Mechanistic Target of Rapamycin (mTOR) Inhibitors.

Mechanistic target of rapamycin (mTOR) inhibitors are macrocyclic lactone antibiotics derived from Streptomyces hygroscopicus that prevent T lymphocyte activation and B cell differentiation. Unlike calcineurin inhibitors (CNIs) that inhibit cytokine production, mTOR inhibitors block the cytokine signal transduction to arrest cells in the G1 to S phase. This class of drugs is commonly used for post-transplantation and cancer management because of its immunosuppressive and antiproliferative properties, respectively.

Circulating Cholesterol Levels May Link to the Factors Influencing Parkinson's Risk.

Objectives: A growing literature suggests that circulating cholesterol levels have been associated with Parkinson's disease (PD). In this study, we investigated a possible causal basis for the cholesterol-PD link.

Methods: Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine.

Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders.

Objectives: We demonstrated recently that the T1 relaxation rate (R1) captured short-term Mn exposure in welders with chronic, relatively low exposure levels in a cross-sectional study. In the current study, we used a longitudinal design to examine whether R1 values reflect the short-term dynamics of Mn exposure.

Methods: Twenty-nine welders were evaluated at baseline and 12 months.

Seasonal variation in muscle sympathetic nerve activity.

Epidemiologic data suggest there are seasonal variations in the incidence of severe cardiac events with peak levels being evident in the winter. Whether autonomic indices including muscle sympathetic nerve activity (MSNA) vary with season remains unclear. In this report, we tested the hypothesis that resting MSNA varies with the seasons of the year with peak levels evident in the winter.

Parvovirus B19 nonstructural protein-induced damage of cellular DNA and resultant apoptosis.

Parvovirus B19 is a widespread virus with diverse clinical presentations. The viral nonstructural protein, NS1, binds to and cleaves the viral genome, and induces apoptosis when transfected into nonpermissive cells, such as hepatocytes. We hypothesized that the cytotoxicity of NS1 in such cells results from chromosomal DNA damage caused by the DNA-nicking and DNA-attaching activities of NS1.

Prolyl-peptidyl isomerase, Pin1, phosphorylation is compromised in association with the expression of the HFE polymorphic allele, H63D.

There is substantial interest in HFE gene variants as putative risk factors in neurodegenerative diseases such as Alzheimer disease (AD). Previous studies in cell models have shown the H63D HFE variant to result in increased cellular iron, oxidative stress, glutamate dyshomeostasis, and an increase in tau phosphorylation; all processes thought to contribute to AD pathology. Pin1 is a prolyl-peptidyl cis/trans isomerase that can regulate the dephosphorylation of the amyloid and tau proteins.

Third generation antipsychotic drugs: partial agonism or receptor functional selectivity?

Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second).

Expression of the HFE allelic variant H63D in SH-SY5Y cells affects tau phosphorylation at serine residues.

A number of genetic association studies have appeared that address HFE gene variants in neurodegenerative disorders. However, the cellular impact of HFE in the nervous system has received little attention. To begin to address the role of the HFE allelic variants on cellular events associated with neurodegeneration, we examined the hypothesis that HFE polymorphisms are associated with alterations in tau phosphorylation in a human neuroblastoma cell line (SH-SY5Y).

HFE polymorphisms affect cellular glutamate regulation.

HFE gene variants are relatively common genetic variants in Caucasians. The H63D HFE genetic variant has been repeatedly associated with a number of neurodegenerative diseases. We developed neuroblastoma cell lines expressing different HFE polymorphisms to explore the mechanisms behind these associations.

A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges with respect to diagnosis and monitoring of disease progression.

Objectives: To identify a biomarker panel that elucidates ALS disease pathogenesis, distinguishes patients with ALS from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile.

Methods: We obtained CSF samples by lumbar puncture from 41 patients with ALS and 33 neurologic disease controls.

N-Glycans of ADAMTS13 modulate its secretion and von Willebrand factor cleaving activity.

Severe deficiency of ADAMTS13, a plasma metalloprotease, leads to thrombotic thrombocytopenic purpura. ADAMTS13 contains 10 putative N-glycosylation sites in or near its metalloprotease sequence, spacer region, thrombospondin type 1 repeat no. 4 (TSR no.