Development of benzoquinoquinoxaline derivatives as triplex-specific probes: Recognition of DNA structures at repeats sequences

Bergquist, Helen (Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics)

Doctoral thesis, 2011-05-10
ISBN: 978-91-7447-296-7

Keywords: Triplex, H-DNA, BQQ, BQQ-OP, BQQ-Bodipy, triplet repeat, DNA, non-B-DNA, pkd1, frataxin, Friedreich's ataxia

Automatic identification of gait events using an instrumented sock

In addition of the potential of using textile-based transducers in future devices, I also think in a possible help to assess gait objectively (to help improve the measurement of the ICARS scale)

Journal of NeuroEngineering and Rehabilitation 2011, 8:32 doi:10.1186/1743-0003-8-32
Published: 27 May 2011, OPEN ACCESS

Stephen J Preece, Laurence P J Kenney, Matthew J Major, Tilak Dias, Edward Lay and Bosco T Fernandes

Background
Textile-based transducers are an emerging technology in which piezo-resistive properties of materials are used to measure an applied strain. By incorporating these sensors into a sock, this technology offers the potential to detect critical events during the stance phase of the gait cycle. This could prove useful in several applications, such as functional electrical stimulation (FES) systems to assist gait.
Methods
We investigated the output of a knitted resistive strain sensor during walking and sought to determine the degree of similarity between the sensor output and the ankle angle in the sagittal plane. In addition, we investigated whether it would be possible to predict three key gait events, heel strike, heel lift and toe off, with a relatively straight-forward algorithm. This worked by predicting gait events to occur at fixed time offsets from specific peaks in the sensor signal.
Results
Our results showed that, for all subjects, the sensor output exhibited the same general characteristics as the ankle joint angle. However, there were large between-subjects differences in the degree of similarity between the two curves. Despite this variability, it was possible to accurately predict gait events using a simple algorithm. This algorithm displayed high levels of trial-to-trial repeatability.
Conclusions
This study demonstrates the potential of using textile-based transducers in future devices that provide active gait assistance.

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Translating Stem Cell Research Into Therapies

Medical News Today, Article Date: 26 May 2011

The perspective on translating neural stem cell research into clinical therapeutics is part of a special issue of Neuron devoted to neural stem cells and neurogenesis

Original scientific paper: Translating Stem Cell Studies to the Clinic for CNS Repair: Current State of the Art and the Need for a Rosetta Stone
Karen Aboody, Alexandra Capela, Nilofar Niazi, Jeffrey H. Stern, and Sally Temple

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DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases

PLoS ONE 6(5): e19800. doi:10.1371/journal.pone.0019800
Alexandrov BS, Valtchinov VI, Alexandrov LB, Gelev V, Dagon Y, et al. 2011

OPEN ACCESS

Abstract
Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS–related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications.

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Effects of Erythropoietin on Frataxin Levels and Mitochondrial Function in Friedreich Ataxia - a Dose-Response Trial.

Cerebellum. 2011 May 20. [Epub ahead of print]

Nachbauer W, Hering S, Seifert M, Steinkellner H, Sturm B, Scheiber-Mojdehkar B, Reindl M, Strasak A, Poewe W, Weiss G, Boesch S.
Source
Department of Neurology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

Keywords: Friedreich ataxia (FRDA), frataxin, recombinant human erythropoietin (rhuEPO), dose-response interactions, single doses (5,000, 10,000 and 30,000 IU), serum erythropoietin levels, iron metabolism, mitochondrial function, ataxia rating did not reveal clinical improvement, ferritin decrease.

Stem cell technology for neurodegenerative diseases

Annals of Neurology, (2011) DOI: 10.1002/ana.22487

J. Simon Lunn PhD, Stacey A. Sakowski PhD, Junguk Hur PhD, Eva L. Feldman MD PhD,
Department of Neurology – University of Michigan, Ann Arbor, MI

Keywords: stem cell technologies, neurodegenerative diseases, stem cell therapies.

First step in a possible therapeutic approach using stem cells for Friedreich's ataxia

Sent by: Dr. Jonathan Jones, Neuroscience Institute, Miguel Hernández University, San Juan, Alicante, 03550 SPAIN

The Experimental Embryology lab in the Neuroscience Institute in Alicante, Spain, is researching on the possible use of bone marrow and/or adipose tissue-derived mesenchymal stem cells for the treatment of Friedreich's Ataxia. To this end, stem cells are injected intrathecally into the spinal cord of a FA mouse model, where the cells will attach to the dorsal root ganglion. Here, the cells will release trophic factors to protect the large sensory neurons from death, which is reflected in an improvement in motor skills. This is a first step in a possible therapeutic approach using stem cells for Friedreich's ataxia.

___________________________________________________________________________

More information about the project (Spanish)

Research Fellowship: Visual dissection of GAA-mediated mechanisms of FRDA repression and identification of novel candidate factors involved in frataxin function

Principal Researchers: Dr Michele Lufino and Dr Richard Wade-Martins,
Department of Physiology, Anatomy and Genetics, University of Oxford.

Developing a Balanced Business Model for Gene Therapy

HUMAN GENE THERAPY 22:1–4 (June 2011),DOI: 10.1089/hum.2011.2504

"Research and outcomes like these give hope not only to patients, but to doctors who have spent years developing gene therapies for diseases that have not responded as well to traditional therapy.The promise shown by the results also create hope that gene therapy can finally emerge as avibrant segment, after years in which biopharma companies, physicians, insurers, and government regulators have struggled to develop a sustainable business model."

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Friedreich's Ataxia: Phenotypic variability: 4-case reports (two sets of siblings)

Published in Fisioterapia. 2010;32:190-4. - vol.32 núm 04
Gago Fernández, I.; Seco Calvo, J.

Keywords: clinical phenotype, Friedreich's Ataxia, activities of Daily Life, Health Quality of Life, Questionnaire of Health, multisystem involvement, phenotypic variability.

An investigation to determine the efficacy and safety of lentivirus mediated FXN gene delivery for the correction of Friedreich ataxia

Principal researchers: Dr Mark Pook and Dr Michael Themis Brunel University,
Uxbridge, UK

In children with Friedreich ataxia, muscle and ataxia parameters are associated

Developmental Medicine & Child Neurology, 53: 529–534. doi: 10.1111/j.1469-8749.2011.03931.x (Article first published online: 16 MAY 2011)

SIVAL, D. A., POUWELS, M. E., VAN BREDERODE, A., MAURITS, N. M., VERSCHUUREN-BEMELMANS, C. C., BRUNT, E. R., DU MARCHIE SARVAAS, G. J., VERBEEK, R. J., BROUWER, O. F. and VAN DER HOEVEN, J. H. (2011).

Keywords: Friedreich ataxia (FRDA), ataxia, International Cooperative Ataxia Rating Scale (ICARS), muscle weakness, muscle ultrasound density (MUD), muscle force, sensory evoked potentials, and ICARS scores, FXN gene analysis, persistently absent sensory evoked potentials, leg muscle force.

Next Generation Gamers: Computer Games Aid Recovery From Stroke

Could be also useful in the FA rehabilitation?

Medical News Today. 15 May 2011
Computer games are not just for kids. New research published in Journal of NeuroEngineering and Rehabilitation, a BioMed Central open access journal, shows that computer games can speed up and improve a patient's recovery from paralysis after stroke.

Scientific paper:
"Robotically Facilitated Virtual Rehabilitation of Arm Transport Integrated With Finger Movement in Persons with Hemiparesis"
Alma S Merians, Gerard G Fluet, Qinyin Qiu, Soha Saleh, Ian Lafond, Amy Davidow and Sergei V Adamovich
Journal of NeuroEngineering and Rehabilitation (in press)

Santhera Presents Positive Data from IONIA Open-Label Extension Study in Friedreich's Ataxia at the Fourth International Friedreich's Ataxia Scientific Conference

Liestal, Switzerland, May 5, 2011 – Santhera Pharmaceuticals (SIX: SANN) announced today that it will present positive data from an open-label extension study (IONIA-E) evaluating Ca-tena® for the treatment of Friedreich’s Ataxia. The findings indicate that Catena® can offer therapeutic benefit to pediatric patients by improving overall neurological function, particu-larly fine motor skills, and speech. Data will be presented by the principal investigator of the study, Dr. David Lynch from Children’s Hospital of Philadelphia (CHOP) on May 7 2011 in Strasbourg, France at the 4th International Friedreich’s Ataxia Scientific Conference [1].

Translational Research Projects: University of Innsbruck

Rainer Schneider, Institute of Biochemistry, Department of Neurology, Medical University of Innsbruck, (13.05.2011)


Translational Research Program
TRP233 Mechanism of Frataxin increase dependent on Erythropoietin

Keywords Friedreich Ataxia, erythropoietin, Translation, MID1/alpha4, frataxin, mTOR



Translational-Research-Projekte:


Rainer SCHNEIDER, Institut für Biochemie
Mechanismus Erythropoietin-abhängiger Frataxin-Erhöhung


Außerdem werden zwei Translational-Research-Projekte mit insgesamt rund 700.000 Euro gefördert. Das Translational-Research-Programm dient zur Förderung weiterführender bzw. orientierter Grundlagenforschung an der Schnittstelle zur angewandten Forschung, die auf selbst gewonnenen wissenschaftlichen Erkenntnissen bzw. (bei Projekten an der Schnittstelle zwischen Kunst und Wissenschaft) auf eigener künstlerischer Tätigkeit aufbaut, auf konkrete Anwendungsziele oder/und einen zu entwickelnden wirtschaftlichen, gesellschaftlichen oder kulturellen Nutzen ausgerichtet ist.

ALTERED ZINC TRANSPORT DISRUPTS MITOCHONDRIAL PROTEIN PROCESSING/IMPORT IN FRAGILE X-ASSOCIATED TREMOR/ATAXIA SYNDROME.

Hum Mol Genet. 2011 May 10. [Epub ahead of print]

Napoli E, Ross-Inta C, Wong S, Omanska-Klusek A, Barrow C, Iwahashi C, Garcia-Arocena D, Sakaguchi D, Berry-Kravis E, Hagerman R, Hagerman PJ, Giulivi C.
Source

Department of Molecular Biosciences, School of Veterinary Medicine.

Keywords: Fragile X-associated tremor/ataxia syndrome (FXTAS), common phenotypic traits shared by Friedreich's ataxia, gait ataxia, loss of coordination, iron homeostasis, mature frataxin protein expression, zinc, iron, desferrioxamine.

Early Changes in Left Ventricular Long-Axis Function in Friedreich Ataxia: Relation with the FXN Gene Mutation and Cardiac Structural Change

Journal of the American Society of Echocardiography, In Press, Corrected Proof, Available online 12 May 2011, doi:10.1016/j.echo.2011.04.004

Philip M. Mottram, Martin B. Delatycki, Lesley Donelan, John S. Gelman, Louise Corben and Roger E. Peverill

Keywords: Friedreich ataxia (FRDA), GAA triplet expansion, FXN gene, LV systolic dysfunction, Echocardiography, Left ventricular hypertrophy, Systole, Tissue Doppler imaging.

Idebenone Induces Apoptotic Cell Death in the Human Dopaminergic Neuroblastoma SHSY-5Y Cells.

Neurotox Res. 2011 May 3. [Epub ahead of print]

Tai KK, Pham L, Truong DD.

The Parkinson's and Movement Disorder Research Laboratory, Long Beach Memorial Medical Center, 2801 Atlantic Ave., Long Beach, CA, USA

Keywords: Idebenone, coenzyme Q10 analog, antioxidant, Friedreich Ataxia, neurodegenerative diseases, Parkinson's disease, dopaminergic neuroblastoma SHSY-5Y cells, Idebenone-induced cell death, genomic DNA fragmentation, accumulation of cytochrome c, apoptotic. protein BAX, caspase-3, high concentrations.

Estrogen Protection in Friedreich's Ataxia Skin Fibroblasts

Endocrinology, doi:10.1210/en.2011-0184, published online on May 3, 2011

Timothy E. Richardson, Shao-Hua Yang, Yi Wen and James W. Simpkins

Institute for Aging and Alzheimer's Disease Research, Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107

Keywords: Estrogens, neurodegenerative diseases, 17β-estradiol (E2), estrogen-like compounds, Friedreich's ataxia (FRDA), FRDA skin fibroblasts, estrogen receptor-α, estrogen receptor-β, G protein-coupled receptor 30, antioxidant properties, phenolic compounds, phenolic E2-like compounds.

The heart in Friedreich's Ataxia: Basic findings and clinical implications

Progress in Pediatric Cardiology - May 2011 (Vol. 31, Issue 2, Pages 103-109, DOI: 10.1016/j.ppedcard.2011.02.007)

R. Mark Payne

Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, United States

Keywords: Friedreich's Ataxia, mitochondrial disease, frataxin, GAA triplet expansion, progressive neuropathy, hypertrophic cardiomyopathy, arrhythmias, heart failure, cardiovascular stress intolerance, histone deacetylase inhibitors, enzyme replacement.

Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons

Genome Res. Published in Advance April 5, 2011, doi: 10.1101/gr.112755.110

Kazuya Iwamoto 1,2,7,8, Miki Bundo 1,2,7, Junko Ueda 1, Michael C. Oldham 3, Wataru Ukai 4, Eri Hashimoto 4, Toshikazu Saito 4, Daniel H. Geschwind 5,6 and Tadafumi Kato 1,8

1 Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Japan; 2Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo 7-3-1 Hongo, Japan; 3 Department of Neurology, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, USA; 4 Department of Neuropsychiatry, Sapporo Medical University, Japan;
5 Program in Neurogenetics, Department of Neurology, and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, USA; 6 Department of Human Genetics, University of California, USA

Keywords: Epigenome, mammalian brain cells, DNA methylation, hypomethylation, transcription-factor binding sites, central nervous system.

Sleep disorders in cerebellar ataxias

Arq. Neuro-Psiquiatr. vol.69 no.2a São Paulo Apr. 2011, doi: 10.1590/S0004-282X2011000200021

José L. Pedroso; Pedro Braga-Neto; André C. Felício; Camila C.H. Aquino; Lucila B. Fernandes do Prado; Gilmar Fernandes do Prado; Orlando G.P. Barsottini

Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo SP, Brazil

"Data on sleep disorders in patients with FA is poor."