The Diagnostic Experiences of Women With Polycystic Ovary Syndrome (PCOS) in Ontario, Canada.

Polycystic ovary syndrome (PCOS) is the most common endocrine syndrome that disproportionally affects women of childbearing age (~8% to 13% of women worldwide). If unmanaged, it can lead to chronic, lifelong complications. Over the past decade, improvements in diagnostic guidelines have not produced an expected reduction in the diagnostic timeframe.

Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease.

We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive "multi-omic" analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, indicating conserved pathobiology in disease.

Measuring Resilience in Two Generations: Psychometric Properties of Available Instruments.

Background And Purpose: This study examines measures of resilience to identify the best available measure for future research to assess efficacy of a low-cost intervention that enhances resilience of older adults and youth (i.e., intergenerational transfer of ethnic culture).

ALS and FTD: an epigenetic perspective.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two fatal neurodegenerative diseases seen in comorbidity in up to 50 % of cases. Despite tremendous efforts over the last two decades, no biomarkers or effective therapeutics have been identified to prevent, decelerate, or stop neuronal death in patients. While the identification of multiple mutations in more than two dozen genes elucidated the involvement of several mechanisms in the pathogenesis of both diseases, identifying the hexanucleotide repeat expansion in C9orf72, the most common genetic abnormality in ALS and FTD, opened the door to the discovery of several novel pathogenic biological routes, including chromatin remodeling and transcriptome alteration.

Epithelial PIK3R1 (p85) and TP53 Regulate Survivin Expression during Adaptation to Ileocecal Resection.

Intestinal adaptation to small-bowel resection (SBR) after necrotizing enterocolitis expands absorptive surface areas and promotes enteral autonomy. Survivin increases proliferation and blunts apoptosis. The current study examines survivin in intestinal epithelial cells after ileocecal resection.

C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins.

Neuronal inclusions of poly(GA), a protein unconventionally translated from G4C2 repeat expansions in C9ORF72, are abundant in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) caused by this mutation. To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS. These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation.

Antioxidant properties of mesalamine in colitis inhibit phosphoinositide 3-kinase signaling in progenitor cells.

Background: Mesalamine, 5-aminosalicylic acid (5-ASA), is a potent antioxidant and is known to enhance peroxisome proliferator-activated receptor γ activity in the intestine. Our previous studies suggested reduced Phosphoinositide 3-Kinase (PI3K)/β-catenin signaling as a mechanism for 5-ASA chemoprevention in chronic ulcerative colitis (CUC). We now hypothesize that 5-ASA mediates changes in intestinal epithelial cell (IEC) reactive oxygen species during colitis to affect phosphatase and tensin homolog (PTEN), PI3K, and β-catenin signaling.

p53 mediates TNF-induced epithelial cell apoptosis in IBD.

Chronic ulcerative colitis (CUC) is characterized by increased intestinal epithelial cell (IEC) apoptosis associated with elevated tumor necrosis factor (TNF), inducible nitric oxide synthase (iNOS), and p53. We previously showed that p53 is increased in crypt IECs in human colitis and is needed for IEC apoptosis in chronic dextran sulfate sodium-colitis. Herein, we examined the roles of TNF and iNOS in regulating p53-induced IEC apoptosis in CUC.

Radiofrequency ablation for dysplasia in Barrett's esophagus restores β-catenin activation within esophageal progenitor cells.

Background And Aims: Endoscopic therapies for Barrett's esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of β-Catenin occurs in SPCs and may be a marker of activated SPCs.

p53 and PUMA independently regulate apoptosis of intestinal epithelial cells in patients and mice with colitis.

Background & Aims: Inflammatory bowel disease (IBD) is associated with increased apoptosis of intestinal epithelial cells (IECs). Mutations in the tumor suppressor p53 appear during early stages of progression from colitis to cancer. We investigated the role of p53 and its target, p53-upregulated modulator of apoptosis (PUMA), in inflammation-induced apoptosis of IECs.

Phosphoinositide 3-kinase signaling mediates beta-catenin activation in intestinal epithelial stem and progenitor cells in colitis.

Background & Aims: Mechanisms responsible for crypt architectural distortion in chronic ulcerative colitis (CUC) are not well understood. Data indicate that serine/threonine protein kinase Akt (Akt) signaling cooperates with Wingless (Wnt) to activate beta-catenin in intestinal stem and progenitor cells through phosphorylation at Ser552 (P-beta-catenin(552)). We investigated whether phosphoinositide 3-kinase (PI3K) is required for Akt-mediated activation of beta-catenin during intestinal inflammation.

Epithelial NF-kappaB enhances transmucosal fluid movement by altering tight junction protein composition after T cell activation.

In inflammatory bowel disease (IBD), aberrant activation of innate and adaptive immune responses enhances mucosal permeability through mechanisms not completely understood. To examine the role of epithelial nuclear factor (NF-kappaB) in IBD-induced enhanced permeability, epithelial-specific IkappaBalpha mutant (NF-kappaB super repressor) transgenic (TG) mice were generated. NF-kB activation was inhibited in TG mice, relative to wild-type mice, following T cell-mediated immune cell activation using an anti-CD3 monoclonal antibody.

SV40 reporter viruses.

Three simian virus 40 (SV40) reporter viruses were constructed in this study. One expresses the green fluorescent protein (GFP) as a fusion protein with the first exon of large-T (LT) antigen and is useful for live-cell imaging. A second reporter virus has a FLAG epitope tag at the C-terminus of large-T antigen (vC-LT(FLAG)), and a third has the FLAG tag at the N-terminus of LT (vN-LT(FLAG)).

Role of SV40 ST antigen in the persistent infection of mesothelial cells.

Viral DNA is maintained episomally in SV40 infected mesothelial cells and virus is produced at low but steady rates. High copy numbers of the viral DNA are maintained in a WT infection where both early antigens are expressed. In the absence of ST, cells are immortal but non-transformed and the infected cells maintain only a few copies of episomal viral DNA.

The notch regulator MAML1 interacts with p53 and functions as a coactivator.

Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53.

Anosmia is very common in the Lewy body variant of Alzheimer's disease.

Background: Olfactory abnormalities are reported in Alzheimer's disease and Parkinson's disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer's disease.

Objective: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer's disease and "pure" Alzheimer's disease.

CORONA, a member of the class III homeodomain leucine zipper gene family in Arabidopsis, regulates stem cell specification and organogenesis.

Organogenesis at the shoot meristem requires a delicate balance between stem cell specification and differentiation. In Arabidopsis thaliana, WUSCHEL (WUS) is a key factor promoting stem cell identity, whereas the CLAVATA (CLV1, CLV2, and CLV3) loci appear to promote differentiation by repressing WUS expression. In a screen for mutations modifying clv1 mutants, we have identified a novel regulator of meristem development we term CORONA (CNA).

Luigi Amaducci memorial award winner's paper 2003. A neurologist's view of Alzheimer's disease and dementia.

Senile dementia was the third most common admission diagnosis for New York psychiatric hospitals at the start of the twentieth century and the distinction between vascular and senile dementia was understood by psychiatrists even then. The term Alzheimer's disease (AD) was originally introduced to distinguish a pre-senile dementia from the common general paresis, but Alzheimer raised the possibility that pre-senile AD might not be distinguishable in clinical or histological terms from senile dementia. By the late 1970s it had become clear that the most common disorder producing dementia in elderly people was clinically and pathologically identical to pre-senile AD.

LMP2A does not require palmitoylation to localize to buoyant complexes or for function.

Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed constitutively in lipid rafts in latently infected B lymphocytes. Lipid rafts are membrane microdomains enriched in cholesterol and sphingolipids selective for specific protein association. Lipid rafts have been shown to be necessary for B-cell receptor (BCR) signal transduction.

Cholesterol-dependent infection of Burkitt's lymphoma cell lines by Epstein-Barr virus.

Epstein-Barr virus (EBV) infection is a multi-step process, first requiring virus binding to the host cell, followed by fusion of the viral envelope with the host cell plasma membrane. Efficient EBV entry into B cells requires, at the minimum, the interaction of the EBV-encoded glycoproteins gp350 with cellular CD21 and gp42 with MHC class II proteins. In this study, use of the cholesterol-binding drugs methyl-beta-cyclodextrin and nystatin efficiently inhibited EBV infection of target Burkitt's lymphoma B-cell lines, indicating an important role for cholesterol and suggesting the involvement of lipid rafts in EBV infection.

Neuropsychological deficits associated with Alzheimer's disease in the very-old: discrepancies in raw vs. standardized scores.

The profiles of neuropsychological deficits associated with Alzheimer's disease (AD) in Young-Old (M age and 70) and Very-Old (M age > 80) patients were compared, along with possible modifying effects of apolipoprotein E (APOE) genotype on these profiles. A comprehensive battery of neuropsychological tests was administered to the two AD patient groups (Young-Old: n = 33; Very-Old: n = 48) and their respective age-matched normal control (NC) groups who remained free of dementia on follow-up examinations over a 1 to 10 year period (Young-Old: n = 43; Very-Old: n = 36). AD and NC groups did not differ in education levels or gender distributions.