Prion Proteins and Neuronal Death in the Cerebellum

The cellular prion protein, a major player in the neuropathology of prion diseases, is believed to control both death and survival pathways in central neurons. However, the cellular and molecular mechanisms underlying these functions remain to be deciphered. This chapter presents cytopathological studies of the neurotoxic effects of infectious prions and cellular prion protein-deficiency on cerebellar neurons in wild-type and transgenic mice. The immunochemical and electron microscopy data collected in situ and ex vivo in cultured organotypic cerebellar slices indicate that an interplay between apoptotic and autophagic pathways is involved in neuronal death induced either by the infectious prions or by prion protein-deficiency

Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81.

International audienceHepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture-derived HCV (HCVcc). Anti-SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI-specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81-HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti-SR-BI antibodies and SR-BI-specific siRNA efficiently inhibited HCV infection independent of lipoprotein. Conclusion: Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV-CD81 interaction

Skunk River Fall 1998

https://openspace.dmacc.edu/skunkriver/1019/thumbnail.jp

Scholarship in occupational therapy faculty: The interaction of cultural forces in academic departments

Over the last two decades there has been heightened interest in redefining faculty scholarship in higher education (Boyer, 1990). Trends have included the development of cultural frameworks for understanding how disciplines and institutions influence faculty work and how socialization processes impact academic career development. Despite the fact that the number of occupational therapy practitioners who have pursued doctoral training in pursuit of an academic career has failed to keep up with the need for qualified faculty, academic interest in developing disciplinary scholars to build the knowledge base of professional practice has been slow to develop. Furthermore, leadership interest in guiding the development of future faculty by studying how current occupational therapy faculty members are developing as scholars has been limited (AOTA, 2003). The purpose of this study was to develop a framework for describing scholarship in occupational therapy faculty members. A theoretically grounded case study design guided the selection of two occupational therapy departments, representing both a research university and a master’s college. Narrative data from occupational therapy faculty members in these institutions provided in-depth perceptions of how faculty members in diverse institutional settings develop a professional identity. Rich understandings of how clinical and academic socialization processes converge as faculty members in academic departments integrate competing influences from the academic culture, the institutional culture, and the professional culture to prioritize faculty work roles. The study revealed that although occupational therapy departments are succeeding within their institutional contexts, personal faculty priorities as clinicianteachers and institutional missions that create an imbalance in roles that favor teaching, continue to disadvantage certain faculty sub-cultures from evolving as disciplinary scholars. The implications of the failure of occupational therapy faculty members to adapt the researcher role as part of a professional identity include barriers to the development of disciplinary knowledge to support practice, and to the development of successful faculty careers that can be advanced in any institutional environment. The study identified a critical role for program leadership to act as change agents within departmental cultures to balance the need for productive disciplinary scholars, as well as effective clinician-teachers

Protocol for electron microscopy ultrastructural localization of the fusogenic lipid phosphatidic acid on plasma membrane sheets from chromaffin cells

Summary: The glycerophospholipid phosphatidic acid (PA) is a key player in regulated exocytosis, but little is known about its localization at the plasma membrane. Here, we provide a protocol for precisely determining the spatial distribution of PA at exocytotic sites by electron microscopy. Using primary bovine chromaffin cells expressing a PA sensor (Spo20p-GFP), we describe the process for cell stimulation and detergent-free preparation of plasma membrane sheets. The protocol can be applied to other cell models and to distinct membrane lipids.For complete details on the use and execution of this protocol, please refer to Tanguy et al. (2020)

2D Materials and Primary Human Dendritic Cells: A Comparative Cytotoxicity Study

International audienceHuman health can be affected by materials indirectly through exposure to the environment or directly through close contact and uptake. With the ever-growing use of 2D materials in many applications such as electronics, medical therapeutics, molecular sensing, and energy storage, it has become more pertinent to investigate their impact on the immune system. Dendritic cells (DCs) are highly important, considering their role as the main link between the innate and the adaptive immune system. By using primary human DCs, it is shown that hexagonal boron nitride (hBN), graphene oxide (GO) and molybdenum disulphide have minimal effects on viability. In particular, it is evidenced that hBN and GO increase DC maturation, while GO leads to the release of reactive oxygen species and pro-inflammatory cytokines. hBN and MoS2 increase T cell proliferation with and without the presence of DCs. hBN in particular does not show any sign of downstream T cell polarization. The study allows ranking of the three materials in terms of inherent toxicity, providing the following trend: GO > hBN ≈ MoS2, with GO the most cytotoxic