The Role of CD40 in Naïve and Memory CD8+ T Cell Responses: a Dissertation

Stimulation of CD40 on APCs through CD40L expressed on helper CD4+ T cells activates and “licenses” the APCs to prime CD8+ T cell responses. While other stimuli, such as TLR agonists, can also activate APCs, it is unclear to what extent they can replace the signals provided by CD40-CD40L interactions. In this study, we used an adoptive transfer system to re-examine the role of CD40 in the priming of naïve CD8+ T cells. We find an approximately 50% reduction in expansion and cytokine production of TCR-transgenic T cells in the absence of CD40 on all APCs, and on dendritic cells in particular. Moreover, CD40-deficient and CD40L-deficient mice fail to develop endogenous CTL responses after immunization and are not protected from a tumor challenge. Surprisingly, the role for CD40 and CD40L are observed even in the absence of CD4+ T cells; in this situation, the CD8+T cell itself provides CD40L. Furthermore, we show that although TLR stimulation improves T cell responses, it cannot fully substitute for CD40. We also investigated whether CD40-CD40L interactions are involved in the generation, maintenance, and function of memory CD8+ T cells. Using a virus infection system as well as a dendritic cell immunization system, we show that the presence of CD40 on DCs and other host APCs influences the survival of activated effector cells and directly affects the number of memory CD8+ T cells that are formed. In addition, memory CD8+ T cell persistence is slightly impaired in the absence of CD40. However, CD40 is not required for reactivation of memory CD8+ T cells. It seems that CD40 signals during priming also contribute to memory CD8+ T cell programming but this function can be independent of CD4+T cells, similar to what we showed for primary responses. Altogether, these results reveal a direct and unique role for CD40L on CD8+ T cells interacting with CD40 on APCs that affects the magnitude and quality of primary as well as memory CD8+ T cell responses

Students' Personal and Academic Attributions of University Withdrawal

A Commission of Inquiry on Canadian University Education recently reported that approximately 42% of full-time undergraduate students who entered Canadian universities in 1985 failed to obtain a degree within five years. While this statistic is startling, perhaps, of greater concern is the apparent lack of interest shown by most Canadian universities in the subject of undergraduate student attrition. As an initial step toward addressing the issue of Canadian university attrition, a conceptual model of undergraduate student withdrawal is proposed. The model is based on the assumption that students are characterized by a wide range of personal and academic variables. Such characteristics interact or co-exist with institutional variables such as campus integration. This interaction results in the quality of student academic performance and the nature of student psychological condition. Poor quality of student academic performance results in institution-initiated undergraduate withdrawal; a variety of psychological variables (e.g., satisfaction, stress) result in student-initiated undergraduate withdrawal. The bases of this model were findings obtained from questioning 498 undergraduate students who had withdrawn from a large Western Canadian university. Personal student characteristics, institutional factors and societal variables frequently emerged as students' attributions of university withdrawal. Student academic performance was validated as the causal factor for institutional-based undergraduate withdrawal and student psychological state appeared critically related to student-based undergraduate withdrawal. From these findings, preadmission counseling, academic and personal student support and an increased commitment to accommodating students are recommended.Récemment, une Commission d'enquête sur l'enseignement supérieur au Canada indiquait que près de 42% des étudiants sous-gradués, inscrits pour la première fois dans les universités canadiennes en 1985, n'avaient pas complété leurs études à l'intérieur d'une période de cinq ans. Suite à cette information, la plus grande surprise est à l'effet de l'apparent manque d'intérêt de la majorité des universités canadiennes par rapport au sujet de l'attrition au niveau sous-gradué. Dans cette article, un modèle conceptuel de l'attrition par rapport à cette population est proposé comme une contribution pouvant faire avancer cette question dans les universités canadiennes. Le modèle est basé sur les prémisses que les étudiants ont des caractéristiques personnelles et académiques variées. Ces caractéristiques interagissent ou coexistent avec des facteurs institutionnels, telle l'intégration dans un établissement universitaire. Cette interaction est le résultat de la qualité de la performance académique de l'étudiant et de la nature de ses conditions psychologiques. Une pauvre qualité de la performance académique de l'étudiant es liée à un départ initié par l'institution, tandis qu'une variété de facteurs psychologiques (exemples: satisfaction, stress) sont liés à un départ initié par l'étudiant sous-gradué. Les bases de ce modèle se dégagent d'une enquête menée auprès de 498 étudiants sous-gradués, qui on quitté une université de l'ouest canadien de grande taille. Les caractéristiques individuelles des étudiants, les facteurs institutionnels et les composantes sociètales émergent fréquemment comme étant le facteur causal du départ (base institutionnelle) et l'état psychologique de l'étudiant et apparu relié au départ (base étudiante). Suite à ces résultats, des services en counseling préalables à l'admission, les supports académique et personnel aux étudiants et une plus grande volonté de répondre aux besoins des étudiants font partie des recommandations

Workplace Giving in Universities: A U.S. Case Study at Indiana University

The phenomenon of workplace giving is underexamined in the scholarly literature; philanthropic gifts by employees to their nonprofit employers have received less attention within national and transnational contexts. This study considered the association between university staff propensity toward “internal workplace giving” and donor characteristics, drawing on literature about organizational commitment and identification as a beginning for advancing theoretical understanding of employee–employer relationships and giving at both the micro-level and meso-level. The sample of 17,038 employees covered 3 years at Indiana University, an American, public, multicampus institution. Despite its specific national and cultural context, the study raises relevant issues about workplace giving. Relational and personal characteristics were found to be significant predictors for determining who donates; using these characteristics to predict giving levels, however, was less successful. The study anticipates a growing need for related research and provides direction for further methodological and theoretical approaches

High-Resolution Chandra Spectroscopy Of Tau Scorpii: A Narrow-Line X-Ray Spectrum From A Hot Star

Long known to be an unusual early-type star by virtue of its hard and strong X-ray emission, tau Scorpii poses a severe challenge to the standard picture of O-star wind-shock X-ray emission. The Chandra HETGS spectrum now provides significant direct evidence that this B0.2 star does not fit this standard wind-shock framework. The many emission lines detected with the Chandra gratings are significantly narrower than what would be expected from a star with the known wind properties of tau Sco, although they are broader than the corresponding lines seen in late-type coronal sources. While line ratios are consistent with the hot plasma on this star being within a few stellar radii of the photosphere, from at least one He-like complex there is evidence that the X-ray emitting plasma is located more than a stellar radius above the photosphere. The Chandra spectrum of Sco is harder and more variable than those of other hot stars, with the exception of the young magnetized O star theta(1) Ori C. We discuss these new results in the context of wind, coronal, and hybrid wind-magnetic models of hot-star X-ray emission

Human-specific transcriptional regulation of CNS development genes by FOXP2.

The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans

Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

An estimated 30% of individuals with autism spectrum disorders (ASD) remain minimally verbal into late childhood, but research on cognition and brain function in ASD focuses almost exclusively on those with good or only moderately impaired language. Here we present a case study investigating auditory processing of GM, a nonverbal child with ASD and cerebral palsy. At the age of 8 years, GM was tested using magnetoencephalography (MEG) whilst passively listening to speech sounds and complex tones. Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech, particularly in the 65–165 ms (M50/M100) time window post-stimulus onset. GM was retested aged 10 years using electroencephalography (EEG) whilst passively listening to pure tone stimuli. Consistent with her MEG response to complex tones, GM showed an unusually early and strong response to pure tones in her EEG responses. The consistency of the MEG and EEG data in this single case study demonstrate both the potential and the feasibility of these methods in the study of minimally verbal children with ASD. Further research is required to determine whether GM's atypical auditory responses are characteristic of other minimally verbal children with ASD or of other individuals with cerebral palsy

The State of State EITCs: An Overview and Their Implications for Low- and Moderate-Income Households

The success of the federal Earned Income Tax Credit (EITC) has prompted numerous states to develop and administer their own EITC programs. This brief presents the results of analyses that used data from a large sample of low- and moderate-income households to learn more about the relationship between state and federal EITCs as well as about their relationships, respective and combined, with financial behaviors and the experience of financial and material hardship. Given that many EITC beneficiaries face substantial risk of experiencing income volatility and financial shocks, insights gained from this brief can assist policymakers in understanding the importance of expanded EITCs and promoting emergency saving at tax time