Enhanced transduction of colonic cell lines in vitro and the inflamed colon in mice by viral vectors, derived from adeno-associated virus serotype 2, using virus-microbead conjugates bearing lectin

<p>Abstract</p> <p>Background</p> <p>Virus-mediated delivery of therapeutic transgenes to the inflamed colon holds a great potential to serve as an effective therapeutic strategy for inflammatory bowel disease, since local, long-term expression of the encoded therapeutic proteins in the colorectal system is potentially achievable. Viral vectors, derived from adeno-associated virus (AAV), should be very useful for such therapeutic strategies, particularly because they can establish long-term expression of transgenes. However, few studies have been carried out to investigate the ability of AAV-based vectors to transduce the inflamed colon.</p> <p>Results</p> <p>AAV, derived from adeno-associated virus serotype 2 (AAV2), showed a limited ability to transduce colonic cell lines <it>in vitro </it>when used in free form. No appreciable enhancement of the transduction efficiency was seen when AAV2 particles were attached stably to the surfaces of microbeads and delivered to target cells in the form of AAV2-microbead conjugates. However, the transduction efficiency of these colonic cell lines was enhanced substantially when a lectin, concanavalin A (Con A), was co-attached to the microbead surfaces, to which AAV2 particles had been conjugated. This considerable infectivity enhancement of AAV2-microbead conjugates by the co-attachment of Con A may be derived from the fact that Con A binds to α-D-mannosyl moieties that are commonly and abundantly present in cell-surface carbohydrate chains, allowing the conjugates to associate stably with target cells. Intracolonical administration of free AAV2 or AAV2-microbead conjugates without Con A into a mouse colitis model by enema showed very poor transduction of the colonic tissue. In contrast, the delivery of AAV2 in the form of AAV2-microbead conjugates bearing Con A resulted in efficient transduction of the inflamed colon.</p> <p>Conclusion</p> <p>AAV2-microbead conjugates bearing Con A can serve as efficient gene transfer agents both for poorly permissive colonic cell lines <it>in vitro </it>and for the inflamed colon in a mouse colitis model. This efficient transduction system for the inflamed colon should be useful for the development of gene therapy strategies for inflammatory bowel disease.</p

Formation of targeted monovalent quantum dots by steric exclusion

Precise control over interfacial chemistry between nanoparticles and other materials remains a significant challenge limiting the broad application of nanotechnology in biology. To address this challenge, we use “Steric Exclusion” to completely convert commercial quantum dots (QDs) into monovalent imaging probes by wrapping the QD with a functionalized oligonucleotide. We demonstrate the utility of these QDs as modular and non-perturbing imaging probes by tracking individual Notch receptors on live cells

Air-Coupled Ultrasonic Transducers for the Detection of Defects in Plates

In order to minimise the problems due to the acoustic impedance mismatch between solids and air, the non destructive testing of materials using ultrasonic transducers generally requires either contact transducers or immersion transducers to be used [1]. Air-coupled transducers however would be very advantageous for testing structures which must be not contaminated with couplant and also for all in-situ industrial applications. Although the propagation of ultrasonic waves from laser generation [2] involves air-coupling, the difficulties due to the experimental set-up of this technique and the financial investment it implies are two major disadvantages

The Role of Choroid Plexus In IVIG-induced Beta-Amyloid Clearance

We have shown that intravenous immunoglobulin (IVIG) contains anti-Aβ autoantibodies and IVIG could induce beta amyloid (Aβ) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Aβ efflux remains unclear. In this study, we used amyloid precursor protein (AβPP) transgenic mice to investigate if the IVIG could induce efflux of Aβ from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Aβ transporter in blood-cerebrospinal fluid barrier (BCB); could mediate this clearance process. We currently provide strong evidence to demonstrate that IVIG could reduce brain Aβ levels by pulling Aβ into the blood system in AβPP transgenic mice. In the mechanistic study, IVIG could induce Aβ efflux through the in-vitro BCB membrane formed by cultured BCB epithelial cells. Both RAP (receptor-associated protein; a functional inhibitor of LRP1), and LRP1 siRNA were able to significantly inhibit the Aβ efflux. Should Aβ prove to be the underlying cause of AD, our results strongly suggest that IVIG could be beneficial in the therapy for Alzheimer's disease (AD) by inducing efflux of Aβ from the brain through the LRP1 in the BCB

Theory, simulation and experimental results of the acoustic detection of magnetization changes in superparamagnetic iron oxide

<p>Abstract</p> <p>Background</p> <p>Magnetic Particle Imaging is a novel method for medical imaging. It can be used to measure the local concentration of a tracer material based on iron oxide nanoparticles. While the resulting images show the distribution of the tracer material in phantoms or anatomic structures of subjects under examination, no information about the tissue is being acquired. To expand Magnetic Particle Imaging into the detection of soft tissue properties, a new method is proposed, which detects acoustic emissions caused by magnetization changes in superparamagnetic iron oxide.</p> <p>Methods</p> <p>Starting from an introduction to the theory of acoustically detected Magnetic Particle Imaging, a comparison to magnetically detected Magnetic Particle Imaging is presented. Furthermore, an experimental setup for the detection of acoustic emissions is described, which consists of the necessary field generating components, i.e. coils and permanent magnets, as well as a calibrated microphone to perform the detection.</p> <p>Results</p> <p>The estimated detection limit of acoustic Magnetic Particle Imaging is comparable to the detection limit of magnetic resonance imaging for iron oxide nanoparticles, whereas both are inferior to the theoretical detection limit for magnetically detected Magnetic Particle Imaging. Sufficient data was acquired to perform a comparison to the simulated data. The experimental results are in agreement with the simulations. The remaining differences can be well explained.</p> <p>Conclusions</p> <p>It was possible to demonstrate the detection of acoustic emissions of magnetic tracer materials in Magnetic Particle Imaging. The processing of acoustic emission in addition to the tracer distribution acquired by magnetic detection might allow for the extraction of mechanical tissue parameters. Such parameters, like for example the velocity of sound and the attenuation caused by the tissue, might also be used to support and improve ultrasound imaging. However, the method can also be used to perform imaging on its own.</p

Regge behaviour of distribution functions and evolution of gluon distribution function in Next-to-Leading order at low-x

Evolution of gluon distribution function from Dokshitzer-Gribov-Lipatov-Altarelli-Parisi (DGLAP) evolution equation in next-to-leading order (NLO) at low-x is presented assuming the Regge behaviour of quarks and gluons at this limit. We compare our results of gluon distribution function with MRST2004, GRV98LO and GRV98NLO parameterizations and show the compatibility of Regge behaviour of quark and gluon distribution functions with perturbative quantum chromodynamics (PQCD) at low-x.Comment: 12 pages, 4 figure

Regge behaviour of distribution functions and t and x-evolutions of gluon distribution function at low-x

In this paper t and x-evolutions of gluon distribution function from Dokshitzer-Gribov-Lipatov-Altarelli-Parisi(DGLAP) evolution equation in leading order(LO) at low-x, assuming the Regge behaviour of quark and gluon at this limit, are presented. We compare our results of gluon distribution function with MRST 2001, MRST 2004 and GRV '98 parameterizations and show the compatibility of Regge behaviour of quark and gluon distribution functions with perturbative quantum chromodynamics(PQCD) at low-x. We also discuss the limitations of Taylor series expansion method used earlier to solve DGLAP evolution equations, in the Regge behaviour of distribution functions.Comment: 19 pages, 7 figure