Cigarette Smoke Suppresses Type I Interferon-Mediated Antiviral Immunity in Lung Fibroblast and Epithelial Cells

The objective of this study was to investigate the impact of cigarette smoke on innate antiviral defense mechanisms; specifically, we examined the effects of cigarette smoke on the induction of type I interferon (IFN). We observed a dose-dependent decrease in the ability of human lung fibroblast and epithelial cells to elicit an antiviral response against a viral double-strand RNA (dsRNA) mimic, polyI:C, in the presence of cigarette smoke-conditioned medium (SCM). Mechanistically, SCM decreases the expression of IFN-stimulated gene 15 (ISG15) and IFN regulatory factor-7 (IRF-7) transcripts and suppresses the nuclear translocation of key transcription factors, nuclear factor-κB (NF-κB) and IRF-3, after polyI:C stimulation. Furthermore, we provide evidence that the intercellular defense strategy against viral infection is also impaired. We observed a decrease in the ability of fibroblasts to elicit an antiviral state in response to IFN-β stimulation. This was associated with decreased nuclear translocation of phosphorylated Stat1 in response to IFN-β treatment. The effects elicited by SCM are reversible and are almost entirely abrogated in the presence of an antioxidant, such as glutathione. Our findings suggest that cigarette smoke affects the immediate-early, inductive, and amplification phases of the type I IFN response

Assessment of cognitive safety in clinical drug development

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks

Perspectives on Social Realism within North American higher music education

This article critically examines the suitability of Social Realist perspectives within North American higher music education, with a particular focus on its relationship with jazz musical knowledges. Social Realist scholarship continues to emerge within the field of education sociology, driven by claims to contribute to student access and opportunity. In spite of this, scholars have continued to critique Social Realist perspectives for various reasons including maintaining an ideological status quo and devaluing the experiences of students, going as far as argue that Social Realist frameworks may in fact limit the access and opportunity espoused by its proponents. Drawing upon past music education literature surrounding Social Realism, this article focuses particularly on the concepts of ‘powerful knowledge,’ ‘generative knowledge,’ and ‘reliablism’ to explore how Social Realism may be ill-positioned to meet its alleged goals of access and opportunity within the North American higher music institution

Brilliant Online : Introduction to Entrepreneurial Changemaking

This project is made possible with funding by the Government of Ontario and through eCampusOntario’s support of the Virtual Learning Strategy.Stage 1: Entrepreneurship & Laying the GroundworkStage 2: How to Validate and Execute Your IdeaStage 3: Prototyping and TestingBrilliant Online: Introduction to Entrepreneurial Changemaking is a series of online modules designed to give aspiring entrepreneurs the knowledge and resources they need to get started. Brilliant Online focuses mainly on the ideation and validation stages of the entrepreneurial journey. Brilliant Online was created by the Brilliant Catalyst at Ontario Tech University. Located in Oshawa, Ontario, Brilliant Catalyst is the university-based incubator and experiential learning hub on campus. Working under the leadership of the Vice-President, Research and Innovation, the Brilliant Catalyst strives to be a leader in entrepreneurial thinking in Ontario, in Canada, and around the world

Adults' Understanding of Extraordinary Mental, Perceptual, and Physical Capacities

Psychologyhttp://deepblue.lib.umich.edu/bitstream/2027.42/85245/1/stzavitz.pd

Local proliferation dominates lesional macrophage accumulation in atherosclerosis

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall1,2. The observation that circulating monocytes give rise to lesional macrophages3–9 has reinforced the concept that monocyte infiltration dictates macrophage build-up. Recent work indicates, however, that macrophages do not depend on monocytes in some inflammatory contexts10. We therefore revisited the mechanism of macrophage accumulation in atherosclerosis. We show that murine atherosclerotic lesions experience a surprisingly rapid, 4-week, cell turnover. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation via the involvement of scavenger receptor (SR)-A. Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease

Understanding Sensory Information Processing Through Simultaneous Multi-area Population Recordings

The goal of sensory neuroscience is to understand how the brain creates its myriad of representations of the world, and uses these representations to produce perception and behavior. Circuits of neurons in spatially segregated regions of brain tissue have distinct functional specializations, and these regions are connected to form a functional processing hierarchy. Advances in technology for recording neuronal activity from multiple sites in multiple cortical areas mean that we are now able to collect data that reflects how information is transformed within and between connected members of this hierarchy. This advance is an important step in understanding the brain because, after the sensory organs have transduced a physical signal, every processing stage takes the activity of other neurons as its input, not measurements of the physical world. However, as we explore the potential of studying how populations of neurons in multiple areas respond in concert, we must also expand both the analytical tools that we use to make sense of these data and the scope of the theories that we attempt to define. In this article, we present an overview of some of the most promising analytical approaches for making inferences from population recordings in multiple brain areas, such as dimensionality reduction and measuring changes in correlated variability, and examine how they may be used to address longstanding questions in sensory neuroscience