Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol

Myeloid-derived suppressor cells (MDSCs) are getting increased attention as one of the main regulatory cells of the immune system. They are induced at sites of inflammation and can potently suppress T cell functions. In the current study, we demonstrate how activation of TRPV1 vanilloid receptors can trigger MDSCs, which in turn, can inhibit inflammation and hepatitis.Polyclonal activation of T cells, following injection of concanavalin A (ConA), in C57BL/6 mice caused acute hepatitis, characterized by significant increase in aspartate transaminase (AST), induction of inflammatory cytokines, and infiltration of mononuclear cells in the liver, leading to severe liver injury. Administration of cannabidiol (CBD), a natural non-psychoactive cannabinoid, after ConA challenge, inhibited hepatitis in a dose-dependent manner, along with all of the associated inflammation markers. Phenotypic analysis of liver infiltrating cells showed that CBD-mediated suppression of hepatitis was associated with increased induction of arginase-expressing CD11b(+)Gr-1(+) MDSCs. Purified CBD-induced MDSCs could effectively suppress T cell proliferation in vitro in arginase-dependent manner. Furthermore, adoptive transfer of purified MDSCs into naïve mice conferred significant protection from ConA-induced hepatitis. CBD failed to induce MDSCs and suppress hepatitis in the livers of vanilloid receptor-deficient mice (TRPV1(-/-)) thereby suggesting that CBD primarily acted via this receptor to induce MDSCs and suppress hepatitis. While MDSCs induced by CBD in liver consisted of granulocytic and monocytic subsets at a ratio of ∼2∶1, the monocytic MDSCs were more immunosuppressive compared to granulocytic MDSCs. The ability of CBD to induce MDSCs and suppress hepatitis was also demonstrable in Staphylococcal enterotoxin B-induced liver injury.This study demonstrates for the first time that MDSCs play a critical role in attenuating acute inflammation in the liver, and that agents such as CBD, which trigger MDSCs through activation of TRPV1 vanilloid receptors may constitute a novel therapeutic modality to treat inflammatory diseases

Protest Cycles and Political Process: American Peace Movements in the Nuclear Age

Since the dawn of the nuclear age small groups of activists have consistently protested both the content of United States national security policy, and the process by which it is made. Only occasionally, however, has concern about nuclear weapons spread beyond these relatively marginal groups, generated substantial public support, and reached mainstream political institutions. In this paper, I use histories of peace protest and analyses of the inside of these social movements and theoretical work on protest cycles to explain cycles of movement engagement and quiescence in terms of their relation to external political context, or the "structure of political opportunity." I begin with a brief review of the relevant literature on the origins of movements, noting parallels in the study of interest groups. Building on recent literature on political opportunity structure, I suggest a theoretical framework for understanding the lifecycle of a social movement that emphasizes the interaction between activist choices and political context, proposing a six-stage process through which challenging movements develop. Using this theoretical framework I examine the four cases of relatively broad antinuclear weapons mobilization in postwar America. I conclude with a discussion of movement cycles and their relation to political alignment, public policy, and institutional politics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68552/2/10.1177_106591299304600302.pd

Textual Concept Critical Analysis: Toward a Research Approach for Language Studies

When the International Society for Language Studies (ISLS) was founded in 2002 and the journal that is now Critical Inquiry in Language Studies (CILS) was in the planning stages, we recognized a need for an interdisciplinary, or perhaps even transdisciplinary (see Kaufman, Moss, & Osborn, 2003), venue for the publication of research on language issues that came from a variety of critical and power-based perspectives. At the same time, there was an intentionality about exploring the development of research methodologies that would be both rigorous and accessible. In the six volumes of CILS that have appeared since its founding, however, this latter goal has remained elusive. In this article, we seek to outline a protocol that we hope will begin a broader conversation to develop this important but still overlooked area

(electronic) Mitochondrial DNA, Early Online: 1-2 !

Abstract This study determined the first complete mitochondrial genome of a demoiselle, Vestalis melania (Odonata, Zygoptera, Calopterygidae) using long-range PCR and a primer walking approach. This mitogenome is 16,685 bp long and contains the entire set of 37 genes and an A þ T-rich control region typically found in insects. Presently, this mitogenome is the largest mitogenome of all available odonates, mainly because of its long A þ T-rich region (2036 bp). The gene arrangement of the V. melania mitogenome is identical to that of other known odonates. The inter-genic spacer s5 shared by the Anisoptera is absent in V. melania, which supports the view that the absence of the s5 spacer is a synapomorphy of the Zygoptera

Stem cell implants for cancer therapy : TRAIL-expressing mesenchymal stem cells target cancer cells in situ

Tumor-specific delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an apoptosis-inducing peptide, at effective doses remains challenging. Herein we demonstrate the utility of a scaffold-based delivery system for sustained therapeutic cell release that capitalizes on the tumor-homing properties of mesenchymal stem cells (MSCs) and their ability to express genetically-introduced therapeutic genes