Efficient Delivery of across the Blood Brain Barrier Using AAVphp Construct in Adult KO Mice Suggests the Feasibility of Gene Therapy for Fragile X Syndrome.

Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. Gene therapy may offer an efficient method to ameliorate the symptoms of this disorder. Methods An AAVphp.

A comparison of curricula: Examining the efficacy of a school-based musical theater intervention.

Students qualifying for services under the Individuals with Disabilities Education Act may experience challenges meeting the socioemotional demands of the school environment, creating a need for targeted interventions that can be delivered within school settings. The current study used a mixed-methods approach to examine the efficacy of a 4-week school-based musical theater intervention delivered to 121 elementary students with intellectual and developmental disabilities. Quantitative analyses of teacher-reported changes in student engagement pre- and post-intervention were conducted to compare student gains made across two intervention curricula, followed by qualitative content analyses of teachers' responses to open-ended survey questions.

A preliminary investigation of a school-based musical theater intervention program for children with intellectual disabilities.

The presence of an intellectual disability may cause a child to have significant deficits in social skills and emotion regulation abilities across development. A vital next step is to find interventions that can be delivered in the school environment and across disability categories that target socioemotional factors. The current study investigated the feasibility of delivering a school-based musical theater program to students with intellectual disability across a range of school settings.

Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.

Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs.

Novel Epigenetic Regulation of Alpha-Synuclein Expression in Down Syndrome.

Alpha-synuclein (SNCA), a presynaptic protein, is significantly reduced in individuals with Down syndrome (DS) and Ts65Dn mice, a mouse model of DS. Methylation analyses of promoter proximal CpG sites indicate similar reduction in Ts65Dn mice compared to control mice. Epigallocatechin-3-gallate (EGCG), a polyphenolic catechin present in green tea extract, increases methylation of SNCA promoter proximal CpG sites and expression in Ts65Dn mice.

Oral health status and needs of homebound elderly in an urban home-based primary care service.

Objectives: This study assessed the oral health status, dental utilization and dental needs of the homebound elderly (HBE) care patients within the Mount Sinai Visiting Doctor program.

Methods: Of the 334 eligible patients, 57% agreed to participate and 95.4% completed the clinical examinations, the Dental Utilization and Needs survey and Geriatric Oral Health Assessment Index conducted in each subject's home by a trained research team.

Assessment of social interaction and anxiety-like behavior in senescence-accelerated-prone and -resistant mice.

Two members of the senescence-accelerated mouse group, SAMP8 and SAMP10, are characterized by learning and memory deficits, while the SAMR1 strain is not. In this study, we used two behavioral tests, social approach and object recognition and compared the results observed for the SAMP strains with those seen in the control strain, SAMR1. In social approach experiments, the 2 SAMP strains showed decreased sociability compared to SAMR1 as shown by their reluctance to spend time near a stranger mouse and increased immobility.

Altered lymphocyte proliferation and innate immune function in scrapie 139A- and ME7-infected mice.

Lymphoid organs play an important role in prion disease development and progression. While the role of lymphoid organs and changes in immune-related genes have been extensively investigated in scrapie-infected animals, innate immunity has not. Previous studies examined lymphocyte function in scrapie-infected C3H/HeJ mice, which exhibit defects in lipopolysaccharide (LPS) response now known to result from a mutation in Toll-like receptor (TLR) 4.

Regulation of α-synuclein expression in Down syndrome.

The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures, stroke, and mental retardation. Studies on RNA and protein expression of genes in DS brain have demonstrated the role of triplicated genes in several DS phenotypes. Significant changes in the expression of nontriplicated genes have also been observed.

Upregulation of beta-catenin expression in down syndrome model Ts65Dn mouse brain.

Trisomy of human chromosome 21 (Hsa 21) causes the pathological characteristics of Down syndrome (DS). Little is known about the mechanisms by which trisomy 21 affects the expression of genes on other chromosomes. Using a mouse model of DS, the Ts65Dn mouse, we have performed mRNA and protein measurements to identify genes on chromosomes not syntenic with Hsa 21 whose expression is affected by the presence of three copies of genes between loci Mrpl39 and Znf295 on mouse chromosome 16 (Mmu 16).

Induction of toll-like receptor 9 signaling as a method for ameliorating Alzheimer's disease-related pathology.

The pathogenesis of Alzheimer's disease (AD) is thought to be related to the accumulation of amyloid beta (Abeta) in amyloid deposits and toxic oligomeric species. Immunomodulation is emerging as an effective means of shifting the equilibrium from Abeta accumulation to clearance; however, excessive cell mediated inflammation and cerebral microhemorrhages are two forms of toxicity which can occur with this approach. Vaccination studies have so far mainly targeted the adaptive immune system.

Physiological properties of astroglial cell lines derived from mice with high (SAMP8) and low (SAMR1, ICR) levels of endogenous retrovirus.

Previous studies have reported that various inbred SAM mouse strains differ markedly with regard to a variety of parameters, such as capacity for learning and memory, life spans and brain histopathology. A potential cause of differences seen in these strains may be based on the fact that some strains have a high concentration of infectious murine leukemia virus (MuLV) in the brain, whereas other strains have little or no virus. To elucidate the effect of a higher titer of endogenous retrovirus in astroglial cells of the brain, we established astroglial cell lines from SAMR1 and SAMP8 mice, which are, respectively, resistant and prone to deficit in learning and memory and shortened life span.

CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils.

Prion diseases are characterized by conversion of the cellular prion protein (PrP(C)) to a protease-resistant conformer, the srapie form of PrP (PrP(Sc)). Humoral immune responses to nondenatured forms of PrP(Sc) have never been fully characterized. We investigated whether production of antibodies to PrP(Sc) could occur in PrP null (Prnp(-/-)) mice and further, whether innate immune stimulation with the TLR9 agonist CpG oligodeoxynucleotide (ODN) 1826 could enhance this process.

Scrapie infection activates the replication of ecotropic, xenotropic, and polytropic murine leukemia virus (MuLV) in brains and spinal cords of senescence-accelerated mice: implication of MuLV in progression of scrapie pathogenesis.

Senescence-accelerated mice (SAMP8) have a short life span, whereas SAMR1 mice are resistant to accelerated senescence. Previously it has been reported that the Akv strain of ecotropic murine leukemia virus (E-MuLV) was detected in brains of SAMP8 mice but not in brains of SAMR1 mice. In order to determine the change of MuLV levels following scrapie infection, we analyzed the E-MuLV titer and the RNA expression levels of E-MuLV, xenotropic MuLV, and polytropic MuLV in brains and spinal cords of scrapie-infected SAM mice.

Clearance and prevention of prion infection in cell culture by anti-PrP antibodies.

Prion diseases are transmissible and invariably fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrP(C)) into a self-replicating and proteinase K (PK)-resistant conformer, scrapie PrP (PrP(Sc)). Humoral immunity may significantly prolong the incubation period and even prevent disease in murine models of prionoses. However, the mechanism(s) of action of anti-PrP monoclonal antibodies (Mabs) remain(s) obscure.

Pouring crown and bridge impressions: helpful hint.

This article describes a time-tested method for avoiding common problems encountered while pouring crown and bridge impressions.

Immunogold study of altered expression of some interendothelial junctional molecules in the brain blood microvessels of diabetic scrapie-infected mice.

Quantitative immunogold procedure was used to study the distribution of molecular components of interendothelial junctions in blood-brain barrier (BBB) microvessels of scrapie infected SJL/J hyperglycemic mice showing obesity and reduced glucose tolerance. Samples of brain (fronto-parietal cerebral cortex and thalamo-hypothalamic region) obtained from hyperglycemic (diabetic) mice and from non- infected, normoglycemic (non-diabetic) SJL/J mice, were processed for immunocytochemical examination. The localization of the following tight junction (TJ)-associated proteins was studied: occludin as an integral membrane (transmembrane) protein, and zonula occludens one (ZO-1) as a peripheral protein.

The mouse model for scrapie: inoculation, clinical scoring, and histopathological techniques.

The mouse is a popular and versatile model for the study of scrapie and other transmissible spongiform encephalopathies. In this chapter, information is given for preparation of infectious material for inoculation and a method of clinical scoring that yields accurate and reproducible quantification of the scrapie incubation period. With the help of histopathological and immunopathological techniques, we can detect brain pathological changes in scrapie-infected animals at the cellular and molecular level.

Mucosal vaccination delays or prevents prion infection via an oral route.

In recent years major outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrP(C) (prion protein cellular), to a toxic and infectious form, PrP(Sc) (prion protein scrapie). None of the prionoses currently have an effective treatment.

Pathological changes in the liver of a senescence accelerated mouse strain (SAMP8): a mouse model for the study of liver diseases.

Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1).