Information-theoretic gene-gene and gene-environment interaction analysis of quantitative traits.

Background: The purpose of this research was to develop a novel information theoretic method and an efficient algorithm for analyzing the gene-gene (GGI) and gene-environmental interactions (GEI) associated with quantitative traits (QT). The method is built on two information-theoretic metrics, the k-way interaction information (KWII) and phenotype-associated information (PAI). The PAI is a novel information theoretic metric that is obtained from the total information correlation (TCI) information theoretic metric by removing the contributions for inter-variable dependencies (resulting from factors such as linkage disequilibrium and common sources of environmental pollutants).

Hyponatraemic encephalopathy as the initial presentation of Guillain-Barre syndrome.

This report deals with an elderly lady with Guillain-Barre Syndrome (GBS), who presented with features of unusually severe hyponatraemia. The hyponatraemia was probably due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The hyponatraemia resolved with water restriction and infusion of hypertonic saline; GBS was treated with human immunoglobulin (IVIG).

Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis.

Background: Cigarette smoking has been linked to higher susceptibility and increased risk of progressive multiple sclerosis (MS). The effects of smoking on MRI characteristics of patients with MS have not been evaluated.

Objectives: To compare the MRI characteristics in cigarette smoker and nonsmoker patients with MS.

MRI characteristics of patients with antiphospholipid syndrome and multiple sclerosis.

MRI findings of primary anti-phospholipid antibody syndrome (PAPLS) are difficult to distinguish from those of multiple sclerosis (MS). Only a few previous studies have compared conventional and non-conventional MRI findings in MS and PAPLS patients. In addition, MRI differences between anti-phospholipid antibody (APLA) positive (+) and APLA negative (-) MS patients have not been reported.

Development of a novel DNA SynCon tetravalent dengue vaccine that elicits immune responses against four serotypes.

The increased transmission and geographic spread of dengue fever (DF) and its most severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), make it one of the most important mosquito-borne viral disease of humans. Four distinct serotypes of dengue viruses are transmitted to humans through the bites of the mosquitoes. Currently there is no vaccine or antiviral drug against DV infections.

Effect of excessive cholesterol and lipopolysaccharide on cerebellar neuronal cells in in vitro and protective role of anti-inflammatory drugs.

The present work was carried out to elucidate the role of NSAIDs, PPARg agonist and HMG CoA inhibitor on cholesterol and lipopolysaccharide (LPS) induced neurodegeneration. The cerebellar, neuronal cells were exposed to cholesterol (10 and 50 microg/ml), LPS (1 ng/ml) or both. Neuroprotective effect of ibuprofen, rofecoxib, simvastatin and pioglitazone was assessed by measuring the neuronal loss, MTT dye assay, nitric oxide, LDH and lipid peroxide measurement.

Molecular genetic relationship of the 3' untranslated region among Thai dengue-3 virus, Bangkok isolates, during 1973-2000.

Dengue virus serotype 3 (DENV-3) was associated with severe dengue epidemics in Thailand during 1973-1999. We studied Thai DENV-3 viruses isolated from hospitalized children in Bangkok with differing disease severity during that period. Viruses were sequenced at their 5' and 3' untranslated regions (UTRs), which are regions that play a pivotal role in viral replication.

Coimmunization with an optimized IL15 plasmid adjuvant enhances humoral immunity via stimulating B cells induced by genetically engineered DNA vaccines expressing consensus JEV and WNV E DIII.

The Japanese encephalitis virus (JEV) and West Nile virus (WNV) are responsible for a large proportion of viral encephalitis in humans. Currently, there is no FDA approved specific treatment for either, though there are attempts to develop vaccines against both viruses. In this study, we proposed novel genetically engineered DNA vaccines against these two neurotrophic flaviviruses.

Lysozyme-mediated formation of protein-silica nano-composites for biosensing applications.

We demonstrate a rapid method for enzyme immobilization directly on a waveguide surface by encapsulation in a silica matrix. Organophosphate hydrolase (OPH), an enzyme that catalytically hydrolyzes organophosphates, was used as a model enzyme to demonstrate the utility of lysozyme-mediated silica formation for enzyme stabilization. Silica morphology and the efficiency of OPH encapsulation were directly influenced by the precursor choice used in silica formation.

Differential regulation of HIF-1alpha isoforms in murine macrophages by TLR4 and adenosine A(2A) receptor agonists.

Adenosine A(2A)R and TLR agonists synergize to induce an "angiogenic switch" in macrophages, down-regulating TNF-alpha and up-regulating VEGF expression. This switch involves transcriptional regulation of VEGF by HIF-1, transcriptional induction of HIF-1alpha by LPS (TLR4 agonist), and A(2A)R-dependent post-transcriptional regulation of HIF-1alpha stability. Murine HIF-1alpha is expressed as two mRNA isoforms: HIF-1alphaI.

Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset.

Purpose: To evaluate retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT) in children with acquired demyelinating diseases.

Methods: This is a cross-sectional study of patients seen between 2006-2008 at the Pediatric MS Center of the Jacobs Neurological Institute. Consensus definitions for pediatric demyelinating disease were followed.

Pre-ischemic treatment with memantine reversed the neurochemical and behavioural parameters but not energy metabolites in middle cerebral artery occluded rats.

In the present study, memantine (MN) an uncompetitive N-methyl-D-aspartate (NMDA) open channel blocker has been investigated for its suitable therapeutic time-window on the basis of its influence on behavioural and biochemical changes in rats subjected to transient focal ischemia. MN (20 mg/kg, ip) was administered at pre, during and post ischemic state and the extent of neuroprotection was compared to ascertain its therapeutic time-window in stroke treatment. Neuroprotective effect was assessed by measuring glutamate, glutamine synthetase, glutathione, Na+K+ATPase, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD), lactate and pyruvate levels.

Mechanisms of interferon-beta effects on bone homeostasis.

Restoration of dysregulated bone homeostasis is a therapeutic goal in many diseases including osteoporosis, rheumatoid arthritis and metastatic cancer. The molecular pathways regulating bone remodeling are major therapeutic targets, and studies continue to reveal endogenous factors that may be pathologically up- or down-regulated and lead to an uncoupling of bone formation and resorption. The purpose of this commentary is to highlight new mechanisms of bone homeostatic regulation mediated through the induction of endogenous interferon-beta (IFN-beta).

Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos (Linn.) in hyperlipidaemic models of Wistar albino rats.

Lipid lowering effect of 50% ethanolic extract of the leaves of A. marmelos (Linn.) was evaluated in triton and diet induced hyperlipidaemic models of Wistar albino rats.

Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro.

Background: Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect.

The interaction index, a novel information-theoretic metric for prioritizing interacting genetic variations and environmental factors.

We developed an information-theoretic metric called the Interaction Index for prioritizing genetic variations and environmental variables for follow-up in detailed sequencing studies. The Interaction Index was found to be effective for prioritizing the genetic and environmental variables involved in GEI for a diverse range of simulated data sets. The metric was also evaluated for a 103-SNP Crohn's disease dataset and a simulated data set containing 9187 SNPs and multiple covariates that was modeled on a rheumatoid arthritis data set.

Nonengraftment haploidentical cellular immunotherapy for refractory malignancies: tumor responses without chimerism.

Allogeneic bone marrow transplantation relies on immunosuppression, which controls graft-versus-host disease (GVHD) and allows engraftment at the expense of diminished graft versus-tumor (GVT) activity. Advances in hematologic transplantation have prompted the development of effective, less-toxic regimens that attempt to balance GVH and GVT immunoreactions. We analyzed the safety and efficacy of haploidentical transplantation in a Phase I/II nonimmunosuppressive, nonmyeloablative setting.

Diagnosis of anomalous origin of left coronary artery from pulmonary artery in an adult by 64-slice CT angiography.

Anomalous origin of Left Coronary Artery from Pulmonary Artery (ALCAPA) presenting in adult age is a rare entity. We report an adult patient with exertional angina, who was diagnosed to have ALCAPA conclusively and non-invasively by 64-slice CT angiography.

Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis.

Purpose: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients.

Methods: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained.

Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis.

Objective: The aim of the study was to determine whether the presence of anti-Epstein-Barr virus (EBV) antibodies is associated with MRI measures of brain injury and neurodegeneration in patients with multiple sclerosis (MS).

Methods: 135 patients with MS (86 women, 49 men) underwent brain MRI and testing for antibodies against EBV. MRI measurements included gadolinium enhancing lesion volume, T1 and T2 lesion volumes and fractions of whole brain parenchyma (BPF), white matter and grey matter (GMF).

Suppression of constitutively expressed cyclooxygenase-2 in the epididymis of mice by nimesulide decreases sperm motility.

Significant levels of constitutive cyclooxygenase-2 (COX-2) are present in the male reproductive organs of rodents, especially in the vas deferens and epididymis. In the epididymis, the sperm storehouse, COX-2 is thought to play a vital role in altering the membrane lipids of sperm. The present study aims at localizing COX-2 in the epididymis and analyzing the effects of the preferential COX-2 inhibitor nimesulide.

1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists.

This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues.

A dedicated powder diffraction beamline at the advanced photon source: commissioning and early operational results.

A new dedicated high-resolution high-throughput powder diffraction beamline has been built, fully commissioned, and opened to general users at the Advanced Photon Source. The optical design and commissioning results are presented. Beamline performance was examined using a mixture of the NIST Si and Al(2)O(3) standard reference materials, as well as the LaB6 line-shape standard.