Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

Recovering Subjects: Investment in an Era of Reconciliation

This doctoral project examines reconciliation and how Canada’s Indian Residential Schools Settlement Agreement (2005) was designed to provide reparations to former students who were harmed in residential schools. In the past three decades, many Indigenous leaders and organizations identified a need for public investment to address historical injustice. In response, settler governments reframe these demands as opportunities for economic investment that is guaranteed to produce self-esteem and social inclusion for Indigenous peoples. This dissertation documents and problematizes an ideological shift whereby demand for redress and restitution give way to an investment rationale that is used to bypass demands for self-determination (Green 2015). Therefore, in this study I ask: how do investment discourses structure Indigenous-settler relationships? What is specific about the application of investment rationale when deployed during redress and reconciliation processes? In order to answer these questions I use a multi-site methodology to examine material and symbolic reparations, such as the Independent Assessment Process, the Truth and Reconciliation Commission, and therapeutic health supports. I draw on governmentality literatures to argue that an investment rationale disciplines individual compensation claimants through categories of harm and legal accounting processes to construct Indigenous subjects as dysfunctional and wage employment as emancipatory. I then examine how Indigenous health supports are subject to disinvestment, which effectively marginalizes Indigenous conceptualizations of health that privilege self-determination. Finally, I explore how the Truth and Reconciliation Commission routinely valorizes “mutually beneficial partnerships” as a template for contemporary Indigenous-settler relationships. My analysis thus contributes to the field of settler colonial studies and reveals how investment rationale is deployed to contain the cost of reparations and to create a politics of exchange where a return can be recovered from monies allotted to reparative strategies. The expected return that is desired by the settler state is, ultimately, the assimilation of Indigenous peoples’ into neoliberal citizenship

Investigation of EMIC wave scattering as the cause for the BARREL 17 January 2013 relativistic electron precipitation event: A quantitative comparison of simulation with observations

Abstract Electromagnetic ion cyclotron (EMIC) waves were observed at multiple observatory locations for several hours on 17 January 2013. During the wave activity period, a duskside relativistic electron precipitation (REP) event was observed by one of the Balloon Array for Radiation belt Relativistic Electron Losses (BARREL) balloons and was magnetically mapped close to Geostationary Operational Environmental Satellite (GOES) 13. We simulate the relativistic electron pitch angle diffusion caused by gyroresonant interactions with EMIC waves using wave and particle data measured by multiple instruments on board GOES 13 and the Van Allen Probes. We show that the count rate, the energy distribution, and the time variation of the simulated precipitation all agree very well with the balloon observations, suggesting that EMIC wave scattering was likely the cause for the precipitation event. The event reported here is the first balloon REP event with closely conjugate EMIC wave observations, and our study employs the most detailed quantitative analysis on the link of EMIC waves with observed REP to date. Key PointsQuantitative analysis of the first balloon REP with closely conjugate EMIC wavesOur simulation suggests EMIC waves to be a viable cause for the REP eventThe adopted model is proved to be applicable to simulating the REP event

Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility

Multiple sclerosis (MS) is an inflammatory disease of the CNS that is characterized by BBB dysfunction and has a much higher incidence in females. Compared with other strains of mice, EAE in the SJL mouse strain models multiple features of MS, including an enhanced sensitivity of female mice to disease; however, the molecular mechanisms that underlie the sex- and strain-dependent differences in disease susceptibility have not been described. We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that regulates BBB permeability by destabilizing adherens junctions. S1PR2 expression was increased in disease-susceptible regions of the CNS of both female SJL EAE mice and female patients with MS compared with their male counterparts. Pharmacological blockade or lack of S1PR2 signaling decreased EAE disease severity as the result of enhanced endothelial barrier function. Enhanced S1PR2 signaling in an in vitro BBB model altered adherens junction formation via activation of Rho/ROCK, CDC42, and caveolin endocytosis-dependent pathways, resulting in loss of apicobasal polarity and relocation of abluminal CXCL12 to vessel lumina. Furthermore, S1PR2-dependent BBB disruption and CXCL12 relocation were observed in vivo. These results identify a link between S1PR2 signaling and BBB polarity and implicate S1PR2 in sex-specific patterns of disease during CNS autoimmunity

Perceived Preparedness and Self-Efficacy of Counselors in Training in Online Programs

The purpose of this transcendental, phenomenological study was to describe master’s-level Counselors-in-Training (CITs) perceived preparedness to treat real clients before transitioning to their practicum or internship experience. Adult learning theory and self-efficacy development theory guided this study. The research questions included a) How do master-level CITs describe their experience of perceived preparedness to real clients before transitioning to their practicum or internship experience? b) How do study participants describe the influence that the counseling program curriculum, including structure and practicum timing, had on their readiness to transition to practicum or internship? c) How do study participants describe the influence that clinical supervision had on their readiness to transition to practicum or internship? d) How did study participants perceive their experiences with anxiety, apprehension, or dread before transitioning to practicum or internship? What do they feel would have decreased any of these perceived distresses? Data collection methods included semi-structured interviews, visual representations, and reflective journaling. Data was analyzed using Moustakas’ (1994) modified version of the Van Kaam method- horizontalization, reduction, clustering, theme development, validation, and textural and structural descriptions for the meaning of experiences. Four main themes emerged through data analysis: a) external factors were a major source of increased confidence or preparedness, (b) lack of engagement was a major factor for decreased confidence or preparedness, c) a perceived disconnect between course content and how to apply the knowledge while conducting counseling sessions, and d) overall feelings of anxiety and apprehension were present

The Sloan Digital Sky Survey Reverberation Mapping Project: Technical Overview

The Sloan Digital Sky Survey Reverberation Mapping project (SDSS-RM) is a dedicated multi-object RM experiment that has spectroscopically monitored a sample of 849 broad-line quasars in a single 7 deg$^2$ field with the SDSS-III BOSS spectrograph. The RM quasar sample is flux-limited to i_psf=21.7 mag, and covers a redshift range of 0.1<z<4.5. Optical spectroscopy was performed during 2014 Jan-Jul dark/grey time, with an average cadence of ~4 days, totaling more than 30 epochs. Supporting photometric monitoring in the g and i bands was conducted at multiple facilities including the CFHT and the Steward Observatory Bok telescopes in 2014, with a cadence of ~2 days and covering all lunar phases. The RM field (RA, DEC=14:14:49.00, +53:05:00.0) lies within the CFHT-LS W3 field, and coincides with the Pan-STARRS 1 (PS1) Medium Deep Field MD07, with three prior years of multi-band PS1 light curves. The SDSS-RM 6-month baseline program aims to detect time lags between the quasar continuum and broad line region (BLR) variability on timescales of up to several months (in the observed frame) for ~10% of the sample, and to anchor the time baseline for continued monitoring in the future to detect lags on longer timescales and at higher redshift. SDSS-RM is the first major program to systematically explore the potential of RM for broad-line quasars at z>0.3, and will investigate the prospects of RM with all major broad lines covered in optical spectroscopy. SDSS-RM will provide guidance on future multi-object RM campaigns on larger scales, and is aiming to deliver more than tens of BLR lag detections for a homogeneous sample of quasars. We describe the motivation, design and implementation of this program, and outline the science impact expected from the resulting data for RM and general quasar science.Comment: 25 pages, submitted to ApJS; project website at http://www.sdssrm.or

Mount Mazama and Crater Lake : A Study of the Botanical and Human Responses to a Geologic Event

Crater Lake, located in the southern Cascade mountains of Oregon, is the seventh deepest lake in the world. Unlike a majority of the deepest lakes in the world, found in continental rift valleys, Crater Lake is in the caldera of a volcano. For the young at heart and mind, those willing to descend (and ascend) about 700 feet to Cleetwood Cove can undertake a boat tour of Crater Lake. From the boat, Crater Lake is more than just a beautiful blue lake; it becomes the inside of a volcano, where the response of people and plants to a geologic event can be investigated. The catastrophic eruption of Mount Mazama 7,700 years ago affected both plant and human populations. Before pumice and ash from the volcano blanketed the landscape like freshly fallen snow, the forests to the east of Mount Mazama were dominated by ponderosa and lodgepole pine. Within the immediate vicinity of the volcano all life was obliterated; the force of the eruptive material toppled vegetation and buried it with ash and pumice. Through the recovery process of succession, life has slowly returned to Crater Lake. Forests surrounding the lake are now dominated by mountain hemlock, whitebark pine, and lodgepole pine. These plants not only depict the process of succession, but also of adaptation to a volcanic environment. Factors restricting establishment and growth of plants are controlled by the nonliving environment. Climate, geologic activities, elevation, and time all contribute to the availability of water, soil, nutrients, and sunlight, which directly affect plant growth. Heavy winter snows, which linger until July, and very little summer rain, control soil moisture and the length of the growing season at Crater Lake. Volcanic activity dictates the parent material, which with time breaks down forming soil. The properties of the soil determine its ability to hold water and the concentrations and availability of nutrients. Pumice soils provide developing plants with low nutrient supplies and affect the growth of plants with extreme surface temperature fluctuations. Volcanic cinder has a very low capacity to hold water and nutrients, thus restricting plant growth. People have lived in the Pacific Northwest for at least the last 10,000 years. Direct archaeological evidence of life near Mount Mazama is scarce. Those occupation sites closest to the volcano were covered with pumice and ash from the climactic eruptions. Sites protected from the eruptive material and sites farther away provide archaeologists a glimpse into the cultures of the Basin and Range Province. People living around Mount Mazama were predominantly nomadic; their survival depended on available resources. The catastrophic eruption of Mount Mazama and the subsequent devastation of the land disrupted their lives. As the environment recovered from the eruption, the people also recovered. They were forced to find alternative food sources, fuels, and shelters. The indigenous people's perceptions of this natural disaster are understood indirectly through the use of archaeological data and folklore. Their stories tell of angry gods and stalwart ancestors. Llao, the God of the underworld, and Skell, the God of light, were often at war, Llao from Mount Mazama and Skell from Mount Shasta. Although the origins of such legends are difficult to trace, they emphasize the perceptions of those who lived in the shadow of this mystical volcano. People's limited understanding of the volcano thus triggered their reverence for the place