OPEN ACCESS
Journal of NeuroEngineering and Rehabilitation 2009, 6:38doi:10.1186/1743-0003-6-38
Published: 30 October 2009
Abstract (provisional)
Background
One of the main scientific and technological challenges of rehabilitation bioengineering is the development of innovative methodologies, based on the use of appropriate technological devices, for an objective assessment of patients undergoing a rehabilitation treatment. Such tools should be as fast and cheap to use as clinical scales, which are currently the daily instruments most widely used in the routine clinical practice.
Methods
A human-centered approach was used in the design and development of a mechanical structure equipped with eight force/torque sensors that record quantitative data during the initiation of a predefined set of Activities of Daily Living (ADL) tasks, in isometric conditions.
Results
Preliminary results validated the appropriateness, acceptability and functionality of the proposed platform, that has become now a tool used for clinical research in three clinical centres.
Conclusions
This paper presented the design and development of an innovative platform for whole-body force and torque measurements on human subjects. The platform has been designed to perform accurate quantitative measurements in isometric conditions with the specific aim to address the needs for functional assessment tests of patients undergoing a rehabilitation treatment as a consequence of a stroke. The versatility of the system also enlightens several other interesting possible areas of application for therapy in neurorehabilitation, for research in basic neuroscience, and more.
Link to full text: http://www.jneuroengrehab.com/content/pdf/1743-0003-6-38.pdf
Saturday, October 31, 2009
Friday, October 30, 2009
Progressive GAA·TTC Repeat Expansion in Human Cell Lines
OPEN ACCESS
Scott Ditch, Mimi C. Sammarco, Ayan Banerjee, Ed Grabczyk*
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America
Abstract
Trinucleotide repeat expansion is the genetic basis for a sizeable group of inherited neurological and neuromuscular disorders. Friedreich ataxia (FRDA) is a relentlessly progressive neurodegenerative disorder caused by GAA·TTC repeat expansion in the first intron of the FXN gene. The expanded repeat reduces FXN mRNA expression and the length of the repeat tract is proportional to disease severity. Somatic expansion of the GAA·TTC repeat sequence in disease-relevant tissues is thought to contribute to the progression of disease severity during patient aging. Previous models of GAA·TTC instability have not been able to produce substantial levels of expansion within an experimentally useful time frame, which has limited our understanding of the molecular basis for this expansion. Here, we present a novel model for studying GAA·TTC expansion in human cells. In our model system, uninterrupted GAA·TTC repeat sequences display high levels of genomic instability, with an overall tendency towards progressive expansion. Using this model, we characterize the relationship between repeat length and expansion. We identify the interval between 88 and 176 repeats as being an important length threshold where expansion rates dramatically increase. We show that expansion levels are affected by both the purity and orientation of the repeat tract within the genomic context. We further demonstrate that GAA·TTC expansion in our model is independent of cell division. Using unique reporter constructs, we identify transcription through the repeat tract as a major contributor to GAA·TTC expansion. Our findings provide novel insight into the mechanisms responsible for GAA·TTC expansion in human cells.
Link to full text: http://www.plosgenetics.org/article/fetchObjectAttachment.action;jsessionid=1C3EDADDCEC7DDCE3438B379DC71EE00?uri=info%3Adoi%2F10.1371%2Fjournal.pgen.1000704&representation=PDF
Scott Ditch, Mimi C. Sammarco, Ayan Banerjee, Ed Grabczyk*
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America
Abstract
Trinucleotide repeat expansion is the genetic basis for a sizeable group of inherited neurological and neuromuscular disorders. Friedreich ataxia (FRDA) is a relentlessly progressive neurodegenerative disorder caused by GAA·TTC repeat expansion in the first intron of the FXN gene. The expanded repeat reduces FXN mRNA expression and the length of the repeat tract is proportional to disease severity. Somatic expansion of the GAA·TTC repeat sequence in disease-relevant tissues is thought to contribute to the progression of disease severity during patient aging. Previous models of GAA·TTC instability have not been able to produce substantial levels of expansion within an experimentally useful time frame, which has limited our understanding of the molecular basis for this expansion. Here, we present a novel model for studying GAA·TTC expansion in human cells. In our model system, uninterrupted GAA·TTC repeat sequences display high levels of genomic instability, with an overall tendency towards progressive expansion. Using this model, we characterize the relationship between repeat length and expansion. We identify the interval between 88 and 176 repeats as being an important length threshold where expansion rates dramatically increase. We show that expansion levels are affected by both the purity and orientation of the repeat tract within the genomic context. We further demonstrate that GAA·TTC expansion in our model is independent of cell division. Using unique reporter constructs, we identify transcription through the repeat tract as a major contributor to GAA·TTC expansion. Our findings provide novel insight into the mechanisms responsible for GAA·TTC expansion in human cells.
Link to full text: http://www.plosgenetics.org/article/fetchObjectAttachment.action;jsessionid=1C3EDADDCEC7DDCE3438B379DC71EE00?uri=info%3Adoi%2F10.1371%2Fjournal.pgen.1000704&representation=PDF
Thursday, October 29, 2009
Researchers Find Brain Cell Transplants Help Repair Neural Damage
ScienceDaily (Oct. 29, 2009) — A Swiss research team has found that using an animal's own brain cells (autologous transplant) to replace degenerated neurons in select brain areas of donor primates with simulated but asymptomatic Parkinson's disease and previously in a motor cortex lesion model, provides a degree of brain protection and may be useful in repairing brain lesions and restoring function. (read more)
Neuroprotective effects of blockers for T-type calcium channels
Molecular Neurodegeneration 2009, 4:44doi:10.1186/1750-1326-4-44
Published: 28 October 2009
OPEN ACCESS
Norelle C Wildburger , Avary Lin-Ye , Michelle A Baird , Debin Lei and Jianxin Bao
Abstract
Cognitive and functional decline with age is correlated with deregulation of intracellular calcium, which can lead to neuronal death in the brain. Previous studies have found protective effects of various calcium channel blockers in pathological conditions. However, little has been done to explore possible protective effects of blockers for T-type calcium channels, which forms a family of FDA approved anti-epileptic drugs. In this study, we found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel antagonists. The family of low-voltage activated, or T-type calcium channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their respective main pore-forming alpha subunits: alpha 1G, alpha 1H, and alpha 1I. Among these three subunits, alpha 1H is highly expressed in hippocampus and certain cortical regions. However, T-type calcium channel blockers can protect neurons derived from alpha 1H-/- mice, suggesting that neuroprotection demonstrated by these drugs is not through the alpha 1H subunit. In addition, blockers for T-type calcium channels were not able to confer any protection to neurons in long-term cultures, while blockers of L-type calcium channels could protect neurons. These data indicate a new function of blockers for T-type calcium channels, and also suggest different mechanisms to regulate neuronal survival by calcium signaling pathways. Thus, our findings have important implications in the development of new treatment for age-related neurodegenerative disorders.
Link to full text: http://www.molecularneurodegeneration.com/content/pdf/1750-1326-4-44.pdf
Published: 28 October 2009
OPEN ACCESS
Norelle C Wildburger , Avary Lin-Ye , Michelle A Baird , Debin Lei and Jianxin Bao
Abstract
Cognitive and functional decline with age is correlated with deregulation of intracellular calcium, which can lead to neuronal death in the brain. Previous studies have found protective effects of various calcium channel blockers in pathological conditions. However, little has been done to explore possible protective effects of blockers for T-type calcium channels, which forms a family of FDA approved anti-epileptic drugs. In this study, we found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel antagonists. The family of low-voltage activated, or T-type calcium channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their respective main pore-forming alpha subunits: alpha 1G, alpha 1H, and alpha 1I. Among these three subunits, alpha 1H is highly expressed in hippocampus and certain cortical regions. However, T-type calcium channel blockers can protect neurons derived from alpha 1H-/- mice, suggesting that neuroprotection demonstrated by these drugs is not through the alpha 1H subunit. In addition, blockers for T-type calcium channels were not able to confer any protection to neurons in long-term cultures, while blockers of L-type calcium channels could protect neurons. These data indicate a new function of blockers for T-type calcium channels, and also suggest different mechanisms to regulate neuronal survival by calcium signaling pathways. Thus, our findings have important implications in the development of new treatment for age-related neurodegenerative disorders.
Link to full text: http://www.molecularneurodegeneration.com/content/pdf/1750-1326-4-44.pdf
Epilepsy Drugs Could Treat Alzheimer's And Parkinson's
ScienceDaily (Oct. 29, 2009) — Researchers in the USA have discovered a potential new function for anti-epileptic drugs in treating neurodegenerative disorders such as Alzheimer's and Parkinson's disease. The study, published in BioMed Central's open access journal Molecular Neurodegeneration, found that neurons in the brain were protected after treatment with T-type calcium-channel blockers, which are commonly used to treat epilepsy. (read more)
Saturday, October 24, 2009
Erythropoietin: a multimodal neuroprotective agent
Nadiya Byts and Anna-Leena Siren
Experimental & Translational Stroke Medicine 2009, 1:4doi:10.1186/2040-7378-1-4
Published: 21 October 2009
OPEN ACCESS
Abstract (provisional)
The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent.
The complete article is available as a provisional PDF . CLICK HERE
Experimental & Translational Stroke Medicine 2009, 1:4doi:10.1186/2040-7378-1-4
Published: 21 October 2009
OPEN ACCESS
Abstract (provisional)
The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent.
The complete article is available as a provisional PDF . CLICK HERE
Direct Fe2+ Sensing by Iron-responsive Messenger RNA·Repressor Complexes Weakens Binding*
October 30, 2009 The Journal of Biological Chemistry, 284, 30122-30128.
1. Mateen A. Khan‡, 2. William E. Walden§, 3. Dixie J. Goss‡,1 and 4. Elizabeth C. Theil¶‖,2
1. From the ‡Department of Chemistry, Hunter College, City University of New York, New York, New York 10065,
2. the §Department of Microbiology and Immunology, University of Illinois, Chicago, Illinois 60612-7334,
3. the ¶Children's Hospital Oakland Research Institute, Oakland, California 94609, and
4. the ‖Department of Nutrition Science and Toxicolology, University of California, Berkeley, California 94720
Keywords: Fe2+, ferritin, mitochondrial aconitase messenger, regulatory proteins (IRPs),iron-induced mRNA translation.
1. Mateen A. Khan‡, 2. William E. Walden§, 3. Dixie J. Goss‡,1 and 4. Elizabeth C. Theil¶‖,2
1. From the ‡Department of Chemistry, Hunter College, City University of New York, New York, New York 10065,
2. the §Department of Microbiology and Immunology, University of Illinois, Chicago, Illinois 60612-7334,
3. the ¶Children's Hospital Oakland Research Institute, Oakland, California 94609, and
4. the ‖Department of Nutrition Science and Toxicolology, University of California, Berkeley, California 94720
Keywords: Fe2+, ferritin, mitochondrial aconitase messenger, regulatory proteins (IRPs),iron-induced mRNA translation.
Friday, October 23, 2009
Next generation sequence analysis for mitochondrial disorders
Valeria Vasta , Sarah B Ng , Emily H Turner , Jay Shendure and Si Houn Hahn
Genome Medicine 2009, 1:100doi:10.1186/gm100
Published: 23 October 2009
OPEN ACCESS
Link to full text
Background
Mitochondrial disorders can originate from mutations in one of many nuclear genes controlling the organelle function or in the mitochondrial genome (mitochondrial DNA (mtDNA)). The large numbers of potential culprit genes, together with the little guidance offered by most clinical phenotypes as to which gene may be causative, are a great challenge for the molecular diagnosis of these disorders.
Methods
We developed a novel targeted resequencing assay for mitochondrial disorders relying on microarray-based hybrid capture coupled to next-generation sequencing. Specifically, we subjected the entire mtDNA genome and the exons and intron-exon boundary regions of 362 known or candidate causative nuclear genes to targeted capture and resequencing. We here provide proof-of-concept data by testing one HapMap DNA sample and two positive control samples.
Results
Over 94% of the targeted regions were captured and sequenced with appropriate coverage and quality, allowing reliable variant calling. Pathogenic mutations blindly tested in patients' samples were 100% concordant with previous Sanger sequencing results: a known mutation in Pyruvate dehydrogenase alpha 1 subunit (PDHA1), a novel splicing and a known coding mutation in Hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) were correctly identified. Of the additional variants recognized, 90 to 94% were present in dbSNP while 6 to 10% represented new alterations. The novel nonsynonymous variants were all in heterozygote state and mostly predicted to be benign. The depth of sequencing coverage of mtDNA was extremely high, suggesting that it may be feasible to detect pathogenic mtDNA mutations confounded by low level heteroplasmy. Only one sequencing lane of an eight lane flow cell was utilized for each sample, indicating that a cost-effective clinical test can be achieved.
Conclusions
Our study indicates that the use of next generation sequencing technology holds great promise as a tool for screening mitochondrial disorders. The availability of a comprehensive molecular diagnostic tool will increase the capacity for early and rapid identification of mitochondrial disorders. In addition, the proposed approach has the potential to identify new mutations in candidate genes, expanding and redefining the spectrum of causative genes responsible for mitochondrial disorders.
................................................................
Focus: Genes targeted for capture and sequencing....Enzymes...FXN,
New variants and mutations identified in the samples..... FXN [Genbank:NM_000144.3]:c.626A>G (p.Asp209Gly) het
Genome Medicine 2009, 1:100doi:10.1186/gm100
Published: 23 October 2009
OPEN ACCESS
Link to full text
Background
Mitochondrial disorders can originate from mutations in one of many nuclear genes controlling the organelle function or in the mitochondrial genome (mitochondrial DNA (mtDNA)). The large numbers of potential culprit genes, together with the little guidance offered by most clinical phenotypes as to which gene may be causative, are a great challenge for the molecular diagnosis of these disorders.
Methods
We developed a novel targeted resequencing assay for mitochondrial disorders relying on microarray-based hybrid capture coupled to next-generation sequencing. Specifically, we subjected the entire mtDNA genome and the exons and intron-exon boundary regions of 362 known or candidate causative nuclear genes to targeted capture and resequencing. We here provide proof-of-concept data by testing one HapMap DNA sample and two positive control samples.
Results
Over 94% of the targeted regions were captured and sequenced with appropriate coverage and quality, allowing reliable variant calling. Pathogenic mutations blindly tested in patients' samples were 100% concordant with previous Sanger sequencing results: a known mutation in Pyruvate dehydrogenase alpha 1 subunit (PDHA1), a novel splicing and a known coding mutation in Hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) were correctly identified. Of the additional variants recognized, 90 to 94% were present in dbSNP while 6 to 10% represented new alterations. The novel nonsynonymous variants were all in heterozygote state and mostly predicted to be benign. The depth of sequencing coverage of mtDNA was extremely high, suggesting that it may be feasible to detect pathogenic mtDNA mutations confounded by low level heteroplasmy. Only one sequencing lane of an eight lane flow cell was utilized for each sample, indicating that a cost-effective clinical test can be achieved.
Conclusions
Our study indicates that the use of next generation sequencing technology holds great promise as a tool for screening mitochondrial disorders. The availability of a comprehensive molecular diagnostic tool will increase the capacity for early and rapid identification of mitochondrial disorders. In addition, the proposed approach has the potential to identify new mutations in candidate genes, expanding and redefining the spectrum of causative genes responsible for mitochondrial disorders.
................................................................
Focus: Genes targeted for capture and sequencing....Enzymes...FXN,
New variants and mutations identified in the samples..... FXN [Genbank:NM_000144.3]:c.626A>G (p.Asp209Gly) het
The conserved Trp-155 in human frataxin as a hotspot for oxidative stress related chemical modifications
Biochemical and Biophysical Research Communications
Ana R. Correiaa, Saw Y. Owb, Phillip C. Wrightb and Cláudio M. Gomesa, Corresponding Author Contact Information, E-mail The Corresponding Author
aInstituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2780-756 Oeiras, Portugal
bDepartment of Chemical and Process Engineering, ChELSI, University of Sheffield, Sheffield S10 2TN, UK
Received 15 October 2009.
Available online 22 October 2009.
Keywords: Friedreich’s Ataxia, Frataxin, Protein Folding, Protein Flexibility, Metallochaperone, Oxidative Stress, Fenton reactions, carbonylation, nitration.
Ana R. Correiaa, Saw Y. Owb, Phillip C. Wrightb and Cláudio M. Gomesa, Corresponding Author Contact Information, E-mail The Corresponding Author
aInstituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2780-756 Oeiras, Portugal
bDepartment of Chemical and Process Engineering, ChELSI, University of Sheffield, Sheffield S10 2TN, UK
Received 15 October 2009.
Available online 22 October 2009.
Keywords: Friedreich’s Ataxia, Frataxin, Protein Folding, Protein Flexibility, Metallochaperone, Oxidative Stress, Fenton reactions, carbonylation, nitration.
Thursday, October 22, 2009
Students Invite Chemists Everywhere To Help With Orphaned Drugs, Diseases
Medical News Today, 21 Oct 2009
Suppose you had a disease for which there's a proven cure, but nobody makes the drug. Where do you turn?
The Cure for Needy Project (http://www.cureforneedy.org)
Suppose you had a disease for which there's a proven cure, but nobody makes the drug. Where do you turn?
The Cure for Needy Project (http://www.cureforneedy.org)
Wednesday, October 21, 2009
Redox Control of the Cell Cycle in Health and Disease
Online Ahead of Print: October 21, 2009
Ehab H. Sarsour, Maneesh G. Kumar, Leena Chaudhuri, Amanda L. Kalen, Prabhat C. Goswami, Jurgen Bernhagen, Claudia Castro, Peter M. Chumakov, Tohru Fukai, Fuyuki Ishikawa, Hugo Monteiro, Hasan Mukhtar, Mark Smith, Rhian Touyz. Antioxidants & Redox Signaling. doi:10.1089/ars.2009.2513.
Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa.
Keywords: reactive oxygen species (ROS), second messengers, quiescence (G0),proliferation (G1, S, G2, and M), cancer, wound healing, fibrosis, cardiovascular diseases, diabetes, and neurodegenerative diseases.
Ehab H. Sarsour, Maneesh G. Kumar, Leena Chaudhuri, Amanda L. Kalen, Prabhat C. Goswami, Jurgen Bernhagen, Claudia Castro, Peter M. Chumakov, Tohru Fukai, Fuyuki Ishikawa, Hugo Monteiro, Hasan Mukhtar, Mark Smith, Rhian Touyz. Antioxidants & Redox Signaling. doi:10.1089/ars.2009.2513.
Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa.
Keywords: reactive oxygen species (ROS), second messengers, quiescence (G0),proliferation (G1, S, G2, and M), cancer, wound healing, fibrosis, cardiovascular diseases, diabetes, and neurodegenerative diseases.
Children With Brain-Damage Often Have Cold Feet
Medicalnewstoday, Article Date: 21 Oct 2009
Many wheelchair-using children with neurological disorders have much colder hands and feet than other children, and most receive no special help even though they have had these problems for a long time, is revealed in at thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden.
(read more)
Many wheelchair-using children with neurological disorders have much colder hands and feet than other children, and most receive no special help even though they have had these problems for a long time, is revealed in at thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden.
(read more)
Monday, October 19, 2009
Inherited Neuromuscular Diseases (book )
Translation from Pathomechanisms to Therapies
Series: Advances in Experimental Medicine and Biology , Vol. 652
Espinós, Carmen; Felipo, Vicente; Palau, Francesc (Eds.)
2009, XIII, 304 p., Hardcover
ISBN: 978-90-481-2812-9
Keywords: muscular dystrophies, mitochondrial disorders, peripheral neuropathies, spinal muscular atrophy, motoneurone disease, Friedreich ataxia, genetics, neuromuscular disorders, peripheral nervous system, cellular biology, pathomechanisms, therapies and treatments.
Series: Advances in Experimental Medicine and Biology , Vol. 652
Espinós, Carmen; Felipo, Vicente; Palau, Francesc (Eds.)
2009, XIII, 304 p., Hardcover
ISBN: 978-90-481-2812-9
Keywords: muscular dystrophies, mitochondrial disorders, peripheral neuropathies, spinal muscular atrophy, motoneurone disease, Friedreich ataxia, genetics, neuromuscular disorders, peripheral nervous system, cellular biology, pathomechanisms, therapies and treatments.
Idebenone Appears Safe in Patients With Friedreich's Ataxia: Presented at ANA
Doctor's Guide Publishing Limited.
Presentation title: SNT-MC17/Idebenone to Treat Friedreich's Ataxia: Preliminary Phase 3 Safety Data. Poster T-80]
Keywords: blinded interim safety analysis, Friedreich's ataxia, clinical trial, idebenone, severe events, supraventricular extrasystole, reduced visual acuity, fatigue, anxiety, flatulence/abdominal discomfort, electrocardiograms, vital signs, laboratory test, SNT-MC17, headache, nausea, diarrhoea, vomiting, abdominal pain, upper abdominal pain, fatigue, hypercholesterolaemia, rash, flatulence, pruritus.
Presentation title: SNT-MC17/Idebenone to Treat Friedreich's Ataxia: Preliminary Phase 3 Safety Data. Poster T-80]
Keywords: blinded interim safety analysis, Friedreich's ataxia, clinical trial, idebenone, severe events, supraventricular extrasystole, reduced visual acuity, fatigue, anxiety, flatulence/abdominal discomfort, electrocardiograms, vital signs, laboratory test, SNT-MC17, headache, nausea, diarrhoea, vomiting, abdominal pain, upper abdominal pain, fatigue, hypercholesterolaemia, rash, flatulence, pruritus.
Saturday, October 17, 2009
The N-terminus of mature human frataxin is intrinsically unfolded
FEBS Journal, Early View (Articles online in advance of print)
Published Online: 16 Oct 2009
Journal compilation © 2009 Federation of European Biochemical Societies
Filippo Prischi 1 , Clelia Giannini 2 , Salvatore Adinolfi 3 and Annalisa Pastore 3
1 Dipartimento di Biologia Molecolare, University of Siena, Siena, Italy
2 Dipartimento di Chimica Organica ed Industriale, University of Milano, Italy
3 National Institute for Medical Research, MRC, The Ridgeway, London, UK
KEYWORDS: dynamics, Friedreich's ataxia, IUPs, NMR, structure, Frataxin, mitochondrial protein, neurodegenerative disease, globular domain, N-terminal, unfolded, iron-binding.
Published Online: 16 Oct 2009
Journal compilation © 2009 Federation of European Biochemical Societies
Filippo Prischi 1 , Clelia Giannini 2 , Salvatore Adinolfi 3 and Annalisa Pastore 3
1 Dipartimento di Biologia Molecolare, University of Siena, Siena, Italy
2 Dipartimento di Chimica Organica ed Industriale, University of Milano, Italy
3 National Institute for Medical Research, MRC, The Ridgeway, London, UK
KEYWORDS: dynamics, Friedreich's ataxia, IUPs, NMR, structure, Frataxin, mitochondrial protein, neurodegenerative disease, globular domain, N-terminal, unfolded, iron-binding.
Friday, October 16, 2009
Scientists Map First Complete Human Epigenome, The Driver Of Gene Expression
Scientists Map First Complete Human Epigenome, The Driver Of Gene Expression
Genetics News From Medical News Today
When scientists mapped the DNA sequence of 3 billion bases in the human genome they uncovered the master blueprint of what makes a human being; now a team in the US has produced a high resolution map of the first complete human epigenome, the driver of gene expression that regulates how all the options offered in the genome are put together to make the unique person that grows in a particular environment.
Genetics News From Medical News Today
When scientists mapped the DNA sequence of 3 billion bases in the human genome they uncovered the master blueprint of what makes a human being; now a team in the US has produced a high resolution map of the first complete human epigenome, the driver of gene expression that regulates how all the options offered in the genome are put together to make the unique person that grows in a particular environment.
Thursday, October 15, 2009
Cell's Powerhouses Dismantled: Complete Inventory Of All Proteins In Mitochondria
ScienceDaily (Oct. 15, 2009) — All of life is founded on the interactions of millions of proteins. These are the building blocks for cells and form the molecular mechanisms of life. The problem is that proteins are extremely difficult to study, particularly because there are so many of them and they appear in all sizes and weights. Now, Kris Gevaert from VIB/Ghent University and colleagues from the universities of Freiburg and Bochum have achieved a breakthrough in protein research. Using yeast, they have succeeded in making virtually the complete inventory of all the proteins in the mitochondria, the energy producers found in every cell.
Full text in ScienceDaily : http://www.sciencedaily.com/releases/2009/10/091015123602.htm
Full text in ScienceDaily : http://www.sciencedaily.com/releases/2009/10/091015123602.htm
alpha-tocopherol beta-Oxidation Localized to Rat Liver Mitochondria
Free Radic Biol Med. 2009 Oct 8
Mustacich DJ, Leonard SW, Patel NK, Traber MG.
Linus Pauling Institute, Oregon State University, Corvallis, OR.
Keywords: dietary supplements, vitamin E (alpha-tocopherol), hepatic metabolism, microsomes, peroxisomes, trolox, alpha-CEHC, "mitochondrial role in alpha-tocopherol metabolism".
Mustacich DJ, Leonard SW, Patel NK, Traber MG.
Linus Pauling Institute, Oregon State University, Corvallis, OR.
Keywords: dietary supplements, vitamin E (alpha-tocopherol), hepatic metabolism, microsomes, peroxisomes, trolox, alpha-CEHC, "mitochondrial role in alpha-tocopherol metabolism".
Wednesday, October 14, 2009
Cerebellar Contributions to Adaptive Control of Saccades in Humans
The Journal of Neuroscience, October 14, 2009, 29(41):12930-12939; doi:10.1523/JNEUROSCI.3115-09.2009
Minnan Xu-Wilson,1 Haiyin Chen-Harris,1 David S. Zee,2 and Reza Shadmehr1
1Departments of Biomedical Engineering and 2Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205
Keywords: cerebellum, internal feedback correct, saccades, cerebellar damage, dysmetria.
Minnan Xu-Wilson,1 Haiyin Chen-Harris,1 David S. Zee,2 and Reza Shadmehr1
1Departments of Biomedical Engineering and 2Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205
Keywords: cerebellum, internal feedback correct, saccades, cerebellar damage, dysmetria.
Nutrition, Brain Aging, and Neurodegeneration
The Journal of Neuroscience, October 14, 2009, 29(41):12795-12801; doi:10.1523/JNEUROSCI.3520-09.2009
James Joseph,1 Greg Cole,2 Elizabeth Head,3 and Donald Ingram4
1USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, 2Geriatric Research, Education and Clinical Centers, Veterans Affairs Medical Center, and Department of Medicine, University of California, Los Angeles, Sepulveda, California 91343, 3University of Kentucky Sanders-Brown Center on Aging, Lexington, Kentucky 40536, and 4Pennington Biomedical Center, Baton Rouge, Louisiana 70808
Unfortunately we all know what is the FA, and these tips are not enough, but they are interesting.
James Joseph,1 Greg Cole,2 Elizabeth Head,3 and Donald Ingram4
1USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, 2Geriatric Research, Education and Clinical Centers, Veterans Affairs Medical Center, and Department of Medicine, University of California, Los Angeles, Sepulveda, California 91343, 3University of Kentucky Sanders-Brown Center on Aging, Lexington, Kentucky 40536, and 4Pennington Biomedical Center, Baton Rouge, Louisiana 70808
Unfortunately we all know what is the FA, and these tips are not enough, but they are interesting.
Long-Term Safety and Tolerability of Idebenone in Friedreich's Ataxia Patients (MICONOS Extension)
Official Title: A Phase III Open-Label, Single-Group, Extension Study to Obtain Long-Term Safety and Tolerability Data of Idebenone in the Treatment of Friedreich's Ataxia Patients.
This study is currently recruiting participants.
Verified by Santhera Pharmaceuticals, October 2009
First Received: October 13, 2009
Sponsored by: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00993967
This study is currently recruiting participants.
Verified by Santhera Pharmaceuticals, October 2009
First Received: October 13, 2009
Sponsored by: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00993967
Stress ossidativo ed anomalie citoscheletriche nell’Atassia di Friedreich
Piemonte, Fiorella
Gaeta, Laura Maria
UNIVERSITÀ DEGLI STUDI DI ROMA "TOR VERGATA", FACOLTA' DI MEDICINA, DOTTORATO DI RICERCA IN BIOTECNOLOGIE MEDICHE E MEDICINA MOLECOLARE
Issue Date: 6-Aug-2009
Keywords: Atassia di Friedreich, glutatione, proteine glutationilate, citoscheletro, stress ossidativo, regolazione redox.
Link to full text: http://dspace.uniroma2.it/dspace/bitstream/2108/994/1/TESI+DI+DOTTORATO.pdf
Gaeta, Laura Maria
UNIVERSITÀ DEGLI STUDI DI ROMA "TOR VERGATA", FACOLTA' DI MEDICINA, DOTTORATO DI RICERCA IN BIOTECNOLOGIE MEDICHE E MEDICINA MOLECOLARE
Issue Date: 6-Aug-2009
Keywords: Atassia di Friedreich, glutatione, proteine glutationilate, citoscheletro, stress ossidativo, regolazione redox.
Link to full text: http://dspace.uniroma2.it/dspace/bitstream/2108/994/1/TESI+DI+DOTTORATO.pdf
A comparison of three measures of upper limb function in Friedreich ataxia.
J Neurol. 2009 Oct 13.
Corben LA, Tai G, Wilson C, Collins V, Churchyard AJ, Delatycki MB.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Rd, Parkville, VIC, 3052, Australia.
Keywords: Friedreich Ataxia (FRDA), false negative results, upper limb function, the Nine Hole Peg Test (9HPT), Box and Blocks Test (BBT), Jebsen Taylor Hand Function Test (JTHFT),Friedreich Ataxia Functional Composite (FAFC) test, clinical studies, terapeutic trials, age at disease onset, disease duration, Friedreich Ataxia Rating Scale (FARS).
Corben LA, Tai G, Wilson C, Collins V, Churchyard AJ, Delatycki MB.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Rd, Parkville, VIC, 3052, Australia.
Keywords: Friedreich Ataxia (FRDA), false negative results, upper limb function, the Nine Hole Peg Test (9HPT), Box and Blocks Test (BBT), Jebsen Taylor Hand Function Test (JTHFT),Friedreich Ataxia Functional Composite (FAFC) test, clinical studies, terapeutic trials, age at disease onset, disease duration, Friedreich Ataxia Rating Scale (FARS).
Tuesday, October 13, 2009
Antioxidants and other pharmacological treatments for Friedreich ataxia.
Cochrane Database Syst Rev. 2009 Oct 7;4:CD007791
Kearney M, Orrell RW, Fahey M, Pandolfo M.
General Practice, Irish College of General Practitioners, Dunlavin, County Wicklow, Ireland.
Keywords: Friedreich ataxia, autosomal recessive, neurological disorder, slurred speech, scoliosis, pes cavus, heart abnormalities, antioxidants, controlled trials, international Co-operative Ataxia Rating Scale (ICARS),left ventricular heart mass, magnetic resonance imaging, echocardiography, idebenone.
Kearney M, Orrell RW, Fahey M, Pandolfo M.
General Practice, Irish College of General Practitioners, Dunlavin, County Wicklow, Ireland.
Keywords: Friedreich ataxia, autosomal recessive, neurological disorder, slurred speech, scoliosis, pes cavus, heart abnormalities, antioxidants, controlled trials, international Co-operative Ataxia Rating Scale (ICARS),left ventricular heart mass, magnetic resonance imaging, echocardiography, idebenone.
Lipid Oxidation and Peroxidation in CNS Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities
Rao Muralikrishna Adibhatla, James Franklin Hatcher, Savita Khanna, Shrinivas K. Kulkarni, Pamela Maher, Cesare Mancuso, Stanley I. Rapoport, Mark Smith, Bobby Thomas, Tatsurou Yagami. Antioxidants & Redox Signaling. -Not available-, ahead of print. doi:10.1089/ars.2009.2668.
Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.Cardiovascular Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. William S. Middleton Veterans Affairs Hospital, Madison, Wisconsin.
Keywords: Reactive oxygen species (ROS), oxidative phosphorylation, NAD(P)H oxidases, arachidonic acid oxidative metabolism, endogenous antioxidant defenses, Nrf2/ARE, Oxidative stress, lipids, cell death, oxidized phospholipids, 4-hydroxynonenal, 4-oxo-2-nonenal, acrolein, neurodegenerative diseases (AD, ALS, bipolar disorder, epilepsy, Friedreich's ataxia, HD, MS, NBIA, NPC, PD, peroxisomal disorders, schizophrenia, Wallerian degeneration, Zellweger syndrome), CNS traumas (stroke, TBI, SCI), free iron, Fenton reaction, cholesterol, lipid oxidation/peroxidation.
Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.Cardiovascular Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. William S. Middleton Veterans Affairs Hospital, Madison, Wisconsin.
Keywords: Reactive oxygen species (ROS), oxidative phosphorylation, NAD(P)H oxidases, arachidonic acid oxidative metabolism, endogenous antioxidant defenses, Nrf2/ARE, Oxidative stress, lipids, cell death, oxidized phospholipids, 4-hydroxynonenal, 4-oxo-2-nonenal, acrolein, neurodegenerative diseases (AD, ALS, bipolar disorder, epilepsy, Friedreich's ataxia, HD, MS, NBIA, NPC, PD, peroxisomal disorders, schizophrenia, Wallerian degeneration, Zellweger syndrome), CNS traumas (stroke, TBI, SCI), free iron, Fenton reaction, cholesterol, lipid oxidation/peroxidation.
Saturday, October 10, 2009
Risk/Benefit assessment, advantages over other drugs and targeting methods in the use of deferiprone as a pharmaceutical antioxidant in iron loading and non iron loading conditions.
Hemoglobin. 2009;33(5):386-97.
Kontoghiorghes GJ, Efstathiou A, Kleanthous M, Michaelides Y, Kolnagou A.
Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus.
Keywords: oxidative stress, brain, heart, liver, kidneys, classical antioxidants, deferiprone, mobilizing labile iron and copper, free radicals, high therapeutic index, tissue penetration, rapid iron binding, clearance, iron complex, toxicity, cardiomyopathy, thalassemia, diabetic nephropathy, glomerulonephritis, kidney disease, Friedreich's Ataxia, Fanconi Anemia, deferoxamine (DFO), deferasirox (DFRA).
Kontoghiorghes GJ, Efstathiou A, Kleanthous M, Michaelides Y, Kolnagou A.
Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus.
Keywords: oxidative stress, brain, heart, liver, kidneys, classical antioxidants, deferiprone, mobilizing labile iron and copper, free radicals, high therapeutic index, tissue penetration, rapid iron binding, clearance, iron complex, toxicity, cardiomyopathy, thalassemia, diabetic nephropathy, glomerulonephritis, kidney disease, Friedreich's Ataxia, Fanconi Anemia, deferoxamine (DFO), deferasirox (DFRA).
Thursday, October 8, 2009
Friedreich ataxia: a computational dynamic model of the key proteins involved in the yeast Fe–S cluster biogenesis
Friedreich ataxia: a computational dynamic model of the key proteins involved in the yeast Fe–S cluster biogenesis
New Biotechnology
Volume 25, Supplement 1, September 2009, Pages S342-S343
Abstracts of the 14th European Congress on BiotechnologyBarcelona, Spain 13–16 September, 2009
I. Amela1, J. Cedano1, P. Delicado2 and E. Querol1
1Universitat Autònoma de Barcelona, Bellatera - Barcelona, Spain
2Universitat Politècnica de Catalunya, Barcelona, Spain
New Biotechnology
Volume 25, Supplement 1, September 2009, Pages S342-S343
Abstracts of the 14th European Congress on BiotechnologyBarcelona, Spain 13–16 September, 2009
I. Amela1, J. Cedano1, P. Delicado2 and E. Querol1
1Universitat Autònoma de Barcelona, Bellatera - Barcelona, Spain
2Universitat Politècnica de Catalunya, Barcelona, Spain
Characterizing gait, locomotor status, and disease severity in children and adolescents with friedreich ataxia.
J Neurol Phys Ther. 2009 Sep;33(3):144-9.
Croarkin E, Maring J, Pfalzer L, Harris-Love M, Siegel K, Diprospero N.
National Institutes of Health (E.C., K.S.), Bethesda, MD; George Washington University, Physical Therapy Program (J.M., M.H.L.), Washington, DC; University of Michigan School of Health Related Professions and Studies (L.P.), Ann Arbor, Michigan; and National Institute of Neurological Disorders and Stroke (N.D.P.), Bethesda, Maryland.
KEYWORDS: gait parameters, children, adolescents, Friedreich ataxia (FA), disease severity, Friedreich Ataxia Rating Scale (FARS), walk.
Croarkin E, Maring J, Pfalzer L, Harris-Love M, Siegel K, Diprospero N.
National Institutes of Health (E.C., K.S.), Bethesda, MD; George Washington University, Physical Therapy Program (J.M., M.H.L.), Washington, DC; University of Michigan School of Health Related Professions and Studies (L.P.), Ann Arbor, Michigan; and National Institute of Neurological Disorders and Stroke (N.D.P.), Bethesda, Maryland.
KEYWORDS: gait parameters, children, adolescents, Friedreich ataxia (FA), disease severity, Friedreich Ataxia Rating Scale (FARS), walk.
Mystery About Proteins That Package The Genome Solved
Florida State University. "Mystery About Proteins That Package The Genome Solved." ScienceDaily 8 October 2009
Keywords: regulate gene expression, histones, packaging DNA, genes are turned on or off,
Keywords: regulate gene expression, histones, packaging DNA, genes are turned on or off,
Wednesday, October 7, 2009
Molecular signatures of disease brain endothelia provide new sites for CNS-directed enzyme therapy
Nature Medicine 15, 1215 - 1218 (2009)
Published online: 13 September 2009 | doi:10.1038/nm.2025
Published online: 13 September 2009 | doi:10.1038/nm.2025
Yong Hong Chen1, Michael Chang2 & Beverly L Davidson1,3
- Department of Internal Medicine, Iowa City, Iowa, USA.
- Departments of Molecular Physiology & Biophysics, Iowa City, Iowa, USA.
- Department of Neurology, University of Iowa, Iowa City, Iowa, USA.
Keywors: Brain vasculature, neural cells, microvessel, enzyme replacement therapy, central nervous system (CNS), endothelia, neurons, glia, adeno-associated virus (AAV), biodistribution.
Glutaredoxins: roles in iron homeostasis
Trends in Biochemical Sciences
Article in Press,
Nicolas Rouhier1, , Jérémy Couturier1, Michael K. Johnson2 and Jean-Pierre Jacquot1
1Unité Mixte de Recherches 1136 INRA Nancy University, Interactions Arbres Microorganismes, IFR 110 EFABA, Faculté des Sciences, BP 239 54506, Vandoeuvre Cedex, France
2Department of Chemistry and Center for Metalloenzyme Studies, University of Georgia, Athens, GA 30602, USA
Available online 5 October 2009.
Article in Press,
Nicolas Rouhier1, , Jérémy Couturier1, Michael K. Johnson2 and Jean-Pierre Jacquot1
1Unité Mixte de Recherches 1136 INRA Nancy University, Interactions Arbres Microorganismes, IFR 110 EFABA, Faculté des Sciences, BP 239 54506, Vandoeuvre Cedex, France
2Department of Chemistry and Center for Metalloenzyme Studies, University of Georgia, Athens, GA 30602, USA
Available online 5 October 2009.
Sunday, October 4, 2009
Mitochondria - A neglected drug target.
Curr Opin Investig Drugs. 2009 Oct;10(10):1022-4.
Murphy MP.
Murphy MP.
Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK. mpm@mrc-mbu.cam.ac.uk.
Saturday, October 3, 2009
No Link Between Suicide and Stop-Smoking Drugs
By Kristina Fiore, Staff Writer, MedPage Today
Published: October 02, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
Keywords: varenicline (Chantix)
Published: October 02, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
Keywords: varenicline (Chantix)
Friday, October 2, 2009
Diverse effects in Friedreich's ataxia place PGC-1alpha center-stage.
Clin Genet. 2009 Oct;76(4):345-7
Metzler M.
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada. martina@cmmt.ubc.ca
Metzler M.
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada. martina@cmmt.ubc.ca
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