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1

Comparative Study on the Therapeutic Potential of Neurally Differentiated Stem Cells in a Mouse Model of Multiple Sclerosis  

PubMed Central

Background Transplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using a mouse model of MS, we evaluated the therapeutic potential of NSCs derived from ES cells by two different neural differentiation protocols that utilized adherent culture conditions and compared their effect to primary NSCs derived from the subventricular zone (SVZ). Methodology/Principal Findings The proliferation and secretion of pro-inflammatory cytokines by antigen-stimulated splenocytes was reduced in the presence of SVZ-NSCs, while ES cell-derived NSCs exerted differential immunosuppressive effects. Surprisingly, intravenously injected NSCs displayed no significant therapeutic impact on clinical and pathological disease outcomes in mice with experimental autoimmune encephalomyelitis (EAE) induced by recombinant myelin oligodendrocyte glycoprotein, independent of the cell source. Studies tracking the biodistribution of transplanted ES cell-derived NSCs revealed that these cells were unable to traffic to the CNS or peripheral lymphoid tissues, consistent with the lack of cell surface homing molecules. Attenuation of peripheral immune responses could only be achieved through multiple high doses of NSCs administered intraperitoneally, which led to some neuroprotective effects within the CNS. Conclusion/Significance Systemic transplantation of these NSCs does not have a major influence on the clinical course of rMOG-induced EAE. Improving the efficiency at which NSCs home to inflammatory sites may enhance their therapeutic potential in this model of CNS autoimmunity. PMID:22514711

Payne, Natalie L.; Sun, Guizhi; Herszfeld, Daniella; Tat-Goh, Pollyanna A.; Verma, Paul J.; Parkington, Helena C.; Coleman, Harold A.; Tonta, Mary A.; Siatskas, Christopher; Bernard, Claude C. A.

2012-01-01

2

Differential Effects of Oxygen and Oxidation Reduction Potential on the Multiplication of Three Species of Anaerobic Intestinal Bacteria  

PubMed Central

The sensitivity of three strains of anaerobic intestinal bacteria, Clostridium perfringens, Bacteroides fragilis, and Peptococcus magnus, to the differential effects of oxygen and adverse oxidation-reduction potential was measured. The multiplication of the three organisms was inhibited in the presence of oxygen whether the medium was at a negative oxidation-reduction potential (Eh of -50 mV), poised by the intermittent addition of dithiothreitol, or at a positive oxidation-reduction potential (Eh of near +500 mV). However, when these organisms were cultured in the absence of oxygen, no inhibition was observed, even when the oxidation-reduction potential was maintained at an average Eh of +325 mV by the addition of potassium ferricyanide. When the cultures were aerated, the growth patterns of the three organisms demonstrated different sensitivities to oxygen. P. magnus was found to be the most sensitive. After 2 h of aerobic incubation, no viable organisms could be detected. B. fragilis was intermediately sensitive to oxygen with no viable organisms detected after 5 h of aerobic incubation. C. perfringens was the least sensitive. Under conditions of aerobic incubation, viable organisms survived for 10 h. During the experiments with Clostridium, no spores were observed by spore staining. PMID:173238

Walden, William C.; Hentges, David J.

1975-01-01

3

Multiple symbol differential detection  

NASA Technical Reports Server (NTRS)

A differential detection technique for multiple phase shift keying (MPSK) signals is provided which uses a multiple symbol observation interval on the basis of which a joint decision is made regarding the phase of the received symbols. In accordance with the invention, a first difference phase is created between first and second received symbols. Next, the first difference phase is correlated with the possible values thereof to provide a first plurality of intermediate output signals. A second difference phase is next created between second and third received symbols. The second difference phase is correlated with plural possible values thereof to provide a second plurality of intermediate output signals. Next, a third difference phase is created between the first and third symbols. The third difference phase is correlated with plural possible values thereof to provide a third plurality of intermediate output signals. Each of the first plurality of intermediate outputs are combined with each of the second plurality of intermediate outputs and each of the third plurality of intermediate outputs to provide a plurality of possible output values. Finally, a joint decision is made by choosing from the plurality of possible output values the value which represents the best combined correlation of the first, second and third difference values with the possible values thereof.

Divsalar, Dariush (inventor); Simon, Marvin K. (inventor)

1991-01-01

4

Label-Free Morphology-Based Prediction of Multiple Differentiation Potentials of Human Mesenchymal Stem Cells for Early Evaluation of Intact Cells  

PubMed Central

Precise quantification of cellular potential of stem cells, such as human bone marrow–derived mesenchymal stem cells (hBMSCs), is important for achieving stable and effective outcomes in clinical stem cell therapy. Here, we report a method for image-based prediction of the multiple differentiation potentials of hBMSCs. This method has four major advantages: (1) the cells used for potential prediction are fully intact, and therefore directly usable for clinical applications; (2) predictions of potentials are generated before differentiation cultures are initiated; (3) prediction of multiple potentials can be provided simultaneously for each sample; and (4) predictions of potentials yield quantitative values that correlate strongly with the experimental data. Our results show that the collapse of hBMSC differentiation potentials, triggered by in vitro expansion, can be quantitatively predicted far in advance by predicting multiple potentials, multi-lineage differentiation potentials (osteogenic, adipogenic, and chondrogenic) and population doubling potential using morphological features apparent during the first 4 days of expansion culture. In order to understand how such morphological features can be effective for advance predictions, we measured gene-expression profiles of the same early undifferentiated cells. Both senescence-related genes (p16 and p21) and cytoskeleton-related genes (PTK2, CD146, and CD49) already correlated to the decrease of potentials at this stage. To objectively compare the performance of morphology and gene expression for such early prediction, we tested a range of models using various combinations of features. Such comparison of predictive performances revealed that morphological features performed better overall than gene-expression profiles, balancing the predictive accuracy with the effort required for model construction. This benchmark list of various prediction models not only identifies the best morphological feature conversion method for objective potential prediction, but should also allow clinicians to choose the most practical morphology-based prediction method for their own purposes. PMID:24705458

Sasaki, Hiroto; Takeuchi, Ichiro; Okada, Mai; Sawada, Rumi; Kanie, Kei; Kiyota, Yasujiro; Honda, Hiroyuki; Kato, Ryuji

2014-01-01

5

Multiple Intelligences for Differentiated Learning  

ERIC Educational Resources Information Center

There is an intricate literacy to Gardner's multiple intelligences theory that unlocks key entry points for differentiated learning. Using a well-articulated framework, rich with graphic representations, Williams provides a comprehensive discussion of multiple intelligences. He moves the teacher and students from curiosity, to confidence, to…

Williams, R. Bruce

2007-01-01

6

Integration of Multiple Signaling Regulates through Apoptosis the Differential Osteogenic Potential of Neural Crest-Derived and Mesoderm-Derived Osteoblasts  

PubMed Central

Neural crest-derived (FOb) and mesoderm-derived (POb) calvarial osteoblasts are characterized by distinct differences in their osteogenic potential. We have previously demonstrated that enhanced activation of endogenous FGF and Wnt signaling confers greater osteogenic potential to FOb. Apoptosis, a key player in bone formation, is the main focus of this study. In the current work, we have investigated the apoptotic activity of FOb and POb cells during differentiation. We found that lower apoptosis, as measured by caspase-3 activity is a major feature of neural crest-derived osteoblast which also have higher osteogenic capacity. Further investigation indicated TGF-? signaling as main positive regulator of apoptosis in these two populations of calvarial osteoblasts, while BMP and canonical Wnt signaling negatively regulate the process. By either inducing or inhibiting these signaling pathways we could modulate apoptotic events and improve the osteogenic potential of POb. Taken together, our findings demonstrate that integration of multiple signaling pathways contribute to imparting greater osteogenic potential to FOb by decreasing apoptosis. PMID:23536803

Li, Shuli; Meyer, Nathaniel P.; Quarto, Natalina; Longaker, Michael T.

2013-01-01

7

Hertz Potentials and Differential Geometry  

E-print Network

. . . . . . . . . . . . . . . . . . . . . . . 34 C. Non-Trivial Topology . . . . . . . . . . . . . . . . . . . . . 35 V HERTZ POTENTIALS AND DIFFERENTIAL GEOMETRY : 36 A. Hertz Potential 2-Forms . . . . . . . . . . . . . . . . . . . 36 B. Gauge Invariance... . . . . . . . . . . . . . . . . . . . . . . . 37 C. Scalar Hertz Potentials . . . . . . . . . . . . . . . . . . . . 39 D. Higher-Order Gauge Transformations . . . . . . . . . . . . 47 E. Non-Trivial Topology . . . . . . . . . . . . . . . . . . . . . 49 v CHAPTER Page VI APPLICATIONS...

Bouas, Jeffrey David

2011-08-08

8

Full potential multiple scattering theory  

SciTech Connect

A practical method for performing self-consistent electronic structure calculations based upon full-potential multiple-scattering theory is presented. Solutions to the single site Schroedinger equation are obtained by solving coupled channel integral equations for a potential which is analytically continued out to the circumscribing sphere. This potential coincides with the full cell potential inside each atomic cell. Scattering matrices and wavefunctions for the full cell potential are obtained from surface Wronskian relations. The charge density is obtained from the single particle Green`s function. This Green`s function is computed using the cell scattering matrices and wavefunctions using the layer multiple scattering theory. Self consistent solutions require a solution at each iteration to the Poisson equation. The Poisson equation is solved using a variational cellular method. In the approach a local solution to each cell is augmented by adding a series of regular harmonics (solutions to Laplace`s equation). Minimizing the coulomb energy, subject to continuity of the potential across all cell boundary provides an expression for the coefficients of the regular harmonics. This method is applied to BCC Nb. Calculated properties converge well in angular momentum and show comparable accuracy to full potential linearized muffin-tin orbital calculations.

MacLaren, J.M. [Tulane Univ., New Orleans, LA (United States). Dept. of Physics

1994-10-20

9

Multiple-Bit Differential Detection of OQPSK  

NASA Technical Reports Server (NTRS)

A multiple-bit differential-detection method has been proposed for the reception of radio signals modulated with offset quadrature phase-shift keying (offset QPSK or OQPSK). The method is also applicable to other spectrally efficient offset quadrature modulations. This method is based partly on the same principles as those of a multiple-symbol differential-detection method for M-ary QPSK, which includes QPSK (that is, non-offset QPSK) as a special case. That method was introduced more than a decade ago by the author of the present method as a means of improving performance relative to a traditional (two-symbol observation) differential-detection scheme. Instead of symbol-by-symbol detection, both that method and the present one are based on a concept of maximum-likelihood sequence estimation (MLSE). As applied to the modulations in question, MLSE involves consideration of (1) all possible binary data sequences that could have been received during an observation time of some number, N, of symbol periods and (2) selection of the sequence that yields the best match to the noise-corrupted signal received during that time. The performance of the prior method was shown to range from that of traditional differential detection for short observation times (small N) to that of ideal coherent detection (with differential encoding) for long observation times (large N).

Simon, Marvin

2005-01-01

10

Multiplate magnetorheological fluid limited slip differential clutch  

NASA Astrophysics Data System (ADS)

This study focuses on the design and characterization of a multi-plate magneto-rheological fluid (MRF) limited slip differential (LSD) clutch. Three-dimensional electromagnetic finite element analyzes are performed to optimize the MRF LSD clutch design. The torque transfer capacity of the clutch is predicted utilizing Bingham-Plastic constitutive model of the MRF. The MRF LSD clutch is tested at different velocities and applied magnetic fields. The clutch heating is also examined under different operating conditions to determine the thermal effects on the torque transfer performance of the multi-plate clutch.

Kavlicoglu, Barkan M.; Gordaninejad, Faramarz; Evrensel, Cahit A.; Fuchs, Alan; Korol, George

2003-08-01

11

Estimating differential expression from multiple indicators  

PubMed Central

Regardless of the advent of high-throughput sequencing, microarrays remain central in current biomedical research. Conventional microarray analysis pipelines apply data reduction before the estimation of differential expression, which is likely to render the estimates susceptible to noise from signal summarization and reduce statistical power. We present a probe-level framework, which capitalizes on the high number of concurrent measurements to provide more robust differential expression estimates. The framework naturally extends to various experimental designs and target categories (e.g. transcripts, genes, genomic regions) as well as small sample sizes. Benchmarking in relation to popular microarray and RNA-sequencing data-analysis pipelines indicated high and stable performance on the Microarray Quality Control dataset and in a cell-culture model of hypoxia. Experimental-data-exhibiting long-range epigenetic silencing of gene expression was used to demonstrate the efficacy of detecting differential expression of genomic regions, a level of analysis not embraced by conventional workflows. Finally, we designed and conducted an experiment to identify hypothermia-responsive genes in terms of monotonic time-response. As a novel insight, hypothermia-dependent up-regulation of multiple genes of two major antioxidant pathways was identified and verified by quantitative real-time PCR. PMID:24586062

Ilmjarv, Sten; Hundahl, Christian Ansgar; Reimets, Riin; Niitsoo, Margus; Kolde, Raivo; Vilo, Jaak; Vasar, Eero; Luuk, Hendrik

2014-01-01

12

Differential diagnosis of suspected multiple sclerosis: a consensus approach  

PubMed Central

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision. PMID:18805839

Miller, DH; Weinshenker, BG; Filippi, M; Banwell, BL; Cohen, JA; Freedman, MS; Galetta, SL; Hutchinson, M; Johnson, RT; Kappos, L; Kira, J; Lublin, FD; McFarland, HF; Montalban, X; Panitch, H; Richert, JR; Reingold, SC; Polman, CH

2008-01-01

13

Smooth Coordination and Navigation for Multiple Differential-Drive Robots  

E-print Network

, and report on the quality and ability of the robots using the two algorithms to navigate to their goalsSmooth Coordination and Navigation for Multiple Differential-Drive Robots Jamie Snape, Stephen J. Guy, Jur van den Berg, and Dinesh Manocha Abstract Multiple independent robots sharing the workspace

North Carolina at Chapel Hill, University of

14

Multiple symbol differential detection of uncoded and trellis coded MPSK  

NASA Technical Reports Server (NTRS)

A differential detection for MPSK, which uses a multiple symbol observation interval, is presented and its performance analyzed and simulated. The technique makes use of maximum-likelihood sequence estimation of the transmitted phases rather than symbol-by-symbol detection as in conventional differential detection. As such the performance of this multiple symbol detection scheme fills the gap between conventional (two-symbol observation) differentially coherent detection of MPSK and ideal coherent of MPSK with differential encoding. The amount of improvement gained over conventional differential detection depends on the number of phases, M, and the number of additional symbol intervals added to the observation. What is particularly interesting is that substantial performance improvement can be obtained for only one or two additional symbol intervals of observation. The analysis and simulation results presented are for uncoded and trellis coded MPSK.

Divsalar, Dariush; Simon, Marvin K.; Shahshahani, Mehrdad

1989-01-01

15

Multiple scattering theory for space filling potentials  

SciTech Connect

Multiple scattering theory (MST) provides an efficient technique for solving the wave equation for the special case of muffin-tin potentials. Here MST is extended to treat space filling non-muffin tin potentials and its validity, accuracy and efficiency are tested by application of the two dimensional empty lattice test. For this test it is found that the traditional formulation of MST does not coverage as the number of partial waves is increased. A simple modification of MST, however, allows this problem to be solved exactly and efficiently. 15 refs., 3 tabs.

Butler, W.H. (Oak Ridge National Lab., TN (USA)); Brown, R.G. (Duke Univ., Durham, NC (USA). Dept. of Physics); Nesbet, R.K. (IBM Research Div., San Jose, CA (USA). Almaden Research Center)

1990-01-01

16

[1983] Differential invariance of multiplicity on analytic varieties.pdf  

E-print Network

The question considered here is “How basic an invariant is multiplicity?” i.e. how does it behave under topological or differentiable deformation of the pair (A,P)'? Our main result is the .... [The implications 1=>2=>3 are trivial. For 3=>1, choose ...

17

Differential diagnosis of multiple sclerosis: contribution of magnetic resonance techniques.  

PubMed

It is widely accepted that magnetic resonance imaging (MRI) findings are not totally specific for the diagnosis of multiple sclerosis. White matter lesions that mimic those of multiple sclerosis may be detected in both normal volunteers and patients harbouring different diseases. Virtually all the characteristic features of multiple sclerosis are sometimes encountered in other conditions affecting predominantly the white matter. Different conditions such as vasculitis, subcortical atherosclerotic leukoencephalopathy, Lyme disease, or acute disseminated encephalomyelitis can be virtually indistinguishable from multiple sclerosis on conventional MR images. Also the FLAIR technique adds little to the differential diagnosis. The calculation of magnetisation transfer ratio (MT ratio) may be useful to better characterise some entities, such as vasculitis, from multiple sclerosis. PMID:9647278

Triulzi, F; Scotti, G

1998-05-01

18

Multiple-symbol differential detection of GMSK for mobile communications  

Microsoft Academic Search

A new multiple differential detection (MDD) sequence estimator is described which uses a decision feedback for the demodulation of a GMSK signal. This technique is based upon a maximum-likelihood sequence estimation of the transmitted phases rather than on a symbol-by-symbol detection. An upper and a lower bound on the bit error probability of the described detector in the case of

Andrea Abrardo; Giuliano Benelli; Gianfranco R. Cau

1995-01-01

19

Differential and limited expression of mutant alleles in multiple myeloma.  

PubMed

Recent work has delineated mutational profiles in multiple myeloma and reported a median of 52 mutations per patient, as well as a set of commonly mutated genes across multiple patients. In this study, we have used deep sequencing of RNA from a subset of these patients to evaluate the proportion of expressed mutations. We find that the majority of previously identified mutations occur within genes with very low or no detectable expression. On average, 27% (range, 11% to 47%) of mutated alleles are found to be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type allele is suppressed. Even in the absence of an overall change in gene expression, the presence of differential allelic expression within malignant cells highlights the important contribution of RNA-sequencing in identifying clinically significant mutational changes relevant to our understanding of myeloma biology and also for therapeutic applications. PMID:25237203

Rashid, Naim U; Sperling, Adam S; Bolli, Niccolo; Wedge, David C; Van Loo, Peter; Tai, Yu-Tzu; Shammas, Masood A; Fulciniti, Mariateresa; Samur, Mehmet K; Richardson, Paul G; Magrangeas, Florence; Minvielle, Stephane; Futreal, P Andrew; Anderson, Kenneth C; Avet-Loiseau, Herve; Campbell, Peter J; Parmigiani, Giovanni; Munshi, Nikhil C

2014-11-13

20

Fabry Disease - Underestimated in the Differential Diagnosis of Multiple Sclerosis?  

PubMed Central

Objective Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings. Methods Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease. Results Four patients were identified as having a “possible” history of MS, and 7 patients as “definite” cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load. Conclusion There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis. PMID:24015197

Bottcher, Tobias; Rolfs, Arndt; Tanislav, Christian; Bitsch, Andreas; Kohler, Wolfgang; Gaedeke, Jens; Giese, Anne-Katrin; Kolodny, Edwin H.; Duning, Thomas

2013-01-01

21

Multiple Symbol Differential Stack Algorithm for Unitary Space-Frequency Modulation  

Microsoft Academic Search

Differential unitary space-frequency modulation reduces the complexity of multiple-input multiple-output-orthogonal frequency division multiplexing (MIMO-OFDM) systems significantly. But the conventional single symbol differential detection (SSDD) results in a high error floor over a severe multipath spreading channel. To overcome this limitation, a multiple symbol differential stack algorithm is proposed by embedding a recursion of maximum-likelihood metric in the stack algorithm. The

Ying Li; Xin Wang; Jibo Wei

2007-01-01

22

MULTIPLE SOLUTIONS TO LOGARITHMIC SCHRODINGER EQUATIONS WITH PERIODIC POTENTIAL  

E-print Network

^ RN Q(x)u2 log u2 dx. Problem (1.1) admits applications related to quantum mechanics, quantum opticsMULTIPLE SOLUTIONS TO LOGARITHMIC SCHR¨ODINGER EQUATIONS WITH PERIODIC POTENTIAL MARCO SQUASSINA AND ANDRZEJ SZULKIN Abstract. We study a class of logarithmic Schr¨odinger equations with periodic potential

Szulkin, Andrzej

23

THY-1 Receptor Expression Differentiates Cardiosphere-Derived Cells with Divergent Cardiogenic Differentiation Potential  

PubMed Central

Summary Despite over a decade of intense research, the identity and differentiation potential of human adult cardiac progenitor cells (aCPC) remains controversial. Cardiospheres have been proposed as a means to expand aCPCs in vitro, but the identity of the progenitor cell within these 3D structures is unknown. We show that clones derived from cardiospheres could be subdivided based on expression of thymocyte differentiation antigen 1 (THY-1/CD90) into two distinct populations that exhibit divergent cardiac differentiation potential. One population, which is CD90+, expressed markers consistent with a mesenchymal/myofibroblast cell. The second clone type was CD90? and could form mature, functional myocytes with sarcomeres albeit at a very low rate. These two populations of cardiogenic clones displayed distinct cell surface markers and unique transcriptomes. Our study suggests that a rare aCPC exists in cardiospheres along with a mesenchymal/myofibroblast cell, which demonstrates incomplete cardiac myocyte differentiation. PMID:24936447

Gago-Lopez, Nuria; Awaji, Obinna; Zhang, Yiqiang; Ko, Christopher; Nsair, Ali; Liem, David; Stempien-Otero, April; MacLellan, W. Robb

2014-01-01

24

LETTER TO THE EDITOR: Potential in stochastic differential equations: novel construction  

NASA Astrophysics Data System (ADS)

There is a whole range of emergent phenomena in a complex network such as robustness, adaptiveness, multiple-equilibrium, hysteresis, oscillation and feedback. Those non-equilibrium behaviours can often be described by a set of stochastic differential equations. One persistent important question is the existence of a potential function. Here we demonstrate that a dynamical structure built into stochastic differential equation allows us to construct such a global optimization potential function. We present an explicit construction procedure to obtain the potential and relevant quantities. In the procedure no reference to the Fokker-Planck equation is needed. The availability of the potential suggests that powerful statistical mechanics tools can be used in nonequilibrium situations.

Ao, P.

2004-01-01

25

Differential Encoding for Multiple Amplitude and Phase Shift Keying Systems  

Microsoft Academic Search

Because of the symmetry in most two-dimensional signal constellations, ambiguities exist at the receiver as to the exact phase orientation of the received signal set. In PSK systems, this ambiguity is resolved by the use of differential encoding. This paper presents differential encoding techniques which can be used with a variety of symmetric signal sets to remove their phase ambiguity.

1978-01-01

26

LeafWaterPotential ofDifferentially Salinized Plants  

Microsoft Academic Search

Waterandosmotic potential energies were measuredwiththermocouple psv- chrometers, atintervals during a 4-week period, ingrowing leaves ofbean(Phaseolus vulgaris, var.BlueLake) andbarley (Hordeum vulgare, var.Liberty) plants having rootsequally split between 2 differentially salinized nutrient solutions. Theosmoticpotentials ofplants with halftheir rootsinsaline solutions wereabouthalfway between theosmoticpotentials ofplants growninnonsaline solutions andthose growninsaline solutions. By theendofthe4-week measurementperiod, thebeansandbarley werealmostmature.The finaldryweights of shoots ofplants withhalftheir rootsinsaline solutions were abouthalfway

W. R. Gardner; C. Gerloff

1969-01-01

27

Computing derivatives of a gravity potential by using automatic differentiation  

NASA Astrophysics Data System (ADS)

A new method, based on automatic differentiation technique, has been proposed in this paper to compute the derivatives of the gravity potential. Using this method we can obtain derivatives up to any order. Instead of explicit expressions of the derivatives we use an iterative scheme to simultaneously compute the value of all the desired derivatives. The algorithm here presented can be easily parallelized by using OpenMP with the consequent improvement in CPU-time efficiency.

Abad, Alberto; Lacruz, Elvis

2013-10-01

28

Biophysical Characteristics Reveal Neural Stem Cell Differentiation Potential  

PubMed Central

Background Distinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers. Methodology/Principal Findings We used dielectrophoresis (DEP) to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates. Conclusions/Significance We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors. PMID:21980464

Mulhall, Hayley J.; Marchenko, Steve A.; Hoettges, Kai F.; Estrada, Laura C.; Lee, Abraham P.; Hughes, Michael P.; Flanagan, Lisa A.

2011-01-01

29

Differential host defense against multiple parasites in ants  

Microsoft Academic Search

Host–parasite interactions are ideal systems for the study of coevolutionary processes. Although infections with multiple\\u000a parasite species are presumably common in nature, most studies focus on the interactions of a single host and a single parasite.\\u000a To the best of our knowledge, we present here the first study on the dependency of parasite virulence and host resistance\\u000a in a multiple

Christoph von Beeren; Munetoshi Maruyama; Rosli Hashim; Volker Witte

2011-01-01

30

Application of Differential Evolution Algorithm on Self-Potential Data  

PubMed Central

Differential evolution (DE) is a population based evolutionary algorithm widely used for solving multidimensional global optimization problems over continuous spaces, and has been successfully used to solve several kinds of problems. In this paper, differential evolution is used for quantitative interpretation of self-potential data in geophysics. Six parameters are estimated including the electrical dipole moment, the depth of the source, the distance from the origin, the polarization angle and the regional coefficients. This study considers three kinds of data from Turkey: noise-free data, contaminated synthetic data, and Field example. The differential evolution and the corresponding model parameters are constructed as regards the number of the generations. Then, we show the vibration of the parameters at the vicinity of the low misfit area. Moreover, we show how the frequency distribution of each parameter is related to the number of the DE iteration. Experimental results show the DE can be used for solving the quantitative interpretation of self-potential data efficiently compared with previous methods. PMID:23240004

Li, Xiangtao; Yin, Minghao

2012-01-01

31

Differential encoding for multiple amplitude and phase shift keying systems  

NASA Technical Reports Server (NTRS)

Because of the symmetry in most two-dimensional signal constellations, ambiguities exist at the receiver as to the exact phase orientation of the received signal set. In PSK systems, this ambiguity is resolved by the use of differential encoding. This paper presents differential encoding techniques which can be used with a variety of symmetric signal sets to remove their phase ambiguity. While not proven to be optimum, the techniques do have low performance penalties relative to the uncoded performance. The key to reducing the performance penalty is to use the minimum amount of differential encoding necessary to resolve the ambiguity. Examples of encoding techniques for several common signal constellations are given, including their performance penalties.

Weber, W. J., III

1978-01-01

32

Multiple bit differential detection of offset quadrature phase-shift-keying  

NASA Technical Reports Server (NTRS)

Analogous to multiple symbol differential detectionof quadrature phase-shift-keying (QPSK), a multiple bit differential detection scheme is described for offset QPSK that also exhibits continuous improvement in performance with increasing observation interval. Being derived from maximum-likelihood (ML) considerations, the proposed scheme is purported to be the most power efficient scheme for such a modulation and detection method. Extension of the results to shaped offset QPSK is also possible.

Simon, M.

2003-01-01

33

Differential Proteomics Reveals Multiple Components in Retrogradely Transported  

E-print Network

differential proteomics ap- proach in the freshwater mollusk Lymnaea stagnalis. This invertebrate model nervous injury-correlated retro- gradely transported proteins in nerves of the mollusk Lymnaea. A comprehensive of RGP51 expression by RNA interference inhibits regener- ative outgrowth of adult Lymnaea neurons

Fainzilber, Michael

34

Multiple Hypnotizabilities: Differentiating the Building Blocks of Hypnotic Response  

ERIC Educational Resources Information Center

Although hypnotizability can be conceptualized as involving component subskills, standard measures do not differentiate them from a more general unitary trait, partly because the measures include limited sets of dichotomous items. To overcome this, the authors applied full-information factor analysis, a sophisticated analytic approach for…

Woody, Erik Z.; Barnier, Amanda J.; McConkey, Kevin M.

2005-01-01

35

Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients  

PubMed Central

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls. PMID:23401793

Messinis, L.; Kosmidis, M. H.; Vlahou, C.; Malegiannaki, A. C.; Gatzounis, G.; Dimisianos, N.; Karra, A.; Kiosseoglou, G.; Gourzis, P.; Papathanasopoulos, P.

2013-01-01

36

A study of impulsive multiterm fractional differential equations with single and multiple base points and applications.  

PubMed

We discuss the existence and uniqueness of solutions for initial value problems of nonlinear singular multiterm impulsive Caputo type fractional differential equations on the half line. Our study includes the cases for a single base point fractional differential equation as well as multiple base points fractional differential equation. The asymptotic behavior of solutions for the problems is also investigated. We demonstrate the utility of our work by applying the main results to fractional-order logistic models. PMID:24578623

Liu, Yuji; Ahmad, Bashir

2014-01-01

37

System for measuring multiphase flow using multiple pressure differentials  

DOEpatents

An improved method and system for measuring a multi-phase flow in a pressure flow meter. An extended throat venturi is used and pressure of the multi-phase flow is measured at three or more positions in the venturi, which define two or more pressure differentials in the flow conduit. The differential pressures are then used to calculate the mass flow of the gas phase, the total mass flow, and the liquid phase. The system for determining the mass flow of the high void fraction fluid flow and the gas flow includes taking into account a pressure drop experienced by the gas phase due to work performed by the gas phase in accelerating the liquid phase.

Fincke, James R. (Idaho Falls, ID)

2003-01-01

38

Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing?  

PubMed

Ageing skeletal muscle displays declines in size, strength, and functional capacity. Given the acknowledged role that the systemic environment plays in reduced regeneration (Conboy et al. [2005] Nature 433: 760-764), the role of resident satellite cells (termed myoblasts upon activation) is relatively dismissed, where, multiple cellular divisions in-vivo throughout the lifespan could also impact on muscular deterioration. Using a model of multiple population doublings (MPD) in-vitro thus provided a system in which to investigate the direct impact of extensive cell duplications on muscle cell behavior. C(2) C(12) mouse skeletal myoblasts (CON) were used fresh or following 58 population doublings (MPD). As a result of multiple divisions, reduced morphological and biochemical (creatine kinase, CK) differentiation were observed. Furthermore, MPD cells had significantly increased cells in the S and decreased cells in the G1 phases of the cell cycle versus CON, following serum withdrawal. These results suggest continued cycling rather than G1 exit and thus reduced differentiation (myotube atrophy) occurs in MPD muscle cells. These changes were underpinned by significant reductions in transcript expression of: IGF-I and myogenic regulatory factors (myoD and myogenin) together with elevated IGFBP5. Signaling studies showed that decreased differentiation in MPD was associated with decreased phosphorylation of Akt, and with later increased phosphorylation of JNK1/2. Chemical inhibition of JNK1/2 (SP600125) in MPD cells increased IGF-I expression (non-significantly), however, did not enhance differentiation. This study provides a potential model and molecular mechanisms for deterioration in differentiation capacity in skeletal muscle cells as a consequence of multiple population doublings that would potentially contribute to the ageing process. PMID:21826704

Sharples, Adam P; Al-Shanti, Nasser; Lewis, Mark P; Stewart, Claire E

2011-12-01

39

Stem cells are captivating because they have the potential to make multiple cell types yet maintain their undifferentiated  

E-print Network

1575 Stem cells are captivating because they have the potential to make multiple cell types yet maintain their undifferentiated state. Recent studies of Drosophila and mammalian neural stem cells have shed light on how stem cells regulate self-renewal versus differentiation and have revealed

Doe, Chris

40

Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential[S  

PubMed Central

Arachidonic acid (AA) is a major PUFA that has been implicated in the regulation of adipogenesis. We examined the effect of a short exposure to AA at different stages of 3T3-L1 adipocyte differentiation. AA caused the upregulation of fatty acid binding protein 4 (FABP4/aP2) following 24 h of differentiation. This was mediated by the prostaglandin F2? (PGF2?), as inhibition of cyclooxygenases or PGF2? receptor signaling counteracted the AA-mediated aP2 induction. In addition, calcium, protein kinase C, and ERK are all key elements of the pathway through which AA induces the expression of aP2. We also show that treatment with AA during the first 24 h of differentiation upregulates the expression of the transcription factor Fos-related antigen 1 (Fra-1) via the same pathway. Finally, treatment with AA for 24 h at the beginning of the adipocyte differentiation is sufficient to inhibit the late stages of adipogenesis through a Fra-1-dependent pathway, as Fra-1 knockdown rescued adipogenesis. Our data show that AA is able to program the differentiation potential of preadipocytes by regulating gene expression at the early stages of adipogenesis. PMID:25325755

Nikolopoulou, Evanthia; Papacleovoulou, Georgia; Jean-Alphonse, Frederic; Grimaldi, Giulia; Parker, Malcolm G.; Hanyaloglu, Aylin C.; Christian, Mark

2014-01-01

41

Differential Regulation of the Multiple Flagellins in Spirochetes?  

PubMed Central

The expression of flagellin genes in most bacteria is typically regulated by the flagellum-specific sigma28 factor FliA, and an anti-sigma28 factor, FlgM. However, the regulatory hierarchy in several bacteria that have multiple flagellins is more complex. In these bacteria, the flagellin genes are often transcribed by at least two different sigma factors. The flagellar filament in spirochetes consists of one to three FlaB core proteins and at least one FlaA sheath protein. Here, the genetically amenable bacterium Brachyspira hyodysenteriae was used as a model spirochete to investigate the regulation of its four flagellin genes, flaA, flaB1, flaB2, and flaB3. We found that the flaB1 and flaB2 genes are regulated by sigma28, whereas the flaA and flaB3 genes are controlled by sigma70. The analysis of a flagellar motor switch fliG mutant further supported this proposition; in the mutant, the transcription of flaB1 and flaB2 was inhibited, but that of flaA and flaB3 was not. In addition, the continued expression of flaA and flaB3 in the mutant resulted in the formation of incomplete flagellar filaments that were hollow tubes and consisted primarily of FlaA. Finally, our recent studies have shown that each flagellin unit contributes to the stiffness of the periplasmic flagella, and this stiffness directly correlates with motility. The regulatory mechanism identified here should allow spirochetes to change the relative ratio of these flagellin proteins and, concomitantly, vary the stiffness of their flagellar filament. PMID:20304988

Li, Chunhao; Sal, Melanie; Marko, Michael; Charon, Nyles W.

2010-01-01

42

Habitat differentiation within the large-carnivore community of Norway's multiple-use landscapes  

Microsoft Academic Search

Summary 1. The re-establishment of large carnivores in Norway has led to increased conflicts and the adoption of regional zoning for these predators. When planning the future distribution of large car- nivores, it is important to consider details of their potential habitat tolerances and strength of inter- specific differentiation. We studied differentiation in habitat and kill sites within the large-carnivore

Roel May; Jiska van Dijk; Petter Wabakken; Jon E. Swenson; John D. C. Linnell; Barbara Zimmermann; John Odden; Hans C. Pedersen; Reidar Andersen; Arild Landa

2008-01-01

43

p53 Abnormalities and Potential Therapeutic Targeting in Multiple Myeloma  

PubMed Central

p53 abnormalities are regarded as an independent prognostic marker in multiple myeloma. Patients harbouring this genetic anomaly are commonly resistant to standard therapy. Thus, various p53 reactivating agents have been developed in order to restore its tumour suppressive abilities. Small molecular compounds, especially, have gained popularity in its efficacy against myeloma cells. For instance, promising preclinical results have steered both nutlin-3 and PRIMA-1 into phase I/II clinical trials. This review summarizes different modes of p53 inactivation in myeloma and highlights the current p53-based therapies that are being utilized in the clinic. Finally, we discuss the potential and promise that the novel small molecules possess for clinical application in improving the treatment outcome of myeloma. PMID:25028664

Teoh, P. J.; Chng, W. J.

2014-01-01

44

Sigma-2 Receptor as Potential Indicator of Stem Cell Differentiation  

PubMed Central

Purpose The sigma-2 (?2) receptor is a potential biomarker of proliferative status of solid tumors. Specific synthetic probes using N-substituted-9-azabicyclo[3.3.1]nonan-3?-yl carbamate analogs have been designed and implemented for experimental cancer diagnosis and therapy. Procedures We employed the fluorescently-labeled ?2 receptor probe, SW120, to evaluate ?2 receptor expression in human stem cells (SC), including: bone marrow stromal (BMSC), neural progenitor (NPC), amniotic fluid (AFSC), hematopoetic (HSC) and embryonic stem cells (ESC). We concurrently evaluated the intensity of SW120 and 5-ethynyl-2?-deoxyuridine (EdU) relative to passage number and multipotency. Results We substantiated significantly higher ?2 receptor density among proliferating SC relative to lineage-restricted cell types. Additionally, cellular internalization of the ?2 receptor in SC was consistent with receptor-mediated endocytosis and confocal microscopy indicated SW120 specific co-localization with a fluorescent marker of lysosomes in all SC imaged. Conclusion These results suggest that ?2 receptors may serve to monitor stem cell differentiation in future experimental studies. PMID:21614680

Haller, Jodi L.; Panyutin, Irina; Chaudhry, Aneeka; Zeng, Chenbo; Mach, Robert H.; Frank, Joseph A.

2011-01-01

45

Studying Differential Item Functioning via Latent Variable Modeling: A Note on a Multiple-Testing Procedure  

ERIC Educational Resources Information Center

This note is concerned with a latent variable modeling approach for the study of differential item functioning in a multigroup setting. A multiple-testing procedure that can be used to evaluate group differences in response probabilities on individual items is discussed. The method is readily employed when the aim is also to locate possible…

Raykov, Tenko; Marcoulides, George A.; Lee, Chun-Lung; Chang, Chi

2013-01-01

46

Application of automatic differentiation to trajectory optimization via direct multiple shooting  

NASA Astrophysics Data System (ADS)

Automatic differentiation, also called computational differentiation and algorithmic differentiation, is the process of computing the derivatives or Taylor series of functions from the computer source code implementing the functions. To date, general-purpose trajectory optimization codes have relied on finite-differencing to compute the gradients needed by the nonlinear programming (NLP) algorithms within the codes. These codes typically support the selection of an arbitrary objective and constraint set from a library of a few hundred output variables. The use of automatic differentiation in these trajectory optimization programs can provide objective and constraint gradients to the same precision as the underlying functions without requiring the generation of hundreds of analytic derivative expressions by hand or via symbolic algebra packages. This work combines automatic differentiation with a direct multiple shooting method and uses the resulting method to solve a pair of example problems. The first is the well-known lunar launch problem, while the second is a launch vehicle ascent problem similar in complexity to that which would be computed by a program such as the Program to Optimize Simulated Trajectories (POST) for use in vehicle design studies. Results include comparisons of convergence behavior of the NLP problem and solution accuracy. Tests comparing the use of Euler angles versus quaternion elements as control variables demonstrate the versatility of automatic differentiation. For loose convergence levels automatic differentiation provided faster convergence than finite differencing on the launcher ascent problem. For tight accuracy requirements, automatic differentiation resulted in fewer major iterations on the lunar launch problem.

Garza, David Marcelo

2003-10-01

47

Multiple input multiple output underwater communication based on differential amplitude phase shift keying modulation.  

PubMed

The MIMO-OFDM combining time, spatial, and frequency diversity can effectively improve channel capacity and transmission efficiency of underwater acoustic (UWA) communication system. Space-time coding needs a large number of pilot signals to estimate UWA channel at the receiving end, which increases the complexity of the systems and limits the communication rate. For this, space-time coding combined with differential amplitude phase shift keying modulation (DAPSK) is proposed in this paper. It can complete the decoding without any prior knowledge of UWA channel, reducing the complexity of the system, saving channel resources and improving the transmission efficiency. Simulation analysis on UWA MIMO-OFDM systems shows this algorithm is feasible, which provides a feasible method for high-speed transmission in UWA communication. PMID:25236149

Xia, Xu; Yin, Jingwei

2014-04-01

48

SyStemCell: A Database Populated with Multiple Levels of Experimental Data from Stem Cell Differentiation Research  

PubMed Central

Elucidation of the mechanisms of stem cell differentiation is of great scientific interest. Increasing evidence suggests that stem cell differentiation involves changes at multiple levels of biological regulation, which together orchestrate the complex differentiation process; many related studies have been performed to investigate the various levels of regulation. The resulting valuable data, however, remain scattered. Most of the current stem cell-relevant databases focus on a single level of regulation (mRNA expression) from limited stem cell types; thus, a unifying resource would be of great value to compile the multiple levels of research data available. Here we present a database for this purpose, SyStemCell, deposited with multi-level experimental data from stem cell research. The database currently covers seven levels of stem cell differentiation-associated regulatory mechanisms, including DNA CpG 5-hydroxymethylcytosine/methylation, histone modification, transcript products, microRNA-based regulation, protein products, phosphorylation proteins and transcription factor regulation, all of which have been curated from 285 peer-reviewed publications selected from PubMed. The database contains 43,434 genes, recorded as 942,221 gene entries, for four organisms (Homo sapiens, Mus musculus, Rattus norvegicus, and Macaca mulatta) and various stem cell sources (e.g., embryonic stem cells, neural stem cells and induced pluripotent stem cells). Data in SyStemCell can be queried by Entrez gene ID, symbol, alias, or browsed by specific stem cell type at each level of genetic regulation. An online analysis tool is integrated to assist researchers to mine potential relationships among different regulations, and the potential usage of the database is demonstrated by three case studies. SyStemCell is the first database to bridge multi-level experimental information of stem cell studies, which can become an important reference resource for stem cell researchers. The database is available at http://lifecenter.sgst.cn/SyStemCell/. PMID:22807998

Zeng, Lingyao; Sun, Jiehuan; Li, Wei; Sun, Han; He, Ying; Li, Jing; Zhang, Guoqing; Wang, Chuan; Li, Yixue; Xie, Lu

2012-01-01

49

SyStemCell: a database populated with multiple levels of experimental data from stem cell differentiation research.  

PubMed

Elucidation of the mechanisms of stem cell differentiation is of great scientific interest. Increasing evidence suggests that stem cell differentiation involves changes at multiple levels of biological regulation, which together orchestrate the complex differentiation process; many related studies have been performed to investigate the various levels of regulation. The resulting valuable data, however, remain scattered. Most of the current stem cell-relevant databases focus on a single level of regulation (mRNA expression) from limited stem cell types; thus, a unifying resource would be of great value to compile the multiple levels of research data available. Here we present a database for this purpose, SyStemCell, deposited with multi-level experimental data from stem cell research. The database currently covers seven levels of stem cell differentiation-associated regulatory mechanisms, including DNA CpG 5-hydroxymethylcytosine/methylation, histone modification, transcript products, microRNA-based regulation, protein products, phosphorylation proteins and transcription factor regulation, all of which have been curated from 285 peer-reviewed publications selected from PubMed. The database contains 43,434 genes, recorded as 942,221 gene entries, for four organisms (Homo sapiens, Mus musculus, Rattus norvegicus, and Macaca mulatta) and various stem cell sources (e.g., embryonic stem cells, neural stem cells and induced pluripotent stem cells). Data in SyStemCell can be queried by Entrez gene ID, symbol, alias, or browsed by specific stem cell type at each level of genetic regulation. An online analysis tool is integrated to assist researchers to mine potential relationships among different regulations, and the potential usage of the database is demonstrated by three case studies. SyStemCell is the first database to bridge multi-level experimental information of stem cell studies, which can become an important reference resource for stem cell researchers. The database is available at http://lifecenter.sgst.cn/SyStemCell/. PMID:22807998

Yu, Jian; Xing, Xiaobin; Zeng, Lingyao; Sun, Jiehuan; Li, Wei; Sun, Han; He, Ying; Li, Jing; Zhang, Guoqing; Wang, Chuan; Li, Yixue; Xie, Lu

2012-01-01

50

[Baeocytes in the cyanobacterium Pleurocapsa sp.: characterization of the differentiated cells produced by multiple fission].  

PubMed

Electron microscopy of cyanobacteria Pleurocapsa sp. CALU 1126 revealed that multiple fission proceeds by successive binary fissions. The cultivation conditions were determined when the number of baeocytes (products of multiple fission) was comparable with that of macrocytes (products of binary fission), and cell sorting was achieved for the first time. Juvenile baeocytes were shown to differ from macrocytes in: (1) the absence of sheath; (2) the linear-peripheral configuration of their lamellar system; (3) lower content of phycobiliproteins and higher content of carotenoids; (4) the set of PSII polypeptides. Baeocytes can therefore be considered differentiated cells characterized by the uncoupling between energy and biosynthetic metabolism. PMID:18365724

Pinevich, A V; Averina, S G; Gavrilova, O V; Migunova, A V

2008-01-01

51

Differential Activities of Thalidomide and Isoprenoid Biosynthetic Pathway Inhibitors in Multiple Myeloma Cells  

PubMed Central

Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis was observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP. PMID:19646757

Holstein, Sarah A.; Tong, Huaxiang; Hohl, Raymond J.

2013-01-01

52

Adenosine: a potential mediator of immunosuppression in multiple organ failure  

Microsoft Academic Search

Multiple organ failure following a variety of insults, including, trauma, shock and pancreatitis, is the cause of 50–80% of all deaths in surgical intensive care units. In most patients, infections secondary to a general immunosuppressive state serve to trigger the development of multiple organ failure. This immunosuppressive state may be a consequence of excessive release of adenosine into the extracellular

György Haskó; Edwin A Deitch; Csaba Szabó; Zoltán H Németh; E. Sylvester Vizi

2002-01-01

53

Single- and Multiple-Objective Optimization with Differential Evolution and Neural Networks  

NASA Technical Reports Server (NTRS)

Genetic and evolutionary algorithms have been applied to solve numerous problems in engineering design where they have been used primarily as optimization procedures. These methods have an advantage over conventional gradient-based search procedures became they are capable of finding global optima of multi-modal functions and searching design spaces with disjoint feasible regions. They are also robust in the presence of noisy data. Another desirable feature of these methods is that they can efficiently use distributed and parallel computing resources since multiple function evaluations (flow simulations in aerodynamics design) can be performed simultaneously and independently on ultiple processors. For these reasons genetic and evolutionary algorithms are being used more frequently in design optimization. Examples include airfoil and wing design and compressor and turbine airfoil design. They are also finding increasing use in multiple-objective and multidisciplinary optimization. This lecture will focus on an evolutionary method that is a relatively new member to the general class of evolutionary methods called differential evolution (DE). This method is easy to use and program and it requires relatively few user-specified constants. These constants are easily determined for a wide class of problems. Fine-tuning the constants will off course yield the solution to the optimization problem at hand more rapidly. DE can be efficiently implemented on parallel computers and can be used for continuous, discrete and mixed discrete/continuous optimization problems. It does not require the objective function to be continuous and is noise tolerant. DE and applications to single and multiple-objective optimization will be included in the presentation and lecture notes. A method for aerodynamic design optimization that is based on neural networks will also be included as a part of this lecture. The method offers advantages over traditional optimization methods. It is more flexible than other methods in dealing with design in the context of both steady and unsteady flows, partial and complete data sets, combined experimental and numerical data, inclusion of various constraints and rules of thumb, and other issues that characterize the aerodynamic design process. Neural networks provide a natural framework within which a succession of numerical solutions of increasing fidelity, incorporating more realistic flow physics, can be represented and utilized for optimization. Neural networks also offer an excellent framework for multiple-objective and multi-disciplinary design optimization. Simulation tools from various disciplines can be integrated within this framework and rapid trade-off studies involving one or many disciplines can be performed. The prospect of combining neural network based optimization methods and evolutionary algorithms to obtain a hybrid method with the best properties of both methods will be included in this presentation. Achieving solution diversity and accurate convergence to the exact Pareto front in multiple objective optimization usually requires a significant computational effort with evolutionary algorithms. In this lecture we will also explore the possibility of using neural networks to obtain estimates of the Pareto optimal front using non-dominated solutions generated by DE as training data. Neural network estimators have the potential advantage of reducing the number of function evaluations required to obtain solution accuracy and diversity, thus reducing cost to design.

Rai, Man Mohan

2006-01-01

54

Control of matric water potential by temperature differential  

NASA Technical Reports Server (NTRS)

A method for controlling relative humidity based on temperature differentials, rather than on salt solutions, is described. This method has the following advantages: (1) it does not exhibit the anomalous CO2 solution effects that we have found to occur with salt solutions; (2) humidity is continuously adjustable without sample removal; (3) circulation of the atmosphere results in short equilibration times.

Palmer, R. J. Jr; Nienow, J. A.; Friedmann, E. I.

1987-01-01

55

Differential Diagnosis Tool for Parkinsonian Syndrome Using Multiple Structural Brain Measures  

PubMed Central

Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and cerebellar subtype (MSA-C) from Parkinson's disease is difficult in the early stage of the disease. To identify the correlative pattern of brain changes for differentiating parkinsonian syndromes, we applied discriminant analysis techniques by magnetic resonance imaging (MRI). T1-weighted volume data and diffusion tensor images were obtained by MRI in eighteen patients with MSA-C, 12 patients with MSA-P, 21 patients with Parkinson's disease, and 21 healthy controls. They were evaluated using voxel-based morphometry and tract-based spatial statistics, respectively. Discriminant functions derived by step wise methods resulted in correct classification rates of 0.89. When differentiating these diseases with the use of three independent variables together, the correct classification rate was the same as that obtained with step wise methods. These findings support the view that each parkinsonian syndrome has structural deviations in multiple brain areas and that a combination of structural brain measures can help to distinguish parkinsonian syndromes. PMID:23573171

Ota, Miho; Nakata, Yasuhiro; Ito, Kimiteru; Kamiya, Kouhei; Ogawa, Masafumi; Murata, Miho; Obu, Satoko; Kunugi, Hiroshi; Sato, Noriko

2013-01-01

56

Hyperhomocysteinemia potentiates hyperglycemia-induced inflammatory monocyte differentiation and atherosclerosis.  

PubMed

Hyperhomocysteinemia (HHcy) is associated with increased diabetic cardiovascular diseases. However, the role of HHcy in atherogenesis associated with hyperglycemia (HG) remains unknown. To examine the role and mechanisms by which HHcy accelerates HG-induced atherosclerosis, we established an atherosclerosis-susceptible HHcy and HG mouse model. HHcy was established in mice deficient in cystathionine ?-synthase (Cbs) in which the homocysteine (Hcy) level could be lowered by inducing transgenic human CBS (Tg-hCBS) using Zn supplementation. HG was induced by streptozotocin injection. Atherosclerosis was induced by crossing Tg-hCBS Cbs mice with apolipoprotein E-deficient (ApoE(-/-)) mice and feeding them a high-fat diet for 2 weeks. We demonstrated that HHcy and HG accelerated atherosclerosis and increased lesion monocytes (MCs) and macrophages (MØs) and further increased inflammatory MC and MØ levels in peripheral tissues. Furthermore, Hcy-lowering reversed circulating mononuclear cells, MC, and inflammatory MC and MC-derived MØ levels. In addition, inflammatory MC correlated positively with plasma Hcy levels and negatively with plasma s-adenosylmethionine-to-s-adenosylhomocysteine ratios. Finally, l-Hcy and d-glucose promoted inflammatory MC differentiation in primary mouse splenocytes, which was reversed by adenoviral DNA methyltransferase-1. HHcy and HG, individually and synergistically, accelerated atherosclerosis and inflammatory MC and MØ differentiation, at least in part, via DNA hypomethylation. PMID:25008174

Fang, Pu; Zhang, Daqing; Cheng, Zhongjian; Yan, Chenghui; Jiang, Xiaohua; Kruger, Warren D; Meng, Shu; Arning, Erland; Bottiglieri, Teodoro; Choi, Eric T; Han, Yaling; Yang, Xiao-Feng; Wang, Hong

2014-12-01

57

Serum-free spheroid suspension culture maintains mesenchymal stem cell proliferation and differentiation potential.  

PubMed

There have been many clinical trials recently using ex vivo-expanded human mesenchymal stem cells (MSCs) to treat several disease states such as graft-versus-host disease, acute myocardial infarction, Crohn's disease, and multiple sclerosis. The use of MSCs for therapy is expected to become more prevalent as clinical progress is demonstrated. However, the conventional 2-dimensional (2D) culture of MSCs is laborious and limited in scale potential. The large dosage requirement for many of the MSC-based indications further exacerbates this manufacturing challenge. In contrast, expanding MSCs as spheroids does not require a cell attachment surface and is amenable to large-scale suspension cell culture techniques, such as stirred-tank bioreactors. In the present study, we developed and optimized serum-free media for culturing MSC spheroids. We used Design of Experiment (DoE)-based strategies to systematically evaluate media mixtures and a panel of different components for effects on cell proliferation. The optimization yielded two prototype serum-free media that enabled MSCs to form aggregates and proliferate in both static and dynamic cultures. MSCs from spheroid cultures exhibited the expected immunophenotype (CD73, CD90, and CD105) and demonstrated similar or enhanced differentiation potential toward all three lineages (osteogenic, chondrogenic, adipogenic) as compared with serum-containing adherent MSC cultures. Our results suggest that serum-free media for MSC spheroids may pave the way for scale-up production of MSCs in clinically relevant manufacturing platforms such as stirred tank bioreactors. PMID:24616445

Alimperti, Stella; Lei, Pedro; Wen, Yuan; Tian, Jun; Campbell, Andrew M; Andreadis, Stelios T

2014-01-01

58

Potential role of daratumumab in the treatment of multiple myeloma  

PubMed Central

Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options. With the introduction of monoclonal antibodies for multiple myeloma, new options for treatment in the relapsed setting are on the horizon. Among the new immunologic agents is daratumumab (DARA), a humanized antibody to CD38 with potent multifaceted antitumor activity. Phase I and II clinical trials have demonstrated significant reduction in serum M-protein and bone marrow plasma cell percentage in refractory patients, with an acceptable toxicity profile. Moreover, ex vivo studies have shown that DARA may be particularly useful in combination with currently used anti-myeloma agents. With a recent breakthrough drug designation by the US Food and Drug Administration, DARA shows promise as mono- and combination therapy for the treatment of relapsed/refractory multiple myeloma. PMID:24971019

Khagi, Yulian; Mark, Tomer M

2014-01-01

59

Inflation differentials among the Euro area countries: Potential causes and consequences  

Microsoft Academic Search

In this paper we review the development, potential causes and macroeconomic implications of inflation differentials in the euro area. We also present some new evidence based on an estimated New Keynesian style model of the euro area economies. Our empirical analysis suggests that the observed inflation differentials since the start of EMU were mainly driven by temporary shocks combined with

Boris Hofmann; Hermann Remsperger

2005-01-01

60

Habitat differentiation within the large-carnivore community of Norway's multiple-use landscapes  

PubMed Central

The re-establishment of large carnivores in Norway has led to increased conflicts and the adoption of regional zoning for these predators. When planning the future distribution of large carnivores, it is important to consider details of their potential habitat tolerances and strength of inter-specific differentiation. We studied differentiation in habitat and kill sites within the large-carnivore community of south-eastern Norway. We compared habitat selection of the brown bear Ursus arctos L., Eurasian lynx Lynx lynx L., wolf Canis lupus L. and wolverine Gulo gulo L., based on radio-tracking data. Differences in kill site locations were explored using locations of documented predator-killed sheep Ovis aries L. We modelled each species’ selection for, and differentiation in, habitat and kill sites on a landscape scale using resource selection functions and multinomial logistic regression. Based on projected probability of occurrence maps, we estimated continuous patches of habitat within the study area. Although bears, lynx, wolves and wolverines had overlapping distributions, we found a clear differentiation for all four species in both habitat and kill sites. The presence of bears, wolves and lynx was generally associated with rugged, forested areas at lower elevations, whereas wolverines selected rugged terrain at higher elevations. Some degree of sympatry was possible in over 40% of the study area, although only 1·5% could hold all four large carnivores together. Synthesis and applications. A geographically differentiated management policy has been adopted in Norway, aimed at conserving viable populations of large carnivores while minimizing the potential for conflicts. Sympatry of all four carnivores will be most successful if regional zones are established of adequate size spanning an elevational gradient. High prey densities, low carnivore densities, low dietary overlap and scavenging opportunities have most probably led to reduced competitive exclusion. Although regional sympatry enhances the conservation of an intact guild of large carnivores, it may well increase conflict levels and resistance to carnivore conservation locally. PMID:19330031

May, Roel; van Dijk, Jiska; Wabakken, Petter; Swenson, Jon E; Linnell, John DC; Zimmermann, Barbara; Odden, John; Pedersen, Hans C; Andersen, Reidar; Landa, Arild

2008-01-01

61

Multiple Large Bowel Resections: Potential Risk Factor For Anastomotic Leak  

PubMed Central

Objectives Identify risk factors of anastomotic leak (AL) after large bowel resection (LBR) for ovarian cancer (OC) and compare outcomes between AL and no AL. Methods All cases of AL after LBR for OC between 01/01/1994-05/20/2011 were identified and matched 1:2 with controls for age (+/?5years), sub-stage (IIIA/IIIB;IIIC;IV), and date of surgery (+/?4years). Patient-specific and intraoperative risk factors, use of protective stomas, and outcomes were abstracted. A stratified conditional logistic regression model was fit to determine the association between each factor and AL. Results 42 AL cases were evaluable and matched with 84 controls. Two-thirds of the AL had stage IIIC disease and >90% of both cases and controls were cytoreduced to <1cm residual disease. No patient-specific risk factors were associated with AL (pre-operative albumin was not available for most patients). Rectosigmoid resection coupled with additional LBR was associated with AL (OR=2.73, 95%CI 1.13–6.59, P=0.025), and protective stomas were associated with decreased risk of AL (0% vs. 10.7%, P=0.024). AL had longer length of stay (P<0.001), were less likely to start chemotherapy (P=0.020), and had longer time to chemotherapy (P=0.007). Cases tended to have higher 90-day mortality (P=0.061) and were more likely to have poorer overall survival (HR=2.05, 95%CI 1.18–3.57, P=0.011). Conclusions Multiple LBRs appear to be associated with increased risk of AL and protective stomas with decreased risk. Since AL after OC cytoreduction significantly delays chemotherapy and negatively impacts survival, surgeons should strongly consider temporary diversion in selected patients (poor nutritional status, multiple LBRs, previous pelvic radiation, very low anterior resection, steroid use). PMID:23578541

Kalogera, Eleftheria; Dowdy, Sean C.; Mariani, Andrea; Weaver, Amy L.; Aletti, Giovanni; Bakkum-Gamez, Jamie N.; Cliby, William A.

2013-01-01

62

Differential meta-analysis of RNA-seq data from multiple studies  

PubMed Central

Background High-throughput sequencing is now regularly used for studies of the transcriptome (RNA-seq), particularly for comparisons among experimental conditions. For the time being, a limited number of biological replicates are typically considered in such experiments, leading to low detection power for differential expression. As their cost continues to decrease, it is likely that additional follow-up studies will be conducted to re-address the same biological question. Results We demonstrate how p-value combination techniques previously used for microarray meta-analyses can be used for the differential analysis of RNA-seq data from multiple related studies. These techniques are compared to a negative binomial generalized linear model (GLM) including a fixed study effect on simulated data and real data on human melanoma cell lines. The GLM with fixed study effect performed well for low inter-study variation and small numbers of studies, but was outperformed by the meta-analysis methods for moderate to large inter-study variability and larger numbers of studies. Conclusions The p-value combination techniques illustrated here are a valuable tool to perform differential meta-analyses of RNA-seq data by appropriately accounting for biological and technical variability within studies as well as additional study-specific effects. An R package metaRNASeq is available on the CRAN (http://cran.r-project.org/web/packages/metaRNASeq). PMID:24678608

2014-01-01

63

Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse.  

PubMed

Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or NCC-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function. These data show that Hoxa3 has multiple complex and tissue-specific functions during patterning, differentiation and morphogenesis of the thymus and parathyroids. PMID:25249461

Chojnowski, Jena L; Masuda, Kyoko; Trau, Heidi A; Thomas, Kirk; Capecchi, Mario; Manley, Nancy R

2014-10-01

64

Integrated Model of Multiple Kernel Learning and Differential Evolution for EUR/USD Trading  

PubMed Central

Currency trading is an important area for individual investors, government policy decisions, and organization investments. In this study, we propose a hybrid approach referred to as MKL-DE, which combines multiple kernel learning (MKL) with differential evolution (DE) for trading a currency pair. MKL is used to learn a model that predicts changes in the target currency pair, whereas DE is used to generate the buy and sell signals for the target currency pair based on the relative strength index (RSI), while it is also combined with MKL as a trading signal. The new hybrid implementation is applied to EUR/USD trading, which is the most traded foreign exchange (FX) currency pair. MKL is essential for utilizing information from multiple information sources and DE is essential for formulating a trading rule based on a mixture of discrete structures and continuous parameters. Initially, the prediction model optimized by MKL predicts the returns based on a technical indicator called the moving average convergence and divergence. Next, a combined trading signal is optimized by DE using the inputs from the prediction model and technical indicator RSI obtained from multiple timeframes. The experimental results showed that trading using the prediction learned by MKL yielded consistent profits. PMID:25097891

Deng, Shangkun; Sakurai, Akito

2014-01-01

65

Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis  

PubMed Central

Background This study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity. Methods CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC/MS/MS). Patients were stratified based on drug modifying therapies (DMTs) including interferon beta, glatiramer acetate and natalizumab. Results The level of plasma CEL, but not CML, was significantly higher in DMT-naïve MS patients when compared to HCs (P < 0.001). Among MS patients, 91% had higher than mean plasma CEL observed in HCs. DMTs reduced CML and CEL plasma levels by approximately 13% and 40% respectively. CML and CEL plasma levels correlated with the rate of MS clinical relapse. Conclusion Our results suggest that AGEs in general and CEL in particular could be useful biomarkers in MS clinical practice. Longitudinal studies are warranted to determine any causal relationship between changes in plasma level of AGEs and MS disease pathology. These studies will pave the way for use of AGE inhibitors and AGE-breaking agents as new therapeutic modalities in MS. PMID:21034482

2010-01-01

66

Nonlinear Schrodinger equations with multiple-well potential  

E-print Network

We consider the stationary solutions for a class of Schrodinger equations with a N-well potential and a nonlinear perturbation. By means of semiclassical techniques we prove that the dominant term of the ground state solutions is described by a N-dimensional Hamiltonian system, where the coupling term among the coordinates is a tridiagonal Toeplitz matrix. In particular we consider the case of N=4 wells, where we show the occurrence of spontaneous symmetry-breaking bifurcation effect. In particular, in the limit of large focusing nonlinearity we prove that the ground state stationary solutions consist of N wavefunctions localized on a single well.

Andrea Sacchetti

2011-07-29

67

Evaluation of various brain structures in multiple sclerosis with multimodality evoked potentials, blink reflex and nystagmography  

Microsoft Academic Search

Pattern reversal visual evoked potentials (VEP), blink reflexes, auditory brainstem evoked potentials (ABEP), spinal and scalp recorded somatosensory evoked potentials (SSEP), and nystagmographic records were investigated in 55 patients with multiple sclerosis (MS), who were separated in different categories of probability according to the clinical history, symptoms, and signs. The combined use of different electrophysiological methods forms a sensitive battery

W. Tackmann; H. Strenge; R. Barth; A. Sojka-Raytscheff

1980-01-01

68

Potential of Multiple Dendroclimatic Proxies for the Prairies?  

NASA Astrophysics Data System (ADS)

Concern to establish the nature and rate of climatic changes, should serve to reinforce our determination to understand similar details of the 'natural' (i.e. non-anthropogenic) variability of climate. Dendrochronology offers great potential for studying climatic and environmental variability at local and regional levels, because of the wide geographical distribution of suitable sites, high temporal resolution (annual or even seasonal), continuous and relatively long, absolutely-dated, well replicated and environmentally sensitive (i.e. accurate) characteristics of tree rings. Patterns within the annual rings of Quercus (oak) species, suggest that environmental factors influence the size and density of vessels within the ring, either by acting as a limiting factor for growth or through fine tuning of the wood structure to environmental factors. The purpose of this study is to investigate growth responses (annual, early- and late-wood widths) of Q. macrocarpa to regional climatic variability affecting the Canadian Prairies. Results indicate that annual ring widths, as well as early- and late- wood chronologies from southeastern Saskatchewan capture regional signals related to moisture and drought conditions. Correlations suggest that late-wood measurements are more strongly representative of annual ring-widths, than are early-wood widths, and can therefore be applied for investigating seasonal fluctuations in climatic data. Correlations with precipitation and PDSI values indicate that annual, early- and latewood chronologies are useful proxies for investigating large scale climatic fluctuations, and present the opportunity for further investigation of the effects of indices that represent major modes of climate variability, such as the effects of El Niño/Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) patterns that are thought to influence climate within the Prairie region. This study is novel in terms of sub-annual analysis of tree-rings in a region that previously lacked dendrochronological research.

Vanstone, J. R.; Sauchyn, D. J.

2009-05-01

69

Neuronal differentiation potential of human adipose-derived mesenchymal stem cells.  

PubMed

Adult mesenchymal stem cells derived from adipose tissue (A-MSC) have the capacity to differentiate in vitro into mesenchymal as well as endodermal and ectodermal cell lineages. We investigated the neuronal differentiation potential of human A-MSC with a protocol which included sphere formation and sequential culture in brain-derived neurotrophic factor (BDNF) and retinoic acid (RA). After 30 days, about 57% A-MSC showed morphological, immunocytochemical and electrophysiological evidence of initial neuronal differentiation. In fact, A-MSC displayed elongated shape with protrusion of two or three cellular processes, selectively expressed nestin and neuronal molecules (including GABA receptor and tyroxine hydroxilase) in the absence of glial phenotypic markers. Differentiated cells showed negative membrane potential (-60 mV), delayed rectifier potassium currents and TTX-sensitive sodium currents. Such changes were stable for at least 7 days after removal of differentiation medium. In view of these results and the easy availability of adipose tissue, A-MSC may be a ready source of adult MSC with neuronal differentiation potential, an useful tool to treat neurodegenerative diseases. PMID:18564036

Anghileri, Elena; Marconi, Silvia; Pignatelli, Angela; Cifelli, Pierangelo; Galié, Mirco; Sbarbati, Andrea; Krampera, Mauro; Belluzzi, Ottorino; Bonetti, Bruno

2008-10-01

70

Telomerase reconstitution immortalizes human fetal hepatocytes without disrupting their differentiation potential  

Microsoft Academic Search

Background & Aims: The availability of in vitro expandable human hepatocytes would greatly advance liver-directed cell therapies. Therefore, we examined whether human fetal hepatocytes are amenable to telomerase-mediated immortalization without inducing a transformed phenotype and disrupting their differentiation potential. Telomerase is a ribonucleoprotein that plays a pivotal role in maintaining telomere length and chromosome stability. Human somatic cells, including hepatocytes,

Henning Wege; Hai T. Le; Michael S. Chui; Li Liu; Jian Wu; Ranjit Giri; Harmeet Malhi; Baljit S. Sappal; Vinay Kumaran; Sanjeev Gupta; Mark A. Zern

2003-01-01

71

Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging  

Microsoft Academic Search

BACKGROUND: Dental pulp stem cells (DPSCs) can be driven into odontoblast, osteoblast, and chondrocyte lineages in different inductive media. However, the differentiation potential of naive DPSCs after serial passaging in the routine culture system has not been fully elucidated. RESULTS: DPSCs were isolated from human\\/rat dental pulps by the magnetic activated cell sorting based on STRO-1 expression, cultured and passaged

Jinhua Yu; Huixia He; Chunbo Tang; Guangdong Zhang; Yuanfei Li; Ruoning Wang; Junnan Shi; Yan Jin

2010-01-01

72

Multiple isoforms of mitochondrial glutathione S-transferases and their differential induction under oxidative stress.  

PubMed Central

The mitochondrial respiratory chain, which consumes approx. 85-90% of the oxygen utilized by cells, is a major source of reactive oxygen species (ROS). Mitochondrial genetic and biosynthetic systems are highly susceptible to ROS toxicity. Intramitochondrial glutathione (GSH) is a major defence against ROS. In the present study, we have investigated the nature of the glutathione S-transferase (GST) pool in mouse liver mitochondria, and have purified three distinct forms of GST: GSTA1-1 and GSTA4-4 of the Alpha family, and GSTM1-1 belonging to the Mu family. The mitochondrial localization of these multiple GSTs was confirmed using a combination of immunoblot analysis, protease protection assay, enzyme activity, N-terminal amino acid sequencing, peptide mapping and confocal immunofluorescence analysis. Additionally, exogenously added 4-hydroxynonenal (HNE), a reactive byproduct of lipid peroxidation, to COS cells differentially affected the cytosolic and mitochondrial GSH pools in a dose- and time-dependent manner. Our results show that HNE-mediated mitochondrial oxidative stress caused a decrease in the GSH pool, increased membrane lipid peroxidation, and increased levels of GSTs, glutathione peroxidase and Hsp70 (heat-shock protein 70). The HNE-induced oxidative stress persisted for longer in the mitochondrial compartment, where the recovery of GSH pool was slower than in the cytosolic compartment. Our study, for the first time, demonstrates the presence in mitochondria of multiple forms of GSTs that show molecular properties similar to those of their cytosolic counterparts. Our results suggest that mitochondrial GSTs may play an important role in defence against chemical and oxidative stress. PMID:12020353

Raza, Haider; Robin, Marie-Anne; Fang, Ji-Kang; Avadhani, Narayan G

2002-01-01

73

Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.  

PubMed

Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us to report new sets of genes that according to their gene expression and physical interactions are predicted to be differentially expressed in MS versus healthy subjects, and in MS patients in relapse versus remission. Some of these genes may be useful biomarkers for diagnosing MS and predicting relapses in MS patients. PMID:21676896

Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

2011-09-15

74

Differential School Effects among Low, Middle, and High Social Class Composition Schools: A Multiple Group, Multilevel Latent Growth Curve Analysis  

ERIC Educational Resources Information Center

This study uses large-scale survey data and a multiple group, multilevel latent growth curve model to examine differential school effects between low, middle, and high social class composition public schools. The results show that the effects of school inputs and school practices on learning differ across the 3 subpopulations. Moreover, student…

Palardy, Gregory J.

2008-01-01

75

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model.  

PubMed

Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting myeloma growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of myeloma within the BM are required. Herein we have developed a clinically relevant, three-dimensional (3D) myeloma BM coculture model that mimics bone cell/cancer cell interactions within the bone microenvironment. The coculture model and clinical samples were used to investigate myeloma growth, osteogenesis inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillarylike assembly of endothelial cells and cell adhesion-mediated drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA (miR) signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically relevant tool to model cancer growth within the bone-useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel bone anabolic miRs in MM opens more opportunities for novel approaches to cancer therapy via stromal miR modulation. PMID:25205118

Reagan, Michaela R; Mishima, Yuji; Glavey, Siobhan V; Zhang, Yong; Manier, Salomon; Lu, Zhi Ning; Memarzadeh, Masoumeh; Zhang, Yu; Sacco, Antonio; Aljawai, Yosra; Shi, Jiantao; Tai, Yu-Tzu; Ready, John E; Kaplan, David L; Roccaro, Aldo M; Ghobrial, Irene M

2014-11-20

76

Periventricular Lesions Help Differentiate Neuromyelitis Optica Spectrum Disorders from Multiple Sclerosis  

PubMed Central

Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered (“type A”) or jagged-bordered (“type B”) pattern. On sagittal FLAIR, the images were evaluated for presence of “Dawson's fingers.” Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and “jagged-bordered” periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases. PMID:24665366

Loh, John P.; Saba, Luca; Omari, Mirza; Herbert, Joseph; Kister, Ilya

2014-01-01

77

Multiplication  

NSDL National Science Digital Library

How sharp are your multiplication skills? Give these great math games a try ! Play Asteroids blaster and test your multiplication skills. How fast can you solve the problem... play a round of Baseball multiplication and see! Multiplication is fun and delicious with Crazy Cones. Help Lemonade Larry determine the correct amount! Test your multiplication skills with Tic Tac Toe! ...

Ms.roberts

2009-02-24

78

The grain production potential assessment with Multiple Cropping Index (MCI) in China  

NASA Astrophysics Data System (ADS)

This paper retrieved the information of cropland and MCI (Multiple Cropping Index) of China in 2000 and 2009 with SPOT NDVI time series data and utilized meteorological data and statistical data released by the state to calculate potential MCI and statistical MCI. Then, the MCI potential of China and grain production potential based on MCI were calculated in order to analyze the potential spatial distribution characteristics of MCI and the potential spatial pattern characteristics. The national mean MCI potentials in 2000 and 2009 are 0.485 and 0.506 respectively calculated with the remote sensing method and statistical method. And the grain productivity potentials of China based on MCI are 51% and 53% respectively. The improvement of MCI potential not only increases hydrothermal utilization rate and the utilization rate of cropland but also enormously enhances the food security degree of China and provides more available cropland area for the economic development.

Gao, Zhiqiang; Ning, Jicai; Gao, Wei

2014-10-01

79

On orthogonality constrained multiple core-hole states and optimized effective potential method.  

PubMed

An attempt to construct a multiple core-hole state within the optimized effective potential (OEP) methodology is presented. In contrast to the conventional ?-self-consistent field method for hole states, the effects of removing an electron is achieved using some orthogonality constraints imposed on the orbitals so that a Slater determinant describing a hole state is constrained to be orthogonal to that of a neutral system. It is shown that single, double, and multiple core-hole states can be treated within a unified framework and can be easily implemented for atoms and molecules. For this purpose, a constrained OEP method proposed earlier for excited states (Glushkov and Levy, J. Chem. Phys. 2007, 126, 174106) is further developed to calculate single and double core ionization energies using a local effective potential expressed as a direct mapping of the external potential. The corresponding equations, determining core-hole orbitals from a one-particle Schrödinger equation with a local potential as well as correlation corrections derived from the second-order many-body perturbation theory are given. One of the advantages of the present direct mapping formulation is that the effective potential, which plays the role of the Kohn-Sham potential, has the symmetry of the external potential. Single and double core ionization potentials computed with the presented scheme were found to be in agreement with data available from experiment and other calculations. We also discuss core-hole state local potentials for the systems studied. PMID:22696265

Glushkov, V N; Assfeld, X

2012-10-01

80

Computational Studies of Multiple-Particle Nonlinear Dynamics in a Spatio-Temporally periodic potential  

E-print Network

The spatio-temporally periodic (STP) potential is interesting in Physics due to the intimate coupling between its time and spatial components. In this paper we begin with a brief discussion of the dynamical behaviors of a single particle in a STP potential and then examine the dynamics of multiple particles interacting in a STP potential via the electric Coulomb potential. For the multiple particle case, we focus on the occurrence of bifurcations when the amplitude of the STP potential varies. It is found that the particle concentration of the system plays an important role; the type of bifurcations that occur and the number of attractors present in the Poincar\\'e sections depend on whether the number of particles in the simulation is even or odd. In addition to the nonlinear dynamical approach we also discuss dependence of the squared fractional deviation of particles kinetic energy of the multiple particle system on the amplitude of the STP potential which can be used to elucidate certain transitions of states; this approach is simple and useful particularly for experimental studies of complicated interacting systems.

Owen D. Myers; Junru Wu; Jeffrey S. Marshall; Christopher M. Danforth

2014-09-03

81

Adipogenic Potential of Multiple Human Adenoviruses In Vivo and In Vitro in Animals  

NSDL National Science Digital Library

Journal Article ÃÂAdipogenic potential of multiple human adenoviruses in vivo and in vitro in animals,ÃÂ by Leah D. Whigham, Barbara A. Israel, and Richard L. Atkinson, found in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

Leah D. Whigham (University of Wisconsin-Madison Departments of Medicine and Nutritional Sciences); MD Richard L. Atkinson (Obetech Obesity Research Center); Barbara A. Israel (University of Wisconsin-Madison Department of Pathological Sciences)

2006-01-01

82

Appearance potential spectroscopy with a photon counting detector and multiple scattering spectral interpretation.  

PubMed

We describe a soft x-ray appearance potential spectroscopy apparatus, which uses a windowless hyperpure Ge detector operated in the photon counting mode. Direct comparisons of recorded spectra with the self-convolution of x-ray absorption spectra and with ab initio simulations in the multiple scattering framework are reported and discussed. PMID:22938308

Amidani, L; Pasquini, L; Boscherini, F

2012-08-01

83

Appearance potential spectroscopy with a photon counting detector and multiple scattering spectral interpretation  

SciTech Connect

We describe a soft x-ray appearance potential spectroscopy apparatus, which uses a windowless hyperpure Ge detector operated in the photon counting mode. Direct comparisons of recorded spectra with the self-convolution of x-ray absorption spectra and with ab initio simulations in the multiple scattering framework are reported and discussed.

Amidani, L.; Pasquini, L.; Boscherini, F. [Department of Physics and CNISM, University of Bologna, viale C. Berti Pichat 6/2, 40127 Bologna (Italy)

2012-08-15

84

Differentiation of ocular fundus fluorophores by fluorescence lifetime imaging using multiple excitation and emission wavelengths  

NASA Astrophysics Data System (ADS)

Ocular fundus autofluorescence imaging has been introduced into clinical diagnostics recently. It is in use for the observation of the age pigment lipofuscin, a precursor of age - related macular degeneration (AMD). But other fluorophores may be of interest too: The redox pair FAD - FADH II provides information on the retinal energy metabolism, advanced glycation end products (AGE) indicate protein glycation associated with pathologic processes in diabetes as well as AMD, and alterations in the fluorescence of collagen and elastin in connective tissue give us the opportunity to observe fibrosis by fluorescence imaging. This, however, needs techniques able to differentiate particular fluorophores despite limited permissible ocular exposure as well as excitation wavelength (limited by the transmission of the human ocular lens to >400 nm). We present an ophthalmic laser scanning system (SLO), equipped with picosecond laser diodes (FWHM 100 ps, 446 nm or 468 nm respectively) and time correlated single photon counting (TCSPC) in two emission bands (500 - 560 nm and 560 - 700 nm). The decays were fitted by a bi-exponential model. Fluorescence spectra were measured by a fluorescence spectrometer fluorolog. Upon excitation at 446 nm, the fluorescence of AGE, FAD, and lipofuscin were found to peak at 503 nm, 525 nm, and 600 nm respectively. Accordingly, the statistical distribution of the fluorescence decay times was found to depend on the different excitation wavelengths and emission bands used. The use of multiple excitation and emission wavelengths in conjunction with fluorescence lifetime imaging allows us to discriminate between intrinsic fluorophores of the ocular fundus. Taken together with our knowledge on the anatomical structure of the fundus, these findings suggest an association of the short, middle and long fluorescence decay time to the retinal pigment epithelium, the retina, and connective tissue respectively.

Hammer, M.; Schweitzer, D.; Schenke, S.; Becker, W.; Bergmann, A.

2006-10-01

85

Water Vapor, Differential Rates of Warming, Available Potential Energy, and the Hadley Circulation  

NASA Astrophysics Data System (ADS)

In 1686 Halley advanced the idea that trade winds and monsoon circulations were tied to differential patterns in solar heating. Hadley (1735) soon added the important concept of conservation of angular momentum. Lorenz (1955) described how temperature gradients produced the potential energy, maintaining the general circulation. The differential heating patterns that drive the Hadley circulation arise through variations in insolation and water vapor-related warming. Water vapor is a very effective greenhouse gas, and the tropical-to-extra tropical water vapor gradient increases the longwave radiation absorbed at the surface, increasing the meridional temperature gradient. Increases in water vapor are accepted as one robust feature of anthropogenic climate change. While it is generally accepted that that the 'rich will get richer' (in the sense that moist regions will see a disproportionate increase in water vapor), there has been relatively little discussion of how these differential changes in moisture will translate into differential changes in water vapor related increases in longwave radiation. These increases in longwave radiation may result in a tendency for the 'warm to get warmer' and the Hadley circulation to intensify. In this presentation we examine this issue using i) a single column plane-parallel radiative transfer model, ii) reanalysis climate fields, iii) sea surface temperature observations, and iv) historical climate change simulations drawn from the phase 5 coupled model intercomparison project (CMIP5) archive. We conclude with an examination of potential impacts on arid and semi-arid zones.

Funk, C. C.; Dettinger, M. D.

2012-12-01

86

Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells  

Microsoft Academic Search

The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is inefficient. It has been assumed that the somatic differentiation state provides a barrier for efficient reprogramming; however, direct evidence for this notion is lacking. Here, we tested the potential of mouse hematopoietic cells at different stages of

Sarah Eminli; Adlen Foudi; Matthias Stadtfeld; Nimet Maherali; Tim Ahfeldt; Gustavo Mostoslavsky; Hanno Hock; Konrad Hochedlinger

2009-01-01

87

Cell differentiation along multiple pathways accompanied by changes in histone acetylation status.  

PubMed

Post-translational modification of histones is fundamental to the regulation of basic nuclear processes and subsequent cellular events, including differentiation. In this study, we analyzed acetylated forms of histones H2A, H2B, and H4 during induced differentiation in mouse (mESCs) and human (hESCs) embryonic stem cells and during induced enterocytic differentiation of colon cancer cells in vitro. Endoderm-like differentiation of mESCs induced by retinoic acid and enterocytic differentiation induced by histone deacetylase inhibitor sodium butyrate were accompanied by increased mono-, di-, and tri-acetylation of histone H2B and a pronounced increase in di- and tri-acetylation of histone H4. In enterocytes, mono-acetylation of histone H2A also increased and tetra-acetylation of histone H4 appeared only after induction of this differentiation pathway. During differentiation of hESCs, we observed increased mono-acetylation and decreased tri-acetylation of H2B. Mono-, di-, and tri-acetylation of H4 were reduced, manifested by a significant increase in nonacetylated H4 histones. Levels of acetylated histones increased during induced differentiation in mESCs and during histone deacetylase (HDAC) inhibitor-induced enterocytic differentiation, whereas differentiation of human ESCs was associated with reduced acetylation of histones H2B and H4. PMID:24697692

Legartová, So?a; Kozubek, Stanislav; Franek, Michal; Zdráhal, Zbyn?k; Lochmanová, Gabriela; Martinet, Nadine; Bártová, Eva

2014-04-01

88

Shifted excitation Raman difference spectroscopy at multiple wavelengths for in-situ meat species differentiation  

NASA Astrophysics Data System (ADS)

Two miniaturized Raman measurement heads containing microsystem diode lasers emitting at 783 and 671 nm suitable for shifted excitation Raman difference spectroscopy (SERDS) were applied for the non-invasive in situ differentiation of selected meat species. This allows using the fingerprint characteristics of Raman spectra without a disturbing fluorescence background. At 783 nm, two emission lines with a spectral shift of 0.5 nm (7 cm-1) and optical powers of up to 110 mW were realized. For 671 nm excitation, the spectral shift amounts to 0.6 nm (12 cm-1) and optical powers of up to 40 mW were obtained. In both cases, meat Raman spectra could be recorded with integration times of 10 s. The investigations were carried out using selected cuts from the most commonly consumed meat species in the US and Europe, i.e. beef, pork, chicken, and turkey. A principal components analysis of the SERDS spectra revealed a clear separation of the meat species into four distinct groups for both excitation wavelengths. This classification is based on the myoglobin content and gradual differences of protein Raman band intensities and positions. The results demonstrate the potential of SERDS as rapid and non-destructive screening method for the discrimination of selected meat species.

Sowoidnich, Kay; Kronfeldt, Heinz-Detlef

2012-09-01

89

Differentiation  

NSDL National Science Digital Library

This is an activity about lunar magmatic differentiation, in which learners simulate the process of geological differentiation. The activity ends with an extension question that asks about the makeup of the highlands of the Moon. This activity is in Unit 2 of the Exploring the Moon teacher's guide and is designed for use especially, but not exclusively, with the Lunar Sample Disk program.

90

Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases  

SciTech Connect

A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases.

Scott, R.E.; Maercklein, P.B.

1985-05-01

91

Exact distorted-wave approach to multiple-scattering theory for general potentials  

E-print Network

We present a new approach to real-space multiple-scattering theory for molecules and clusters, based on the two-potential (distorted-wave) Lippmann-Schwinger equation formalism. Our approach uses a recently developed form [D. L. Foulis, Phys. Rev. A70, 022706 (2004)], for the partial-wave expansions of the exact time-independent single-particle Green function for a general potential, to solve exactly the scattering problem for the distorting potential. The multiple-scattering problem for the full multicenter molecular potential is then developed along familiar lines, within a partition of space consisting of non-overlapping atomic spheres, but relative to the distorting potential. To achieve this some new general Green-function re-expansion formulas are derived, as well as further developments of our earlier partial-wave expansions. Based on the division of the multicenter molecular potential into the non-singular distorting potential and a remaining singular part we develop explicitly the secular equations of our approach and prove a result concerning the symmetry of the atomic matrices. The new secular equations are similar in overall form to those of related methods, requiring coupled radial Schr\\"odinger-equation solutions for each atomic center, together with atomic-sphere surface integrals, but no volume integrals. We treat both continuum (scattering) states and bound states within the same framework, and consider also the case of an outer sphere.

D. L. Foulis

2008-06-03

92

Swine flu vaccine adjuvants and multiple sclerosis - Is there potential for harmful effect?  

PubMed

Vaccines are generally considered a simple compound and clinicians are sometimes unaware of the possible dangers related to the new adjuvanted vaccine approach. Due to their cost effectiveness and in order to obtain stronger response with a lower antigen dose, adjuvanted vaccines are preferred during pandemics. Adjuvants are strong immunostimulants and may be harmful in some special patient groups, such as in multiple sclerosis. There is a significant need for the effort among clinicians to heighten the awareness of the potential harms. In patient groups like multiple sclerosis, it is very important to advise vaccination with non-adjuvanted vaccines. Pure vaccine (without adjuvant) must be obtained for these groups. PMID:20171793

Oztürk, Serefnur

2010-07-01

93

Kernel Mechanisms for Supporting Differentiated Services and Content-Aware Request Distribution in Web Clusters Providing Multiple Services  

Microsoft Academic Search

In this paper, we have designed and implemented a kernel-level Web-based QoS (WQoS) mechanism that could efficiently support differentiated services when serving multiple diverse types of Web requests in a cluster-based Web server system. Our mechanism is implemented at kernel level to effectively reduce the number of protection domain switches and data copying between kernel space and user space to

Chun-Hung Wu; Mei-Ling Chiang; Tsung-Lin Lu

2010-01-01

94

Benchmarking in a differentially heated rotating annulus experiment: Multiple equilibria in the light of laboratory experiments and simulations  

NASA Astrophysics Data System (ADS)

In the framework of the German Science Foundation's (DFG) priority program 'MetStröm' various laboratory experiments have been carried out in a differentially heated rotating annulus configuration in order to test, validate and tune numerical methods to be used for modeling large-scale atmospheric processes. This classic experimental set-up is well known since the late 1940s and is a widely studied minimal model of the general mid-latitude atmospheric circulation. The two most relevant factors of cyclogenesis, namely rotation and meridional temperature gradient are quite well captured in this simple arrangement. The tabletop-size rotating tank is divided into three sections by coaxial cylindrical sidewalls. The innermost section is cooled whereas the outermost annular cavity is heated, therefore the working fluid (de-ionized water) in the middle annular section experiences differential heat flow, which imposes thermal (density) stratification on the fluid. At high enough rotation rates the isothermal surfaces tilt, leading to baroclinic instability. The extra potential energy stored in this unstable configuration is then converted into kinetic energy, exciting drifting wave patterns of temperature and momentum anomalies. The signatures of these baroclinic waves at the free water surface have been analysed via infrared thermography in a wide range of rotation rates (keeping the radial temperature difference constant) and under different initial conditions (namely, initial spin-up and "spin-down"). Paralelly to the laboratory simulations of BTU Cottbus-Senftenberg, five other groups from the MetStröm collaboration have conducted simulations in the same parameter regime using different numerical approaches and solvers, and applying different initial conditions and perturbations for stability analysis. The obtained baroclinic wave patterns have been evaluated via determining and comparing their Empirical Orthogonal Functions (EOFs), drift rates and dominant wave modes. Thus certain "benchmarks" have been created that can later be used as test cases for atmospheric numerical model validation. Both in the experiments and in the numerics multiple equilibrium states have been observed in the form of hysteretic behavior depending on the initial conditions. The precise quantification of these state and wave mode transitions may shed light to some aspects of the basic underlying dynamics of the baroclinic annulus configuration, still to be understood.

Vincze, Miklos; Harlander, Uwe; Borchert, Sebastian; Achatz, Ulrich; Baumann, Martin; Egbers, Christoph; Fröhlich, Jochen; Hertel, Claudia; Heuveline, Vincent; Hickel, Stefan; von Larcher, Thomas; Remmler, Sebastian

2014-05-01

95

Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment  

Microsoft Academic Search

Understanding the mechanisms of immune cell migration to multiple sclerosis lesions offers significant therapeutic potential. This study focused on the chemokines CXCL12 (SDF-1) and CXCL13 (BCA-1), both of which regulate B cell migration in lymphoid tissues. We report that immunohistologically CXCL12 was constitutively expressed in CNS parenchyma on blood vessel walls. In both active and chronic inactive multiple sclerosis lesions

Markus Krumbholz; Diethilde Theil; Sabine Cepok; Bernhard Hemmer; Pia Kivisakk; Richard M. Ransohoff; Monika Hofbauer; Cinthia Farina; Tobias Derfuss; Caroline Hartle; Jia Newcombe; Reinhard Hohlfeld; Edgar Meinl

2006-01-01

96

Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma.  

PubMed

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In this study, differentially expressed miRNAs in tumor tissues and adjacent non-tumor tissues were detected by miRNA microarrays. Stem-loop real-time reverse transcription PCR was conducted to verify the candidate miRNAs discovered by microarray analysis. The data showed that hsa-miR-338-3p, hsa-miR?218 and hsa-miR-139-5p were downregulated in tumor tissues compared with adjacent non-tumor tissues, while hsa-miR?183, hsa-miR-574-5p, hsa-miR-21* and hsa-miR?601 were upregulated in tumor tissues. Multiple regression analysis revealed the aberrant expression of hsa-miR-338-3p, hsa?miR-139-5p, hsa-miR?574-5p and hsa-miR-601 increased the risk of esophageal cancer. Furthermore, we found hsa-miR-21* was significantly increased in heavy drinking patients. Therefore, there is a set of differentially expressed miRNAs in esophageal cancer which may be associated with the incidence and development of ESCC. Differential expression profiles of miRNAs in ESCC may be promising biomarkers for the early screening of high-risk populations and early detection. PMID:23124769

Yang, Miao; Liu, Ran; Sheng, Jingyi; Liao, Juan; Wang, Yi; Pan, Enchun; Guo, Wei; Pu, Yuepu; Yin, Lihong

2013-01-01

97

IL-12 Directs Further Maturation of Ex Vivo Differentiated NK Cells with Improved Therapeutic Potential  

PubMed Central

The possibility to modulate ex vivo human NK cell differentiation towards specific phenotypes will contribute to a better understanding of NK cell differentiation and facilitate tailored production of NK cells for immunotherapy. In this study, we show that addition of a specific low dose of IL-12 to an ex vivo NK cell differentiation system from cord blood CD34+ stem cells will result in significantly increased proportions of cells with expression of CD62L as well as KIRs and CD16 which are preferentially expressed on mature CD56dim peripheral blood NK cells. In addition, the cells displayed decreased expression of receptors such as CCR6 and CXCR3, which are typically expressed to a lower extent by CD56dim than CD56bright peripheral blood NK cells. The increased number of CD62L and KIR positive cells prevailed in a population of CD33+NKG2A+ NK cells, supporting that maturation occurs via this subtype. Among a series of transcription factors tested we found Gata3 and TOX to be significantly downregulated, whereas ID3 was upregulated in the IL-12-modulated ex vivo NK cells, implicating these factors in the observed changes. Importantly, the cells differentiated in the presence of IL-12 showed enhanced cytokine production and cytolytic activity against MHC class I negative and positive targets. Moreover, in line with the enhanced CD16 expression, these cells exhibited improved antibody-dependent cellular cytotoxicity for B-cell leukemia target cells in the presence of the clinically applied antibody rituximab. Altogether, these data provide evidence that IL-12 directs human ex vivo NK cell differentiation towards more mature NK cells with improved properties for potential cancer therapies. PMID:24498025

Sturtzel, Caterina; Tordoir, Marleen; Schlechta, Bernhard; Groenewegen, Dirk; Hofer, Erhard

2014-01-01

98

On the differential diagnosis of multiple personality in the forensic context?  

Microsoft Academic Search

The problems of diagnosing multiple personality disorder in a forensic context are discussed, and illustrated by the case of Stute u. Kenneth Birrnchi (1979), a defendant who was both charged with first degree murder and suspected of having the disorder. Because of the secondary gain (e.g., avoiding the death penalty) associated with the diagnosis of multiplicity in such a case,

Martin T. Orne; David F. Dinges; Emily Carota Orne

1984-01-01

99

Aqueous ethanolic extract of Tinospora cordifolia as a potential candidate for differentiation based therapy of glioblastomas.  

PubMed

Glioblastomas are the most aggressive primary brain tumors and their heterogeneity and complexity often renders them non responsive to various conventional treatments. Search for herbal products having potential anti-cancer activity is an active area of research in the Indian traditional system of medicine i.e., Ayurveda. Tinospora cordifolia, also named as 'heavenly elixir' is used in various ayurvedic decoctions as panacea to treat several body ailments. The current study investigated the anti-brain cancer potential of 50% ethanolic extract of Tinospora cordifolia (TCE) using C6 glioma cells. TCE significantly reduced cell proliferation in dose-dependent manner and induced differentiation in C6 glioma cells, resulting in astrocyte-like morphology as indicated by phase contrast images, GFAP expression and process outgrowth data of TCE treated cells which exhibited higher number and longer processes than untreated cells. Reduced proliferation of cells was accompanied by enhanced expression of senescence marker, mortalin and its translocation from perinuclear to pancytoplasmic spaces. Further, TCE showed anti-migratory and anti-invasive potential as depicted by wound scratch assay and reduced expression of plasticity markers NCAM and PSA-NCAM along with MMP-2 and 9. On analysis of the cell cycle and apoptotic markers, TCE treatment was seen to arrest the C6 cells in G0/G1 and G2/M phase, suppressing expression of G1/S phase specific protein cyclin D1 and anti-apoptotic protein Bcl-xL, thus supporting its anti-proliferative and apoptosis inducing potential. Present study provides the first evidence for the presence of anti-proliferative, differentiation-inducing and anti-migratory/anti-metastatic potential of TCE in glioma cells and possible signaling pathways involved in its mode of action. Our primary data suggests that TCE and its active components may prove to be promising phytotherapeutic interventions in gliobalstoma multiformae.  PMID:24205314

Mishra, Rachana; Kaur, Gurcharan

2013-01-01

100

Comparison of the profiles of the potential teachers in different disciplines based on multiple intelligences theory (Samsun City Sample)  

Microsoft Academic Search

In this study, the profiles based on multiple intelligences theory of a total of 908 potential teachers studying in Science, Social Sciences, Mathematics, Music, Art and Physical Education at Ondokuz May?s University are compared. Multiple intelligences inventory which was taken from Saban has been used to determine the intelligence areas of the potential teachers. The collected data has been evaluated

Hasan Sözen; Merve Sözen; Atilla Tekat

2009-01-01

101

Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro  

SciTech Connect

Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but strong in MSC. • Osteogenic differentiation is significantly stronger for CDC than for MSC.

Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Rychly, Joachim, E-mail: joachim.rychly@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Müller-Hilke, Brigitte, E-mail: brigitte.mueller-hilke@med.uni-rostock.de [Institute of Immunology, Rostock University Medical Center, Schillingallee 68, D-18057 Rostock (Germany); Bader, Rainer, E-mail: rainer.bader@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Lochner, Katrin, E-mail: katrin.lochner@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

2013-11-01

102

Relay Selection Based Double-Differential Transmission for Cooperative Networks with Multiple Carrier Frequency Offsets: Model, Analysis, and Optimization  

NASA Astrophysics Data System (ADS)

Due to the distributed nature, cooperative networks are generally subject to multiple carrier frequency offsets (MCFOs), which make the channels time-varying and drastically degrade the system performance. In this paper, to address the MCFOs problem in detect-andforward (DetF) multi-relay cooperative networks, a robust relay selection (RS) based double-differential (DD) transmission scheme, termed RSDDT, is proposed, where the best relay is selected to forward the source's double-differentially modulated signals to the destination with the DetF protocol. The proposed RSDDT scheme can achieve excellent performance over fading channels in the presence of unknown MCFOs. Considering double-differential multiple phase-shift keying (DDMPSK) is applied, we first derive exact expressions for the outage probability and average bit error rate (BER) of the RSDDT scheme. Then, we look into the high signal-to-noise ratio (SNR) regime and present simple and informative asymptotic outage probability and average BER expressions, which reveal that the proposed scheme can achieve full diversity. Moreover, to further improve the BER performance of the RSDDT scheme, we investigate the optimum power allocation strategy among the source and the relay nodes, and simple analytical solutions are obtained. Numerical results are provided to corroborate the derived analytical expressions and it is demonstrated that the proposed optimum power allocation strategy offers substantial BER performance improvement over the equal power allocation strategy.

Zhao, Kun; Zhang, Bangning; Pan, Kegang; Liu, Aijun; Guo, Daoxing

2014-07-01

103

Raman spectroscopic analysis of gunshot residue offering great potential for caliber differentiation.  

PubMed

Near-infrared (NIR) Raman microspectroscopy combined with advanced statistics was used to differentiate gunshot residue (GSR) particles originating from different caliber ammunition. The firearm discharge process is analogous to a complex chemical reaction. The reagents of this process are represented by the chemical composition of the ammunition, firearm, and cartridge case. The specific firearm parameters determine the conditions of the reaction and thus the subsequent product, GSR. We found that Raman spectra collected from these products are characteristic for different caliber ammunition. GSR particles from 9 mm and 0.38 caliber ammunition, collected under identical discharge conditions, were used to demonstrate the capability of confocal Raman microspectroscopy for the discrimination and identification of GSR particles. The caliber differentiation algorithm is based on support vector machines (SVM) and partial least squares (PLS) discriminant analyses, validated by a leave-one-out cross-validation method. This study demonstrates for the first time that NIR Raman microspectroscopy has the potential for the reagentless differentiation of GSR based upon forensically relevant parameters, such as caliber size. When fully developed, this method should have a significant impact on the efficiency of crime scene investigations. PMID:22448891

Bueno, Justin; Sikirzhytski, Vitali; Lednev, Igor K

2012-05-15

104

Multi-scale Renormalization Group Methods for Effective Potentials with Multiple Scalar Fields  

E-print Network

Multi-scale renormalization group (RG) methods are reviewed and applied to the analysis of the effective potential for radiative symmetry breaking with multiple scalar fields, allowing an extension of the Gildener & Weinberg (GW) method beyond the weak coupling limit. A model containing two interacting real scalar fields is used to illustrate multi-scale RG methods and the multi-scale RG functions of this model are calculated to one-loop order for the $\\beta$ function and two-loop order for the anomalous mass dimension. The introduction of an extra renormalization scale allows the mapping of the effective potential in this model onto an RG-equivalent form with an O(2) symmetric structure along a particular trajectory in the multiple renormalization-scale space, leading to a simplified form of the effective potential. It is demonstrated that the physical content of the effective potential in the original model, referenced to a single conventional renormalization scale, can be extracted from a particular RG...

Steele, T G; McKeon, D G C

2014-01-01

105

Why do multiple traits determine mating success? Differential use in female choice and male competition in a water boatman  

PubMed Central

Mating success is often determined by multiple traits, but why this occurs is largely unknown. Much attention has been paid to female preferences for multiple traits, but surprisingly few researchers have addressed the possibility that multiple traits are important because they serve different functions in female choice and male–male competition. Differential trait function could result from a conflict of interest between the sexes or from constraints forcing the sexes to pay attention to different traits. I show that traits determined at distinct life-history stages differ in their importance in female choice and male–male competition in a water boatman Sigara falleni. Juvenile conditions determined body and foreleg pala size and were the main determinants of mating success under female choice, whereas adult conditions determined body mass and influenced mating success when male competition was included. This differential use of condition-dependent traits under the two selection regimes appeared to arise partly from a conflict between the sexes, since the two selection forces (female choice and male competition) conflict for selection on pala size, and partly from constraints, as females appeared unable to assess adult condition. PMID:15875569

Candolin, Ulrika

2004-01-01

106

WNT3 Is a Biomarker Capable of Predicting the Definitive Endoderm Differentiation Potential of hESCs  

PubMed Central

Generation of functional cells from human pluripotent stem cells (PSCs) through in vitro differentiation is a promising approach for drug screening and cell therapy. However, the observed large and unavoidable variation in the differentiation potential of different human embryonic stem cell (hESC)/induced PSC (iPSC) lines makes the selection of an appropriate cell line for the differentiation of a particular cell lineage difficult. Here, we report identification of WNT3 as a biomarker capable of predicting definitive endoderm (DE) differentiation potential of hESCs. We show that the mRNA level of WNT3 in hESCs correlates with their DE differentiation efficiency. In addition, manipulations of hESCs through WNT3 knockdown or overexpression can respectively inhibit or promote DE differentiation in a WNT3 level-dependent manner. Finally, analysis of several hESC lines based on their WNT3 expression levels allowed accurate prediction of their DE differentiation potential. Collectively, our study supports the notion that WNT3 can serve as a biomarker for predicting DE differentiation potential of hESCs. PMID:24052941

Jiang, Wei; Zhang, Donghui; Bursac, Nenad; Zhang, Yi

2013-01-01

107

Identification of a Proximal Progenitor Population from Murine Fetal Lungs with Clonogenic and Multilineage Differentiation Potential  

PubMed Central

Summary Lung development-associated diseases are major causes of morbidity and lethality in preterm infants and children. Access to the lung progenitor/stem cell populations controlling pulmonary development during embryogenesis and early postnatal years is essential to understand the molecular basis of such diseases. Using a Nkx2-1mCherry reporter mouse, we have identified and captured Nkx2-1-expressing lung progenitor cells from the proximal lung epithelium during fetal development. These cells formed clonal spheres in semisolid culture that could be maintained in vitro and demonstrated self-renewal and expansion capabilities over multiple passages. In-vitro-derived Nkx2-1-expressing clonal spheres differentiated into a polarized epithelium comprised of multiple cell lineages, including basal and secretory cells, that could repopulate decellularized lung scaffolds. Nkx2-1 expression thus defines a fetal lung epithelial progenitor cell population that can be used as a model system to study pulmonary development and associated pediatric diseases. PMID:25358791

Bilodeau, Melanie; Shojaie, Sharareh; Ackerley, Cameron; Post, Martin; Rossant, Janet

2014-01-01

108

Differentiation  

NSDL National Science Digital Library

The derivative refers to the rate of change, or slope, of a function. Differentiation refers to the calculation of a derivative. Derivatives are used throughout applied mathematics and science. The derivative of a function is the instantaneous rate of change of a function evaluated at each point.

Joiner, David; The Shodor Education Foundation, Inc.

109

Numerical solution of potential flow about arbitrary 2-dimensional multiple bodies  

NASA Technical Reports Server (NTRS)

A procedure for the finite-difference numerical solution of the lifting potential flow about any number of arbitrarily shaped bodies is given. The solution is based on a technique of automatic numerical generation of a curvilinear coordinate system having coordinate lines coincident with the contours of all bodies in the field, regardless of their shapes and number. The effects of all numerical parameters involved are analyzed and appropriate values are recommended. Comparisons with analytic solutions for single Karman-Trefftz airfoils and a circular cylinder pair show excellent agreement. The technique of application of the boundary-fitted coordinate systems to the numerical solution of partial differential equations is illustrated.

Thompson, J. F.; Thames, F. C.

1982-01-01

110

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation  

PubMed Central

Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors—namely, precancerous stem cells (pCSCs) —have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers. PMID:17356702

Chen, Li; Shen, Rulong; Ye, Yin; Pu, Xin-An; Liu, Xingluo; Duan, Wenrui; Wen, Jing; Zimmerer, Jason; Wang, Ying; Liu, Yan; Lasky, Larry C.; Heerema, Nyla A.; Perrotti, Danilo; Ozato, Keiko; Kuramochi-Miyagawa, Satomi; Nakano, Toru; Yates, Allen J.; Carson III, William E.; Lin, Haifan; Barsky, Sanford H.; Gao, Jian-Xin

2007-01-01

111

Isorotation and differential rotation in a magnetic mirror with imposed E Multiplication-Sign B rotation  

SciTech Connect

Doppler spectroscopy of helium impurities in the Maryland Centrifugal Experiment reveals the simultaneous existence of isorotating and differentially rotating magnetic surfaces. Differential rotation occurs at the innermost surfaces and is conjectured to cause plasma voltage oscillations of hundreds of kilohertz by periodically changing the current path inductance. High-speed images show the periodic expulsion of plasma near the mirror ends at the same frequencies. In spite of this, the critical ionization velocity limit is exceeded, with respect to the vacuum field definition, for at least 0.5 ms.

Romero-Talamas, C. A.; Elton, R. C.; Young, W. C.; Reid, R.; Ellis, R. F. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States)

2012-07-15

112

Platelet Rich Concentrate Promotes Early Cellular Proliferation and Multiple Lineage Differentiation of Human Mesenchymal Stromal Cells In Vitro  

PubMed Central

Platelet rich concentrate (PRC) is a natural adjuvant that aids in human mesenchymal stromal cell (hMSC) proliferation in vitro; however, its role requires further exploration. This study was conducted to determine the optimal concentration of PRC required for achieving the maximal proliferation, and the need for activating the platelets to achieve this effect, and if PRC could independently induce early differentiation of hMSC. The gene expression of markers for osteocytes (ALP, RUNX2), chondrocytes (SOX9, COL2A1), and adipocytes (PPAR-?) was determined at each time point in hMSC treated with 15% activated and nonactivated PRC since maximal proliferative effect was achieved at this concentration. The isolated PRC had approximately fourfold higher platelet count than whole blood. There was no significant difference in hMSC proliferation between the activated and nonactivated PRC. Only RUNX2 and SOX9 genes were upregulated throughout the 8 days. However, protein expression study showed formation of oil globules from day 4, significant increase in ALP at days 6 and 8 (P ? 0.05), and increased glycosaminoglycan levels at all time points (P < 0.05), suggesting the early differentiation of hMSC into osteogenic and adipogenic lineages. This study demonstrates that the use of PRC increased hMSC proliferation and induced early differentiation of hMSC into multiple mesenchymal lineages, without preactivation or addition of differentiation medium.

Shani, Samuel; Vasudevaraj Naveen, Sangeetha; Murali, Malliga Raman; Puvanan, Karunanithi; Abbas, Azlina Amir; Kamarul, Tunku

2014-01-01

113

IGFBP-rP1, a potential molecule associated with colon cancer differentiation  

PubMed Central

Background In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes. Results In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate. Conclusion IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process. PMID:20977730

2010-01-01

114

Activities for Differentiated Instruction Addressing All Levels of Bloom's Taxonomy and Eight Multiple Intelligences.  

ERIC Educational Resources Information Center

This manuscript contains 13 curriculum units designed to enhance differentiated instruction for learners with special needs from grades 1-12, including gifted students. It integrates Benjamin S. Bloom's levels of cognitive understanding with Howard Gardner's eight domains of intelligence to provide a framework for individualized instruction. Each…

Rule, Audrey C., Ed.; Lord, Linda Hurley, Ed.

115

Commentary: Differentiated Measures of Temperament and Multiple Pathways to Childhood Disorders  

ERIC Educational Resources Information Center

Provided is a commentary on articles written for a special section on temperament and childhood disorders. Temperament's contributions to the development of childhood disorders are considered both generally and specifically. Questions are raised about the use of terminology in the field, particularly the term difficult. Differentiation of outcomes…

Rothbart, Mary K.

2004-01-01

116

MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets.  

PubMed

MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level. Research on miRNAs has highlighted their importance in neural development, but the specific functions of neurally enriched miRNAs remain poorly understood. We report here the expression profile of miRNAs during neuronal differentiation in the human neuroblastoma cell line SH-SY5Y. Six miRNAs were significantly upregulated during differentiation induced by all-trans-retinoic acid and brain-derived neurotrophic factor. We demonstrated that the ectopic expression of either miR-124a or miR-125b increases the percentage of differentiated SH-SY5Y cells with neurite outgrowth. Subsequently, we focused our functional analysis on miR-125b and demonstrated the important role of this miRNA in both the spontaneous and induced differentiations of SH-SH5Y cells. miR-125b is also upregulated during the differentiation of human neural progenitor ReNcell VM cells, and miR-125b ectopic expression significantly promotes the neurite outgrowth of these cells. To identify the targets of miR-125b regulation, we profiled the global changes in gene expression following miR-125b ectopic expression in SH-SY5Y cells. miR-125b represses 164 genes that contain the seed match sequence of the miRNA and/or that are predicted to be direct targets of miR-125b by conventional methods. Pathway analysis suggests that a subset of miR-125b-repressed targets antagonizes neuronal genes in several neurogenic pathways, thereby mediating the positive effect of miR-125b on neuronal differentiation. We have further validated the binding of miR-125b to the miRNA response elements of 10 selected mRNA targets. Together, we report here for the first time the important role of miR-125b in human neuronal differentiation. PMID:19635812

Le, Minh T N; Xie, Huangming; Zhou, Beiyan; Chia, Poh Hui; Rizk, Pamela; Um, Moonkyoung; Udolph, Gerald; Yang, Henry; Lim, Bing; Lodish, Harvey F

2009-10-01

117

Differential neuronal representation of spatial attention dependent on relative target locations during multiple object tracking.  

PubMed

Humans can simultaneously track multiple moving objects with attention. The number of objects that can be tracked is known to be larger when visual stimuli are presented bilaterally rather than presented unilaterally. To elucidate the underlying neuronal mechanism, we trained monkeys to covertly track a single or multiple object(s). We found that neurons in the lateral prefrontal cortex exhibited greater activity for the target passing through the receptive field (RF) than for distractors. During multiple-object tracking, response enhancement for one target presented in the RF was stronger when the other target was located in the opposite than the same visual hemifield. Because the neuronal modulation did not differ depending on relative target locations with respect to upper and lower visual hemifields, the distance between the targets does not explain the results. We propose that inherent, anatomical separation of visual processing for contralateral and ipsilateral visual fields might constrain cognitive capacity. PMID:25057198

Matsushima, Ayano; Tanaka, Masaki

2014-07-23

118

REM sleep behaviour disorder differentiates pure autonomic failure from multiple system atrophy with autonomic failure  

PubMed Central

Ten patients with primary autonomic failure, followed up in a prospective clinical and laboratory study, were finally diagnosed as pure autonomic failure or multiple system atrophy with autonomic failure. Polysomnographic studies were performed in all patients. Whereas all four patients with multiple system atrophy complained of sleep related episodes suggesting REM sleep behaviour disorder (RBD) confirmed by polysomnography, RBD remained absent in the remaining six patients with pure autonomic failure. The data indicate that RBD is an important clinical feature, often heralding multiple system atrophy, but which is absent throughout the course of pure autonomic failure; its recognition can thus be useful in the prognostic evaluation of early primary autonomic failure syndromes.?? PMID:9598693

Plazzi, G.; Cortelli, P.; Montagna, P.; De Monte, A.; Corsini, R.; Contin, M.; Provini, F.; Pierangeli, G.; Lugaresi, E.

1998-01-01

119

Differential Regulation and Predictive Potential of MacroH2A1 Isoforms in Colon Cancer  

PubMed Central

Histone variant macroH2A1 has two splice isoforms, macroH2A1.1 and macroH2A1.2, with tissue- and cell-specific expression patterns. Although macroH2A1.1 is mainly found in differentiated, nonproliferative tissues, macroH2A1.2 is more generally expressed, including in tissues with ongoing cell proliferation. Consistently, studies in breast and lung cancer have demonstrated a strong correlation between macroH2A1.1 levels and proliferation, which is not the case for macroH2A1.2. This is the first study to assess the differential regulation and predictive potential of macroH2A1 isoforms in colon cancer. We found that macroH2A1.1 mRNA was down-regulated in primary colorectal cancer samples compared to matched normal colon tissue, whereas macroH2A1.2 was up-regulated. At the protein level, down-regulation of macroH2A1.1 correlated significantly with patient outcome (P = 0.0012), and loss of macroH2A1.1 was associated with a worse outcome. Over the course of Caco-2 cell differentiation, macroH2A1.1 was up-regulated at both the RNA and protein levels, whereas macroH2A1.2 was slightly down-regulated at the RNA level and stable at the protein level. These changes were accompanied by an antiproliferative phenotype exhibiting features of cellular senescence. Loss of macroH2A1.1 in vitro was characterized by a phenotype associated with cell growth and metastasis. These data demonstrate that macroH2A1 isoforms are differentially regulated in colon cancer, reflecting the degree of cellular differentiation. Notably, macroH2A1.1 expression predicts survival in colon cancer, thus identifying macroH2A1.1 as a novel colon cancer biomarker. PMID:22542848

Sporn, Judith C.; Jung, Barbara

2013-01-01

120

Differential positioning and close spatial proximity of translocation-prone genes in nonmalignant B-cells from multiple myeloma patients.  

PubMed

Accumulating evidence suggests that spatial proximity of potential chromosomal translocation partners influences translocation probability. It is not known, however, whether genome organization differs in nonmalignant cells from patients as compared to their cellular counterparts from healthy donors. This could contribute to translocation potential causing cancer. Multiple myeloma is a hematopoietic cancer of the B-lineage, characterized by karyotypic instability, including chromosomal translocations involving the IGH locus and several translocation partners. Utilizing 3-D FISH and confocal imaging, we investigate whether nuclear spatial positioning of the translocation-prone gene loci, IGH, FGFR3, and CCND1 differs in nonmalignant cell subsets from multiple myeloma patients as compared to positioning in their corresponding healthy donor cell subsets. 3-D analysis software was used to determine the spatial proximity of potential translocation pairs and the radial distribution of each gene. We observed that in all cell subsets, the translocation-prone gene loci are intermediately located in the nucleus, while a control locus occupies a more peripheral position. In nonmalignant B-cells from multiple myeloma patients, however, the translocation-prone gene loci display a more central nuclear position and close spatial proximity. Our results demonstrate that gene positioning in nonmalignant B-cells from multiple myeloma patients differs from that in healthy donors, potentially contributing to translocation probability in patient cells. We speculate that genome reorganization in patient B-cells may closely reflect gene positioning at the time the multiple myeloma-specific translocation initially formed, thus influencing translocation probability between proximal loci in the B-cell population from which the malignancy emerged. PMID:22489023

Martin, Lorri D; Harizanova, Jana; Zhu, George; Righolt, Christiaan H; Belch, Andrew R; Mai, Sabine; Pilarski, Linda M

2012-08-01

121

Reconstruction of Multiple Gastric Electrical Wave Fronts Using Potential Based Inverse Methods  

PubMed Central

The ability to reconstruct gastric electrical activity (termed slow waves) non-invasively from potential field measurements made on the torso surface would be a useful tool to aid in the clinical diagnosis of a number of gastric disorders. This is mathematically akin to the inverse problem of electrocardiography. To investigate this problem, an anatomically realistic torso model and an electrical stomach model were used to simulate potentials on the stomach and skin surfaces arising from normal gastric electrical activity. Gaussian noise was added to the torso potentials to represent experimental signal noise. The stomach potentials, activation profiles and gastric slow wave velocities were inversely reconstructed from the torso potentials, using the Tikhonov-Greensite inverse method with regularisation determined using an L-curve method. The inverse solutions were then compared with the known input solutions. The reconstructed solutions were able to represent the presence of multiple propagating wave fronts, determine average activation times to within 5 s and average velocities to within 1 mm/s. When more virtual body surface electrodes were used in the inverse calculations, the accuracy of the reconstructed activity improved. PMID:22254568

Kim, J. H. K.; Pullan, A. J.; Cheng, L. K.

2014-01-01

122

Meaning Change, Multiple Routes, and the Role of Differentiation in Conceptual Change: Alternatives to Resubsumption?  

ERIC Educational Resources Information Center

The three commentaries on the resubsumption theory highlight three key ideas: that the term "conceptual change", as commonly used, is ambiguous between "change in the meaning of a concept" and "change in what someone believes"; that there are multiple routes to successful learning of conceptual subject matters; and that the noticing of a…

Ohlsson, Stellan

2009-01-01

123

Gender and Perceived Illness Severity: Differential Indicators of Employment Concerns for Adults with Multiple Sclerosis?  

ERIC Educational Resources Information Center

Although research has indicated a link between gender and perceived illness severity and the employment status of people with multiple sclerosis (MS), it has not addressed questions regarding the relationship between those variables and specific types of employment concerns. In this study, a sample of 1,310 adults with MS replied to a mail survey…

Roessler, Richard T.; Turner, Ronna C.; Robertson, Judith L.; Rumrill,Phillip D.

2005-01-01

124

Modeling Differential Item Functioning Using a Generalization of the Multiple-Group Bifactor Model  

ERIC Educational Resources Information Center

The authors present a generalization of the multiple-group bifactor model that extends the classical bifactor model for categorical outcomes by relaxing the typical assumption of independence of the specific dimensions. In addition to the means and variances of all dimensions, the correlations among the specific dimensions are allowed to differ…

Jeon, Minjeong; Rijmen, Frank; Rabe-Hesketh, Sophia

2013-01-01

125

Ultrafast differential transmission spectroscopy of excitonic transitions in InGaNGaN multiple quantum wells  

E-print Network

materials using the InGaN system have led to the commercialization of blue, green, and amber light Received 6 June 2002; accepted 15 January 2003 Room-temperature carrier dynamics in InGaN/GaN multiple and excitonic bleaching is consistent with the theoretical value of the piezoelectric field in the strained InGaN

Cartwright, Alexander N.

126

Bone marrow-derived human mesenchymal stem cells express cardiomyogenic proteins but do not exhibit functional cardiomyogenic differentiation potential.  

PubMed

Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC-mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1(+) mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration. PMID:22309203

Siegel, Georg; Krause, Petra; Wöhrle, Stefanie; Nowak, Patrick; Ayturan, Miriam; Kluba, Torsten; Brehm, Bernhard R; Neumeister, Birgid; Köhler, David; Rosenberger, Peter; Just, Lothar; Northoff, Hinnak; Schäfer, Richard

2012-09-01

127

Differential access for publicly-posted composite documents with multiple workflow participants  

Microsoft Academic Search

A novel mechanism for providing and enforcing differential access control for publicly-posted composite documents is proposed. The concept of a document is rapidly changing: individual file-based, traditional formats can no longer accommodate the required mixture of differently formatted parts: individual images, video\\/audio clips, PowerPoint presentations, html-pages, Word documents, Excel spreadsheets, pdf files, etc. Multi-part composite documents are created and managed

Helen Y. Balinsky; Steven J. Simske

2010-01-01

128

Stretchable energy-harvesting tactile electronic skin capable of differentiating multiple mechanical stimuli modes.  

PubMed

The first stretchable energy-harvesting electronic-skin device capable of differentiating and generating energy from various mechanical stimuli, such as normal pressure, lateral strain, bending, and vibration, is presented. A pressure sensitivity of 0.7 kPa(-1) is achieved in the pressure region <1 kPa with power generation of tens of ?W cm(-2) from a gentle finger touch. PMID:25256696

Park, Steve; Kim, Hyunjin; Vosgueritchian, Michael; Cheon, Sangmo; Kim, Hyeok; Koo, Ja Hoon; Kim, Taeho Roy; Lee, Sanghyo; Schwartz, Gregory; Chang, Hyuk; Bao, Zhenan

2014-11-01

129

PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells  

Microsoft Academic Search

Rosiglitazone (Rosi), a member of the thiazolidinedione class of drugs used to treat type 2 diabetes, activates the adipocyte-specific transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma). This activation causes bone loss in animals and humans, at least in part due to suppression of osteoblast differentiation from marrow mesenchymal stem cells (MSC). In order to identify mechanisms by which PPARgamma2 suppresses

Keith R. Shockley; Oxana P. Lazarenko; Piotr J. Czernik; Clifford J. Rosen; Gary A. Churchill; Czernik B Lecka

2009-01-01

130

Two fast VME transient recorder systems with 12 bits and multiple differential inputs  

Microsoft Academic Search

This article describes two on-site developed, VME transient recorder systems, with 12 bit resolution, eight (four) differential input channels, sampling frequency up to 1.25 (20) MSPS and 512 (250 or 1000) kWords of memory per channel. Autonomous operation is guaranteed by standard static random access memory, under the control of a programmable logic array device for address generation. This device

C. Correia; A. Combo; M. Correia; P. Coelho; B. B. Carvalho; J. Sousa; C. A. F. Varandas

1999-01-01

131

Increases in Insulin-Like Growth Factor Binding Protein2 Accompany Decreases in Proliferation and Differentiation When Porcine Muscle Satellite Cells Undergo Multiple Passages1  

Microsoft Academic Search

Subjecting cloned porcine myogenic satellite cells to multiple passages leads to decreased rates of cell division and myotube formation. Because IGF have been implicated in the regulation of muscle cell proliferation and differentiation, the present study was conducted to characterize secretion of IGF-I and IGF-binding proteins (IGFBP) in cultures of cloned porcine satellite cells at two stages of multiple passaging.

J. M. Fligger; P. V. Malven; M. E. Doumit; R. A. Merkel; A. L. Grant

2010-01-01

132

Calcium currents of olfactory bulb juxtaglomerular cells: profile and multiple conductance plateau potential simulation.  

PubMed

The olfactory glomerulus is the locus of information transfer between olfactory sensory neurons and output neurons of the olfactory bulb. Juxtaglomerular cells (JGCs) may influence intraglomerular processing by firing plateau potentials that support multiple spikes. It is unclear what inward currents mediate this firing pattern. In previous work, we characterized potassium currents of JGCs. We focus here on the inward currents using whole cell current clamp and voltage recording in a rat in vitro slice preparation, as well as computer simulation. We first showed that sodium current was not required to mediate plateau potentials. Voltage clamp characterization of calcium current (I(Ca)) determined that I(Ca) consisted of a slow activating, rapidly inactivating (?(10%-90% rise) 6-8 ms, ?(inactivation) 38-77 ms) component I(cat1), similar to T-type currents, and a sustained (?(inactivation)>500 ms) component I(cat2), likely composed of L-type and P/Q-type currents. We used computer simulation to test their roles in plateau potential firing. We robustly modeled I(cat1) and I(cat2) to Hodgkin-Huxley schemes (m(3)h and m(2), respectively) and simulated a JGC plateau potential with six conductances: calcium currents as above, potassium currents from our prior study (A-type I(kt1), D-type I(kt2), delayed rectifier I(kt3)), and a fast sodium current (I(Na)). We demonstrated that I(cat1) was required for mediating the plateau potential, unlike I(Na) and I(cat2), and its ?(inactivation) determined plateau duration. We also found that I(kt1) dictated plateau potential shape more than I(kt2) and I(kt3). The influence of these two transient and opposing conductances suggests a unique mechanism of plateau potential physiology. PMID:21704681

Masurkar, A V; Chen, W R

2011-09-29

133

Singularity analysis of multiple upward continuations to detect edges in potential field data  

NASA Astrophysics Data System (ADS)

In geophysical applications, a number of filters are available to sharpen, de-noise or enhance the data in order to facilitate the interpretation. However, such filters are often implemented in the Fourier domain. Hence, they are not local, acting on all features simultaneously. Detecting strong gradients and edges in potential field data are one of the important tasks to infer geological structures indicating the edges of source bodies. Edges are identified by local singularity analysis combing multiple depth level upward continuations are provided by authors. Sources close to the surface induce short-wavelength anomalies in the signal, whereas sources deep underground induce long-wavelength anomalies in the signal. Upward continuation allows the data to be smooth, attenuates short wavelengths in the signal stronger than long wavelengths so as to highlight deep sources that might be hidden by shallow sources or noise. A useful of local singularity model based on multifractal theory suggested by Qiuming Cheng has gained significant attention in characterizing mineralization and predicting mineral deposits. Especially, this model has had impressive successes in the weak anomaly identification, interpolation for geochemical data. Thus, we create the multiple upward continuation grids of the observed potential field data at various heights. We recommend to add a small value to shift the raw data (>0), and reduce the magnetic data to the pole firstly or even convert it to pseudogravity. Then the singularity indexes are estimated by the multiple heights versus upward continuations under the power law. We take the airborne gravity data and aeromagnetic data in the East Tianshan mountains with desert cover area in Xinjiang province, China as a case study. The singularity spatial distribution for the gravity data in the East Tianshan mountains area indicates the regional deep faults and The singularity spatial distribution for the aeromagnetic data implies the probable host anomaly geobodies of iron-related ore deposits.

Chen, Z.; Cheng, Q.; Lovejoy, S.

2012-12-01

134

The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis  

Microsoft Academic Search

SUMMARY Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS\\/MM phe- notype in transgenic mice with Em-directed expression of the XBP-1 spliced isoform (XBP-1s), a fac- tor governing unfolded protein\\/ER stress response and plasma-cell development. Em-XBP-1s eli- cited elevated serum Ig and skin

Daniel R. Carrasco; Kumar Sukhdeo; Marina Protopopova; Raktim Sinha; Miriam Enos; Mei Zheng; Mala Mani; Joel Henderson; Geraldine S. Pinkus; Nikhil Munshi; James Horner; Elena V. Ivanova; Alexei Protopopov; Kenneth C. Anderson; Giovanni Tonon; Ronald A. DePinho

2007-01-01

135

Multiple pathways are involved in DNA degradation during keratinocyte terminal differentiation  

PubMed Central

Loss of the nucleus is a critical step in keratinocyte terminal differentiation. To elucidate the mechanisms involved, we focused on two characteristic events: nuclear translocation of N-terminal fragment of profilaggrin and caspase-14-dependent degradation of the inhibitor of caspase-activated DNase (ICAD). First, we demonstrated that epidermal mesotrypsin liberated a 55-kDa N-terminal fragment of profilaggrin (FLG-N) and FLG-N was translocated into the nucleus. Interestingly, these cells became TUNEL positive. Mutation in the mesotrypsin-susceptible Arg-rich region between FLG-N and the first filaggrin domain abolished these changes. Furthermore, caspase-14 caused limited proteolysis of ICAD, followed by accumulation of caspase-activated DNase (CAD) in TUNEL-positive nuclei. Knockdown of both proteases resulted in a significant increase of remnant nuclei in a skin equivalent model. Immunohistochemical study revealed that both caspase-14 and mesotrypsin were markedly downregulated in parakeratotic areas of lesional skin from patients with atopic dermatitis and psoriasis. Collectively, our results indicate that at least two pathways are involved in the DNA degradation process during keratinocyte terminal differentiation. PMID:24743736

Yamamoto-Tanaka, M; Makino, T; Motoyama, A; Miyai, M; Tsuboi, R; Hibino, T

2014-01-01

136

Improved Filon-type asymptotic methods for highly oscillatory differential equations with multiple time scales  

NASA Astrophysics Data System (ADS)

In this paper we consider multi-frequency highly oscillatory second-order differential equations x?(t)+Mx(t)=f(t,x(t),x?(t)) where high-frequency oscillations are generated by the linear part Mx(t), and M is positive semi-definite (not necessarily nonsingular). It is known that Filon-type methods are effective approach to numerically solving highly oscillatory problems. Unfortunately, however, existing Filon-type asymptotic methods fail to apply to the highly oscillatory second-order differential equations when M is singular. We study and propose an efficient improvement on the existing Filon-type asymptotic methods, so that the improved Filon-type asymptotic methods can be able to numerically solving this class of multi-frequency highly oscillatory systems with a singular matrix M. The improved Filon-type asymptotic methods are designed by combining Filon-type methods with the asymptotic methods based on the variation-of-constants formula. We also present one efficient and practical improved Filon-type asymptotic method which can be performed at lower cost. Accompanying numerical results show the remarkable efficiency.

Wang, Bin; Wu, Xinyuan

2014-11-01

137

Broad spectrum late blight resistance in potato differential set plants MaR8 and MaR9 is conferred by multiple stacked R genes.  

PubMed

Phytophthora infestans is the causal agent of late blight in potato. The Mexican species Solanum demissum is well known as a good resistance source. Among the 11 R gene differentials, which were introgressed from S. demissum, especially R8 and R9 differentials showed broad spectrum resistance both under laboratory and under field conditions. In order to gather more information about the resistance of the R8 and R9 differentials, F1 and BC1 populations were made by crossing Mastenbroek (Ma) R8 and R9 clones to susceptible plants. Parents and offspring plants were examined for their pathogen recognition specificities using agroinfiltration with known Avr genes, detached leaf assays (DLA) with selected isolates, and gene-specific markers. An important observation was the discrepancy between DLA and field trial results for Pi isolate IPO-C in all F1 and BC1 populations, so therefore also field trial results were included in our characterization. It was shown that in MaR8 and MaR9, respectively, at least four (R3a, R3b, R4, and R8) and seven (R1, Rpi-abpt1, R3a, R3b, R4, R8, R9) R genes were present. Analysis of MaR8 and MaR9 offspring plants, that contained different combinations of multiple resistance genes, showed that R gene stacking contributed to the Pi recognition spectrum. Also, using a Pi virulence monitoring system in the field, it was shown that stacking of multiple R genes strongly delayed the onset of late blight symptoms. The contribution of R8 to this delay was remarkable since a plant that contained only the R8 resistance gene still conferred a delay similar to plants with multiple resistance genes, like, e.g., cv Sarpo Mira. Using this "de-stacking" approach, many R gene combinations can be made and tested in order to select broad spectrum R gene stacks that potentially provide enhanced durability for future application in new late blight resistant varieties. PMID:22109085

Kim, Hyoun-Joung; Lee, Heung-Ryul; Jo, Kwang-Ryong; Mortazavian, S M Mahdi; Huigen, Dirk Jan; Evenhuis, Bert; Kessel, Geert; Visser, Richard G F; Jacobsen, Evert; Vossen, Jack H

2012-03-01

138

Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla  

SciTech Connect

Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. The histone demethylase, lysine (K)-specific demethylase 2A (KDM2A), is evolutionarily conserved and ubiquitously expressed members of the JmjC-domain-containing histone demethylase family. A previous study determined that KDM2A can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2A is involved in the other cell lineages differentiation of MSCs. Here, we show that depletion of KDM2A by short hairpin RNAs can enhance adipogenic and chondrogenic differentiation potentials in human stem cells from apical papilla (SCAPs). We found that the stemness-related genes, SOX2, and the embryonic stem cell master transcription factor, NANOG were significantly increased after silence of KDM2A in SCAPs. Moreover, we found that knock-down of the KDM2A co-factor, BCOR also up-regulated the mRNA levels of SOX2 and NANOG. Furthermore, Chromatin immunoprecipitation assays demonstrate that silence of KDM2A increased the histone H3 Lysine 4 (H3K4) trimethylation in the SOX2 and NANOG locus and regulates its expression. In conclusion, our results suggested that depletion of KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of SCAPs by up-regulated SOX2 and NANOG, BCOR also involved in this regulation as co-factor, and provided useful information to understand the molecular mechanism underlying directed differentiation in MSCs. - Highlights: • Depletion of KDM2A enhances adipogenic/chondrogenic differentiation in SCAPs. • Depletion of KDM2A enhances the differentiation of SCAPs by activate SOX2 and NANOG. • Silence of KDM2A increases histone H3 Lysine 4 trimethylation in SOX2 and NANOG. • BCOR is co-factor of KDM2A involved in the differentiation regulation.

Dong, Rui [Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China); Yao, Rui [Department of Pediatrics, Stomatological Hospital of Nankai University, Tianjin 300041 (China); Du, Juan [Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China); Wang, Songlin [Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China); Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing 100069 (China); Fan, Zhipeng, E-mail: zpfan@ccmu.edu.cn [Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China)

2013-11-01

139

Identification of potential biomarkers from microarray experiments using multiple criteria optimization  

PubMed Central

Microarray experiments are capable of determining the relative expression of tens of thousands of genes simultaneously, thus resulting in very large databases. The analysis of these databases and the extraction of biologically relevant knowledge from them are challenging tasks. The identification of potential cancer biomarker genes is one of the most important aims for microarray analysis and, as such, has been widely targeted in the literature. However, identifying a set of these genes consistently across different experiments, researches, microarray platforms, or cancer types is still an elusive endeavor. Besides the inherent difficulty of the large and nonconstant variability in these experiments and the incommensurability between different microarray technologies, there is the issue of the users having to adjust a series of parameters that significantly affect the outcome of the analyses and that do not have a biological or medical meaning. In this study, the identification of potential cancer biomarkers from microarray data is casted as a multiple criteria optimization (MCO) problem. The efficient solutions to this problem, found here through data envelopment analysis (DEA), are associated to genes that are proposed as potential cancer biomarkers. The method does not require any parameter adjustment by the user, and thus fosters repeatability. The approach also allows the analysis of different microarray experiments, microarray platforms, and cancer types simultaneously. The results include the analysis of three publicly available microarray databases related to cervix cancer. This study points to the feasibility of modeling the selection of potential cancer biomarkers from microarray data as an MCO problem and solve it using DEA. Using MCO entails a new optic to the identification of potential cancer biomarkers as it does not require the definition of a threshold value to establish significance for a particular gene and the selection of a normalization procedure to compare different experiments is no longer necessary. PMID:23634293

Sanchez-Pena, Matilde L; Isaza, Clara E; Perez-Morales, Jaileene; Rodriguez-Padilla, Cristina; Castro, Jose M; Cabrera-Rios, Mauricio

2013-01-01

140

Identification of potential biomarkers from microarray experiments using multiple criteria optimization.  

PubMed

Microarray experiments are capable of determining the relative expression of tens of thousands of genes simultaneously, thus resulting in very large databases. The analysis of these databases and the extraction of biologically relevant knowledge from them are challenging tasks. The identification of potential cancer biomarker genes is one of the most important aims for microarray analysis and, as such, has been widely targeted in the literature. However, identifying a set of these genes consistently across different experiments, researches, microarray platforms, or cancer types is still an elusive endeavor. Besides the inherent difficulty of the large and nonconstant variability in these experiments and the incommensurability between different microarray technologies, there is the issue of the users having to adjust a series of parameters that significantly affect the outcome of the analyses and that do not have a biological or medical meaning. In this study, the identification of potential cancer biomarkers from microarray data is casted as a multiple criteria optimization (MCO) problem. The efficient solutions to this problem, found here through data envelopment analysis (DEA), are associated to genes that are proposed as potential cancer biomarkers. The method does not require any parameter adjustment by the user, and thus fosters repeatability. The approach also allows the analysis of different microarray experiments, microarray platforms, and cancer types simultaneously. The results include the analysis of three publicly available microarray databases related to cervix cancer. This study points to the feasibility of modeling the selection of potential cancer biomarkers from microarray data as an MCO problem and solve it using DEA. Using MCO entails a new optic to the identification of potential cancer biomarkers as it does not require the definition of a threshold value to establish significance for a particular gene and the selection of a normalization procedure to compare different experiments is no longer necessary. PMID:23634293

Sánchez-Peña, Matilde L; Isaza, Clara E; Pérez-Morales, Jaileene; Rodríguez-Padilla, Cristina; Castro, José M; Cabrera-Ríos, Mauricio

2013-04-01

141

Identification of multiple differentially expressed messenger RNAs in normal and pathological trophoblast.  

PubMed

In an attempt to assess the molecular basis of phenotypic alterations present in the gestational trophoblastic diseases (GTDs) and to identify genes whose expression is specifically associated to these placental proliferative disorders we performed differential display techniques. Initially 19 candidate gene fragments were identified and differential expression was confirmed in eight of these fragments by Northern blot analysis. At the mRNA level ribosomal L26 (rL26), ribosomal L27 (rL27), a new Krüppel type zinc finger protein and TIS11d were preferentially expressed in normal early placenta (NEP) relative to complete hydatidiform mole (CHM), persistent gestational trophoblastic disease (PGTD) and choriocarcinoma JEG-3 cell line. In contrast, heterogeneous ribonucleoprotein A1 (hnRNPA1), the ferritin light chain mRNA, and the uncharacterized protein KIAA0992 were predominantly expressed in JEG-3 cell line. Finally, decorin, a prototype member of an expanding family of small leucine-rich proteoglycans, showed high expression in CHM. In addition we demonstrated by immunohistochemistry analysis that increased decorin mRNA in CHM reflected a genuine augmentation in average steady state mRNA levels within cells. Taken together, these findings provide several interesting candidates for regulation of tumorigenic expression as well as early placentation development, including those involved in protein synthesis (rL26 and rL27), metabolism (ferritin light chain), intercellular communication (decorin) and regulation of gene expression (Krüppel-like zinc finger, TIS11d and hnRNPA1). Information about such alterations in gene expression could be useful for elucidating the genetic events associated to gestational trophoblastic pathogenesis, developing new diagnostic markers, or determining novel therapeutic targets. PMID:12566248

Durand, S; Abadie, P; Angeletti, S; Genti-Raimondi, S

2003-01-01

142

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation  

PubMed Central

Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development. PMID:23457234

Weinberg, Peter; Flames, Nuria; Sawa, Hitoshi; Garriga, Gian; Hobert, Oliver

2013-01-01

143

Medicago truncatula symbiotic peptide NCR247 contributes to bacteroid differentiation through multiple mechanisms.  

PubMed

Symbiosis between rhizobia soil bacteria and legume plants results in the formation of root nodules where plant cells are fully packed with nitrogen fixing bacteria. In the host cells, the bacteria adapt to the intracellular environment and gain the ability for nitrogen fixation. Depending on the host plants, the symbiotic fate of bacteria can be either reversible or irreversible. In Medicago and related legume species, the bacteria undergo a host-directed multistep differentiation process culminating in the formation of elongated and branched polyploid bacteria with definitive loss of cell division ability. The plant factors are nodule-specific symbiotic peptides. Approximately 600 of them are nodule-specific cysteine-rich (NCR) peptides produced in the rhizobium-infected plant cells. NCRs are targeted to the endosymbionts, and concerted action of different sets of peptides governs different stages of endosymbiont maturation, whereas the symbiotic function of individual NCRs is unknown. This study focused on NCR247, a cationic peptide exhibiting in vitro antimicrobial activities. We show that NCR247 acts in those nodule cells where bacterial cell division is arrested and cell elongation begins. NCR247 penetrates the bacteria and forms complexes with many bacterial proteins. Interaction with FtsZ required for septum formation is one of the host interventions for inhibiting bacterial cell division. Complex formation with the ribosomal proteins affects translation and contributes to altered proteome and physiology of the endosymbiont. Binding to the chaperone GroEL amplifies the NCR247-modulated biological processes. We show that GroEL1 of Sinorhizobium meliloti is required for efficient infection, terminal differentiation, and nitrogen fixation. PMID:24706863

Farkas, Attila; Maróti, Gergely; Durg?, Hajnalka; Györgypál, Zoltán; Lima, Rui M; Medzihradszky, Katalin F; Kereszt, Attila; Mergaert, Peter; Kondorosi, Éva

2014-04-01

144

Medicago truncatula symbiotic peptide NCR247 contributes to bacteroid differentiation through multiple mechanisms  

PubMed Central

Symbiosis between rhizobia soil bacteria and legume plants results in the formation of root nodules where plant cells are fully packed with nitrogen fixing bacteria. In the host cells, the bacteria adapt to the intracellular environment and gain the ability for nitrogen fixation. Depending on the host plants, the symbiotic fate of bacteria can be either reversible or irreversible. In Medicago and related legume species, the bacteria undergo a host-directed multistep differentiation process culminating in the formation of elongated and branched polyploid bacteria with definitive loss of cell division ability. The plant factors are nodule-specific symbiotic peptides. Approximately 600 of them are nodule-specific cysteine-rich (NCR) peptides produced in the rhizobium-infected plant cells. NCRs are targeted to the endosymbionts, and concerted action of different sets of peptides governs different stages of endosymbiont maturation, whereas the symbiotic function of individual NCRs is unknown. This study focused on NCR247, a cationic peptide exhibiting in vitro antimicrobial activities. We show that NCR247 acts in those nodule cells where bacterial cell division is arrested and cell elongation begins. NCR247 penetrates the bacteria and forms complexes with many bacterial proteins. Interaction with FtsZ required for septum formation is one of the host interventions for inhibiting bacterial cell division. Complex formation with the ribosomal proteins affects translation and contributes to altered proteome and physiology of the endosymbiont. Binding to the chaperone GroEL amplifies the NCR247-modulated biological processes. We show that GroEL1 of Sinorhizobium meliloti is required for efficient infection, terminal differentiation, and nitrogen fixation. PMID:24706863

Farkas, Attila; Maroti, Gergely; Durgo, Hajnalka; Gyorgypal, Zoltan; Lima, Rui M.; Medzihradszky, Katalin F.; Kereszt, Attila; Mergaert, Peter; Kondorosi, Eva

2014-01-01

145

PPAR?2 NUCLEAR RECEPTOR CONTROLS MULTIPLE REGULATORY PATHWAYS OF OSTEOBLAST DIFFERENTIATION FROM MARROW MESENCHYMAL STEM CELLS  

PubMed Central

Rosiglitazone (Rosi), a member of the thiazolidinedione class of drugs used to treat type 2 diabetes, activates the adipocyte-specific transcription factor peroxisome proliferator-activated receptor gamma (PPAR?). This activation causes bone loss in animals and humans, at least in part due to suppression of osteoblast differentiation from marrow mesenchymal stem cells (MSC). In order to identify mechanisms by which PPAR?2 suppresses osteoblastogenesis and promotes adipogenesis in MSC, we have analyzed the PPAR?2 transcriptome in response to Rosi. A total of 4,252 transcriptional changes resulted when Rosi (1 ?M) was applied to the U-33 marrow stromal cell line stably transfected with PPAR?2 (U-33/?2) as compared to non-induced U-33/?2 cells. Differences between U-33/?2 and U-33 cells stably transfected with empty vector (U-33/c) comprised 7,928 transcriptional changes, independent of Rosi. Cell type-, time- and treatment-specific gene clustering uncovered distinct patterns of PPAR?2 transcriptional control of MSC lineage commitment. The earliest changes accompanying Rosi activation of PPAR?2 included effects on Wnt, TGF?/BMP and G-protein signaling activities, as well as sustained induction of adipocyte-specific gene expression and lipid metabolism. While suppression of osteoblast phenotype is initiated by a diminished expression of osteoblast-specific signaling pathways, induction of the adipocyte phenotype is initiated by adipocyte-specific transcriptional regulators. This indicates that distinct mechanisms govern the repression of osteogenesis and the stimulation of adipogenesis. The co-expression patterns found here indicate that PPAR?2 has a dominant role in controlling osteoblast differentiation and suggests numerous gene-gene interactions that could lead to the identification of a “master” regulatory scheme directing this process. PMID:19115254

Shockley, Keith R.; Lazarenko, Oxana P.; Czernik, Piotr J.; Rosen, Clifford J.; Churchill, Gary A.; Lecka-Czernik, Beata

2009-01-01

146

Method and system for measuring multiphase flow using multiple pressure differentials  

DOEpatents

An improved method and system for measuring a multiphase flow in a pressure flow meter. An extended throat venturi is used and pressure of the multiphase flow is measured at three or more positions in the venturi, which define two or more pressure differentials in the flow conduit. The differential pressures are then used to calculate the mass flow of the gas phase, the total mass flow, and the liquid phase. The method for determining the mass flow of the high void fraction fluid flow and the gas flow includes certain steps. The first step is calculating a gas density for the gas flow. The next two steps are finding a normalized gas mass flow rate through the venturi and computing a gas mass flow rate. The following step is estimating the gas velocity in the venturi tube throat. The next step is calculating the pressure drop experienced by the gas-phase due to work performed by the gas phase in accelerating the liquid phase between the upstream pressure measuring point and the pressure measuring point in the venturi throat. Another step is estimating the liquid velocity in the venturi throat using the calculated pressure drop experienced by the gas-phase due to work performed by the gas phase. Then the friction is computed between the liquid phase and a wall in the venturi tube. Finally, the total mass flow rate based on measured pressure in the venturi throat is calculated, and the mass flow rate of the liquid phase is calculated from the difference of the total mass flow rate and the gas mass flow rate.

Fincke, James R. (Idaho Falls, ID)

2001-01-01

147

Reconstruction of multiple gastric electrical wave fronts using potential-based inverse methods  

NASA Astrophysics Data System (ADS)

One approach for non-invasively characterizing gastric electrical activity, commonly used in the field of electrocardiography, involves solving an inverse problem whereby electrical potentials on the stomach surface are directly reconstructed from dense potential measurements on the skin surface. To investigate this problem, an anatomically realistic torso model and an electrical stomach model were used to simulate potentials on stomach and skin surfaces arising from normal gastric electrical activity. The effectiveness of the Greensite-Tikhonov or the Tikhonov inverse methods were compared under the presence of 10% Gaussian noise with either 84 or 204 body surface electrodes. The stability and accuracy of the Greensite-Tikhonov method were further investigated by introducing varying levels of Gaussian signal noise or by increasing or decreasing the size of the stomach by 10%. Results showed that the reconstructed solutions were able to represent the presence of propagating multiple wave fronts and the Greensite-Tikhonov method with 204 electrodes performed best (correlation coefficients of activation time: 90%; pacemaker localization error: 3 cm). The Greensite-Tikhonov method was stable with Gaussian noise levels up to 20% and 10% change in stomach size. The use of 204 rather than 84 body surface electrodes improved the performance; however, for all investigated cases, the Greensite-Tikhonov method outperformed the Tikhonov method.

Kim, J. H. K.; Pullan, A. J.; Cheng, L. K.

2012-08-01

148

Reconstruction of multiple gastric electrical wave fronts using potential based inverse methods  

PubMed Central

One approach, commonly used in the field of electrocardiography, involves solving an inverse problem whereby electrical potentials on the stomach surface are directly reconstructed from dense potential measurements on the skin surface. To investigate this problem, an anatomically realistic torso model and an electrical stomach model were used to simulate potentials on stomach and skin surfaces arising from normal gastric electrical activity. The effectiveness of the Greensite-Tikhonov or the Tikhonov inverse methods were compared under the presence of 10% Gaussian noise with either 84 or 204 body surface electrodes. The stability and accuracy of the Greensite-Tikhonov method was further investigated by introducing varying levels of Gaussian signal noise or by increasing or decreasing the size of the stomach by 10%. Results showed that the reconstructed solutions were able to represent the presence of propagating multiple wave fronts and the Greensite-Tikhonov method with 204 electrodes performed best (Correlation coefficients of activation time: 90%; Pacemaker localization error: 3 cm). The Greensite-Tikhonov method was stable with Gaussian noise levels up to 20% and 10% change in stomach size. The use of 204 rather than 84 body surface electrodes improved the performance; however, for all investigated cases, the Greensite-Tikhonov method outperformed the Tikhonov method. PMID:22842812

Kim, J HK; Pullan, A J; Cheng, L K

2012-01-01

149

Barrier potential design criteria in multiple-quantum-well-based solar-cell structures  

NASA Technical Reports Server (NTRS)

The barrier potential design criteria in multiple-quantum-well (MQW)-based solar-cell structures is reported for the purpose of achieving maximum efficiency. The time-dependent short-circuit current density at the collector side of various MQW solar-cell structures under resonant condition was numerically calculated using the time-dependent Schroedinger equation. The energy efficiency of solar cells based on the InAs/Ga(y)In(1-y)As and GaAs/Al(x)Ga(1-x)As MQW structues were compared when carriers are excited at a particular solar-energy band. Using InAs/Ga(y)In(1-y)As MQW structures it is found that a maximum energy efficiency can be achieved if the structure is designed with barrier potential of about 450 meV. The efficiency is found to decline linearly as the barrier potential increases for GaAs/Al(x)Ga(1-x)As MQW-structure-based solar cells.

Mohaidat, Jihad M.; Shum, Kai; Wang, W. B.; Alfano, R. R.

1994-01-01

150

Multiple-scattering Green-function method for space-filling cell potentials  

NASA Astrophysics Data System (ADS)

It is shown that the equations of multiple-scattering theory (MST) originally derived for scattering off collections of muffin-tin (MT) potentials, i.e., potential cells bounded by nonoverlapping spheres, remain valid in the case of arbitrarily shaped, nonoverlapping, and particularly space-filling potential cells. Specifically, it is shown that in the angular momentum representation the total scattering (transition) matrix, the Green function, the Bloch function for a translationally invariant material, and the Lloyd formula for the change in the integrated density of states have forms that are invariant with respect to the partition of a given potential into nonoverlapping cells, and with respect to the choice of the cell centers. An analytic proof is provided for the vanishing of near-field corrections (NFC's) long conjectured to arise when the spheres bounding individual cells overlap one another or adjacent potentials. Thus, the well-known MST expressions, originally derived for the case of MT potentials, for obtaining the solution of the Schrödinger equation and hence determining the band structure and the charge density of materials, ordered or disordered, are rigorously valid in the completely general case of arbitrarily shaped cells. The differences between this work and previous attempts to generalize MST to non-MT space-filling potentials are discussed. It is pointed out that in calculations involving non-MT potential cells, particular attention must be paid to the question of convergence of expansions in angular momentum eigenstates. This convergence is tested numerically in terms of cluster calculations and through the calculation of the electronic structure of elemental bcc Nb and fcc Zr and Rh. The results of the cluster calculations confirm the vanishing of NFC's in the cases studied, while the electronic-structure calculations indicate the rather rapid convergence that can be expected in applications of MST to close-packed structures. The conclusions that can be drawn from the analytic and computational aspects of the present work are summarized in the final section, along with our plans for future work.

Gonis, A.; Zhang, X.-G.; Nicholson, D. M.

1989-07-01

151

Melanocytic differentiation is present in a significant proportion of nonpigmented diffuse neurofibromas: a potential diagnostic pitfall.  

PubMed

Whereas the pigmented (melanotic) variant of diffuse neurofibroma (DNF) with positivity for melanocytic markers is well recognized, expression of melanocytic markers in nonpigmented DNF has not been systematically studied. We analyzed 28 unselected consecutive DNFs for expression of melanocytic markers, including melan A, microphthalmia transcription factor (MITF), and HMB-45 antigen. For comparison, we also analyzed 40 localized skin neurofibromas and 7 intraneural neurofibromas. One case of nonpigmented DNF was analyzed by electron microscopy. Of the 28 DNFs studied by immunohistochemistry, 3 were pigmented and 25 nonpigmented. The 3 pigmented DNFs and 9 of 25 (36%) nonpigmented DNFs expressed melan A, MITF, and HMB-45 antigen. These markers were expressed either focally or more diffusely, typically in a minority of the lesional cells, and usually both in the dermal and subcutaneous portion of the DNF. Melan A was expressed in the largest number of the lesional cells (up to 50%), whereas only a small fraction of the melan A-positive cells (from 5% to 10% in most cases) also expressed HMB-45 antigen. None of the 47 non-DNFs expressed these markers. Ultrastructurally, melanosomes were present in some cells in nonpigmented DNF that expressed the melanocytic markers. Twenty-three of 28 (82%) DNFs, including 10 of 12 (83%) DNFs with melanocytic differentiation, were associated with neurofibromatosis type 1. Expression of melanocytic markers, including melan A, HMB-45 antigen, and MITF in DNF is a potential pitfall in differential diagnosis with melanocytic lesions that may clinically or histopathologically resemble DNF, in particular congenital melanocytic nevus with neurotization and neurofibroma-like melanoma. PMID:23715161

Pižem, Jože; Nicholson, Kimberly M; Mraz, Jerica; Prieto, Victor G

2013-08-01

152

Parallel Multiplicative Target Screening Against Divergent Bacterial Replicases: Identification of Specific Inhibitors with Broad Spectrum Potential  

PubMed Central

Typically, biochemical screens that employ pure macromolecular components focus on single targets or a small number of interacting components. Researches rely on whole cell screens for more complex systems. Bacterial DNA replicases contain multiple subunits that change interactions with each stage of a complex reaction. Thus, the actual number of targets is a multiple of the proteins involved. It is estimated that the overall replication reaction contains up to 100 essential targets, many suitable for discovery of antibacterial inhibitors. We have developed an assay, using purified protein components, where inhibitors of any of the essential targets can be detected through a common readout. Use of purified components allows each protein to be set within the linear range where the readout is proportional to the extent of inhibition of the target. By performing assays against replicases from model Gram-negative and Gram-positive bacteria in parallel, we show that it is possible to distinguish compounds that inhibit only a single bacterial replicase from those that exhibit broad spectrum potential. PMID:20184361

Dallmann, H. Garry; Fackelmayer, Oliver J.; Tomer, Guy; Chen, Joe; Wiktor-Becker, Anna; Ferrara, Tracey; Pope, Casey; Oliveira, Marcos T.; Burgers, Peter M. J.; Kaguni, Laurie S.; McHenry, Charles S.

2010-01-01

153

Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation  

Microsoft Academic Search

Mammalian transcriptome analysis has uncovered tens of thousands of novel transcripts of unknown function (TUFs). Classical and recent examples suggest that the majority of TUFs may underlie vital intracellular functions as non-coding RNAs because of their low coding potentials. However, only a portion of TUFs have been studied to date, and the functional significance of TUFs remains mostly uncharacterized. To

Kunio Kikuchi; Makiha Fukuda; Tomoya Ito; Mitsuko Inoue; Takahide Yokoi; Suenori Chiku; Toutai Mitsuyama; Kiyoshi Asai; Tetsuro Hirose; Yasunori Aizawa

2009-01-01

154

Multiple Solutions for Nonhomogeneous Neumann Differential Inclusion Problems by the p(x)-Laplacian  

PubMed Central

A class of nonlinear Neumann problems driven by p(x)-Laplacian with a nonsmooth locally Lipschitz potential (hemivariational inequality) was considered. The approach used in this paper is the variational method for locally Lipschitz functions. More precisely, Weierstrass theorem and Mountain Pass theorem are used to prove the existence of at least two nontrivial solutions. PMID:24453903

Zhou, Qing-Mei

2013-01-01

155

Potential multiple steady-states in the long-term carbon cycle  

E-print Network

Modelers of the long term carbon cycle in Earth history have previously assumed there is only one stable climatic steady state. Here we investigate the possibility of multiple steady states. We find them in Abiotic World, lacking any biotic influence, resulting from possible variations in planetary albedo in different temperature, atmospheric carbon dioxide level regimes, with the same weathering forcing balancing a volcanic source to the atmosphere, ocean pool. In Plant World modeling relevant to the Phanerozoic, we include the additional effects of biotic enhancement of weathering on land, organic carbon burial, oxidation of reduced organic carbon in terrestrial sediments and the variation of biotic productivity with temperature, finding a second stable steady state appearing between twenty and fifty degrees C. The very warm early Triassic climate may be the prime candidate for an upper temperature steady state. Given our results, the anthropogenic driven rise of atmospheric carbon dioxide could potentially...

Tennenbaum, Stephen; Schwartzman, David

2013-01-01

156

In vitro assessment of mesenchymal stem cells immunosuppressive potential in multiple sclerosis patients.  

PubMed

Mesenchymal stem cells (MSC) are promising for multiple sclerosis (MS) treatment. However, clinical results remain controversial, and no criteria are available for predicting the efficiency of MSC therapy. Using an in vitro model of lymphocytes and MSC cocultivation we revealed that the Index of MSC Suppression of myelin-induced memory T cells proliferation was stronger than that of PHA-stimulated proliferation and inversely correlated with patients'EDSS score. In vitro expression of CD119 (IFNGR1) in mitogen/myelin-stimulated T cells increased in the presence of MSC being inversely correlated with T-lymphocytes proliferation. The Index of MSC Suppression and CD119 expression in T-lymphocytes may be useful when assessing MSC immunosuppressive potential in MS patients. PMID:23089549

Zafranskaya, Marina M; Nizheharodova, Darya B; Yurkevich, Mariya Yu; Lamouskaya, Natallia V; Motuzova, Yana M; Bagatka, Svetlana S; Ivanchik, Halina I; Fedulov, Alexander S

2013-01-01

157

The potential of miRNAs as biomarkers for multiple myeloma.  

PubMed

Since the discovery of the link between miRNA and cancer, miRNAs have been investigated in virtually all tumors. Their ability to add a novel level of gene regulation and to target genes apparently not linked to each other has greatly intrigued researchers and physicians alike. In this review, the role of miRNAs in multiple myeloma (MM) is summarized, with particular attention to their potential as biomarkers. The promising role of circulating miRNAs in diagnosis and risk stratification is also discussed, as well as preliminary results of miRNA-based therapeutic approaches. Finally, the critical issues in miRNA analysis in MM and ongoing strategies to solve them are discussed. The ability to standardize miRNA analysis procedures will permit the inclusion of miRNA evaluation alongside available stratification tools, paving the way for personalized medicine in MM. PMID:25098410

Rocci, Alberto; Hofmeister, Craig C; Pichiorri, Flavia

2014-11-01

158

Affinity maturation leads to differential expression of multiple copies of a kappa light-chain transgene.  

PubMed

Transgenic animals containing rearranged heavy or light chains are used to study the process of hypermutation, which characterizes the maturation of the antibody response. LK6 mice contain five copies of a transgene coding for a light chain produced in response to the hapten 2-phenyloxazolone. We have selected hybridomas from secondary responses that express the transgene as the only light chain. Some of these hybridomas contain transgene copies carrying mutations known to improve antibody affinity. We have analysed the expression of the five transgene copies in those hybridomas. We report here that the somatic hypermutation process can affect the successful expression of antibody light-chain transgenes. When mutations that improve the antibody affinity appear in one transgene copy, antigenic selection favours cells that downregulate the other copies at multiple levels of gene expression, including examples where nonsense mutations correlate with a drop in messenger RNA level. PMID:8487865

Lozano, F; Rada, C; Jarvis, J M; Milstein, C

1993-05-20

159

Differential performance of Chinese volleyball athletes and nonathletes on a multiple-object tracking task.  

PubMed

The difference between athletes and nonathletes on the performance of a multiple-object tracking (MOT) task was examined. Participants were 17 national professional volleyball athletes and 20 age-matched nonathletes who were university students and attended basic volleyball training classes. Across trials, the number of distractors and the color and form of the targets were manipulated. A negative correlation was observed between the number of distractors and participants' reaction time. Further, all participants responded faster when the target color changed during a trial than when it remained consistent. Athletes had faster reaction time than nonathletes independent of the number of distractors or target manipulation. Male athletes also had faster overall reaction time than female athletes. The implications of these findings for athletic training are discussed. PMID:20178275

Zhang, Xuemin; Yan, Ming; Yangang, Liao

2009-12-01

160

The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis  

PubMed Central

Summary Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with E?-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. E?-XBP-1s elicited elevated serum Ig and skin alterations. With age, E?-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of E?-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis. PMID:17418411

Carrasco, Daniel R.; Sukhdeo, Kumar; Protopopova, Marina; Sinha, Raktim; Enos, Miriam; Carrasco, Daniel E.; Zheng, Mei; Mani, Mala; Henderson, Joel; Pinkus, Geraldine S.; Munshi, Nikhil; Horner, James; Ivanova, Elena V.; Protopopov, Alexei; Anderson, Kenneth C.; Tonon, Giovanni; DePinho, Ronald A.

2007-01-01

161

The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis.  

PubMed

Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Emu-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Emu-XBP-1s elicited elevated serum Ig and skin alterations. With age, Emu-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Emu-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis. PMID:17418411

Carrasco, Daniel R; Sukhdeo, Kumar; Protopopova, Marina; Sinha, Raktim; Enos, Miriam; Carrasco, Daniel E; Zheng, Mei; Mani, Mala; Henderson, Joel; Pinkus, Geraldine S; Munshi, Nikhil; Horner, James; Ivanova, Elena V; Protopopov, Alexei; Anderson, Kenneth C; Tonon, Giovanni; DePinho, Ronald A

2007-04-01

162

Time response of a controllable multiplate magnetorheological fluid limited slip differential clutch  

NASA Astrophysics Data System (ADS)

This study focuses on investigation of the time response of a controllable limited slip differential (LSD) clutch consisting of an on-off close-loop control system and a magneto-rheological fluid (MRF). The control law of the controller is based on velocity feedback where the main goal is to keep the relative velocity of the input and output shafts of the clutch less than a predetermined threshold value. The response time of the control system (including the DAQ system and the computer) and the MRF LSD clutch is examined both theoretically and experimentally. System identification experiments are performed to determine the parameters such as bearing friction coefficients, dry and viscous clutch torque coefficients. These coefficients are used in theoretical response time analysis of the MRF LSD clutch using MATLAB Simulink. It is demonstrated that, the simple on-off closed-loop control system is feasible for this clutch application. The response time reduces by increasing solenoid current and increasing velocity. The theoretical model predictions are in good agreement with the experimental results.

Cobanoglu, Nigar; Gordaninejad, Faramarz; Evrensel, Cahit A.; Liu, Yanming; Kavlicoglu, Barkan M.; Korol, George

2003-08-01

163

Geochemical consequences of flow differentiation in a multiple injection dike (Trinity ophiolite, N. California)  

NASA Astrophysics Data System (ADS)

A clinopyroxene-rich dike of the Trinity ophiolite sheeted-dike complex shows three different magmatic pulses, probably injected in a short period of time (no well developed chilled margin) and important variations of the clinopyroxene and plagioclase percentages between its core (highly porphyritic) and margins (aphyric). This variation, interpreted as related to a flow differentiation phenomenon (mechanical phenocryst redistribution), has important geochemical consequences. It produces increases in the FeO, MgO, CaO, Cr and Ni contents from the margin to the core, together with increases in the clinopyroxene percentage, and decreases in the SiO 2, Zr, Y, Nb and REE contents together with a decrease in the percentage of the fine-grained groundmass toward the core of the dike. This mineralogical redistribution, which also affects the incompatible trace element ratios because of the difference in plagioclase and clinopyroxene mineral/liquid partition coefficients, illustrate the importance of fractionation processes outside of a magma chamber.

Brouxel, Marc

1991-01-01

164

Climate impacts at multiple scales: evidence for differential population responses in juvenile Chinook salmon.  

PubMed

1. We explored differential population responses to climate in 18 populations of threatened spring-summer Chinook salmon Onchorynchus tshawytscha in the Salmon River basin, Idaho. 2. Using data from a long-term mark-release-recapture study of juvenile survival, we found that fall stream flow is the best predictor of average survival across all populations. 3. To determine whether all populations responded similarly to climate, we used a cluster analysis to group populations that had similar annual fluctuations in survival. The populations grouped into four clusters, and different environmental factors were important for different clusters. 4. Survival in two of the clusters was negatively correlated with summer temperature, and survival in the other two clusters was positively correlated with minimum fall stream flow, which in turn depends on snow pack from the previous winter. 5. Using classification and regression tree analysis, we identified stream width and stream temperature as key habitat factors that shape the responses of individual populations to climate. 6. Climate change will likely have different impacts on different populations within this metapopulation, and recognizing this diversity is important for accurately assessing risks. PMID:16922845

Crozier, Lisa; Zabel, Richard W

2006-09-01

165

Idiopathic inflammatory demyelinating diseases of the central nervous system: differentiating between acute disseminated encephalomyelitis and malignant multiple sclerosis.  

PubMed

Multiple sclerosis (MS) is the most frequent demyelinating disorder of the central nervous system (CNS). However, at presentation, it is frequently difficult to differentiate between malignant MS (MMS) and other fulminant CNS demyelinating diseases like acute disseminated encephalomyelitis (ADEM). The literature contains many case reports of ADEM but few series. We report on four representative cases of acute demyelinating diseases, together with evaluation of treatment, course and follow-up. We also present clinical, laboratory, neuropathologic, neuroimaging and data on therapeutic options, including follow-up, in order to establish distinguishing characteristics of MMS and ADEM. Good clinical outcome from a postinfectious, monophasic episode, correlating with regressive demyelinating lesions on MRI, after more than 2 years differentiate best. Therapeutic efficacy, prior infection and initial MRI lesions seem to be of limited value. Despite the advances of neuroimaging and laboratory techniques, objective parameters are still missing, but findings on basic immunologic mechanisms of humoral and cellular response might provide further insight. Copyright 1999 Harcourt Publishers Ltd. PMID:10835172

Haase; Faustmann; Diener

1999-05-01

166

Identification of Multiple Subsets of Ventral Interneurons and Differential Distribution along the Rostrocaudal Axis of the Developing Spinal Cord  

PubMed Central

The spinal cord contains neuronal circuits termed Central Pattern Generators (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor neurons and multiple interneuron cell types, many of which are derived from four distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3. While significant progress has been made on elucidating the molecular and genetic mechanisms that control ventral interneuron differentiation, little is known about their distribution along the antero-posterior axis of the spinal cord and their diversification. Here, we report that V0, V1 and V2 interneurons exhibit distinct organizational patterns at brachial, thoracic and lumbar levels of the developing spinal cord. In addition, we demonstrate that each cardinal class of ventral interneurons can be subdivided into several subsets according to the combinatorial expression of different sets of transcription factors, and that these subsets are differentially distributed along the rostrocaudal axis of the spinal cord. This comprehensive molecular profiling of ventral interneurons provides an important resource for investigating neuronal diversification in the developing spinal cord and for understanding the contribution of specific interneuron subsets on CPG circuits and motor control. PMID:23967072

Francius, Cedric; Harris, Audrey; Rucchin, Vincent; Hendricks, Timothy J.; Stam, Floor J.; Barber, Melissa; Kurek, Dorota; Grosveld, Frank G.; Pierani, Alessandra; Goulding, Martyn; Clotman, Frederic

2013-01-01

167

Induction of osteoblast differentiation indexes by PTHrP in MG-63 cells involves multiple signaling pathways.  

PubMed

Parathyroid hormone (PTH)-related peptide (PTHrP) can modulate the proliferation and differentiation of a number of cell types including osteoblasts. PTHrP can activate a G protein-coupled PTH/PTHrP receptor, which can interface with several second-messenger systems. In the current study, we have examined the signaling pathways involved in stimulated type I collagen and alkaline phosphatase expression in the human osteoblast-derived osteosarcoma cells, MG-63. By use of Northern blotting and histochemical analysis, maximum induction of these two markers of osteoblast differentiation occurred after 8 h of treatment with 100 nM PTHrP-(1-34). Chemical inhibitors of adenylate cyclase (H-89) or of protein kinase C (chelerythrine chloride) each diminished PTHrP-mediated type I collagen and alkaline phosphatase stimulation in a dose-dependent manner. These effects of PTHrP could also be blocked by inhibiting the Ras-mitogen-activated protein kinase (MAPK) pathway with a Ras farnesylation inhibitor, B1086, or with a MAPK inhibitor, PD-98059. Transient transfection of MG-63 cells with a mutant form of Galpha, which can sequester betagamma-subunits, showed significant downregulation of PTHrP-stimulated type I collagen expression, as did inhibition of phosphatidylinositol 3-kinase (PI 3-kinase) by wortmannin. Consequently, the betagamma-PI 3-kinase pathway may be involved in PTHrP stimulation of Ras. Collectively, these results demonstrate that, acting via its G protein-coupled receptor, PTHrP can induce indexes of osteoblast differentiation by utilizing multiple, perhaps parallel, signaling pathways. PMID:11500304

Carpio, L; Gladu, J; Goltzman, D; Rabbani, S A

2001-09-01

168

Differential diagnosis of posterior fossa multiple sclerosis lesions--neuroradiological aspects.  

PubMed

Various infratentorial pathological conditions can mimic multiple sclerosis (MS) both clinically and radiologically. We review the inflammatory, vascular, neoplastic and metabolic conditions which show features similar to those of MS on magnetic resonance imaging (MRI). Behcet's disease, Lyme disease, progressive multifocal leukoencephalopathy, neurosarcoidosis, Whipple's disease, listeria rhombencephalitis, Bickerstaff's brainstem encephalitis, vasculitis due to systemic lupus erythematosus, and acute disseminated encephalomyelitis produce inflammatory lesions similar to those of MS in the brainstem and cerebellum. Neoplastic diseases, in particular pontine gliomas and lymphomas, can mimic MS. Vascular ischaemic lesions, either due to infarction produced by occlusion of a major posterior circulation artery or due to small vessel vasculopathy, can lead to posterior fossa lesions. The MRI changes of central pontine myelinolysis can also mimic MS. Diffuse axonal injury, radiation and chemotherapy induce lesions that resemble MS, however the clinical history will exclude these possibilities. Finally, we discuss a few conditions which are similar to MS in clinical presentation but have different MRI appearances, such as brainstem cavernomas, posterior fossa tumoural lesions, aneurysms and vascular loops producing neurovascular conflicts. Analysis of the MRI findings with clinical history and laboratory data helps to narrow down the diagnosis of the infratentorial pathology. PMID:11794484

Falini, A; Kesavadas, C; Pontesilli, S; Rovaris, M; Scotti, G

2001-11-01

169

Differentiation of Neuromyelitis Optica from Multiple Sclerosis on Spinal Magnetic Resonance Imaging  

PubMed Central

In order to examine the accuracy of magnetic resonance imaging (MRI)–based diagnosis of neuromyelitis optica (NMO) versus multiple sclerosis (MS), we performed a retrospective, rater-blinded review of 29 cases of NMO and 30 cases of MS using the criteria of long (more than three vertebral levels), continuous lesions with a central cord location for NMO and more peripheral and patchy lesions for MS. Using these criteria, two raters were able to distinguish the two conditions with a good degree of confidence, particularly when the imaging was performed at the time of an acute cord attack. The sensitivity and specificity for diagnosis of NMO were 86.2% and 93.3%, respectively, for Rater A and 96.4% and 78.6%, respectively, for Rater B, with a kappa value of 0.72. Thus there are significant differences in lesion characteristics that allow the distinction on spinal cord imaging between MS and NMO with a moderately high degree of confidence. The location of the lesion as evident on MRI of the spine can be regarded as a distinguishing diagnostic feature between MS and NMO. PMID:24453753

Khan, Majid; Schlakman, Bruce; Penman, Alan; Gatlin, Joseph; Herndon, Robert

2012-01-01

170

Multiple regression, ANN (RBF, MLP) and ANFIS models for prediction of swell potential of clayey soils  

NASA Astrophysics Data System (ADS)

In the recent years, new techniques such as; artificial neural networks and fuzzy inference systems were employed for developing of the predictive models to estimate the needed parameters. Soft computing techniques are now being used as alternate statistical tool. Determination of swell potential of soil is difficult, expensive, time consuming and involves destructive tests. In this paper, use of MLP and RBF functions of ANN (artificial neural networks), ANFIS (adaptive neuro-fuzzy inference system) for prediction of S% (swell percent) of soil was described, and compared with the traditional statistical model of MR (multiple regression). However the accuracies of ANN and ANFIS models may be evaluated relatively similar. It was found that the constructed RBF exhibited a high performance than MLP, ANFIS and MR for predicting S%. The performance comparison showed that the soft computing system is a good tool for minimizing the uncertainties in the soil engineering projects. The use of soft computing will also may provide new approaches and methodologies, and minimize the potential inconsistency of correlations.

Yilmaz, Isik; Kaynar, Oguz

2010-05-01

171

Data Visualization Speeds Review of Potential Adverse Drug Events in Patients on Multiple Medications  

PubMed Central

Patients on multiple medications are at increased risk for adverse drug events. While physicians can reduce this risk by regularly reviewing the side-effect profiles of their patients’ medications, this process can be time-consuming. We created a decision support system designed to expedite reviewing potential adverse reactions through information visualization. The system includes a database containing 16,340 unique drug and side-effect pairs, representing 250 common medications. A numeric score is assigned to each pair reflecting the strength of association between drug and effect. Based on these scores, the system generates graphical adverse reaction maps for any user-selected combination of drugs. A study comparing speed and accuracy of retrieving side-effect data using this tool versus UpToDate® demonstrated a 60% reduction in time to complete a query (61 seconds vs. 155 seconds, p<0.0001) with no decrease in accuracy. These findings suggest that information visualization can significantly expedite review of potential adverse drug events. PMID:19995616

Duke, Jon D.; Li, Xiaochun; Grannis, Shaun J.

2010-01-01

172

Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways  

PubMed Central

The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune response. PMID:25030899

Gruber, Andreas J.; Grandy, William A.; Balwierz, Piotr J.; Dimitrova, Yoana A.; Pachkov, Mikhail; Ciaudo, Constance; van Nimwegen, Erik; Zavolan, Mihaela

2014-01-01

173

Comparative Evaluation of Differentiation Potential of Menstrual Blood- Versus Bone Marrow- Derived Stem Cells into Hepatocyte-Like Cells  

PubMed Central

Menstrual blood has been introduced as an easily accessible and refreshing stem cell source with no ethical consideration. Although recent works have shown that menstrual blood stem cells (MenSCs) possess multi lineage differentiation capacity, their efficiency of hepatic differentiation in comparison to other stem cell resources has not been addressed so far. The aim of this study was to investigate hepatic differentiation capacity of MenSCs compared to bone marrow-derived stem cells (BMSCs) under protocols developed by different concentrations of hepatocyte growth factor (HGF) and oncostatin M (OSM) in combination with other components in serum supplemented or serum-free culture media. Such comparison was made after assessment of immunophenotye, trans-differentiation potential, immunogenicity and tumorigeicity of these cell types. The differential expression of mature hepatocyte markers such as albumin (ALB), cytokeratin 18 (CK-18), tyrosine aminotransferase and cholesterol 7 alpha-hydroxylase activities (CYP7A1) at both mRNA and protein levels in differentiating MenSCs was significantly higher in upper concentration of HGF and OSM (P1) compared to lower concentration of these factors (P2). Moreover, omission of serum during differentiation process (P3) caused typical improvement in functions assigned to hepatocytes in differentiated MenSCs. While up-regulation level of ALB and CYP7A1 was higher in differentiated MenSCs compared to driven BMSCs, expression level of CK-18, detected level of produced ALB and glycogen accumulation were lower or not significantly different. Therefore, based on the overall comparable hepatic differentiation ability of MenSCs with BMSCs, and also accessibility, refreshing nature and lack of ethical issues of MenSCs, these cells could be suggested as an apt and safe alternative to BMSCs for future stem cell therapy of chronic liver diseases. PMID:24505254

Zarnani, Amir-Hassan; Akhondi, Mohammad-Mehdi; Ahani, Ali; Ghaempanah, Zahra; Naderi, Mohammad Mehdi; Eghtesad, Saman; Kazemnejad, Somaieh

2014-01-01

174

Multiple gradient echo propeller (MGREP) MRI: Technical development and potential applications  

NASA Astrophysics Data System (ADS)

The PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction) magnetic resonance imaging (MRI) technique has inherent advantages over other fast imaging methods, including robust motion correction, reduced image distortion, and resistance to off-resonance effects. These features make PROPELLER highly desirable for T2*-sensitive imaging, high-resolution diffusion imaging, and many other applications. However, PROPELLER has been predominantly implemented as a fast spin-echo (FSE) technique, which is insensitive to T2* contrast, and requires time-inefficient signal averaging to achieve adequate signal-to-noise ratio (SNR) for many applications. These issues presently constrain the potential clinical utility of FSE-based PROPELLER. In this research, our aim was to extend and enhance the potential applications of PROPELLER MRI by developing a novel multiple gradient echo PROPELLER (MGREP) technique that can overcome the aforementioned limitations. The MGREP pulse sequence was designed to acquire multiple gradient-echo images simultaneously, without any increase in total scan time or RF energy deposition relative to FSE-based PROPELLER. A new parameter was also introduced for direct user-control over gradient echo spacing, to allow variable sensitivity to T2* contrast. In parallel to pulse sequence development, an improved algorithm for motion correction was also developed and evaluated against the established method through extensive simulations. The potential advantages of MGREP over FSE-based PROPELLER were illustrated via three specific applications: (1) quantitative T2* measurement, (2) time-efficient signal averaging, and (3) high-resolution diffusion imaging. Relative to the FSE-PROPELLER method, the MGREP sequence was found to yield quantitative T2* values, increase SNR by ˜40% without any increase in acquisition time or RF energy deposition, and noticeably improve image quality in high-resolution diffusion maps. In addition, the new motion algorithm was found to improve the performance considerably in motion-artifact reduction. Overall, this work demonstrated a number of enhancements and extensions to existing PROPELLER techniques. The new technical capabilities of PROPELLER imaging, developed in this thesis research, are expected to serve as the foundation for further expanding the scope of PROPELLER applications.

Poonawalla, Aziz Hatim

175

Dispersal syndrome differentiation of Pinus armandii in Southwest China: Key elements of a potential selection mosaic  

NASA Astrophysics Data System (ADS)

Pinus armandii is a species of pine native to China with a wide geographical distribution and large-wingless seeds (about 300 mg). The study is to determine the variation in seed dispersal traits among populations within a relative small geographic scale and furthermore to explore if the trait differentiation results in the differences in dispersers, in particular nutcrackers ( Nucifraga caryocatactes) and scatter-hoarding rodents. We conducted studies at five sites at different elevations in northwest Yunnan Province. The study sites are separated by 10-200 km and divided into populations partly isolated by mountains and rivers. The cone and seed traits diverged significantly among the five study sites while the traits among individual trees at each site did not differ significantly. Nutcrackers and scatter-hoarding rodents presented conflicting preference in cone and seed traits: nutcrackers preferred smaller cones with smaller seeds, which increased the foraging efficiency of nutcrackers; while scatter-hoarding rodents tended to cache larger seeds. Consistent with variation in preferences by nutcrackers and scatter-hoarding rodents, in nutcracker-dominated sites, pines were characterized by smaller cones, smaller seeds, and thinner seed coats; while in sites where nutcrackers were not abundant, pines had relatively larger cones with larger seeds, which could enhance caching activities by scatter-hoarding rodents. The study provided some key elements for potential selection mosaic on cone and seed traits of a long-lived perennial tree among populations with limited geographical range.

Chen, Fan; Chen, Jin

2011-11-01

176

Differential neural responses to humans vs. robots: an event-related potential study.  

PubMed

Do we perceive humanoid robots as human beings? Recent neuroimaging studies have reported similarity in the neural processing of human and robot actions in the superior temporal sulcus area but a differential neural response in the premotor area. These studies suggest that the neural activity of the occipitotemporal region would not be affected by appearance information. Unlike those studies, in this study, by using the inversion effect as an index, we demonstrated for the first time that the appearance information of a presented action affects neural responses in the occipitotemporal region. In event-related potential (ERP) studies, the inversion effect is the phenomenon whereby an upright face- and body-sensitive ERP component in the occipitotemporal region is enhanced and delayed up to 200 ms in response to an inverted face and body, but not to an inverted object. We used three kinds of walking animation with different appearance information (human, robot, and point-light) as well as inverted stimuli of each appearance. The anatomical structure and walking speed of the presented stimuli were all identical. The results showed that the inversion effect occurred in the right occipitotemporal region only in response to human appearance, and not robotic and point-light appearances. That is, the amplitude of the inverted condition of human appearance was significantly larger than that of the upright condition only. Our results, which are contrary to other recent neuroimaging studies, suggested that appearance information affects the neural response in the occipitotemporal region. PMID:17658496

Hirai, Masahiro; Hiraki, Kazuo

2007-08-24

177

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients.  

PubMed

Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-I] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-I DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-I infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1361867

Kitze, B; Turner, R W; Burchhardt, M; Poser, S; Hunsmann, G; Weber, T

1992-11-01

178

Developing Multiple Diverse Potential Designs for Heat Transfer Utilizing Graph Based Evolutionary Algorithms  

SciTech Connect

This paper examines the use of graph based evolutionary algorithms (GBEAs) to find multiple acceptable solutions for heat transfer in engineering systems during the optimization process. GBEAs are a type of evolutionary algorithm (EA) in which a topology, or geography, is imposed on an evolving population of solutions. The rates at which solutions can spread within the population are controlled by the choice of topology. As in nature geography can be used to develop and sustain diversity within the solution population. Altering the choice of graph can create a more or less diverse population of potential solutions. The choice of graph can also affect the convergence rate for the EA and the number of mating events required for convergence. The engineering system examined in this paper is a biomass fueled cookstove used in developing nations for household cooking. In this cookstove wood is combusted in a small combustion chamber and the resulting hot gases are utilized to heat the stove’s cooking surface. The spatial temperature profile of the cooking surface is determined by a series of baffles that direct the flow of hot gases. The optimization goal is to find baffle configurations that provide an even temperature distribution on the cooking surface. Often in engineering, the goal of optimization is not to find the single optimum solution but rather to identify a number of good solutions that can be used as a starting point for detailed engineering design. Because of this a key aspect of evolutionary optimization is the diversity of the solutions found. The key conclusion in this paper is that GBEA’s can be used to create multiple good solutions needed to support engineering design.

David J. Muth Jr.

2006-09-01

179

Theoretical and experimental study of Differential Pulse Voltammetry at spherical electrodes: Measuring diffusion coefficients and formal potentials  

Microsoft Academic Search

Rigorous and approximate analytical expressions are deduced for Differential Pulse Voltammetry at spherical electrodes of any size, including microelectrodes, when the electrogenerated species is soluble in the electrolytic solution. From these, we examine the utility of DPV for the determination of diffusion coefficients and formal potentials, establishing the optimum conditions for this purpose. The experimental validation of the theoretical results

Ángela Molina; Eduardo Laborda; Emma I. Rogers; Francisco Martínez-Ortiz; Carmen Serna; Juan G. Limon-Petersen; Neil V. Rees; Richard G. Compton

2009-01-01

180

Uncertainty assessment of spatially distributed nitrate reduction potential in groundwater using multiple geological realizations  

NASA Astrophysics Data System (ADS)

Spatially distributed nitrate reduction potential in groundwater was estimated for the clay till dominated Norsminde fjord catchment in Denmark using the distributed hydrological model MIKE SHE. The nitrate transport was simulated using particle tracking and nitrate was assumed to be instantaneously reduced at the redox interface. Spatially distributed depths of the redox interface were estimated based on the spatial patterns in groundwater recharge and sediment redox capacity. Uncertainty of the estimated nitrate reduction due to geological uncertainty was assessed using multiple geological realizations. The geological realizations were generated using the geostatistical software TProGS and either conditioned based on borehole data only or soft conditioned based on both borehole data and geophysical data. Finally an upscaling of the predicted nitrate reduction was done in order to evaluate the change in uncertainty with increasing scale. The study showed that the uncertainty (one standard deviation) of the estimated nitrate reduction potential (in percentage of nitrate input) on the original 100 m model scale was 25% if only using borehole data and 19% if combining the borehole data with geophysical data. The uncertainty on the model predictions decreased with increasing aggregation scale. The decrease in uncertainty was most apparent the first 500 m, where after the uncertainty started to level off. This scale corresponded well to the mean length of the sand units within the clay till. It is concluded that using geophysical data in combination with borehole data in generation of geological realizations can help decrease uncertainty on the estimated nitrate reduction and that the predictive capability of distributed models is constrained by the spatial resolution of key data such as geology.

Hansen, A. L.; Gunderman, D.; He, X.; Refsgaard, J. C.

2014-11-01

181

Motor evoked potentials in clinically isolated syndrome suggestive of multiple sclerosis.  

PubMed

The aim of the present study was to determine the sensitivity and the profile of motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We measured the central motor conduction time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients, the triple stimulation technique (TST) was also performed. AR was abnormal in 50% of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the highest sub-clinical sensitivity and the best positive predictive value. In the absence of clinical pyramidal signs, an early AR decrease seems to result from demyelination inducing excessive temporal dispersion of the MEP, while in territories with clinical pyramidal signs, it seems to result from conduction failure, which suggests that clinical pyramidal signs may be attributable to conduction failure. This study demonstrates that MEP, especially the AR, is sensitive to motor pathway dysfunction right from the early stages of MS. PMID:19153175

Rico, A; Audoin, B; Franques, J; Eusebio, A; Reuter, F; Malikova, I; Ali Cherif, A; Pouget, J; Pelletier, J; Attarian, S

2009-03-01

182

Multiple Spike Time Patterns Occur at Bifurcation Points of Membrane Potential Dynamics  

PubMed Central

The response of a neuron to repeated somatic fluctuating current injections in vitro can elicit a reliable and precisely timed sequence of action potentials. The set of responses obtained across trials can also be interpreted as the response of an ensemble of similar neurons receiving the same input, with the precise spike times representing synchronous volleys that would be effective in driving postsynaptic neurons. To study the reproducibility of the output spike times for different conditions that might occur in vivo, we somatically injected aperiodic current waveforms into cortical neurons in vitro and systematically varied the amplitude and DC offset of the fluctuations. As the amplitude of the fluctuations was increased, reliability increased and the spike times remained stable over a wide range of values. However, at specific values called bifurcation points, large shifts in the spike times were obtained in response to small changes in the stimulus, resulting in multiple spike patterns that were revealed using an unsupervised classification method. Increasing the DC offset, which mimicked an overall increase in network background activity, also revealed bifurcation points and increased the reliability. Furthermore, the spike times shifted earlier with increasing offset. Although the reliability was reduced at bifurcation points, a theoretical analysis showed that the information about the stimulus time course was increased because each of the spike time patterns contained different information about the input. PMID:23093916

Toups, J. Vincent; Fellous, Jean-Marc; Thomas, Peter J.; Sejnowski, Terrence J.; Tiesinga, Paul H.

2012-01-01

183

Diagnostic Accuracy of Apparent Diffusion Coefficient and 123I-Metaiodobenzylguanidine for Differentiation of Multiple System Atrophy and Parkinson's Disease  

PubMed Central

Background It is often hard to differentiate Parkinson’s disease (PD) and parkinsonian variant of multiple system atrophy (MSA-P), especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively. Purpose We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC) test for MSA-P and 123I-metaiodobenzylguanidine (MIBG) scintigram for PD, especially in early-stage patients. Methods The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson’s Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC), sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated. Results ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD). AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ?3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis) and 47.7% and 92.3% for the MIBG test (PD diagnosis). Conclusions Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results. PMID:23613784

Umemura, Atsushi; Oeda, Tomoko; Hayashi, Ryutaro; Tomita, Satoshi; Kohsaka, Masayuki; Yamamoto, Kenji; Sawada, Hideyuki

2013-01-01

184

Oscillatory Protein Expression Dynamics Endows Stem Cells with Robust Differentiation Potential  

PubMed Central

The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems. PMID:22073296

Kaneko, Kunihiko

2011-01-01

185

Endothelium Trans Differentiated from Wharton's Jelly Mesenchymal Cells Promote Tissue Regeneration: Potential Role of Soluble Pro-Angiogenic Factors  

PubMed Central

Background Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. Methods Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). Results hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. Conclusion These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors. PMID:25412260

Aguilera, Valeria; Briceño, Luis; Contreras, Hector; Lamperti, Liliana; Sepúlveda, Esperanza; Díaz-Perez, Francisca; León, Marcelo; Veas, Carlos; Maura, Rafael; Toledo, Jorge Roberto; Fernández, Paulina; Covarrubias, Ambart; Zuñiga, Felipe Andrés; Radojkovic, Claudia; Escudero, Carlos; Aguayo, Claudio

2014-01-01

186

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury  

SciTech Connect

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

2013-08-15

187

SITE-SPECIFIC PHOSPHORYLATION OF CXCR4 IS DYNAMICALLY REGULATED BY MULTIPLE KINASES AND RESULTS IN DIFFERENTIAL MODULATION OF CXCR4  

E-print Network

1 SITE-SPECIFIC PHOSPHORYLATION OF CXCR4 IS DYNAMICALLY REGULATED BY MULTIPLE KINASES AND RESULTS IN DIFFERENTIAL MODULATION OF CXCR4 SIGNALING John M. Busillo1 , Sylvain Armando2 , Rajarshi Sengupta3 , Olimpia head: CXCR4 phosphorylation and regulation Address correspondence to: Jeffrey L. Benovic, Dept

Meucci, Olimpia

188

Multiple-Locus Variable-Number Tandem-Repeat Analysis Is a Suitable Tool for Differentiation of Mycoplasma hyopneumoniae Strains without Cultivation?  

PubMed Central

An assay based on multiple-locus variable-number tandem-repeat analysis allowed differentiating and studying diversity and persistence of Mycoplasma hyopneumoniae strains in pig herds without prior cultivation. The test had a discriminatory index of >0.99 and was applied reliably to porcine bronchoalveolar lavage fluid and tracheal swabs. PMID:21389157

Vranckx, K.; Maes, D.; Calus, D.; Villarreal, I.; Pasmans, F.; Haesebrouck, F.

2011-01-01

189

Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology.  

PubMed

We sought to biologically characterize and identify a subpopulation of urine-derived stem cells (USCs) with the capacity for multipotent differentiation. We demonstrated that single USCs can expand to a large population with 60-70 population doublings. Nine of 15 individual USC clones expressed detectable levels of telomerase and have long telomeres. These cells expressed pericyte and mesenchymal stem cell markers. Upon induction with appropriate media in vitro, USCs differentiated into bladder-associated cell types, including functional urothelial and smooth muscle cell lineages. When the differentiated USCs were seeded onto a scaffold and subcutaneously implanted into nude mice, multilayered tissue-like structures formed consisting of urothelium and smooth muscle. Additionally, USCs were able to differentiate into endothelial, osteogenic, chondrogenic, adipogenic, skeletal myogenic, and neurogenic lineages but did not form teratomas during the 1-month study despite telomerase activity. USCs may be useful in cell-based therapies and tissue engineering applications, including urogenital reconstruction. PMID:23666768

Bharadwaj, Shantaram; Liu, Guihua; Shi, Yingai; Wu, Rongpei; Yang, Bin; He, Tongchuan; Fan, Yuxin; Lu, Xinyan; Zhou, Xiaobo; Liu, Hong; Atala, Anthony; Rohozinski, Jan; Zhang, Yuanyuan

2013-09-01

190

Cellular network entropy as the energy potential in Waddington's differentiation landscape  

NASA Astrophysics Data System (ADS)

Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.

Banerji, Christopher R. S.; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X.; Teschendorff, Andrew E.

2013-10-01

191

Cosmogenic 10Be in quartz and magnetite: Using the same nuclide in multiple minerals to quantify differential weathering  

NASA Astrophysics Data System (ADS)

Cosmogenic 10Be in detrital quartz has been widely used to quantify spatially averaged erosion rates for entire catchments. Here we show how the technique can be expanded to quantify the relative weathering rates of different minerals in catchment soils. As a case in point, we consider magnetite and quartz, which should share the same relationship between 10Be production rate and depth during erosion to the surface. However, the minerals likely do not share the same susceptibility to chemical weathering. We expect quartz to be enriched relative to magnetite due to differential chemical erosion in soils. Quartz should therefore have a longer soil residence time than magnetite. Thus, 10Be should be more concentrated in quartz than magnetite, at a ratio that depends on both the 10Be production-rate ratio and the relative enrichment of the two minerals. Here we develop a theoretical basis for interpreting 10Be ratios in multiple minerals and show preliminary data from catchments in the Southern Sierra Critical Zone Observatory, where chemical erosion rates are well constrained by geochemical mass balance.

Rogers, H. E.; Riebe, C. S.; Granger, D. E.

2013-12-01

192

Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity  

NASA Astrophysics Data System (ADS)

Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3?- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bon?s metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in perivascular cells population. It is one of the mechanisms of the osteogenic process intensity decrease in bones due to lowering support loading on the bone skeleton. In particular this is confirmed by the fact that in the zones of adaptive remodeling we found fibroblasts and fibrosis zones - areas filled with non mineralized collagen fibrils on the bones surfaces. Hence it should be considered that lowering (removal) support loading slows down (or blocks) osteogenic differentiation of the perivascular cells part and stimulates differentiation of the fibroblast cells. Obtained data considered as one of the cellular mechanisms of the adaptive reactions development in spongy bone under microgravity which could lead to the bone mass loss.

Rodionova, Natalia; Katkova, Olena

193

Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells  

SciTech Connect

For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs.

Chen, P.-Y. [Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan (China); Huang, Lynn L.H. [Institute of Biotechnology, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China) and Institute of Clinical Medicine, National Cheng Kung University, Tainan 70101, Taiwan (China)]. E-mail: lynn@mail.ncku.edu.tw; Hsieh, H.-J. [Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan (China)]. E-mail: hjhsieh@ntu.edu.tw

2007-08-17

194

Changes in the Potential Multiple Cropping System in Response to Climate Change in China from 1960-2010  

PubMed Central

The multiple cropping practice is essential to agriculture because it has been shown to significantly increase the grain yield and promote agricultural economic development. In this study, potential multiple cropping systems in China are calculated based on meteorological observation data by using the Agricultural Ecology Zone (AEZ) model. Following this, the changes in the potential cropping systems in response to climate change between the 1960s and the 2010s were subsequently analyzed. The results indicate that the changes of potential multiple cropping systems show tremendous heterogeneity in respect to the spatial pattern in China. A key finding is that the magnitude of change of the potential cropping systems showed a pattern of increase both from northern China to southern China and from western China to eastern China. Furthermore, the area found to be suitable only for single cropping decreased, while the area suitable for triple cropping increased significantly from the 1960s to the 2000s. During the studied period, the potential multiple cropping index (PMCI) gap between rain-fed and irrigated scenarios increased from 18% to 24%, which indicated noticeable growth of water supply limitations under the rain-fed scenario. The most significant finding of this research was that from the 1960s to the 2000s climate change had led to a significant increase of PMCI by 13% under irrigated scenario and 7% under rain-fed scenario across the whole of China. Furthermore, the growth of the annual mean temperature is identified as the main reason underlying the increase of PMCI. It has also been noticed that across China the changes of potential multiple cropping systems under climate change were different from region to region. PMID:24312511

Liu, Luo; Xu, Xinliang; Zhuang, Dafang; Chen, Xi; Li, Shuang

2013-01-01

195

Changes in the potential multiple cropping system in response to climate change in China from 1960-2010.  

PubMed

The multiple cropping practice is essential to agriculture because it has been shown to significantly increase the grain yield and promote agricultural economic development. In this study, potential multiple cropping systems in China are calculated based on meteorological observation data by using the Agricultural Ecology Zone (AEZ) model. Following this, the changes in the potential cropping systems in response to climate change between the 1960s and the 2010s were subsequently analyzed. The results indicate that the changes of potential multiple cropping systems show tremendous heterogeneity in respect to the spatial pattern in China. A key finding is that the magnitude of change of the potential cropping systems showed a pattern of increase both from northern China to southern China and from western China to eastern China. Furthermore, the area found to be suitable only for single cropping decreased, while the area suitable for triple cropping increased significantly from the 1960s to the 2000s. During the studied period, the potential multiple cropping index (PMCI) gap between rain-fed and irrigated scenarios increased from 18% to 24%, which indicated noticeable growth of water supply limitations under the rain-fed scenario. The most significant finding of this research was that from the 1960s to the 2000s climate change had led to a significant increase of PMCI by 13% under irrigated scenario and 7% under rain-fed scenario across the whole of China. Furthermore, the growth of the annual mean temperature is identified as the main reason underlying the increase of PMCI. It has also been noticed that across China the changes of potential multiple cropping systems under climate change were different from region to region. PMID:24312511

Liu, Luo; Xu, Xinliang; Zhuang, Dafang; Chen, Xi; Li, Shuang

2013-01-01

196

Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma  

PubMed Central

Deregulated expression of genes encoding members of the S100 family of calcium-binding proteins has been associated with the malignant progression of multiple tumour types. Using a pharmacological expression reactivation approach, we screened 16 S100 genes for evidence of epigenetic regulation in medulloblastoma, the most common malignant brain tumour of childhood. Four family members (S100A2, S100A4, S100A6 and S100A10) demonstrated evidence of upregulated expression in multiple medulloblastoma cell lines, following treatment with the DNA methyltransferase inhibitor, 5?-aza-2?-deoxycytidine. Subsequent analysis revealed methylation of critical CpG sites located within these four genes in an extended cell line panel. Assessment of these genes in the non-neoplastic cerebellum (from which medulloblastomas develop) revealed strong somatic methylation affecting S100A2 and S100A4, whereas S100A6 and S100A10 were unmethylated. Assessed against these normal tissue-specific methylation states, S100A6 and S100A10 demonstrated tumour-specific hypermethylation in medulloblastoma primary tumours (5 out of 40 and 4 out of 35, respectively, both 12%) and cell lines (both 7 out of 9, 78%), which was associated with their transcriptional silencing. Moreover, S100A6 hypermethylation was significantly associated with the aggressive large cell/anaplastic morphophenotype (P=0.026). In contrast, pro-metastatic S100A4 displayed evidence of hypomethylation relative to the normal cerebellum in a significant proportion primary tumours (7 out of 41, 17%) and cell lines (3 out of 9, 33%), which was associated with its elevated expression. In summary, these data characterise complex patterns of somatic methylation affecting S100 genes in the normal cerebellum and demonstrate their disruption causing epigenetic deregulation of multiple S100 family members in medulloblastoma development. Epigenetic events affecting S100 genes have potential clinical utility and merit further investigation as molecular biomarkers for this disease. PMID:17579622

Lindsey, J C; Lusher, M E; Anderton, J A; Gilbertson, R J; Ellison, D W; Clifford, S C

2007-01-01

197

Motor evoked potentials in multiple sclerosis patients without walking limitation: amplitude vs. conduction time abnormalities.  

PubMed

We used Motor Evoked Potentials (MEPs), elicited by transcranial magnetic stimulation, for assessing a motor pathways dysfunction in a selected group of Multiple Sclerosis (MS) patients, without limitation in walking. We selected 32 Relapsing Remitting MS patients, in remission phase, with EDSS < or = 3.5 and 20 healthy individuals with similar height and age distribution. We measured the following MEP parameters: motor thresholds; central motor conduction time (CMCT); amplitude and area, both expressed as MEP/CMAP ratio. Patients were divided into two groups according to the EDSS score: non-disabled group (ND; EDSS 0-1.5) and disabled group (D; EDSS 2-3.5). Mean average MEP values were significantly different in the patients compared with the controls. Even in MS patients with no or minor neurological signs (ND group), MEP parameters showed differences from controls and furthermore all MEP parameters were significantly different in the D group compared with the ND group. The 75% of the patients had an amplitude or area alteration; this percentage was significantly higher than the percentage of patients with a CMCT alteration (56.2%). In addition, CMCT increase was always associated with reduced amplitude and area, but amplitude and area alterations were present also in patients with normal CMCT. In early stages of MS, the higher percentage shown in alteration of MEP amplitudes and areas as opposed to CMCTs has not previously been highlighted in the literature. Independently of its pathogenesis (demyelination or axonal loss), the amplitude or area decrease should be considered in clinical trials and in follow-up studies, as a marker of the motor pathways dysfunction, at least as much as CMCT increase. PMID:17308868

Gagliardo, Andrea; Galli, Francesca; Grippo, Antonello; Amantini, Aldo; Martinelli, Cristiana; Amato, Maria Pia; Borsini, Walter

2007-02-01

198

Serum prohepcidin levels are potential prognostic markers in patients with multiple myeloma.  

PubMed

Prohepcidin is the prohormone of hepcidin. Anemia is one of the main clinical features in patients with multiple myeloma (MM) and hepcidin may be associated with iron homeostasis in these patients. However, the clinical significance of prohepcidin is not fully understood. In this retrospective study, we measured serum prohepcidin levels using an immunoassay technique to study its clinical significance in 39 MM patients. Serum prohepcidin levels in patients with MM were weakly correlated with alkaline phosphatase (ALP) levels (r=0.32, P=0.048), calculated by Spearman's rank correlation, but not with other clinical data, including hemoglobin, serum iron or ferritin. In addition, patients with severe renal insufficiency [creatinine clearance (CCr) <50 ml/min] had significantly higher prohepcidin levels compared with patients with mild or no renal insufficiency (CCr ?50 ml/min, P=0.047). In contrast, low serum prohepcidin levels less than 110 ng/ml were an independent predictor of poor overall survival [hazard ratio (HR), 5.29; 95% confidence interval (CI), 1.65-17.03] in addition to serum creatinine levels of at least 2 mg/dl (HR, 5.32; CI, 1.10-25.64), serum calcium (HR, 3.53; CI, 1.01-12.33) and ECOG performance status grade 4 (HR, 4.15; CI, 1.32-13.09) in the multivariate analysis using Cox proportional hazards model. In the subset of 31 MM patients with CCr ?50 ml/min, low serum prohepcidin (HR, 5.65; CI, 1.60-19.95) was an indicator of poor prognosis in multivariate analysis. These results indicate that serum prohepcidin levels may be associated with ALP and renal function but not iron homeostasis, in MM patients. In addition, lower serum prohepcidin levels are potential independent indicators of poor overall survival in MM patients regardless of renal function. PMID:23170109

Haraguchi, Kouichi; Uto, Hirofumi; Ohnou, Nobuhito; Tokunaga, Masahito; Tokunaga, Mayumi; Utsunomiya, Atae; Hanada, Shuichi; Tsubouchi, Hirohito

2012-10-01

199

Phosphoprotein enriched in astrocytes (PEA)-15: A potential therapeutic target in multiple disease states  

PubMed Central

Phosphoprotein enriched in astrocytes-15 (PEA-15) is a cytoplasmic protein that sits at an important junction in intracellular signalling and can regulate diverse cellular processes, such as proliferation and apoptosis, dependent upon stimulation. Regulation of these processes occurs by virtue of the unique interaction of PEA-15 with other signalling proteins. PEA-15 acts as a cytoplasmic tether for the mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 (ERK1/2) preventing nuclear localisation. In order to release ERK1/2, PEA-15 requires to be phosphorylated via several potential pathways. PEA-15 (and its phosphorylation state) therefore regulates many ERK1/2-dependent processes, including proliferation, via regulating ERK1/2 nuclear translocation. In addition, PEA-15 contains a death effector domain (DED) which allows interaction with other DED-containing proteins. PEA-15 can bind the DED-containing apoptotic adaptor molecule, Fas-associated death domain protein (FADD) which is also dependent on the phosphorylation status of PEA-15. PEA-15 binding of FADD can inhibit apoptosis as bound FADD cannot participate in the assembly of apoptotic signalling complexes. Through these protein–protein interactions, PEA-15-regulated cellular effects have now been investigated in a number of disease-related studies. Changes in PEA-15 expression and regulation have been observed in diabetes mellitus, cancer, neurological disorders and the cardiovascular system. These changes have been suggested to contribute to the pathology related to each of these disease states. As such, new therapeutic targets based around PEA-15 and its associated interactions are now being uncovered and could provide novel avenues for treatment strategies in multiple diseases. PMID:24657708

Greig, Fiona H.; Nixon, Graeme F.

2014-01-01

200

Interleukin-1? promotes long-term potentiation in patients with multiple sclerosis.  

PubMed

The immune system shapes synaptic transmission and plasticity in experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis (MS). These synaptic adaptations are believed to drive recovery of function after brain lesions, and also learning and memory deficits and excitotoxic neurodegeneration; whether inflammation influences synaptic plasticity in MS patients is less clear. In a cohort of 59 patients with MS, we found that continuous theta-burst transcranial magnetic stimulation did not induce the expected long-term depression (LTD)-like synaptic phenomenon, but caused persisting enhancement of brain cortical excitability. The amplitude of this long-term potentiation (LTP)-like synaptic phenomenon correlated with the concentration of the pro-inflammatory cytokine interleukin-1? (IL-1?) in the cerebrospinal fluid. In MS and EAE, the brain and spinal cord are typically enriched of CD3(+) T lymphocyte infiltrates, which are, along with activated microglia and astroglia, a major cause of inflammation. Here, we found a correlation between the presence of infiltrating T lymphocytes in the hippocampus of EAE mice and synaptic plasticity alterations. We observed that T lymphocytes from EAE, but not from control mice, release IL-1? and promote LTP appearance over LTD, thereby mimicking the facilitated LTP induction observed in the cortex of MS patients. EAE-specific T lymphocytes were able to suppress GABAergic transmission in an IL-1?-dependent manner, providing a possible synaptic mechanism able to lower the threshold of LTP induction in MS brains. Moreover, in vivo blockade of IL-1? signaling resulted in inflammation and synaptopathy recovery in EAE hippocampus. These data provide novel insights into the pathophysiology of MS. PMID:23892937

Mori, Francesco; Nisticò, Robert; Mandolesi, Georgia; Piccinin, Sonia; Mango, Dalila; Kusayanagi, Hajime; Berretta, Nicola; Bergami, Alessandra; Gentile, Antonietta; Musella, Alessandra; Nicoletti, Carolina G; Nicoletti, Ferdinando; Buttari, Fabio; Mercuri, Nicola B; Martino, Gianvito; Furlan, Roberto; Centonze, Diego

2014-03-01

201

Potential Benefits of Nintendo Wii Fit Among People with Multiple Sclerosis  

PubMed Central

We examined the potential of Nintendo Wii Fit (Nintendo Co, Ltd, Kyoto, Japan) to increase physical activity (PA) behavior and health among people with multiple sclerosis (MS). The study consisted of a repeated-measures design with a baseline control period and involved 30 people with MS who had the ability to walk 25 feet with or without a cane (26 individuals were included in the analyses). Nintendo Wii was set up in the homes of participants, who were prescribed a Wii Fit exercise program lasting 14 weeks, 3 days a week. The Physical Activity and Disability Survey, Modified Fatigue Impact Scale, and 36-item Short Form Health Status Survey were administered three times before participants gained access to Wii Fit (control period, at 2-week intervals), and three times after they received Wii Fit (posttest 1: immediately after; posttest 2: 7 weeks after; posttest 3: 14 weeks after). Mobility, balance, strength, and weight were assessed at the first pretest, immediately prior to obtaining access to Wii Fit, and 7 weeks after obtaining access to Wii Fit. Results from the questionnaires indicated that PA significantly improved at week 7, but at week 14, PA levels declined relative to week 7 and the difference was no longer significant compared with the control period. Physical assessments indicated that balance and strength significantly improved at week 7. One adverse event was reported (repetitive knee injury). Physical assessments indicated that people with MS may be able to improve their fitness levels by using Wii Fit. Future studies should incorporate behavior change strategies to promote long-term use of Wii Fit, and explore whether individuals with more severe symptoms of MS can safely use Wii Fit. PMID:24453702

Finlayson, Marcia

2011-01-01

202

Effects of long-term differential fertilization on eukaryotic microbial communities in an arable soil: a multiple barcoding approach.  

PubMed

To understand the fine-scale effects of changes in nutrient availability on eukaryotic soil microorganisms communities, a multiple barcoding approach was used to analyse soil samples from four different treatments in a long-term fertilization experiment. We performed PCR amplification on soil DNA with primer pairs specifically targeting the 18S rRNA genes of all eukaryotes and three protist groups (Cercozoa, Chrysophyceae-Synurophyceae and Kinetoplastida) as well as the ITS gene of fungi and the 23S plastid rRNA gene of photoautotrophic microorganisms. Amplicons were pyrosequenced, and a total of 88,706 quality filtered reads were clustered into 1232 operational taxonomic units (OTU) across the six data sets. Comparisons of the taxonomic coverage achieved based on overlapping assignment of OTUs revealed that half of the eukaryotic taxa identified were missed by the universal eukaryotic barcoding marker. There were only little differences in OTU richness observed between organic- (farmyard manure), mineral- and nonfertilized soils. However, the community compositions appeared to be strongly structured by organic fertilization in all data sets other than that generated using the universal eukaryotic 18S rRNA gene primers, whereas mineral fertilization had only a minor effect. In addition, a co-occurrence based network analysis revealed complex potential interaction patterns between OTUs from different trophic levels, for example between fungivorous flagellates and fungi. Our results demonstrate that changes in pH, moisture and organic nutrients availability caused shifts in the composition of eukaryotic microbial communities at multiple trophic levels. PMID:24888892

Lentendu, Guillaume; Wubet, Tesfaye; Chatzinotas, Antonis; Wilhelm, Christian; Buscot, François; Schlegel, Martin

2014-07-01

203

Saliva soluble HLA as a potential marker of response to interferon-?1a in multiple sclerosis: A preliminary study  

Microsoft Academic Search

OBJECTIVE: Potential surrogate markers of disease activity, including response to therapy, are particularly important in a neurological disorder such as multiple sclerosis (MS) which often has a fluctuating course. Based upon previous studies in our laboratory, we hypothesized that measurement of soluble HLA (sHLA) molecules class II in saliva of MS patients can serve as marker of therapeutic response to

Alireza Minagar; Irena Adamashvili; Roger E Kelley; Eduardo Gonzalez-Toledo; Jerry McLarty; Stacy J Smith

2007-01-01

204

Expression Profiles Provide Insights into Early Malignant Potential and Skeletal Abnormalities in Multiple Endocrine Neoplasia Type 2B Syndrome Tumors  

Microsoft Academic Search

Identifying the molecular basis for genotype-phenotype correlations in human diseases has direct implications for understanding the disease process and hence for the identification of potential therapeutic targets. To this end, we performed microarray expression analysis on benign (pheochromocytomas) and malignant (medullary thyroid carcinomas, MTCs) tumors from patients with multiple endocrine neoplasia (MEN) type 2A or 2B, related syndromes that result

Sanjay Jain; Mark A. Watson; Mary K. DeBenedetti; Yuji Hiraki; Jeffrey F. Moley; Jeffrey Milbrandt

2004-01-01

205

Spectroelectrochemical Determination of the Redox Potential of Cytochrome c via Multiple Regression An Undergraduate Instrumental Analysis or Biochemistry Laboratory Exercise  

Microsoft Academic Search

This laboratory exercise can be used in an undergraduate course in Biochemistry or Instrumental Methods. Bovine cytochrome c is reduced in the presence of DCIP in an enzyme- coupled redox reaction. The reduction is monitored spectroscopically and the concentrations of the individual species are determined from Beer's law via multiple regression. The redox potential of cytochrome c is estimated from

Graham T. Whitaker; Eugene A. Belogay; Eugene T. Smith

206

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis  

Microsoft Academic Search

Objective: To evaluate motor cortex excitability changes by transcranial magnetic stimulation (TMS) following repetitive muscle contractions in patients with multiple sclerosis (MS); to state whether a typical pattern of post-exercise motor evoked potentials (MEPs) is related to clinical fatigue in MS.Methods: In 41 patients with definite MS (32 with fatigue and 9 without fatigue according to Fatigue Severity Scale) and

A Perretti; P Balbi; G Orefice; L Trojano; L Marcantonio; V Brescia-Morra; S Ascione; F Manganelli; G Conte; L Santoro

2004-01-01

207

The Effect of the Residual Ion Potential on the Fully Differential Cross Section of Helium for Ionization by Electron Impact  

SciTech Connect

We have carried out calculations for the fully differential cross section of the ionization of helium by electron projectiles. In order to study the effect of the residual ion potential, we employed three models, and tested them for the coplanar and perpendicular plane geometry. In spite of the simplicity of our models, the results for the coplanar case are in fair agreement with the available experimental data. The results for the perpendicular geometry need more improvement.

Toth, A.; Nagy, L. [Faculty of Physics, Babes-Bolyai University, str. Kogalniceanu nr.1, 400084 Cluj (Romania)

2011-10-03

208

Effects of potential xenoestrogens (DEHP, nonylphenol and PCB) on sexual differentiation in juvenile Atlantic salmon ( Salmo salar)  

Microsoft Academic Search

The effects of 17?-estradiol and potential xenoestrogens were investigated on Atlantic salmon (Salmo salar). Juvenile salmon fed diets containing 15 and 30mg 17?-estradiol kg?1 food for 4weeks after yolk-sac resorption differentiated into 88 and 100% phenotypic females, respectively. The reference group, fed uncontaminated food, consisted of 49% females. A significant overrepresentation of phenotypic females (64%) was recorded in the group

L. Norrgren; A. Blom; P. L. Andersson; H. Börjeson; D. G. J. Larsson; P.-E. Olsson

1999-01-01

209

A label-free high throughput resistive-pulse sensor for simultaneous differentiation and measurement of multiple particle-laden analytes  

NASA Astrophysics Data System (ADS)

We describe an all-electronic, label-free, resistive-pulse sensor that utilizes multiple microchannels for parallel detection, counting and differentiation of multiple biological particles simultaneously. Four particle solutions, including 20 µm and 40 µm polymethacrylate particles, Juniper Scopulorum (Rocky Mountain Juniper) pollen and Populus deltidoes (Eastern Cottonwood) pollen, were loaded to the four peripheral reservoirs, respectively, and were driven to the central reservoir through four microchannels, all operating simultaneously for particle detection and counting. Experiments demonstrated that this sensor was able to differentiate and count multiple particle solutions simultaneously through its four microchannels fabricated on polymer membranes. Thus the sensing throughput has been improved significantly in contrast to typical Coulter counters without sacrificing accuracy, sensitivity and reliability. Furthermore, the experimental results also proved the feasibility of differentiating various pollens from polymethacrylate microparticles with the multi-channel resistive-pulse sensor. The differentiation is based on difference in size and surface charge for the bioparticles, with no need for labeling of samples. Possible improvements and extensions to other biological particle detection are discussed.

Jagtiani, Ashish V.; Sawant, Rupesh; Zhe, Jiang

2006-08-01

210

Evaluation of evoked potentials and lymphocyte subsets as possible markers of multiple sclerosis: one year follow up of 30 patients.  

PubMed Central

Evoked potentials and T-lymphocyte helper/suppressor ratio (H/S) were evaluated serially together with neurological status in 30 definite multiple sclerosis patients to evaluate their possible role in monitoring disease progression. Evoked potentials in many cases reflected the clinical status of the pathways tested, but some exceptions were observed, probably due to subclinical relapses or physical factors. In some instances the occurrence of subclinical relapses was suggested by increased H/S ratios. Serial H/S values increased in parallel with clinical and subclinical relapses, and seemed to show specific patterns in relation to the type of clinical course (relapsing, stable, chronic progressive). Our results suggest that evoked potentials and H/S ratio serial analysis can contribute to a better assessment of the progress of multiple sclerosis. PMID:3489075

Ghezzi, A; Zaffaroni, M; Caputo, D; Montanini, R; Cazzullo, C L

1986-01-01

211

Possibilities and Potential Barriers: Learning to Plan for Differentiated Instruction in Elementary Science  

ERIC Educational Resources Information Center

Research indicates that differentiated practices enhance the likelihood of meeting the needs of students who find literacy learning challenging (Tobin & McInnes, 2008; Tomlinson, 2003). The aim of the professional development project described here was to leverage these findings and to build the foundation for future research exploring if…

Tobin, Ruthanne; Tippett, Christine D.

2014-01-01

212

Differential neural responses to humans vs. robots: An event-related potential study  

Microsoft Academic Search

Do we perceive humanoid robots as human beings? Recent neuroimaging studies have reported similarity in the neural processing of human and robot actions in the superior temporal sulcus area but a differential neural response in the premotor area. These studies suggest that the neural activity of the occipitotemporal region would not be affected by appearance information. Unlike those studies, in

Masahiro Hirai; Kazuo Hiraki

2007-01-01

213

Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells  

Microsoft Academic Search

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order

James D Kretlow; Yu-Qing Jin; Wei Liu; Wen Jie Zhang; Tan-Hui Hong; Guangdong Zhou; L Scott Baggett; Antonios G Mikos; Yilin Cao

2008-01-01

214

Wild-type p53 differentially affects tumorigenic and metastatic potential of murine metastatic cell variants  

Microsoft Academic Search

The structure and the function of the p53 gene were studied in two metastatic cell variants derived from Lewis lung carcinoma. Single missense mutation at codon 334 was detected in the p53 gene of both cell variants. In spite of the identical mutation, the in vitro and in vivo growth rates of the two cell variants were differentially affected by

Maria Giulia Rizzo; Silvia Soddu; Giulio Tibursi; Bruno Calabretta; Ada Sacchi

1993-01-01

215

[The diagnostic significance of auditory evoked brain stem potentials in multiple sclerosis].  

PubMed

30 patients suffering from multiple sclerosis were examined by BERA among other audiological tests. In 47% we stated significant pathological BERA-latencies, in 53% pathological interpeak-intervals. The most patients have symptoms of brainstem, but 3 cases spinal symptoms. There are no constant correlations to subjective hearing threshold measurements. According to literature BERA, especially the measurement of interpeak-intervals, increases diagnostic security of the diagnosis multiple sclerosis. PMID:2704769

Fritsche, F; Templin, A; Knothe, J

1989-01-01

216

Evidence-based assessment of potential use of fingolimod in treatment of relapsing multiple sclerosis  

PubMed Central

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system and represents one of the most common causes of chronic neurologic disability in young adults. All the current disease-modifying drugs are administered parenterally, and can be associated with varying degrees of injection site or infusion-related reactions. Together with other side effects, the parenteral route of administration is one of the key factors affecting adherence to therapy in multiple sclerosis. Fingolimod (FTY720) is an immunomodulator that acts on sphingosine 1-phosphate (S1P) receptors and is the first oral drug approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis. Downmodulation of S1P receptor type 1 (S1P1) slows the egress of lymphocytes from lymph nodes and recirculation to the central nervous system, reduces astrogliosis, and inhibits angiogenesis during chronic neuroinflammation. Fingolimod also regulates the migration of B cells and dendritic cells, and enhances endothelial barrier function. Results from Phase II and III clinical trials provide robust evidence of the efficacy of fingolimod in relapsing-remitting multiple sclerosis. While some caution should be exercised in terms of safety issues, the introduction of fingolimod represents a great advance in the treatment of relapsing-remitting multiple sclerosis. The pharmacologic data on fingolimod and its efficacy and safety in multiple sclerosis are reviewed in this paper. PMID:21468239

Portaccio, Emilio

2011-01-01

217

Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: differential relationships with structural magnetic resonance imaging.  

PubMed

Multiple sclerosis (MS), a central nervous system (CNS) neurodegenerative disorder, involves lesions of both white and gray matter and reported cognitive impairments that include processing speed (PS), executive function, and working memory (WM). This study closely examined the specifics of these cognitive deficits and their relationship to structural brain damage. A visual n-back task with 3 WM load conditions was used to assess WM performance (task accuracy), PS (reaction time, RT), and a novel measure of processing efficiency (standard deviation of RT, RTSD) in MS patients and controls. These behavioral measures were related to quantitative magnetic resonance imaging (MRI) measures of white and gray matter integrity. Even when MS patients performed as well as controls, as seen for low WM load (0-back), they responded more slowly and were less efficient in their speed of responding. Accuracy findings indicated that the correct match trials were superior to correct nonmatch trials at differentiating MS patients from controls. Further, decreased accuracy during the highest WM load condition was associated with global damage that included both gray and white matter atrophy, while slowed PS and particularly processing inefficiency were associated primarily with white matter atrophy in MS. Importantly, relationships between PS, processing efficiency, performance accuracy, and structural MRI measures were seen only during the highest WM load condition, the condition that required the most executive control. These findings suggest that the MRI/behavioral relationships that were present exclusively during the 2-back condition may reflect connectivity involving frontal cortical systems, the site for executive control. PMID:22047454

Covey, Thomas J; Zivadinov, Robert; Shucard, Janet L; Shucard, David W

2011-12-01

218

Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential.  

PubMed

Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological "niches" for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1(+) as well as Sca-1(+)/CD44(+)double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor gamma (Ppargamma), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation. PMID:20496083

Valorani, M G; Germani, A; Otto, W R; Harper, L; Biddle, A; Khoo, C P; Lin, W R; Hawa, M I; Tropel, P; Patrizi, M P; Pozzilli, P; Alison, M R

2010-07-01

219

Progenitor tumours from Emu-bcl-2-myc transgenic mice have lymphomyeloid differentiation potential and reveal developmental differences in cell survival.  

PubMed Central

Mice expressing both a bcl-2 and a myc transgene within the B lymphoid cell compartment invariably develop novel immature haemopoietic tumours. The likely cell of origin of these tumours was identified by a common pattern of cell surface marker expression on a subset of cells comprising approximately 1% of normal mouse bone marrow. The bcl-2-myc tumour cells could be induced to differentiate into either B lymphocytes or macrophages in culture with certain cytokines and feeder cells. Analysis of their progression into the B lymphoid lineage revealed that Igk locus transcription can precede Igh as well as Igk rearrangement. Surprisingly, the undifferentiated tumour cells died rapidly in culture, even in the presence of multiple cytokines, but they proliferated on monolayers of stromal cells derived from haemopoietic tissues. Thus, even with Bcl-2 levels that protect more differentiated cells, these immature bi-potential progenitor cells require a stromal-induced signal for survival. These results provide insight into the process of lineage commitment and suggest new levels of control of cell survival during early steps in haemopoietic development. Images PMID:8670887

Strasser, A; Elefanty, A G; Harris, A W; Cory, S

1996-01-01

220

Differential regulation by organic compounds and heavy metals of multiple laccase genes in the aquatic hyphomycete Clavariopsis aquatica.  

PubMed

To advance the understanding of the molecular mechanisms controlling microbial activities involved in carbon cycling and mitigation of environmental pollution in freshwaters, the influence of heavy metals and natural as well as xenobiotic organic compounds on laccase gene expression was quantified using quantitative real-time PCR (qRT-PCR) in an exclusively aquatic fungus (the aquatic hyphomycete Clavariopsis aquatica) for the first time. Five putative laccase genes (lcc1 to lcc5) identified in C. aquatica were differentially expressed in response to the fungal growth stage and potential laccase inducers, with certain genes being upregulated by, e.g., the lignocellulose breakdown product vanillic acid, the endocrine disruptor technical nonylphenol, manganese, and zinc. lcc4 is inducible by vanillic acid and most likely encodes an extracellular laccase already excreted during the trophophase of the organism, suggesting a function during fungal substrate colonization. Surprisingly, unlike many laccases of terrestrial fungi, none of the C. aquatica laccase genes was found to be upregulated by copper. However, copper strongly increases extracellular laccase activity in C. aquatica, possibly due to stabilization of the copper-containing catalytic center of the enzyme. Copper was found to half-saturate laccase activity already at about 1.8 ?M, in favor of a fungal adaptation to low copper concentrations of aquatic habitats. PMID:22544244

Solé, Magali; Müller, Ines; Pecyna, Marek J; Fetzer, Ingo; Harms, Hauke; Schlosser, Dietmar

2012-07-01

221

Differential Regulation by Organic Compounds and Heavy Metals of Multiple Laccase Genes in the Aquatic Hyphomycete Clavariopsis aquatica  

PubMed Central

To advance the understanding of the molecular mechanisms controlling microbial activities involved in carbon cycling and mitigation of environmental pollution in freshwaters, the influence of heavy metals and natural as well as xenobiotic organic compounds on laccase gene expression was quantified using quantitative real-time PCR (qRT-PCR) in an exclusively aquatic fungus (the aquatic hyphomycete Clavariopsis aquatica) for the first time. Five putative laccase genes (lcc1 to lcc5) identified in C. aquatica were differentially expressed in response to the fungal growth stage and potential laccase inducers, with certain genes being upregulated by, e.g., the lignocellulose breakdown product vanillic acid, the endocrine disruptor technical nonylphenol, manganese, and zinc. lcc4 is inducible by vanillic acid and most likely encodes an extracellular laccase already excreted during the trophophase of the organism, suggesting a function during fungal substrate colonization. Surprisingly, unlike many laccases of terrestrial fungi, none of the C. aquatica laccase genes was found to be upregulated by copper. However, copper strongly increases extracellular laccase activity in C. aquatica, possibly due to stabilization of the copper-containing catalytic center of the enzyme. Copper was found to half-saturate laccase activity already at about 1.8 ?M, in favor of a fungal adaptation to low copper concentrations of aquatic habitats. PMID:22544244

Sole, Magali; Muller, Ines; Pecyna, Marek J.; Fetzer, Ingo; Harms, Hauke

2012-01-01

222

Adiponectin and leptin: Potential tools in the differential diagnosis of pediatric diabetes?  

Microsoft Academic Search

The incidence of type 1 and type 2 diabetes mellitus in the pediatric population has increased over the past decade. The practitioner\\u000a is often faced with the challenge of differentiating between type 1 and type 2 diabetes at the time of initial diagnosis because\\u000a of the overlap of clinical and laboratory characteristics between these two entities. Adipokines are proteins secreted

Milagros Gloria Huerta

2006-01-01

223

Potential Usefulness of Curvature Based Description for Differential Diagnosis of Pulmonary Nodules  

Microsoft Academic Search

\\u000a This paper examines the problem of obtaining a representation of the three-dimensional(3-D) pulmonary nodule images, which\\u000a is a key problem in discriminating benign and malignant nodules for differential diagnosis of the lung cancer using thin-section\\u000a CT images. A curvature based approach is developed with the aim of characterizing internal intensity structures of benign\\u000a and malignant nodules. This approach makes use

Yoshiki Kawata; Noboru Niki; Hironobu Ohmatsu; Masahiko Kusumoto; Ryutaro Kakinuma; Kensaku Mori; Kenji Eguchi; Masahiro Kaneko; Noriyuki Moriyama

1999-01-01

224

Differential Global Positioning System: potential for geographical information system database management  

Microsoft Academic Search

The primary problem for managers of digital topographic data is maintaining an accurate and up-to-date database. Traditional spatial-data-collection techniques and mapping procedures are expensive and, as a result, occur infrequently. However, the NAVSTAR Global Positioning System (GPS) now provides for the collection of timely, cost-effective spatial information. In this study, differential GPS data were collected for an area of rapid

P Treitz; L Elliot; P Howarth

1993-01-01

225

Crucial transcription factors in tendon development and differentiation: their potential for tendon regeneration.  

PubMed

Tendons that connect muscles to bone are often the targets of sports injuries. The currently unsatisfactory state of tendon repair is largely attributable to the limited understanding of basic tendon biology. A number of tendon lineage-related transcription factors have recently been uncovered and provide clues for the better understanding of tendon development. Scleraxis and Mohawk have been identified as critical transcription factors in tendon development and differentiation. Other transcription factors, such as Sox9 and Egr1/2, have also been recently reported to be involved in tendon development. However, the molecular mechanisms and application of these transcription factors remain largely unclear and this prohibits their use in tendon therapy. Here, we systematically review and analyze recent findings and our own data concerning tendon transcription factors and tendon regeneration. Based on these findings, we provide interaction and temporal programming maps of transcription factors, as a basis for future tendon therapy. Finally, we discuss future directions for tendon regeneration with differentiation and trans-differentiation approaches based on transcription factors. PMID:24705622

Liu, Huanhuan; Zhu, Shouan; Zhang, Can; Lu, Ping; Hu, Jiajie; Yin, Zi; Ma, Yue; Chen, Xiao; OuYang, Hongwei

2014-05-01

226

c-Kit identifies a subpopulation of mesenchymal stem cells in adipose tissue with higher telomerase expression and differentiation potential.  

PubMed

The stromal vascular fraction (SVF) of adipose tissue is an easy to obtain source of adipose tissue-derived stem cells (ADSCs). We and others have achieved significant but suboptimal therapeutic effects with ADSCs in various settings, mainly due to low rates of differentiation into specific cell types and with the downside of undesired side effects as a consequence of the undifferentiated ADSCs. These data prompted us to find new stem cell-specific markers for ADSCs and/or subpopulations with higher differentiation potential to specific lineages. We found a subpopulation of human ADSCs, marked by c-Kit positiveness, resides in a perivascular location, and shows higher proliferative activity and self-renewal capacity, higher telomerase activity and expression, higher in vitro adipogenic efficiency, a higher capacity for the maintenance of cardiac progenitors, and higher pancreatogenic and hepatogenic efficiency independently of CD105 expression. Our data suggests that the isolation of ADSC subpopulations with anti-c-Kit antibodies allows for the selection of a more homogeneous subpopulation with increased cardioprotective properties and increased adipogenic and endodermal differentiation potential, providing a useful tool for specific therapies in regenerative medicine applications. PMID:24713343

Blazquez-Martinez, A; Chiesa, M; Arnalich, F; Fernandez-Delgado, J; Nistal, M; De Miguel, M P

2014-01-01

227

Multilineage Differentiation Potential of Bone and Cartilage Cells Derived from Explant Culture  

Microsoft Academic Search

To date, mesenchymal stem cells (MSCs) from various tissues have been reported, but the yield and differentia- tion potential of different tissue-derived MSCs is still not clear. This study was undertaken in an attempt to investigate the multilineage stem cell potential of bone and cartilage explant cultures in comparison with bone marrow derived mesen- chymal stem cells (BMSCs). The results

Zareen Yameen; David Leavesley; Zee Upton; Yin Xiao

2009-01-01

228

Potential of a unique antibody gene signature to predict conversion to clinically definite multiple sclerosis  

Microsoft Academic Search

We identified a unique antibody gene mutation pattern (i.e. “signature”) in cerebrospinal fluid (CSF) B cells from multiple sclerosis (MS) patients not present in control populations. Prevalence of the signature in CSF B cells of patients at risk to develop MS predicted conversion to MS with 91% accuracy in a small cohort of clinically isolated syndrome patients. If confirmed, signature

Elizabeth M. Cameron; Sade Spencer; Jonathan Lazarini; Christopher T. Harp; E. Sally Ward; Mark Burgoon; Gregory P. Owens; Michael K. Racke; Jeffrey L. Bennett; Elliot M. Frohman; Nancy L. Monson

2009-01-01

229

A SIMPLE MULTIPLE SCATTERING - DEPOLARIZATION RELATION OF WATER CLOUDS AND ITS POTENTIAL APPLICATIONS  

Microsoft Academic Search

An empirical relationship is derived between multiple scattering fraction and linear depolarization ratio using Monte Carlo simulations of water clouds measured by backscatter lidar. This relationship is shown to hold for water clouds with a wide range of extinction coefficients, mean droplet sizes, and droplet size distribution widths. The relationship is also shown to persist for various instrument fields-of-view, and

Luc R. Bissonnette; Gilles Roy; Matthew McGill; Charles R. Trepte

230

NOTES performed using multiple ports of entry: Current experience and potential implications for urologic applications.  

PubMed

An isolated transgastric port raises serious limitations in performing natural orifice translumenal endoscopic surgery (NOTES) complex procedures in the urology field. In an attempt to overcome these limitations, several solutions has been advanced, such as the hybrid approach (adding a single abdominal port access) or the pure NOTES combined approach (joining multiple natural orifice ports). To review the current state of experimental and clinical results of multiple ports in NOTES, a literature search of PubMed was performed, seeking publications from January 2002 to 2008 on NOTES. In addition, we looked at pertinent abstracts of annual meetings of the American Urological Association, the European Association of Urology, and the World Congress of Endourology from 2007. Multiple ports of entry seem to be necessary, mainly for moderately complex procedures. Thus, we could find studies using the hybrid approach (combination of transgastric or transvaginal access with a single transabdominal port), or using the pure NOTES combined approach (transgastric and transvesical, transvaginal and transcolonic, or transgastric and transvaginal). There is still limited experience in humans using these approaches, and no comparative studies exist to date. It is predictable that for moderately complex procedures, we will need multiple ports, so the transvaginal-transabdominal (hybrid) approach is the most appealing, whereas in a pure NOTES perspective, the transgastric-transvesical approach seems to be the preferred approach. We are waiting for new equipment and instruments that are more appropriate for these novel techniques. PMID:19405809

Lima, Estevao; Rolanda, Carla; Correia-Pinto, Jorge

2009-05-01

231

The Potential for Improved Boundary Layer Cloud Optical Depth Retrievals from the Multiple Directions of MISR  

Microsoft Academic Search

The Multiangle Imaging Spectroradiometer (MISR) views the earth with nine cameras, ranging from a 70° zenith angle viewing forward through nadir to 70° viewing aft. MISR does not have an operational cloud optical depth retrieval algorithm, but previous research has hinted that solar reflection measured in multiple directions might improve cloud optical depth retrievals. This study explores the optical depth

K. Franklin Evans; Alexander Marshak; Tamás Várnai

2008-01-01

232

The Intelligent Curriculum: Using Multiple Intelligences To Develop Your Students' Full Potential.  

ERIC Educational Resources Information Center

This guide offers teaching models based on the theory of multiple intelligences (MI) and applies these models to the design of lessons that address the unique learning needs of all students. The first chapter makes the case for integrating MI into the curriculum. The second chapter describes the capacities of the various intelligences. Chapters 3…

Lazear, David

233

Capacity to make medical treatment decisions in multiple sclerosis: A potentially remediable deficit  

Microsoft Academic Search

Ability to make decisions about medical treatment is compromised in significant numbers of people with neurological and psychiatric illness, and this incapacity frequently corresponds with compromised neuropsychological function. Although cognitive deficits occur often in people with multiple sclerosis (MS), no research has studied decisional capacity in that disease. The present investigation examined ability to understand treatment disclosures, which is a

Michael R. Basso; Philip J. Candilis; Jay Johnson; Courtney Ghormley; Dennis R. Combs; Taeh Ward

2010-01-01

234

The potential use of stem cells in multiple sclerosis: An overview of the preclinical experience  

Microsoft Academic Search

The reported neurodegeneration process in multiple sclerosis may explain the lack of efficacy of the currently used immunomodulating modalities and the irreversible axonal damage, which results in accumulating disability. Efforts for neuroprotective treatments have not been, so far, successful in clinical studies in other CNS diseases. Therefore, for MS, the use of stem cells may provide a logical solution, since

Dimitrios Karussis; Ibrahim Kassis

2008-01-01

235

The Differential Effect of Toxoplasma Gondii Infection on the Stability of BCL2-Family Members Involves Multiple Activities  

PubMed Central

The regulation of mitochondrial permeability, a key event in the initiation of apoptosis is governed by the opposing actions of the pro- and anti-apoptotic members of the BCL2-family of proteins. The BCL2-family can be classified further based on the number of BCL-homology (BH) domains they encode. Pathogen mediated modulation of BCL2-family members play a significant role in their ability to affect the apoptotic pathways in the infected host cell. The protozoan parasite Toxoplasma gondii establishes a profound blockade of apoptosis noted by a requirement for host NF?B activity and correlating with the selective degradation of pro-apoptotic BCL2-family members. In this study, we explore the potential activities associated with the inherent stability of the anti-apoptotic BCL2 as well as the selective degradation of the pro-apoptotic proteins BAX, BAD, and BID. We find that multiple activities govern the relative stability of BCL2-family members suggesting a complex and balanced network of stability-enhancing and–destabilizing activities are perturbed by parasite infection. The data leave open the possibility for both parasite induced host activities as well as the direct consequence of parasite effectors in governing the relative levels of BCL2-proteins in the course of infection. PMID:21716958

Carmen, John Cherrington; Sinai, Anthony Peter

2011-01-01

236

MRI of optic nerve and postchiasmal visual pathways and visual evoked potentials in secondary progressive multiple sclerosis  

Microsoft Academic Search

We studied the relationship between abnormalities shown by MRI and functional disturbances in the visual pathway as assessed\\u000a by the visual evoked potential (VEP) in 25 patients with established multiple sclerosis (MS); only 4 of whom had a history\\u000a of acute optic neuritis. Optic nerve MRI was abnormal in 19 (76 %) and is thus useful in detecting subclinical disease.

M. B. Davies; R. Williams; N. Haq; L. Pelosi; C. P. Hawkins

1998-01-01

237

The Potential of Water Vapor & Precipitation Estimation with a Differential-frequency Radar  

NASA Technical Reports Server (NTRS)

In the presence of rain, the radar return powers from a three-frequency radar, with center frequency at 22.235 GHz and upper and lower frequencies chosen with equal water vapor absorption coefficients, can be used to estimate water vapor density and parameters of the precipitation. A linear combination of differential measurements between the center and lower frequencies on one hand and the upper and lower frequencies on the other provide an estimate of differential water vapor absorption. Conversely, the difference in radar reflectivity factors (in dB) between the upper and lower frequencies is independent of water vapor absorption and can be used to estimate the median mass diameter of the hydrometeors. For a down-looking radar, path-integrated estimates of water vapor absorption may be possible under rain-free as well as raining conditions by using the surface returns at the three frequencies. Cross-talk or interference between the precipitation and water vapor estimates depends on the frequency separation of the channels as well as on the phase state and the median mass diameter of the hydrometeors. Simulations of the retrieval of water vapor absorption show that the largest source of variability arises from the variance in the measured radar return powers while the largest biases occur in the mixed-phase region. Use of high pulse repetition frequencies and signal whitening methods may be needed to obtain the large number of independent samples required. Measurements over a fractional bandwidth, defined as the ratio of the difference between the upper and lower frequencies to the center frequency, up to about 0.2 should be passible in a differential frequency mode, where a single transceiver and antenna are used. Difficulties in frequency allocation may require alternative choices of frequency where the water vapor absorptions at the low and high frequencies are unequal. We consider the degradation in the retrieval accuracy when the frequencies are not optimum.

Meneghini, Robert; Liao, Liang; Tian, Lin

2006-01-01

238

The potential of dental stem cells differentiating into neurogenic cell lineage after cultivation in different modes in vitro.  

PubMed

Abstract Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases. PMID:25072651

Yang, Chao; Sun, Liang; Li, Xinghan; Xie, Li; Yu, Mei; Feng, Lian; Jiang, Zongting; Guo, Weihua; Tian, Weidong

2014-10-01

239

Differential Detection of Potentially Hazardous Fusarium Species in Wheat Grains by an Electronic Nose  

PubMed Central

Fungal infestation on wheat is an increasingly grave nutritional problem in many countries worldwide. Fusarium species are especially harmful pathogens due to their toxic metabolites. In this work we studied volatile compounds released by F. cerealis, F. graminearum, F. culmorum and F. redolens using SPME-GC/MS. By using an electronic nose we were able to differentiate between infected and non-infected wheat grains in the post-harvest chain. Our electronic nose was capable of distinguishing between four wheat Fusaria species with an accuracy higher than 80%. PMID:21695232

Eifler, Jakob; Martinelli, Eugenio; Santonico, Marco; Capuano, Rosamaria; Schild, Detlev; Di Natale, Corrado

2011-01-01

240

Physicochemical Control of Adult Stem Cell Differentiation: Shedding Light on Potential Molecular Mechanisms.  

National Technical Information Service (NTIS)

Realization of the exciting potential for stem-cell-based biomedical and therapeutic applications, including tissue engineering, requires an understanding of the cell-cell and cell-environment interactions. To this end, recent efforts have been focused on...

I. Titushkin, J. Shin, M. Cho, S. Sun

2010-01-01

241

Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells.  

PubMed

The mechanical properties of adipose-derived stem cell (ASC) clones correlate with their ability to produce tissue-specific metabolites, a finding that has dramatic implications for cell-based regenerative therapies. Autologous ASCs are an attractive cell source due to their immunogenicity and multipotent characteristics. However, for practical applications ASCs must first be purified from other cell types, a critical step which has proven difficult using surface-marker approaches. Alternative enrichment strategies identifying broad categories of tissue-specific cells are necessary for translational applications. One possibility developed in our lab uses single-cell mechanical properties as predictive biomarkers of ASC clonal differentiation capability. Elastic and viscoelastic properties of undifferentiated ASCs were tested via atomic force microscopy and correlated with lineage-specific metabolite production. Cell sorting simulations based on these "mechanical biomarkers" indicated they were predictive of differentiation capability and could be used to enrich for tissue-specific cells, which if implemented could dramatically improve the quality of regenerated tissues. PMID:22615348

González-Cruz, Rafael D; Fonseca, Vera C; Darling, Eric M

2012-06-12

242

Exendin-4 induces cell adhesion and differentiation and counteracts the invasive potential of human neuroblastoma cells.  

PubMed

Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties. PMID:23990978

Luciani, Paola; Deledda, Cristiana; Benvenuti, Susanna; Squecco, Roberta; Cellai, Ilaria; Fibbi, Benedetta; Marone, Ilaria Maddalena; Giuliani, Corinna; Modi, Giulia; Francini, Fabio; Vannelli, Gabriella Barbara; Peri, Alessandro

2013-01-01

243

Comparison of Proliferative and Multilineage Differentiation Potential of Sheep Mesenchymal Stem Cells Derived from Bone Marrow, Liver, and Adipose Tissue  

PubMed Central

Background Background: Despite major progress in our general knowledge related to the application of adult stem cells, finding alternative sources for bone marrow Mesenchymal Stem Cells (MSCs) has remained to be challenged. In this study successful isolation, multilineage differentiation, and proliferation potentials of sheep MSCs derived from bone marrow, adipose tissue, and liver were widely investigated. Methods The primary cell cultures were prepared form tissue samples obtained from sheep 30-35 day fetus. Passage-3 cells were plated either at varying cell densities or different serum concentrations for a week. The Population Doubling Time (PDT), growth curves, and Colony Forming Unit (CFU) of MSCs was determined. The stemness and trilineage differentiation potential of MSCs were analyzed by using molecullar and cytochemical staining approaches. The data was analyzed through one way ANOVA using SigmaStat (ver. 2). Results The highest PDT and lowest CFU were observed in adipose tissue group compared with other groups (p<0.001). Comparing different serum concentrations (5, 10, 15, and 20%), irrespective of cell sources, the highest proliferation rate was achieved in the presence of 20% serum (p<0.001). Additionally, there was an inverse relation between cell seeding density at culture initiation and proliferation rate, except for L-MSC at 300 cell seeding density. Conclusion All three sources of fetal sheep MSCs had the identical trilineage differentiation potential. The proliferative capacity of liver and bone marrow derived MSCs were similar at different cell seeding densities except for the higher fold increase in B-MSCs at 2700 cells/cm 2 density. Moreover, the adipose tissue derived MSCs had the lowest proliferative indices. PMID:23799179

Heidari, Banafsheh; Shirazi, Abolfazl; Akhondi, Mohammad Mehdi; Hassanpour, Hossein; Behzadi, Bahareh; Naderi, Mohammad Mehdi; Sarvari, Ali; Borjian, Sara

2013-01-01

244

Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential  

PubMed Central

Introduction Aging people's bone regeneration potential is always impaired. Bone marrow stromal cells (MSCs) contain progenitors of osteoblasts. Donor age may affect MSCs’ proliferation and differentiation potential, but the genomic base is still unknown. Due to recent research's indication that a core circadian component, brain and muscle ARNT-like 1 protein (BMAL1), has a role in premature aging, we investigated the normal aging mechanism in mice with their MSCs and Bmal1 gene/protein level. Material and methods 1, 6 and 16 month old C57BL/6 mice were used and the bone marrow stromal cells were gained and cultured at early passage. Bmal1 gene and protein level were detected in these cells. Marrow stromal cells were also induced to differentiate to osteoblasts or adipocytes. Three groups of mice MSCs were compared on proliferation by flow cytometry, on cell senescence by SA-?-gal expression and after osteo-induction on osteogenic potential by the expression of osterix (Osx), alkaline phosphatase (ALP) and osteocalcin (OCN). Results Bmal1 gene and protein level as well as S-phase fraction of the cell cycle decreased in MSCs along with the aging process. At the same time, SA-?-gal+ levels increased, especially in the aged mice MSCs. When induced to be osteogenic, Osx gene expression and ALP activity declined in the mid-age and aged mice MSCs, while OCN protein secretion deteriorated in the aged mice MSCs. Conclusions These findings demonstrate that mouse MSCs changed with their proliferation and osteo-differentiation abilities at different aging stages, and that Bmal1 is related to the normal aging process in MSCs. PMID:22457671

Chen, Yijia; Xu, Xiaomei; Tan, Zhen; Ye, Cui; Chen, Yangxi

2012-01-01

245

Multiple solutions for quasilinear elliptic equations with a finite potential well  

NASA Astrophysics Data System (ADS)

We consider multiplicity of solutions for a class of quasilinear problems which has received considerable attention in the past, including the so called Modified Nonlinear Schrödinger Equations. By combining a new variational approach via q-Laplacian regularization and the compactness arguments from [4] we establish infinitely many bound state solutions for the quasilinear Schrödinger type equations, extending the earlier work of [4] for semilinear equations.

Liu, Jia-Quan; Wang, Zhi-Qiang

2014-10-01

246

Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential  

Microsoft Academic Search

Cellular interactions with microenviron- mental components are critical in multiple myeloma (MM) and impede effective disease treatment. Mem- branal-embedded tetraspanins, associated with metasta- sis suppression, are underexpressed in MM. We aimed to investigate the consequences of CD81\\/CD82 tet- raspanins over-expression in MM cell lines. CAG and RPMI 8226 were transfected with pEGFP-N1\\/C1 fu- sion vectors of CD81\\/CD82. Employing flow cytometry,

Tali Tohami; Liat Drucker; Hava Shapiro; Judith Radnay; Michael Lishner

2007-01-01

247

Surface potentials and ionization equilibrium in Y-type deposition of multiple Langmuir–Blodgett films  

Microsoft Academic Search

Conditions for depositions of multiple LB films for different divalent cations were determined experimentally at the pKA of the system. The pKA of the fatty acid–subphase salt system is the pH at which half of the fatty acid heads are dissociated. Stable Y-type depositions take place in full immersion\\/removal cycles. Under certain conditions, full depositions occur only during the downstroke

M. Elena Diaz Martin; Ramon L. Cerro

2005-01-01

248

Exploring Potential Sources of Differential Vulnerability and Susceptibility in Risk From Environmental Hazards to Expand the Scope of Risk Assessment  

PubMed Central

Genetic factors, other exposures, individual disease states and allostatic load, psychosocial stress, and socioeconomic position all have the potential to modify the response to environmental exposures. Moreover, many of these modifiers covary with the exposure, leading to much higher risks in some subgroups. These are not theoretical concerns; rather, all these patterns have already been demonstrated in studies of the effects of lead and air pollution. However, recent regulatory impact assessments for these exposures have generally not incorporated these findings. Therefore, differential risk and vulnerability is a critically important but neglected area within risk assessment, and should be incorporated in the future. PMID:22021315

Bellinger, David; Glass, Thomas

2011-01-01

249

UNAIDS 'multiple sexual partners' core indicator: promoting sexual networks to reduce potential biases  

PubMed Central

UNAIDS proposed a set of core indicators for monitoring changes in the worldwide AIDS epidemic. This paper explores the validity and effectiveness of the ‘multiple sexual partners’ core indicator, which is only partially captured with current available data. The paper also suggests an innovative approach for collecting more informative data that can be used to provide an accurate measure of the UNAIDS’s ‘multiple sexual partners’ core indicator. Specifically, the paper addresses three major limitations associated with the indicator when it is measured with respondents’ sexual behaviors. First, the indicator assumes that a person’s risk of contracting HIV/AIDS/STIs is merely a function of his/her own sexual behavior. Second, the indicator does not account for a partner’s sexual history, which is very important in assessing an individual’s risk level. Finally, the 12-month period used to define a person’s risks can be misleading, especially because HIV/AIDS theoretically has a period of latency longer than a year. The paper concludes that, programmatically, improvements in data collection are a top priority for reducing the observed bias in the ‘multiple sexual partners’ core indicator. PMID:24647127

Dimbuene, Zacharie Tsala; Emina, Jacques B.O.; Sankoh, Osman

2014-01-01

250

Sox17 as a candidate regulator of myeloid restricted differentiation potential.  

PubMed

Sry related high mobility group box 17 (Sox17), which is a marker of endodermal cells and a transcriptional regulator, has a critical role in the maintenance of fetal and neonatal hematopoietic stem cells (HSC). Sox17 has been identified as a key regulator of the development and differentiation of fetal hematopoietic progenitors from the aorta-gonad-mesonephros (AGM) region. The co-culture of Sox17-transduced hematopoietic progenitor cells (CD45(low) c-Kit(high) cells) from AGM regions on OP9 stromal cells gives rise to multipotential hematopoietic stem/progenitor cells. Here, we show that in a primary transplantation experiment, Sox17-transduction in CD45(low) c-Kit(high) cells of embryonic day (E) 10.5 AGM increased the absolute number of common myeloid progenitors (CMPs) in the bone marrow (BM) of recipient mice in comparison to that of granulocyte/macrophage progenitors (GMPs) and the megakaryocyte/erythroid progenitors (MEPs). When Sox17-transduced cells were cultured with OP9 stromal cells, Sox17-transduced GMPs (Sox17-GMPs), Sox17-transduced CMPs (Sox17-CMPs), and Sox17-transduced MEPs (Sox17-MEPs) were generated. Sox17-GMPs and Sox17-CMPs maintained their self-renewal capacity and the hematopoietic ability upon co-culture with the OP9 stromal cells for some passages. Moreover, Sox17-GMPs exhibited the increase in expression of c-Mpl and GATA-2 in comparison to GMPs of BM and Sox17-CMPs showed the increase in expression of c-Mpl, NF-E2, and ?-globin genes in comparison to CMPs of BM. Furthermore, when Sox17-transduced cells were cultured in methylcellulose to examine the colony-forming ability, Sox17-GMPs and Sox17-CMPs maintained the formation of mixed colonies for some passages. Taken together, Sox17 is suggested to regulate the maintenance and differentiation of hematopoietic progenitors derived from AGM regions at midgestation, in particular myeloid progenitors. PMID:25093513

Anani, Maha; Nobuhisa, Ikuo; Osawa, Mitsujiro; Iwama, Atsushi; Harada, Kaho; Saito, Kiyoka; Taga, Tetsuya

2014-08-01

251

Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells.  

PubMed

Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O2) and hypoxia (2% O2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1? under hypoxia. Taken together, we suggest that growing ASCs under 2% O2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects. PMID:24785372

Choi, Jane Ru; Pingguan-Murphy, Belinda; Wan Abas, Wan Abu Bakar; Noor Azmi, Mat Adenan; Omar, Siti Zawiah; Chua, Kien Hui; Wan Safwani, Wan Kamarul Zaman

2014-05-30

252

Sexual differentiation in the distribution potential of northern jaguars (Panthera onca)  

USGS Publications Warehouse

We estimated the potential geographic distribution of jaguars in the southwestern United States and northwestern Mexico by modeling the jaguar ecological niche from occurrence records. We modeled separately the distribution of males and females, assuming records of females probably represented established home ranges while male records likely included dispersal movements. The predicted distribution for males was larger than that for females. Eastern Sonora appeared capable for supporting male and female jaguars with potential range expansion into southeastern Arizona. New Mexico and Chihuahua contained environmental characteristics primarily limited to the male niche and thus may be areas into which males occasionally disperse.

Boydston, Erin E.; Lopez Gonzalez, Carlos A.

2005-01-01

253

Differential effects of cocaine, alcohol, and nicotine dependence on olfactory evoked potentials  

Microsoft Academic Search

Olfactory evoked potentials (OEP) were elicited by odorous and nonodorous stimuli in 50 adult subjects: 26 subjects with histories of either cocaine (n = 19) or alcohol (n = 7) dependence, 10 with histories of nicotine but no other drug dependence, 2 with clinical anosmia of peripheral origin, and 12 subjects without drug or olfactory disorders. The presentation of nonodorous

Lance O. Bauer; April E. Mott

1996-01-01

254

Identification of the Dopamine D3 Receptor in Oligodendrocyte Precursors: Potential Role in Regulating Differentiation and  

E-print Network

Identification of the Dopamine D3 Receptor in Oligodendrocyte Precursors: Potential Role mark- ers of specific stages of oligodendrocyte development indi- cated that D3r expression occurred in precursors and in imma- ture oligodendrocytes but not in mature oligodendrocytes (i.e., A2B5 007 01 and A2B5

Bongarzone, Ernesto R.

255

Exposure to Potentially Traumatic Events in Early Childhood: Differential Links to Emergent Psychopathology  

ERIC Educational Resources Information Center

Research NeedsObjective: To examine associations between exposure to potentially traumatic events (PTEs) and clinical patterns of symptoms and disorders in preschool children. Method: Two hundred and thirteen referred and non-referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family…

Briggs-Gowan, Margaret J.; Carter, Alice S.; Clark, Roseanne; Augustyn, Marilyn; McCarthy, Kimberly J.; Ford, Julian D.

2010-01-01

256

SUMOylation of ATRIP potentiates DNA damage signaling by boosting multiple protein interactions in the ATR pathway.  

PubMed

The ATR (ATM [ataxia telangiectasia-mutated]- and Rad3-related) checkpoint is a crucial DNA damage signaling pathway. While the ATR pathway is known to transmit DNA damage signals through the ATR-Chk1 kinase cascade, whether post-translational modifications other than phosphorylation are important for this pathway remains largely unknown. Here, we show that protein SUMOylation plays a key role in the ATR pathway. ATRIP, the regulatory partner of ATR, is modified by SUMO2/3 at K234 and K289. An ATRIP mutant lacking the SUMOylation sites fails to localize to DNA damage and support ATR activation efficiently. Surprisingly, the ATRIP SUMOylation mutant is compromised in the interaction with a protein group, rather than a single protein, in the ATR pathway. Multiple ATRIP-interacting proteins, including ATR, RPA70, TopBP1, and the MRE11-RAD50-NBS1 complex, exhibit reduced binding to the ATRIP SUMOylation mutant in cells and display affinity for SUMO2 chains in vitro, suggesting that they bind not only ATRIP but also SUMO. Fusion of a SUMO2 chain to the ATRIP SUMOylation mutant enhances its interaction with the protein group and partially suppresses its localization and functional defects, revealing that ATRIP SUMOylation promotes ATR activation by providing a unique type of protein glue that boosts multiple protein interactions along the ATR pathway. PMID:24990965

Wu, Ching-Shyi; Ouyang, Jian; Mori, Eiichiro; Nguyen, Hai Dang; Maréchal, Alexandre; Hallet, Alexander; Chen, David J; Zou, Lee

2014-07-01

257

Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling  

PubMed Central

Colorectal cancers (CRCs) express the WNT effector protein ?-catenin in a heterogeneous subcellular pattern rather than uniformly in the nucleus. In this study, we investigated this important aspect of molecular heterogeneity in CRCs by analyzing its basis and relationship with tumor initiating capability. CRC cells expressing the highest WNT expression showed only a marginal increase in tumor initiation capacity. Notably, high WNT activity correlated with a coincident activation of robust MAPK signaling, which when upregulated by KRAS expression or downregulated by EGFR inhibition elicited parallel effects on WNT activity. These findings suggested that on its own high WNT activity may not be a reliable signifier of tumor-initiating potential or stem-like potential. Further, they suggest that MAPK signaling is a critical modifier of intratumoral heterogeneity that contributes signiificantly to determining the impact of WNT activity on stemness phenotypes inCRC cells. PMID:22318865

Horst, David; Chen, Justina; Morikawa, Teppei; Ogino, Shuji; Kirchner, Thomas; Shivdasani, Ramesh A

2012-01-01

258

TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials  

PubMed Central

Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs) in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia. PMID:24106720

Dorantes-Acosta, Elisa; Balandran, Juan Carlos; Arriaga-Pizano, Lourdes; Purizaca, Jessica; Huerta-Yepez, Sara; Jimenez, Elva; Aguilera, Wendy; Medina-Sanson, Aurora; Mayani, Hector

2013-01-01

259

Potential of comprehensive toxico-proteomics: quantitative and differential mining of functional proteomes from native samples.  

PubMed

It is becoming increasingly clear that the interactions of targets and biomarkers, drug modes of action and molecular mechanisms of side-effects and toxic effects are much more complex than previously anticipated, basically due to physiological compensation and cross-talk. Single genes often lead to hundreds or even thousands of functional protein molecules, modified at the post-translational level. Thus, the comprehensive analysis of proteins (proteomics) teaches us that physiological activity means dynamic, multidimensional processes among many thousands of different proteins within higher systems of organisation and correlation. Crucial for control and relevant reduction of this enormous complexity, which will enable new kinds of molecular drug screening, as well as a new type of molecular toxicology, is a consequently differential and quantitative protein analysis. Precise knowledge of key protein isoforms with specific post-translational modifications within kinetic and contextual relationships is accessible by powerful new technologies, which have emerged to analyse the surprisingly ambiguous world of proteins, where single molecular modules are involved in a diversity of often opposing signal transduction pathways in a most flexible way. PMID:23577445

Schrattenholz, André; Klemm, Martina; Cahill, Michael

2004-06-01

260

Mitochondrial DNA of Anisakis simplex s.s. as a potential tool for differentiating populations.  

PubMed

Anisakis simplex s.s. specimens from Gadus morhua, Gadus ogac, Reinhardtius hippoglossoides, Clupea harengus, Micromesistius poutassou, Pleurogrammus monopterygius, and Oncorhynchus nerka, caught in the north Atlantic and Pacific, were examined. Identity of the parasite species was confirmed using a molecular key. All specimens were used for amplifying a part of the non-coding sequence of the AT-rich region, flanked by the nad6-nad4L-trnW-trnE-rrnS-trnS2, and trnN-trnY-nad1 genes. This part of the mtDNA was chosen as a promising fragment, which could yield information regarding population differentiation. The number of samples and their geographical origin was sufficient to compare the 2 regions. The Bayesian analysis provided strong support for a population split into 2 groups, one representing A. simplex s.s. samples from the Pacific, and the other representing all the Atlantic samples. It is highly probable that observed subpopulations were constituted after the connection between the Atlantic and Pacific had been closed and movement between these 2 oceans was prevented. PMID:19530887

Kijewska, Agnieszka; Dzido, Joanna; Rokicki, Jerzy

2009-12-01

261

Differential Protein Mapping of Ovarian Serous Adenocarcinomas: Identification of Potential Markers for Distinct Tumor Stage  

PubMed Central

Ovarian serous carcinomas (OSCs) comprise over half of all ovarian carcinomas and account for the majority of ovarian cancer-related deaths. We used a 2-dimensional liquid-based protein mapping strategy to characterize global protein expression patterns in 19 OSC tumor samples from 15 different patients to facilitate molecular classification of tumor stage. Protein expression profiles were produced, using pI-based separation in the first dimension and hydrophobicity-based separation in the second dimension, over a pH range of 4.0-7.0. Hierarchical clustering was applied to protein maps to indicate the tumor interrelationships. The 19 tumor samples could be classified into two different groups, one group associated with low stage (Stage 1) tumors and the other group associated with high stage (Stages 3/4) tumors. Proteins that were differentially expressed in different groups were selected for identification by LTQ-ESI-MS/MS. Fourteen of the selected proteins were over-expressed in the low stage tumors; 46 of the proteins were over-expressed in the high stage tumors. These proteins are known to play an important role in cellular functions such as glycolysis, protein biosynthesis, and cytoskeleton rearrangement and may serve as markers associated with different stages of OSCs. To further confirm the stage-dependent protein identifications, Lamin A/C and Vimentin expression in ovarian serous carcinomas was assessed by immunohistochemistry using ovarian tumor tissue microarrays for 66 samples. PMID:19159301

Wang, Yanfei; Wu, Rong; Cho, Kathleen R.; Thomas, Dafydd G.; Gossner, Gabrielle; Liu, J. Rebecca; Giordano, Thomas J.; Shedden, Kerby A.; Misek, David E.

2008-01-01

262

Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles  

Microsoft Academic Search

Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from\\u000a ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize\\u000a the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association,\\u000a cytotoxic and inflammatory potential of spherical and sheet-shaped

Boon Chin Heng; Xinxin Zhao; Eng Chok Tan; Nurulain Khamis; Aarti Assodani; Sijing Xiong; Christiane Ruedl; Kee Woei Ng; Joachim Say-Chye Loo

263

Detection of multiple potentially pathogenic bacteria in Matang mangrove estuaries, Malaysia.  

PubMed

The deltaic estuarine system of the Matang Mangrove Forest Reserve of Malaysia is a site where several human settlements and brackish water aquaculture have been established. Here, we evaluated the level of fecal indicator bacteria (FIB) and the presence of potentially pathogenic bacteria in the surface water and sediments. Higher levels of FIB were detected at downstream sampling sites from the fishing village, indicating it as a possible source of anthropogenic pollution to the estuary. Enterococci levels in the estuarine sediments were higher than in the surface water, while total coliforms and E. coli in the estuarine sediments were not detected in all samples. Also, various types of potentially pathogenic bacteria, including Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae were isolated. The results indicate that the Matang estuarine system is contaminated with various types of potential human bacterial pathogens which might pose a health risk to the public. PMID:24820641

Ghaderpour, Aziz; Mohd Nasori, Khairul Nazrin; Chew, Li Lee; Chong, Ving Ching; Thong, Kwai Lin; Chai, Lay Ching

2014-06-15

264

A general model for the repassivation potential as a function of multiple aqueous solution species  

Microsoft Academic Search

A general model for predicting the localized corrosion repassivation potential of alloys in multicomponent electrolyte solutions is described. The model assumes that the status of localized corrosion is determined by competitive processes at the metal–salt film–solution interfaces leading to either metal salt or oxide formation. The model successfully predicts the observed effects of aggressive species, such as chloride and bromide,

A. Anderko; N. Sridhar; D. S. Dunn

2004-01-01

265

Muscarinic Receptor Activity Has Multiple Effects on the Resting Membrane Potentials of CA1 Hippocampal Interneurons  

Microsoft Academic Search

Inhibitory interneurons appear to be an important target for the muscarinic actions of cholinergic inputs to the hippocampus. We investigated the effect of muscarinic receptor activity on the membrane potential (Vm ) and currents of rat hippocampal CA1 interneurons using whole-cell recording from visually identified CA1 interneurons. The predominant response observed was a muscarinic depolarization that was detected in interneurons

A. Rory McQuiston; Daniel V. Madison

1999-01-01

266

The Point of Conflict: Risking Worth through the Multiple Potentialities of Reflected Selves  

ERIC Educational Resources Information Center

This article adopts an existentialist lens to examine the phenomenon of entering conflict with other human beings and the potential effects of such engagement on identity. In particular, it explores a teacher's active engagement (or lack thereof) in conflict as a response to the humiliation or degradation of a student. The comfort of a secure…

Weddington, Hank S.

2008-01-01

267

Screening of Predicted Secreted Antigens from Mycobacterium bovis Identifies Potential Novel Differential Diagnostic Reagents? †  

PubMed Central

To date, the most promising vaccination strategies for the control of bovine tuberculosis (TB) focus on improving the efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG). However, vaccination with BCG results in sensitization of animals to bovine tuberculin and compromises tests currently used for diagnosis of bovine TB infection. Thus, the development of specific diagnostic reagents capable of discriminating between infected and uninfected vaccinated animals (DIVA) is of high priority. To test the hypothesis that M. bovis-secreted proteins are likely to contain immunogenic antigens that can be used to increase the specificity of diagnostic tests, we screened 379 pools of overlapping peptides representing 119 antigens for their ability to stimulate a gamma inferferon (IFN-?) response in vitro using whole blood from both TB reactor and BCG-vaccinated animals. Peptide pools representing antigens Rv3020c and Rv2346c induced responses in 61% and 57% of the TB reactor animals, respectively, without inducing responses in any BCG-vaccinated animal studied. Furthermore, individual peptides contained within pools recognized by BCG vaccinates were identified that were specific and induced IFN-? responses in TB reactor animals. From these results, we constructed a cocktail of nine peptides representing multiple antigen targets that was recognized by 54% of TB reactor animals but also failed to induce responses in any BCG-vaccinated animal studied. In summary, we have identified three peptide cocktails for prioritization in larger trials to discriminate between M. bovis infection and BCG vaccination. PMID:20668139

Jones, Gareth J.; Hewinson, R. Glyn; Vordermeier, H. Martin

2010-01-01

268

Proteomic Profiling in Multiple Sclerosis Clinical Courses Reveals Potential Biomarkers of Neurodegeneration  

PubMed Central

The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000–25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ?1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin ?4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p?=?0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS. PMID:25098164

Liguori, Maria; Qualtieri, Antonio; Tortorella, Carla; Direnzo, Vita; Bagala, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

2014-01-01

269

Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord: immunophenotypic characterization and differentiation potential  

PubMed Central

Introduction Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identical in vitro conditions, to compare these sources for research or an allogeneic therapy cell bank. Methods The BM-MSCs, AT-MSCs and UC-MSCs were cultured and evaluated in vitro for their osteogenic, adipogenic and chondrogenic differentiation potential. Additionally, MSCs were assessed for CD105, CD44, CD34, CD90 and MHC-II markers by flow cytometry, and MHC-II was also assessed by immunocytochemistry. To interpret the flow cytometry results, statistical analysis was performed using ANOVA. Results The harvesting and culturing procedures of BM-MSCs, AT-MSCs and UC-MSCs were feasible, with an average cell growth until the third passage of 25 days for BM-MSCs, 15 days for AT-MSCs and 26 days for UC-MSCs. MSCs from all sources were able to differentiate into osteogenic (after 10 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs), adipogenic (after 8 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs) and chondrogenic (after 21 days for BM-MSCs, AT-MSCs and UC-MSCs) lineages. MSCs showed high expression of CD105, CD44 and CD90 and low or negative expression of CD34 and MHC-II. The MHC-II was not detected by immunocytochemistry techniques in any of the MSCs studied. Conclusions The BM, AT and UC are feasible sources for harvesting equine MSCs, and their immunophenotypic and multipotency characteristics attained minimal criteria for defining MSCs. Due to the low expression of MHC-II by MSCs, all of the sources could be used in clinical trials involving allogeneic therapy in horses. However, the BM-MSCs and AT-MSCs showed fastest ‘‘in vitro’’ differentiation and AT-MSCs showed highest cell growth until third passage. These findings suggest that BM and AT may be preferable for cell banking purposes. PMID:24559797

2014-01-01

270

Sexual differentiation of the zebra finch song system: potential roles for sex chromosome genes  

PubMed Central

Background Recent evidence suggests that some sex differences in brain and behavior might result from direct genetic effects, and not solely the result of the organizational effects of steroid hormones. The present study examined the potential role for sex-biased gene expression during development of sexually dimorphic singing behavior and associated song nuclei in juvenile zebra finches. Results A microarray screen revealed more than 2400 putative genes (with a false discovery rate less than 0.05) exhibiting sex differences in the telencephalon of developing zebra finches. Increased expression in males was confirmed in 12 of 20 by qPCR using cDNA from the whole telencephalon; all of these appeared to be located on the Z sex chromosome. Six of the genes also showed increased expression in one or more of the song control nuclei of males at post-hatching day 25. Although the function of half of the genes is presently unknown, we have identified three as: 17-beta-hydroxysteroid dehydrogenase type IV, methylcrotonyl-CoA carboxylase, and sorting nexin 2. Conclusion The data suggest potential influences of these genes in song learning and/or masculinization of song system morphology, both of which are occurring at this developmental stage. PMID:19309515

Tomaszycki, Michelle L; Peabody, Camilla; Replogle, Kirstin; Clayton, David F; Tempelman, Robert J; Wade, Juli

2009-01-01

271

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders  

PubMed Central

Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound ?9-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPAR? receptors agonism, intracellular (Ca2+) increase, etc.), on CBD behavioural effects. PMID:23108553

Campos, Alline Cristina; Moreira, Fabricio Araujo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimaraes, Francisco Silveira

2012-01-01

272

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.  

PubMed

Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound ?(9)-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPAR? receptors agonism, intracellular (Ca(2+)) increase, etc.), on CBD behavioural effects. PMID:23108553

Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

2012-12-01

273

Non-cell-autonomous microRNA165 acts in a dose-dependent manner to regulate multiple differentiation status in the Arabidopsis root.  

PubMed

In the development of multicellular organisms, cell fate is usually determined by exchanging positional information. Animals employ a class of intercellular signaling molecules that specify different cell fates by their dosage, but the existence of an equivalent system has not been demonstrated in plants, except that the growth regulator auxin has been proposed to act in a similar manner in certain developmental contexts. Recently, it has been reported that, in the Arabidopsis root meristem, endodermis-derived microRNA (miR) 165/166 non-cell-autonomously suppress the expression of the Class III HD-ZIP transcription factor PHABULOSA (PHB) in the peripheral stele, thereby specifying xylem differentiation. Here, we show that the miR165/166-dependent suppression of PHB is required not only for xylem specification, but also for differentiation of the pericycle, as well as for ground tissue patterning. Furthermore, using a plant system that allows quantitative control of miR165 production in the ground tissue, we show that endodermis-derived miR165 acts in a dose-dependent manner to form a graded distribution of PHB transcripts across the stele. These results reveal a previously unidentified role of miR165 in the differentiation of a broad range of root cell types and suggest that endodermis-derived miR165 acts in a dose-dependent manner to control multiple differentiation status in the Arabidopsis root. PMID:21558378

Miyashima, Shunsuke; Koi, Satoshi; Hashimoto, Takashi; Nakajima, Keiji

2011-06-01

274

Exposure to potentially traumatic events in early childhood: differential links to emergent psychopathology  

PubMed Central

Objective To examine associations between exposure to potentially traumatic events (PTEs) and clinical patterns of symptoms and disorders in preschool children. Method Two hundred and thirteen referred and non-referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family violence and non-interpersonal events) and recent stressful life events were assessed with the Preschool Age Psychiatric Assessment (PAPA) and Child Life Events Scale. Child psychiatric symptoms and disorders were assessed with parent-reports in the PAPA, a comprehensive, developmentally sensitive interview. Sociodemographic risk, parental anxiety and depressive symptoms (Center for Epidemiologic Studies Depression, Beck Anxiety Inventory), and child developmental level (Mullen Scales of Early Learning) also were assessed. Results Violence exposure was broadly associated with psychiatric status in the areas of depression, separation anxiety, posttraumatic stress, and conduct problems, whereas potentially traumatic non-interpersonal exposure was associated with phobic anxiety. The majority of the associations between violence exposure and preschoolers’ symptoms were significant even when other key factors, including economic disadvantage and parental mood and anxiety symptoms, were controlled statistically. However, parental depressive/anxious symptoms may have partially or fully mediated the relationships between violence exposure and depressive and conduct symptoms. Conclusions Evidence of robust associations between violence exposure and early childhood internalizing and externalizing disorders and symptoms highlights the need for longitudinal prospective research concerning neurodevelopmental mechanisms and pathways. Findings underscore the relevance of assessing trauma exposure, particularly interpersonal violence, to identify young children at risk. PMID:20840502

Briggs-Gowan, Margaret J.; Carter, Alice S.; Clark, Roseanne; Augustyn, Marilyn; McCarthy, Kimberly J.; Ford, Julian D.

2011-01-01

275

Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma  

PubMed Central

We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1)?pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3?pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (?68.3?pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. PMID:24967406

Won, Eun-Jeong; Kim, Hye-Ran; Choi, Hyun-Jung; Park, Hye-Ri; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

2014-01-01

276

Is T-bet a potential therapeutic target in multiple sclerosis?  

PubMed

Treatments for multiple sclerosis (MS) have changed over the past years as our understanding of immunology and neuroscience has evolved. Experimental autoimmune encephalomyelitis (EAE) continues to remain the major model for MS and has been a major vehicle in the development of new therapeutic targets for MS, including new agents such as natalizumab, fingolimod, and dimethyl fumarate. As progress in the molecular understanding of immunology continues, many observations in EAE are pursued with the ultimate goal of defining the pathophysiology of MS and development of innovative treatments for the disease. Although many consider MS to be a T cell-mediated autoimmune disease directed against myelin antigens, the exact cause of the disease is still unknown. For many years, it was thought that myelin-specific T cells that secreted interferon-? and were proinflammatory were the major T cell subset that mediated the disease, but recent studies on the cytokine phenotype of pathogenic T cells in EAE and MS have opened debate on this issue. Work over the past several years suggests that the transcription factor T-bet appears to be an important factor in T cell encephalitogenicity; however, recent data suggest that it is also dispensable in certain situations, particularly for Th17 cells. Understanding the molecular mechanisms responsible for T cell encephalitogenicity in MS and other autoimmune diseases will be essential in the development of specific therapies for these inflammatory diseases. PMID:25084179

Racke, Michael K; Yang, Yuhong; Lovett-Racke, Amy E

2014-08-01

277

A generalized Grubbs-Beck test statistic for detecting multiple potentially influential low outliers in flood series  

USGS Publications Warehouse

he Grubbs-Beck test is recommended by the federal guidelines for detection of low outliers in flood flow frequency computation in the United States. This paper presents a generalization of the Grubbs-Beck test for normal data (similar to the Rosner (1983) test; see also Spencer and McCuen (1996)) that can provide a consistent standard for identifying multiple potentially influential low flows. In cases where low outliers have been identified, they can be represented as “less-than” values, and a frequency distribution can be developed using censored-data statistical techniques, such as the Expected Moments Algorithm. This approach can improve the fit of the right-hand tail of a frequency distribution and provide protection from lack-of-fit due to unimportant but potentially influential low flows (PILFs) in a flood series, thus making the flood frequency analysis procedure more robust.

Cohn, T. A.; England, J. F.; Berenbrock, C. E.; Mason, R. R.; Stedinger, J. R.; Lamontagne, J. R.

2013-01-01

278

A generalized Grubbs-Beck test statistic for detecting multiple potentially influential low outliers in flood series  

NASA Astrophysics Data System (ADS)

The Grubbs-Beck test is recommended by the federal guidelines for detection of low outliers in flood flow frequency computation in the United States. This paper presents a generalization of the Grubbs-Beck test for normal data (similar to the Rosner (1983) test; see also Spencer and McCuen (1996)) that can provide a consistent standard for identifying multiple potentially influential low flows. In cases where low outliers have been identified, they can be represented as "less-than" values, and a frequency distribution can be developed using censored-data statistical techniques, such as the Expected Moments Algorithm. This approach can improve the fit of the right-hand tail of a frequency distribution and provide protection from lack-of-fit due to unimportant but potentially influential low flows (PILFs) in a flood series, thus making the flood frequency analysis procedure more robust.

Cohn, T. A.; England, J. F.; Berenbrock, C. E.; Mason, R. R.; Stedinger, J. R.; Lamontagne, J. R.

2013-08-01

279

Determination of ?s from a differential-jet-multiplicity distribution in e+e- collisions at ?s =29 and 91 GeV  

NASA Astrophysics Data System (ADS)

We measured the differential jet-multiplicity distribution in e+e- annihilation with the Mark II detector. This distribution is compared with the second-order QCD prediction and ?s is determined to be 0.123+/-0.009+/-0.005 at ?s~=MZ (at the SLAC Linear Collider) and 0.149+/-0.002+/-0.007 at ?s=29 GeV (at the SLAC storage ring PEP). The running of ?s between these two center-of-mass energies is consistent with the QCD prediction.

Komamiya, S.; Le Diberder, F.; Abrams, G. S.; Adolphsen, C. E.; Averill, D.; Ballam, J.; Barish, B. C.; Barklow, T.; Barnett, B. A.; Bartelt, J.; Bethke, S.; Blockus, D.; Bonvicini, G.; Boyarski, A.; Brabson, B.; Breakstone, A.; Bulos, F.; Burchat, P. R.; Burke, D. L.; Cence, R. J.; Chapman, J.; Chmeissani, M.; Cords, D.; Coupal, D. P.; Dauncey, P.; Destaebler, H. C.; Dorfan, D. E.; Dorfan, J. M.; Drewer, D. C.; Elia, R.; Feldman, G. J.; Fernandes, D.; Field, R. C.; Ford, W. T.; Fordham, C.; Frey, R.; Fujino, D.; Gan, K. K.; Gatto, C.; Gero, E.; Gidal, G.; Glanzman, T.; Goldhaber, G.; Gomez Cadenas, J. J.; Gratta, G.; Grindhammer, G.; Grosse-Wiesmann, P.; Hanson, G.; Harr, R.; Harral, B.; Harris, F. A.; Hawkes, C. M.; Hayes, K.; Hearty, C.; Heusch, C. A.; Hildreth, M. D.; Himel, T.; Hinshaw, D. A.; Hong, S. J.; Hutchinson, D.; Hylen, J.; Innes, W. R.; Jacobsen, R. G.; Jaros, J. A.; Jung, C. K.; Kadyk, J. A.; Kent, J.; King, M.; Klein, S. R.; Koetke, D. S.; Koska, W.; Kowalski, L. A.; Kozanecki, W.; Kral, J. F.; Kuhlen, M.; Labarga, L.; Lankford, A. J.; Larsen, R. R.; Levi, M. E.; Litke, A. M.; Lou, X. C.; Lüth, V.; McKenna, J. A.; Matthews, J. A.; Mattison, T.; Milliken, B. D.; Moffeit, K. C.; Munger, C. T.; Murray, W. N.; Nash, J.; Ogren, H.; O'shaughnessy, K. F.; Parker, S. I.; Peck, C.; Perl, M. L.; Perrier, F.; Petradza, M.; Pitthan, R.; Porter, F. C.; Rankin, P.; Riles, K.; Rouse, F. R.; Rust, D. R.; Sadrozinski, H. F.; Schaad, M. W.; Schumm, B. A.; Seiden, A.; Smith, J. G.; Snyder, A.; Soderstrom, E.; Stoker, D. P.; Stroynowski, R.; Swartz, M.; Thun, R.; van Kooten, R.; Voruganti, P.; Wagner, S. R.; Watson, S.; Weber, P.; Weigend, A.; Weinstein, A. J.; Weir, A. J.; Wicklund, E.; Woods, M.; Wu, D. Y.; Yurko, M.; Zaccardelli, C.; von Zanthier, C.

1990-02-01

280

Electronic and transport properties of T-graphene nanoribbon: Symmetry-dependent multiple Dirac points, negative differential resistance and linear current-bias characteristics  

NASA Astrophysics Data System (ADS)

Based on the tight-binding method and density functional theory, band structures and transport properties of T-graphene nanoribbons are investigated. By constructing and solving the tight-binding Hamiltonian, we derived the analytic expressions of the linear dispersion relation and Fermi velocity of Dirac-like fermions for armchair T-graphene nanoribbons. Multiple Dirac points, which are triggered by the mirror symmetry of armchair T-graphene nanoribbons, are observed. The number and positions of multiple Dirac points can be well explained by our analytic expressions. Tight-binding results are confirmed by the results from density functional calculations. Moreover, armchair T-graphene nanoribbons exhibit negative differential resistance, whereas zigzag T-graphene nanoribbons have linear current-bias voltage characteristics near the Fermi level.

Dai, C. J.; Yan, X. H.; Xiao, Y.; Guo, Y. D.

2014-08-01

281

Loss of the Osteogenic Differentiation Potential during Senescence Is Limited to Bone Progenitor Cells and Is Dependent on p53  

PubMed Central

DNA damage can lead to the induction of cellular senescence. In particular, we showed that exposure to ionizing radiation (IR) leads to the senescence of bone marrow-derived multipotent stromal cells (MSC) and osteoblast-like stromal cells (OB–SC), a phenotype associated with bone loss. The mechanism by which IR leads to bone dysfunction is not fully understood. One possibility involves that DNA damage-induced senescence limits the regeneration of bone progenitor cells. Another possibility entails that bone dysfunction arises from the inability of accumulating senescent cells to fulfill their physiological function. Indeed, we show here that exposure to IR prevented the differentiation and mineralization functions of MSC, an effect we found was limited to this population as more differentiated OB–SC could still form mineralize nodules. This is in contrast to adipogenesis, which was inhibited in both IR-induced senescent MSC and 3T3-L1 pre-adipocytes. Furthermore, we demonstrate that IR-induced loss of osteogenic potential in MSC was p53-dependent, a phenotype that correlates with the inability to upregulate key osteogenic transcription factors. These results are the first to demonstrate that senescence impacts osteogenesis in a cell type dependent manner and suggest that the accumulation of senescent osteoblasts is unlikely to significantly contribute to bone dysfunction in a cell autonomous manner. PMID:24009740

Despars, Genevieve; Carbonneau, Cynthia L.; Bardeau, Pascal; Coutu, Daniel L.; Beausejour, Christian M.

2013-01-01

282

Triterpene saponosides from Lysimachia ciliata differentially attenuate invasive potential of prostate cancer cells.  

PubMed

Neither androgen ablation nor chemotherapeutic agents are effective in reducing the risk of prostate cancer progression. On the other hand, multifaceted effects of phytochemicals, such as triterpene saponins, on cancer cells have been suggested. A promising safety and tolerability profile indicate their possible application in the treatment of advanced prostate cancers. We analyzed the specificity, selectivity and versatility of desglucoanagalloside B effects on human prostate cancer cells derived from prostate cancer metastases to brain (DU-145 cells) and bone (PC-3 cells). Prominent growth arrest and apoptotic response of both cell types was observed in the presence of sub-micromolar desglucoanagalloside B concentrations. This was accompanied by cytochrome c release and caspase 3/7 activation. A relatively low cytostatic and pro-apoptotic response of cancer cells to a desglucoanagalloside B analog, anagallosaponin IV, illustrated the specificity of the effects of desglucoanagalloside B, whereas the low sensitivity of normal prostate PNT2 cells to desglucoanagalloside B showed the selectivity of its action. Inhibition of cancer cell motility was observed in the presence of both saponins, however only desglucoanagalloside B attenuated cancer cell invasive potential, predominantly through an effect on cell elastic properties. These data demonstrate the versatility of its effects on prostate cancer cells. In contrast to PNT2 cells, cancer cells tested in this study were relatively resistant to mitoxantrone. The multifaceted action of desglucoanagalloside B on basic cellular traits, crucial for prostate cancer progression, opens perspectives for elaboration of combined palliative therapies and new prostate cancer prophylaxis regimens. PMID:23954719

Koczurkiewicz, Paulina; Podolak, Irma; Skrzeczy?ska-Moncznik, Joanna; Sarna, Micha?; Wójcik, Katarzyna Anna; Ryszawy, Damian; Galanty, Agnieszka; Lasota, S?awomir; Madeja, Zbigniew; Czy?, Jaros?aw; Michalik, Marta

2013-10-25

283

Increases in intracellular calcium via activation of potentially multiple phospholipase C isozymes in mouse olfactory neurons  

PubMed Central

Phospholipase C (PLC) and internal Ca2+ stores are involved in a variety of cellular functions. However, our understanding of PLC in mammalian olfactory sensory neurons (OSNs) is generally limited to its controversial role in odor transduction. Here we employed single-cell Ca2+ imaging and molecular approaches to investigate PLC-mediated Ca2+ responses and its isozyme gene transcript expression. We found that the pan-PLC activator m-3M3FBS (25 ?M) induces intracellular Ca2+ increases in vast majority of isolated mouse OSNs tested. Both the response amplitude and percent responding cells depend on m-3M3FBS concentrations. In contrast, the inactive analog o-3M3FBS fails to induce Ca2+ responses. The m-3M3FBS-induced Ca2+ increase is blocked by the PLC inhibitor U73122, while its inactive analog U73433 has no effect. Removal of extracellular Ca2+ does not change significantly the m-3M3FBS-induced Ca2+ response amplitude. Additionally, in the absence of external Ca2+, we found that a subset of OSNs respond to an odorant mixture with small Ca2+ increases, which are significantly suppressed by U73122. Furthermore, using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction, we found that multiple PLC isozyme gene transcripts are expressed in olfactory turbinate tissue in various levels. Using RNA in situ hybridization analysis, we further show expression of ?4, ?1, ?2 gene transcripts in OSNs. Taken together, our results establish that PLC isozymes are potent enzymes for mobilizing intracellular Ca2+ in mouse OSNs and provide molecular insight for PLC isozymes-mediated complex cell signaling and regulation in the peripheral olfactory epithelium. PMID:25374507

Szebenyi, Steven A.; Ogura, Tatsuya; Sathyanesan, Aaron; AlMatrouk, Abdullah K.; Chang, Justin; Lin, Weihong

2014-01-01

284

Clinicopathological significance and potential drug target of p15INK4B in multiple myeloma  

PubMed Central

Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. In addition to genetic changes, gene hypermethylation is an alternative mechanism of tumor suppressor gene inactivation in MM. The cyclin-dependent kinase inhibitor 1 (CDKN2B or p15INK4B) gene lies adjacent to the tumor suppressor gene, cyclin-dependent kinase inhibitor 2 (CDKN2A), and is frequently mutated and deleted in a wide variety of tumors, including MM. However, there is a lack of systematic analysis of p15 epigenetic modification such as methylation in MM from different studies that can provide more powerful estimation of an effect. In this study, we have systematically reviewed the studies of p15INK4B promoter methylation in MM and quantified the association between p15INK4B promoter methylation and MM using meta-analysis methods. We observed that the frequency of p15INK4B methylation is significantly higher in MM patients than in normal healthy controls. The pooled odds ratio (OR) from ten studies including 394 MM and 99 normal individuals is 0.08, while confidence interval (CI) is 0.03–0.21 (P<0.00001). This indicates that p15INK4B inactivation through methylation plays an important role in the pathogenesis of MM. In addition, the frequency of p15INK4B methylation was significantly higher in patients with MM than in those with asymptomatic monoclonal gammopathy of undetermined significance. The pooled OR from four studies is 0.40, 95% CI =0.21–0.78 (P=0.007). These results suggest that silencing of p15INK4B gene expression by epigenetic modification such as promoter hypermethylation plays a role not only in the initiation of MM but also in plasma cell malignant transformation, disease progression, and development. PMID:25382971

Li, Jun; Bi, Lintao; Lin, Yumei; Lu, Zhenxia; Hou, Gang

2014-01-01

285

Shrub Encroachment Impacts the Potential for Multiple Use Conflicts on Public Land  

NASA Astrophysics Data System (ADS)

Public rangelands in North America are typically managed under a multiple use policy that includes livestock grazing and wildlife management. In this article we report on the landscape level extent of grassland loss to shrub encroachment in a portion of the Rocky Mountain Forest Reserve in southwestern Alberta, Canada, and review the associated implications for simultaneously supporting livestock and wildlife populations while maintaining range health on this diminishing vegetation type. Digitized aerial photographs of 12 km of valley bottom from 1958 and 1974 were co-registered to ortho-rectified digital imagery taken in 1998, and an un-supervised classification used to determine areas associated with grassland and shrubland in each year. Field data from 2002 were over-layed using GPS coordinates to refine the classification using a calibration-validation procedure. Over the 40-year study period, open grasslands declined from 1,111 ha in 1958 to 465 ha in 1998, representing a 58% decrease. Using mean production data for grass and shrub dominated areas we then quantified aggregate changes in grazing capacity of both primary (grassland) and secondary (shrubland) habitats for livestock and wildlife. Total declines in grazing capacity from 1958 to 1998 totaled 2,744 Animal Unit Months (AUMs) of forage (-39%), including a 58% decrease in primary (i.e., open grassland) range, which was only partly offset by the availability of 1,357 AUMs within less productive and less accessible shrubland habitats. Our results indicate shrub encroachment has been extensive and significantly reduced forage availability to domestic livestock and wildlife, and will increase the difficulty of conserving remaining grasslands. Although current grazing capacities remain marginally above those specified by regulated grazing policies, it is clear that continued habitat change and decreases in forage availability are likely to threaten the condition of remaining grasslands. Unless shrub encroachment is arrested or grassland restoration initiated, reductions in aggregate ungulate numbers may be necessary.

Burkinshaw, Angela M.; Bork, Edward W.

2009-09-01

286

Differentiation Potential of Pancreatic Fibroblastoid Cells/Stellate Cells: Effects of Peroxisome Proliferator-Activated Receptor Gamma Ligands  

PubMed Central

Pancreatic stellate cells have been investigated mostly for their activation process, supposed to support the development of pancreatic disease. Few studies have been presented on reversal of the activation process in vitro. Thiazolidinediones (TZDs) have been used as antidiabetics and have now been reported to exert antifibrotic activity. We tested effects of natural and synthetic ligands of peroxisome proliferator-activated receptor gamma (PPAR?) on human pancreatic fibroblastoid cells (hPFCs) in search for specificity of action. Ciglitazone, as a prototype of TZDs, was shown to have reversible growth inhibitory effects on human pancreatic fibroblastoid cells/stellate cells. Cells treated with ciglitazone for three days showed enhanced lipid content and induction of proteins involved in lipid metabolism. Collagen synthesis was reduced in hPFC. Interaction of PPAR? with DNA binding sites upon ligand binding was shown by gel shift analysis. These findings point toward a potential for adipocyte differentiation in human pancreatic fibroblastoid cells. PMID:22007221

Kruse, M.-L.; Hopf-Jensen, S.; Timke, C.; Agricola, B.; Sparmann, G.; Schmid, A.; Sipos, B.; Arlt, A.; Schafer, H.

2011-01-01

287

A Numerical Approach to Solving Nonlinear Differential Equations on a Grid with Potential Applicability to Computational Fluid Dynamics  

E-print Network

A finite element method for solving nonlinear differential equations on a grid, with potential applicability to computational fluid dynamics (CFD), is developed and tested. The current method facilitates the computation of solutions of a high polynomial degree on a grid. A high polynomial degree is achieved by interpolating both the value, and the value of the derivatives up to a given order, of continuously distributed unknown variables. The two-dimensional lid-driven cavity, a common benchmark problem for CFD methods, is used as a test case. It is shown that increasing the polynomial degree has some advantages, compared to increasing the number of grid-points, when solving the given benchmark problem using the current method. The current method yields results which agree well with previously published results for this test case.

Tveit, Jesper

2014-01-01

288

The Potential of TaqMan Array Cards for Detection of Multiple Biological Agents by Real-Time PCR  

PubMed Central

The TaqMan Array Card architecture, normally used for gene expression studies, was evaluated for its potential to detect multiple bacterial agents by real-time PCR. Ten PCR assays targeting five biological agents (Bacillus anthracis, Burkholderia mallei, Burkholderia pseudomallei, Francisella tularensis, and Yersinia pestis) were incorporated onto Array Cards. A comparison of PCR performance of each PCR in Array Card and singleplex format was conducted using DNA extracted from pure bacterial cultures. When 100 fg of agent DNA was added to Array Card channels the following levels of agent detection (where at least one agent PCR replicate returned a positive result) were observed: Y. pestis 100%, B. mallei & F. tularensis 93%; B. anthracis 71%; B. pseudomallei 43%. For B. mallei & pseudomallei detection the BPM2 PCR, which detects both species, outperformed PCR assays specific to each organism indicating identification of the respective species would not be reproducible at the 100 fg level. Near 100% levels of detection were observed when 100 fg of DNA was added to each PCR in singleplex format with singleplex PCRs also returning sporadic positives at the 10 fg per PCR level. Before evaluating the use of Array Cards for the testing of environmental and clinical sample types, with potential levels of background DNA and PCR inhibitors, users would therefore have to accept a 10-fold reduction in sensitivity of PCR assays on the Array Card format, in order to benefit for the capacity to test multiple samples for multiple agents. A two PCR per agent strategy would allow the testing of 7 samples for the presence of 11 biological agents or 3 samples for 23 biological agents per card (with negative control channels). PMID:22540014

Rachwal, Phillip A.; Rose, Helen L.; Cox, Victoria; Lukaszewski, Roman A.; Murch, Amber L.; Weller, Simon A.

2012-01-01

289

Differential Radiosensitizing Potential of Temozolomide in MGMT Promoter Methylated Glioblastoma Multiforme Cell Lines  

SciTech Connect

Purpose: To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated {gamma}-irradiation. Methods and Materials: Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of {gamma}-irradiation. Repeated TMZ doses were given before and concurrent with irradiation treatment. Immediately plated clonogenic cell-survival curves were determined for both the single-dose and the fractionated irradiation experiments. To establish the net effect of clonogenic cell survival and cell proliferation, growth curves were determined, expressed as the number of surviving cells. Results: All three cell lines showed MGMT promoter methylation, lacked MGMT protein expression, and were sensitive to TMZ. The isotoxic TMZ concentrations used were in a clinically feasible range of 10 {mu}mol/L (AMC-3046), 3 {mu}mol/L (VU-109), and 2.5 {mu}mol/L (VU-122). Temozolomide was able to radiosensitize two cell lines (AMC 3046 and VU-122) using single-dose irradiation. A reduction in the number of surviving cells after treatment with the combination of TMZ and fractionated irradiation was seen in all three cell lines, but only AMC 3046 showed a radiosensitizing effect. Conclusions: This study on TMZ-sensitive GBM cell lines shows that TMZ can act as a radiosensitizer and is at least additive to {gamma}-irradiation. Enhancement of the radiation response by TMZ seems to be independent of the epigenetically silenced MGMT gen000.

Nifterik, Krista A. van [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Department of Neurogenetics, Academic Medical Center, Amsterdam (Netherlands); Berg, Jaap van den [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Stalpers, Lukas J.A. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Lafleur, M. Vincent M. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Leenstra, Sieger [Department of Neurosurgery, Academic Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Hulsebos, Theo J.M. [Department of Neurogenetics, Academic Medical Center, Amsterdam (Netherlands); Sminia, Peter [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)], E-mail: p.sminia@vumc.nl

2007-11-15

290

The heterodimeric sweet taste receptor has multiple potential ligand binding sites.  

PubMed

The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. Although crystal structures are not available for the sweet taste receptor, useful homology models can be developed based on appropriate templates. The amino terminal domain, cysteine rich domain and transmembrane helix domain of T1R2 and T1R3 have been modeled based on the crystal structures of metabotropic glutamate receptor type 1, tumor necrosis factor receptor, and bovine rhodopsin, respectively. We have used homology models of the sweet taste receptors, molecular docking of sweet ligands to the receptors, and site-directed mutagenesis of the receptors to identify potential ligand binding sites of the sweet taste receptor. These studies have led to a better understanding of the structure and function of this heterodimeric receptor, and can act as a guide for rational structure-based design of novel non-caloric sweeteners, which can be used in the fighting against obesity and diabetes. PMID:17168764

Cui, Meng; Jiang, Peihua; Maillet, Emeline; Max, Marianna; Margolskee, Robert F; Osman, Roman

2006-01-01

291

Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation  

PubMed Central

Purpose The purpose of this study was to develop a framework for analyzing retinal pigment epithelium (RPE) expression profiles from zebrafish eye mutants. Methods The fish model we used was SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (smarca4), a retinal dystrophic mutant with a previously described retinal phenotype and expression profiles. Histological and Affymetrix GeneChip analyses were conducted to characterize the RPE defects and underlying differential expression, respectively. Results Histological analysis revealed that smarca4 RPE was formed, but its differentiation was abnormal. In particular, ultrastructural analysis of smarca4 RPE by transmission electron microscopy demonstrated several defects in melanogenesis. The nature of these defects also suggests that the cytoskeletal dynamics, which are tightly linked with melanogenesis, were impaired in smarca4 RPE. To compare the expression profile of normal wild-type (WT) and smarca4 RPE, the gene expression profiles of microdissected retinas and RPE-attached retinas were measured with Affymetrix GeneChip analysis. The RPE expression values were then estimated from these samples by subtracting the retinal expression values from the expression values of the RPE-attached retinas. A factorial analysis was conducted using the expression values of the RPE, retinal, and whole-embryo samples. Specific rules (contrasts) were built using the coefficients of the resulting fitted models to select for three groups of genes: 1) smarca4-regulated RPE genes, 2) smarca4-regulated retinal genes, and 3) smarca4-regulated RPE genes that are not differentially expressed in the retina. Interestingly, the third group consists of 39 genes that are highly related to cytoskeletal dynamics, melanogenesis, and paracrine and intracellular signal transduction. Conclusions Our analytical framework provides an experimental approach to identify differentially-regulated genes in the retina and the RPE of zebrafish mutants in which both of these tissues are affected by the underlying mutation. Specifically, we have used the method to identify a group of 39 genes that can potentially explain the melanogenesis defect in the smarca4 RPE. In addition, several genes in this group are secreted signaling molecules. Thus, this observation further implicates that the smarca4 RPE might play a role in the retinal dystrophic phenotype in smarca4. PMID:24426776

Ma, Ping; Collery, Ross; Trowbridge, Sara; Zhong, Wenxuan; Leung, Yuk Fai

2014-01-01

292

Determination of Pu content in a Spent Fuel Assembly by Measuring Passive Total Neutron count rate and Multiplication with the Differential Die-Away Instrument  

SciTech Connect

Inspired by approach of Bignan and Martin-Didier (ESARDA 1991) we introduce novel (instrument independent) approach based on multiplication and passive neutron. Based on simulations of SFL-1 the accuracy of determination of {sup tot}Pu content with new approach is {approx}1.3-1.5%. Method applicable for DDA instrument, since it can measure both multiplication and passive neutron count rate. Comparison of pro's & con's of measuring/determining of {sup 239}Pu{sub eff} and {sup tot}Pu suggests a potential for enhanced diversion detection sensitivity.

Henzl, Vladimir [Los Alamos National Laboratory; Croft, Stephen [Los Alamos National Laboratory; Swinhoe, Martyn T. [Los Alamos National Laboratory; Tobin, Stephen J. [Los Alamos National Laboratory

2012-07-13

293

Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum  

PubMed Central

Background Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (<30?Mb), and approximately 20 to 30% triacylglyceride (TAG) accumulation on a dry cell basis has been reported under different growth conditions. To elucidate P. tricornutum gene expression profiles during nutrient-deprivation and lipid-accumulation, cell cultures were grown with a nitrate to phosphate ratio of 20:1 (N:P) and whole-genome transcripts were monitored over time via RNA-sequence determination. Results The specific Nile Red (NR) fluorescence (NR fluorescence per cell) increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC) levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold) at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases). Conclusions The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous DIC levels. Based upon overall low gene expression levels for fatty acid synthesis, the results also suggest that the build-up of precursors to the acetyl-CoA carboxylases may play a more significant role in TAG synthesis rather than the actual enzyme levels of acetyl-CoA carboxylases per se. The presented insights into the types and timing of cellular responses to inorganic carbon will help maximize photoautotrophic carbon flow to lipid accumulation. PMID:22672912

2012-01-01

294

Following a tick bite: double infections by tick-borne encephalitis virus and the spirochete Borrelia and other potential multiple infections.  

PubMed

In Central Europe and large parts of Asia, tick-borne-encephalitis (TBE) and Lyme borreliosis caused by the spirochetal bacterium of the genus Borrelia are among the most common diseases transmitted by the bite of a tick. When in regions with overlapping TBE virus and Borrelia endemicity, a tick bite causes the victim to become ill, it is important that appropriate serological and other laboratory investigations form part of the differential diagnosis. Account must always be taken of the fact that a tick bite may be followed by a double infection with the TBE virus and Borrelia. For this reason, a comprehensive diagnostic work-up aimed at detecting co-infection by both pathogens, even when the tick bite occurs in an endemic region for both pathogens but the initial clinical symptoms suggest an infection with only one of the two pathogens. The present article discusses a number of published cases of a co-infection with TBE virus and Borrelia and other potential multiple infections. PMID:21848518

Bröker, M

2012-05-01

295

Diagnostic potential of near-infrared Raman spectroscopy in the stomach: differentiating dysplasia from normal tissue.  

PubMed

Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically probing the biomolecular changes associated with diseased transformation. The purpose of this study was to explore near-infrared (NIR) Raman spectroscopy for identifying dysplasia from normal gastric mucosa tissue. A rapid-acquisition dispersive-type NIR Raman system was utilised for tissue Raman spectroscopic measurements at 785 nm laser excitation. A total of 76 gastric tissue samples obtained from 44 patients who underwent endoscopy investigation or gastrectomy operation were used in this study. The histopathological examinations showed that 55 tissue specimens were normal and 21 were dysplasia. Both the empirical approach and multivariate statistical techniques, including principal components analysis (PCA), and linear discriminant analysis (LDA), together with the leave-one-sample-out cross-validation method, were employed to develop effective diagnostic algorithms for classification of Raman spectra between normal and dysplastic gastric tissues. High-quality Raman spectra in the range of 800-1800 cm(-1) can be acquired from gastric tissue within 5 s. There are specific spectral differences in Raman spectra between normal and dysplasia tissue, particularly in the spectral ranges of 1200-1500 cm(-1) and 1600-1800 cm(-1), which contained signals related to amide III and amide I of proteins, CH(3)CH(2) twisting of proteins/nucleic acids, and the C=C stretching mode of phospholipids, respectively. The empirical diagnostic algorithm based on the ratio of the Raman peak intensity at 875 cm(-1) to the peak intensity at 1450 cm(-1) gave the diagnostic sensitivity of 85.7% and specificity of 80.0%, whereas the diagnostic algorithms based on PCA-LDA yielded the diagnostic sensitivity of 95.2% and specificity 90.9% for separating dysplasia from normal gastric tissue. Receiver operating characteristic (ROC) curves further confirmed that the most effective diagnostic algorithm can be derived from the PCA-LDA technique. Therefore, NIR Raman spectroscopy in conjunction with multivariate statistical technique has potential for rapid diagnosis of dysplasia in the stomach based on the optical evaluation of spectral features of biomolecules. PMID:18195711

Teh, S K; Zheng, W; Ho, K Y; Teh, M; Yeoh, K G; Huang, Z

2008-01-29

296

Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: Differential relationships with structural magnetic resonance imaging  

Microsoft Academic Search

Multiple sclerosis (MS), a central nervous system (CNS) neurodegenerative disorder, involves lesions of both white and gray matter and reported cognitive impairments that include processing speed (PS), executive function, and working memory (WM). This study closely examined the specifics of these cognitive deficits and their relationship to structural brain damage. A visual n-back task with 3 WM load conditions was

Thomas J. Covey; Robert Zivadinov; Janet L. Shucard; David W. Shucard

2011-01-01

297

Improved Detection of Differential Information-Processing Speed Deficits Between Two Disease-Course Types of Multiple Sclerosis  

Microsoft Academic Search

Patients with multiple sclerosis (MS) frequently demonstrate impairments of information-processing speed (IPS) on measures such as the Paced Auditory Serial Addition Test (PASAT; D. M. A. Gronwall, 1977). The authors have previously shown that their new PASAT scoring method (mean dyad score) is better correlated in comparison with more traditional PASAT scoring method(s), with magnetic resonance imaging measurement of the

Peter J. Snyder; Joseph C. Cappelleri; Catherine J. Archibald; John D. Fisk

2001-01-01

298

None pilot-tones and training sequence assisted OFDM technology based on multiple-differential amplitude phase shift keying.  

PubMed

This paper proposes a novel none pilot-assisted orthogonal frequency division multiplexing (OFDM) technology based on multi-differential amplitude phase shift keying (mDAPSK) for optical OFDM system. It doesn't require any bandwidth-consuming pilot tones or training sequence for channel estimation due to the differential detection during demodulation. In the experiment, a 41.31 Gb/s 64DAPSK-OFDM signal without pilot tones is successfully transmitted over 160-km single mode fiber (SMF). The performance comparison between multi-quadrature amplitude modulation (mQAM) and mDAPSK is also given in the experiment, and the results indicate a prospect of this technology in optical OFDM system. PMID:23037437

Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Yu, Jianjun

2012-09-24

299

Linking potential denitrification rates to microbial gene abundances in multiple boreal ecosystems  

NASA Astrophysics Data System (ADS)

The composition and functioning of boreal ecosystems are vulnerable to changes in climate, leading to changes in season length, fire regimes, and soil moisture status. To investigate the influence of vegetation and soil moisture on microbial nitrogen cycling several disparate boreal ecosystems was studied. The two primary objectives were to: (1) determine whether process rates could be predicted solely from soil physical and chemical characteristics and (2) determine if the abundance of functional genes could be an additional explanatory variable. Surface soils were sampled along an elevation-driven hydrologic gradient at the Bonanza Creek LTER that corresponds with five plant communities typical of interior Alaska. The plant communities included a black spruce stand, a deciduous stand, a tussock grassland, an emergent fen, and a rich fen. We examined the chemical composition of the surface organic moss and soil, measured gross N-mineralization, potential rates of nitrification and denitrification (DEA), and abundances of several functional groups of microorganisms from soil cores collected in mid summer. We used quantitative PCR to assess the gene abundances of ammonia oxidizers and denitrifiers based on a functional gene approach. Here, we focus on potential denitrification rates (PDR), and abundance of denitrifyers carrying NirS and NirK genes (nitrate reductase) and NosZ genes (nitrous oxide reductase). PDR increased dramatically with increasing soil moisture along the gradient, from 1 mg N/m2/h at the dry black spruce site to 300 mg N/m2/h in the rich fen, which is very high compared to other poorly drained soil environments. PDR were linearly related to the abundance of functional genes from the microorganisms responsible for this process. Abundances of NirS, NirK and NosZ genes correlated significantly to PDR (r2 = 0.61 p < 0.0001, r2 = 0.45 p < 0.0003, r2 = 0.81 p < 0.0001, respectively). In addition, PDR were better explained by functional gene abundances than by other biophysical data (e.g. soil moisture, soil temperature, soil C, soil N). This study demonstrates that rates of PDR are strongly affected by the moisture regime, and qPCR is a robust tool for understanding linkages between microbial populations and biogeochemical process rates. Quantitative analyses of different microbial functional groups across landscapes could be established as a sensitive indicator of changes in nitrogen processing.

Petersen, D. G.; Blazewicz, S.; Herman, D. J.; Firestone, M. K.; Waldrop, M. P.

2010-12-01

300

Knockdown of Human TCF4 Affects Multiple Signaling Pathways Involved in Cell Survival, Epithelial to Mesenchymal Transition and Neuronal Differentiation  

PubMed Central

Haploinsufficiency of TCF4 causes Pitt-Hopkins syndrome (PTHS): a severe form of mental retardation with phenotypic similarities to Angelman, Mowat-Wilson and Rett syndromes. Genome-wide association studies have also found that common variants in TCF4 are associated with an increased risk of schizophrenia. Although TCF4 is transcription factor, little is known about TCF4-regulated processes in the brain. In this study we used genome-wide expression profiling to determine the effects of acute TCF4 knockdown on gene expression in SH-SY5Y neuroblastoma cells. We identified 1204 gene expression changes (494 upregulated, 710 downregulated) in TCF4 knockdown cells. Pathway and enrichment analysis on the differentially expressed genes in TCF4-knockdown cells identified an over-representation of genes involved in TGF-? signaling, epithelial to mesenchymal transition (EMT) and apoptosis. Among the most significantly differentially expressed genes were the EMT regulators, SNAI2 and DEC1 and the proneural genes, NEUROG2 and ASCL1. Altered expression of several mental retardation genes such as UBE3A (Angelman Syndrome), ZEB2 (Mowat-Wilson Syndrome) and MEF2C was also found in TCF4-depleted cells. These data suggest that TCF4 regulates a number of convergent signaling pathways involved in cell differentiation and survival in addition to a subset of clinically important mental retardation genes. PMID:24058414

Forrest, Marc P.; Waite, Adrian J.; Martin-Rendon, Enca; Blake, Derek J.

2013-01-01

301

Exercise body surface potential mapping in single and multiple coronary artery disease  

SciTech Connect

Body surface ST integral maps were recorded in 36 coronary artery disease (CAD) patients at: rest; peak, angina-limited exercise; and, 1 and 5 min of recovery. They were compared to maps of 15 CAD patients who exercised to fatigue, without angina, and eight normal subjects. Peak exercise heart rates were similar (NS) in all groups. With exercise angina, patients with two and three vessel CAD had significantly (p less than 0.05) greater decrease in the body surface sum of ST integral values than patients with single vessel CAD. CAD patients with exercise fatigue, in the absence of angina, had decreased ST integrals similar (NS) to patients with single vessel CAD who manifested angina and the normal control subjects. There was, however, considerable overlap among individuals; some patients with single vessel CAD had as much exercise ST integral decrease as patients with three vessel CAD. All CAD patients had persistent ST integral decreases at 5 min of recovery and there was a direct correlation of the recovery and peak exercise ST changes. Exercise ST changes correlated, as well, with quantitative CAD angiographic scores, but not with thallium perfusion scores. These data suggest exercise ST integral body surface mapping allows quantitation of myocardium at ischemic risk in patients with CAD, irrespective of the presence or absence of ischemic symptoms during exercise. A major potential application of this technique is selection of CAD therapy guided by quantitative assessment of ischemic myocardial risk.

Montague, T.J.; Witkowski, F.X.; Miller, R.M.; Johnstone, D.E.; MacKenzie, R.B.; Spencer, C.A.; Horacek, B.M. (Univ. of Alberta, Edmonton (Canada))

1990-06-01

302

Comparative Analysis of Proliferation and Differentiation Potentials of Stem Cells from Inflamed Pulp of Deciduous Teeth and Stem Cells from Exfoliated Deciduous Teeth  

PubMed Central

Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of proliferation and differentiation, and they represent good cell sources for mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply of SHEDs is limited. A previous study found that stem cells could be isolated from inflamed tissues, but it is unknown whether primary dental pulp diagnosed with irreversible pulpitis might contain stem cells with appropriate tissue regeneration capacity. In this study, we aimed to isolate stem cells from both inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to compare their proliferation and differentiation potentials. Our results showed that SCIDs were positive for cell surface markers, including CD105, CD90, and CD146, and they had high proliferation ability and osteogenic, adipogenic, and chondrogenic differentiation potentials. There was no significant difference in proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of inflammatory factors, including IL-1?, IL-6, and TNF-?, was expressed at similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-? protein. In conclusion, our in vitro results showed that SCIDs have proliferation and differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new potentially applicable source for MSC mediated tissue regeneration. PMID:25045714

Yu, Shi; Diao, Shu; Wang, Jinsong; Ding, Gang; Yang, Dongmei; Fan, Zhipeng

2014-01-01

303

Comparative analysis of proliferation and differentiation potentials of stem cells from inflamed pulp of deciduous teeth and stem cells from exfoliated deciduous teeth.  

PubMed

Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of proliferation and differentiation, and they represent good cell sources for mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply of SHEDs is limited. A previous study found that stem cells could be isolated from inflamed tissues, but it is unknown whether primary dental pulp diagnosed with irreversible pulpitis might contain stem cells with appropriate tissue regeneration capacity. In this study, we aimed to isolate stem cells from both inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to compare their proliferation and differentiation potentials. Our results showed that SCIDs were positive for cell surface markers, including CD105, CD90, and CD146, and they had high proliferation ability and osteogenic, adipogenic, and chondrogenic differentiation potentials. There was no significant difference in proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of inflammatory factors, including IL-1?, IL-6, and TNF-?, was expressed at similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-? protein. In conclusion, our in vitro results showed that SCIDs have proliferation and differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new potentially applicable source for MSC mediated tissue regeneration. PMID:25045714

Yu, Shi; Diao, Shu; Wang, Jinsong; Ding, Gang; Yang, Dongmei; Fan, Zhipeng

2014-01-01

304

Dopaminergic and opiate agonists and antagonists differentially decrease multiple schedule responding maintained by sucrose\\/ethanol and sucrose  

Microsoft Academic Search

Similar neurobiological mechanisms are hypothesized to influence ethanol- and food-related reinforcement processes. This study examined the ability of compounds with dopaminergic or opiate activity to selectively alter responding maintained by a sucrose\\/ethanol solution in comparison to a sucrose solution. Long-Evans rats were trained to press a lever using 5% sucrose\\/10% ethanol and 5% sucrose as the reinforcers on a multiple

Craig J. Slawecki; Clyde W. Hodge; Herman H. Samson

1997-01-01

305

Differential Expression of Adenine Nucleotide Converting Enzymes in Mitochondrial Intermembrane Space: A Potential Role of Adenylate Kinase Isozyme 2 in Neutrophil Differentiation  

PubMed Central

Adenine nucleotide dynamics in the mitochondrial intermembrane space (IMS) play a key role in oxidative phosphorylation. In a previous study, Drosophila adenylate kinase isozyme 2 (Dak2) knockout was reported to cause developmental lethality at the larval stage in Drosophila melanogaster. In addition, two other studies reported that AK2 is a responsible gene for reticular dysgenesis (RD), a human disease that is characterized by severe combined immunodeficiency and deafness. Therefore, mitochondrial AK2 may play an important role in hematopoietic differentiation and ontogenesis. Three additional adenine nucleotide metabolizing enzymes, including mitochondrial creatine kinases (CKMT1 and CKMT2) and nucleoside diphosphate kinase isoform D (NDPK-D), have been found in IMS. Although these kinases generate ADP for ATP synthesis, their involvement in RD remains unclear and still an open question. In this study, mRNA and protein expressions of these mitochondrial kinases were firstly examined in mouse ES cells, day 8 embryos, and 7-week-old adult mice. It was found that their expressions are spatiotemporally regulated, and Ak2 is exclusively expressed in bone marrow, which is a major hematopoietic tissue in adults. In subsequent experiments, we identified increased expression of both AK2 and CKMT1 during macrophage differentiation and exclusive production of AK2 during neutrophil differentiation using HL-60 cells as an in vitro model of hematopoietic differentiation. Furthermore, AK2 knockdown specifically inhibited neutrophil differentiation without affecting macrophage differentiation. These data suggest that AK2 is indispensable for neutrophil differentiation and indicate a possible causative link between AK2 deficiency and neutropenia in RD. PMID:24587121

Tanimura, Ayako; Horiguchi, Taigo; Miyoshi, Keiko; Hagita, Hiroko; Noma, Takafumi

2014-01-01

306

Multiple functions of a Zic-like gene in the differentiation of notochord, central nervous system and muscle in Ciona savignyi embryos.  

PubMed

Multiple functions of a Zic-like zinc finger transcription factor gene (Cs-ZicL) were identified in Ciona savignyi embryos. cDNA clones for Cs-ZicL, a beta-catenin downstream genes, were isolated and the gene was transiently expressed in the A-line notochord/nerve cord lineage and in B-line muscle lineage from the 32-cell stage and later in a-line CNS lineage from the 110-cell stage. Suppression of Cs-ZicL function with specific morpholino oligonucleotide indicated that Cs-ZicL is essential for the formation of A-line notochord cells but not of B-line notochord cells, essential for the CNS formation and essential for the maintenance of muscle differentiation. The expression of Cs-ZicL in the A-line cells is downstream of beta-catenin and a beta-catenin-target gene, Cs-FoxD, which is expressed in the endoderm cells from the 16-cell stage and is essential for the differentiation of notochord. In spite of its pivotal role in muscle specification, the expression of Cs-ZicL in the muscle precursors is independent of Cs-macho1, which is another Zic-like gene encoding a Ciona maternal muscle determinant, suggesting another genetic cascade for muscle specification independent of Cs-macho1. Cs-ZicL may provide a future experimental system to explore how the gene expression in multiple embryonic regions is controlled and how the single gene can perform different functions in multiple types of embryonic cells. PMID:12015299

Imai, Kaoru S; Satou, Yutaka; Satoh, Nori

2002-06-01

307

A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model.  

PubMed

Schizophrenia is a chronic and severe psychiatric disorder that is highly heritable. While both common and rare genetic variants contribute to disease risk, many questions still remain about disease etiology. We performed a genome-wide analysis of copy number variants (CNVs) in 166 schizophrenia subjects and 52 psychiatrically healthy controls. First, overall CNV characteristics were compared between cases and controls. The only statistically significant finding was that deletions comprised a greater proportion of CNVs in cases. High interest CNVs were then identified as conservative using the following filtering criteria: (i) known deleterious CNVs; (ii) CNVs?>1?Mb that were novel (not found in a database of control individuals); and (iii) CNVs?<1?Mb that were novel and that overlapped the coding region of a gene of interest. Cases did not harbor a higher proportion of conservative CNVs in comparison to controls. However, similar to previous reports, cases had a slightly higher proportion of individuals with clinically significant CNVs (known deleterious or conservative CNVs?>1?Mb) or with multiple conservative CNVs. Two case individuals with the highest burden of conservative CNVs also share a recurrent 15q11.2 BP1-2 deletion, indicating a role for a potential multiple-hit CNV model for schizophrenia. In total, we report three 15q11.2 BP1-2 deletion individuals with schizophrenia, adding to a growing body of evidence that this CNV is involved in disease etiology. © 2014 Wiley Periodicals, Inc. PMID:25228354

Rudd, Danielle S; Axelsen, Michael; Epping, Eric A; Andreasen, Nancy C; Wassink, Thomas H

2014-12-01

308

Bone marrow stromal cell lines having high potential for osteoclast-supporting activity express PPAR?1 and show high potential for differentiation into adipocytes  

Microsoft Academic Search

Bone marrow stromal cells support osteoclast differentiation by expressing receptor activator of NF-kB ligand (RANKL). Although\\u000a several bone marrow stromal cell lines have been established and characterized, the differentiation stage of the supporting\\u000a cells for osteoclast differentiation remains unclear. We have established several bone marrow stromal cell lines from transgenic\\u000a mice harboring the temperature-sensitive SV40 large T antigen. Some of

Katsuhisa Takagi; Akira Kudo

2008-01-01

309

An Empirical Muscle Intracellular Action Potential Model with Multiple Erlang Probability Density Functions based on a Modified Newton Method  

PubMed Central

The convolution of the transmembrane current of an excitable cell and a weighting function generates a single fiber action potential (SFAP) model by using the volume conductor theory. Here, we propose an empirical muscle IAP model with multiple Erlang probability density functions (PDFs) based on a modified Newton method. In addition, we generate SFAPs based on our IAP model and referent sources, and use the peak-to-peak ratios (PPRs) of SFAPs for model verification. Through this verification, we find that the relation between an IAP profile and the PPR of its SFAP is consistent with some previous studies, and our IAP model shows close profiles to the referent sources. Moreover, we simulate and discuss some possible ionic activities by using the Erlang PDFs in our IAP model, which might present the underlying activities of ions or their channels during an IAP.

Kim, Gyutae; Ferdjallah, Mohammed M; McKenzie, Frederic D

2013-01-01

310

Multiple stepwise pattern for potential of mean force in unfolding the thrombin binding aptamer in complex with Sr2+  

NASA Astrophysics Data System (ADS)

Using all-atom molecular dynamics simulation in conjunction with umbrella sampling, we obtained the unfolding free energy and the force extension profiles of the thrombin binding DNA aptamer (15-TBA) in complex with Sr2+ (Protein Data Bank code: 1RDE). The resulting potential of mean force (PMF) displays a multiple stepwise pattern with distinct plateau regions. The detailed analysis of the simulation result indicated that each plateau was created by the interplay of the metal ion interacting with self-arranging guanine bases and the successive uptakes of water molecules. The current PMF simulation provides a quantitative description of the unfolding process of 15-TBA DNA driven by stretching and gives molecular insight on its detailed changes of base pair interactions in the presence of the metal cation.

Yang, Changwon; Jang, Soonmin; Pak, Youngshang

2011-12-01

311

Multiple pulmonary nodules with high metabolic activity: Potential benefit of multiple nodule biopsies by video-assisted thoracic surgery: A case report  

PubMed Central

The aim of this study was to assess complex cases of multiple pulmonary nodules (PNs) with high metabolic activity that may have benefited from being managed in a manner outside the formal guidelines. The study describes the case of a patient with multiple highly metabolically-active PNs, where an original diagnosis of lung cancer metastasis was proposed. Following a failed transbronchial lung biopsy (TBLB), multiple nodule biopsies by video-assisted thoracic surgery (VATS) were performed, and a diagnosis of lymphoepithelioma-like carcinoma (LELC; stage IA) and tuberculosis was reached. This case report demonstrated that multiple nodule biopsies by VATS were effective and were able to improve the prognosis without delay. PMID:24137183

WANG, JINLIN; LI, SHIYUE; LIU, JUN; GU, YINGYING; CHEN, PING

2013-01-01

312

Piper cubeba targets multiple aspects of the androgen-signalling pathway. A potential phytotherapy against prostate cancer growth?  

PubMed

Despite the high prevalence of prostate cancer (PC) in the Western world, there is a dearth of effective medication. Since the androgen-signalling pathway is very much involved in PC growth and development, we investigated the potential of Piper cubeba L. extract, P9605, in targeting multiple events simultaneously within this pathway. This may be more effective compared to an antiandrogen monotherapy. Our results indicated that P9605 inhibited proliferation in androgen-dependent LNCaP human prostate cancer cells by reducing DNA synthesis and inducing apoptosis. This antigrowth effect was less pronounced in androgen-independent PC-3 prostate cancer cell lines. P9605 potently inhibited 5 alpha-reductase II activity, which is responsible for converting testosterone to its active form, dihydrotestosterone (DHT), in the prostate. It also acted as an antagonist at recombinant wild-type androgen receptors (AR). P9605 suppressed cell growth and prostate-specific antigen (PSA) secretion stimulated by physiological concentrations of DHT in LNCaP cells. Interestingly, it down-regulated AR levels. In conclusion, our findings suggest that P9605 may potentially retard the growth of androgen-dependent PC via several mechanisms. PMID:18080233

Yam, Jianying; Kreuter, Matthias; Drewe, Juergen

2008-01-01

313

Population Differentiation and Species Formation in the Deep Sea: The Potential Role of Environmental Gradients and Depth  

PubMed Central

Ecological speciation probably plays a more prominent role in diversification than previously thought, particularly in marine ecosystems where dispersal potential is great and where few obvious barriers to gene flow exist. This may be especially true in the deep sea where allopatric speciation seems insufficient to account for the rich and largely endemic fauna. Ecologically driven population differentiation and speciation are likely to be most prevalent along environmental gradients, such as those attending changes in depth. We quantified patterns of genetic variation along a depth gradient (1600-3800m) in the western North Atlantic for a protobranch bivalve (Nuculaatacellana) to test for population divergence. Multilocus analyses indicated a sharp discontinuity across a narrow depth range, with extremely low gene flow inferred between shallow and deep populations for thousands of generations. Phylogeographical discordance occurred between nuclear and mitochondrial loci as might be expected during the early stages of species formation. Because the geographic distance between divergent populations is small and no obvious dispersal barriers exist in this region, we suggest the divergence might reflect ecologically driven selection mediated by environmental correlates of the depth gradient. As inferred for numerous shallow-water species, environmental gradients that parallel changes in depth may play a key role in the genesis and adaptive radiation of the deep-water fauna. PMID:24098590

Jennings, Robert M.; Etter, Ron J.; Ficarra, Lynn

2013-01-01

314

Seed dimorphism, nutrients and salinity differentially affect seed traits of the desert halophyte Suaeda aralocaspica via multiple maternal effects  

PubMed Central

Background Maternal effects may influence a range of seed traits simultaneously and are likely to be context-dependent. Disentangling the interactions of plant phenotype and growth environment on various seed traits is important for understanding regeneration and establishment of species in natural environments. Here, we used the seed-dimorphic plant Suaeda aralocaspica to test the hypothesis that seed traits are regulated by multiple maternal effects. Results Plants grown from brown seeds had a higher brown:black seed ratio than plants from black seeds, and germination percentage of brown seeds was higher than that of black seeds under all conditions tested. However, the coefficient of variation (CV) for size of black seeds was higher than that of brown seeds. Seeds had the smallest CV at low nutrient and high salinity for plants from brown seeds and at low nutrient and low salinity for plants from black seeds. Low levels of nutrients increased size and germinability of black seeds but did not change the seed morph ratio or size and germinability of brown seeds. High levels of salinity decreased seed size but did not change the seed morph ratio. Seeds from high-salinity maternal plants had a higher germination percentage regardless of level of germination salinity. Conclusions Our study supports the multiple maternal effects hypothesis. Seed dimorphism, nutrient and salinity interacted in determining a range of seed traits of S. aralocaspica via bet-hedging and anticipatory maternal effects. This study highlights the importance of examining different maternal factors and various offspring traits in studies that estimate maternal effects on regeneration. PMID:23006315

2012-01-01

315

Identification of differentially-expressed genes potentially implicated in drought response in pitaya (Hylocereus undatus) by suppression subtractive hybridization and cDNA microarray analysis.  

PubMed

Drought is one of the most severe threats to the growth, development and yield of plant. In order to unravel the molecular basis underlying the high tolerance of pitaya (Hylocereus undatus) to drought stress, suppression subtractive hybridization (SSH) and cDNA microarray approaches were firstly combined to identify the potential important or novel genes involved in the plant responses to drought stress. The forward (drought over drought-free) and reverse (drought-free over drought) suppression subtractive cDNA libraries were constructed using in vitro shoots of cultivar 'Zihonglong' exposed to drought stress and drought-free (control). A total of 2112 clones, among which half were from either forward or reverse SSH library, were randomly picked up to construct a pitaya cDNA microarray. Microarray analysis was carried out to verify the expression fluctuations of this set of clones upon drought treatment compared with the controls. A total of 309 expressed sequence tags (ESTs), 153 from forward library and 156 from reverse library, were obtained, and 138 unique ESTs were identified after sequencing by clustering and blast analyses, which included genes that had been previously reported as responsive to water stress as well as some functionally unknown genes. Thirty six genes were mapped to 47 KEGG pathways, including carbohydrate metabolism, lipid metabolism, energy metabolism, nucleotide metabolism, and amino acid metabolism of pitaya. Expression analysis of the selected ESTs by reverse transcriptase polymerase chain reaction (RT-PCR) corroborated the results of differential screening. Moreover, time-course expression patterns of these selected ESTs further confirmed that they were closely responsive to drought treatment. Among the differentially expressed genes (DEGs), many are related to stress tolerances including drought tolerance. Thereby, the mechanism of drought tolerance of this pitaya genotype is a very complex physiological and biochemical process, in which multiple metabolism pathways and many genes were implicated. The data gained herein provide an insight into the mechanism underlying the drought stress tolerance of pitaya, as well as may facilitate the screening of candidate genes for drought tolerance. PMID:24076355

Fan, Qing-Jie; Yan, Feng-Xia; Qiao, Guang; Zhang, Bing-Xue; Wen, Xiao-Peng

2014-01-01

316

Blink Reflexes Elicited by Electrical, Acoustic and Visual Stimuli. II. Their Relation to Visual-Evoked Potentials and Auditory Brain Stem Evoked Potentials in the Diagnosis of Multiple Sclerosis  

Microsoft Academic Search

Blink reflexes, elicited by flashes of light, tone bursts and electrical stimuli, as well as checkerboard reversal visual-evoked potentials and brain stem auditory evoked potentials were investigated in 55 patients with different degrees of diagnostic probability of multiple sclerosis. It was demonstrated that electrically and acoustically elicited blink reflexes are simple but rather sensitive methods of indicating brain stem lesions.

W. Tackmann; T. Ettlin

1982-01-01

317

Mutations in the Arabidopsis peroxisomal ABC transporter COMATOSE allow differentiation between multiple functions in planta: insights from an allelic series.  

PubMed

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal beta-oxidation. A new allelic series and a homology model based on the bacterial ABC transporter, Sav1866, provide novel insights into structure-function relations of ABC subfamily D proteins. In contrast to ALDP, where the majority of mutations result in protein absence from the peroxisomal membrane, all CTS mutants produced stable protein. Mutation of conserved residues in the Walker A and B motifs in CTS nucleotide-binding domain (NBD) 1 resulted in a null phenotype but had little effect in NBD2, indicating that the NBDs are functionally distinct in vivo. Two alleles containing mutations in NBD1 outside the Walker motifs (E617K and C631Y) exhibited resistance to auxin precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) but were wild type in all other tests. The homology model predicted that the transmission interfaces are domain-swapped in CTS, and the differential effects of mutations in the conserved "EAA motif" of coupling helix 2 supported this prediction, consistent with distinct roles for each NBD. Our findings demonstrate that CTS functions can be separated by mutagenesis and the structural model provides a framework for interpretation of phenotypic data. PMID:19019987

Dietrich, Daniela; Schmuths, Heike; De Marcos Lousa, Carine; Baldwin, Jocelyn M; Baldwin, Stephen A; Baker, Alison; Theodoulou, Frederica L; Holdsworth, Michael J

2009-01-01

318

Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis  

PubMed Central

Background: Optic pathway involvement in multiple sclerosis is frequently the initial sign in the disease process. In most clinical applications, pattern visual evoked potential (PVEP) is used in the assessment of optic pathway involvement. Objective: To question the value of PVEP against color vision assessment in the diagnosis of subclinical optic pathway involvement. Materials and Methods: This prospective, cross-sectional study included 20 multiple sclerosis patients without a history of optic neuritis, and 20 healthy control subjects. Farnsworth-Munsell (FM) 100-Hue testing and PVEPs to 60-min arc and 15-min arc checks by using Roland-Consult RetiScan® system were performed. P100 amplitude, P100 latency in PVEP and total error scores (TES) in FM 100-Hue test were assessed. Results: Expanded Disability Status Scale score and the time from diagnosis were 2.21 ± 2.53 (ranging from 0 to 7) and 4.1 ± 4.4 years. MS group showed significantly delayed P100 latency for both checks (P < 0.001). Similarly, MS patients had significantly increased total error scores (TES) in FM-100 Hue (P < 0.001). The correlations between TESs and PVEP amplitudes / latencies were insignificant for both checks (P > 0.05 for all). 14 MS patients (70%) had an increased TESs in FM-100 Hue, 11 (55%) MS patients had delayed P100 latency and 9 (45%) had reduced P100 amplitude. The areas under the ROC curves were 0.944 for FM-100 Hue test, 0.753 for P100 latency, and 0.173 for P100 amplitude. Conclusions: Color vision testing seems to be more sensitive than PVEP in detecting subclinical visual pathway involvement in MS. PMID:23514643

Gundogan, Fatih C; Tas, Ahmet; Altun, Salih; Oz, Oguzhan; Erdem, Uzeyir; Sobaci, Gungor

2013-01-01

319

Using human plasma supplemented medium to cultivate human bone marrow-derived mesenchymal stem cell and evaluation of its multiple-lineage potential.  

PubMed

The objective of this study was to evaluate the proliferation and the multiple-lineage differentiation capacity when bone marrow mesenchymal stem cells (BMSCs) were cultured short-term in autologous serum/plasma instead of fetal calf serum (FCS). The BMSCs from 12 donors were cultivated individually in 10% autogenic plasma or serum, with or without bFGF and EGF growth factors. Cell proliferation was examined by a Tetrazolium assay (MTT) after passages 1, 3, and 5. A medium supplemented with 10% human plasma or serum was sufficient to propagate BMSCs. However, no significant proliferation was shown when bFGF and EGF (20 ng/mL each) were added into the medium with autologous serum/plasma. We examined, inductions of adipogenesis, osteogenesis, and chondrocytogenesis, as capacities of multiple-lineage differentiation of cultivated BMSCs (passages 8). Differentiation was investigated by both RT-PCR and immunohistochemistry staining (IHC). Qualitative evidence demonstrated the differentiation capacity was preserved in cultivated BMSCs with autologous serum/plasma. PMID:16387155

Lin, H-T; Tarng, Y-W; Chen, Y-C; Kao, C-L; Hsu, C-J; Shyr, Y-M; Ku, H-H; Chiou, S H

2005-12-01

320

Downregulation of miR122 by grainyhead-like 2 restricts the hepatocytic differentiation potential of adult liver progenitor cells.  

PubMed

Late fetal and adult livers are reported to contain bipotential liver stem/progenitor cells (LPCs), which share surface markers, including epithelial cell adhesion molecule (EpCAM), with cholangiocytes and differentiate into both hepatocytes and cholangiocytes. However, recent results do not necessarily support the idea that LPCs contribute significantly to cellular turnover and regeneration by supplying new hepatocytes. Here, we examined the colony-forming capability of EpCAM(+) cells isolated from mouse livers between E17 and 11?weeks of age. We found that the number of bipotential colonies was greatly reduced between 1 and 6?weeks, indicating that the number of LPCs decreases during postnatal development. Moreover, bipotential colonies derived from adult LPCs contained substantially fewer albumin(+) cells than those from neonatal LPCs. We further examined the differentiation potential of neonatal and adult LPCs by transplantation and found that neonatal cells differentiated into mature hepatocytes in recipient livers more frequently than adult LPCs. Since we previously reported that the transcription factor grainyhead-like 2 (GRHL2) expressed in EpCAM(+) cells inhibits hepatocytic differentiation, we examined whether targets of GRHL2 might block hepatocytic differentiation. DNA and microRNA microarrays revealed that miR122, the expression of which correlates with hepatocytic differentiation, was greatly reduced in adult as compared with neonatal EpCAM(+) cells. Indeed, GRHL2 negatively regulates the promoter/enhancer activity of the Mir122 gene. Our results indicate that neonatal but not adult EpCAM(+) LPCs have great potential to produce albumin(+) hepatocytes. GRHL2 suppresses transcription of miR122 and thereby restricts the differentiation potential of adult LPCs. PMID:25406394

Tanimizu, Naoki; Kobayashi, Seiji; Ichinohe, Norihisa; Mitaka, Toshihiro

2014-12-01

321

The Effects of Differential Reddening and Stellar Rotation on the Appearance of Multiple Populations in Star Clusters: The Case of Trumpler 20  

NASA Astrophysics Data System (ADS)

We present a detailed analysis of the upper main sequence of the ~1.3 Gyr old open cluster Trumpler 20. High-accuracy BVI photometry combined with the Very Large Telescope/FLAMES medium-resolution spectroscopy of 954 stars is essential to understanding the unusual appearance of the color-magnitude diagram (CMD), initially suggesting multiple populations in Trumpler 20. We show that differential reddening is a dominant contributor to the apparent splitting/widening of the main-sequence turnoff region. At its extreme, the excess differential reddening reaches ?(B - V) ~ 0.1 while the adopted minimum reddening for the cluster is E(B - V) = 0.36. A unique sample of measured projected rotational velocities indicates that stellar rotation is high near the main-sequence turnoff, reaching vsin i ~ 180 km s-1. By dividing the upper main-sequence stars into two equal groups of slow and fast rotators, we find that fast rotators have a marginal blueshift of ?(V - I) ~ -0.01, corresponding to a difference in the median vsin i of ~60 km s-1 between these subsamples. We conclude that stellar rotation has an insignificant effect on the morphology of the upper main sequence of this intermediate-age open cluster. Trumpler 20 appears to contain a single coeval population of stars but there is evidence that the red clump is extended.

Platais, I.; Melo, C.; Quinn, S. N.; Clem, J. L.; de Mink, S. E.; Dotter, A.; Kozhurina-Platais, V.; Latham, D. W.; Bellini, A.

2012-05-01

322

Differential Effects of TR Ligands on Hormone Dissociation Rates: Evidence for Multiple Ligand Entry/Exit Pathways  

PubMed Central

Some nuclear receptor (NR) ligands promote dissociation of radiolabeled bound hormone from the buried ligand binding cavity (LBC) more rapidly than excess unlabeled hormone itself. This result was interpreted to mean that challenger ligands bind allosteric sites on the LBD to induce hormone dissociation, and recent findings indicate that ligands bind weakly to multiple sites on the LBD surface. Here, we show that a large fraction of thyroid hormone receptor (TR) ligands promote rapid dissociation (T1/2 <2 hours) of radiolabeled T3 versus T3 (T1/2 ?5–7 hours). We cannot discern relationships between this effect and ligand size, activity or affinity for TR?. One ligand, GC-24, binds the TR LBC and (weakly) to the TR?-LBD surface that mediates dimer/heterodimer interaction, but we cannot link this interaction to rapid T3 dissociation. Instead, several lines of evidence suggest that the challenger ligand must interact with the buried LBC to promote rapid T3 release. Since previous molecular dynamics simulations suggest that TR ligands leave the LBC by several routes, we propose that a subset of challenger ligands binds and stabilizes a partially unfolded intermediate state of TR that arises during T3 release and that this effect enhances hormone dissociation. PMID:19729063

Lima, Suzana T. Cunha; Nguyen, Ngoc-Ha; Togashi, Marie; Apriletti, James W.; Nguyen, Phuong; Polikarpov, Igor; Scanlan, Thomas S.; Baxter, John D.; Webb, Paul

2009-01-01

323

Comparative analysis of in vitro osteo\\/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP)  

Microsoft Academic Search

ObjectiveThe aim of this study was to compare the in vitro osteo\\/odontogenic differentiation potential of mesenchymal stem cells (MSCs) derived from the dental pulp (dental pulp stem cells – DPSCs) or the apical papilla (stem cells from the apical papilla – SCAP) of permanent developing teeth.

A. Bakopoulou; G. Leyhausen; J. Volk; A. Tsiftsoglou; P. Garefis; P. Koidis; W. Geurtsen

2011-01-01

324

Adenosine Triphosphate Binding Cassette (ABC) Transporters Are Expressed and Regulated During Terminal Keratinocyte Differentiation: A Potential Role for ABCA7 in Epidermal Lipid Reorganization  

Microsoft Academic Search

Central aspects of the cellular lipid trafficking mechanisms that occur during keratinocyte differentiation are still not well understood. In the past years, evidence has accumulated to suggest that members of the superfamily of adenosine triphosphate binding cassette (ABC) transporters are critically involved in the transmembrane transport of cellular lipids. To test the hypothesis that ABC molecules are potentially involved in

Danuta Kielar; Wolfgang E Kaminski; Gerhard Liebisch; Armin Piehler; Jürgen J Wenzel; Christoph Möhle; Susanne Heimerl; Thomas Langmann; Sven O Friedrich; Alfred Böttcher; Stefan Barlage; Wolfgang Drobnik; Gerd Schmitz

2003-01-01

325

Neuropathies of the optic nerve and visual evoked potentials with special reference to color vision and differential light threshold measured with the computer perimeter OCTOPUS  

Microsoft Academic Search

The contrast evoked potentials (VEPs) to different check sizes were recorded in about 200 cases of discrete optic neuropathies (ON) of different origin. Differential light threshold (DLT) was tested with the computer perimeter OCTOPUS. Saturated and desaturated tests were applied to evaluate the degree of acquired color vision deficiency. Delayed VEP responses are not confined to optic neuritis (RBN) alone

Hannes Wildberger

1984-01-01

326

Synergism between multiple virus-induced factor-binding elements involved in the differential expression of interferon A genes.  

PubMed

Comparative transfection analysis of murine interferon A4 and interferon A11 promoter constructs transiently transfected in mouse L929 and human HeLa S3 cells infected with Newcastle disease virus showed that the second positive regulatory domain I-like domain (D motif), located between nucleotides -57 and -46 upstream of the transcription start site, contributes to the activation of virus-induced transcription of the interferon (IFN)-A4 gene promoter by cooperating with the positive regulatory domain I-like and TG-like domains previously described. Electrophoretic mobility shift assay performed with the virus-inducible fragments containing these motifs indicated that the binding activity that we have denoted as virus-induced factor (Génin, P., Bragança, J., Darracq, N., Doly, J., and Civas, A. (1995) Nucleic Acids Res. 23, 5055-5063) is different from interferon-stimulated gene factor 3. It binds to the D motif but not to the virus-unresponsive form of the D motif disrupted by a G-57 --> C substitution. We show that the low levels of IFN-A11 gene expression are caused essentially by the lack of two inducible enhancer domains disrupted by the A-78 --> G and the G-57 --> C substitutions. These data suggest a model taking account of the differential regulation of IFN-A gene family members. They also suggest that virus-induced factor may correspond to the primary transcription factor directly activated by virus that is involved in the initiation of IFN-A gene transcription. PMID:9268360

Bragança, J; Génin, P; Bandu, M T; Darracq, N; Vignal, M; Cassé, C; Doly, J; Civas, A

1997-08-29

327

The Potential of Gait Analysis to Contribute to Differential Diagnosis of Early Stage Dementia: Current Research and Future Directions  

ERIC Educational Resources Information Center

Early differential diagnosis of dementia is becoming increasingly important as new pharmacologic therapies are developed, as these treatments are not equally effective for all types of dementia. Early detection and differential diagnosis also facilitates informed family decision making and timely access to appropriate services. Information about…

Morgan, Debra; Funk, Melanie; Crossley, Margaret; Basran, Jenny; Kirk, Andrew; Bello-Haas, Vanina Dal

2007-01-01

328

Mitochondrial analysis of a Byzantine population reveals the differential impact of multiple historical events in South Anatolia  

PubMed Central

The archaeological site of Sagalassos is located in Southwest Turkey, in the western part of the Taurus mountain range. Human occupation of its territory is attested from the late 12th millennium BP up to the 13th century AD. By analysing the mtDNA variation in 85 skeletons from Sagalassos dated to the 11th–13th century AD, this study attempts to reconstruct the genetic signature potentially left in this region of Anatolia by the many civilizations, which succeeded one another over the centuries until the mid-Byzantine period (13th century BC). Authentic ancient DNA data were determined from the control region and some SNPs in the coding region of the mtDNA in 53 individuals. Comparative analyses with up to 157 modern populations allowed us to reconstruct the origin of the mid-Byzantine people still dwelling in dispersed hamlets in Sagalassos, and to detect the maternal contribution of their potential ancestors. By integrating the genetic data with historical and archaeological information, we were able to attest in Sagalassos a significant maternal genetic signature of Balkan/Greek populations, as well as ancient Persians and populations from the Italian peninsula. Some contribution from the Levant has been also detected, whereas no contribution from Central Asian population could be ascertained. PMID:21224890

Ottoni, Claudio; Ricaut, Francois-X; Vanderheyden, Nancy; Brucato, Nicolas; Waelkens, Marc; Decorte, Ronny

2011-01-01

329

Tracing Learning of Three Representations with the Differentiation Competency Framework  

Microsoft Academic Search

The support of technology for working with multiple representations of functions has substantial potential for teaching calculus. For teaching differentiation, these representations relate to finding difference quotients, finding gradients of curves and tangents , and using symbolic differentiation rules. For students to use them all and link them together requires a wide range of skills, which have been organised into

Margaret Kendal; Kaye Stacey

2003-01-01

330

Melanomas with concordant loss of multiple melanocytic differentiation proteins: immune escape that may be overcome by targeting unique or undefined antigens.  

PubMed

Melanoma-reactive HLA-A x 0201-restricted cytotoxic T lymphocyte (CTL) lines generated in vitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pme117/gp100. However, a subset of melanomas fail to be lysed by these T cells. In the present report, four different HLA-A x 0201+ melanoma cell lines not lysed by melanoma-reactive allogeneic CTL have been evaluated in detail. All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pme117/gp100, gp75/ trp-1, and MART-1/Melan-A. This concordant loss of multiple MDP explains their resistance to lysis by melanoma-reactive allogeneic CTL and confirms that a subset of melanomas may be resistant to tumor vaccines directed against multiple MDP-derived epitopes. All four melanoma lines expressed normal levels of HLAA x 0201, and all were susceptible to lysis by xenoreactive-peptide-dependent HLA-A x 0201-specific CTL clones, indicating that none had identifiable defects in antigen-processing pathways. Despite the lack of shared MDP-derived antigens, one of these MDP-negative melanomas, DM331, stimulated an effective autologous CTL response in vitro, which was restricted to autologous tumor reactivity. MHC-associated peptides isolated by immunoaffinity chromatography from HLA-A1 and HLA-A2 molecules of DM331 tumor cells included at least three peptide epitopes recognized by DM331 CTL and restricted by HLA-A1 or by HLA-A x 0201. Recognition of these CTL epitopes cannot be explained by defined, shared melanoma antigens; instead, unique or undefined antigens must be responsible for the autologous-cell-specific anti-melanoma response. These findings suggest that immunotherapy directed against shared melanoma antigens should be supplemented with immunotherapy directed against unique antigens or other undefined antigens, especially in patients whose tumors do not express MDP. PMID:10752474

Slingluff, C L; Colella, T A; Thompson, L; Graham, D D; Skipper, J C; Caldwell, J; Brinckerhoff, L; Kittlesen, D J; Deacon, D H; Oei, C; Harthun, N L; Huczko, E L; Hunt, D F; Darrow, T L; Engelhard, V H

2000-03-01

331

Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm  

E-print Network

Sox2 is expressed in developing foregut endoderm, with highest levels in the future esophagus and anterior stomach. By contrast, Nkx2.1 (Titf1) is expressed ventrally, in the future trachea. In humans, heterozygosity for SOX2 is associated with anopthalmiaesophageal-genital syndrome (OMIM 600992), a condition including esophageal atresia (EA) and tracheoesophageal fistula (TEF), in which the trachea and esophagus fail to separate. Mouse embryos heterozygous for the null allele, Sox2 EGFP, appear normal. However, further reductions in Sox2, using Sox2 LP and Sox2 COND hypomorphic alleles, result in multiple abnormalities. Approximately 60 % of Sox2 EGFP/COND embryos have EA with distal TEF in which Sox2 is undetectable by immunohistochemistry or western blot. The mutant esophagus morphologically resembles the trachea, with ectopic expression of Nkx2.1, a columnar, ciliated epithelium, and very few p63 + basal cells. By contrast, the abnormal foregut of Nkx2.1-null embryos expresses elevated Sox2 and p63, suggesting reciprocal regulation of Sox2 and Nkx2.1 during early dorsal/ventral foregut patterning. Organ culture experiments further suggest that FGF signaling from the ventral mesenchyme regulates Sox2 expression in the endoderm. In the 40% Sox2 EGFP/COND embryos in which Sox2 levels are ~18 % of wild type there is no TEF. However, the esophagus is still abnormal, with luminal mucus-producing cells, fewer p63 + cells, and ectopic expression of genes normally expressed in glandular stomach and intestine. In all hypomorphic embryos the forestomach has an abnormal phenotype, with reduced keratinization, ectopic mucus cells and columnar epithelium. These findings suggest that Sox2 plays a second role in establishing the boundary between the keratinized, squamous esophagus/forestomach and glandular hindstomach.

Jianwen Que; Tadashi Okubo; James R. Goldenring; Ki-taek Nam; Reiko Kurotani; Edward E. Morrisey; Olena Taranova; Larysa H. Pevny; Brigid L. M. Hogan

332

Multiple adaptive responses of Australian native perennial legumes with pasture potential to grow in phosphorus- and moisture-limited environments  

PubMed Central

Background and Aims Many Australian legumes have evolved in low-phosphorus (P) soils and low-rainfall areas. Therefore a study was made of the interaction of soil [P] and water availability on growth, photosynthesis, water-use efficiency (WUE) and P nutrition of two Australian native legumes with pasture potential, Cullen australasicum and C. pallidum, and the widely grown exotic pasture legume, lucerne (Medicago sativa). Methods Plants were grown in a glasshouse at 3, 10 and 30 mg P kg?1 dry soil for 5 months. At week 10, two drought treatments were imposed, total pot dried (all-dry) and only top soil dried (top-dry), while control pots were maintained at field capacity. Key Results Shoot dry weight produced by lucerne was never higher than that of C. australasicum. For C. pallidum only, shoot dry weight was reduced at 30 mg P kg?1 dry soil. The small root system of the Cullen species was quite plastic, allowing plants to access P and moisture efficiently. Lucerne always had a higher proportion of its large root system in the top soil layer compared with Cullen species. All species showed decreased photosynthesis, leaf water potential and stomatal conductance when exposed to drought, but the reductions were less for Cullen species, due to tighter stomatal control, and consequently they achieved a higher WUE. All species showed highest rhizosphere carboxylate concentrations in the all-dry treatment. For lucerne only, carboxylates decreased as P supply increased. Citrate was the main carboxylate in the control and top-dry treatments, and malate in the all-dry treatment. Conclusions Multiple adaptive responses of Cullen species and lucerne favoured exploitation of low-P soils under drought. The performance of undomesticated Cullen species, relative to that of lucerne, shows their promise as pasture species for environments such as in south-western Australia where water and P are limiting, especially in view of a predicted drying and warming climate. PMID:20421234

Suriyagoda, Lalith D. B.; Ryan, Megan H.; Renton, Michael; Lambers, Hans

2010-01-01

333

Differential Entrainment and Learning-Related Dynamics of Spike and Local Field Potential Activity in the Sensorimotor and Associative Striatum  

PubMed Central

Parallel cortico-basal ganglia loops are thought to have distinct but interacting functions in motor learning and habit formation. In rats, the striatal projection neuron populations (MSNs) in the dorsolateral and dorsomedial striatum, respectively corresponding to sensorimotor and associative regions of the striatum, exhibit contrasting dynamics as rats acquire T-maze tasks (Thorn et al., 2010). Here, we asked whether these patterns could be related to the activity of local interneuron populations in the striatum and to the local field potential activity recorded simultaneously in the corresponding regions. We found that dorsolateral and dorsomedial striatal fast-spiking interneurons exhibited task-specific and training-related dynamics consistent with those of corresponding MSN populations. Moreover, both MSNs and interneuron populations in both regions became entrained to theta-band (5–12 Hz) frequencies during task acquisition. However, the predominant entrainment frequencies were different for the sensorimotor and associative zones. Dorsolateral striatal neurons became entrained mid-task to oscillations centered ?5 Hz, whereas simultaneously recorded neurons in the dorsomedial region became entrained to higher frequency (?10 Hz) rhythms. These region-specific patterns of entrainment evolved dynamically with the development of region-specific patterns of interneuron and MSN activity, indicating that, with learning, these two striatal regions can develop different frequency-modulated circuit activities in parallel. We suggest that such differential entrainment of sensorimotor and associative neuronal populations, acquired through learning, could be critical for coordinating information flow throughout each trans-striatal network while simultaneously enabling nearby components of the separate networks to operate independently. PMID:24553926

Thorn, Catherine A.

2014-01-01

334

Variable Metastatic Potentials Correlate with Differential Plectin and Vimentin Expression in Syngeneic Androgen Independent Prostate Cancer Cells  

PubMed Central

Prostate cancer is a clinically heterogeneous disease, ranging from indolent asymptomatic disease to very aggressive metastatic and life threatening forms of the disease. Distant metastasis represents the major lethal cause of prostate cancer. The most critical clinical challenge in the management of the patients is identifying those individuals at risk of developing metastatic disease. To understand the molecular mechanisms of prostate cancer metastasis and identify markers with metastatic potential, we have analyzed protein expression in two syngeneic prostate cancer cells lines PC3-N2 and PC3-ML2 using isobaric tags for relative and absolute quantitation labeling and multi-dimensional protein identification technology liquid chromatography matrix assisted laser desorption ionization tandem mass spectrometry. PC3-N2 is lowly metastatic while PC3-ML2 highly metastatic. A total of 1,756 proteins were identified in the analyses with 130 proteins showing different expression levels (p<0.01) in the two cell lines. Out of these, 68 proteins were found to be significantly up-regulated while 62 are significantly down-regulated in PC3-ML2 cells compared with PC3-N2 cells. The upregulation of plectin and vimentin which were the most significantly differentially expressed were validated by Western blot and their functional relevance with respect to invasion and migration was determined by siRNA gene silencing. To our knowledge, this study is the first to demonstrate that up-regulation of vimentin and plectin expression positively correlates with the invasion and metastasis of androgen-independent PCA. PMID:23717685

Burch, Tanya C.; Watson, Megan T.; Nyalwidhe, Julius O.

2013-01-01

335

Autonomous isolation, long-term culture and differentiation potential of adult salivary gland-derived stem/progenitor cells.  

PubMed

Salivary gland stem/progenitor cells belong to the endodermal lineage and may serve as good candidates to replace their dysfunctional counterparts. The objective of this study was to isolate large numbers of salivary gland tissue-derived stem cells (SGSCs) from adult rats in order to develop a clinically applicable method that does not involve sorting or stem cell induction by duct ligation. We analysed SGSCs isolated from normal rat salivary glands to determine whether they retained the major characteristics of stem cells, self-renewal and multipotency, especially with respect to the various endodermal cell types. SGSCs expressed high levels of integrin ?6?1 and c-kit, which are surface markers of SGSCs. In particular, the integrin ?6?1(+) /c-kit(+) salivary gland cells maintained the morphology, proliferation activity and multipotency of stem cells for up to 92 passages in 12 months. Furthermore, we analysed the capacity of SGSCs to differentiate into endoderm lineage cell types, such as acinar-like and insulin-secreting cells. When cultured on growth factor reduced matrigel, the morphology of progenitor cells changed to acinar-like structures and these cells expressed the acinar cell-specific marker, ?-amylase, and tight junction markers. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid. These data demonstrate that adult salivary stem/progenitor cells may serve as a potential source for cell therapy in salivary gland hypofunction and diabetes. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22915381

Baek, Hyunjung; Noh, Yoo Hun; Lee, Joo Hee; Yeon, Soo-In; Jeong, Jaemin; Kwon, Heechung

2014-09-01

336

Alterations of field potentials in isotropic cardiomyocyte cell layers induced by multiple endogenous pacemakers under normal and hypothermal conditions.  

PubMed

The use of autonomous contracting randomly grown cardiomyocyte monolayers cultivated on microelectrode arrays (MEAs) represents an accepted experimental setting for preclinical experimental research in the field of cardiac electrophysiology. A dominant pacemaker forces a monolayer to adhere to a regular and synchronized contraction. Randomly distributed multiple pacemakers interfere with this dominant center, resulting in more or less frequent changes of propagation direction. This study aims to characterize the impact of changing propagation directions at single electrodes of the MEA on the four intrinsic parameters of registered field potentials (FPs) FPrise, FPMIN, FPpre, and FPdur and conduction velocity (CV) under normal and hypothermal conditions. Primary cultures of chicken cardiomyocytes (n = 18) were plated directly onto MEAs and FPs were recorded in a temperature range between 37 and 29°C. The number and spatiotemporal distribution of biological and artificial pacemakers of each cell layer inside and outside of the MEA registration area were evaluated using an algorithm developed in-house. In almost every second myocardial cell layer, interfering autonomous pacemakers were detected at stable temperatures, showing random spatial distributions with similar beating rates. Additionally, a temperature-dependent change of the dominant pacemaker center was observed in n = 16 experiments. A significant spread-direction-dependent variation of CV, FPrise, FPMIN, and FPpre up to 14% could be measured between different endogenous pacemakers. In conclusion, based on our results, disregarding the spatial origin of excitation may lead to misinterpretations and erroneous conclusions of FP parameters in the verification of research hypotheses in cellular electrocardiology. PMID:25085965

Kienast, R; Stöger, M; Handler, M; Hanser, F; Baumgartner, C

2014-10-01

337

Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation  

PubMed Central

Persistent forms of synaptic plasticity are widely thought to require the synthesis of new proteins. This feature of long-lasting forms of plasticity largely has been demonstrated using inhibitors of general protein synthesis, such as either anisomycin or emetine. However, these drugs, which inhibit elongation, cannot address detailed questions about the regulation of translation initiation, where the majority of translational control occurs. Moreover, general protein synthesis inhibitors cannot distinguish between cap-dependent and cap-independent modes of translation initiation. In the present study, we took advantage of two novel compounds, 4EGI-1 and hippuristanol, each of which targets a different component of the eukaryotic initiation factor (eIF)4F initiation complex, and investigated their effects on long-term potentiation (LTP) at CA3-CA1 synapses in the hippocampus. We found that 4EGI-1 and hippuristanol both attenuated long-lasting late-phase LTP induced by two different stimulation paradigms. We also found that 4EGI-1 and hippuristanol each were capable of blocking the expression of newly synthesized proteins immediately after the induction of late-phase LTP. These new pharmacological tools allow for a more precise dissection of the role played by translational control pathways in synaptic plasticity and demonstrate the importance of multiple aspects of eIF4F in processes underlying hippocampal LTP, laying the foundation for future studies investigating the role of eIF4F in hippocampus-dependent memory processes. PMID:23054596

Hoeffer, Charles A.; Santini, Emanuela; Ma, Tao; Arnold, Elizabeth C.; Whelan, Ashley M.; Wong, Helen; Pierre, Philippe; Pelletier, Jerry

2013-01-01

338

Molecular dynamics simulations with many-body potentials on multiple GPUs—The implementation, package and performance  

NASA Astrophysics Data System (ADS)

Molecular dynamics (MD) is an important research tool extensively applied in materials science. Running MD on a graphics processing unit (GPU) is an attractive new approach for accelerating MD simulations. Currently, GPU implementations of MD usually run in a one-host-process-one-GPU (OHPOG) scheme. This scheme may pose a limitation on the system size that an implementation can handle due to the small device memory relative to the host memory. In this paper, we present a one-host-process-multiple-GPU (OHPMG) implementation of MD with embedded-atom-model or semi-empirical tight-binding many-body potentials. Because more device memory is available in an OHPMG process, the system size that can be handled is increased to a few million or more atoms. In comparison with the serial CPU implementation, in which Newton's third law is applied to improve the computational efficiency, our OHPMG implementation has achieved a 28.9x-86.0x speedup in double precision, depending on the system size, the cut-off ranges and the number of GPUs. The implementation can also handle a group of small simulation boxes in one run by combining the small boxes into a large box. This approach greatly improves the GPU computing efficiency when a large number of MD simulations for small boxes are needed for statistical purposes.

Hou, Qing; Li, Min; Zhou, Yulu; Cui, Jiechao; Cui, Zhenguo; Wang, Jun

2013-09-01

339

Evaluation of Antioxidant Potential of "Maltese Mushroom" (Cynomorium coccineum) by Means of Multiple Chemical and Biological Assays  

PubMed Central

Cynomorium coccineum is an edible, non-photosynthetic plant widespread along the coasts of the Mediterranean Sea. The medicinal properties of Maltese mushroom—one of the oldest vernacular names used to identify this species—have been kept in high regard since ancient times to the present day. We evaluated the antioxidant potential of fresh specimens of C. coccineum picked in Sardinia, Italy. Both aqueous and methanolic extracts were tested by using multiple assay systems (DPPH, FRAP, TEAC, ORAC-PYR). Total phenolics and flavonoids were also determined. Gallic acid and cyanidin 3-O-glucoside were identified as the main constituents and measured. Both extracts showed antioxidant capacities; ORAC-PYR assay gave the highest antioxidant value in both cases. The methanolic extract was further investigated with in vitro biological models of lipid oxidation; it showed a significant activity in preventing cholesterol degradation and exerted protection against Cu2+-mediated degradation of the liposomal unsaturated fatty acids. Results of the present study demonstrate that the extracts of C. coccineum show a significant total antioxidant power and also exert an in vitro protective effect in different bio-assays of oxidative stress. Therefore, Maltese mushroom can be considered a valuable source of antioxidants and phytochemicals useful in the preparation of nutraceuticals and functional foods. PMID:23344249

Zucca, Paolo; Rosa, Antonella; Tuberoso, Carlo I. G.; Piras, Alessandra; Rinaldi, Andrea C.; Sanjust, Enrico; Dessi, Maria A.; Rescigno, Antonio

2013-01-01

340

Amniotic fluid derived stem cells give rise to neuron-like cells without a further differentiation potential into retina-like cells  

PubMed Central

Amniotic fluid contains heterogeneous cell types and has become an interesting source for obtaining fetal stem cells. These stem cells have a high proliferative capacity and a good differentiation potential and may thus be suitable for regenerative medicine. As there is increasing evidence, that these stem cells are also able to be directed into the neural lineage, in our study we investigated the neuronal and glial differentiation potential of these cells, so that they may also be applied to cure degenerative diseases of the retina. Mesenchymal stem cells were isolated from routine prenatal amniocentesis at 15 to 18 weeks of pregnancy of human amniotic fluid and expanded in the cell culture. Cells were cultivated according to standard procedures for mesenchymal stem cells and were differentiated along the neural lineage using various protocols. Furthermore, it was also tried to direct them into cell types of the retina as well as into endothelial cells. Cells of more than 72 amniotic fluid samples were collected and characterized. While after induction neural-like phenotypes could actually be detected, which was confirmed using neural marker proteins such as GFAP and ßIII tubulina further differentiation into retinal like cells could not reliably be shown. These data suggest that amniotic fluid derived cells are an interesting cell source, which may also give rise to neural-like cells. However, a more specific differentiation into neuronal and glial cells could not unequivocally be shown, so that further investigations have to becarried out. PMID:23862099

Hartmann, K; Raabe, O; Wenisch, S; Arnhold, S

2013-01-01

341

Combined effect of nerve growth factor and brain?derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms.  

PubMed

Neural stem cells (NSCs) are important pluripotent stem cells, which have potential applications in cell replacement therapy. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been demonstrated to exert a marked impact on the proliferation and differentiation of NSCs. The effects of NGF, BDNF, and BDNF combined with NGF on NSC neuronal differentiation and the possible mechanisms for these effects were investigated in this study. An adherent monolayer culture was employed to obtain highly homogeneous NSCs. The cells were divided into four groups: Control, NGF, BDNF and combination (BDNF + NGF) groups. Neuron differentiation was examined using immunocytochemistry and phospho-extracellular signal?regulated kinase (p?ERK) levels were analyzed using western blotting. Reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the HES1, HES5, MASH1, NGN1 and NeuroD transcription factors at different time intervals following neurotrophin?induced differentiation. NGF and BDNF were observed to induce NSC neuronal differentiation, and ?-tubulin III-positive cells and p-ERK expression levels were highest in the NGF + BDNF combination group at all time points. The proportion of ?-tubulin ??positive neurons in each group was associated with the expression levels of MASH1, NGN1 and NeuroD in the group. In conclusion, BDNF combined with NGF significantly improved NSC neuronal differentiation, which may provide support for the practical application of NSCs in neurodegenerative diseases. PMID:25051506

Liu, Feifei; Xuan, Aiguo; Chen, Yan; Zhang, Jundu; Xu, Liping; Yan, Qijiang; Long, Dahong

2014-10-01

342

Combined effect of nerve growth factor and brain-derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms  

PubMed Central

Neural stem cells (NSCs) are important pluripotent stem cells, which have potential applications in cell replacement therapy. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been demonstrated to exert a marked impact on the proliferation and differentiation of NSCs. The effects of NGF, BDNF, and BDNF combined with NGF on NSC neuronal differentiation and the possible mechanisms for these effects were investigated in this study. An adherent monolayer culture was employed to obtain highly homogeneous NSCs. The cells were divided into four groups: Control, NGF, BDNF and combination (BDNF + NGF) groups. Neuron differentiation was examined using immunocytochemistry and phospho-extracellular signal-regulated kinase (p-ERK) levels were analyzed using western blotting. Reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the HES1, HES5, MASH1, NGN1 and NeuroD transcription factors at different time intervals following neurotrophin-induced differentiation. NGF and BDNF were observed to induce NSC neuronal differentiation, and ?-tubulin III-positive cells and p-ERK expression levels were highest in the NGF + BDNF combination group at all time points. The proportion of ?-tubulin III-positive neurons in each group was associated with the expression levels of MASH1, NGN1 and NeuroD in the group. In conclusion, BDNF combined with NGF significantly improved NSC neuronal differentiation, which may provide support for the practical application of NSCs in neurodegenerative diseases. PMID:25051506

LIU, FEIFEI; XUAN, AIGUO; CHEN, YAN; ZHANG, JUNDU; XU, LIPING; YAN, QIJIANG; LONG, DAHONG

2014-01-01

343

Using Multiple Endmember Spectral Mixture Analysis of MODIS Data for Computing the Fire Potential Index in Southern California  

NASA Astrophysics Data System (ADS)

The Fire Potential Index (FPI) is currently the only operationally used wildfire susceptibility index in the United States that incorporates remote sensing data in addition to meteorological information. Its remote sensing component utilizes relative greenness derived from a NDVI time series as a proxy for computing the ratio of live to dead vegetation. This study investigates the potential of Multiple Endmember Spectral Mixture Analysis (MESMA) as a more direct and physically reasonable way of computing the live ratio and applying it for the computation of the FPI. A time series of 16-day reflectance composites of Moderate Resolution Imaging Spectroradiometer (MODIS) data was used to perform the analysis. Endmember selection for green vegetation (GV), non- photosynthetic vegetation (NPV) and soil was performed in two stages. First, a subset of suitable endmembers was selected from an extensive library of reference and image spectra for each class using Endmember Average Root Mean Square Error (EAR), Minimum Average Spectral Angle (MASA) and a count-based technique. Second, the most appropriate endmembers for the specific data set were selected from the subset by running a series of 2-endmember models on representative images and choosing the ones that modeled the majority of pixels. The final set of endmembers was used for running MESMA on southern California MODIS composites from 2000 to 2006. 3- and 4-endmember models were considered. The best model was chosen on a per-pixel basis according to the minimum root mean square error of the models at each level of complexity. Endmember fractions were normalized by the shade endmember to generate realistic fractions of GV and NPV. In order to validate the MESMA-derived GV fractions they were compared against live ratio estimates from RG. A significant spatial and temporal relationship between both measures was found, indicating that GV fraction has the potential to substitute RG in computing the FPI. To further test this hypothesis the live ratio estimates obtained from MESMA were used to compute daily FPI maps for southern California from 2001 to 2006. A validation with historical wildfire data from the MODIS Active Fire product was carried out over the same time period using logistic regression. Initial results show that MESMA-derived GV fraction can be used successfully for generating FPI maps of southern California.

Schneider, P.; Roberts, D. A.

2007-12-01

344

Defective chondrocyte proliferation and differentiation in osteochondromas of MHE patients  

Microsoft Academic Search

Multiple hereditary exostoses (MHE) is an autosomal dominant skeletal disorder caused by mutations in one of the two EXT genes and characterized by multiple osteochondromas that generally arise near the ends of growing long bones. Defective endochondral ossification is likely to be involved in the formation of osteochondromas. In order to investigate potential changes in chondrocyte proliferation and\\/or differentiation during

Catherine Benoist-Lasselin; Emmanuel de Margerie; Linda Gibbs; Sarah Cormier; Caroline Silve; Gisèle Nicolas; Martine LeMerrer; Jean-Francois Mallet; Arnold Munnich; Jacky Bonaventure; Louise Zylberberg; Laurence Legeai-Mallet

2006-01-01

345

Roles of Wnt\\/?-catenin signaling in adipogenic differentiation potential of adipose-derived mesenchymal stem cells  

Microsoft Academic Search

Wnt\\/?-catenin signaling pathway controls differentiation of various cells by regulating the expression of target genes. ?-Catenin plays a central role in Wnt\\/?-catenin signaling pathway. To investigate the molecular mechanisms of fate determination in adipose-derived mesenchymal stem cells (AMSCs), we investigated effects of Wnt3a and ?-catenin, two key members of the Wnt\\/?-catenin signaling, in adipogenic differentiation of porcine AMSCs. We demonstrated

Hui-Xia Li; Xiao Luo; Rong-Xin Liu; Ying-Juan Yang; Gong-She Yang

2008-01-01

346

Mangiferin Reduces the Inhibition of Chondrogenic Differentiation by IL-1? in Mesenchymal Stem Cells from Subchondral Bone and Targets Multiple Aspects of the Smad and SOX9 Pathways  

PubMed Central

Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1?-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1? (IL-1?). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-?, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y–box (SRY-box) containing gene 9 (SOX9), type 2?1 collagen (Col2?1), cartilage link protein, and aggrecan. In IL-1?-stimulated MSCs, mangiferin significantly reversed the production of TGF-?, BMP-2, BMP-4, SOX9, Col2?1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1?-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2?1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways. PMID:25216336

Huh, Jeong-Eun; Koh, Pil-Seong; Seo, Byung-Kwan; Park, Yeon-Chul; Baek, Yong-Hyun; Lee, Jae-Dong; Park, Dong-Suk

2014-01-01

347

Different sleep onset criteria at the multiple sleep latency test (MSLT): an additional marker to differentiate central nervous system (CNS) hypersomnias.  

PubMed

Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idiopathic hypersomnia (IH) without long sleep time] and REM sleep [narcolepsy without cataplexy (NwoC) and narcolepsy with cataplexy (NC)]-related hypersomnias of central origin. We analysed sleep onset characteristics at the multiple sleep latency test (MSLT) applying simultaneously two sleep onset criteria in 44 NC, seven NwoC and 16 IH consecutive patients referred for subjective EDS complaint. Sleep latency (SL) at MSLT was assessed both as the time elapsed to the occurrence of a single epoch of sleep Stage 1 NREM (SL) and of unequivocal sleep [three sleep Stage 1 NREM epochs or any other sleep stage epoch, sustained SL (SusSL)]. Idiopathic hypersomnia patients showed significantly (P<0.0001) longer SusSL than SL (7.7±2.5 versus 5.6±1.3 min, respectively) compared to NwoC (5.8±2.5 versus 5.3±2.2 min) and NC patients (4.1±3 versus 3.9±3 min). A mean difference threshold between SusSL and SL ?27 s reached a diagnostic value to discriminate IH versus NC and NwoC sufferers (sensitivity 88%; specificity 82%). Moreover, NC patients showed better subjective sleepiness perception than NwoC and IH cases in the comparison between naps with or without sleep occurrence. Simultaneous application of the two widely used sleep onset criteria differentiates IH further from NC and NwoC patients: IH fluctuate through a wake-Stage 1 NREM sleep state before the onset of sustained sleep, while NC and NwoC shift abruptly into a sustained sleep. The combination of SusSL and SL determination at MSLT should be tested as an additional objective differential criterion for EDS disorders. PMID:20337903

Pizza, Fabio; Vandi, Stefano; Detto, Stefania; Poli, Francesca; Franceschini, Christian; Montagna, Pasquale; Plazzi, Giuseppe

2011-03-01

348

Common gamma chain (?c) cytokines differentially potentiate TNFR family signaling in antigen-activated CD8+ T cells  

PubMed Central

Background Several members of the common gamma chain (gc) cytokine family are already approved (IL-2) or actively being developed as vaccine adjuvants and cancer immunotherapies. Studies have indicated that co-administration of gc cytokines may enhance the efficacy of immunotherapies that function via direct activation of co-stimulatory T cell receptors. To define the specific influence of gc cytokines on the co-stimulatory capacity of CD8+ T cells and identify combinations with synergistic potential, we investigated the direct impact of gc cytokines on the differentiation and transcriptional profile of recently antigen-primed CD8+ T cells. Methods Naïve CD8+ T cells were activated with peptide-pulsed APCs. After 48 hours, CD8+ T cells were harvested and re-cultured in media supplemented with IL-2, IL-4, IL-7, IL-15 or IL-21. After 24 hours, cells were analyzed by cytokine bead array, flow cytometry, and mRNA micro-array. Gene networks responsible for specific CD8+ T cell functions were constructed through literature-meta review and publicly available annotation databases. Gene expression data from the experimental groups was imported into this network to visualize the impact of each gc cytokine on the functional polarization of recently-activated CD8+ T cells. Results Among the gc cytokines, IL-2 induced the greatest increase in the expression of co-stimulatory receptors in recently-activated CD8+ T cells. IL-2 increased significantly expression of 4-1BB, GITR, ICOS and OX40, at both the transcriptional and protein level. IL-2 also drove the greatest increase in cellular proliferation and the most robust shift towards a pro-survival phenotype, compared with the other gc cytokines. Both IL-4 and IL-21 enhanced expression of cytotoxic effector proteins, but drove distinct phenotypic polarizations, Th2/Tc2 and NK-like, respectively. Conclusions Overall, these observations suggest that among gc cytokines, IL-2 may be uniquely capable of synergizing with therapeutic strategies that combine immunization with agonists of co-stimulatory T cell receptors. Previous studies have shown that the timing of IL-2 treatment relative to immunization plays a key role in defining the CD8+ T cell response, and the findings from this study indicate that administration of exogenous IL-2 shortly after the initial antigen-priming event has concluded may augment the receptivity of these cells to subsequent TNFR co-stimulation. PMID:25411639

2014-01-01

349

Potential diagnostic biomarkers: differential expression of LMP2/?1i and cyclin B1 in human uterine leiomyosarcoma.  

PubMed

Aims and background. Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/?1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/?1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition. Methods and study design. Fifty-seven patients (age range: 32-83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of ?-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/?1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor. Results. The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/?1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples. Conclusions. The expression pattern of LMP2/?1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/?1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS. PMID:25296613

Hayashi, Takuma; Horiuchi, Akiko; Sano, Kenji; Hiraoka, Nobuyoshi; Ichimura, Tomoyuki; Sudo, Tamotsu; Ishiko, Osamu; Yaegashi, Nobuo; Aburatani, Hiroyuki; Konishi, Ikuo

2014-01-01

350

Different perspectives of patients and health care professionals on the potential benefits and risks of blastocyst culture and multiple embryo transfer  

Microsoft Academic Search

BACKGROUND: A trade-off exists between the risk of multiple pregnancy and prospects of pregnancy itself in assisted reproduction. Blastocyst culture and embryo transfer after ~5 days may be one method of reconciling this dilemma, although a controversial one. METHODS AND RESULTS: We presented a questionnaire to groups of patients, embryologists and clinicians to solicit views on the potential benefits and

G. M. Hartshorne; R. J. Lilford

2002-01-01

351

ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential  

SciTech Connect

Human Mesenchymal Stem Cells (hMSC), derived mainly from adult bone marrow, are valuable models for the study of processes involved in stem cell self-renewal and differentiation. As the Extracellular signal-Regulated Kinase (ERK) signalling pathway is a major contributor to cellular growth, differentiation and survival, we have studied the functions of this kinase in hMSC activity. Ablation of ERK2 gene expression (but not ERK1) by RNA interference significantly reduced proliferation of hMSC. This reduction was due to a defect in Cyclin D1 expression and subsequent arrest in the G0/G1 phase of the cell cycle. hMSC growth is enhanced through culture medium supplementation with growth factors (GFs) such as Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF) or Epidermal Growth Factor (EGF). However, these supplements could not rescue the defect observed after ERK2 knockdown, suggesting a common signalling pathway used by these GFs for proliferation. In contrast, ERK1/2 may be dissociated from chemotactic signalling induced by the same GFs. Additionally, hMSCs were capable of differentiating into adipocytes even in the absence of either ERK1 or ERK2 proteins. Our data show that hMSCs do not require cell division to enter the adipogenic differentiation process, indicating that clonal amplification of these cells is not a critical step. However, cell-cell contact seems to be an essential requirement to be able to differentiate into mature adipocytes.

Carcamo-Orive, Ivan; Tejados, Naiara; Delgado, Jesus; Gaztelumendi, Ainhoa [Fundacion Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Department, Paseo Mikeletegi, 61 Bajo 20009, San Sebastian (Spain); Otaegui, David [Unidad Experimental, Hospital Donostia, San Sebastian (Spain); Lang, Valerie [Proteomics Unit, CIC bioGUNE, Ed. 801A Parque Tecnologico de Bizkaia, Derio 48160 (Spain); Trigueros, Cesar [Fundacion Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Department, Paseo Mikeletegi, 61 Bajo 20009, San Sebastian (Spain)], E-mail: ctrigueros@inbiomed.org

2008-05-01

352

High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.  

PubMed

Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9?MDa) and two types of HMWHA (High-1.9?MDa and 6?MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6?MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-? induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1619-1627, 2014. PMID:25196420

Sato, Eiichi; Ando, Takashi; Ichikawa, Jiro; Okita, Genki; Sato, Nobutaka; Wako, Masanori; Ohba, Tetsuro; Ochiai, Satoshi; Hagino, Tetsuo; Jacobson, Richard; Haro, Hirotaka

2014-12-01

353

Influence of stack arrangement on performance of multiple-stack solid oxide fuel cells with non-uniform potential operation  

Microsoft Academic Search

The performance of multiple-stack solid oxide fuel cells (SOFCs) with different stack arrangements is compared with respect to the presence of an in-stack pressure drop. It was demonstrated in our previous work that when a multiple-stack SOFC is arranged in series and the operating voltages are allowed to vary among the different stacks, an improved performance over a conventional SOFC

S. Assabumrungrat; N. Ruangrassamee; S. Vivanpatarakij; N. Laosiripojana; A. Arpornwichanop

2009-01-01

354

Constitutive Proteasomal Degradation of TWIST-1 in Epithelial Ovarian Cancer Stem Cells Impacts Differentiation and Metastatic Potential  

PubMed Central

Epithelial-mesenchymal transition (EMT) is a critical process for embryogenesis but is abnormally activated during cancer metastasis and recurrence. This process enables epithelial cancer cells to acquire mobility and traits associated with stemness. It is unknown whether epithelial stem cells or epithelial cancer stem cells are able to undergo EMT, and what molecular mechanism regulates this process in these specific cell types. We found that Epithelial Ovarian Cancer Stem cells (EOC stem cells) are the source of metastatic progenitor cells through a differentiation process involving EMT and Mesenchymal-Epithelial Transition (MET). We demonstrate both in vivo and in vitro the differentiation of EOC stem cells into mesenchymal spheroid-forming cells (MSFCs) and their capacity to initiate an active carcinomatosis. Furthermore, we demonstrate that human EOC stem cells injected i.p in mice are able to form ovarian tumors, suggesting that the EOC stem cells have the ability to “home” to the ovaries and establish tumors. Most interestingly, we found that TWIST1 is constitutively degraded in EOC stem cells, and that the acquisition of TWIST1 requires additional signals that will trigger the differentiation process. These findings are relevant for understanding the differentiation and metastasis process in EOC stem cells. PMID:22349827

Yin, Gang; Alvero, Ayesha B.; Craveiro, Vinicius; Holmberg, Jennie C.; Fu, Han-Hsuan; Montagna, Michele K.; Yang, Yang; Chefetz-Menaker, Ilana; Nuti, Sudhakar; Rossi, Michael; Silasi, Dan-Arin; Rutherford, Thomas; Mor, Gil

2013-01-01

355

Heterochromatin Protein 1? Epigenetically Regulates Cell Differentiation and Exhibits Potential as a Therapeutic Target for Various Types of Cancers  

PubMed Central

Heterochromatin protein 1 (HP1) is a chromosomal protein that participates in both chromatin packaging and gene silencing. Three HP1 isoforms (?, ?, and ?) occur in mammals, but their functional differences are still incompletely understood. In this study, we found that HP1? levels are decreased during adipocyte differentiation, whereas HP1? and ? levels are expressed constitutively during adipogenesis in cultured preadipocyte cells. In addition, ectopic overexpression of HP1? inhibited adipogenesis. Furthermore, we did not detect any HP1? protein in the differentiated cells of various normal human tissues. These results suggest that the loss of HP1? is required for cell differentiation to occur. On the other hand, the methylation levels of lysine 20 (K20) on histone H4 showed a significant correlation with HP1? expression in both these preadipocyte cells and normal tissue samples. However, all cancer tissues examined were positive for HP1? but were often negative for trimethylated histone H4 K20. Thus, a dissociation of the correlation between HP1? expression and histone H4 K20 trimethylation may reflect the malfunction of epigenetic control. Finally, suppression of HP1? expression restrained cell growth in various cancer-derived cell lines, suggesting that HP1? may be an effective target for gene therapy against various human cancers. Taken together, our results demonstrate the novel function of HP1? in the epigenetic regulation of both cell differentiation and cancer development. PMID:19056850

Takanashi, Masakatsu; Oikawa, Kosuke; Fujita, Koji; Kudo, Motoshige; Kinoshita, Masao; Kuroda, Masahiko

2009-01-01

356

Neuroblastic Differentiation Potential of the Human Retinoblastoma Cell Lines Y-79 and WERI-Rb1 Maintained in an Organ Culture System  

PubMed Central

The differentiation potential of the human retinoblastoma cell lines Y-79 and WERI-Rb 1 was evaluated in vitro for up to 120 days in a matrix system and in rotary suspension for 30 days. Matrix cultures were grown with 10% fetal calf serum (FCS), with and without differentiation-promoting agents. The latter were applied for a total of 5-45 days (usually 30 days) and included 7S nerve growth factor, dibutyryl cyclic AMP, sodium butyrate, retinoic acid, hydrocortisone, and ascorbic acid. Fully defined, serum-free medium and medium containing 5 or 15% FCS were also used for matrix cultures, and medium with 5 or 10% FCS for suspension cultures. By immunoperoxidase (performed on matrix cultures, both untreated and treated for 30 days with differentiation-promoting agents), the cells of both line were positive for neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP2), class III ?-tubulin (human h?4) isotype, and synaptophysin. In addition, the WERI-Rb1 cells expressed 200 kd neurofilament protein (NFP-H) and retinal S-antigen. Both lines were invariably negative for glial fibrillary acidic (GFA) protein, myelin-associated glycoprotein, myelin basic protein, the epitope recognized by the Leu-7 monoclonal antibody, opsin, and hydroxyindole-0-methyltransferase. In the Y-79 line the presence of NSE and the absence of NF proteins-H, M and -L, of GFA protein, and of retinal S-antigen were confirmed biochemically. No differentiated features were found by electron microscopy in either line. Thus, in the matrix system employed, both lines exhibited solely a potential for neuroblastic differentiation, which was more advanced in the WERI-Rb1 line, as reflected by the antigenic expression of NFP-H and of retinal S-antigen. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:2643884

Herman, Mary M.; Perentes, Elias; Katsetos, Christos D.; Darcel, Francoise; Frankfurter, Anthony; Collins, V. Peter; Donoso, Larry A.; Eng, Lawrence F.; Marangos, Paul J.; Wiechmann, Allan F.; May, Estelle E.; Thomas, Christine B.; Rubinstein, Lucien J.

1989-01-01

357

The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells  

PubMed Central

Summary Exploitation of embryonic stem cells (ESC) for therapeutic use and biomedical applications is severely hampered by the risk of teratocarcinoma formation. Here, we performed a screen of selected epi-modulating compounds and demonstrate that a transient exposure of mouse ESC to MS-275 (Entinostat), a class I histone deacetylase inhibitor (HDAC), modulates differentiation and prevents teratocarcinoma formation. Morphological and molecular data indicate that MS-275-primed ESCs are committed towards neural differentiation, which is supported by transcriptome analyses. Interestingly, in vitro withdrawal of MS-275 reverses the primed cells to the pluripotent state. In vivo, MS275-primed ES cells injected into recipient mice give only rise to benign teratomas but not teratocarcinomas with prevalence of neural-derived structures. In agreement, MS-275-primed ESC are unable to colonize blastocysts. These findings provide evidence that a transient alteration of acetylation alters the ESC fate. PMID:24167717

Franci, Gianluigi; Casalino, Laura; Petraglia, Francesca; Miceli, Marco; Menafra, Roberta; Radic, Branka; Tarallo, Valeria; Vitale, Monica; Scarfo, Marzia; Pocsfalvi, Gabriella; Baldi, Alfonso; Ambrosino, Concetta; Zambrano, Nicola; Patriarca, Eduardo; De Falco, Sandro; Minchiotti, Gabriella; Stunnenberg, Hendrik G.; Altucci, Lucia

2013-01-01

358

Comparative proteomics of colon cancer stem cells and differentiated tumor cells identifies BIRC6 as a potential therapeutic target.  

PubMed

Patients with liver metastases from colon carcinoma show highly variable responses to chemotherapy and tumor recurrence is frequently observed. Therapy-resistant cancer stem cells have been implicated in drug resistance and tumor recurrence. However, the factors determining therapy resistance and tumor recurrence are poorly understood. The aim of this study was to gain insight into these mechanisms by comparing the proteomes of patient-derived cancer stem cell cultures and their differentiated isogenic offspring. We established colonosphere cultures derived from resection specimens of liver metastases in patients with colon cancer. These colonospheres, enriched for colon cancer stem cells, were used to establish isogenic cultures of stably differentiated nontumorigenic progeny. Proteomics based on one-dimensional gel electrophoresis coupled to nano liquid chromatography tandem MS was used to identify proteome differences between three of these paired cultures. The resulting data were analyzed using Ingenuity Pathway Software. Out of a total data set of 3048 identified proteins, 32 proteins were at least twofold up-regulated in the colon cancer stem cells when compared with the differentiated cells. Pathway analysis showed that "cell death " regulation is strikingly different between the two cell types. Interestingly, one of the top-up-regulated proteins was BIRC6, which belongs to the class of Inhibitor of Apoptosis Proteins. Knockdown of BIRC6 sensitized colon cancer stem cells against the chemotherapeutic drugs oxaliplatin and cisplatin. This study reveals that differentiation of colon cancer stem cells is accompanied by altered regulation of cell death pathways. We identified BIRC6 as an important mediator of cancer stem cell resistance against cisplatin and oxaliplatin. Targeting BIRC6, or other Inhibitors of Apoptosis Proteins, may help eradicating colon cancer stem cells. PMID:21788403

Van Houdt, W J; Emmink, B L; Pham, T V; Piersma, S R; Verheem, A; Vries, R G; Fratantoni, S A; Pronk, A; Clevers, H; Borel Rinkes, I H M; Jimenez, C R; Kranenburg, O

2011-12-01

359

Identification of proteins differentially expressed in gastric cancer cells with high metastatic potential for invasion to lymph nodes  

Microsoft Academic Search

In a search for proteins involved in cancer metastasis, we analyzed proteomes of the human gastric cancer cell OCUM-2M and\\u000a its metastatic subline OCUM-2MLN. We observed that aspartate aminotransferase (AAT), D-site binding protein (DBP), and anterior\\u000a gradient protein 2 (AGR2) are differentially expressed in metastatic OCUM-2MLN cells. Measurement of protein expression in\\u000a clinical samples indicated that DBP and AAT are

Do Hee Lee; Youra Lee; Joohyun Ryu; Sung Goo Park; Sayeon Cho; Je-Jung Lee; Chan Choi; Byoung Chul Park

2011-01-01

360

A feasibility study of an in vitro differentiation potential toward insulin-producing cells by dental tissue-derived mesenchymal stem cells.  

PubMed

Dental tissue-derived mesenchymal stem cells have been proposed as an alternative source for mesenchymal stem cells. Here, we investigated the differentiation ability toward insulin producing cells (IPCs) of human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs). These cells expressed mesenchymal stem cell surface markers and were able to differentiate toward osteogenic and adipogenic lineages. Upon 3 step-IPCs induction, hDPSCs exhibited more colony number than hPDLSCs. The mRNA upregulation of pancreatic endoderm/islet markers was noted. However, the significant increase was noted only for PDX-1, NGN-3, and INSULIN mRNA expression of hDPSCs. The hDPSCs-derived IPCs expressed PRO-INSULIN and released C-PEPTIDE upon glucose stimulation in dose-dependent manner. After IPCs induction, the Notch target, HES-1 and HEY-1, mRNA expression was markedly noted. Notch inhibition during the last induction step or throughout the protocol disturbed the ability of C-PEPTIDE release upon glucose stimulation. The results suggested that hDPSCs had better differentiation potential toward IPCs than hPDLSCs. In addition, the Notch signalling might involve in the differentiation regulation of hDPSCs into IPCs. PMID:25181343

Sawangmake, Chenphop; Nowwarote, Nunthawan; Pavasant, Prasit; Chansiripornchai, Piyarat; Osathanon, Thanaphum

2014-09-26

361

New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics  

PubMed Central

Human mesenchymal stem cells (hMSCs) are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2) and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG) box transcription factor 9 (SOX9) is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis. PMID:23766767

Giuliani, Nicola; Lisignoli, Gina; Magnani, Marina; Racano, Costantina; Dalla Palma, Benedetta; Spolzino, Angelica; Manferdini, Cristina; Abati, Caterina; Toscani, Denise; Facchini, Andrea; Aversa, Franco

2013-01-01

362

Identification of three microsatellites at the human myelin oligodendrocyte glycoprotein (MOG) locus, a gene potentially involved in multiple sclerosis  

SciTech Connect

The gene encoding MOG is located on the short arm of chromosome 6, less than 120 kb telomeric to HLA-F. We have cloned the MOG gene from a cosmid library. Using tandemly repeated dinucleotides, we probed the genomic region containing the human MOG gene in order to identify and localize polymorphic markers: three microsatellites were characterized in that region. Using a polymerase chain reaction-based technique, we studied length variability for these three markers among 173 healthy individuals and 167 multiple sclerosis patients. Heterozygosity varied from 50% to 60% according to the marker. Pairwise studies showed significant linkage disequilibrium between some alleles. Multiple sclerosis patients and controls were not shown to have statistically significant differences in the MOG region. Further studies on the coding regions are in progress in order to exclude any involvement of the MOG gene in multiple sclerosis.

Borot, N.; Dolbois, L. [C.I.G.H.-C.N.R.S., Toulouse (France); Coppin, H. [U395 INSERM Purpan, Toulouse (France)] [and others

1994-09-01

363

The Application of Multiobjective Genetic Algorithm to the Parameter Optimization of Single-Well Potential Stochastic Resonance Algorithm Aimed at Simultaneous Determination of Multiple Weak Chromatographic Peaks  

PubMed Central

Simultaneous determination of multiple weak chromatographic peaks via stochastic resonance algorithm attracts much attention in recent years. However, the optimization of the parameters is complicated and time consuming, although the single-well potential stochastic resonance algorithm (SSRA) has already reduced the number of parameters to only one and simplified the process significantly. Even worse, it is often difficult to keep amplified peaks with beautiful peak shape. Therefore, multiobjective genetic algorithm was employed to optimize the parameter of SSRA for multiple optimization objectives (i.e., S/N and peak shape) and multiple chromatographic peaks. The applicability of the proposed method was evaluated with an experimental data set of Sudan dyes, and the results showed an excellent quantitative relationship between different concentrations and responses. PMID:24526920

Xiang, Bingren; Wu, Xiaohong; Liu, Dan

2014-01-01

364

A novel human high-risk ependymoma stem cell model reveals the differentiation inducing potential of the histone deacetylase inhibitor Vorinostat  

PubMed Central

Incompletely resectable ependymomas are associated with a poor prognosis despite intensive radio- and chemotherapy. Novel treatments have been difficult to develop due to the lack of appropriate models. Here, we report on the generation of a high risk cytogenetic group 3 and molecular group C ependymoma model (DKFZ-EP1NS) which is based on primary ependymoma cells obtained from a patient with metastatic disease. This model displays stem cell features like self renewal capacity, differentiation capacity and specific marker expression. In vivo transplantation showed a high tumorigenic potential of these cells, and xenografts phenotypically recapitulated the original tumor in a niche dependent manner. DKFZ-EP1NS cells harbor transcriptome plasticity, enabling a shift from a neural stem cell-like program towards a profile of primary ependymoma tumor upon in vivo transplantation. Serial transplantation of DKFZ-EP1NS cells from orthotopic xenografts yielded secondary tumors in half the time compared to the initial transplantation. The cells were resistant to temozolomide, vincristine and cisplatin, but responded to histone deacetylase inhibitor (HDACi)-treatment in therapeutically achievable concentrations. In vitro treatment of DKFZ-EP1NS cells with the HDACi Vorinostat induced neuronal differentiation associated with loss of stem cell-specific properties. In summary, this is the first ependymoma model of a cytogenetic group 3 and molecular subgroup C ependymoma based on a human cell line with stem cell-like properties, which we used to demonstrate the differentiation inducing therapeutic potential of HDACi. PMID:21863243

Milde, Till; Kleber, Susanne; Korshunov, Andrey; Witt, Hendrik; Hielscher, Thomas; Koch, Philipp; Kopp, Hans-Georg; Jugold, Manfred; Deubzer, Hedwig E.; Oehme, Ina; Lodrini, Marco; Gröne, Hermann-Josef; Benner, Axel; Brüstle, Oliver; Gilbertson, Richard J.; von Deimling, Andreas; Kulozik, Andreas E.; Pfister, Stefan M.; Martin-Villalba, Ana; Witt, Olaf

2013-01-01

365

Differential regulation of multiple brain-derived neurotrophic factor transcripts in the postnatal and adult rat hippocampus during development, and in response to kainate administration.  

PubMed

Brain-derived neurotrophic factor (BDNF) is expressed at high levels in the hippocampus, where it has been implicated in physiological functions such as the modulation of synaptic strength as well as in the pathophysiology of epileptic seizures. BDNF expression is highly regulated and the BDNF gene can generate multiple transcript isoforms by alternate splicing of four 5' exons (exons I-IV) to one 3' exon (exon V). To gain insight into the regulation of different BDNF transcripts in specific hippocampal subfields during postnatal development, exon-specific riboprobes were used. Our data shows that BDNF exon I and exon II mRNAs are regulated in hippocampal subfields during postnatal development, in contrast to BDNF exon III and exon IV mRNA, which remain relatively stable through this period. Further, exons I and II show distinct temporal patterns of expression in the hippocampus: BDNF I mRNA peaks in adulthood in contrast to BDNF II mRNA which peaks at postnatal day 14 (P14). Finally, we have addressed whether kainate treatment in postnatal pups and adults regulates BDNF through the recruitment of the same, or distinct, BDNF promoters. Our data indicates that kainate-induced seizures induce strikingly different expression of distinct BDNF transcripts, both in magnitude as well as spatial patterns in the hippocampal subfields, of pups as compared to adults. These results suggest that kainate-mediated seizures differentially recruit BDNF promoters in the developing postnatal hippocampus in contrast to the adult hippocampus to achieve a hippocampal subfield specific regulation of exon-specific BDNF mRNAs. PMID:15519687

Sathanoori, Malini; Dias, Brian G; Nair, Amrita R; Banerjee, Sunayana B; Tole, Shubha; Vaidya, Vidita A

2004-11-01

366

Differential human multiple myeloma cell line responsiveness to interferon-alpha. Analysis of transcription factor activation and interleukin 6 receptor expression.  

PubMed Central

Although IFN-alpha is commonly used as maintenance treatment for multiple myeloma patients, its effectiveness is varied. In this study, we have used a panel of IL-6 responsive myeloma cell lines that vary remarkably in responsiveness to IFN-alpha. Three cell lines were growth arrested by IFN-alpha; however, IFN-alpha significantly stimulated growth of the fourth cell line, KAS-6/1. Our studies have focused on elucidating the mechanism of differential IFN-alpha responsiveness. First, we have shown that IFN-alpha-stimulated growth of the KAS-6/1 cells did not result from induction of autocrine IL-6 expression. Second, analysis of Stats 1, 2, and 3 and IFN regulatory factor-1 (IRF-1) and IRF-2 activation failed to reveal differences between the IFN-alpha growth-arrested or growth-stimulated cells. Third, although IFN-alpha treatment of the IFN-alpha growth-inhibited cell lines reduced IL-6 receptor (IL-6R) expression, IFN-alpha also reduced KAS-6/1 IL-6R expression. Finally, although IFN-alpha treatment reduced IL-6R numbers on each cell line, analysis of Stat protein activation revealed that the receptors were still functional. We conclude that myeloma cell responsiveness to IFN-alpha is heterogeneous and that mechanisms of IFN-alpha-mediated growth inhibition other than IL-6R downregulation must exist in myeloma. Identification of these mechanisms may allow development of agents that are more universally effective than IFN-alpha. PMID:9022078

Jelinek, D F; Aagaard-Tillery, K M; Arendt, B K; Arora, T; Tschumper, R C; Westendorf, J J

1997-01-01

367

The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation.  

PubMed

Terminal differentiation is associated with repression in the expression of the proliferation potential proteins (P2P) subset of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins. We report here the cloning and characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple murine tissues and in proliferating 3T3T cells, but not in terminally differentiated 3T3T adipocytes. Evidence that this cDNA can encode peptides with domains for hnRNP association was established by showing that such peptides are recognized by two monoclonal antibodies known to detect core hnRNP proteins, and by showing that the C130 monoclonal antibody, produced against a cDNA-derived fusion protein, also selectively detects native P2P hnRNP proteins. In addition, P2P-R cDNA-derived fusion proteins bind single-stranded nucleic acids, and a P2P-R cDNA-derived antisense oligonucleotide selectively represses P2P expression. Because terminal differentiation is associated with modulation in Rb1 function, we assayed if products of this cDNA might interact with Rb1. Evidence that the P2P-R cDNA encodes a protein domain that binds Rb1 was established using a glutathione S-transferase fusion protein to selectively precipitate Rb1 from cellular extracts. Data also show that this binding is reduced by competition with the adenovirus E1a protein, indicating that binding occurs through the "pocket" domain of Rb1. These results establish that the P2P-R cDNA encodes protein domains involved in both hnRNP association and Rb1 binding and complement recent reports that localize Rb1 to sites of RNA processing in the nucleus. PMID:9037032

Witte, M M; Scott, R E

1997-02-18

368

The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation  

PubMed Central

Terminal differentiation is associated with repression in the expression of the proliferation potential proteins (P2P) subset of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins. We report here the cloning and characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple murine tissues and in proliferating 3T3T cells, but not in terminally differentiated 3T3T adipocytes. Evidence that this cDNA can encode peptides with domains for hnRNP association was established by showing that such peptides are recognized by two monoclonal antibodies known to detect core hnRNP proteins, and by showing that the C130 monoclonal antibody, produced against a cDNA-derived fusion protein, also selectively detects native P2P hnRNP proteins. In addition, P2P-R cDNA-derived fusion proteins bind single-stranded nucleic acids, and a P2P-R cDNA-derived antisense oligonucleotide selectively represses P2P expression. Because terminal differentiation is associated with modulation in Rb1 function, we assayed if products of this cDNA might interact with Rb1. Evidence that the P2P-R cDNA encodes a protein domain that binds Rb1 was established using a glutathione S-transferase fusion protein to selectively precipitate Rb1 from cellular extracts. Data also show that this binding is reduced by competition with the adenovirus E1a protein, indicating that binding occurs through the “pocket” domain of Rb1. These results establish that the P2P-R cDNA encodes protein domains involved in both hnRNP association and Rb1 binding and complement recent reports that localize Rb1 to sites of RNA processing in the nucleus. PMID:9037032

Witte, Michael M.; Scott, Robert E.

1997-01-01

369

Downregulation of PPAR? by miR-548d-5p suppresses the adipogenic differentiation of human bone marrow mesenchymal stem cells and enhances their osteogenic potential  

PubMed Central

Background Human bone marrow mesenchymal stem cells (hBMSCs) are multipotent cells that can differentiate into a variety of cell types. Elevated expression of peroxisome proliferator-activated receptor-? (PPAR?) promotes the adipogenic differentiation of hBMSCs, and reduces their osteogenic differentiation. MicroRNAs (miRNAs) have been shown to play important roles in the regulation of hBMSCs differentiation. Because bioinformatic analysis has indicated that PPAR? is a candidate target of miR-548d-5p, the aim of this study was to assess the impact of miR-548d-5p on the dexamethasone-induced adipogenic differentiation of hBMSCs. Methods A quantitative RT-PCR (qRT-PCR) assay was used to compare miR-548d-5p expression levels in dexamethasone-induced hBMSCs and uninduced control cells. Oil red O staining, cellular triglyceride (TG) content, and the mRNA and protein levels of PPAR? and CCAAT/enhancer binding protein ? (C/EBP?) were used to evaluate the adipogenic differentiation of hBMSCs. Alkaline phosphatase (ALP) activity and levels of osteocalcin (OCN) and Runx2 were used to evaluate the osteogenic potential of hBMSCs. Results Compared with untreated cells, miR-548d-5p expression levels were downregulated during dexamethasone-induced adipogenic differentiation of hBMSCs. In contrast to the profuse Oil Red O staining in the cytoplasm of dexamethasone?+?scrambled miRNA-treated cells, there was limited staining in the cytoplasm of dexamethasone?+?miR-548d-5p-treated cells, indicating the absence of adipocytes. Moreover, compared with scrambled miRNA-treated cells, treatment with miR-548d-5p suppressed cellular levels of PPAR? and C/EBP? mRNA and protein, and cell TG content (P?differentiation of hBMSCs. By directly targeting and downregulating PPAR?, miR-548d-5p suppresses the dexamethasone-induced adipogenic differentiation of hBMSCs and enhances their osteogenic potential. Our findings suggest that miR-548d-5p has potential in the treatment of corticosteroid-induced osteonecrosis of the femoral head. PMID:24929254

2014-01-01

370

Preference for Physicians as Information Providers by Women with Multiple Sclerosis: A Potential Cause for Communication Problems?  

ERIC Educational Resources Information Center

Discussion of the causes of communication problems between physicians and chronically ill patients focuses on the information-seeking patterns of women with multiple sclerosis (MS). A survey investigated whether a woman's general orientation to information or the length of time she had MS affected her choice of information resource. (Author/LRW)

Baker, Lynda M.

1997-01-01

371

Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations.  

PubMed

Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages. PMID:23379639

Gopinathan, Gokul; Kolokythas, Antonia; Luan, Xianghong; Diekwisch, Thomas G H

2013-06-15

372

Potential utility of p53 immunopositivity in differentiation of adenocarcinomas from reactive epithelial atypias of the lung.  

PubMed

Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin- biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias. PMID:8912831

Cagle, P T; Fraire, A E; Greenberg, S D; Cox, A; Brown, R W

1996-11-01

373

Developmental Expression of Smoc1 and Smoc2 Suggests Potential Roles in Fetal Gonad and Reproductive Tract Differentiation  

PubMed Central

SMOC1 and SMOC2 are matricellular proteins thought to influence growth factor signaling, migration, proliferation and angiogenesis. We examined the expression and regulation of Smoc1 and Smoc2 in fetal gonad/mesonephros complexes to discover possible roles for these genes in gonad and mesonephros development. Smoc1 was upregulated at ~E10.75 in a center-to-poles wave in pre-Sertoli and pre-granulosa cells and its expression was greatly reduced in Wt1, Sf1 and Fog2 mutants. After E13.5, Smoc1 was downregulated in an anterior-to-posterior wave in granulosa cells but persisted in Sertoli cells, suggesting a sexually dimorphic requirement in supporting cell lineage differentiation. Smoc2 was expressed in Leydig cells, mesonephroi, and Wnt4 mutant ovaries, but not wildtype ovaries. Using organ culture, we determined that Smoc2 expression was dependent on Hedgehog signaling in testes, mesonephroi, and kidneys. Overall, these results demonstrate that SMOC1 and SMOC2 may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. PMID:19842175

Pazin, Dorothy E.; Albrecht, Kenneth H.

2010-01-01

374

Event-related potentials differentiate the effects of aging on word and nonword repetition in explicit and implicit memory tasks  

Microsoft Academic Search

Explicit memory declines with age while implicit memory remains largely intact. These experiments extended behavioral findings by recording event-related potentials (ERPs) in young and elderly adults during repetition priming and recognition memory paradigms. Words and pronounceable nonwords repeated after 1 of 3 delays. Stimuli were categorized as either word-nonword or old-new. Repeated items elicited more positive-going potentials in bom tasks.

Diane Swick; Robert T. Knight

1997-01-01

375

ROCK Inhibitor Y-27632 Increases Thaw-Survival Rates and Preserves Stemness and Differentiation Potential of Human Wharton’s Jelly Stem Cells After Cryopreservation  

Microsoft Academic Search

The ROCK inhibitor Y-27632 inhibits apoptosis and increases proliferation of frozen-thawed cells. We examined the role of\\u000a Y-27632 on human umbilical cord Wharton’s jelly stem cells (hWJSCs) for (1) thaw-survival (2) proliferation and (3) preservation\\u000a of stemness and differentiation potential after cryopreservation. hWJSCs were allotted to 4 groups [Gp I: Untreated hWJSC\\u000a controls; Gp II: Pretreatment with Y-27632 (10 ?M) for

Kalamegam Gauthaman; Chui-Yee Fong; Arjunan Subramanian; Arijit Biswas; Ariff Bongso

2010-01-01

376

Identification of Proteins Differentially Expressed in Gastric Cancer Cells with High Metastatic Potential for Invasion to Lymph Nodes  

PubMed Central

In a search for proteins involved in cancer metastasis, we analyzed proteomes of the human gastric cancer cell OCUM-2M and its metastatic subline OCUM-2MLN. We observed that aspartate aminotransferase (AAT), D-site binding protein (DBP), and anterior gradient protein 2 (AGR2) are differentially expressed in metastatic OCUM- 2MLN cells. Measurement of protein expression in clinical samples indicated that DBP and AAT are also downregulated in metastatic adenocarcinoma. Additionally, urokinase- type tissue plasminogen activator is up-regulated in OCUM-2MLN cells and also in metastatic gastric cancer samples. Collectively, these results raise a possibility that AAT, DBP and AGR2 are functionally implicated in the invasiveness of gastric cancer cells. PMID:21533548

Lee, Do Hee; Lee, Youra; Ryu, Joohyun; Park, Sung Goo; Cho, Sayeon; Lee, Je-Jung; Choi, Chan; Park, Byoung Chul

2011-01-01

377

Coordinate-Independent Computations on Differential Equations  

E-print Network

This project investigates the computational representation of differentiable manifolds, with the primary goal of solving partial differential equations using multiple coordinate systems on general n- dimensional spaces. ...

Lin, Kevin K.

1998-03-01

378

Defense potentials to NaCl in a mangrove, Bruguiera parviflora: differential changes of isoforms of some antioxidative enzymes.  

PubMed

In order to assess the role of the antioxidative defense system against salt treatment, the activities of some antioxidative enzymes and levels of antioxidants were monitored in a true mangrove, Bruguiera parviflora, subjected to varying levels of NaCl under hydroponic culture. In the leaves of B. parviflora, salt treatment preferentially enhanced the content of H2O2 as well as the activity of ascorbate peroxidase (APX), guaiacol peroxidase (GPX), glutathione reductase (GR), and superoxide dismutase (SOD), whereas it induced the decrease of total ascorbate and glutathione (GSH+GSSG) content as well as catalase (CAT) activity. Analysis of isoforms of antioxidative enzymes by native PAGE and activity staining revealed that leaves of B. parviflora had one isoform each of Mn-SOD and Cu/Zn-SOD and three isoforms of Fe-SOD. Expression of Mn-SOD and Fe-SOD-2 was preferentially elevated by NaCl. Similarly, out of the six isoforms of GPX, the GPX-1, 2, 3 and 6 were enhanced by salt treatment but the levels of GPX-4 and -5 changed minimally as compared to those of a control. Activity staining gel revealed only one prominent isoform of APX and two isoforms of GR (GR-1 and GR-2), all of these isoforms increased upon salt exposure. Four CAT-isoforms were identified, among which the prominent CAT-2 isoform level was maximally reduced, suggesting differential down regulation of CAT isoforms by NaCl. The concentrations of malondialdehyde (MDA), a product of lipid peroxidation, remained unchanged in leaves of the plant treated with different concentrations of NaCl. This suggests that plants are protected against activated oxygen species by the elevated levels of certain antioxidative enzymes, thus avoiding lipid peroxidation during salt exposure. The differential changes in the levels of the isoforms due to NaCl treatment may be useful as markers for recognizing salt tolerance in mangroves. PMID:15202709

Parida, Asish Kumar; Das, Anath Bandhu; Mohanty, Prasanna

2004-05-01

379

Prostaglandin E2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation.  

PubMed

Prostaglandin E(2) (PGE(2)), a prostanoid synthesized from arachidonic acid via the cyclooxygenase pathway, is a modulator of physiological responses including inflammation, fever, and muscle regeneration. Several patents have been filed that are related to PGE(2), one of them being directly related to skeletal muscles. In this report, we first summarize the key patents describing inventions for the utilization of PGE(2) for either diagnostic or therapeutic purposes, including skeletal muscle. In the second part of our work we present new and exciting data that demonstrates that PGE(2) accelerates skeletal muscle myogenic differentiation. Our discovery resulted from our recent and novel concept of bone-muscle crosstalk. Bone and muscle are anatomically intimate endocrine organs and we aimed to determine whether this anatomical intimacy also translates into a biochemical communication from bone cells to muscle cells at the in vitro level. The effects of MLOY4 osteocyte-like cell conditioned medium (CM) and three osteocyte-secreted factors, PGE(2), sclerostin and monocyte chemotactic protein (MCP-3), on C2C12 myogenic differentiation were evaluated using morphological analyses, a customized 96-gene PCR array, and measurements of intracellular calcium levels. MLO-Y4 CM and PGE(2), but not sclerostin and MCP-3, induced acceleration of myogenesis of C2C12 myoblasts that was linked with significant modifications in intracellular calcium homeostasis. This finding should further stimulate the pursuit of new patents to explore the use of PGE(2) and the new concept of bone-muscle crosstalk for the development and application of inventions designed to treat muscle diseases characterized by enhanced muscle wasting, such as sarcopenia. PMID:23092433

Mo, Chenglin; Romero-Suarez, Sandra; Bonewald, Lynda; Johnson, Mark; Brotto, Marco

2012-12-01

380

Differential recovery of the electroretinogram, visually evoked cortical potential, and electrically evoked cortical potential following vitrectomy: implications for acute testing of an implanted retinal prosthesis.  

PubMed

To determine the extent to which electrophysiologic tests of the afferent visual pathway are affected by vitrectomy, the procedure was performed in 15 eyes of 11 adult Dutch-belted rabbits. An electroretinogram (ERG), visually evoked cortical potential (VECP), and electrically evoked cortical potential (EECP) were obtained preoperatively and sequentially after surgery. For electrical stimulations, biphasic impulses were delivered to the retina. Post-vitrectomy declines of 49, 25, and 41% from the median baseline amplitudes and increases of 13, 18, and 17% from the median baseline latency values were found for ERG, VECP, and EECP, respectively. At 90 min, 13 to 30% of eyes still had an amplitude more than 10% below baseline on at least one of the three tests, whereas 10 to 47% of eyes had an abnormal latency more than 10% above baseline on at least one of the three tests. Amplitudes were more likely than latencies to return to near baseline, but for eyes that remained subnormal, the decline was greater for amplitudes than latencies. Significant alterations in retinal function, manifested by declines in amplitudes and increases in latencies of the ERG, VECP, and EECP, persist in a large proportion of eyes up to 90 min post-vitrectomy. PMID:15558366

Montezuma, Sandra R; Rizzo, Joseph F; Ziv, Ofer R

2004-03-01