The PARP inhibitor Rucaparib synergizes with radiation to attenuate atypical teratoid rhabdoid tumor growth.

Background: Atypical teratoid rhabdoid tumors (ATRT) are highly aggressive pediatric brain tumors. The available treatments rely on toxic chemotherapy and radiotherapy, which themselves can cause poor outcomes in young patients. Poly (ADP-ribose) polymerases (PARP), multifunctional enzymes which play an important role in DNA damage repair and genome stability have emerged as a new target in cancer therapy.

Effect of a high intensity quadriceps fatigue protocol on knee joint mechanics and muscle activation during gait in young adults.

The purpose of this study was to determine the effect of impaired quadriceps function on knee joint biomechanics and neuromuscular function during gait. Surface electromyograms, three-dimensional motion and ground reaction forces were collected during gait before and after 20 healthy adults completed a high intensity quadriceps fatigue protocol. Pattern recognition techniques were utilized to examine changes in amplitude and temporal characteristics of all gait variables.

Genetic dissection of a mitochondria-vacuole signaling pathway in yeast reveals a link between chronic oxidative stress and vacuolar iron transport.

Deletion of two homologous genes, MRS3 and MRS4, that encode mitochondrial iron transporters affects the activity of the vacuolar iron importer Ccc1. Ccc1 levels are decreased in Deltamrs3Deltamrs4 cells, but the activity of the transporter is increased, resulting is reduced cytosolic iron. Overexpression of CCC1 in Deltamrs3Deltamrs4 cells results in a severe growth defect due to decreased cytosolic iron, referred to as the mitochondria-vacuole signaling (MVS) phenotype.

Performance on the CERAD Word List Memory task: a comparison of university-based and community-based groups.

Background: Evaluation of patients for Alzheimer's disease often compares an individual's performance on cognitive tests to established norms. The purpose of this study was to compare performance on the CERAD Word List Memory tasks in normal controls from an Alzheimer's disease registry and in community volunteers.

Methods: Scores on Word List Memory tasks were evaluated in cognitively intact participants enrolled in a university-based Alzheimer's disease registry (n=103) and in a sample of community volunteers (n=51).

Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating impaired insight.

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia.

Associations between circulating sex steroid hormones and cognition in normal elderly women.

Objective: To provide exploratory analyses of associations between levels of several sex hormones and cognitive performance in elderly women.

Background: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Comparing cognitive performance across or between conditions associated with different hormone levels, such as phases of the menstrual cycle, surgical menopause, and estrogen replacement therapy suggests conditions with higher levels of estrogen are associated with better verbal memory and possibly worse visuospatial ability.

Lifelong estrogen exposure and cognitive performance in elderly women.

Fluctuating endogenous and exogenous estrogens influence cognition in women. In this study, cognitive functioning in elderly women was examined by applying methodology used in understanding the effects of chronic estrogen exposure on hormone-sensitive tissue other than the brain. An index, combining menstrual, reproductive, and physical markers associated with estrogen levels, was developed for elderly, nondemented, predominantly Caucasian women (n = 87).

Expression of engineered human 17 beta-estradiol dehydrogenase in a prokaryotic system.

Objective: 17 beta estradiol dehydrogenase (17 beta DH) is a model for pyridine-dependent steroid-converting enzymes. To define the structural and functional parameters of 17 beta DH, we created an expression system for production of abundant, homogeneous enzyme.

Methods: A full-length 17 beta DH cDNA clone was engineered into the inducible expression vector pMON 5839.

Molecular cloning of testicular 20 alpha-hydroxysteroid dehydrogenase: identity with aldose reductase.

Complementary DNA (cDNA) clones encoding bovine testicular 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) have been isolated from a bovine testicular lambda gt11 library using polyclonal antibodies against 20 alpha-HSD and DNA probe hybridization. Nucleotide sequencing of three independently isolated clones was used to establish a composite cDNA sequence that encodes the enzyme. It contains a coding sequence of 921 nucleotides, a stop codon, and a 264-nucleotide 3'-noncoding segment which allowed deduction of the amino acid sequence of the enzyme.

Hydrogen bonding in steroidogenesis: studies on new heterocyclic analogs of estrone that inhibit human estradiol 17 beta-dehydrogenase.

New heterocyclic analogs of estrone are reported that inhibit estradiol 17 beta-dehydrogenase (E2-17 beta DH) from human placenta. The inhibitors are efficiently synthesized in two steps from estrone (or its 3-O-methyl ether), giving fully characterized analogs with pyrazole or isoxazole fused to the 16,17-position on the D ring. Dixon plots of enzyme kinetic data show the heterocyclic steroids are competitive inhibitors of E2-17 beta DH.

Estradiol 17 beta-dehydrogenase: full enzymatic activity in the absence of zinc.

The precise catalytic mechanism of the steroid interconverting enzyme, human placental estradiol 17 beta-dehydrogenase (EC 1.1.1.

Re-examination of CPM performance and neglect in lateralized brain injury.

The current study examines the effects of lateralized brain injury on Raven's Coloured Progressive Matrices (CPM) performance. Archival data on 106 unilateral brain-damage patients, 59 with right hemisphere damage and 47 with left, was utilized to examine four aspects of differential performance. Right brain-damaged subjects performed significantly lower than left brain-damaged subjects overall on the CPM.

Stereospecificity of hydrogen transfer between progesterone and cofactor by human placental estradiol-17 beta dehydrogenase.

We have previously shown that human placental estradiol-17 beta dehydrogenase (EC 1.1.1.

Stereospecificity of hydrogen transfer by bovine testicular 20 alpha-hydroxysteroid dehydrogenase.

The stereospecificity of hydrogen transfer between steroid (17-hydroxyprogesterone) and both natural cofactors by bovine testicular 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) has been determined. Cofactors used in these studies, [4-pro-S-3H]NADH ([4B-3H]NADH) and [4-pro-S-3H]NADPH ([4B-3H]NADPH) were generated with human placental estradiol 17 beta-dehydrogenase (EC 1.1.

Isolation and sequencing of a complementary deoxyribonucleic acid clone encoding human placental 17 beta-estradiol dehydrogenase: identification of the putative cofactor binding site.

17 beta-Estradiol dehydrogenase (EC 1.1.1.

Human placental estradiol 17 beta-dehydrogenase: evidence for inverted substrate orientation ("wrong-way" binding) at the active site.

Human placental estradiol 17 beta-dehydrogenase (EC 1.1.1.

Human placental estradiol 17 beta-dehydrogenase: sequence of a histidine-bearing peptide in the catalytic region.

The amino acid sequence of an octapeptide from the catalytic site of human placental estradiol 17 beta-dehydrogenase (EC 1.1.1.

Human placental estradiol 17 beta-dehydrogenase. Identification of a single histidine residue affinity-labeled by both 3-bromoacetoxyestrone and 12 beta-bromoacetoxy-4-estrene-3,17-dione.

Human placental estradiol 17 beta-dehydrogenase (EC 1.1.1.

Isolation of histidyl peptides of the steroid-binding site of human placental estradiol 17 beta-dehydrogenase.

Human placental estradiol 17 beta-dehydrogenase (E.C. 1.