Transposon Tn7 Preferentially Inserts into GAA•TTC Triplet Repeats under Conditions Conducive to Y•R•Y Triplex Formation

Mancuso M, Sammarco MC, Grabczyk E, 2010 Transposon Tn7 Preferentially Inserts into GAA•TTC Triplet Repeats under Conditions Conducive to Y•R•Y Triplex Formation. PLoS ONE 5(6): e11121. doi:10.1371/journal.pone.0011121

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Abstract

BACKGROUND: Expansion of an unstable GAA*TTC repeat in the first intron of the FXN gene causes Friedreich ataxia by reducing frataxin expression. Structure formation by the repeat has been implicated in both frataxin repression and GAA*TTC instability. The GAA*TTC sequence is capable of adopting multiple non-B DNA structures including Y*R*Y and R*R*Y triplexes. Lower pH promotes the formation of Y*R*Y triplexes by GAA*TTC. Here we used the bacterial transposon Tn7 as an in vitro tool to probe whether GAA*TTC repeats can attract a well-characterized recombinase. METHODOLOGY/PRINCIPAL FINDINGS: Tn7 showed a pH-dependent preference for insertion into uninterrupted regions of a Friedreich ataxia patient-derived repeat, inserting 48, 39 and 14 percent of the time at pH 7, pH 8 and pH 9, respectively. Moreover, Tn7 also showed orientation and region specific insertion within the repeat at pH 7 and pH 8, but not at pH 9. In contrast, transposon Tn5 showed no strong preference for or against the repeat during in vitro transposition at any pH tested. Y*R*Y triplex formation was reduced in predictable ways by transposon interruption of the GAA*TTC repeat. However, transposon interruptions in the GAA*TTC repeats did not increase the in vitro transcription efficiency of the templates. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that transposon Tn7 will recognize structures that form spontaneously in GAA*TTC repeats and insert in a specific orientation within the repeat. The conditions used for in vitro transposition span the physiologically relevant range suggesting that long GAA*TTC repeats can form triplex structures in vivo, attracting enzymes involved in DNA repair, recombination and chromatin modification.

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Researchers create new 'smart' nanocapsule delivery system for use in protein therapy

UCLA Newsroom, Wileen Wong Kromhout December 17, 2009


Protein therapy — the delivery of healthy proteins directly into human cells to replace malfunctioning proteins — is considered one of the most direct and safe approaches for treating diseases. But its effectiveness has been limited by low delivery efficiency and the poor stability of proteins, which are frequently broken down and digested by cells' protease enzymes before they reach their intended target.     read more

More Discovered About The Composition Of Human Spinal Fluid

Medicalnewstoday, Article Date: 12 Jun 2010

A team of scientsts has sharply expanded scientific knowledge of the composition of human spinal fluid. The researchers have identified 2,630 proteins that reside in fluid that is considered "normal," a number nearly three times as great as the total number of proteins previously identified. Another striking finding was that more than half (56%) of the proteins were relatively unique to the spinal fluid and not found in blood.    read more

Longitudinal tracking of gait and balance impairments in cerebellar disease

Movement Disorders, Published Online: 11 Jun 2010, DOI 10.1002/mds.23169

Sussanne M. Morton, PhD, PT 1, Ya-Weng Tseng, PhD, PT 2, Kathleen M. Zackowski, PhD, OTR 3 4 5, Jaclyn R. Daline, PT, DPT 6, Amy J. Bastian, PhD, PT 3 4 5 *
1Graduate Program in Physical Therapy and Rehabilitation Science, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
2Department of Physical Therapy, Temple University, Philadelphia, Pennsylvania, USA
3Kennedy Krieger Institute, Baltimore, Maryland, USA
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
5Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
6Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri, USA

Keywords: ICARS,cerebellum, walking, ataxia, clinical assessment, sensitivity

Obstacles to Stem Cell Therapy Cleared

ScienceDaily (June 8, 2010) — Researchers at Lund University have come up with a new technique to prevent tumours developing in connection with stem cell transplantations. read more


Original paper: Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors. R. Sachdeva, M. E. Jonsson, J. Nelander, A. Kirkeby, C. Guibentif, B. Gentner, L. Naldini, A. Bjorklund, M. Parmar, J. Jakobsson. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1006568107

Erythropoietin Activates Mitochondrial Biogenesis and Couples Red Cell Mass to Mitochondrial Mass in the Heart

Circulation Research. 2010;106:1722, doi: 10.1161/CIRCRESAHA.109.214353

 

Martha S. Carraway, Hagir B. Suliman, W. Schuyler Jones, Chien-Wen Chen, Abdelwahid Babiker, Claude A. Piantadosi
From the Departments of Medicine (Pulmonary [M.S.C., C.-W.C., C.A.P.] and Cardiology [W.S.J.]), Anesthesiology (H.B.S., A.B., C.A.P.), and Pathology (C.A.P.), Duke University Medical Center Durham, NC. Present address for M.S.C.: Environmental Public Health Division, US Environmental Protection Agency, Chapel Hill, NC. Present address for C.-W.C.: Division of Chest Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan. Present address for A.B.: Department of Virology and Immunology, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia.

A Closer Look at Stem Cell Treatments

The International Society for Stem Cell Research (ISSCR)  has launched this new Web site "A Closer Look at Stem Cell Treatments", it's aimed to patients, their families and doctors,  it contains information that can be very useful to make decisions about the new promising stem cell treatments. The ISSCR urges individuals to be cautious and to learn the facts before making any decision.


"Una mirada cercana a los tratamientos con células madre",
La Sociedad Internacional para la Investigación con Células Madre (ISSCR) ha puesto en marcha este nuevo sitio Web "Una mirada cercana a los tratamientos con células madre", está dirigida a los pacientes, sus familias y los médicos, contiene información que puede ser muy útil para tomar decisiones acerca de los nuevos y prometedores tratamientos con células madre. La ISSCR insta a tener cuidado y estudiar los detalles antes de tomar cualquier decisión.

Treatment of neurological scoliosis of more than 1008 by using a hybrid contstruct (pedicle screws plus universal clamps)

La Rosa G, Giglio G, Oggiano L.
Treatment of neurological scoliosis of more than 1008 by using a hybrid contstruct (pedicle screws plus universal clamps). Paper #F484. To be presented at the EFORT Congress 2010. June 2-5, 2010. Madrid.

Hybrid construct provides adequate correction of deformity in patients with neurological scoliosi. 
Italian orthopaedists reported a low rate of complications when treating patients with high-grade neurological scoliosis using a hybrid construct that combined lumbar pedicle screws, Universal Clamps (Zimmer) and thoracic hooks...... read more

Frataxin and mitochondrial Fe-S cluster biogenesis.

The Journal of biological chemistry (3 June 2010)

Timothy L. Stemmler1, Emmanuel Lesuisse2, Debkumar Pain3, Andrew Dancis4.

Wayne State University School of Medicine, United States; CNRS-Universite Paris Diderot, France; UMDNJ, New Jersey Medical School, United States; 4 University of Pennsylvania, United States

Keyword: Friedreich's ataxia, neurodegenerative disease, frataxin, mitochondrial protein, Fe-S cluster, Isu, iron, cysteine desulfurase Nfs1.

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Breakthrough In Stem Cell Culturing

Medical News Today, Article Date: 02 Jun 2010
For the first time, human embryonic stem cells have been cultured under chemically controlled conditions without the use of animal substances, which is essential for future clinical uses. The method has been developed by researchers at Karolinska Institutet and is presented in the journal Nature Biotechnology.  read more