blunted reactivity and poorer recovery following laboratory stressors than healthy controls. Childhood FAP with low cardiovascular reactivity and higher background stress had poorer perceived general health compared with healthy controls. FAP is associated with a long-term vulnerability to stress and poorer health.

Children consider others prior behavior to evaluate whether they are likely to provide accurate information in the future. Prior research has demonstrated that the ability to complete a goal in action or language is viewed as an indication that one should be trusted to provide additional information (Koenig, Clement, & Harris, 2004; Koenig, & Harris, 2005; Pasquini ,Corriveau, Koenig, & Harris, 2007; Rakoczy, Warneken, & Tomasello, 2009). The present studies describe two additional indicators of trustworthiness that children and adults use to assess source reliability. Children and adults identified which of two actors completed a goal by the use of action (Study 1) or language (Study 2) most efficiently and then subsequently trusted the efficient actor to provide accurate information about new words. In both studies individuals who were considered efficient at completing goals were trusted to provide label but not tool information. This suggests that learning in some domains may rely more heavily on testimony, while observations may be more important in other domains. In Study 1, preschoolers considered the relative expediency with which two actresses reached a goal to determine who would be more likely to provide accurate label information. In Study 2, monolingual adults, and Spanish-English bilingual 6-year-olds and adults, considered whether two storybook characters adhered to pragmatic norms in different contexts. Adults who were able to identify the characters who adhered to pragmatic norms trusted label information provided by the norm adhering characters. Bilingual children were able to identify which character adhered to the pragmatic norms but they did not selectively trust the norm adhering individuals as sources of label information.

Thesis (Ph. D.)--University OF MICHIGAN.

The aim of this study was to compare the neuromotor development of preterm and full-term infants over the first year of life. Thirty-six preterm infants born at less than 37 weeks gestation and who were neurologically normal at 12 months of age were evaluated on a variety of neuromotor assessments at term, and three, six, nine and twelve months adjusted age. The results were compared to a cross-sectional group of fifteen full-term infants, evaluated on the same reflex and motor assessments. Preterm infants performed significantly more poorly than the full-term infants, with particular lags noted at term and at three and twelve months of age. No significant differences were found between groups of preterm infants born at (i) 24-26, (ii) 27-29, and (iii) $ geq$30 weeks gestation. The differences between the preterm and full-term infants were attributed to factors associated with preterm birth and the evaluation procedures.

Needless to say, it is imperative for workers in the neurological field to know and understand the circulatory system of the Central Nervous System. The basal vessels of the brain, especially the circle of Willis and basilar artery are of particular interest and importance as they are the main and only source of metabolism to such vital structures as basal ganglia, hypothalamus, midbrain and pons. Many investigators have therefore contributed to the knowledge of the course, tributary area, variations, anomalies etc., from the anatomical, physiological and pathological aspects.

Although tissue human growth hormone receptors (GHRs) have been identified from as early as the first trimester of fetal life, little is known about their functional role. We recently reported that fetal hGHRs appear to be relatively immature or have adapted to the in utero environment [194]. To further characterize these age-related differences, we have examined certain aspects of the hGHR structure as well as its signalling pathways. Initial cDNA sequencing and immunoblotting analyses showed no difference in hGHR molecular size. We then used RT-PCR to investigate levels of an alternatively spliced mRNA for a truncated (1--279) hGHR (T) which acts as a dominant negative to the full-length (FL) receptor; however, fetal hepatocytes showed T/FL ratios similar to postnatal liver (0.07 +/- 0.02 vs. 0.09 +/- 0.01, M +/- SEM). Western blotting was used to assess developmental differences in the relative abundance of downstream signalling factors. Stimulatory Jak and Stat proteins were detected in all fetal hepatocytes and postnatal livers tested (13 weeks fetal age to 62 years). (Abstract shortened by UMI.)

The vertebrate body is patterned asymmetrically along the left-right axis. Left-right patterning is required to establish correct asymmetric organ formation and positioning, and ultimately it is essential for normal physiological functioning. Misregulation in this process can lead to severe physiological defects in multiple organs, including the heart and gut. Pitx2c is a paired-like homeodomain transcription factor and is crucial for translating left-right signals into asymmetric morphogenesis. It is asymmetrically expressed in the left lateral plate mesoderm and continues to be expressed on the left side of organ primordia that are destined to become asymmetrically formed or positioned organs. Previous work studying Pitx2c has demonstrated its evolutionarily conserved role in left-right patterning. While the homeodomain is important for Pitx2c's function, our lab identified a putative interaction domain in the N-terminus of Pitx2c that is required for its function in left-right patterning. To further characterize the role of Pitx2c, I used a yeast two-hybrid screen to identify candidate protein interaction partners of its N-terminus. Thirty-two candidates were identified from the screen. Candidates that were isolated at least twice were prioritized for further analysis. After eliminating non-coding clones, false positive interactions, and confirming interactions of the candidate putative interaction domains with the Pitx2c N-terminus in yeast, six candidates remained: Anti-silencing function 1 homolog B (S. cerevisiae; Asf1b), Eukaryotic translation initiation factor 3, subunit A (Eif3a), Eukaryotic translation initiation factor 3, subunit M (Eif3m), Niemann-Pick C type 2 (Npc2), Serine/arginine-rich splicing factor 2 (Srsf2), and Serine/arginine-rich splicing factor 15 (Srsf15). mRNA Expression patterns of these six Pitx2c candidate protein interaction partners was analyzed by whole mount in situ hybridization and compared to Pitx2c expression patterns. All candidates were expressed symmetrically in the embryo, including tissues where Pitx2c is asymmetrically expressed. In the chick embryo, Npc2 and Srsf2 were expressed in a tissue-specific manner from HH stage 10 to HH stage 26, while Eif3a and Eif3m were broadly expressed throughout the embryo from HH stage 10 and only became enriched in particular tissues at HH stage 24 to HH stage 26. All candidates were coexpressed with Pitx2c in the looped heart tube. Only Srsf2 was coexpressed with Pitx2c in the lateral plate mesoderm. The known functions of these candidates are consistent with the known role of Pitx2c in transcriptional regulation and suggests new roles for Pitx2c in mRNA processing and translational regulation during left-right patterning. / Le corps des vertébrés est structuré asymétriquement le long de l'axe gauche-droit. La latéralité est requise afin d'établir la formation des organes ainsi que leur positionnement qui, ultimement, sont essentielles pour un fonctionnement physiologique normal des vertébrés. Lors de ce processus, une mauvaise régulation peut causer des troubles physiologiques sévères dans plusieurs organes incluant le cœur et l'intestin.Le facteur de transcription homéodomaine Pitx2c joue un rôle essentiel lors de la traduction des signaux gauche-droit en morphogénèse asymétrique des organes. Pitx2c est exprimé de façon asymétrique dans le mésoderme de la plaque latérale gauche et continu d'être exprimé du côté gauche des futurs organes asymétriques. Quelques études ont démontré que Pitx2c a un rôle qui est conservé lors de l'évolution dans la latéralité. Le rôle de l'homéodomaine est important pour la fonction de Pitx2c et nous avons démontré dans notre laboratoire qu'un domaine d'interaction de la partie N-terminale de Pitx2c est aussi important pour sa fonction lors de la latéralité.Afin de caractériser d'avantage le rôle de Pitx2c, j'ai utilisé la méthode de double hybride afin d'identifier des protéines candidates d'interaction avec la partie N-terminale de Pitx2c. Trente-deux candidats ont été sélectionnés. De ce nombre, les faux positifs ainsi que les candidats qui représentent région la non-codante d'une protéine ont été supprimés ce qui a permis de réduire la liste à six candidats : Anti-silencing function 1 homolog B (S. cerevisiae; Asf1b), Eukaryotic translation initiation factor 3, subunit A (Eif3a), Eukaryotic translation initiation factor 3, subunit M (Eif3m), Niemann-Pick C type 2 (Npc2), Serine/arginine-rich splicing factor 2 (Srsf2), ainsi que Serine/arginine-rich splicing factor 15 (Srsf15).Les patrons d'expression des six protéines candidates potentielles d'interaction avec Pitx2c ont été examinés par hybridation in situ et ont été comparé avec le patron d'expression de Pitx2c. Chez tous les candidats, l'expression asymétrique dans les embryons de poulet a été observée incluant dans les tissus où Pitx2c est aussi exprimé asymétriquement. Npc2 et Srsf2 sont exprimés de façon spécifique dans certains tissus à partir du stade HH10 chez le poulet. Eif3a et Eif3m sont largement exprimés dans les embryons à partir du stade HH10 mais leur expression est enrichie dans certains tissus à partir du stade HH22. L'expression de tous les candidats coïncide avec celle de Pitx2c dans la courbure du tube cardiaque. Seulement l'expression de Srsf2 coïncide avec celle de Pitx2c dans le mésoderme de la plaque latérale gauche. Les fonctions des différents candidats suggèrent que ces partenaires potentiels d'interactions de la partie N-terminale de Pitx2c pourraient jouer un rôle important lors de la régulation de la transcription, la formation de l'ARN messager et la régulation de la traduction lors de la latéralité.

Introduction: Current epidemiological evidence suggests that asthma and allergic conditions have an etiological component rooted in prenatal development. One of the associated risk factors is the exposure of the conceptus to prenatal maternal stress (PNMS). Current information on the effects of PNMS on postnatal immunity is limited to animal studies with scattered methodologies and two human studies with methodological constraints. The present state of knowledge does not allow drawing definitive conclusions and new studies are needed. Objectives: The main goal of the study presented in this thesis is to analyze the influence of PNMS on the immune system, and to determine which factors from the stressor and the stressed subject are relevant for this phenomenon. Methods: A comprehensive review of the animal literature was conducted to determine which aspects of immunity are most affected by PNMS, which factors intervene in this relationship, and what are the potentially global consequences of PNMS-induced changes on postnatal immunity and health. The available studies were analyzed by the timing (by Window of Vulnerability), type and duration/frequency of the stressor, and by the species, sex and age at assessment of the offspring. These conclusions were used to construct the hypotheses to test in Project Ice Storm, a human study that has been assessing prospectively the consequences of PNMS exposure caused by a natural disaster. Immunity was tested in 37 adolescents (average age 13½ years) whose mothers were pregnant at the time of the storm, measuring their major leukocyte populations and cytokine production capacity using flow cytometry. Results: The review of the animal literature indicated that PNMS affects multiple aspects of postnatal immunity. The most replicated findings were changes in the production of immune-inflammatory mediators (cytokines), and alterations in cell populations. Globally, PNMS might induce the development of a T-helper 2 immune phenotype, which potentially explains the epidemiological link between asthma and PNMS. The timing of the exposure to PNMS was determinant for the effect of PNMS on T lymphocyte populations, and the sex of the offspring influenced the manifestation and direction of cytokine production changes. The human study confirmed that PNMS influences postnatal immunity, indicated that PNMS effects depend on the objective exposure to the stressor rather than on maternal distress, showed that there is an enhanced but not exclusive vulnerability of CD4+ cells to PNMS in early pregnancy, and showed that IL-1β, IL-6 and TNF-α were altered, with TNF-alpha showing different levels in males and females. Conclusion: PNMS exposure has long-term consequences on immunity in animals and humans. Its effects are pervasive and determined by factors from the stressor and the subject. Some of the alterations induced by PNMS could be linked to the development of immune-related disorders such as asthma. / Introduction : Les données épidémiologiques actuelles suggèrent que l'asthme et les allergies ont une composante étiologique liée au développement prénatal. Un des facteurs de risque associé à ce lien est l'exposition du fœtus au stress maternel prénatal (SMP). Les effets nocifs du SMP sur la vie postnatale ont été documentés aux niveaux anatomique, physiologique, et comportemental. Cependant, les preuves actuelles sur les effets du SMP sur l'immunité postnatale sont limitées à des études animales avec des méthodologies diverses ainsi qu'à deux études chez l'humain présentant des contraintes méthodologiques. Les connaissances actuelles ne permettent pas de tirer des conclusions définitives; de nouvelles études sont requises. Objectifs : Le but principal de l'étude présentée dans cette thèse est d'analyser l'influence du SMP sur le système immunitaire, et de déterminer quels éléments du facteur de stress et du sujet stressé sont impliqués dans ce phénomène. Cette connaissance permettrait d'améliorer la compréhension des mécanismes sous-jacents responsables de l'influence du SMP sur l'immunité postnatale. Méthode : Une revue de la littérature a été effectuée afin de déterminer quels éléments du système immunitaire sont davantage affectés par le SMP, quels facteurs interviennent dans cette relation, et quelles sont les conséquences potentielles des changements induits par le SMP sur l'immunité postnatale et la santé. Cela a été effectué en analysant les études disponibles en considérant le temps (par Période de vulnérabilité), le type et la durée/fréquence du facteur de stress, ainsi que l'espèce, le sexe et l'âge du rejeton à l'évaluation. Les conclusions tirées de cette revue ont été utilisées pour définir les hypothèses à tester dans le cadre d'une étude humaine qui investigue de façon prospective les conséquences de l'exposition au SMP dû à un désastre naturel : le Projet Verglas. L'immunité a été testée chez 37 adolescents de cette cohorte (âge moyen 13 ans ½) en mesurant leurs populations de leucocytes ainsi que la production de cytokine in vitro en utilisant la cytométrie en flux. Résultats : La revue de la littérature animale indique que le SMP affecte de multiples aspects de l'immunité postnatale. Les découvertes les plus répliquées sont un changement dans la production de cytokines et une altération dans les populations de cellules. Globalement, le SMP peut induire le développement d'un phénotype de réponse immunitaire de type 2, qui pourrait potentiellement expliquer le lien épidémiologique entre l'asthme et le SMP. La période d'exposition au SMP (début de la grossesse) était déterminante pour l'effet du SMP sur les populations de lymphocytes T, et le sexe du rejeton influençait la manifestation et la direction des changements dans la production de cytokines. L'étude humaine confirme que le SMP influence l'immunité postnatale, que les effets du SMP dépendent de l'exposition objective au facteur de stress plutôt que la détresse maternelle, qu'il existe une vulnérabilité accrue mais non exclusive des cellules CD4+ au SMP tôt dans la grossesse, et enfin que les cytokines IL-1β, IL-6, et TNF-α sont altérés. Les niveaux de TNF-alpha étant différents entre les garçons et les filles. Conclusion : L'exposition au SMP a des conséquences à long-terme sur l'immunité animale et humaine. Ses effets sont invasifs et sont déterminés par des caractéristiques du facteur de stress et du sujet. Des altérations induites par le SMP peuvent être liées au développement de troubles immunitaires tel que l'asthme.

No description available.