Neural Stem Cells Achieve and Maintain Pluripotency without Feeder Cells

Background: Differentiated cells can be reprogrammed into pluripotency by transduction of four defined transcription factors. Induced pluripotent stem cells (iPS cells) are expected to be useful for regenerative medicine as well as basic research. Recently, the report showed that mouse embryonic fibroblasts (MEF) cells are not essential for reprogramming. However, in using fibroblasts as donor cells for reprogramming, individual fibroblasts that had failed to reprogram could function as feeder cells. Methodology/Principal Finding: Here, we show that adult mouse neural stem cells (NSCs), which are not functional feeder cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2, Klf4, and c-Myc) under feeder-free conditions. The iPS cells, generated from NSCs expressing the Oct4-GFP reporter gene, could proliferate for more than two months (passage 20). Generated and maintained without feeder cells, these iPS cells expressed pluripotency markers (Oct4 and Nanog), the promoter regions of Oct4 and Nanog were hypomethylated, could differentiated into to all three germ layers in vitro, and formed a germline chimera. These data indicate that NSCs can achieve and maintain pluripotency under feeder-free conditions. Conclusion/Significance: This study suggested that factors secreted by feeder cells are not essential in the initial/early stages of reprogramming and for pluripotency maintenance. This technology might be useful for a human system, as

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA)

Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/ behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = − 2.12, p = .055), GABA/Glx ratio (t(12) = − 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met ‘clinical responder’ criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee

Finite-element analysis of microstructure evolution in the cogging of an Alloy 718 ingot

Microstructural changes during the cogging of an Alloy 718 ignot processed by (vacuum induction melting)/(vacuum arc re-melting) were predicted using the combined approach of three-dimensional finite element simulation and modeling for the recrystallization and grain growth. In order to establish recrystallization and grain growth models for Alloy 718 ingot, hot compression and isothermal heat treatment tests were carried out at different temperatures and strain rates. The constitutive equations for metadynamic and static-recrystallization behavior were generated using the experimental data collected from various references. From the experimental results, it was found that the dissolution temperature of delta-phase (Ni3Nb) played an important role in the microstructural refinement of Alloy 718 ingot. The predicted grain size and its distribution were compared with the microstructures of the cogged billet, and the reliability of the prediction was discussed. (c) 2006 Elsevier B.V. All rights reserved.X1139sciescopu

Flow softening behavior during high temperature deformation of AZ31Mg alloy

In the present study, the flow softening behavior occurring during high temperature deformation of AZ31 Mg alloy was investigated. Flow softening of AZ31 Mg alloy was considered to arise mainly due to thermal softening by deformation heating and microstructural softening by dynamic recrystallization (DRX). Artificial neural networks method was used to derive the accurate amounts of thermal softening by deformation heating. To quantify the microstructural softening, a series of mechanical tests (high temperature compressions and load relaxation tests) were conducted at various temperatures (250-500 degrees C) and strain rates (10(-4)-10(2)/s). To verify the proposed formulations, the hot-forging of AZ31 Mg alloy was conducted at the condition of 250 degrees C, 0.5/s (optimum DRX condition) with the 970 tonnes press. The Finite Element Method (FEM) was also used to simulate the hot-forging of AZ31 Mg alloy using identical conditions as experimental ones. The effect of DRX kinetics on microstructure evolution (fraction of recrystallization and recrystallized grain sizes) was implemented in a commercial FEM code followed by remapping of the state variables of temperatures, strain rates and strains. The predicted grain sizes and fractions of DRX showed good agreement with experimental results. (c) 2006 Elsevier B.V. All rights reserved.X1157sciescopu

Tensile test criterion of transformation-induced elasticity and plasticity alloys for load-displacement measurement

The tensile test criterion to obtain a reliable stress-strain curve from load-displacement data of metallic materials exhibiting twinning or phase transformation was developed especially for environments that do not allow the use of an extensometer. The study shows that neither ASTM E8/E8M standard specimen nor strip-shaped specimen geometry was appropriate for converting load-displacement data to an actual stress-strain curve; the former exhibited an undesired two-stage yield, while the latter revealed premature fracture. To solve these problems, the relationship between the specimen geometries and load displacement data was carefully analyzed for dog-bone type specimens having a minimized fillet radius; it was found that the ratio of grip width W-gr, to gauge width W-ga should be higher than the ratio of fracture stress to the first yield stress 0.1. Otherwise, a second yield always occurred when the stress reached a value close to sigma(1) W-gr/W-ga, obstructing the data analysis to reconstruct the actual stress-strain curve from load-displacement data. Finally, a methodology to verify whether the tensile test satisfied the criterion was suggested in terms of a nominal strain hardening rate.11sciescopu

Temperature dependence of the electronic structure of two-dimensional Na gas on the Si(111)-7 x 7 surface

The temperature dependence of the irreversible phase transition from a two-dimensional gas to an ordered zero-dimensional solid on the Si(111)-7 x 7 surface was studied using photoemission spectroscopy. With increasing Na coverage, the two-dimensional Na gas, which is a state of highly mobile Na atoms, undergoes a phase transition into ordered zero-dimensional magic nanoclusters at room temperature. The critical Na coverage of the phase transition was found to increase with reduced temperature. This was used to develop a gas-solid phase diagram of Na atoms on the Si(111)-7 x 7 surface as a function of Na coverage and sample temperature based on the electronic structure. The temperature dependence of the phase transition can be ascribed to the suppression of the thermal energy that is required to overcome the energetic barrier between the two-dimensional gas and the zero-dimensional solid at low temperature, where three different hopping mechanisms are related to the phase transition.1121sciescopu

INFLUENCE OF INITIAL MICROSTRUCTURE ON HOT WORKABILITY OF Ti-6Al-4V ALLOY

Hot workability of Ti-6Al-4V alloy with different initial microstructures was investigated by considering processing maps and the dynamic material deformation behavior. The emphasis has been focused on the effect of initial microstructure (equiaxed versus bimodal structure). Process maps were generated using the dynamic material model (DMM), unifying the relationships between constitutive deformation behavior, hot workability and microstructures evolution. Also, the flow instability was investigated using the various flow instability criteria and microstructural analysis. To establish the processing maps with different initial microstructures, high temperature compression tests were carried out at various temperatures and strain rates up to a true strain of 0.7. Microstructural changes occurring during the deformation were analyzed in terms of high temperature deformation mechanisms. Finally the useful instability criterion for predicting the forming defects was suggested through the compression test results with different temperatures and strain rates.X112sciescopu