Indiana University

About: Indiana University is a education organization based out in Bloomington, Indiana, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 64480 authors who have published 150058 publications receiving 6392902 citations. The organization is also known as: Indiana University system & indiana.edu.

The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception.

Abstract: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates for the detection of AD in its preclinical stages; (5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an additional 550 participants.

Molecular cloning and functional expression of a mu-opioid receptor from rat brain.

Abstract: Opioid drugs act on specific receptors to modulate a wide range of physiological functions. There are at least three types of opioid receptors, mu, delta, and kappa. Using a cDNA probe for a mouse delta-opioid receptor in low stringency hybridization, a clone has been isolated from a rat brain cDNA library. This clone contains an open reading frame of 1194 base pairs, with a deduced polypeptide of 398 amino acid residues. The predicted protein exhibits the structural features of guanine nucleotide-binding protein-coupled receptors and displays a high degree of sequence homology with the mouse delta-opioid receptor. When transfected into COS-7 cells, the cDNA conferred a binding site with subnanomolar affinity for [3H]diprenorphine, a high affinity ligand for all three types of opioid receptors. This site also displayed nanomolar affinity for [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO), a mu-selective agonist, whereas its affinities for the delta-selective agonist [D-Pen2,5]-enkephalin and the kappa-selective agonist U-50488 were in the micromolar range. Several mu-selective antagonists, including naloxonazine, beta-funaltrexamine, and cyprodime, were capable of displacing [3H]diprenorphine binding with nanomolar potency. The pharmacological profile of this binding site thus suggests that it is a mu-type opioid receptor, which we designated MOR-1. In COS-7 cells expressing MOR-1 and stimulated with forskolin, treatment with DAGO decreased the steady state levels of cAMP; this inhibitory effect of DAGO was blocked by naloxonazine. These results suggest that this mu-opioid receptor is functionally coupled to the inhibition of adenylyl cyclase.

CYP2D6 Genotype, Antidepressant Use, and Tamoxifen Metabolism During Adjuvant Breast Cancer Treatment

Abstract: Background The efficacy of tamoxifen therapy for the treatment of breast cancer varies widely among individuals. Plasma concentrations of the active tamoxifen metabolite endoxifen are associated with the cytochrome P450 (CYP) 2D6 genotype. We examined the effects of concomitant use of selective serotonin reuptake inhibitor antidepressants, which are CYP2D6 enzyme inhibitors commonly prescribed to treat hot flashes in women who take tamoxifen, and genotypes for genes that encode tamoxifen-metabolizing enzymes on plasma concentrations of tamoxifen and its metabolites. Methods Eighty patients with newly diagnosed with breast cancer who were beginning tamoxifen therapy (20 mg/day orally), 24 of whom were taking CYP2D6 inhibitors, were genotyped for common alleles of the CYP2D6, CYP2C9, CYP3A5, and sulfotransferase (SULT) 1A1 genes. Plasma concentrations of tamoxifen and its metabolites were measured after 1 and 4 months of tamoxifen therapy. Differences in plasma concentrations of tamoxifen and its metabolites between genotype groups were analyzed by the Wilcoxon rank sum test. All statistical tests were two-sided. Results Among all women, plasma endoxifen concentrations after 4 months of tamoxifen therapy were statistically significantly lower in subjects with a CYP2D6 homozygous variant genotype (20.0 nM, 95% confidence interval [CI] = 11.1 to 28.9 nM) or a heterozygous genotype (43.1 nM, 95% CI = 33.3 to 52.9 nM) than in those with a homozygous wild-type genotype (78.0 nM, 95%CI = 65.9 to 90.1 nM) (both P = .003). Among subjects who carried a homozygous wild-type genotype, the mean plasma endoxifen concentration for those who were using CYP2D6 inhibitors was 58% lower than that for those who were not (38.6 nM versus 91.4 nM, difference = -52.8 nM, 95% CI = -86.1 to -19.5 nM, P = .0025). The plasma endoxifen concentration was slightly reduced in women taking venlafaxine, a weak inhibitor of CYP2D6, whereas the plasma endoxifen concentration was reduced substantially in subjects who took paroxetine (a potent inhibitor of CYP2D6). Genetic variations of CYP2C9, CYP3A5, or SULT1A1 had no statistically significant associations with plasma concentrations of tamoxifen or its metabolites. Conclusion Interactions between CYP2D6 polymorphisms and coadministered antidepressants and other drugs that are CYP2D6 inhibitors may be associated with altered tamoxifen activity.

Making Learning Fun: Quest Atlantis, A Game Without Guns.

Abstract: This article describes the Quest Atlantis (QA) project, a learning and teaching project that employs a multiuser, virtual environment to immerse children, ages 9–12, in educational tasks. QA combines strategies used in commercial gaming environments with lessons from educational research on learning and motivation. It allows users at participating elementary schools and after-school centers to travel through virtual spaces to perform educational activities, talk with other users and mentors, and build virtual personae. Our work has involved an agenda and process that may be called socially-responsive design, which involves building sociotechnical structures that engage with and potentially transform individuals and their contexts of participation. This work sits at the intersection of education, entertainment, and social commitment and suggests an expansive focus for instructional designers. The focus is on engaging classroom culture and relevant aspects of student life to inspire participation consistent with social commitments and educational goals interpreted locally.