Performance of AAV8 vectors expressing human factor IX from a hepatic-selective promoter following intravenous injection into rats

Background: Vectors based on adeno-associated virus-8 (AAV8) have shown efficiency and efficacy for liver-directed gene therapy protocols following intravascular injection, particularly in relation to haemophilia gene therapy. AAV8 has also been proposed for gene therapy targeted at skeletal and cardiac muscle, again via intravascular injection. It is important to assess vector targeting at the level of virion accumulation and transgene expression in multiple species to ascertain potential issues relating to species variation in infectivity profiles. Methods: We used AAV8 vectors expressing human factor IX (FIX) from the liver-specific LP-1 promoter and administered this virus via the intravascular route of injection into 12 week old Wistar Kyoto rats. We assessed FIX levels in serum by ELISA and transgene expression at sacrifice by immunohistochemistry using anti-FIX antibodies. Vector DNA levels in organs we determined by real time PCR. Results: Administration of 1 × 1011 or 5 × 1011 scAAV8-LP1-hFIX vector particles/rat resulted in efficient production of physiological hFIX levels, respectively in blood assessed 4 weeks post-injection. This was maintained for the 4 month duration of the study. At 4 months we observed liver persistence of vector with minimal non-hepatic distribution. Conclusion: Our results demonstrate that AAV8 is a robust vector for delivering therapeutic genes into rat liver following intravascular injection

Solar Atmospheric Oscillations and the Chromospheric Magnetic Topology

We investigate the oscillatory properties of the quiet solar chromosphere in relation to the underlying photosphere, with particular regard to the effects of the magnetic topology. We perform a Fourier analysis on a sequence of line-of-sight velocities measured simultaneously in a photospheric (Fe I 709.0 nm) and a chromospheric line (Ca II 854.2 nm). The velocities were obtained from full spectroscopic data acquired at high spatial resolution with the Interferometric BIdimensional Spectrometer (IBIS). The field of view encompasses a full supergranular cell, allowing us to discriminate between areas with different magnetic characteristics. We show that waves with frequencies above the acoustic cut-off propagate from the photosphere to upper layers only in restricted areas of the quiet Sun. A large fraction of the quiet chromosphere is in fact occupied by ``magnetic shadows'', surrounding network regions, that we identify as originating from fibril-like structures observed in the core intensity of the Ca II line. We show that a large fraction of the chromospheric acoustic power at frequencies below the acoustic cut-off, residing in the proximity of the magnetic network elements, directly propagates from the underlying photosphere. This supports recent results arguing that network magnetic elements can channel low-frequency photospheric oscillations into the chromosphere, thus providing a way to input mechanical energy in the upper layers.Comment: 4 pages, 3 figure, A&A Letters in pres

Letter from Mrs. T. E. McIntosh

Letter concerning engineering courses at Utah Agricultural College

The Impact of New EUV Diagnostics on CME-Related Kinematics

We present the application of novel diagnostics to the spectroscopic observation of a Coronal Mass Ejection (CME) on disk by the Extreme Ultraviolet Imaging Spectrometer (EIS) on the Hinode spacecraft. We apply a recently developed line profile asymmetry analysis to the spectroscopic observation of NOAA AR 10930 on 14-15 December 2006 to three raster observations before and during the eruption of a 1000km/s CME. We see the impact that the observer's line-of-sight and magnetic field geometry have on the diagnostics used. Further, and more importantly, we identify the on-disk signature of a high-speed outflow behind the CME in the dimming region arising as a result of the eruption. Supported by recent coronal observations of the STEREO spacecraft, we speculate about the momentum flux resulting from this outflow as a secondary momentum source to the CME. The results presented highlight the importance of spectroscopic measurements in relation to CME kinematics, and the need for full-disk synoptic spectroscopic observations of the coronal and chromospheric plasmas to capture the signature of such explosive energy release as a way of providing better constraints of CME propagation times to L1, or any other point of interest in the heliosphere.Comment: Accepted to appear in Solar Physics Topical Issue titled "Remote Sensing of the Inner Heliosphere". Manuscript has 14 pages, 5 color figures. Movies supporting the figures can be found in http://download.hao.ucar.edu/pub/mscott/papers/Weathe

Acupuncture's Effects in Treating the Sequelae of Acute and Chronic Spinal Cord Injuries: A Review of Allopathic and Traditional Chinese Medicine Literature

Each year, there are an estimated 12 000 individuals who sustain a spinal cord injury (SCI) in the United States. Improved understanding of the pathophysiology of SCI and its sequelae has over the past 50 years led to the development of medical treatments (especially urologic) that have enhanced short- and long-term survival from these injuries. The prevalence of individuals with SCI in this country is ~250 000 individuals; and beyond the incalculable personal consequences of these devastating neurologic injuries, substantial direct and indirect societal costs result from the sequelae of SCI including paralysis, sensory loss, chronic pain, decubiti and bladder and/or bowel incontinence. The purpose of this treatise is to review the allopathic and traditional Chinese medicine (TCM) literature available through MEDLINE, PubMed and eCAM search engines that discuss the potential uses of acupuncture to treat acute and chronic spinal cord injuries and their sequelae, and present the neurophysiologic mechanisms for acupuncture's beneficial effects. There is evidence that use of electroacupuncture in acute SCI may significantly improve long-term neurologic recovery from these injuries both in terms of motor, sensory and bowel/bladder function with essentially no risk. Acupuncture may even improve neurourologic function in individuals with chronic SCI, and help with management with chronic pain associated with these injuries

Neurogenic Bladder

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented