Delineating neuroinflammation, parasite CNS invasion, and blood-brain barrier dysfunction in an experimental murine model of human African trypanosomiasis

Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness. In addition, we have measured the trypanosome load present in the brain using quantitative Taqman PCR and assessed the severity of the neuroinflammatory reaction at specific time points over the course of the infection. Contrast enhanced – MRI detected a significant degree of BBB impairment in mice at 14 days following trypanosome infection, which increased in a step-wise fashion as the disease progressed. Parasite DNA was present in the brain tissue on day 7 after infection. This increased significantly in quantity by day 14 post-infection and continued to rise as the infection advanced. A progressive increase in neuroinflammation was detected following trypanosome infection, reaching a significant level of severity on day 14 post-infection and rising further at later time-points. In this model stage-2 disease presents at 21 days post-infection. The combination of the three methodologies indicates that changes in the CNS become apparent prior to the onset of established stage-2 disease. This could in part account for the difficulties associated with defining specific criteria to distinguish stage-1 and stage-2 infections and highlights the need for improved staging diagnostics

Windswept

craft of making forges a strong connection to my ancestors who also engaged in textiles and clothing. Draping fabric, hearing the whir of the sewing machine, and hand-printing pattern on cloth recalls images of making doll clothes alongside my mother and watching my grandmother knit spectacular patterns from memory

Gamification of Smart Meter Home Display Units Using Targeted Reward Mechanics.

This research is part of a TSB funded feasibility study (ARIA) and is the preliminary reward based design concept for a game to accompany electricity Smart Meters’ Home Display Units. The purpose is to engage players in the game for an extended period so they would similarly engage in using their Home Display Units in order to lower their electricity consumption and modify their behaviour. This paper looks at reward within computer games and establishes a visual framework for displaying the reward mechanics used in games in the form of “Three Corners of Reward”. It establishes the link between personal reward, material reward and competitive reward through three drivers, intrinsic, extrinsic and social play which is then linked to player demographics. It this case the target market require a spread of male and female, but majority female with a broad appeal to many age groups

Assessing Teacher Beliefs about Early Literacy Curriculum Implementation

McKenney, S., Bradley, B., & Boschman, F. (2011, 8-12 April). Assessing Teacher Beliefs about Early Literacy Curriculum Implementation. Presentation at AERA annual meeting, New Orleans.Against the backdrop of growing international concern for a narrowing view of early literacy, this study was initiated to determine how teachers of four-year-olds view their task of fostering early literacy. This paper reports on the first steps to design and validate an instrument which captures teachers’ perceptions of: early literacy content goals; developmentally appropriate and effective pedagogical practices related to each content goal; and their own competencies to offer a suitable environment for developing early literacy. The content validity of the instrument was evaluated by an expert screening; the reliability and practicality of the instrument are being assessed through a pilot study involving 40 teachers from two countries; this paper reports on the findings from the first 20 teachers. Validation findings indicate that the instrument appears to be reliable. The findings from the pilot run show that teachers focus on decoding skills most; there is some attention to book orientation and understanding, and relatively little to the functions of written language

Peer Influence in Initiation to Heroin Use

Much research on heroin initiation shows that most people use heroin initially with friends or family. However, there is little research examining why those who use heroin would initiate others to its use, and conversely, whether and why one might try to prevent initial heroin use in others. Following recent work on peer influence on crime and delinquency, we test the hypothesis that those with higher levels of self-control are less likely to initiate others to heroin use and are more likely to try to prevent others from using for the first time. The sample included 370 persons entering an opioid withdrawal program. We find that those with low self-control are more likely to initiate others, but there is no relationship between self-control and trying to prevent initiation. We further investigate self-reported motives for initiating others, and find a mix of self-interested and more altruistic motives for initiating others

Teams and Tasks: A Temporal Framework for the Effects of Interpersonal Interventions on Team Performance

Researchers have studied interpersonal interventions as a means of increasing the performance of work teams. However, for short-term teams working on contrived tasks of short duration—a combination common in research studies—interpersonal interventions do not seem to affect team performance as much as task interventions. Yet, for short-term teams working on real tasks of longer duration and for ongoing teams, the effects of interpersonal interventions on team performance are more positive. This article presents a temporal framework of teams and tasks that predicts the expectation of benefit, which in turn mediates the effectiveness of interpersonal interventions on team performance

Prolonged-acting, multi-targeting gallium nanoparticles potently inhibit growth of both HIV and mycobacteria in co-infected human macrophages.

Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, macrophage and dendritic cell). Therefore, we hypothesized that one way this can be achieved is through drug-targeting by a nanoformulated drug that ideally would be active against both HIV and TB. Accordingly, we validated macrophage targeted long acting (sustained drug release) gallium (Ga) nanoformulation against HIV-mycobacterium co-infection. The multi-targeted Ga nanoparticle agent inhibited growth of both HIV and TB in the macrophage. The Ga nanoparticles reduced the growth of mycobacterium and HIV for up to 15 days following single drug loading. These results provide a potential new approach to treat HIV-TB co-infection that could eventually lead to improved clinical outcomes

Preservice Teacher Reflections About Short-Term Summer Study Abroad Experiences in Italy

This chapter studies 21 preservice teachers\u27 blog reflections about working in an Italian classroom and living with a host family during a four-week study abroad program in Northern Italy. During the program, preservice teachers were required to blog about their experiences living and studying abroad using personal blog sites. To encourage more candid reflection about the program, the blog posts could be related to any aspect of the program preservice teachers chose to reflect on. After setting the context of the study through description of the study abroad program and its requirements, the authors present qualitative findings regarding preservice teachers\u27 (a) thoughts related to their observations of Italian classrooms, (b) thoughts related to becoming an Italian language learner, and (c) lessons learned from the study abroad experience. Findings discuss preservice teachers\u27 reflections on making sense of educational and cultural differences, experiences as Italian language learners, and opportunities for professional and personal growth

Trypanosoma brucei brucei invasion and T-cell infiltration of the brain parenchyma in experimental sleeping sickness: timing and correlation with functional changes

Background: The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. Methodology: Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses. Principal findings: Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion. Conclusion: These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging