IS SPECIAL EDUCATION A LIFE SENTENCE? EXAMINING DISPROPORTIONALITY IN THE DECLASSIFICATION RATES OF STUDENTS OF COLOR IN AN URBAN SCHOOL DISTRICT

Federal law states that any student suspected of having a disability must meet initial eligibility requirements to qualify for special education services. Furthermore, an individual education program (IEP) team is required by federal law to re-evaluate each student with a qualified disability tri-annually to assess his or her ongoing need for such services. The pathway toward initial eligibility is explicitly outlined within federal legislation; however, the law does not explicate an avenue for declassification or exiting from special education. As a result, many students may remain in special education and are labeled as students with a disability when they may no longer require the specialized instruction or related services provided through special education. The reality is that special education has evolved into a trapdoor, not a doorway to opportunity - as it was intended to be (Maydosz, 2014). The purpose of this phenomenological study was to examine the extent to which, if at all, the perceptions/attitudes of members of the committee on special education (CSE) and the subcommittee of special education (SCSE) about race and ability influence decision making and declassification during the special education process. The study examined whether a relationship existed between perceptions of race and ability and the disproportionate declassification rates in an urban school district. The study explored this phenomenon through a conceptual framework that synthesizes Ladson-Billings’ (2007) four forms of educational debt (economic, historical, sociopolitical, and moral) that have accumulated over time and negatively impact students of color. The conceptual framework s¬¬erved as a foundation for and framed the theoretical framework\u27s discussion, which is Connor, Ferri, and Annamma’s (2016) Dis/ability Critical Race Studies in Education (DisCrit). The researcher conducted one-on-one, in-depth, and semi-structured virtual interviews with five administrators (principals and assistant principals), seven general education teachers, three special education department chairs, four general education teachers, and one school counselor. The research questions helped reveal their lived experiences. Findings suggest that among CSE members, there are (a) mixed perceptions and attitudes toward declassification, (b) variances in the understanding of the declassification and special education process, and (c) a myriad of experiences, biases, and perceptions about race and ability exist that may influence declassification, as well as (d) an understanding that multiple factors influence declassification, (e) the belief that declassification is rare, (f) an understanding that multiple factors influence declassification, (g) an emphasis on mainstreaming within the urban school district, and (h) an acceptance that barriers exist that prevent educational stakeholders from accurately assessing students’ abilities

Chronic Opisthorchis viverrini Infection and Associated Hepatobiliary Disease Is Associated with Iron Loaded M2-like Macrophages

Chronic Opisthorchis viverrini-induced hepatobiliary disease is associated with significant leukocyte infiltration, including activated macrophages; however, the polarization of infiltrating macrophages remains to be fully characterized. In this study, we characterized macrophage polarization and phenotype in chronic O. viverrini-induced hepatobiliary disease in humans and hamsters using gene expression and histochemical analysis. Chronic O. viverrini infection and associated hepatobiliary diseases were associated with iron loaded M2-like macrophages in both humans and hamsters. This study provides suggestive evidence that iron loaded M2-like macrophages promote hepatobiliary disease in chronic O. viverrini infection

Regulatory mechanisms mediated by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer

Considerable progress has been made during the past twenty years towards elucidating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of mRNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes. Molecular mechanisms have since been discovered to explain how this nuclear receptor can be targeted for preventing and treating skin cancer. This includes the regulation of terminal differentiation, mitotic signaling, endoplasmic reticulum stress, and cellular senescence. Interestingly, the effects of activating PPARβ/δ can preferentially target keratinocytes with genetic mutations associated with skin cancer. This review provides the history and current understanding of how PPARβ/δ can be targeted for both non-melanoma skin cancer and melanoma, and postulates how future approaches that modulate PPARβ/δ signaling may be developed for the prevention and treatment of these diseases

Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system’s contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8-hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8-hu HSC/Hep mouse, which supports HCV infection, human T-cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long-term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV-infected humanized mice. HCV infection also induced HCV-specific T-cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti-human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV-infected humanized mice. We discuss the limitation and future improvements of the AFC8-hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer

Modeling hepatitis B virus infection, immunopathology and therapy in mice

Despite the availability of a preventive vaccine, chronic hepatitis B virus (HBV) infection-induced liver diseases continue to be a major global public health problem. HBV naturally infects only humans and chimpanzees. This narrow host range has hindered our ability to study the characteristics of the virus and how it interacts with its host. It is thus important to establish small animal models to study HBV infection, persistence, clearance and the immunopathogenesis of chronic hepatitis B. In this review, we briefly summarize currently available animal models for HBV research, then focus on mouse models, especially the recently developed humanized mice that can support HBV infection and immunopathogenesis in vivo. This article is part of a symposium in Antiviral Research on “From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B: an unfinished story.

Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

Production of immunodeficient (ID) models in non-murine animal species had been extremely challenging until the advent of gene-editing tools: first zinc finger nuclease (ZFN), then transcription activator-like effector nuclease (TALEN), and most recently clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR)/Cas9. We and others used those gene-editing tools to develop ID rabbits carrying a loss of function mutation in essential immune genes, such as forkhead box protein N1 (FOXN1), recombination activating gene 1/2 (RAG1/2), and interleukin 2 receptor subunit gamma (IL2RG). Like their mouse counterparts, ID rabbits have profound defects in their immune system and are prone to bacterial and pneumocystis infections without prophylactic antibiotics. In addition to their use as preclinical models for primary immunodeficient diseases, ID rabbits are expected to contribute significantly to regenerative medicine and cancer research, where they serve as recipients for allo- and xeno-grafts, with notable advantages over mouse models, including a longer lifespan and a much larger body size. Here we provide a concise review of the history and current status of the development of ID rabbits, as well as future perspectives of this new member in the animal model family

Generation of a humanized mouse model with both human immune system and liver cells to model hepatitis C virus infection and liver immunopathogenesis

Establishing a small animal model that accurately recapitulates hepatotropic pathogens, including hepatitis C virus (HCV) infection and immunopathogenesis, is essential for the study of hepatitis virus–induced liver disease and for therapeutics development. This protocol describes our recently developed humanized mouse model for studying HCV and other hepatotropic infections, human immune response and hepatitis and liver fibrosis. The first 5-h stage is the isolation of human liver progenitor and hematopoietic stem cells from fetal liver. Next, AFC8 immunodeficient mice are transplanted with the isolated progenitor/stem cells. This generally takes 2 h. The transplanted mice are then treated for a month with the mouse liver apoptosis–inducing AFC8 dimerizer and left for an additional 2-month period to permit human liver and immune cell growth as well as system reconstitution and development before inoculation with HCV clinical isolates. HCV infection, human immune response and liver disease are observed with high incidence from approximately 2 months after inoculation

Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding

Peroxisome proliferator activated receptors (PPARs δ, α and γ) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328) in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design

A Humanized Mouse Model to Study Hepatitis C Virus Infection, Immune Response, and Liver Disease

Studies of hepatitis C virus (HCV) infection, immunopathogenesis, and resulting liver diseases have been hampered by the lack of a small animal model. We developed humanized mice with human immune system and liver tissues to improve the studies of hepatitis C pathogenesis and treatment

High macrophage activities are associated with advanced periductal fibrosis in chronic Opisthorchis viverrini infection

Liver fluke infection caused by Opisthorchis viverrini induces several hepatobiliary conditions including advanced periductal fibrosis (APF ) and cholangiocarcinoma (CCA ), but >25% of the infected population develops APF and 1% develop CCA . The innate immune response is the first line of defence, and macrophages are critical regulators of fibrosis. We hypothesized that macrophages from infected individuals have different capacities to either promote or suppress periductal fibrosis. We compared phagocytic activities of macrophages of healthy individuals and O viverrini‐ infected individuals ± APF , and found that macrophages from infected individuals with APF ingested significantly higher numbers of beads compared with healthy controls and O viverrini‐ infected individuals without APF . To further investigate proteolytic activity, we monitored real‐time phagosomal proteolysis of beads conjugated to DQ ‐BODIPY ‐BSA using live cell imaging. We show that macrophages from O viverrini‐ infected individuals with APF also have elevated phagosomal proteolysis activity, which is consistent with their increased phagocytic activity. Additionally, stimulated ROS production by blood monocytes was higher in individuals with APF compared with healthy controls and infected individuals without APF . These results suggest that during O viverrini infection, macrophages with high phagocytic and proteolytic activities together with elevated ROS production are the phenotypes that can promote tissue damage, which results in periductal fibrosis