Murine and human myogenic cells identified by elevated aldehyde dehydrogenase activity: Implications for muscle regeneration and repair

Background: Despite the initial promise of myoblast transfer therapy to restore dystrophin in Duchenne muscular dystrophy patients, clinical efficacy has been limited, primarily by poor cell survival post-transplantation. Murine muscle derived stem cells (MDSCs) isolated from slowly adhering cells (SACs) via the preplate technique, induce greater muscle regeneration than murine myoblasts, primarily due to improved post-transplantation survival, which is conferred by their increased stress resistance capacity. Aldehyde dehydrogenase (ALDH) represents a family of enzymes with important morphogenic as well as oxidative damage mitigating roles and has been found to be a marker of stem cells in both normal and malignant tissue. In this study, we hypothesized that elevated ALDH levels could identify murine and human muscle derived cell (hMDC) progenitors, endowed with enhanced stress resistance and muscle regeneration capacity. Methodology/Principal Findings: Skeletal muscle progenitors were isolated from murine and human skeletal muscle by a modified preplate technique and unfractionated enzymatic digestion, respectively. ALDHhisubpopulations isolated by fluorescence activate cell sorting demonstrated increased proliferation and myogenic differentiation capacities compared to their ALDHlocounterparts when cultivated in oxidative and inflammatory stress media conditions. This behavior correlated with increased intracellular levels of reduced glutathione and superoxide dismutase. ALDHhimurine myoblasts were observed to exhibit an increased muscle regenerative potential compared to ALDHlomyoblasts, undergo multipotent differentiation (osteogenic and chondrogenic), and were found predominately in the SAC fraction, characteristics that are also observed in murine MDSCs. Likewise, human ALDHhihMDCs demonstrated superior muscle regenerative capacity compared to ALDHlohMDCs. Conclusions: The methodology of isolating myogenic cells on the basis of elevated ALDH activity yielded cells with increased stress resistance, a behavior that conferred increased regenerative capacity of dystrophic murine skeletal muscle. This result demonstrates the critical role of stress resistance in myogenic cell therapy as well as confirms the role of ALDH as a marker for rapid isolation of murine and human myogenic progenitors for cell therapy. © 2011 Vella et al

Distributed and scalable XML document processing architecture for E-commerce systems

XML has became a very important emerging standard for E-commerce because of its flexibility and universality. Many software designers are actively developing new systems to handle information in XML formats. We propose a generic architecture for processing XML. We have designed an XML processing system using the latest technologies, such as XML, XSLT (XML Stylesheet Language Transformation), HTTP and Java servlets. Our design is very generic, flexible, scalable, extensible, and also suitable for distributed network environments. A main application of the architecture and the system is to support data exchange in E-commerce systems.published_or_final_versio

End-to-End Learning of Video Super-Resolution with Motion Compensation

Learning approaches have shown great success in the task of super-resolving an image given a low resolution input. Video super-resolution aims for exploiting additionally the information from multiple images. Typically, the images are related via optical flow and consecutive image warping. In this paper, we provide an end-to-end video super-resolution network that, in contrast to previous works, includes the estimation of optical flow in the overall network architecture. We analyze the usage of optical flow for video super-resolution and find that common off-the-shelf image warping does not allow video super-resolution to benefit much from optical flow. We rather propose an operation for motion compensation that performs warping from low to high resolution directly. We show that with this network configuration, video super-resolution can benefit from optical flow and we obtain state-of-the-art results on the popular test sets. We also show that the processing of whole images rather than independent patches is responsible for a large increase in accuracy.Comment: Accepted to GCPR201

Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration

Introduction. Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle. Methods. We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24§ssup§-/-§esup§) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function. Results: Our results indicate that MDSPCs isolated from Zmpste24§ssup§-/- §esup§mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24§ssup§-/- §esup§MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24§ssup§-/- §esup§MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro. Conclusions: These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells. © 2013 Song et al.; licensee BioMed Central Ltd

An elementary stringy estimate of transport coefficients of large temperature QCD

Modeling QCD at large temperature with a simple holographic five dimensional theory encoding minimal breaking of conformality, allows for the calculation of all the transport coefficients, up to second order, in terms of a single parameter. In particular, the shear and bulk relaxation times are provided. The result follows by deforming the AdS background with a scalar dual to a marginally relevant operator, at leading order in the deformation parameter.Comment: 11 pages; v2: comments and references adde

The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models

YesNon-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use.University of Bradfor

QCD corrections to J/ψJ/\psi plus Z0Z^0-boson production at the LHC

The $J/\psi+Z^0$ associated production at the LHC is an important process in investigating the color-octet mechanism of non-relativistic QCD in describing the processes involving heavy quarkonium. We calculate the next-to-leading order (NLO) QCD corrections to the $J/\psi +Z^0$ associated production at the LHC within the factorization formalism of nonrelativistic QCD, and provide the theoretical predictions for the distribution of the $J/\psi$ transverse momentum. Our results show that the differential cross section at the leading-order is significantly enhanced by the NLO QCD corrections. We conclude that the LHC has the potential to verify the color-octet mechanism by measuring the $J/\psi+Z^0$ production events.Comment: 14 page revtex, 5 eps figures, to appear in JHEP. fig5 and the corresponding analysis are correcte

Benchmark performance of low-cost Sb2Se3 photocathodes for unassisted solar overall water splitting

Determining cost-effective semiconductors exhibiting desirable properties for commercial photoelectrochemical water splitting remains a challenge. Herein, we report a Sb2Se3 semiconductor that satisfies most requirements for an ideal high-performance photoelectrode, including a small band gap and favourable cost, optoelectronic properties, processability, and photocorrosion stability. Strong anisotropy, a major issue for Sb2Se3, is resolved by suppressing growth kinetics via close space sublimation to obtain high-quality compact thin films with favourable crystallographic orientation. The Sb2Se3 photocathode exhibits a high photocurrent density of almost 30mAcm(-2) at 0V against the reversible hydrogen electrode, the highest value so far. We demonstrate unassisted solar overall water splitting by combining the optimised Sb2Se3 photocathode with a BiVO4 photoanode, achieving a solar-to-hydrogen efficiency of 1.5% with stability over 10h under simulated 1 sun conditions employing a broad range of solar fluxes. Low-cost Sb2Se3 can thus be an attractive breakthrough material for commercial solar fuel production. While photoelectrochemical water splitting offers an integrated means to convert sunlight to a renewable fuel, cost-effective light-absorbers are rare. Here, authors report Sb2Se3 photocathodes for high-performance photoelectrochemical water splitting devices

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

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