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1

Isolation and Multiple Differentiation Potential Assessment of Human Gingival Mesenchymal Stem Cells  

PubMed Central

The aim of this study was to isolate human mesenchymal stem cells (MSCs) from the gingiva (GMSCs) and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs) and dermal stem cells (DSCs) cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F) and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP) activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN) and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPAR?-2 expression for the adipogenic differentiation). Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM) was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source. PMID:25405732

Gao, Yuan; Zhao, Guizhi; Li, Dongxia; Chen, Xin; Pang, Jianliang; Ke, Jie

2014-01-01

2

Multiple Differential Aperture Microscopy  

SciTech Connect

Differential-aperture X-ray microscopy (DAXM) is a powerful approach to 3D tomography with particular relevance to X-ray microdiffraction. With DAXM, scattering from submicron volumes can be resolved. However, the method is intrinsically a scanning technique where every resolved volume element (voxel) requires at least one area-detector readout. Previous applications of DAXM have used a single wire for knife-edge step profiling. Here, we demonstrate a way to accelerate DAXM measurements using multiple wires. A proof-of-principle experiment with a three-wire prototype showed that the speed of measurements can be tripled, but careful calibrations of wires will be required to maintain the spatial accuracy. In addition, related possibilities for accelerating measurements are briefly discussed.

Chung, Jin-Seok [ORNL; Isa, Saliman Anavami [ORNL; Greene, Virgil [ORNL; Broadwater, Ombreyan Q [ORNL; Liu, W. [Argonne National Laboratory (ANL); Ice, Gene E [ORNL

2007-01-01

3

Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells  

PubMed Central

Disease relapse remains a major factor limiting the survival of cancer patients. In the plasma cell malignancy multiple myeloma (MM), nearly all patients ultimately succumb to disease relapse and progression despite new therapies that have improved remission rates. Tumor regrowth indicates that clonogenic growth potential is continually maintained, but the determinants of self-renewal in MM are not well understood. Normal stem cells are regulated by extrinsic niche factors, and the tumor microenvironment (TME) may similarly influence tumor cell clonogenic growth and self-renewal. Growth differentiation factor 15 (GDF15) is aberrantly secreted by bone marrow stromal cells (BMSCs) in MM. We found that GDF15 is produced by BMSCs after direct contact with plasma cells and enhances the tumor-initiating potential and self-renewal of MM cells in a protein kinase B- and SRY (sex-determining region Y)-box–dependent manner. Moreover, GDF15 induces the expansion of MM tumor-initiating cells (TICs), and changes in the serum levels of GDF15 were associated with changes in the frequency of clonogenic MM cells and the progression-free survival of MM patients. These findings demonstrate that GDF15 plays a critical role in mediating the interaction among mature tumor cells, the TME, and TICs, and strategies targeting GDF15 may affect long-term clinical outcomes in MM. PMID:24345755

Tanno, Toshihiko; Lim, Yiting; Wang, Qiuju; Chesi, Marta; Bergsagel, P. Leif; Matthews, Geoff; Johnstone, Ricky W.; Ghosh, Nilanjan; Borrello, Ivan; Huff, Carol Ann

2014-01-01

4

Multiple differential-aperture microscopy.  

SciTech Connect

Differential-aperture X-ray microscopy (DAXM) is a powerful approach to 3D tomography with particular relevance to X-ray microdiffraction. With DAXM, scattering from submicron volumes can be resolved. However, the method is intrinsically a scanning technique where every resolved volume element (voxel) requires at least one area-detector readout. Previous applications of DAXM have used a single wire for knife-edge step profiling. Here, we demonstrate a way to accelerate DAXM measurements using multiple wires. A proof-of-principle experiment with a three-wire prototype showed that the speed of measurements can be tripled, but careful calibrations of wires will be required to maintain the spatial accuracy. In addition, related possibilities for accelerating measurements are briefly discussed.

Chung, J.-S.; Isa, S.; Greene, V.; Broadwater, O.; Liu, W.; Ice, G. E.; ORNL; Soongsil Univ.; South Carolina State Univ.

2007-01-01

5

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

6

Nonclassical potential solutions of partial differential equations  

Microsoft Academic Search

For a given scalar partial differential equation (PDE), a potential variable can be introduced through a conservation law. Such a conservation law yields an equivalent system (potential system) of PDEs with the given dependent variable and the potential variable as its dependent variables. Often there is also another equivalent scalar PDE (potential equation) with the potential variable as its dependent

GEORGE W. BLUMAN; ZHENYA YAN

2005-01-01

7

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

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

2014-01-01

8

Hertz Potentials and Differential Geometry  

E-print Network

, and I present techniques for introducing gauge terms of arbitrary order. Finally, I give a treatment of one application of Hertz potentials, namely calculating electromagnetic Casimir interactions for a couple of systems....

Bouas, Jeffrey David

2011-08-08

9

Potential Therapeutic Targets Identified in Multiple Myeloma  

Cancer.gov

Description: Researchers have identified molecular changes in multiple myeloma cells that activate an important biological pathway associated with cell growth and survival, thereby revealing potential new targets for drugs to treat this cancer. The researchers, led by a team from the NCI, have shown that malignant cells in multiple myeloma frequently harbor mutations that activate what is called the NF-kappaB signaling pathway, which plays a key role in promoting cell growth and preventing programmed cell death.

10

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

11

Abnormal Tr1 differentiation in multiple sclerosis  

PubMed Central

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). In the recent years, accumulating evidence has supported an immunosuppressive role for regulatory T cells (Tregs). Most studies in the context of autoimmunity have focused on the defects of the CD4+CD25high Tregs. However, we recently demonstrated an altered function of Tr1 Treg cells in MS, characterized by a lack of IL-10 secretion. Therefore, several major regulatory T cell defects are involved in human autoimmune disease. Hence, the induction of Tregs or the stimulation of Treg activity may be beneficial for the treatment of such diseases. PMID:17936368

Astier, Anne L.; Hafler, David A.

2007-01-01

12

Differential Item Functioning Detection Using the Multiple Indicators, Multiple Causes Method with a Pure Short Anchor  

ERIC Educational Resources Information Center

The multiple indicators, multiple causes (MIMIC) method with a pure short anchor was proposed to detect differential item functioning (DIF). A simulation study showed that the MIMIC method with an anchor of 1, 2, 4, or 10 DIF-free items yielded a well-controlled Type I error rate even when such tests contained as many as 40% DIF items. In general,…

Shih, Ching-Lin; Wang, Wen-Chung

2009-01-01

13

Fano Multiple-Symbol Differential Detectors for Differential Unitary Space-Time Modulation  

Microsoft Academic Search

We present a class of suboptimal multiple-symbol differential detectors (MSDDs) for differential unitary space-time (ST) codes in a time-selective Rayleigh flat-fading channel. These noncoherent detectors, termed Fano ST-MSDDs, employ the well-known Fano algorithm as their decoding engines. Their bit-error rate (BER) performance is excellent, as there is no irreducible error floor, even at very high fade rates. Compared with the

Patrick K. M. Pun; Paul K. M. Ho

2007-01-01

14

A multiple mapping conditioning model for differential diffusion  

NASA Astrophysics Data System (ADS)

This work introduces modeling of differential diffusion within the multiple mapping conditioning (MMC) turbulent mixing and combustion framework. The effect of differential diffusion on scalar variance decay is analyzed and, following a number of publications, is found to scale as Re-1/2. The ability to model the differential decay rates is the most important aim of practical differential diffusion models, and here this is achieved in MMC by introducing what is called the side-stepping method. The approach is practical and, as it does not involve an increase in the number of MMC reference variables, economical. In addition we also investigate the modeling of a more refined and difficult to reproduce differential diffusion effect - the loss of correlation between the different scalars. For this we develop an alternative MMC model with two reference variables but which also makes use of the side-stepping method. The new models are successfully validated against DNS results available in literature for homogenous, isotropic two scalar mixing.

Dialameh, L.; Cleary, M. J.; Klimenko, A. Y.

2014-02-01

15

Multiple Intelligences: A Wealth of Human Potential.  

ERIC Educational Resources Information Center

This issue focuses on the multiple types of intelligences that students and teachers possess, and provides tips for using this information in the business education classroom. The following articles are included: "How Do Students Learn Best and How Can Teachers Best Help Them?"; "Multiple Intelligences in Action in the Business Classroom";…

Keying In, 1997

1997-01-01

16

Potential of Urinary Metabolites for Diagnosing Multiple Sclerosis Teklab Gebregiworgis,,  

E-print Network

Potential of Urinary Metabolites for Diagnosing Multiple Sclerosis Teklab Gebregiworgis ABSTRACT: A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use healthy and MS drug-treated EAE mice. Multiple sclerosis (MS) is a demyelinating disease of the central

Powers, Robert

17

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

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

2013-01-01

18

Differential Gene Expression between Sensory Neocortical Areas: Potential Roles  

E-print Network

Differential Gene Expression between Sensory Neocortical Areas: Potential Roles for Ten_m3 and Bcl6 and efferent projections are forming. We identified 122 molecules that are differentially expressed between the regions and confirmed by quantitative polymerase chain reaction 95% of the 20 genes tested. Two genes were

Kreiman, Gabriel

19

Differential autonomic nervous system activity in multiple personality disorder.  

PubMed

The cardinal feature of multiple personality disorder (MPD) is the existence of two or more alter personality states that exchange control over the behaviour of an individual. Numerous clinical reports suggest that these alter personality states exhibit distinct physiological differences. We investigated differential autonomic nervous system (ANS) activity across nine subjects with MPD and five controls, who produced "alter" personality states by simulation and by hypnosis or deep relaxation. Eight of the nine MPD subjects consistently manifested physiologically distinct alter personality states. Three of the five controls were also produced physiologically distinct states, but these differed from those of the MPD subjects. A habituation paradigm demonstrated carryover effects at the ANS levels from one state to the next for both groups. PMID:2333357

Putnam, F W; Zahn, T P; Post, R M

1990-03-01

20

Multiple Differential-Amplifier MMICs Embedded in Waveguides  

NASA Technical Reports Server (NTRS)

Compact amplifier assemblies of a type now being developed for operation at frequencies of hundreds of gigahertz comprise multiple amplifier units in parallel arrangements to increase power and/or cascade arrangements to increase gains. Each amplifier unit is a monolithic microwave integrated circuit (MMIC) implementation of a pair of amplifiers in differential (in contradistinction to single-ended) configuration. Heretofore, in cascading amplifiers to increase gain, it has been common practice to interconnect the amplifiers by use of wires and/or thin films on substrates. This practice has not yielded satisfactory results at frequencies greater than 200 Hz, in each case, for either or both of two reasons: Wire bonds introduce large discontinuities. Because the interconnections are typically tens of wavelengths long, any impedance mismatches give rise to ripples in the gain-vs.-frequency response, which degrade the performance of the cascade.

Kangaslahti, Pekka; Schlecht, Erich

2010-01-01

21

Differential item functioning analysis by applying multiple comparison procedures.  

PubMed

Analysis within a Rasch measurement framework aims at development of valid and objective test score. One requirement of both validity and objectivity is that items do not show evidence of differential item functioning (DIF). A number of procedures exist for the assessment of DIF including those based on analysis of contingency tables by Mantel-Haenszel tests and partial gamma coefficients. The aim of this paper is to illustrate Multiple Comparison Procedures (MCP) for analysis of DIF relative to a variable defining a very large number of groups, with an unclear ordering with respect to the DIF effect. We propose a single step procedure controlling the false discovery rate for DIF detection. The procedure applies for both dichotomous and polytomous items. In addition to providing evidence against a hypothesis of no DIF, the procedure also provides information on subset of groups that are homogeneous with respect to the DIF effect. A stepwise MCP procedure for this purpose is also introduced. PMID:25562333

Eusebi, Paolo; Kreiner, Svend

2015-01-01

22

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

23

The clinical potential of blood-proteomics in multiple sclerosis  

PubMed Central

Background The aetiology of multiple sclerosis (MS) remains unknown. This hampers molecular diagnosis and the discovery of bio-molecular markers. Consequently, MS diagnostic procedures are complex and criteria for assessing therapeutic efficacy are controversial, suggesting that a pathophysiological rather than an aetiological approach to the disease would be more appropriate. In this regard, blood-proteomics represents a still-unexplored tool. We investigated the potential of proteomics as applied to peripheral blood mononuclear cells (PBMCs) for differentiating treatment-naive RR-MS patients from healthy controls and from IFN-treated RR-MS patients. Methods A comparative analysis of PBMC proteins isolated from 13 unselected IFN-treated RR-MS patients, 6 IFN-untreated RR-MS patients and 14 matched healthy controls was performed using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. We considered the volume of each spot, expressed as a percentage of the total volume of all spots in the gel. Heuristic clustering was applied to a composite population made up of a random sequence of gels from the different groups in comparison. For the differentially expressed proteins, we applied the Student's t-test to identify only those down- or up-regulated at least 2.5-fold [Ratio(R)???2.5] with respect to the homologous spots of the compared groups. Results Rho-GDI2, Rab2 and Cofilin1 were found to be associated with down-regulated and naïve group phenotypes; Cortactin and Fibrinogen beta-Chain Precursor were found to be associated with down-regulated and group-related IFN-treated RR-MS phenotypes. Thus, by means of similarity analysis, the proteomes were homogeneously segregated into three distinct groups corresponding to naive, IFN-treated and healthy control subjects. Interestingly, no separation was found between IFN-treated and healthy controls. Moreover, the molecular phenotypes were consistent with disease pathogenesis. Conclusions We demonstrated for the first time, albeit only with preliminary data, the aprioristic possibility of distinguishing naive and IFN-treated MS groups from controls, and naive from IFN-treated MS patients using a blood sample-based methodology (i.e. proteomics) alone. The functional profile of the identified molecules provides new pathophysiological insight into MS. Future development of these techniques could open up novel applications in terms of molecular diagnosis and therapy monitoring in MS patients. PMID:23692923

2013-01-01

24

Sox9 Potentiates BMP2-Induced Chondrogenic Differentiation and Inhibits BMP2-Induced Osteogenic Differentiation  

PubMed Central

Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering. PMID:24551211

Liao, Junyi; Hu, Ning; Zhou, Nian; Lin, Liangbo; Zhao, Chen; Yi, Shixiong; Fan, Tingxu; Bao, Wei; Liang, Xi; Chen, Hong; Xu, Wei; Chen, Cheng; Cheng, Qiang; Zeng, Yongming; Si, Weike; Yang, Zhong; Huang, Wei

2014-01-01

25

Multiple differentiation capacity of STRO-1+/CD146+ PDL mesenchymal progenitor cells.  

PubMed

Although mesenchymal progenitor cells can be isolated from periodontal ligament (PDL) tissues using stem cell markers STRO-1 and CD146, the proportion of these cells that have the capacity to differentiate into multiple cell lineages remains to be determined. This study was designed to quantify the proportions of primary human PDL cells that can undergo multilineage differentiation and to compare the magnitude of these capabilities relative to bone marrow-derived mesenchymal stem cells (MSCs) and parental PDL (PPDL) cells. PDL mesenchymal progenitor (PMP) cells were isolated from PPDL cells using the markers STRO-1 and CD146. The colony-forming efficiency and multilineage differentiation potential of PMP, PPDL, and MSCs under chondrogenic, osteogenic, and adipogenic conditions were determined. Flow cytometry revealed that on average 2.6% of PPDL cells were STRO-1(+)/CD146(+), whereas more than 63% were STRO-1(-)/CD146(-). Colony-forming efficiency of STRO-1(+)/CD146(+) PMP cells (19.3%) and MSCs (16.7%) was significantly higher than that of PPDL cells (6.8%). Cartilage-specific genes, early markers of osteoblastic differentiation, and adipogenic markers were significantly upregulated under appropriate conditions in PMP cells and MSCs compared to either their noninduced counterparts or induced PPDL cells. Consistent with these findings, immunohistochemistry revealed substantial accumulation of cartilaginous macromolecules, mineralized calcium nodules, and lipid vacuoles under chondrogenic, osteogenic, or adipogenic conditions in PMP and MSC cultures, respectively, compared to noninduced controls or induced PPDL cells. Thus STRO-1(+)/CD146(+) PMP cells demonstrate multilineage differentiation capacity comparable in magnitude to MSCs and could potentially be utilized for regeneration of the periodontium and other tissues. PMID:18593336

Xu, Jinping; Wang, Wei; Kapila, Yvonne; Lotz, Jeffrey; Kapila, Sunil

2009-04-01

26

The neuroprotective potential of flavonoids: a multiplicity of effects  

Microsoft Academic Search

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against\\u000a injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and\\u000a cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein\\u000a and lipid kinase signalling cascades in the brain

David Vauzour; Katerina Vafeiadou; Ana Rodriguez-Mateos; Catarina Rendeiro; Jeremy P. E. Spencer

2008-01-01

27

Multiple Discreteness and Product Differentiation: Demand for Carbonated Soft Drinks  

Microsoft Academic Search

For several of the largest supermarket product categories, such as carbonated soft drinks, canned soups, ready-to-eat cereals, and cookies, consumers regularly purchase assortments of products. Within the category, consumers often purchase multiple products and multiple units of each alternative selected on a given trip. This multiple discreteness violates the single-unit purchase assumption of multinomial logit and probit models. The misspecification

Jean-Pierre Dubé

2004-01-01

28

KCNQ2/3 openers show differential selectivity and site of action across multiple KCNQ channels.  

PubMed

KCNQ2/3 voltage-gated potassium channels conduct low-threshold, slowly activating and non-inactivating currents to repolarize the neuronal resting membrane potential. The channels negatively regulate neuronal excitability and KCNQ2/3 openers are efficacious in hyperexcited states such as epilepsy and pain. We developed and utilized thallium influx assays to profile novel KCNQ2/3 channel openers with respect to selectivity across KCNQ subtypes and on requirement for tryptophan 236 of KCNQ2, a critical residue for activity of the KCNQ opener retigabine. Using distinct chemical series of openers, a quinazolinone series showed relatively poor selectivity across multiple KCNQ channels and lacked activity at the KCNQ2(W236L) mutant channel. In contrast, several novel benzimidazole openers showed selectivity for KCNQ2/3 and KCNQ2 and retain activity at KCNQ2(W236L). Profiling of several hundred KCNQ2/3 openers across multiple diverse chemical series revealed that openers show differential degrees of selectivity across subtypes, with selectivity most difficult to achieve against KCNQ2. In addition, we report the significant finding that KCNQ openers can pharmacologically differentiate between homomeric and heteromeric channels containing subtypes in common. Moreover, most openers assayed were dependent on the W236 for activity, whereas only a small number appear to use a distinct mechanism. Collectively, we provide novel insights into the molecular pharmacology of KCNQ channels by demonstrating differential selectivity and site of action for KCNQ2/3 openers. The high-throughput thallium influx assays should prove useful for rapid characterization of KCNQ openers and in guiding efforts to identify selective compounds for advancement towards the clinic. PMID:21723881

Zhang, Di; Thimmapaya, Rama; Zhang, Xu-Feng; Anderson, David J; Baranowski, John L; Scanio, Marc; Perez-Medrano, Arturo; Peddi, Sridhar; Wang, Zhi; Patel, Jyoti R; DeGoey, David A; Gopalakrishnan, Murali; Honore, Prisca; Yao, Betty B; Surowy, Carol S

2011-08-30

29

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

30

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

31

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

32

A Study of Impulsive Multiterm Fractional Differential Equations with Single and Multiple Base Points and Applications  

PubMed Central

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

33

Multiple solutions of periodic boundary value problems for first order differential equations  

Microsoft Academic Search

By applying the well known Leggett–Williams multiple fixed point theorem and fixed point theorem of cone expansion and compression, this paper investigates the existence of multiple positive solutions of periodic boundary value problems for first order differential equations. Meanwhile, two examples are worked out to demonstrate the main results.

Yansheng Liu

2007-01-01

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

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

36

Isolation, culture, and induced multiple differentiation of Mongolian sheep bone marrow-derived mesenchymal stem cells.  

PubMed

The aim of this paper was to explore the optimal method of isolating, purifying, and proliferating Mongolian sheep bone marrow-derived mesenchymal stem cells (BMSCs) and their multiple differentiation potentialities. Bone marrow (BM) was punctured from ?1-year-old sheep, and BMSCs were harvested through gradient centrifuge and adherent cultures. Analysis of the growth of the passage 1, 5, and 10 cultures revealed an S-shaped growth curve with a population doubling time of 31.2 h. Karyotyping indicated that the chromosome number in the Mongolian sheep was 2n?=?54, comprising 26 pairs of autosomes and one pair of sex chromosomes (XY). RT-PCR demonstrated that OCT4, SOX2, and Nanog genes at passage 3 were positively expressed. The P3 BMSCs were cultured in vitro under inductive environments and induced into adipocytes, osteoblasts, chondrocytes, neural cells, and cardiomyocytes. Their differentiation properties were confirmed by histological staining, such as oil red, Alizarin red, hematoxylin-eosin, toluidine blue, and periodic acid schiff. RT-PCR showed that the specific genes to be induced were all expressed. This proves that the isolated cells are indeed the BMSCs and also provides valuable materials for somatic cell cloning and transgenic research. PMID:24399254

Liu, Zongzheng; Wang, Wei; Gao, Jinfang; Zhou, Huanmin; Zhang, Yanru

2014-05-01

37

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

38

Differential Diagnosis, Clinical Features, and Prognosis of Multiple Sclerosis  

Microsoft Academic Search

The diagnosis and prognosis of multiple sclerosis (MS) has changed dramatically over the years from the first descriptions\\u000a from St. Lidwina of Schiedam (1380–1433) and Augustus D’Este (grandson of George III) between 1822 and 1848 to the pathological\\u000a descriptions of Cruveilhier (1829–1842) and Carswell (1838). Serious study and synthesis of clinical and pathological human\\u000a MS began with the work of

Michael J. Olek

39

Multiple-try differential evolution adaptive Metropolis for efficient solution of highly parameterized models  

NASA Astrophysics Data System (ADS)

Spatially distributed hydrologic models potentially contain hundreds of parameters that need to be derived by calibration against a historical record of input-output data. The quality of this calibration strongly determines the predictive capability of the model and thus its usefulness for science-based decision making and forecasting. Unfortunately, high-dimensional optimization problems are typically difficult to solve. Here we present our recent developments to the Differential Evolution Adaptive Metropolis (DREAM) algorithm (Vrugt et al., 2009) to warrant efficient solution of high-dimensional parameter estimation problems. The algorithm samples from an archive of past states (Ter Braak and Vrugt, 2008), and uses multiple-try Metropolis sampling (Liu et al., 2000) to decrease the required burn-in time for each individual chain and increase efficiency of posterior sampling. This approach is hereafter referred to as MT-DREAM. We present results for 2 synthetic mathematical case studies, and 2 real-world examples involving from 10 to 240 parameters. Results for those cases show that our multiple-try sampler, MT-DREAM, can consistently find better solutions than other Bayesian MCMC methods. Moreover, MT-DREAM is admirably suited to be implemented and ran on a parallel machine and is therefore a powerful method for posterior inference.

Eric, L.; Vrugt, J. A.

2010-12-01

40

Joint analysis of differential gene expression in multiple studies using correlation motifs  

PubMed Central

The standard methods for detecting differential gene expression are mostly designed for analyzing a single gene expression experiment. When data from multiple related gene expression studies are available, separately analyzing each study is not ideal as it may fail to detect important genes with consistent but relatively weak differential signals in multiple studies. Jointly modeling all data allows one to borrow information across studies to improve the analysis. However, a simple concordance model, in which each gene is assumed to be differential in either all studies or none of the studies, is incapable of handling genes with study-specific differential expression. In contrast, a model that naively enumerates and analyzes all possible differential patterns across studies can deal with study-specificity and allow information pooling, but the complexity of its parameter space grows exponentially as the number of studies increases. Here, we propose a correlation motif approach to address this dilemma. This approach searches for a small number of latent probability vectors called correlation motifs to capture the major correlation patterns among multiple studies. The motifs provide the basis for sharing information among studies and genes. The approach has flexibility to handle all possible study-specific differential patterns. It improves detection of differential expression and overcomes the barrier of exponential model complexity. PMID:25143368

Wei, Yingying; Tenzen, Toyoaki; Ji, Hongkai

2015-01-01

41

Joint analysis of differential gene expression in multiple studies using correlation motifs.  

PubMed

The standard methods for detecting differential gene expression are mostly designed for analyzing a single gene expression experiment. When data from multiple related gene expression studies are available, separately analyzing each study is not ideal as it may fail to detect important genes with consistent but relatively weak differential signals in multiple studies. Jointly modeling all data allows one to borrow information across studies to improve the analysis. However, a simple concordance model, in which each gene is assumed to be differential in either all studies or none of the studies, is incapable of handling genes with study-specific differential expression. In contrast, a model that naively enumerates and analyzes all possible differential patterns across studies can deal with study-specificity and allow information pooling, but the complexity of its parameter space grows exponentially as the number of studies increases. Here, we propose a correlation motif approach to address this dilemma. This approach searches for a small number of latent probability vectors called correlation motifs to capture the major correlation patterns among multiple studies. The motifs provide the basis for sharing information among studies and genes. The approach has flexibility to handle all possible study-specific differential patterns. It improves detection of differential expression and overcomes the barrier of exponential model complexity. PMID:25143368

Wei, Yingying; Tenzen, Toyoaki; Ji, Hongkai

2015-01-01

42

The role of cell differentiation in controlling cell multiplication and cancer  

Microsoft Academic Search

It has been suggested that cancer ought to be regarded as a disease of cell differentiation. In multicellular organisms, indeed,\\u000a the control of cell multiplication is linked to cell specialization: During the process of differentiation embryonic cells,\\u000a while cycling, acquire the ability to perform specialized functions. This ability is incompatible with cell cycling which,\\u000a as a consequence, is repressed with

Karl-Hartmut von Wangenheim; Hans-Peter Peterson

2008-01-01

43

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

44

The neuroprotective potential of flavonoids: a multiplicity of effects  

PubMed Central

Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs. PMID:18937002

Vauzour, David; Vafeiadou, Katerina; Rodriguez-Mateos, Ana; Rendeiro, Catarina

2008-01-01

45

A novel differential diagnostic model for multiple primary lung cancer: Differentially-expressed gene analysis of multiple primary lung cancer and intrapulmonary metastasis  

PubMed Central

The incidence of synchronous multiple primary lung cancer (MPLC) is increasing. However, present diagnostic methods are unable to satisfy the individualized treatment requirements of patients with MPLC. The present study aimed to establish a quantitative mathematical model and analyze its diagnostic value for distinguishing between MPLC and cases of the histologically similar disease, intrapulmonary metastasis (IPM). The sum value of the differential expression ratios of four proteins, namely p53, p16, p27 and c-erbB2, was evaluated by immunohistochemically-staining specimens of primary cancers, second separate cancers, metastatic lymph nodes and metastatic cancers. The sum value of the differential expression ratio of the four proteins from the primary tumor and the lymph-node metastasis or metastatic cancer was <90 in the 11 patients with a single metastatic cancer and in the 30 patients with lymph-node metastasis, but was >90 in the 14 patients with different histological types of MPLC. Therefore, a quantitative differentially-expressed gene mathematical model was established as follows: Sum of the differential expression ratios = p16T1 ? T + p27T1 ? T2 + C-erbB2T1 ? T2 + p53T1 ? T2, where T1 is the primary cancer and T2 is the lymph node metastasis, metastatic cancer or the second separate cancer. The quantitative differentially-expressed gene mathematical model is considered to be a useful tool for distinguishing between MPLC and IPM.

CHEN, DALI; MEI, LONGYONG; ZHOU, YUBIN; SHEN, CHENG; XU, HUAN; NIU, ZHONGXI; CHE, GUOWEI

2015-01-01

46

Differential Effects of Alcohol on Working Memory: Distinguishing Multiple Processes  

PubMed Central

We assessed effects of alcohol consumption on different types of working memory (WM) tasks in an attempt to characterize the nature of alcohol effects on cognition. The WM tasks varied in two properties of materials to be retained in a two-stimulus comparison procedure. Conditions included (1) spatial arrays of colors, (2) temporal sequences of colors, (3) spatial arrays of spoken digits, and (4) temporal sequences of spoken digits. Alcohol consumption impaired memory for auditory and visual sequences, but not memory for simultaneous arrays of auditory or visual stimuli. These results suggest that processes needed to encode and maintain stimulus sequences, such as rehearsal, are more sensitive to alcohol intoxication than other WM mechanisms needed to maintain multiple concurrent items, such as focusing attention on them. These findings help to resolve disparate findings from prior research into alcohol’s effect on WM and on divided attention. The results suggest that moderate doses of alcohol impair WM by affecting certain mnemonic strategies and executive processes rather than by shrinking the basic holding capacity of WM. PMID:18179311

Saults, J. Scott; Cowan, Nelson; Sher, Kenneth J.; Moreno, Matthew V.

2008-01-01

47

Differential ontogeny of multiple opioid receptors (mu, delta, and kappa)  

SciTech Connect

We investigated the postnatal ontogeny of opioid receptors in rat brain under assay conditions which, when combined with computerized analysis, effectively reflect the developmental profile of high affinity binding to mu, delta, and kappa subpopulations. Concentrations of mu sites were assessed with the selective ligand /sup 3/H-(D-ala2,mePhe4,gly-ol5)enkephalin (DAGO). The other two sites were analyzed in binding assays with less selective radioligands but in the presence of specific unlabeled ligands which suppress cross-reactivity. We utilized /sup 3/H-(D-ala2,D-leu5)enkephalin (DADL) in the presence of 10 nM DAGO to label delta sites and /sup 3/H-ethylketocyclazocine (EKC) in the presence of 100 nM DADL + 100 nM (D-ala2,mePhe4,Met(0)ol5)enkephalin to detect kappa receptors. After birth, the density (femtomoles per milligram of wet weight) of mu sites declined for several days and then rose sharply over the next 2 weeks, increasing 2-fold by adulthood. Delta (delta) sites appeared in the second week postnatal and increased more than 8-fold in the next 2 weeks. Levels of kappa receptors were relatively low at birth and increased slowly (2-fold, overall). Computerized analyses of binding data revealed that DAGO and DADL were binding to single populations of sites throughout the postnatal period. DAGO and EKC affinities did not fluctuate in this period, whereas DADL affinities were low for the first week and then rose to adult levels. In summary, mu, kappa, and delta receptors exhibit differential postnatal developmental profiles. The former two are present at birth, whereas the latter appears in the second week. The postnatal increase for all three sites appear to be preceded by the previously demonstrated emergence of opioid peptides.

Spain, J.W.; Roth, B.L.; Coscia, C.J.

1985-03-01

48

Multiple Component Event-Related Potential (mcERP) Estimation  

NASA Technical Reports Server (NTRS)

We show how model-based estimation of the neural sources responsible for transient neuroelectric signals can be improved by the analysis of single trial data. Previously, we showed that a multiple component event-related potential (mcERP) algorithm can extract the responses of individual sources from recordings of a mixture of multiple, possibly interacting, neural ensembles. McERP also estimated single-trial amplitudes and onset latencies, thus allowing more accurate estimation of ongoing neural activity during an experimental trial. The mcERP algorithm is related to informax independent component analysis (ICA); however, the underlying signal model is more physiologically realistic in that a component is modeled as a stereotypic waveshape varying both in amplitude and onset latency from trial to trial. The result is a model that reflects quantities of interest to the neuroscientist. Here we demonstrate that the mcERP algorithm provides more accurate results than more traditional methods such as factor analysis and the more recent ICA. Whereas factor analysis assumes the sources are orthogonal and ICA assumes the sources are statistically independent, the mcERP algorithm makes no such assumptions thus allowing investigators to examine interactions among components by estimating the properties of single-trial responses.

Knuth, K. H.; Clanton, S. T.; Shah, A. S.; Truccolo, W. A.; Ding, M.; Bressler, S. L.; Trejo, L. J.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

2002-01-01

49

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

50

dCaP: detecting differential binding events in multiple conditions and proteins  

PubMed Central

Background Current ChIP-seq studies are interested in comparing multiple epigenetic profiles across several cell types and tissues simultaneously for studying constitutive and differential regulation. Simultaneous analysis of multiple epigenetic features in many samples can gain substantial power and specificity than analyzing individual features and/or samples separately. Yet there are currently few tools can perform joint inference of constitutive and differential regulation in multi-feature-multi-condition contexts with statistical testing. Existing tools either test regulatory variation for one factor in multiple samples at a time, or for multiple factors in one or two samples. Many of them only identify binary rather than quantitative variation, which are sensitive to threshold choices. Results We propose a novel and powerful method called dCaP for simultaneously detecting constitutive and differential regulation of multiple epigenetic factors in multiple samples. Using simulation, we demonstrate the superior power of dCaP compared to existing methods. We then apply dCaP to two datasets from human and mouse ENCODE projects to demonstrate its utility. We show in the human dataset that the cell-type specific regulatory loci detected by dCaP are significantly enriched near genes with cell-type specific functions and disease relevance. We further show in the mouse dataset that dCaP captures genomic regions showing significant signal variations for TAL1 occupancy between two mouse erythroid cell lines. The novel TAL1 occupancy loci detected only by dCaP are highly enriched with GATA1 occupancy and differential gene expression, while those detected only by other methods are not. Conclusions Here, we developed a novel approach to utilize the cooperative property of proteins to detect differential binding given multivariate ChIP-seq samples to provide better power, aiming for complementing existing approaches and providing new insights in the method development in this field. PMID:25522020

2014-01-01

51

Differential Fault Analysis of AES using a Single Multiple-Byte Fault  

E-print Network

will be even harder to prevent. While these faults may have undesirable effects on normal applications, it canDifferential Fault Analysis of AES using a Single Multiple-Byte Fault Subidh Ali1 , Debdeep. In this paper we present an improved fault attack on the Advanced En- cryption Standard (AES). This paper

52

Compressive Sampling based Multiple Symbol Differential Detection for UWB IR Signals  

E-print Network

heavily stress the analog-to-digital converters (ADCs) causing high power consumption in the digitalCompressive Sampling based Multiple Symbol Differential Detection for UWB IR Signals Shahzad.s.gishkori@tudelft.nl; g.j.t.leus@tudelft.nl; vincenzo.lottici@iet.unipi.it Abstract--In this paper, a compressive sampling

Leus, Geert

53

Initiating Differentiated Instruction in General Education Classrooms with Inclusion Learning Support Students: A Multiple Case Study  

ERIC Educational Resources Information Center

The purpose of this multiple case study was to describe and evaluate the experience of 5 general education teachers from a northeastern urban middle school as they integrated differentiated instruction with students who have specific learning disabilities. Educators are challenged to implement instruction that engages students with specific…

Berbaum, K. A.

2009-01-01

54

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

E-print Network

Differential meta-analysis of RNA-seq data from multiple studies Andrea Rau1,2 Guillemette Marot3 Europe, MODAL ABSTRACT Background: High-throughput sequencing is now regularly used for studies that additional follow-up studies will be conducted to re-address the same biological question. Results: We

Paris-Sud XI, Université de

55

Identifying differential expression in multiple SAGE libraries: an overdispersed log-linear model approach  

Microsoft Academic Search

BACKGROUND: In testing for differential gene expression involving multiple serial analysis of gene expression (SAGE) libraries, it is critical to account for both between and within library variation. Several methods have been proposed, including the t test, tw test, and an overdispersed logistic regression approach. The merits of these tests, however, have not been fully evaluated. Questions still remain on

Jun Lu; John K. Tomfohr; Thomas B. Kepler

2005-01-01

56

Alignment estimation performances of merit function regression with differential wavefront sampling in multiple design configuration optimization  

NASA Astrophysics Data System (ADS)

In our earlier study[12], we suggested a new alignment algorithm called Multiple Design Configuration Optimization (MDCO hereafter) method combining the merit function regression (MFR) computation with the differential wavefront sampling method (DWS). In this study, we report alignment state estimation performances of the method for three target optical systems (i.e. i) a two-mirror Cassegrain telescope of 58mm in diameter for deep space earth observation, ii) a three-mirror anastigmat of 210mm in aperture for ocean monitoring from the geostationary orbit, and iii) on-axis/off-axis pairs of a extremely large telescope of 27.4m in aperture). First we introduced known amounts of alignment state disturbances to the target optical system elements. Example alignment parameter ranges may include, but not limited to, from 800microns to 10mm in decenter, and from 0.1 to 1.0 degree in tilt. We then ran alignment state estimation simulation using MDCO, MFR and DWS. The simulation results show that MDCO yields much better estimation performance than MFR and DWS over the alignment disturbance level of up to 150 times larger than the required tolerances. In particular, with its simple single field measurement, MDCO exhibits greater practicality and application potentials for shop floor optical testing environment than MFR and DWS.

Oh, Eunsong; Kim, Sug-Whan; Cho, Seongick; Ryu, Joo-Hyung

2011-10-01

57

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability  

NASA Technical Reports Server (NTRS)

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

Knuth, Kevin H.; Shah, Ankoor S.; Truccolo, Wilson; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.

2003-01-01

58

Multiple periodic solutions for lattice dynamical systems with superquadratic potentials  

NASA Astrophysics Data System (ADS)

In this paper, we consider one dimensional lattices consisting of infinitely many particles with nearest neighbor interaction. The autonomous dynamical system is described by the following infinite system of second order differential equations q=?i-1'(q-qi)-?i'(qi-q), i?Z, where ?i denotes the interaction potential between two neighboring particles and qi(t) is the state of the i-th particle. Supposing ?i is superquadratic at infinity, for all T>0, we obtain a nonzero T-periodic solution of finite energy which may be nonconstant in some range of period. If in addition ?i(x) is even in x, we also obtain infinitely many geometrically distinct solutions for any period T>0. In particular, a prescribed number of geometrically distinct nonconstant periodic solutions is obtained for some range of period. Since the functional associated to the above system is invariant under the actions of the non-compact group Z and the continuous compact group S1 under our assumptions, in order to prove our results, we need to extend the abstract critical point theorem about strongly indefinite functional developed by Bartsch and Ding [Math. Nachr. 279 (2006) 1267-1288] to a more general class of symmetry.

Sun, Jijiang; Ma, Shiwang

59

Harmonizing multiple methods for reconstructing historical potential and reference evapotranspiration  

USGS Publications Warehouse

Potential evapotranspiration (PET) and reference evapotranspiration (RET) data are usually critical components of hydrologic analysis. Many different equations are available to estimate PET and RET. Most of these equations, such as the Priestley-Taylor and Penman- Monteith methods, rely on detailed meteorological data collected at ground-based weather stations. Few weather stations collect enough data to estimate PET or RET using one of the more complex evapotranspiration equations. Currently, satellite data integrated with ground meteorological data are used with one of these evapotranspiration equations to accurately estimate PET and RET. However, earlier than the last few decades, historical reconstructions of PET and RET needed for many hydrologic analyses are limited by the paucity of satellite data and of some types of ground data. Air temperature stands out as the most generally available meteorological ground data type over the last century. Temperature-based approaches used with readily available historical temperature data offer the potential for long period-of-record PET and RET historical reconstructions. A challenge is the inconsistency between the more accurate, but more data intensive, methods appropriate for more recent periods and the less accurate, but less data intensive, methods appropriate to the more distant past. In this study, multiple methods are harmonized in a seamless reconstruction of historical PET and RET by quantifying and eliminating the biases of the simple Hargreaves-Samani method relative to the more complex and accurate Priestley-Taylor and Penman-Monteith methods. This harmonization process is used to generate long-term, internally consistent, spatiotemporal databases of PET and RET.

Belaineh, Getachew; Sumner, David; Carter, Edward; Clapp, David

2013-01-01

60

Local field potentials reflect multiple spatial scales in V4  

PubMed Central

Local field potentials (LFP) reflect the properties of neuronal circuits or columns recorded in a volume around a microelectrode (Buzsáki et al., 2012). The extent of this integration volume has been a subject of some debate, with estimates ranging from a few hundred microns (Katzner et al., 2009; Xing et al., 2009) to several millimeters (Kreiman et al., 2006). We estimated receptive fields (RFs) of multi-unit activity (MUA) and LFPs at an intermediate level of visual processing, in area V4 of two macaques. The spatial structure of LFP receptive fields varied greatly as a function of time lag following stimulus onset, with the retinotopy of LFPs matching that of MUAs at a restricted set of time lags. A model-based analysis of the LFPs allowed us to recover two distinct stimulus-triggered components: an MUA-like retinotopic component that originated in a small volume around the microelectrodes (~350 ?m), and a second component that was shared across the entire V4 region; this second component had tuning properties unrelated to those of the MUAs. Our results suggest that the LFP reflects neural activity across multiple spatial scales, which both complicates its interpretation and offers new opportunities for investigating the large-scale structure of network processing. PMID:23533106

Mineault, Patrick J.; Zanos, Theodoros P.; Pack, Christopher C.

2013-01-01

61

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

62

Determination of CY, from a Differential Jet -- - Multiplicity Distribution at SLC and PEP  

Microsoft Academic Search

We measure 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 a, is determined to be 0.123*0.009-f 0.005 at fi NN Mz (at SLC) and 0.149f 0.002f0.007 at fi = 29 GeV (at PEP). The running of o, between these two center of mass energies

S. Komamiya; F. Le Diberder; G. S. Abramq; C. E. Adolphsen; D. Averill; J. Ballam; B. C. Barish; T. Barklow; B. A. Barnett; J. Bartelt; S. Bethke; D. Blockq; G. Bonvicini; A. Boyarski; B. Brabson; A. Breakstone; F. Bulos; P. R. Burchat; D. L. Burke; R. J. Cence; J. Chapman; M. Chmeissani; D. Cords; D. P. Coupal; P. Dauncey; H. C. DeStaebler; J. M. Dorfan; D. C. Drewer; R. Elia; G. J. Feldman; D. Fernandes; W. T. Ford; C. Fordham; R. Frey; D. Fujino; K. K. Gan; C. Gatto; E. Gero; G. Gidal; T. Glanzman; G. Goldhaber; J. J. Gomez Cadenas; G. Gratta; G. Grindhammer; P. Grosse-Wiesmann; G. Hanson; R. Harr; B. Harral; C. M. Hawkes; K. Hayes; C. Hearty; C. A. Heusch; M. D. Hildreth; T. Himel; D. A. Hinshaw; S. J. Hong; D. Hutchinson; J. Hylen; W. R. Innes; R. G. Jacobsen; J. A. Jaros; C. K. Jung; J. A. Kadyk; J. Kent; M. King; S. R. Klein; D. S. Koetke; W. Koska; L. A. Kowalski; W. Kozanecki; J. F. Kral; L. Labarga; A. J. Lankford; R. R. Larsen; M. E. Levi; A. M. Litke; X. C. Lou; J. A. McKenna; J. A. J. Matthews; T. Mattison; B. D. Milliken; K. C. Moffeit; C. T. Munger; W. N. Murray; J. Nash; H. Ogren; K. F. O'Shaughnessy; S. I. Parker; C. Peck; M. L. Perl; F. Perrier; M. Petradza; R. Pitthan; F. C. Porter

63

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

64

Undersulfation of Heparan Sulfate Restricts Differentiation Potential of Mouse Embryonic Stem Cells*  

PubMed Central

Heparan sulfate proteoglycans, present on cell surfaces and in the extracellular matrix, interact with growth factors and morphogens to influence growth and differentiation of cells. The sulfation pattern of the heparan sulfate chains formed during biosynthesis in the Golgi compartment will determine the interaction potential of the proteoglycan. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes have a key role during biosynthesis, greatly influencing total sulfation of the heparan sulfate chains. The differentiation potential of mouse embryonic stem cells lacking both NDST1 and NDST2 was studied using in vitro differentiation protocols, expression of differentiation markers, and assessment of the ability of the cells to respond to growth factors. The results show that NDST1 and NDST2 are dispensable for mesodermal differentiation into osteoblasts but necessary for induction of adipocytes and neural cells. Gene expression analysis suggested a differentiation block at the primitive ectoderm stage. Also, GATA4, a primitive endoderm marker, was expressed by these cells. The addition of FGF4 or FGF2 together with heparin rescued the differentiation potential to neural progenitors and further to mature neurons and glia. Our results suggest that the embryonic stem cells lacking both NDST1 and NDST2, expressing a very low sulfated heparan sulfate, can take the initial step toward differentiation into all three germ layers. Except for their potential for mesodermal differentiation into osteoblasts, the cells are then arrested in a primitive ectoderm and/or endoderm stage. PMID:22298785

Forsberg, Maud; Holmborn, Katarina; Kundu, Soumi; Dagälv, Anders; Kjellén, Lena; Forsberg-Nilsson, Karin

2012-01-01

65

Endothelial differentiation potential of human monocyte-derived multipotential cells.  

PubMed

We previously reported a unique CD14(+)CD45(+)CD34(+) type I collagen(+) cell fraction derived from human circulating CD14(+) monocytes, named monocyte-derived multipotential cells (MOMCs). This primitive cell population contains progenitors capable of differentiating along the mesenchymal and neuronal lineages. Here, we investigated whether MOMCs can also differentiate along the endothelial lineage. MOMCs treated with angiogenic growth factors for 7 days changed morphologically and adopted a caudate appearance with rod-shaped microtubulated structures resembling Weibel-Palade bodies. Almost every cell expressed CD31, CD144, vascular endothelial growth factor (VEGF) type 1 and 2 receptors, Tie-2, von Willebrand factor (vWF), endothelial nitric-oxide synthase, and CD146, but CD14/CD45 expression was markedly downregulated. Under these culture conditions, the MOMCs continued to proliferate for up to 7 days. Functional characteristics, including vWF release upon histamine stimulation and upregulated expression of VEGF and VEGF type 1 receptor in response to hypoxia, were indistinguishable between the MOMC-derived endothelial-like cells and cultured mature endothelial cells. The MOMCs responded to angiogenic stimuli and promoted the formation of mature endothelial cell tubules in Matrigel cultures. Finally, in xenogenic transplantation studies using a severe combined immunodeficient mouse model, syngeneic colon carcinoma cells were injected subcutaneously with or without human MOMCs. Cotransplantation of the MOMCs promoted the formation of blood vessels, and more than 40% of the tumor vessel sections incorporated human endothelial cells derived from MOMCs. These findings indicate that human MOMCs can proliferate and differentiate along the endothelial lineage in a specific permissive environment and thus represent an autologous transplantable cell source for therapeutic neovasculogenesis. PMID:16888284

Kuwana, Masataka; Okazaki, Yuka; Kodama, Hiroaki; Satoh, Takashi; Kawakami, Yutaka; Ikeda, Yasuo

2006-12-01

66

Improved detection of differentially expressed genes in microarray experiments through multiple scanning and image integration  

PubMed Central

The variability of results in microarray technology is in part due to the fact that independent scans of a single hybridised microarray give spot images that are not quite the same. To solve this problem and turn it to our advantage, we introduced the approach of multiple scanning and of image integration of microarrays. To this end, we have developed specific software that creates a virtual image that statistically summarises a series of consecutive scans of a microarray. We provide evidence that the use of multiple imaging (i) enhances the detection of differentially expressed genes; (ii) increases the image homogeneity; and (iii) reveals false-positive results such as differentially expressed genes that are detected by a single scan but not confirmed by successive scanning replicates. The increase in the final number of differentially expressed genes detected in a microarray experiment with this approach is remarkable; 50% more for microarrays hybridised with targets labelled by reverse transcriptase, and 200% more for microarrays developed with the tyramide signal amplification (TSA) technique. The results have been confirmed by semi-quantitative RT–PCR tests. PMID:14627839

Romualdi, Chiara; Trevisan, Silvia; Celegato, Barbara; Costa, Germano; Lanfranchi, Gerolamo

2003-01-01

67

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

68

Multiple Sources for Cardiac Stem Cells and Their Cardiogenic Potential  

Microsoft Academic Search

\\u000a The belief that the heart is a terminally differentiated organ was a very well established notion among the scientific community\\u000a until the early 2000s, although several authors tried to challenge this dogma over the years. Nonetheless, myocyte turnover\\u000a was only accepted after the demonstration of the intense proliferation that occurs, in human hearts, acutely after myocardial\\u000a infarction. The first clues

Antonio Paolo Beltrami; Daniela Cesselli; Carlo Alberto Beltrami

69

TEMPI: probabilistic modeling time-evolving differential PPI networks with multiPle information  

PubMed Central

Motivation: Time-evolving differential protein–protein interaction (PPI) networks are essential to understand serial activation of differentially regulated (up- or downregulated) cellular processes (DRPs) and their interplays over time. Despite developments in the network inference, current methods are still limited in identifying temporal transition of structures of PPI networks, DRPs associated with the structural transition and the interplays among the DRPs over time. Results: Here, we present a probabilistic model for estimating Time-Evolving differential PPI networks with MultiPle Information (TEMPI). This model describes probabilistic relationships among network structures, time-course gene expression data and Gene Ontology biological processes (GOBPs). By maximizing the likelihood of the probabilistic model, TEMPI estimates jointly the time-evolving differential PPI networks (TDNs) describing temporal transition of PPI network structures together with serial activation of DRPs associated with transiting networks. This joint estimation enables us to interpret the TDNs in terms of temporal transition of the DRPs. To demonstrate the utility of TEMPI, we applied it to two time-course datasets. TEMPI identified the TDNs that correctly delineated temporal transition of DRPs and time-dependent associations between the DRPs. These TDNs provide hypotheses for mechanisms underlying serial activation of key DRPs and their temporal associations. Availability and implementation: Source code and sample data files are available at http://sbm.postech.ac.kr/tempi/sources.zip. Contact: seungjin@postech.ac.kr or dhwang@dgist.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25161233

Kim, Yongsoo; Jang, Jin-Hyeok; Choi, Seungjin; Hwang, Daehee

2014-01-01

70

A multiplicative product of distributions and a class of ordinary differential equations with distributional coefficients  

E-print Network

We construct a generalization of the multiplicative product of distributions presented by L. H\\"ormander in [L. H\\"ormander, {\\it The analysis of linear partial differential operators I} (Springer-Verlag, 1983)]. The new product is defined in the vector space ${\\mathcal A}(\\bkR)$ of piecewise smooth functions $f: \\bkR \\to \\bkC$ and all their (distributional) derivatives. It is associative, satisfies the Leibniz rule and reproduces the usual pointwise product of functions for regular distributions in ${\\mathcal A}(\\bkR)$. Endowed with this product, the space ${\\mathcal A}(\\bkR)$ becomes a differential associative algebra of generalized functions. By working in the new ${\\mathcal A}(\\bkR)$-setting we determine a method for transforming an ordinary linear differential equation with general solution $\\psi$ into another, ordinary linear differential equation, with general solution $\\chi_{\\Omega} \\psi$, where $\\chi_{\\Omega}$ is the characteristic function of some prescribed interval $\\Omega \\subset \\bkR$.

Dias, Nuno Costa

2009-01-01

71

The role of functional neuroimaging in the differential diagnosis of idiopathic Parkinson’s disease and multiple system atrophy  

Microsoft Academic Search

Parkinsonism is a symptom of a number of neurodegenerative disorders in the elderly. Even though clinical criteria for various parkinsonian disorders have been developed recently, the differential diagnosis of parkinsonian disorders based on clinical symptoms remains unsatisfactory, particularly in early disease stages. Early differential diagnosis on the other hand is important as prognosis and treatment options differ substantially. Multiple system

Thomas Eckert; David Eidelberg

2004-01-01

72

Multiple mesenteric well-differentiated liposarcoma complicated by purulent inflammation: A case report  

PubMed Central

Multiple mesenteric well-differentiated (WD) liposarcoma is an extremely rare entity. The present study describes a case of multiple mesenteric WD liposarcoma, complicated by purulent inflammation, in a 59-year-old male who presented with abdominal pain and pyrexia of unknown origin. A computed tomography scan of the abdomen revealed a large, non-encapsulated mass in the abdomino-pelvic cavity, which was characterized by two components, a main portion of fatty density and a non-adipose solid portion. A re-evaluated CT scan, performed eight days later, revealed an enlargement of the non-adipose mass. A laparotomy was performed, and numerous separated fatty nodules and masses of various sizes were identified within the mesentery of the small intestine. The histological findings were consistent with an adipocytic subtype of multiple mesenteric WD liposarcoma, with the largest of the tumors complicated by purulent inflammation. The multiplicity of these tumors and the concurrent purulent inflammation in the present case make it unique. PMID:25663908

GAO, WEI; WANG, HUAIZHOU; LIU, JINYU; WANG, FUJIANG; DONG, JIANJUN; GENG, JUNZU

2015-01-01

73

Adipogenic differentiation potential of rat adipose tissue-derived subpopulations of stromal cells.  

PubMed

Adipose-derived stromal cells (ASCs) are mostly isolated by enzymatic digestion, centrifugation and adherent growth resulting in a very heterogeneous cell population. Therefore, other cell types in the cell culture can comprise the differentiation and proliferation potential of the ASC population. Recent studies indicated that an antibody-aided isolation of distinct ASC subpopulations provides advantages over the conventional method of ASC isolation. The aim of this study was to investigate the adipogenic differentiation potential of CD29-, CD71-, CD73- and CD90-selected ASCs in vitro. The stromal vascular fraction (SVF) was obtained from rat adipose tissue by enzymatic digestion and centrifugation. Subsequently, CD29(+)-, CD71(+)-, CD73(+)- and CD90(+) cells were isolated by magnetic activated cell sorting (MACS), seeded into culture plates and differentiated into the adipogenic lineage. ASCs isolated by adherent growth only served as controls. Adipogenic differentiation was assessed by Oil Red O staining and quantification of the adiponectin and leptin concentrations in the cell culture supernatants. Statistical analysis was carried out using one-way analysis of variance (ANOVA) followed by the Scheffe's post hoc procedure. The results showed that different subpopulations with different adipogenic differentiation potentials can be isolated by the MACS procedure. The highest adipogenic differentiation potential was determined in the CD29-selected ASC population followed by the unsorted ASC population. The CD71-, CD73- and CD90-selected cells exhibited significantly the lowest adipogenic differentiation potential. In conclusion, the CD29-selected ASCs and the unsorted ASCs exhibited a similar adipogenic differentiation potential. Therefore, we do not see a clear advantage in the application of an anti-CD29-based isolation of ASCs over the conventional technique using adherent growth. However, the research on isolation/purification methods of adipogenic ASCs should continue in order to make this stem cell source even more attractive for future adipose tissue engineering applications. PMID:24947082

Gierloff, M; Petersen, L; Oberg, H-H; Quabius, E S; Wiltfang, J; Açil, Y

2014-10-01

74

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

75

Therapeutic potential of carbon monoxide in multiple sclerosis.  

PubMed

Carbon monoxide (CO) is produced during the catabolism of free haem, catalyzed by haem oxygenase (HO) enzymes, and its physiological roles include vasodilation, neurotransmission, inhibition of platelet aggregation and anti-proliferative effects on smooth muscle. In vivo preclinical studies have shown that exogenously administered quantities of CO may represent an effective treatment for conditions characterized by a dysregulated immune response. The carbon monoxide-releasing molecules (CORMs) represent a group of compounds capable of carrying and liberating controlled quantities of CO in the cellular systems. This review covers the physiological and anti-inflammatory properties of the HO/CO pathway in the central nervous system. It also discusses the effects of CORMs in preclinical models of inflammation. The accumulating data discussed herein support the possibility that CORMs may represent a novel class of drugs with disease-modifying properties in multiple sclerosis. PMID:22235993

Fagone, P; Mangano, K; Coco, M; Perciavalle, V; Garotta, G; Romao, C C; Nicoletti, F

2012-02-01

76

Therapeutic potential of carbon monoxide in multiple sclerosis  

PubMed Central

Summary Carbon monoxide (CO) is produced during the catabolism of free haem, catalyzed by haem oxygenase (HO) enzymes, and its physiological roles include vasodilation, neurotransmission, inhibition of platelet aggregation and anti-proliferative effects on smooth muscle. In vivo preclinical studies have shown that exogenously administered quantities of CO may represent an effective treatment for conditions characterized by a dysregulated immune response. The carbon monoxide-releasing molecules (CORMs) represent a group of compounds capable of carrying and liberating controlled quantities of CO in the cellular systems. This review covers the physiological and anti-inflammatory properties of the HO/CO pathway in the central nervous system. It also discusses the effects of CORMs in preclinical models of inflammation. The accumulating data discussed herein support the possibility that CORMs may represent a novel class of drugs with disease-modifying properties in multiple sclerosis. PMID:22235993

Fagone, P; Mangano, K; Coco, M; Perciavalle, V; Garotta, G; Romao, C C; Nicoletti, F

2012-01-01

77

Multiple antimelanoma potential of dry olive leaf extract.  

PubMed

Various constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno- and chemoresistant type of skin cancer-melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE-treated B16 cells were blocked in the G(0) /G(1) phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying process started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase-independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic. PMID:20568104

Mijatovic, Sanja A; Timotijevic, Gordana S; Miljkovic, Djordje M; Radovic, Julijana M; Maksimovic-Ivanic, Danijela D; Dekanski, Dragana P; Stosic-Grujicic, Stanislava D

2011-04-15

78

Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation.  

PubMed

Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation. SIRT1 has also been shown to be involved in multiple tumors. In addition, new pharmacotherapies have recently been approved that target SIRT1. The purpose of this study was to use immunohistochemistry to characterize SIRT1 protein expression in human soft tissue neoplasms with the hopes of finding new diagnostic and therapeutic modalities. SIRT1 immunoreactivity was reviewed in a series of 164 soft tissue tumors including alveolar soft part sarcoma, angiomyolipoma, clear cell sarcoma, desmoid/fibromatosis, desmoplastic small round cell tumor, Ewing sarcoma, gastrointestinal stromal tumor, glomus tumor, leiomyoma, leiomyosarcoma, lipoma, liposarcoma, malignant peripheral nerve sheath tumor, nodular fasciitis, osteosarcoma, rhabdomyosarcoma, schwannoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, and Wilms tumor. In addition, numerous benign tissues were tested for SIRT1 reactivity. In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stroma, smooth muscle, and striated muscle. A similar pattern of cytoplasmic SIRT1 expression was observed in soft tissue neoplasms with myoid differentiation, namely, angiomyolipoma (100%), glomus tumor (100%), leiomyoma (90%), leiomyosarcoma (76.5%), and rhabdomyosarcoma (87%). The other lesions examined were negative. Although the physiologic role of SIRT1 remains to be clarified in myoid tissues and neoplasms differentiating along these lines, this observation points to a potential role for this marker in diagnostic immunohistochemistry. Furthermore, the recent emergence of drugs capable of selectively inhibiting SIRT1 raises the possibility of a potential application for targeted therapy. Additional studies are necessary to further characterise the role of SIRT1 in myoid tissues and neoplasms. PMID:23332867

Dickson, Brendan C; Riddle, Nicole D; Brooks, John S; Pasha, Theresa L; Zhang, Paul J

2013-06-01

79

Videourodynamic and sphincter motor unit potential analyses in Parkinson's disease and multiple system atrophy  

PubMed Central

OBJECTIVES—Urinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology offer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction.?METHODS—twenty one patients with PD (15 men, six women, mean age 64 (49-76), mean disease duration 4 years (1-8 years), median Hoehn and Yahr grade 3 (1-4), all taking 300 mg/day of levodopa (100-500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48-72), mean disease duration 3 years (0.5-6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the differential diagnosis of these two diseases.?RESULTS—Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-Griffiths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less common than that in MSA (71% of women and 63% of men). Postmicturition residuals >100 ml were absent in patients with PD but were present in 47% of patients with MSA.?CONCLUSION—Patients with PD had less severe urinary dysfunction with little evidence of internal or external sphincter denervation, by contrast with the common findings in MSA. The findings of postmicturition residuals >100 ml, detrusor-external sphincter dyssynergia, open bladder neck at the start of bladder filling, and neurogenic sphincter motor unit potentials are highly suggestive of MSA.?? PMID:11606669

Sakakibara, R; Hattori, T; Uchiyama, T; Yamanishi, T

2001-01-01

80

Single and multiple vibrational resonance in a quintic oscillator with monostable potentials S. Jeyakumari,1  

E-print Network

Single and multiple vibrational resonance in a quintic oscillator with monostable potentials S of vibrational resonance in a damped quintic oscillator with three cases of single well of the potential V x = 1 as VR and gVR at which vibrational resonance occurs. We show that for fixed values of the parameters

Rey Juan Carlos, Universidad

81

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

PubMed Central

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 to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another. Results Differences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors. Conclusion Both increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use. PMID:18957087

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

2008-01-01

82

A chemical basis for differential allelopathic potential of sorghum hybrids on wheat  

Microsoft Academic Search

The basis for differential allelopathic potentials among sorghum (Sorghum bicolor L. Moench) hybrids was investigated by conducting quantitative and qualitative studies of their phenolic contents. Total phenolic content in sorghum plant parts varied within hybrids, among hybrids, and between growing seasons. Inhibition of wheat (Triticum aestivum L.) radicle growth was positively associated (r=0.66) with concentrations of total phenolics contained in

Moncef Ben-Hammouda; Robert J. Kremer; HARRY C. MINOR; Muhammad Sarwar

1995-01-01

83

The non-locality of multiple-scattering corrections to the nucleon-nucleus optical potential  

NASA Astrophysics Data System (ADS)

The Watson multiple-scattering theory is used to generate the first- and second-order optical potentials for nucleon-nucleus elastic scattering at intermediate and high energies. A method is developed for treating exactly the non-locality of the second-order potential and the scattering from the exact calculation is compared to that from a local approximation for the second-order potential. The results are significantly different both for the angular distributions and the polarization.

Johnson, Ronald C.; Martin, D. C.

1972-09-01

84

Compression of the multiple ion-acoustic soliton at the bottom of the space potential  

SciTech Connect

Detailed experimental investigations on compressive phenomena are performed using a double-plasma-type device. When the incident multiple ion-acoustic soliton propagates to the ion-sheath edge, which is produced by the biased reflector to deep negative potential, this multiple soliton is compressed by the accelerated velocities of the second and third pulses and becomes a single soliton at the reflection point. It then resumes the form of a multiple soliton, as if via a recurrence phenomenon, and each pulse of this multiple soliton propagates toward the reflector. These phenomena are caused by an uneven space potential, which in turn is produced by deep negative voltage on the reflector and ion wakefield. Also, the reflection soliton is produced at this reflection point. {copyright} {ital 1997} {ital The American Physical Society}

Nagasawa, T.; Nishida, Y. [Department of Electrical and Electronic Engineering, Utsunomiya University, Utsunomiya, Tochigi 321 (Japan)] [Department of Electrical and Electronic Engineering, Utsunomiya University, Utsunomiya, Tochigi 321 (Japan)

1997-10-01

85

Withania somnifera Water Extract as a Potential Candidate for Differentiation Based Therapy of Human Neuroblastomas  

PubMed Central

Neuroblastoma is an aggressive childhood disease of the sympathetic nervous system. Treatments are often ineffective and have serious side effects. Conventional therapy of neuroblastoma includes the differentiation agents. Unlike chemo-radiotherapy, differentiation therapy shows minimal side effects on normal cells, because normal non-malignant cells are already differentiated. Keeping in view the limited toxicity of Withania somnifera (Ashwagandha), the current study was aimed to investigate the efficacy of Ashwagandha water extract (ASH-WEX) for anti-proliferative potential in neuroblastoma and its underlying signalling mechanisms. ASH-WEX significantly reduced cell proliferation and induced cell differentiation as indicated by morphological changes and NF200 expression in human IMR-32 neuroblastoma cells. The induction of differentiation was accompanied by HSP70 and mortalin induction as well as pancytoplasmic translocation of the mortalin in ASH-WEX treated cells. Furthermore, the ASH-WEX treatment lead to induction of neural cell adhesion molecule (NCAM) expression and reduction in its polysialylation, thus elucidating its anti-migratory potential, which was also supported by downregulation of MMP 2 and 9 activity. ASH-WEX treatment led to cell cycle arrest at G0/G1 phase and increase in early apoptotic population. Modulation of cell cycle marker Cyclin D1, anti-apoptotic marker bcl-xl and Akt-P provide evidence that ASH-WEX may prove to be a promising phytotherapeutic intervention in neuroblatoma related malignancies. PMID:23383150

Kataria, Hardeep; Wadhwa, Renu; Kaul, Sunil C.; Kaur, Gurcharan

2013-01-01

86

Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential  

PubMed Central

Although the therapeutic potential of mesenchymal stem cells (MSC) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of BM-MSC from adult donors. Microarray analysis showed that adult (a)BM-MSC expressing Nanog clustered close to Nanog-expressing neonatal cells. Nanog markedly upregulated genes involved in cell cycle, DNA replication and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of aBM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of aBM-MSC to a similar level as that of neonatal (n)BM-MSC. The effect of Nanog on contractility was mediated – at least in part - through activation of the TGF-? pathway by diffusible factors secreted in the conditioned medium of Nanog-expressing BM-MSC. Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on aBM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration. PMID:22949105

Han, Juhee; Mistriotis, Panagiotis; Lei, Pedro; Wang, Dan; Liu, Song; Andreadis, Stelios T.

2012-01-01

87

Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells.  

PubMed

Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all-trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APL patient and in NB4 cells, but not in normal BMC or PBMC. Therefore, we realized that RA potentiated ATRA-induced macrophage differentiation in APL cells. Further characterization of the induced macrophages showed that they exhibited morphological changes and were able to phagocytose and generate reactive oxygen species. Th also had typical expression of C-C chemokine receptor type 1 (CCR1), CCR2, and intercellular adhesion molecule-1 (ICAM-1). Moreover, the expression of CD11b(+) and CD14(+) cells depended on ERK-NF-?B axis activation. Together, these results indicate that RA potentiates ATRA-induced macrophage differentiation in APL cells. Thus, RA may play an important role as an appurtenant differentiation agent for functional macrophage differentiation in APL. Additionally, the differentiated macrophages might have a normal life span and, they could die. These data indicate that co-treatment with RA and ATRA has potential as an anti-leukemic therapy in APL. PMID:25481858

Heo, Sook-Kyoung; Noh, Eui-Kyu; Yoon, Dong-Joon; Jo, Jae-Cheol; Koh, SuJin; Baek, Jin Ho; Park, Jae-Hoo; Min, Young Joo; Kim, Hawk

2015-01-15

88

Differentiation of idiopathic Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and healthy controls using magnetization transfer imaging  

Microsoft Academic Search

The differentiation of multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from idiopathic Parkinson's disease (IPD) is difficult. Magnetization transfer imaging (MTI), a measure that correlates with myelination and axonal density, was employed in this study in the attempt to distinguish between these disorders. Measurements were carried out in 15 patients with IPD, 12 patients with MSA, 10 patients

Thomas Eckert; Michael Sailer; Joern Kaufmann; Christoph Schrader; Thomas Peschel; Nils Bodammer; Hans-Jochen Heinze; Mircea Ariel Schoenfeld

2004-01-01

89

Voxel based comparison of glucose metabolism in the differential diagnosis of the multiple system atrophy  

NASA Astrophysics Data System (ADS)

Multiple system atrophy (MSA) including striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA) is a group of heterogeneous degenerative neurological disorders, which differ from the idiopathic Parkinson"s disease (IPD) in certain clinical features. The differential diagnosis between IPD and MSA is difficult because of the common of signs and symptoms common. The purpose of this study was comparison of cerebral glucose metabolic differences of SND, OPCA and IPD. The 18F-FDG PET images of SND, OPCA and IPD patients were assessed by statistical pattern analysis using statistical parametric mapping (SPM) and image registration in order to determine the useful metabolic patterns. A total of 11 patients with MSA (5 SND: mean age 61.6+/-8.3 y, M/F 1/4; 6 OPCA: mean age 55.3+/-8.4 y, M/F 3/3), 8 patients (mean age 67.9 10.7y; M/F: 3/5) with IPD were enrolled in this study. All subjects and 22 age matched normal controls underwent 18F-FDG PET. Each of the SND, OPCA and IPD patients were individually compared with the normal control group using a two-sided t-test for SPM (P<0.05). The OPCA group showed significant hypometabolism in the cerebellum and pons compared to the control group, whereas in the patients with SND showed significant hypometabolism in the putamen. SPM also revealed pons, putamen hypometabolism in OPCA and SND patients compared with IPD patients. An assessment of the 18F-FDG PET images using the image registration and statistical analysis might be a useful adjunct to a clinical examination when making a differential diagnosis of Parkinsonism.

Juh, Rahyeong; Suh, Taesuk; Chung, Yongan; Yang, Dongwon

2005-04-01

90

The housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) regulates multiple developmental and metabolic pathways of murine embryonic stem cell neuronal differentiation.  

PubMed

The mechanisms by which mutations of the purinergic housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) cause the severe neurodevelopmental Lesch Nyhan Disease (LND) are poorly understood. The best recognized neural consequences of HPRT deficiency are defective basal ganglia expression of the neurotransmitter dopamine (DA) and aberrant DA neuronal function. We have reported that HPRT deficiency leads to dysregulated expression of multiple DA-related developmental functions and cellular signaling defects in a variety of HPRT-deficient cells, including human induced pluripotent stem (iPS) cells. We now describe results of gene expression studies during neuronal differentiation of HPRT-deficient murine ESD3 embryonic stem cells and report that HPRT knockdown causes a marked switch from neuronal to glial gene expression and dysregulates expression of Sox2 and its regulator, genes vital for stem cell pluripotency and for the neuronal/glial cell fate decision. In addition, HPRT deficiency dysregulates many cellular functions controlling cell cycle and proliferation mechanisms, RNA metabolism, DNA replication and repair, replication stress, lysosome function, membrane trafficking, signaling pathway for platelet activation (SPPA) multiple neurotransmission systems and sphingolipid, sulfur and glycan metabolism. We propose that the neural aberrations of HPRT deficiency result from combinatorial effects of these multi-system metabolic errors. Since some of these aberrations are also found in forms of Alzheimer's and Huntington's disease, we predict that some of these systems defects play similar neuropathogenic roles in diverse neurodevelopmental and neurodegenerative diseases in common and may therefore provide new experimental opportunities for clarifying pathogenesis and for devising new potential therapeutic targets in developmental and genetic disease. PMID:24130677

Kang, Tae Hyuk; Park, Yongjin; Bader, Joel S; Friedmann, Theodore

2013-01-01

91

The Housekeeping Gene Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) Regulates Multiple Developmental and Metabolic Pathways of Murine Embryonic Stem Cell Neuronal Differentiation  

PubMed Central

The mechanisms by which mutations of the purinergic housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) cause the severe neurodevelopmental Lesch Nyhan Disease (LND) are poorly understood. The best recognized neural consequences of HPRT deficiency are defective basal ganglia expression of the neurotransmitter dopamine (DA) and aberrant DA neuronal function. We have reported that HPRT deficiency leads to dysregulated expression of multiple DA-related developmental functions and cellular signaling defects in a variety of HPRT-deficient cells, including human induced pluripotent stem (iPS) cells. We now describe results of gene expression studies during neuronal differentiation of HPRT-deficient murine ESD3 embryonic stem cells and report that HPRT knockdown causes a marked switch from neuronal to glial gene expression and dysregulates expression of Sox2 and its regulator, genes vital for stem cell pluripotency and for the neuronal/glial cell fate decision. In addition, HPRT deficiency dysregulates many cellular functions controlling cell cycle and proliferation mechanisms, RNA metabolism, DNA replication and repair, replication stress, lysosome function, membrane trafficking, signaling pathway for platelet activation (SPPA) multiple neurotransmission systems and sphingolipid, sulfur and glycan metabolism. We propose that the neural aberrations of HPRT deficiency result from combinatorial effects of these multi-system metabolic errors. Since some of these aberrations are also found in forms of Alzheimer's and Huntington's disease, we predict that some of these systems defects play similar neuropathogenic roles in diverse neurodevelopmental and neurodegenerative diseases in common and may therefore provide new experimental opportunities for clarifying pathogenesis and for devising new potential therapeutic targets in developmental and genetic disease. PMID:24130677

Bader, Joel S.; Friedmann, Theodore

2013-01-01

92

Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis  

PubMed Central

Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis. PMID:22676575

2012-01-01

93

Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential  

PubMed Central

Pluripotency can be induced in somatic cells by overexpressing transcription factors, including POU class 5 homeobox 1 (OCT3/4), sex determining region Y-box 2 (SOX2), Krüppel-like factor 4 (KLF4), and myelocytomatosis oncogene (c-MYC). However, some induced pluripotent stem cells (iPSCs) exhibit defective differentiation and inappropriate maintenance of pluripotency features. Here we show that dynamic regulation of human endogenous retroviruses (HERVs) is important in the reprogramming process toward iPSCs, and in re-establishment of differentiation potential. During reprogramming, OCT3/4, SOX2, and KLF4 transiently hyperactivated LTR7s—the long-terminal repeats of HERV type-H (HERV-H)—to levels much higher than in embryonic stem cells by direct occupation of LTR7 sites genome-wide. Knocking down LTR7s or long intergenic non-protein coding RNA, regulator of reprogramming (lincRNA-RoR), a HERV-H–driven long noncoding RNA, early in reprogramming markedly reduced the efficiency of iPSC generation. KLF4 and LTR7 expression decreased to levels comparable with embryonic stem cells once reprogramming was complete, but failure to resuppress KLF4 and LTR7s resulted in defective differentiation. We also observed defective differentiation and LTR7 activation when iPSCs had forced expression of KLF4. However, when aberrantly expressed KLF4 or LTR7s were suppressed in defective iPSCs, normal differentiation was restored. Thus, a major mechanism by which OCT3/4, SOX2, and KLF4 promote human iPSC generation and reestablish potential for differentiation is by dynamically regulating HERV-H LTR7s. PMID:25097266

Ohnuki, Mari; Tanabe, Koji; Sutou, Kenta; Teramoto, Ito; Sawamura, Yuka; Narita, Megumi; Nakamura, Michiko; Tokunaga, Yumie; Nakamura, Masahiro; Watanabe, Akira; Yamanaka, Shinya; Takahashi, Kazutoshi

2014-01-01

94

Multiple lesions of the spleen: differential diagnosis of cystic and solid lesions.  

PubMed

Lesions in the spleen may be encountered in a variety of clinical settings ranging from asymptomatic patients to patients who are critically ill. Etiologies for multifocal splenic lesions include infectious and inflammatory processes, primary vascular and lymphoid neoplasms, metastatic disease, vascular processes, and systemic diseases. There is often overlap in the imaging appearance alone, so the clinical setting is very helpful in differential diagnosis. In the immunocompromised patient, multiple small splenic lesions usually represent disseminated fungal disease and microabscesses. The spleen is a relatively rare site for metastatic disease; patients with metastatic lesions in the spleen usually have disease in other sites as well. Breast, lung, ovary, melanoma, and colon cancer are common primary tumors that metastasize to the spleen. Vascular neoplasms of the spleen represent the majority of the nonhematologic/nonlymphoid neoplasms and commonly produce multifocal lesions. Splenic infarcts may be seen with localized processes such as portal hypertension or pancreatitis, or may arise from an embolic source. Radiologists should be aware of the spectrum of processes that may involve the spleen and the clinical context in which they occur. PMID:17048454

Kamaya, Aya; Weinstein, Stefanie; Desser, Terry S

2006-10-01

95

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

96

Fine Structure of Neurally Differentiated iPS Cells Generated from a Multiple Sclerosis (MS) Patient: A Case Study.  

PubMed

We compared the characteristics of neural cells derived from induced pluripotent stem (iPS) cells from a patient with multiple sclerosis versus neurally differentiated control iPS cells of a healthy individual. The iPS cells were differentiated toward the oligodendrocyte lineage using a four-step protocol established for the differentiation of embryonic stem cells. The resulting cell population was immunostained on day 112 of differentiation for the presence of oligodendrocytes and analyzed by transmission electron microscopy (TEM). Both patient and control samples resembled a mixed population of neural cells rather than oligodendroglia of high purity, including neural stem cell-like cells and possibly oligodendrocytes demonstrable by TEM. PMID:25335881

Herszfeld, Daniella; Payne, Natalie L; Sylvain, Aude; Sun, Guizhi; Bernard, Claude C; Clark, Joan; Sathananthan, Henry

2014-12-01

97

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

98

Multiscale renormalization group methods for effective potentials with multiple scalar fields  

NASA Astrophysics Data System (ADS)

Multiscale 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 and Weinberg method beyond the weak coupling limit. A model containing two interacting real scalar fields is used to illustrate multiscale RG methods and the multiscale RG functions of this model are calculated to one-loop order for the ? 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 a 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 trajectory that connects to this multiscale O (2 )-symmetric form of the effective potential. Extensions of these multiscale methods for effective potentials in models containing multiple scalars with O (M )×O (N ) symmetry are also discussed.

Steele, T. G.; Wang, Zhi-Wei; McKeon, D. G. C.

2014-11-01

99

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

100

Existence and regularity of multiple solutions for infinitely degenerate nonlinear elliptic equations with singular potential  

NASA Astrophysics Data System (ADS)

In this paper, we study the Dirichlet problem for a class of infinitely degenerate nonlinear elliptic equations with singular potential term. By using the logarithmic Sobolev inequality and Hardy's inequality, the existence and regularity of multiple nontrivial solutions have been proved.

Chen, Hua; Luo, Peng; Tian, Shuying

2014-11-01

101

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

102

Multiple Channel Detection of Steady-State Visual Evoked Potentials for Brain-Computer Interfaces  

Microsoft Academic Search

In this paper, novel methods for detecting steady-state visual evoked potentials using multiple electroencephalogram (EEG) signals are presented. The methods are tailored for brain-computer interfacing, where fast and accurate detection is of vital importance for achieving high information transfer rates. High detection accuracy using short time segments is obtained by finding combinations of electrode signals that cancel strong interference signals

Ola Friman; Ivan Volosyak; Axel Graser

2007-01-01

103

Osteonecrosis of the femoral head. Potential treatment with growth and differentiation factors.  

PubMed

Basic and clinical research have shown the efficacy of various cellular mediators (bone morphogenetic proteins, interleukins, angiogenic growth factors) in healing bone defects. The potential application of these growth and differentiation factors to other musculoskeletal conditions, including osteonecrosis of the femoral head, only recently has been explored. Osteonecrosis is a disease of unknown pathogenesis that usually progresses to hip joint destruction necessitating total hip arthroplasty. The pathology involves ischemic events followed by death of bone and marrow elements. A process of repair then is initiated, but unless the lesion is small (less than 15% of the femoral head involved), this repair process is usually ineffective. The net result is weakening of subchondral bone with subsequent collapse of the articular surface. Because the results of hip arthroplasty in patients with osteonecrosis are relatively poor, much focus has been on modalities aimed at femoral head preservation. The surgical alternatives may include core decompression, osteotomy, nonvascularized, and vascularized bone grafting, which might be enhanced with the use of growth and differentiation factors. At least three of these factors are potential candidates as therapeutic modalities: cytokines (such as interleukins, tumor necrosis factors, and signaling molecules such as fibroblast growth factors, platelet derived growth factors, insulinlike growth factors, and transforming growth factor betas), bone morphogenetic proteins, and angiogenic factors. Despite considerable effort, evaluation of these growth and differentiation factors has been hampered by the lack of an animal model that adequately simulates the pathology of osteonecrosis in humans. Therefore, investigators have attempted to model certain aspects of the disease process. Recently, several investigators have attempted to mimic osteonecrosis in the femoral head of large mammals by combinations of devascularization, freezing, osteotomy of the femoral neck, or creation of a head defect. Results from some of these studies have confirmed the potential for growth and differentiation factors to effect more rapid healing and filling of defects with biomechanically competent and viable bone. The application of this therapy shows promise, and clinical studies on efficacy and safety are ongoing. PMID:9917651

Mont, M A; Jones, L C; Einhorn, T A; Hungerford, D S; Reddi, A H

1998-10-01

104

Detection of Olfactory Dysfunction Using Olfactory Event Related Potentials in Young Patients with Multiple Sclerosis  

PubMed Central

Background Several studies reported olfactory dysfunction in patients with multiple sclerosis. The estimate of the incidence of olfactory deficits in multiple sclerosis is uncertain; this may arise from different testing methods that may be influenced by patients' response bias and clinical, demographic and cognitive features. Aims To evaluate objectively the olfactory function using Olfactory Event Related Potentials. Materials and Methods We tested the olfactory function of 30 patients with relapsing remitting multiple sclerosis (mean age of 36.03±6.96 years) and of 30 age, sex and smoking–habit matched healthy controls by using olfactory potentials. A selective and controlled stimulation of the olfactory system to elicit the olfactory event related potentials was achieved by a computer-controlled olfactometer linked directly with electroencephalograph. Relationships between olfactory potential results and patients' clinical characteristics, such as gender, disability status score, disease-modifying therapy, and disease duration, were evaluated. Results Seven of 30 patients did not show olfactory event related potentials. Sixteen of remaining 23 patients had a mean value of amplitude significantly lower than control group (p<0.01). The presence/absence of olfactory event related potentials was associated with dichotomous expanded disability status scale (p?=?0.0433), as well as inversely correlated with the disease duration (r?=??0.3641, p?=?0.0479). Conclusion Unbiased olfactory dysfunction of different severity found in multiple sclerosis patients suggests an organic impairment which could be related to neuroinflammatory and/or neurodegenerative processes of olfactory networks, supporting the recent findings on neurophysiopathology of disease. PMID:25047369

Caminiti, Fabrizia; De Salvo, Simona; De Cola, Maria Cristina; Russo, Margherita; Bramanti, Placido; Marino, Silvia; Ciurleo, Rosella

2014-01-01

105

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

106

A cost-effective differential mobility analyzer (cDMA) for multiple DMA column applications  

SciTech Connect

In aerosol research and applications, a differential mobility analyzer (DMA) is now considered the standard tool for sizing and classifying monodisperse particles in the sub-micrometer and nanometer size ranges. However, DMA application at the pilot or industrial production scale remains infeasible because of the low mass throughput. A simple way to scale up DMA operation is to use multiple DMA columns. The manufacture and maintenance costs of existing DMAs, however, limit such a scale-up. A cost-effective DMA column (named cDMA) has thus been developed in this work to address the above issue. To reduce its manufacturing cost, the prototype was constructed using parts requiring little machining. The cDMA column was also designed for easy maintenance and easy variation of the classification length for any application-specified size range. In this study, prototypes with two particle classification lengths, 1.75 and 4.50 cm, were constructed and their performance was experimentally evaluated at sheath-to-aerosol flowrate ratios of 5:1, 10:1, and 15:1 via the tandem DMA (TDMA) technique. It was concluded that both prototype cDMAs, operated at a sheath/aerosol flowrate ratio less than 15:1 and with a polydisperse aerosol flowrate of 1.0 lpm, achieved sizing resolution comparable to that offered by Nano-DMA. The longer cDMA had comparable transmission efficiency to that of Nano-DMA, and the shorter cDMA exceeded the performance of Nano-DMA. Hence, the cDMA with the shorter (1.75 cm) classification length is better suited for the characterization of macromolecular samples.

Mei, F.; Fu, H.; Chen, D.-R.

2011-05-04

107

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.

108

A Runge-Kutta type scheme for nonlinear stochastic partial differential equations with multiplicative trace class noise  

E-print Network

In this paper a new Runge-Kutta type scheme is introduced for nonlinear stochastic partial differential equations (SPDEs) with multiplicative trace class noise. The proposed scheme converges with respect to the computational effort with a higher order than the well-known linear implicit Euler scheme. In comparison to the infinite dimensional analog of Milstein type scheme recently proposed in [Jentzen & R\\"{o}ckner (2010); A Break of the Complexity of the Numerical Approximation of Nonlinear SPDEs with Multiplicative Noise, arXiv:1001.2751], our scheme has sightly less computational complexity due to avoiding the derivative of the diffusion function. The new scheme can be regarded as an infinite dimensional analog of Runge-Kutta method for finite dimensional stochastic ordinary differential equations (SODEs). Numerical examples are reported to support the theoretical results.

Wang, Xiaojie

2011-01-01

109

Multilineage differentiation potential of fibroblast-like stromal cells derived from human skin.  

PubMed

Adult stem cells that reside in adult tissues have been deemed to possess great potential for clinical application because of their capabilities of self-renewal and differentiation. However, the limitations such as infection risks and low isolation rate make the search for appropriate source to be continued. Here, we demonstrate isolation of progenitors from human foreskin tissue samples, which have fibroblast-like morphology and could be easily propagated for more than 50 passages. These foreskin-derived fibroblast-like stromal cells (FDSCs) expressed CD90, CD105, CD166, CD73, SH3, and SH4, which is similar to the immunophenotypes of human bone marrow-derived mesenchymal stem cells. In comparison with Hs68, the human fibroblast cell line, FDSCs are positive for CD105 and absent for CD54 expression. Further, FDSCs could be induced to differentiate into osteocytes, adipocytes, neural cells, smooth muscle cells, Schwann-like cells, and hepatocyte-like cells. Interestingly, when cultured in Dulbecco's modified Eagle's medium/F12 medium, FDSCs can form spheres with increased expression levels of fibronectin and vimentin. In conclusion, foreskin can serve as a valuable source of multipotent cells with the capabilities for endodermal, mesodermal, and ectodermal cells. Coupled with the advantages of their easy access, isolation, and propagation, these foreskin-derived stromal cells might be of potential use in future studies in stem cell differentiation and therapeutic application. PMID:20001268

Huang, Hsing-I; Chen, Shao-Kuan; Ling, Qing-Dong; Chien, Chih-Cheng; Liu, Hsiao-Tung; Chan, Shu-Hui

2010-05-01

110

ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells.  

PubMed

Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth. PMID:25101689

Szepesi, Áron; Matula, Zsolt; Szigeti, Anna; Várady, György; Szabó, Gyula; Uher, Ferenc; Sarkadi, Balázs; Német, Katalin

2015-01-15

111

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

112

Multiple-symbol double-differential detection based on least-squares and generalized-likelihood ratio criteria  

Microsoft Academic Search

Two algorithms for double-differential detection of multiple phase-shift keying modulation are proposed, based on a least-squares criterion and a generalized-likelihood ratio test, respectively. While both algorithms take advantage of the performance gain obtained by observing the received signal over an observation interval longer than that required for symbol-by-symbol detection, the former has the important advantage of reduced implementation complexity, whereas

Marvin K. Simon; Jianhua Liu; Petre Stoica; Jian Li

2004-01-01

113

Differential Effects of Multiplicity of Infection on Helicobacter pylori Induced Signaling Pathways and Interleukin8 Gene Transcription  

Microsoft Academic Search

Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling\\u000a pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity\\u000a of infection (MOI) independent

Birgit Ritter; Petra Kilian; Marc Rene Reboll; Klaus Resch; Johanna Kay DiStefano; Ronald Frank; Winfried Beil; Mahtab Nourbakhsh

2011-01-01

114

Simultaneous encoding of multiple potential reach directions in dorsal premotor cortex.  

PubMed

We present evidence that the primate brain can simultaneously generate discrete directional signals related to multiple alternative reaching actions before making a decision between them. A monkey performed a task in which the correct target for a reaching movement was specified during two consecutive instructed-delay periods. First, two potential targets were presented; and second, a nonspatial cue identified one of them as the correct movement target. During the first period, two directional signals coexisted in the activity of cells in dorsal premotor cortex (PMd), oriented toward the two potential targets. During the second period, one of these disappeared and the remaining signal predicted the monkey's response choice. These results suggest that, when faced with multiple salient opportunities for reaching, the primate brain performs sensorimotor transformations in parallel to begin planning several reaching movements simultaneously before selecting one for overt execution. PMID:11826082

Cisek, Paul; Kalaska, John F

2002-02-01

115

Determination of spent nuclear fuel assembly multiplication with the differential die-away self-interrogation instrument  

NASA Astrophysics Data System (ADS)

We present a novel method for determining the multiplication of a spent nuclear fuel assembly with a Differential Die-Away Self-Interrogation (DDSI) instrument. The signal, which is primarily created by thermal neutrons, is measured with four 3He detector banks surrounding a spent fuel assembly. The Rossi-alpha distribution (RAD) at early times reflects coincident events from single fissions as well as fission chains. Because of this fact, the early time domain contains information about both the fissile material and spontaneous fission material in the assembly being measured. A single exponential function fit to the early time domain of the RAD has a die-away time proportional to the spent fuel assembly (SFA) multiplication. This correlation was tested by simulating assay of 44 different SFAs with the DDSI instrument. The SFA multiplication was determined with a variance of 0.7%.

Kaplan, Alexis C.; Henzl, Vladimir; Menlove, Howard O.; Swinhoe, Martyn T.; Belian, Anthony P.; Flaska, Marek; Pozzi, Sara A.

2014-09-01

116

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

117

A Monte Carlo method for chemical potential determination in single and multiple occupancy crystals  

E-print Network

We describe a Monte Carlo scheme which, in a single simulation, yields a measurement of the chemical potential of a crystalline solid. Within the isobaric ensemble, this immediately provides an estimate of the system free energy, with statistical uncertainties that are determined precisely and transparently. An extension to multiple occupancy ("cluster") solids permits the direct determination of the cluster chemical potential and hence the equilibrium conditions. We apply the method to a model exhibiting cluster crystalline phases, where we find evidence for an infinite cascade of critical points terminating coexistence between crystals of differing site occupancies.

Nigel B. Wilding; Peter Sollich

2012-09-14

118

Multiple secretoglobin 1A1 genes are differentially expressed in horses  

PubMed Central

Background Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The SCGB1A1 gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple SCGB1A1 gene copies. Non-ciliated lung epithelial cells produce SCGB 1A1 during inhalation of noxious substances to counter airway inflammation. Airway fluid and lung tissue of horses with recurrent airway obstruction (RAO), a chronic inflammatory lung disease affecting mature horses similar to environmentally induced asthma of humans, have reduced total SCGB 1A1 concentration. Herein, we investigated whether horses have distinct expressed SCGB1A1 genes; whether the transcripts are differentially expressed in tissues and in inflammatory lung disease; and whether there is cell specific protein expression in tissues. Results We identified three SCGB1A1 gene copies on equine chromosome 12, contained within a 512-kilobase region. Bioinformatic analysis showed that SCGB1A1 genes differ from each other by 8 to 10 nucleotides, and that they code for different proteins. Transcripts were detected for SCGB1A1 and SCGB1A1A, but not for SCGB1A1P. The SCGB1A1P gene had most inter-individual variability and contained a non-sense mutation in many animals, suggesting that SCGB1A1P has evolved into a pseudogene. Analysis of SCGB1A1 and SCGB1A1A sequences by endpoint-limiting dilution PCR identified a consistent difference affecting 3?bp within exon 2, which served as a gene-specific “signature”. Assessment of gene- and organ-specific expression by semiquantitative RT-PCR of 33 tissues showed strong expression of SCGB1A1 and SCGB1A1A in lung, uterus, Fallopian tube and mammary gland, which correlated with detection of SCGB 1A1 protein by immunohistochemistry. Significantly altered expression of the ratio of SCGB1A1A to SCGB1A1 was detected in RAO-affected animals compared to controls, suggesting different roles for SCGB 1A1 and SCGB 1A1A in this inflammatory condition. Conclusions This is the first report of three SCGB1A1 genes in a mammal. The two expressed genes code for proteins predicted to differ in function. Alterations in the gene expression ratio in RAO suggest cell and tissue specific regulation and functions. These findings may be important for understanding of lung and reproductive conditions. PMID:23253434

2012-01-01

119

Aqueous Ethanolic Extract of Tinospora cordifolia as a Potential Candidate for Differentiation Based Therapy of Glioblastomas  

PubMed Central

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

120

Resolution of multiple sheet-type structures in self-potential measurement  

NASA Astrophysics Data System (ADS)

The resolution of self-potential anomalies due to closely spaced multiple sheet-like bodies by the potential difference and potential gradient is studied in this paper. Self-potential anomalies due to several synthetic models were inverted through a very fast simulated annealing (VFSA) global optimization. Increase in depth to the top, polarization constant and depth extent of the body decreases resolution at a particular target separation. It has been observed that depth to the top and separation between two targets play an important role in the resolution. Vertical sheets at equal depth can be resolved in the potential difference measurement only if they are separated by at least four times their depth, while they can be resolved in the gradient method, if they are separated by twice the depth. Resolution using potential difference becomes more difficult for dipping sheets, although the potential gradient method can resolve them efficiently. Efficacy of potential gradient data in the inversion is demonstrated in the study using synthetic data as well as field measurement from South Purulia Shear Zone related with uranium investigation.

Biswas, Arkoprovo; Sharma, Shashi Prakash

2014-06-01

121

Multiplication  

NSDL National Science Digital Library

Here are some fun games to make practicing multiplication fun!!! Before you start the fun... click Multiplication Tables to review what you already know! Can you figure out the Multiplication Hidden Picture... you better know your math skills first or the picture will burst! It\\'s times to have a \\"blast\\"... Blow me away with theMultiplication Tunnel Blaster Now your ready to join the team! Show me ...

Walker, Ms.

2008-03-26

122

Epithelial-mesenchymal transition-derived cells exhibit multilineage differentiation potential similar to mesenchymal stem cells.  

PubMed

The epithelial-to-mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows breast epithelial cells with stem cell traits. In this report, we have further characterized the EMT-derived cells and shown that these cells are similar to mesenchymal stem cells (MSCs) with the capacity to differentiate into multiple tissue lineages. For this purpose, we induced EMT by ectopic expression of Twist, Snail, or transforming growth factor-beta in immortalized human mammary epithelial cells. We found that the EMT-derived cells and MSCs share many properties including the antigenic profile typical of MSCs, that is, CD44(+), CD24(-), and CD45(-). Conversely, MSCs express EMT-associated genes, such as Twist, Snail, and mesenchyme forkhead 1 (FOXC2). Interestingly, CD140b (platelet-derived growth factor receptor-beta), a marker for naive MSCs, is exclusively expressed in EMT-derived cells and not in their epithelial counterparts. Moreover, functional analyses revealed that EMT-derived cells but not the control cells can differentiate into alizarin red S-positive mature osteoblasts, oil red O-positive adipocytes and alcian blue-positive chondrocytes similar to MSCs. We also observed that EMT-derived cells but not the control cells invade and migrate towards MDA-MB-231 breast cancer cells similar to MSCs. In vivo wound homing assays in nude mice revealed that the EMT-derived cells home to wound sites similar to MSCs. In conclusion, we have demonstrated that the EMT-derived cells are similar to MSCs in gene expression, multilineage differentiation, and ability to migrate towards tumor cells and wound sites. PMID:20572012

Battula, Venkata Lokesh; Evans, Kurt William; Hollier, Brett George; Shi, Yuexi; Marini, Frank C; Ayyanan, Ayyakkannu; Wang, Rui-Yu; Brisken, Cathrin; Guerra, Rudy; Andreeff, Michael; Mani, Sendurai A

2010-08-01

123

Methodology for Estimating Solar Potential on Multiple Building Rooftops for Photovoltaic Systems  

SciTech Connect

In this paper, a methodology for estimating solar potential on multiple building rooftops is presented. The objective of this methodology is to estimate the daily or monthly solar radiation potential on individual buildings in a city/region using Light Detection and Ranging (LiDAR) data and a geographic information system (GIS) approach. Conceptually, the methodology is based on the upward-looking hemispherical viewshed algorithm, but applied using an area-based modeling approach. The methodology considers input parameters, such as surface orientation, shadowing effect, elevation, and atmospheric conditions, that influence solar intensity on the earth s surface. The methodology has been implemented for some 212,000 buildings in Knox County, Tennessee, USA. Based on the results obtained, the methodology seems to be adequate for estimating solar radiation on multiple building rooftops. The use of LiDAR data improves the radiation potential estimates in terms of the model predictive error and the spatial pattern of the model outputs. This methodology could help cities/regions interested in sustainable projects to quickly identify buildings with higher potentials for roof-mounted photovoltaic systems.

Kodysh, Jeffrey B [ORNL; Omitaomu, Olufemi A [ORNL; Bhaduri, Budhendra L [ORNL; Neish, Bradley S [ORNL

2013-01-01

124

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

125

Multiple periodic solutions for system of first-order differential equation  

Microsoft Academic Search

Sufficient conditions have been obtained for the existence of at least two non-negative periodic solutions to a system of first-order nonlinear functional differential equations. Applications to some ecological models are given.

Seshadev Padhi; Smita Pati

2009-01-01

126

Inductance Compensation of Multiple Capacitors With Application to Common- and Differential-Mode Filters  

E-print Network

Capacitor parasitic inductance often limits the high-frequency performance of electromagnetic interference (EMI) filters in both common-mode (CM) and differential-mode (DM) filtering domains. However, these limitations can ...

Pierquet, Brandon J.

127

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

128

Smart SUDS: recognising the multiple-benefit potential of sustainable surface water management systems.  

PubMed

How can we make sustainable urban drainage systems (SUDS) smart? SUDS help us to manage surface water runoff from urban environments but they are capable of delivering much more. This paper looks beyond the water quantity and quality improvement functions of SUDS and investigates the multiple benefits that can be gained by implementing smart SUDS solutions. This work provides a new perspective, using methodologies not normally associated with SUDS research, to determine multiple benefits. The outputs of the work can potentially assist decision-makers, designer and planners in recognising the potential for multiple benefits that can be delivered by SUDS. The ecosystem services (ES) associated with a large redevelopment in Dundee, Scotland, UK, are identified and a public perception study together with public participatory geographical information system (PPGIS) methods was used to confirm the goods and benefits of the SUDS. The paper presents findings on the public perception of SUDS as they provide cultural benefits such as recreation, aesthetics and biodiversity. The results show that greenspace is important when choosing a location, and willingness to pay for greenspace is high in this area. This paper concludes that SUDS provide multi-functional benefits in relation to the ES, thereby justifying the cachet of being termed Smart SUDS. PMID:25633948

Jose, Roshni; Wade, Rebecca; Jefferies, Chris

2015-01-01

129

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

130

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

131

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.

132

Differentiation  

NSDL National Science Digital Library

In the five parts of this video, we define the derivative and then build a cribsheet of rules for expressing the slopes of simple functions and combinations of functions. These include the power rule, the chain rule, the product and quotient rules, and the rules for differentiating sinusoidal functions.

2013-06-21

133

Selected Extracellular microRNA as Potential Biomarkers of Multiple Sclerosis Activity-Preliminary Study.  

PubMed

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90 % of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNA-let-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke(1). Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNA-let-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers' instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose the disease and assess its severity and the efficacy of treatment. The difference in the expression of has-miR-let-7a in the remission group and the control group was statistically significant (p?=?0.002). Similarly, the expression of miRNA-648a in patients in remission was significantly different from the expression in the control group (p?=?0.02). Analysis of the correlation between the expression of miRNA-92a and the severity of the disease as measured by the EDSS scale in patients undergoing relapse showed significant negative linear correlation (r?=?-0.54, p?=?0.01). Higher miR-648a expression correlated with more frequent flare-ups in the joint group of patients in remission and relapse (p?=?0.03). This study is one of the few that demonstrate significantly changed expression of selected extracellular miRNA in plasma of MS patients and correlate those findings with clinical parameters. These observations may suggest that some miRNA subsets may be potential biomarkers for

Kacperska, Magdalena Justyna; Jastrzebski, Karol; Tomasik, Bartlomiej; Walenczak, Jakub; Konarska-Krol, Maria; Glabinski, Andrzej

2014-12-10

134

Motor evoked potentials from the pelvic floor in patients with multiple sclerosis.  

PubMed

The use of motor evoked potentials (MEPs) to study the integrity of pelvic floor motor innervation is poorly described in the literature. This study evaluated the clinical use of pelvic floor MEPs in 16 women with multiple sclerosis. Lower urinary tract dysfunction was assessed with urodynamic investigations. Transcutaneous magnetic stimulation was applied over the motor cortex and spinal roots, and MEPs were recorded from the puborectalis, the external urethral sphincter, and the abductor hallucis muscles. In many patients, responses from the pelvic floor muscles could not be evoked, and central motor conduction times for the puborectalis motor pathways could only be calculated in 56%. There was a poor correlation of abnormal conduction to lower urinary tract dysfunction. It is concluded, that unevokable responses from pelvic floor muscles in a patient with multiple sclerosis should be interpreted with care, and that pelvic floor MEPs have a limited clinical value in the investigation of suspected demyelinating disease. PMID:12640072

Brostrom, S; Frederiksen, J L; Jennum, P; Lose, G

2003-04-01

135

Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells  

PubMed Central

Human mesenchymal stem cells (hMSCs) remodel or regenerate various tissues through several mechanisms. Here, we identified the hMSC-secreted protein SCRG1 and its receptor BST1 as a positive regulator of self-renewal, migration, and osteogenic differentiation. SCRG1 and BST1 gene expression decreased during osteogenic differentiation of hMSCs. Intriguingly, SCRG1 maintained stem cell marker expression (Oct-4 and CD271/LNGFR) and the potentials of self-renewal, migration, and osteogenic differentiation, even at high passage numbers. Thus, the novel SCRG1/BST1 axis determines the fate of hMSCs by regulating their kinetic and differentiation potentials. Our findings provide a new perspective on methods for ex vivo expansion of hMSCs that maintain native stem cell potentials for bone-forming cell therapy. PMID:24413464

Aomatsu, Emiko; Takahashi, Noriko; Sawada, Shunsuke; Okubo, Naoto; Hasegawa, Tomokazu; Taira, Masayuki; Miura, Hiroyuki; Ishisaki, Akira; Chosa, Naoyuki

2014-01-01

136

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. PMID:25436230

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

2014-01-01

137

A path integral method for coarse-graining noise in stochastic differential equations with multiple time scales  

NASA Astrophysics Data System (ADS)

We present a new path integral method to analyze stochastically perturbed ordinary differential equations with multiple time scales. The objective of this method is to derive from the original system a new stochastic differential equation describing the system’s evolution on slow time scales. For this purpose, we start from the corresponding path integral representation of the stochastic system and apply a multi-scale expansion to the associated path integral kernel of the corresponding Lagrangian. As a concrete example, we apply this expansion to a system that arises in the study of random dispersion fluctuations in dispersion-managed fiber-optic communications. Moreover, we show that, for this particular example, the new path integration method yields the same result at leading order as an asymptotic expansion of the associated Fokker-Planck equation.

Schäfer, Tobias; Moore, Richard O.

2011-01-01

138

Differential effects of stress on a murie model of multiple sclerosis.  

E-print Network

Multiple sclerosis (MS) is a demyelinating autoimmune disease that affects the central nervous system (CNS) in humans. Several studies have shown a strong correlation between stressful events and the onset and exacerbation of MS in patients. Based...

Heibel, Jessica

2011-08-08

139

Multiple genotypic aberrances associate to terminal differentiation-deficiency of an oral squamous cell carcinoma in serum-free culture.  

PubMed

Oral squamous cell carcinoma (OSCC) lines proliferative in the serum-free conditions devised for normal oral keratinocytes (NOK) are virtually absent, complicating studies of carcinogenesis. A tongue squamous cell carcinoma generated under conditions for normal cell culture an apparently immortal line (termed LK0412) that has undergone >or=200 population doublings from over a year in culture. LK0412 exhibited epithelial morphology, intermediate filaments, desmosomes, and cytokeratin. Soft agar growth and tumorigenicity in athymic nude mice indicated the malignant phenotype. Compared with NOK, LK0412 exhibited increased indices for proliferation and apoptosis, and a decreased terminal differentiation index. Fetal bovine serum inhibited growth and increased apoptosis but failed to induce terminal differentiation of LK0412; the latter outcome differed clearly from that in NOK. Gene ontology assessment of transcript profiles implicated multiple alterations in biological processes, molecular functions, and cellular components in LK0412. Genetic changes, some that were confirmed to the protein level, included previously proposed OSCC markers, i.e., BAX, CDC2, and TP53, as well as multiple cancer-associated genes not considered for OSCC, e.g., BST2, CRIP1, ISG15, KLRC1, NEDD9, NNMT, and TWIST1. Elevation of p53 protein agreed with a missense mutation detectable in both the LK0412 line and the original tumor specimen. Moderate differentiation characterized the original tumor as well as tumors generated from inoculation of LK0412 in mice. Overall, the results suggest that the LK0412 cell line represent a subgroup of OSCC with unique genomic and phenotypic profiles. LK0412 should be useful to exploration of OSCC development, particularly the deregulated growth and differentiation responsiveness to serum factors. PMID:18452551

Roberg, Karin; Ceder, Rebecca; Farnebo, Lovisa; Norberg-Spaak, Lena; Grafström, Roland C

2008-10-01

140

Novel Multiple-Valued Logic Design Using BiCMOS-Based Negative Differential Resistance Circuit Biased by Two Current Sources  

NASA Astrophysics Data System (ADS)

The paper demonstrates a novel multiple-valued logic (MVL) design using a three-peak negative differential resistance (NDR) circuit, which is made of several Si-based metal-oxide-semiconductor field-effect-transistor (MOS) and SiGe-based heterojunction bipolar transistor (HBT) devices. Specifically, this three-peak NDR circuit is biased by two switch-controlled current sources. Compared to the traditional MVL circuit made of resonant tunneling diode (RTD), this multiple-peak MOS-HBT-NDR circuit has two major advantages. One is that the fabrication of this circuit can be fully implemented by the standard BiCMOS process without the need for molecular-beam epitaxy system. Another is that we can obtain more logic states than the RTD-based MVL design. In measuring, we can obtain eight logic states at the output according to a sequent control of two current sources on and off in order.

Gan, Kwang-Jow; Liang, Dong-Shong; Chen, Yan-Wun

141

Negative mobility and multiple current reversals induced by colored thermal fluctuation in an asymmetric periodic potential  

NASA Astrophysics Data System (ADS)

The phenomena of negative mobility (NM) and multiple current reversals (MCR) are investigated numerically in an asymmetric periodic potential with a Gaussian colored noise under the influence of a periodic driving and a constant bias. Two cases have been considered: the case of noise-induced normal transport and the case of noise-induced anomalous transport. The results indicate: (1) within tailored parameter regimes, a robust and wide range of NM can be obtained for a fixed regime of correlation time; (2) nonzero correlation time can induce and diminish MCR; (3) the asymmetry can induce and significantly facilitate the anomalous transport of inertial Brownian particle.

Yang, B.; Long, F.; Mei, D. C.

2012-12-01

142

Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis  

E-print Network

REVIEW Open Access Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis Sangita Biswas1,2, Stephen H Benedict3, Sharon G Lynch4 and Steven M LeVine1* Abstract... in an increased gastric pH. A prolonged elevation in gastric pH can lead to increased levels of bacteria in the sto- mach and small intestine, which in theory could aggra- vate inflammation in patients with MS. In this review, we will compare the immunological...

Biswas, Sangita; Benedict, Stephen H.; Lynch, Sharon G.; LeVine, Steven M.

2012-06-07

143

Differentiation potential of stem cells from human dental origin - promise for tissue engineering.  

PubMed

Recent studies have revealed the existence of stem cells in various human tissues including dental structures. We aimed to establish primary cell cultures from human dental pulp and periodontal ligament, to identify multipotential adult stem cells in these cultures, and to study the differentiation capacity of these cells to osteogenic and to neuronal fates. Dental pulp and the periodontal ligament were isolated from extracted human wisdom teeth. The extracellular matrix was enzymatically degraded to obtain isolated cells for culturing. Both dental pulp and periodontal ligament derived cultures showed high proliferative capacity and contained a cell population expressing the STRO-1 mesenchymal stem cell marker. Osteogenic induction by pharmacological stimulation resulted in mineralized differentiation as shown by Alizarin red staining in both cultures. When already described standard neurodifferentiation protocols were used, cultures exhibited only transient neurodifferentiation followed by either redifferentiation into a fibroblast-like phenotype or massive cell death. Our new three-step neurodifferentiation protocol consisting of (1) epigenetic reprogramming, then (2) simultaneous PKC/PKA activation, followed by (3) incubation in a neurotrophic medium resulted in robust neurodifferentiation in both pulp and periodontal ligament cultures shown by cell morphology, immunocytochemistry and real time PCR for vimentin and neuron-specific enolase. In conclusion, we report the isolation, culture and characterization of stem cell containing cultures from both human dental pulp and periodontal ligament. Furthermore, our data clearly show that both cultures differentiate into mineralized cells or to a neuronal fate in response to appropriate pharmacological stimuli. Therefore, these cells have high potential to serve as resources for tissue engineering not only for dental or bone reconstruction, but also for neuroregenerative treatments. PMID:20388961

Kadar, K; Kiraly, M; Porcsalmy, B; Molnar, B; Racz, G Z; Blazsek, J; Kallo, K; Szabo, E L; Gera, I; Gerber, G; Varga, G

2009-12-01

144

Evolutionary analysis of the MIXTA gene family highlights potential targets for the study of cellular differentiation.  

PubMed

Differentiated epidermal cells such as trichomes and conical cells perform numerous essential functions in plant biology and are important for our understanding of developmental patterning and cell shape regulation. Many are also commercially significant, such as cotton fibers and trichomes that secrete pharmaceutically useful or herbivore-deterring compounds. Here, we focus on the phylogeny and evolution of the subgroup 9 R2R3 MYB gene transcription factors, which include the MIXTA gene, and that are important for the specification and regulation of plant cellular differentiation. We have sequenced 49 subgroup 9 R2R3 MYB genes from key experimental taxa and combined these sequences with those identified by an exhaustive bioinformatic search, to compile a data set of 223 subgroup 9 R2R3 MYB genes. Our phylogenetic analyses demonstrate, for the first time, the complex evolutionary history of the subgroup 9 R2R3 MYB genes. A duplication event is inferred before the origin of seed plants giving rise to two major gene lineages, here termed SBG9-A and SBG9-B. The evolutionary conservation of the SBG9-B gene lineage has not been previously recognized and its role in cellular differentiation is unknown, thus an entire clade of potential candidate genes for epidermal cell regulation remains to be explored. Using a heterologous transformation bioassay, we provide functional data that implicate members of the SBG9-B lineage in the specification of epidermal projections. Furthermore, we reveal numerous putative duplication events in both SBG9-A and SBG9-B lineages, resolving uncertainty about orthology and paralogy among the subgroup 9 R2R3 MYB genes. Finally, we provide a robust framework over which to interpret existing functional data and to direct ongoing comparative genetic research into the evolution of plant cellular diversity. PMID:23188591

Brockington, Samuel F; Alvarez-Fernandez, Ruben; Landis, Jacob B; Alcorn, Katrina; Walker, Rachel H; Thomas, Murphy M; Hileman, Lena C; Glover, Beverley J

2013-03-01

145

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

146

Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials.  

PubMed

Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells. PMID:25591783

Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S

2015-01-01

147

Preexisting high frequencies of memory CD8+ T cells favors rapid memory differentiation and preservation of proliferative potential upon boosting  

PubMed Central

Summary Memory CD8+ T cell quantity and quality determine protective efficacy against reinfection. Heterologous prime boost vaccination minimizes contraction of anamnestic effectors and maximizes memory CD8+ T cell quantity, but reportedly erodes proliferative potential and protective efficacy. This study exploited heterologous prime boost vaccination to discover parameters regulating effector CD8+ T cell contraction and memory differentiation. When abundant memory T cells were established, boosting induced only 5-8 cell divisions, unusually rapid memory T cell differentiation as measured by phenotype and mitochondrial bioenergetic function, long-lived survival of 50% of effector T cells, and preservation of proliferative potential. Conversely, boosting in situations of low memory CD8+ T cell frequencies induced many cell divisions, increased contraction of effector cells, and caused senescence, low mitochondrial membrane potential, and poorly protective memory. Thus, anamnestic memory T cell differentiation is flexible, and abundant quantity can be achieved while maximizing protective efficacy and preserving proliferative potential. PMID:23890070

Fraser, Kathryn A.; Schenkel, Jason M.; Jameson, Stephen C.; Vezys, Vaiva; Masopust, David

2014-01-01

148

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

149

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.

150

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

151

The potential of block copolymer's directed self-assembly for contact hole shrink and contact multiplication  

NASA Astrophysics Data System (ADS)

The goal of this paper is to investigate the potential of Directed Self-Assembly (DSA) to address contact via level patterning, by either Critical Dimension (CD) shrink or contact multiplication. Using the 300mm pilot line available in LETI and Arkema materials, our approach is based on the graphoepitaxy of PS-b- PMMA block copolymers (BCP). The process consists in the following steps: a) the lithography of guiding patterns, b) the DSA of block copolymers and PMMA removal and finally c) the transfer of PS patterns into the under-layer by plasma etching. Several integration schemes using 193nm dry lithography are evaluated: negative tone development (NTD) resists, a tri-layer approach, frozen resists, etc. The advantages and limitations of each approach are reported. Furthermore, the impact of the BCP on the final patterns characteristics is investigated by tuning different parameters such as the molecular weight of the polymeric constituents and the interaction with the substrate. The optimization of the self-assembly process parameters in terms of film thickness or bake (temperature and time) is also reported. Finally, the transfer capabilities of the PS nanostructures in bulk silicon substrate by using plasma-etching are detailed. These results show that DSA has a high potential to be integrated directly into the conventional CMOS lithography process in order to achieve high-resolution contact holes. Furthermore, in order to prevent design restrictions, this approach may be extended to more complex structures with multiple contacts and nonhexagonal symmetries.

Tiron, R.; Gharbi, A.; Argoud, M.; Chevalier, X.; Belledent, J.; Pimmenta Barros, P.; Servin, I.; Navarro, C.; Cunge, G.; Barnola, S.; Pain, L.; Asai, M.; Pieczulewski, C.

2013-03-01

152

Multiple polymerase chain reaction markers for the differentiation of canine cutaneous peripheral nerve sheath tumours versus canine fibrosarcomas.  

PubMed

Currently canine fibrosarcomas and peripheral nerve sheath tumours (PNSTs) are differentiated by their histopathological phenotype. Preliminary global transcriptomic analysis has identified genes with significant differential expression in both tumour types that may act as potential tumour markers. The aim of the present study was to establish reverse transcriptase polymerase chain reaction (RT-PCR) assays for the differentiation of formalin-fixed and paraffin wax-embedded tumours of both types. Fifty histologically well-defined examples of canine fibrosarcomas and PNSTs were characterized immunohistochemically for the expression of S100, laminin and PGP 9.5. RT-PCR assays for the potential fibrosarcoma markers FHL2-Ex4 and FHL2-Ex9 and the PNST markers GLI1 and CLEC3B were established and tested for their specificity and sensitivity to differentiate fibrosarcomas and PNSTs by their mRNA expression. Immunohistochemical analysis challenged the value of S100, laminin and PGP 9.5 for the diagnosis of PNSTs, since both PNSTs and fibrosarcomas showed similar expression of these proteins. In contrast, a combination of the markers GLI1 and CLEC3B differentiated PNSTs from fibrosarcomas with a sensitivity of 89% and a specificity of 87%. The proposed fibrosarcoma markers FHL2-Ex4 and FHL2-Ex9 failed to separate PNSTs and fibrosarcomas (sensitivity 50%, specificity 88%). The failure of these markers to unequivocally separate fibrosarcomas and PNSTs raises questions as to whether histologically uniform PNSTs are less uniform at the molecular level than expected or if both tumour types, despite their different morphology, are more closely related in terms of their histogenesis than previously thought. PMID:24650889

Meyer, A; Klopfleisch, R

2014-01-01

153

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

154

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

155

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

156

Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis  

Microsoft Academic Search

. Neurological manifestations of gastrointestinal disorders are described, with particular reference to those resembling multiple sclerosis (MS) on clinical or MRI grounds. Patients with celiac disease can present cerebellar ataxia, progressive myoclonic ataxia, myelopathy, or cerebral, brainstem and peripheral nerve involvement. Antigliadin antibodies can be found in subjects with neurological dysfunction of unknown cause, particularly in sporadic cerebellar ataxia (\\

A. Ghezzi; M. Zaffaroni

2001-01-01

157

Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis  

Microsoft Academic Search

Late onset multiple sclerosis (LOMS), defined as the first presentation of clinical symptoms in patients over 50, is not a rare phenomenon as previously thought, since the prevalence ranges between 4% and 9.6% in different studies. The course of the disease is often primary progressive and pyramidal or cerebellar involvement is observed in 60%–70% of the patients at presentation. LOMS

V. Martinelli; M. Rodegher; L. Moiola; G. Comi

2004-01-01

158

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

2014-11-19

159

Identification of circulating microRNAs for the differential diagnosis of Parkinson's disease and Multiple System Atrophy  

PubMed Central

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder which may be misdiagnosed with atypical conditions such as Multiple System Atrophy (MSA), due to overlapping clinical features. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in post-transcriptional gene regulation. We hypothesized that identification of a distinct set of circulating miRNAs (cmiRNAs) could distinguish patients affected by PD from MSA and healthy individuals. Results. Using TaqMan Low Density Array technology, we analyzed 754 miRNAs and found 9 cmiRNAs differentially expressed in PD and MSA patients compared to healthy controls. We also validated a set of 4 differentially expressed cmiRNAs in PD and MSA patients vs. controls. More specifically, miR-339-5p was downregulated, whereas miR-223*, miR-324-3p, and mir-24 were upregulated in both diseases. We found cmiRNAs specifically deregulated in PD (downregulation of miR-30c and miR-148b) and in MSA (upregulation of miR-148b). Finally, comparing MSA and PD, we identified 3 upregulated cmiRNAs in MSA serum (miR-24, miR-34b, miR-148b). Conclusions. Our results suggest that cmiRNA signatures discriminate PD from MSA patients and healthy controls and may be considered specific, non-invasive biomarkers for differential diagnosis. PMID:24959119

Vallelunga, Annamaria; Ragusa, Marco; Di Mauro, Stefania; Iannitti, Tommaso; Pilleri, Manuela; Biundo, Roberta; Weis, Luca; Di Pietro, Cinzia; De Iuliis, Angela; Nicoletti, Alessandra; Zappia, Mario; Purrello, Michele; Antonini, Angelo

2014-01-01

160

SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation.  

PubMed

Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation. PMID:20522714

Ahlfors, Helena; Limaye, Amita; Elo, Laura L; Tuomela, Soile; Burute, Mithila; Gottimukkala, Kamal Vishnu P; Notani, Dimple; Rasool, Omid; Galande, Sanjeev; Lahesmaa, Riitta

2010-09-01

161

SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation  

PubMed Central

Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation. PMID:20522714

Ahlfors, Helena; Limaye, Amita; Elo, Laura L.; Tuomela, Soile; Burute, Mithila; Gottimukkala, Kamal Vishnu P.; Notani, Dimple; Rasool, Omid

2010-01-01

162

Percutaneous method for single-catheter multiple monophasic action potential recordings during magnetocardiographic mapping in spontaneously breathing rodents.  

PubMed

To test the feasibility of a novel method to combine magnetocardiographic (MCG) estimate of ventricular repolarization (VR) and multiple monophasic action potential (MultiMAP) recording in spontaneously breathing rodents with percutaneous sub-xyphoid epicardial placement of a MCG-compatible amagnetic catheter (AC), ten Wistar rats (WRs) and ten guinea pigs (GPs) were studied. Under fluoroscopic control, the AC was moved until four stable MAPs were recorded (fixed inter-electrode distance of 1.2 mm). 36-channel DC-SQUID (sensitivity 20 fT Hz(-½)) were used for MCG mapping. MAPs, differentially amplified (BW: DC-500 Hz), were digitized at 1 kHz. AC pacing provided local ventricular effective refractory period (VERP) estimate. MAP duration (MAPd) was measured at 50% and 90% levels of repolarization. Simultaneous MCG mapping and MultiMAP recording were successful in all animals. Average MAPd50% and MAPd90% were shorter in WRs than in GPs (26.4 ± 2.9 ms versus 110.6 ± 14.3 ms and 60.7 ± 5.4 ms versus 127.7 ± 15.3 ms, respectively). VERP was 51 ± 4.8 ms in WRs and 108.4 ± 12.9 ms in GPs, respectively. The MAP amplitude was 16.9 ± 4.5 in WRs and 16.2 ± 4.2 in GPs. MAP and MCG parameters of VR were in good agreement. All animals survived the procedure. Two also survived a second invasive study; one was followed up until natural death at 52 months. Percutaneous MultiMAP recording is minimally invasive, usually avoids animal sacrifice, is compatible with simultaneous surface MCG mapping and might be used for experimental validation of MCG VR abnormality, to study the arrhythmogenic potential of new drugs and/or animal models of ventricular arrhythmias. PMID:22373565

Brisinda, Donatella; Sorbo, Anna Rita; Venuti, Angela; Fenici, Riccardo

2012-03-01

163

Engineering spatial control of multiple differentiation fates within a stem cell population  

Microsoft Academic Search

The capability to engineer microenvironmental cues to direct a stem cell population toward multiple fates, simultaneously, in spatially defined regions is important for understanding the maintenance and repair of multi-tissue units. We have previously developed an inkjet-based bioprinter to create patterns of solid-phase growth factors (GFs) immobilized to an extracellular matrix (ECM) substrate, and applied this approach to drive muscle-derived

Elmer D. F. Ker; Bur Chu; Julie A. Phillippi; Burhan Gharaibeh; Johnny Huard; Lee E. Weiss; Phil G. Campbell

2011-01-01

164

Stochastic Shell Model for Turbulent Mixing of Multiple Scalars with Mean Gradients and Differential Diffusion  

Microsoft Academic Search

In this paper, we develop a shell model for the velocity and scalar concentrations that, by design, is consistent with the\\u000a eddy damped quasi-normal Markovian (EDQNM) model for multiple mixing scalars. We review the realizable form of the EDQNM model\\u000a derived by Ulitsky and Collins (J Fluid Mech 412:303–329, 2000), which forms the basis for the shell model. The equations

Yanjun Xia; T. Vaithianathan; Lance R. Collins

2010-01-01

165

Logic-In-Control-Architecture-Based Reconfigurable VLSI Using Multiple-Valued Differential-Pair Circuits  

NASA Astrophysics Data System (ADS)

A fine-grain bit-serial multiple-valued reconfigurable VLSI based on logic-in-control architecture is proposed for effective use of the hardware resources. In logic-in-control architecture, the control circuits can be merged with the arithmetic/logic circuits, where the control and arithmetic/logic circuits are constructed by using one or multiple logic blocks. To implement the control circuit, only one state in a state transition diagram is allocated to one logic block, which leads to reduction of the complexity of interconnections between logic blocks. The fine-grain logic block is implemented based on multiple-valued current-mode circuit technology. In the fine-grain logic block, an arbitrary 3-variable binary function can be programmed by using one multiplexer and two universal literal circuits. Three-variable binary functions are used to implement the control circuit. Moreover, the hardware resources can be utilized to construct a bit-serial adder, because full-adder sum and carry can be realized by programming in the universal literal circuit. Therefore, the logic block can be effectively reconfigured for arithmetic/logic and control circuits. It is made clear that the hardware complexity of the control circuit in the proposed reconfigurable VLSI can be reduced in comparison with that of the control circuit based on a typically sequential circuit in the conventional FPGA and the fine-grain field-programmable VLSI reported until now.

Okada, Nobuaki; Kameyama, Michitaka

166

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

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

2013-01-01

167

Nasal pleomorphic adenoma with skeletal muscle differentiation: Potential misdiagnosis as rhabdomyosarcoma  

Microsoft Academic Search

Pleomorphic adenoma can show diverse lines of differentiation in the epithelial and myoepithelial elements, such as cartilage, bone, and fat. Myoid differentiation, however, has not been documented. We report an unusual case of nasal pleomorphic adenoma which shows focal skeletal muscle differentiation. The tumor was discovered only after successful radiation therapy for an undifferentiated carcinoma of the nasopharynx. Apart from

Polly W. Y Lam; John K. C Chan; Vat-Chong Sin

1997-01-01

168

Multiple TORC1-Associated Proteins Regulate Nitrogen Starvation-Dependent Cellular Differentiation in Saccharomyces cerevisiae  

PubMed Central

Background The budding yeast Saccharomyces cerevisiae undergoes differentiation into filamentous-like forms and invades the growth medium as a foraging response to nutrient and environmental stresses. These developmental responses are under the downstream control of effectors regulated by the cAMP/PKA and MAPK pathways. However, the upstream sensors and signals that induce filamentous growth through these signaling pathways are not fully understood. Herein, through a biochemical purification of the yeast TORC1 (Target of Rapamycin Complex 1), we identify several proteins implicated in yeast filamentous growth that directly associate with the TORC1 and investigate their roles in nitrogen starvation-dependent or independent differentiation in yeast. Methodology We isolated the endogenous TORC1 by purifying tagged, endogenous Kog1p, and identified associated proteins by mass spectrometry. We established invasive and pseudohyphal growth conditions in two S. cerevisiae genetic backgrounds (?1278b and CEN.PK). Using wild type and mutant strains from these genetic backgrounds, we investigated the roles of TORC1 and associated proteins in nitrogen starvation-dependent diploid pseudohyphal growth as well as nitrogen starvation-independent haploid invasive growth. Conclusions We show that several proteins identified as associated with the TORC1 are important for nitrogen starvation-dependent diploid pseudohyphal growth. In contrast, invasive growth due to other nutritional stresses was generally not affected in mutant strains of these TORC1-associated proteins. Our studies suggest a role for TORC1 in yeast differentiation upon nitrogen starvation. Our studies also suggest the CEN.PK strain background of S. cerevisiae may be particularly useful for investigations of nitrogen starvation-induced diploid pseudohyphal growth. PMID:22043304

Laxman, Sunil; Tu, Benjamin P.

2011-01-01

169

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

170

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

171

[Infantile perineal protrusion is a harmless condition with multiple differential diagnoses].  

PubMed

Among girls the frequency of infantile perineal protrusion (IPP) is 13%. The skin-coloured protrusion is thought to represent a congenital weakness in the perineum and usually resolves spontaneously. We report a case of a 13 year-old girl who for nine years had been examined and treated for haemorrhoids and other relevant differential diagnoses before being diagnosed with IPP. During this time she developed iatrogenic contact allergy after frequent application of ointment for haemorrhoids. Recognition of this common and harmless condition renders further examination and treatment unnecessary. PMID:21985835

Haastrup, Maija Dalgaard; Bygum, Anette

2011-10-10

172

CD44 in Differentiated Embryonic Stem Cells: Surface Expression and Transcripts Encoding Multiple Variants  

PubMed Central

Expression of the surface-adhesion molecule CD44 was investigated during the in vitro differentiation of the embryonic stem (ES) cell line D3. By immunofluorescence analysis, totipotent, undifferentiated ES cells did not show surface expression of CD44, although two transcripts of approximately 1.6 and 3.3 kb were detected on Northern blots. Following 1 week of differentiation in either suspension or substrate-attached cultures, CD44 appeared on the surface of some D3 cells, and synthesis of an additional 4.5 kb mRNA species was detected on Northern blots. At this stage, at least three distinct transcripts encoding CD44 variants were induced within the cultures, resulting from alternative splicing of additional exons in the variable domains of CD44. From PCR analysis, they all appeared to contain the variable exon v10, and two of them in addition contained v6. Taken together, these results suggest that CD44 may play a role in cell migration and adhesion in the early development of the mouse embryo. PMID:7542511

Haegel, Hélène; Dierich, Andrée

1994-01-01

173

Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report  

PubMed Central

Introduction Molecular imaging of the spine is a rarely used diagnostic method for which only a few case reports exist in the literature. Here, to the best of our knowledge we present the first case of a combination of molecular imaging by single photon emission computer tomography and positron emission tomography used in post-operative spinal diagnostic assessment. Case presentation We present the case of a 50-year-old Caucasian woman experiencing progressive spinal cord compression caused by a vertebral metastasis of a less well differentiated thyroid cancer. Following tumor resection and vertebral stabilization, total thyroidectomy was performed revealing follicular thyroid carcinoma pT2 pNxM1 (lung, bone). During follow-up our patient underwent five radioiodine therapy procedures (5.3 to 5.7 GBq each) over a two-year period. Post-therapeutic I-131 scans showed decreasing uptake in multiple Pulmonary metastases. However, following an initial decrease, stimulated thyroglobulin remained at pathologically increased levels, indicating further neoplastic activity. F18 Fludeoxyglucose positron emission tomography, which was performed in parallel, showed remaining hypermetabolism in the lungs but no hypermetabolism of the spinal lesions correlating with the stable neurological examinations. While on single photon emission computer tomography images Pulmonary hyperfixation of I-131 disappeared (most likely indicating dedifferentiation), there was persistent spinal hyperfixation at the operated level and even higher fixation at the spinal process of L3. Based on the negative results of the spinal F18 fludeoxyglucose positron emission tomography, a decision was made not to operate again on the spine since our patient was completely asymptomatic and the neurological risk seemed to be too high. During further follow-up our patient remained neurologically stable. Conclusions Molecular imaging by F18 fludeoxyglucose positron emission tomography helps to exclude metabolically active spinal metastases and to spare further risky surgery. PMID:22018056

2011-01-01

174

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

175

Renal immunohistochemical investigation for the differentiation of the cause of multiple trauma fatalities.  

PubMed

In fatalities with multiple traumatic injuries, it is important to determine the severity of trauma, the main damaged organ, and the antemortem pathophysiological condition. We examined 63 cases within 48 h of the postmortem interval, which included assaults, slips and falls and falls from heights, traffic accidents, and sharp instrumental injuries. Immunohistochemically, each kidney was stained against hemoglobin (Hb), myoglobin (Mb), superoxide dismutase (SOD), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 150 kDa oxygen regulated protein (ORP150), pulmonary surfactant A (SP-A), and liver-type fatty acid binding protein (L-FABP). Bleeding or circulatory failure induced ORP150, 8-OHdG, and L-FABP in the kidney. Statistical analysis of the immunoreactivity revealed that in battered and/or abused cases, Hb could be considered a specific marker. Hb and Mb were observed in the cases with general severe trauma, such as slips and falls and falls from heights. In traffic accidents, ORP150 could reflect general circulatory failure with bleeding. SP-A was observed in the cases with severe thoracic injuries, such as lung injuries and multiple thoracic fractures. L-FABP appeared in cases with renal circulatory failure as well as renal injury. These findings suggest that immunohistochemical observation of the kidneys could be a useful tool in determining several key factors, such as the severity of injury, the specific damaged organ, and the pathological condition after injury. PMID:22000063

Sugimura, Tomoko; Wang, Elaine Lu; Kashiwagi, Masayuki; Hara, Kenji; Matsusue, Aya; Waters, Brian; Kubo, Shin-ichi

2012-01-01

176

Enhanced noradrenergic activity potentiates fear memory consolidation and reconsolidation by differentially recruiting ?1- and ?-adrenergic receptors.  

PubMed

Consolidation and reconsolidation are phases of memory stabilization that diverge slightly. Noradrenaline is known to influence both processes, but the relative contribution of ?1- and ?-adrenoceptors is unclear. The present study sought to investigate this matter by comparing their recruitment to consolidate and/or reconsolidate a contextual fear memory trace under enhanced noradrenergic activity induced by yohimbine. We report that this ?2-adrenoceptor antagonist was able to potentiate fear memory trace consolidation or reconsolidation when administered immediately after acquisition or retrieval, respectively, resulting in increased freezing expression. In either case, generalization of this response to an unpaired context was also seen when it achieved a ceiling level in the paired context. These effects endured for over 7 d and relied on action at central rather than peripheral sites, but were prevented when a memory trace was not acquired, when memory reactivation was omitted, or when administration of yohimbine was delayed until 6 h after acquiring or retrieving the memory trace. The ?-adrenoceptor antagonist propranolol was able to prevent the above-mentioned effects of yohimbine, while pretreatment with the ?1-adrenoceptor antagonist prazosin blocked only its facilitating effects on memory reconsolidation. These results highlight a differential participation of ?1- and ?-adrenoceptors in fear memory processing. Moreover, it was shown that the ?2-adrenoceptor agonist clonidine, as opposed to yohimbine, mitigates fear expression by weakening memory consolidation or reconsolidation. PMID:23512937

Gazarini, Lucas; Stern, Cristina A Jark; Carobrez, Antônio P; Bertoglio, Leandro J

2013-04-01

177

Fine root branch orders contribute differentially to uptake, allocation, and return of potentially toxic metals.  

PubMed

Growing evidence has revealed high heterogeneity of fine root networks in both structure and function, with different root orders corporately maintaining trees' physiological activities. However, little information is available on how fine root heterogeneity of trees responds to environmental stresses. We examined concentrations of seven potentially toxic metals (Cr, Ni, Cu, Zn, As, Cd, and Pb) within fine root networks and their correlations with root morphological and macro-elemental traits in six Chinese subtropical trees. The contributions of different orders of roots to fine-root metal storage and return were also estimated. Results showed no consistent pattern for the correlation among different metal concentration against root traits. Unlike root metal concentration that generally decreased with root order, root metal storage was commonly lowest in middle root orders. Root senescence was at least comparable to leaf senescence contributing to metal removal. Although the first-order roots constituted 7.2-22.3% of total fine root biomass, they disproportionately contributed to most of metal return fluxes via root senescence. The two distinct root functional modules contributed differentially to metal uptake, allocation, and return, with defensive (lower-order) roots effectively stabilizing and removing toxic metals and bulk buffering (higher-order) roots possessing a persistent but diluted metal pool. Our results suggest a strong association of physiological functions of metal detoxification and metal homeostasis with the structural heterogeneity in fine root architecture. PMID:24044549

Guo, Ying-Ying; Wang, Jun-Jian; Kong, De-Liang; Wang, Wei; Guo, Da-Li; Wang, Yan-Bing; Xie, Qing-Long; Liu, Yang-Sheng; Zeng, Hui

2013-10-15

178

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

179

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

180

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

181

Event-related brain potentials differentiate positive and negative mood adjectives during both supraliminal and subliminal visual processing  

Microsoft Academic Search

This experiment provides brain event-related potential (ERP) evidence for differential processing of visually presented pleasant and unpleasant affectively valent words (mood adjectives) for both supraliminal (40 ms) and subliminal (unmasked, 1 ms) stimulus durations. Unpleasant words elicited a more positive amplitude than pleasant words in both durations. ERP components (P1, N1, P2, P3, and a late positive potential; LP) were

Edward Bernat; Scott Bunce; Howard Shevrin

2001-01-01

182

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

183

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

184

The differential diagnosis of multiple sclerosis: classification and clinical features of relapsing and progressive neurological syndromes.  

PubMed

In the absence of pathognomonic clinical features or a definitive laboratory test, multiple sclerosis (MS) remains ultimately a diagnosis of exclusion. Accurate diagnosis is increasingly important with available disease modifying therapy. Unfortunately the rate of misdiagnosis remains around 5%-10%, indicating that 1 in 20 patients thought to have MS has, instead, a condition resembling MS. In this review we describe conditions that may be confused with MS because they can present as lesions disseminated in time, space, or both. Conditions often confused with MS may be inflammatory (systemic lupus erythematosus, Sjögren's syndrome, vasculitis, sarcoidosis, Behçet's disease), infectious (Lyme disease, syphilis, progressive multifocal leukoencephalopathy, HTLV-1 infection, herpes zoster), genetic (lysosomal disorders, adrenoleukodystrophy, mitochondrial disorders, CADASIL), metabolic (vitamin B12 deficiency), neoplastic (CNS lymphoma) and spinal (degenerative and vascular malformations) diseases. The key to the accurate diagnosis of MS is vigilance for atypical features, suggesting the possibility of an alternative diagnosis. PMID:11794488

Trojano, M; Paolicelli, D

2001-11-01

185

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

2013-01-01

186

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

USGS Publications Warehouse

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 SiO2, 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. ?? 1991.

Brouxel, M.

1991-01-01

187

Hierarchical Bayesian inference for HIV dynamic differential equation models incorporating multiple treatment factors  

PubMed Central

Studies of HIV dynamics in AIDS research are very important in understanding the pathogenesis of HIV-1 infection and also in assessing the effectiveness of antiretroviral (ARV) treatment. Viral dynamic models can be formulated through a system of nonlinear ordinary differential equations (ODE), but there has been only limited development of statistical methodologies for inference. This paper, motivated by an AIDS clinical study, discusses a hierarchical Bayesian nonlinear mixed-effects modeling approach to dynamic ODE models without a closed-form solution. In this model we fully integrate viral load, medication adherence, drug resistance, pharmacokinetics, baseline covariates and time-dependent drug efficacy into the data analysis for characterizing long-term virologic responses. Our method is implemented by a data set from an AIDS clinical study. The results suggest that modeling HIV dynamics and virologic responses with consideration of time-varying clinical factors as well as baseline characteristics may be important for HIV/AIDS studies in providing quantitative guidance to better understand the virologic responses to ARV treatment and to help evaluation of clinical trial design in response to existing therapies. PMID:20661953

Huang, Yangxin; Wu, Hulin; Acosta, Edward P.

2012-01-01

188

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

189

Differential transcription of multiple forms of alpha-2-macroglobulin in carp (Cyprinus carpio) infected with parasites.  

PubMed

Alpha-2-macroglobulin (a2M) is a non-specific protease inhibitor involved in host defense mechanisms, inhibiting both endogenous and exogenous proteases. It is unique among the plasma anti-proteases with respect to the diversity of proteases that it can inactivate. Carp a2M consists of an alpha and beta chain of which the first includes the bioactive regions. Previously, three a2M alpha chain sequences were reported for East-Asian common carp. We studied a2M alpha chain variability in European common carp and report the cloning of a fourth a2M alpha chain with distinct sequence diversity in the bait region. The role of a2M in the immune response to parasites was studied in the liver of carp infected with Trypanoplasma borreli or with Ichthyophthirius multifiliis. Quantitative gene transcription analysis showed a differential regulation of the four isoforms, most clearly seen in infections with I. multifiliis. A2M3 was the only a2M isoform with a highly upregulated transcription during infection, suggesting that this particular isoform is of foremost biological importance. PMID:17662386

Onara, Dalia F; Forlenza, Maria; Gonzalez, Santiago F; Rakus, Krzysztof ?; Pilarczyk, Andrzej; Irnazarow, Ilgiz; Wiegertjes, Geert F

2008-01-01

190

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

191

Multiple forms of mouse antizyme inhibitor 1 mRNA differentially regulated by polyamines.  

PubMed

Antizyme inhibitor 1 (Azin1), a positive regulator of cellular polyamines, is induced by various proliferative stimuli and repressed by polyamines. It has been reported that the translational repression of Azin1 by polyamines involves an upstream open reading frame on the mRNA, but little has been known about polyamine effect on its transcription or splicing. We found multiple forms of Azin1 transcripts formed by alternative splicing and initiation of transcription from putative alternative start sites. One of the novel splice variants, Azin1-X, has a premature termination codon on 5? extension of exon 7, encodes a C-terminal truncated form of protein (Azin1?C), and is subject to nonsense-mediated mRNA decay. 2-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, increased both transcription from the canonical transcription start site and the ratio of the full-length mRNA to Azin1-X mRNA, whereas polyamines show the opposite effect. Thus, polyamines regulate two novel steps of Azin1 expression, namely the transcription and a particular splicing pattern, both of which may affect the level of mRNA encoding the full-length active Azin1 protein. PMID:24077669

Murakami, Yasuko; Ohkido, Makiko; Takizawa, Hiroko; Murai, Noriyuki; Matsufuji, Senya

2014-03-01

192

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

193

Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential.  

PubMed

Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.Leukemia advance online publication, 5 December 2014; doi:10.1038/leu.2014.321. PMID:25388955

Paíno, T; Paiva, B; Sayagués, J M; Mota, I; Carvalheiro, T; Corchete, L A; Aires-Mejía, I; Pérez, J J; Sanchez, M L; Barcena, P; Ocio, E M; San-Segundo, L; Sarasquete, M E; García-Sanz, R; Vidriales, M-B; Oriol, A; Hernández, M-T; Echeveste, M-A; Paiva, A; Blade, J; Lahuerta, J-J; Orfao, A; Mateos, M-V; Gutiérrez, N C; San-Miguel, J F

2014-11-12

194

Circulating endothelial progenitor cells as potential prognostic biomarker in multiple myeloma.  

PubMed

Recent studies suggest that endothelial progenitor cells (EPCs) are mobilized from bone marrow to the peripheral circulation and aid in tumor neovascularization. In this study, circulating EPC (cEPC) numbers were assessed and correlation with clinical and laboratory parameters was determined in 75 patients with multiple myeloma (MM). Higher numbers of cEPCs (defined as CD45-/dim CD34+CD133+CD31+cells) were observed in MM as compared to healthy controls (n = 10; p < 0.001), which increased progressively from stage I to stage III (p < 0.001). A significant decline in cEPC numbers after therapy was observed in patients who attained at least a partial response (n = 47; p < 0.001). cEPCs correlated with response duration, at a baseline cut-off value of 19.6 cEPCs/?L (p = 0.006) and 6.5 cEPCs/?L after therapy (p < 0.001). This study suggests that cEPC numbers and changes in their levels may serve as a potential biomarker of disease severity, response to therapy and treatment outcome in MM. PMID:21973309

Bhaskar, Archana; Gupta, Ritu; Kumar, Lalit; Sharma, Atul; Sharma, Mehar Chand; Kalaivani, Mani; Thakur, Sonu Chand

2012-04-01

195

Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis.  

PubMed

Teriflunomide, being developed as a potential oral treatment for multiple sclerosis (MS) by sanofi-aventis, is the active metabolite of the rheumatoid arthritis drug leflunomide. Both teriflunomide and leflunomide are inhibitors of the mitochondrial enzyme dihydroorotate dehydrogenase, which is critically involved in pyrimidine synthesis. The production of activated T-cells largely depends on de novo pyrimidine synthesis, and thus pyrimidine depletion is thought to result in the inhibition of immune cell proliferation. Therapeutic efficacy of teriflunomide has been demonstrated in vivo in an experimental autoimmune encephalomyelitis model of MS using Dark Agouti rats. In a phase II, randomized, double-blind, placebo-controlled clinical trial of patients with relapsing-remitting MS, treatment with teriflunomide reduced the number of active lesions in the brain and preliminary evidence indicated a slowing in the development of disability. Recently reported data from the phase III TEMSO clinical trial support these initial findings. Compared with current therapies, teriflunomide has the advantage of oral administration. Thus, if good efficacy is demonstrated, teriflunomide may have a role to play in the future treatment of MS. PMID:21157651

Palmer, Alan M

2010-11-01

196

Complement in multiple sclerosis: its role in disease and potential as a biomarker  

PubMed Central

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system with a poorly defined and complex immunopathogenesis. Although initiated by reactive T cells, persistent inflammation is evident throughout the disease course. A contribution from complement has long been suspected, based on the results of pathological and functional studies which have demonstrated complement activation products in MS brain and biological fluids. However, the extent and nature of complement activation and its contribution to disease phenotype and long-term outcome remain unclear. Furthermore, functional polymorphisms in components and regulators of the complement system which cause dysregulation, and are known to contribute to other autoimmune inflammatory disorders, have not been investigated to date in MS in any detail. In this paper we review evidence from pathological, animal model and human functional and genetic studies, implicating activation of complement in MS. We also evaluate the potential of complement components and regulators and their polymorphic variants as biomarkers of disease, and suggest appropriate directions for future research. PMID:19040603

Ingram, G; Hakobyan, S; Robertson, N P; Morgan, B P

2009-01-01

197

Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue.  

PubMed

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I-V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients. PMID:25240278

Pokryszko-Dragan, Anna; Bilinska, Malgorzata; Gruszka, Ewa; Kusinska, El?bieta; Podemski, Ryszard

2015-02-01

198

Modeling multiple time scale firing rate adaptation in a neural network of local field potentials.  

PubMed

In response to stimulus changes, the firing rates of many neurons adapt, such that stimulus change is emphasized. Previous work has emphasized that rate adaptation can span a wide range of time scales and produce time scale invariant power law adaptation. However, neuronal rate adaptation is typically modeled using single time scale dynamics, and constructing a conductance-based model with arbitrary adaptation dynamics is nontrivial. Here, a modeling approach is developed in which firing rate adaptation, or spike frequency adaptation, can be understood as a filtering of slow stimulus statistics. Adaptation dynamics are modeled by a stimulus filter, and quantified by measuring the phase leads of the firing rate in response to varying input frequencies. Arbitrary adaptation dynamics are approximated by a set of weighted exponentials with parameters obtained by fitting to a desired filter. With this approach it is straightforward to assess the effect of multiple time scale adaptation dynamics on neural networks. To demonstrate this, single time scale and power law adaptation were added to a network model of local field potentials. Rate adaptation enhanced the slow oscillations of the network and flattened the output power spectrum, dampening intrinsic network frequencies. Thus, rate adaptation may play an important role in network dynamics. PMID:25319064

Lundstrom, Brian Nils

2015-02-01

199

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

200

Differentiation stage determines reprogramming potential of hematopoietic cells into iPS cells  

PubMed Central

The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is extremely 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 have tested the susceptibilities of hematopoietic cells at different stages of differentiation to be reprogrammed into iPS cells. Surprisingly, hematopoietic stem and progenitor cells give rise to iPS cells up to 300 times more efficiently compared with terminally differentiated B and T cells, yielding reprogramming efficiencies of up to 28%. Our data provide evidence that the differentiation stage of the starting cell has a critical influence on the efficiency of reprogramming into iPS cells. Moreover, we identify adult hematopoietic progenitors as an attractive cell type for applications of iPS technology in research and therapy. PMID:19668214

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

2013-01-01

201

Optimization of a multiple reservoir system operation using a combination of genetic algorithm and discrete differential dynamic programming: a case study in Mae Klong system, Thailand  

Microsoft Academic Search

A combination of genetic algorithm and discrete differential dynamic programming approach (called GA-DDDP) is proposed and developed to optimize the operation of the multiple reservoir system. The demonstration is carried out through application to the Mae Klong system in Thailand. The objective of optimization is to obtain the optimal operating policies by minimizing the total irrigation deficits during a critical

Janejira Tospornsampan; Ichiro Kita; Masayuki Ishii; Yoshinobu Kitamura

2005-01-01

202

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

203

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

204

Use of the peroxidase-antiperoxidase technique for differential staining of multiple cell types in the rat pancreatic islet.  

PubMed

Multiple staining of the endocrine cells of the pancreatic islet was studied in tissue obtained from adult rats. After fixation in Bouin's fluid and processing for light microscopy, the unlabeled peroxidase-antiperoxidase (PAP) technique was performed. Successful staining procedures used variations of the PAP technique with 3,3'-diaminobenzidine (DAB) and 4-chloro-1-naphthol (CN) as chromagens. The purpose of this study was to stain as many of the four primary cell types (A-cells, B-cells, D-cells, PP-cells) as possible either simultaneously or sequentially using photomicroscopy. At optimum antibody titer, there was minimal nonspecific background staining which made it possible to differentiate cell types by intensity of the chromagen. Any two cell types can be shown by using DAB with the first antibody and CN with the second. To demonstrate three cell types simultaneously, three methods which altered dilutions and chromagens were used. The first method consisted of decreasing dilutions of primary antibody with DAB and CN as the chromagens. The second method involved repetitive DAB applications resulting in three intensities of brown. The third method used a DAB immersion after the second cell type was stained. This produced a color differential so the third cell type could be distinguished with CN. To demonstrate the three cell types sequentially, a masking technique was introduced with photomicroscopy. In order to block the preceding complex, the previous cell type (demonstrated by CN) was restained with DAB at an increased dilution. The next cell type was then stained with CN. These four methods were tried in attempts to stain four cell types in the same tissue section. PMID:6205611

deLeo, J A; Schweisthal, M R

1984-07-01

205

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

206

Identification of genes associated with the differentiation potential of adipose-derived stem cells to osteocytes or myocytes.  

PubMed

Adipose-derived stem cells (ADSCs) have been considered as the optimal cells for regenerative medicine because ADSCs have the potential of multi-directional differentiation. To study the mechanisms of ADSCs differentiation, we analyzed microarray of GSE37329. GSE37329 was downloaded from Gene Expression Omnibus including 3 ADSCs, 2 ADSCs-derived osteocytes, and 2 ADSCs-derived myocytes samples. The differentially expressed genes (DEGs) were screened using limma package. Their underlying functions were predicted by gene ontology and pathway enrichment analyses. Besides, the interaction relationships of the proteins encoded by DEGs were obtained from STRING database, and protein-protein interaction (PPI) network was constructed using Cytoscape. Furthermore, modules analysis of PPI network was performed using MCODE in Cytoscape. We screened 662 and 484 DEG separately for the ADSCs-derived osteocytes and myocytes compared with ADSCs. There were 205 common up-regulated and 128 common down-regulated DEGs between the two groups. Function enrichment indicated that these common DEGs, especially, VEGFA, FGF2, and EGR1 may be related to cell differentiation. PPI network for common DEGs also suggested that VEGFA (degree = 29), FGF2 (degree = 17), and EGR1 (degree = 12) might be more important because they had higher connectivity degrees, and they might be involved in cell differentiation by interacting with other genes in module A (e.g., EGR1-NGF and EGR1-LEP), and B (e.g., VEGFA-PDGFD). Additionally, the IGF1 and BTG1 may be, respectively, specific for osteocytes and myocytes differentiation. VEGFA, PDGFD, FGF2, EGR1, NGF, LEP, IGF1, and BTG1 might serve as target genes in regulating ADSCs differentiation. PMID:25385480

Ren, Yizhong; Han, Changxu; Wang, Jingjuan; Jia, Yanbo; Kong, Lingyue; Eerdun, Tu; Wu, Lishuan; Jiang, Dianming

2015-02-01

207

PTSD and Comorbid Disorders in a Representative Sample of Adolescents: The Risk Associated with Multiple Exposures to Potentially Traumatic Events  

ERIC Educational Resources Information Center

Objective: This study compared the impact of multiple exposures to potentially traumatic events (PTEs), including sexual victimization, physical victimization, and witnessed violence, on posttraumatic stress disorder (PTSD) and comorbid conditions (i.e., major depressive episode [MDE], and substance use [SUD]). Methods: Participants were a…

Macdonald, Alexandra; Danielson, Carla Kmett; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2010-01-01

208

Differentiation of Equine Mesenchymal Stromal Cells into Cells of Neural Lineage: Potential for Clinical Applications  

PubMed Central

Mesenchymal stromal cells (MSCs) are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses. PMID:25506367

Cruz Villagrán, Claudia; Amelse, Lisa; Neilsen, Nancy; Dunlap, John; Dhar, Madhu

2014-01-01

209

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

210

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

211

Stereotactic Ablative Radiotherapy: A Potentially Curable Approach to Early-Stage Multiple Primary Lung Cancer  

PubMed Central

BACKGROUND Surgical resection has been the standard treatment for early-stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. We explored here the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. METHODS We reviewed MPLC cases treated with SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) for the second tumor. Four-dimensional CT–based planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. RESULTS For the 101 patients treated with SABR, at a median follow-up interval of 36 months and median overall survival of 46 months, 2-year and 4-year in-field local control rates were 97.4% and 95.7%. 2- and 4-year rates of overall survival (OS) were 73.2% and 47.5% and progression-free survival (PFS) were 67.0% and 58.0%. Patients with metachronous tumors had higher OS and PFS than did patients with synchronous tumors (2-year OS 80.6% metachronous vs. 61.5% synchronous; 4-year OS 52.7% vs. 39.7%; p=0.047; 2-year PFS 84.7% vs. 49.4%; 4-year PFS 75.6% vs. 30.4%; p=0.0001). For patients whose index tumor was treated with surgery or SABR, the incidence of grade ?3 radiation pneumonitis was 3% (2/71), but this increased to 17% (5/30) for patients whose index tumor was treated with conventional radiotherapy. Other grade ?3 toxicities included grade 3 chest wall pain (3/101, 3%) and grade 3 skin toxicity (1/101, 1%). CONCLUSIONS SABR achieves promising long- term tumor control, survival and could be a potential curative treatment of early-stage MPLC. PMID:23798353

Chang, Joe Y.; Liu, Yung-Hsien; Zhu, Zhengfei; Welsh, James W.; Gomez, Daniel R.; Komaki, Ritsuko; Roth, Jack A.; Swisher, Stephen G.

2013-01-01

212

A DNA repair pathway score predicts survival in human multiple myeloma: the potential for therapeutic strategy  

PubMed Central

DNA repair is critical to resolve extrinsic or intrinsic DNA damage to ensure regulated gene transcription and DNA replication. These pathways control repair of double strand breaks, interstrand crosslinks, and nucleotide lesions occurring on single strands. Distinct DNA repair pathways are highly inter-linked for the fast and optimal DNA repair. A deregulation of DNA repair pathways may maintain and promote genetic instability and drug resistance to genotoxic agents in tumor cells by specific mechanisms that tolerate or rapidly bypass lesions to drive proliferation and abrogate cell death. Multiple Myeloma (MM) is a plasma cell disorder characterized by genetic instability and poor outcome for some patients, in which the compendium of DNA repair pathways has as yet not been assessed for a disease-specific prognostic relevance. We design a DNA repair risk score based on the expression of genes coding for proteins involved in DNA repair in MM cells. From a consensus list of 84 DNA repair genes, 17 had a bad prognostic value and 5 a good prognostic value for both event-free and overall survival of previously-untreated MM patients. The prognostic information provided by these 22 prognostic genes was summed within a global DNA repair score (DRScore) to take into account the tight linkage of repair pathways. DRscore was strongly predictive for both patients' event free and overall survivals. Also, DRscore has the potential to identify MM patients whose tumor cells are dependent on specific DNA repair pathways to design treatments that induce synthetic lethality by exploiting addiction to deregulated DNA repair pathways. PMID:24809299

Kassambara, Alboukadel; Gourzones-Dmitriev, Claire; Sahota, Surinder; Rème, Thierry; Moreaux, Jérôme; Goldschmidt, Hartmut; Constantinou, Angelos; Pasero, Philippe; Hose, Dirk; Klein, Bernard

2014-01-01

213

Multiple, correlated covariates associated with differential item functioning (DIF): Accounting for language DIF when education levels differ across languages  

PubMed Central

Differential item functioning (DIF) occurs when a test item has different statistical properties in subgroups, controlling for the underlying ability measured by the test. DIF assessment is necessary when evaluating measurement bias in tests used across different language groups. However, other factors such as educational attainment can differ across language groups, and DIF due to these other factors may also exist. How to conduct DIF analyses in the presence of multiple, correlated factors remains largely unexplored. This study assessed DIF related to Spanish versus English language in a 44-item object naming test. Data come from a community-based sample of 1,755 Spanish- and English-speaking older adults. We compared simultaneous accounting, a new strategy for handling differences in educational attainment across language groups, with existing methods. Compared to other methods, simultaneously accounting for language- and education-related DIF yielded salient differences in some object naming scores, particularly for Spanish speakers with at least 9 years of education. Accounting for factors that vary across language groups can be important when assessing language DIF. The use of simultaneous accounting will be relevant to other cross-cultural studies in cognition and in other fields, including health-related quality of life. PMID:22900138

Gibbons, Laura E.; Crane, Paul K.; Mehta, Kala M.; Pedraza, Otto; Tang, Yuxiao; Manly, Jennifer J.; Narasimhalu, Kaavya; Teresi, Jeanne; Jones, Richard N.; Mungas, Dan

2012-01-01

214

Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke  

PubMed Central

Aims Cerebral small vessel disease (SVD) causes a fifth of all strokes plus diffuse brain damage leading to cognitive decline, physical disabilities and dementia. The aetiology and pathogenesis of SVD are unknown, but largely attributed to hypertension or microatheroma. Methods We used the spontaneously hypertensive stroke-prone rat (SHRSP), the closest spontaneous experimental model of human SVD, and age-matched control rats kept under identical, non-salt-loaded conditions, to perform a blinded analysis of mRNA microarray, qRT-PCR and pathway analysis in two brain regions (frontal and mid-coronal) commonly affected by SVD in the SHRSP at age five, 16 and 21 weeks. Results We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats. All were present at age 5 weeks thus predating blood pressure elevation. ‘Neurological’ and ‘inflammatory’ pathways were more affected than ‘vascular’ functional pathways. Conclusions This set of defects, although individually modest, when acting in combination could explain the SHRSP's susceptibility to microvascular and brain injury, compared with control rats. Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD. PMID:24417612

Bailey, Emma L; McBride, Martin W; Beattie, Wendy; McClure, John D; Graham, Delyth; Dominiczak, Anna F; Sudlow, Cathie LM; Smith, Colin; Wardlaw, Joanna M

2014-01-01

215

Roles of Potential Gradient and Electrode Bandwidth on Negative Differential Resistance in One-Dimensional Band Insulator  

NASA Astrophysics Data System (ADS)

A negative differential resistance (NDR) in a one-dimensional band insulator attached to electrodes is investigated. We systematically examine the effects of an electrode bandwidth and a potential distribution inside the insulator on current–voltage characteristics. We show that, in uncorrelated systems, the NDR is generally caused by a linear potential gradient as well as by a finite electrode bandwidth. In particular, the former reduces the effective bandwidth of the insulator for elastic tunneling by tilting its energy band, so that it brings about the NDR even in the limit of large electrode bandwidth.

Tanaka, Yasuhiro; Yonemitsu, Kenji

2014-12-01

216

"So Much Potential in Reading!" Developing Meaningful Literacy Routines for Students with Multiple Disabilities  

ERIC Educational Resources Information Center

Children with multiple disabilities, often experience challenges in communication, mobility, and learning. Despite these challenges, substantial research exists that documents successful educational methods and strategies for these students. Specifically, students with multiple disabilities have successfully been taught to use a voice output…

Fenlon, Amanda G.; McNabb, Jessica; Pidlypchak, Harmony

2010-01-01

217

[MR tomography following lumbar disk surgery: differential diagnostic potentials using Gd-DTPA].  

PubMed

55 patients were examined by magnetic resonance imaging after lumbar disk operation. The results indicate that with Gd-DTPA there is a significantly increased signal intensity along the surgical approach directly after surgery and during the early postoperative period. Whereas herniated or sequestered disk did not enhance with Gd-DTPA, in epidural fibrosis - regardless of the age of the scarification - diagnostic enhancement was obvious. In 82 percent nerve roots engulfed by scar tissue were differentiated after Gd-DTPA; even enlarged nerve roots and changes of arachnoiditis could be differentiated from each other. PMID:2548244

Steiner, H

1989-08-01

218

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

219

Graphene supports in vitro proliferation and osteogenic differentiation of goat adult mesenchymal stem cells: potential for bone tissue engineering.  

PubMed

Current treatments for bone loss injuries involve autologous and allogenic bone grafts, metal alloys and ceramics. Although these therapies have proved useful, they suffer from inherent challenges, and hence, an adequate bone replacement therapy has not yet been found. We hypothesize that graphene may be a useful nanoscaffold for mesenchymal stem cells and will promote proliferation and differentiation into bone progenitor cells. In this study, we evaluate graphene, a biocompatible inert nanomaterial, for its effect on in vitro growth and differentiation of goat adult mesenchymal stem cells. Cell proliferation and differentiation are compared between polystyrene-coated tissue culture plates and graphene-coated plates. Graphitic materials are cytocompatible and support cell adhesion and proliferation. Importantly, cells seeded on to oxidized graphene films undergo osteogenic differentiation in fetal bovine serum-containing medium without the addition of any glucocorticoid or specific growth factors. These findings support graphene's potential to act as an osteoinducer and a vehicle to deliver mesenchymal stem cells, and suggest that the combination of graphene and goat mesenchymal stem cells provides a promising construct for bone tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25220951

Elkhenany, Hoda; Amelse, Lisa; Lafont, Andersen; Bourdo, Shawn; Caldwell, Marc; Neilsen, Nancy; Dervishi, Enkeleda; Derek, Oshin; Biris, Alexandru S; Anderson, David; Dhar, Madhu

2015-04-01

220

Reliability: Arguments for Multiple Perspectives and Potential Problems with Generalization across Studies.  

ERIC Educational Resources Information Center

Discusses reliability issues in light of recent studies and debates focused on psychometrics versus datametrics terminology and reliabilities generalization. Discusses the way multiple perspectives on score reliability may affect research practice, editorial policies, and reliability generalization across studies. (SLD)

Dimitrov, Dimiter M.

2002-01-01

221

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis  

PubMed Central

Daclizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) isotype that binds to the ?-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor expressed on activated T cells and CD4+CD25+FoxP3+ regulatory T cells. Based on the assumption that it would block the activation and expansion of autoreactive T cells that are central to the immune pathogenesis of multiple sclerosis (MS), daclizumab was tested in several small open-label clinical trials in MS and demonstrated a profound inhibition of inflammatory disease activity. Surprisingly, accompanying mechanistic studies revealed that the most important biological effect of daclizumab was rather a dramatic expansion and activation of immunoregulatory CD56bright natural-killer (NK) cells that correlated with treatment response, while there was no or only minor effect on peripheral T-cell activation and function. These CD56bright NK cells were able to gain access to the central nervous system in MS and kill autologous activated T cells. Additional and relatively large phase IIb clinical trials showed that daclizumab, as add-on or monotherapy in relapsing–remitting (RR) MS, was highly effective in reducing relapse rate, disability progression, and the number and volume of gadolinium-enhancing, T1 and T2 lesions on brain magnetic resonance imaging (MRI), and reproduced the expansion of CD56bright NK cells as a biomarker for daclizumab activity. Daclizumab is generally very well tolerated and has shown a favorable adverse event (AE) profile in transplant recipients. However, several potentially serious and newly emerging AEs (mainly infections, skin reactions, elevated liver function tests and autoimmune phenomena in several body organs) may require strict safety monitoring programs in future clinical practice and place daclizumab together with other new and highly effective MS drugs as a second-line therapy. Ongoing phase III clinical trials in RRMS are expected to provide definite information on the efficacy and safety of daclizumab and to determine its place in the fast-growing armamentarium of MS therapies. PMID:24409199

2014-01-01

222

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis.  

PubMed

Daclizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) isotype that binds to the ?-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor expressed on activated T cells and CD4+CD25+FoxP3+ regulatory T cells. Based on the assumption that it would block the activation and expansion of autoreactive T cells that are central to the immune pathogenesis of multiple sclerosis (MS), daclizumab was tested in several small open-label clinical trials in MS and demonstrated a profound inhibition of inflammatory disease activity. Surprisingly, accompanying mechanistic studies revealed that the most important biological effect of daclizumab was rather a dramatic expansion and activation of immunoregulatory CD56(bright) natural-killer (NK) cells that correlated with treatment response, while there was no or only minor effect on peripheral T-cell activation and function. These CD56(bright) NK cells were able to gain access to the central nervous system in MS and kill autologous activated T cells. Additional and relatively large phase IIb clinical trials showed that daclizumab, as add-on or monotherapy in relapsing-remitting (RR) MS, was highly effective in reducing relapse rate, disability progression, and the number and volume of gadolinium-enhancing, T1 and T2 lesions on brain magnetic resonance imaging (MRI), and reproduced the expansion of CD56(bright) NK cells as a biomarker for daclizumab activity. Daclizumab is generally very well tolerated and has shown a favorable adverse event (AE) profile in transplant recipients. However, several potentially serious and newly emerging AEs (mainly infections, skin reactions, elevated liver function tests and autoimmune phenomena in several body organs) may require strict safety monitoring programs in future clinical practice and place daclizumab together with other new and highly effective MS drugs as a second-line therapy. Ongoing phase III clinical trials in RRMS are expected to provide definite information on the efficacy and safety of daclizumab and to determine its place in the fast-growing armamentarium of MS therapies. PMID:24409199

Milo, Ron

2014-01-01

223

Equine Adipose-Derived Mesenchymal Stem Cells: Phenotype and Growth Characteristics, Gene Expression Profile and Differentiation Potentials  

PubMed Central

Objective Because of the therapeutic application of stem cells (SCs), isolation and characterization of different types of SCs, especially mesenchymal stem cells (MSCs), have gained considerable attention in recent studies. Adipose tissue is an abundant and accessible source of MSCs which can be used for tissue engineering and in particular for treatment of musculoskeletal disorders. This study was aimed to isolate and culture equine adipose-derived MSCs (AT-MSCs) from little amounts of fat tissue samples and determine some of their biological characteristics. Materials and Methods In this descriptive study, only 3-5 grams of fat tissue were collected from three crossbred mares. Immediately, cells were isolated by mechanical means and enzymatic digestion and were cultured in optimized conditions until passage 3 (P3). The cells at P3 were evaluated for proliferative capacities, expression of specific markers, and osteogenic, chondrogenic and adipogenic differentiation potentials. Results Results showed that the isolated cells were plastic adherent with a fibroblast-like phenotype. AT-MSCs exhibited expression of mesenchymal cluster of differentiation (CD) markers (CD29, CD44 and CD90) and not major histocompatibility complex II (MHC-II) and CD34 (hematopoietic marker). Cellular differentiation assays demonstrated the chondrogenic, adipogenic and osteogenic potential of the isolated cells. Conclusion Taken together, our findings reveal that equine MSCs can be obtained easily from little amounts of fat tissue which can be used in the future for regenerative purposes in veterinary medicine.

Alipour, Faezeh; Parham, Abbas; Kazemi Mehrjerdi, Hossein; Dehghani, Hesam

2015-01-01

224

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

Microsoft Academic Search

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

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

2011-01-01

225

Distal-less homeobox 2 promotes the osteogenic differentiation potential of stem cells from apical papilla.  

PubMed

Dental tissue-derived mesenchymal stem cells (MSCs) are a reliable cell source for dental tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. The histone demethylase, lysine (K)-specific demethylase 4B (KDM4B), plays critical roles in the osteogenic commitment of MSCs by up-regulating distal-less homeobox 2 (DLX2) expression. The DLX2 gene is highly expressed in dental tissue-derived MSCs but the roles of DLX2 in osteogenesis are unclear. Here, we investigate DLX2 function in stem cells from apical papilla (SCAPs). We found that, in vitro, DLX2 expression was up-regulated in SCAPs by adding BMP4 and by inducing osteogenesis. The knock-down of DLX2 in SCAPs decreased alkaline phosphatase (ALP) activity and mineralization. DLX2 depletion affected the mRNA expression of ALP, bone sialoprotein (BSP) and osteocalcin (OCN) and inhibited SCAP osteogenic differentiation in vitro. Over-expression of DLX2 enhanced ALP activity, mineralization and the expression of ALP, BSP and OCN in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when DLX2 was activated. Furthermore, DLX2 expression led to the expression of the key transcription factor, osterix (OSX) but not to the expression of runt-related transcription factor 2 (RUNX2). Taken together, these results indicate that DLX2 is stimulated by BMP signaling and enhances SCAP osteogenic differentiation by up-regulating OSX. Thus, the activation of DLX2 signaling might improve tissue regeneration mediated by MSCs of dental origin. These results provide insight into the mechanism underlying the directed differentiation of MSCs of dental origin. PMID:24756434

Qu, Binbin; Liu, Ousheng; Fang, Xiaodan; Zhang, Haixia; Wang, Yuehong; Quan, Hongzhi; Zhang, Jie; Zhou, Jing; Zuo, Jun; Tang, Jianxia; Tang, Zhangui

2014-07-01

226

Differentiation and regeneration potential of mesenchymal progenitor cells derived from traumatized muscle tissue.  

PubMed

Mesenchymal stem cell (MSC) therapy is a promising approach to promote tissue regeneration by either differentiating the MSCs into the desired cell type or by using their trophic functions to promote endogenous tissue repair. These strategies of regenerative medicine are limited by the availability of MSCs at the point of clinical care. Our laboratory has recently identified multipotent mesenchymal progenitor cells (MPCs) in traumatically injured muscle tissue, and the objective of this study was to compare these cells to a typical population of bone marrow derived MSCs. Our hypothesis was that the MPCs exhibit multilineage differentiation and expression of trophic properties that make functionally them equivalent to bone marrow derived MSCs for tissue regeneration therapies. Quantitative evaluation of their proliferation, metabolic activity, expression of characteristic cell-surface markers and baseline gene expression profile demonstrate substantial similarity between the two cell types. The MPCs were capable of differentiation into osteoblasts, adipocytes and chondrocytes, but they appeared to demonstrate limited lineage commitment compared to the bone marrow derived MSCs. The MPCs also exhibited trophic (i.e. immunoregulatory and pro-angiogenic) properties that were comparable to those of MSCs. These results suggest that the traumatized muscle derived MPCs may not be a direct substitute for bone marrow derived MSCs. However, because of their availability and abundance, particularly following orthopaedic injuries when traumatized muscle is available to harvest autologous cells, MPCs are a promising cell source for regenerative medicine therapies designed to take advantage of their trophic properties. PMID:21129154

Jackson, Wesley M; Lozito, Thomas P; Djouad, Farida; Kuhn, Nastaran Z; Nesti, Leon J; Tuan, Rocky S

2011-11-01

227

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

228

Potential for Pancreatic Maturation of Differentiating Human Embryonic Stem Cells Is Sensitive to the Specific Pathway of Definitive Endoderm Commitment  

PubMed Central

This study provides a detailed experimental and mathematical analysis of the impact of the initial pathway of definitive endoderm (DE) induction on later stages of pancreatic maturation. Human embryonic stem cells (hESCs) were induced to insulin-producing cells following a directed-differentiation approach. DE was induced following four alternative pathway modulations. DE derivatives obtained from these alternate pathways were subjected to pancreatic progenitor (PP) induction and maturation and analyzed at each stage. Results indicate that late stage maturation is influenced by the initial pathway of DE commitment. Detailed quantitative analysis revealed WNT3A and FGF2 induced DE cells showed highest expression of insulin, are closely aligned in gene expression patterning and have a closer resemblance to pancreatic organogenesis. Conversely, BMP4 at DE induction gave most divergent differentiation dynamics with lowest insulin upregulation, but highest glucagon upregulation. Additionally, we have concluded that early analysis of PP markers is indicative of its potential for pancreatic maturation. PMID:24743345

Jaramillo, Maria; Mathew, Shibin; Task, Keith; Barner, Sierra; Banerjee, Ipsita

2014-01-01

229

Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells.  

PubMed

Dental pulp stem cells (DPSCs) are an attractive alternative mesenchymal stem cell (MSC) source because of their isolation simplicity compared with the more invasive methods associated with harvesting other MSC sources. However, the isolation method to be favored for obtaining DPSC cultures remains under discussion. This study compares the stem cell properties and multilineage differentiation potential of DPSCs obtained by the two most widely adapted isolation procedures. DPSCs were isolated either by enzymatic digestion of the pulp tissue (DPSC-EZ) or by the explant method (DPSC-OG), while keeping the culture media constant throughout all experiments and in both isolation methods. Assessment of the stem cell properties of DPSC-EZ and DPSC-OG showed no significant differences between the two groups with regard to proliferation rate and colony formation. Phenotype analysis indicated that DPSC-EZ and DPSC-OG were positive for CD29, CD44, CD90, CD105, CD117 and CD146 expression without any significant differences. The multilineage differentiation potential of both stem cell types was confirmed by using standard immuno(histo/cyto)chemical staining together with an in-depth ultrastructural analysis by means of transmission electron microscopy. Our results indicate that both DPSC-EZ and DPSC-OG could be successfully differentiated into adipogenic, chrondrogenic and osteogenic cell types, although the adipogenic differentiation of both stem cell populations was incomplete. The data suggest that both the enzymatic digestion and outgrowth method can be applied to obtain a suitable autologous DPSC resource for tissue replacement therapies of both bone and cartilage. PMID:23715720

Hilkens, P; Gervois, P; Fanton, Y; Vanormelingen, J; Martens, W; Struys, T; Politis, C; Lambrichts, I; Bronckaers, A

2013-07-01

230

Swine Cone and Rod Precursors Arise Sequentially and Display Sequential and Transient Integration and Differentiation Potential Following Transplantation  

PubMed Central

Purpose. We followed cone and rod development in the pig and we correlated development with the potential for cone and rod precursor integration and differentiation following subretinal transplantation. Methods. Rod and cone precursors were identified during development by their position in the outer retina and by immunostaining for markers of differentiation. Embryonic retinal cells from green fluorescent protein (GFP)+ transgenic pigs at different developmental stages were transplanted into adult retinas and integration and differentiation was followed and quantified by immunostaining for markers of cone and rod differentiation. Results. Pig cones and rods are spatially segregated, allowing us to follow rod and cone development in situ. Gestation in the pig is 114 days. By embryonic day (E) 50, postmitotic cone progenitors had formed the outer two rows of the retina. These cone progenitors are marked by expression of Islet1 (ISL1) and Recoverin (RCVRN) (at this embryonic stage, RCVRN exclusively marks these cone precursors). By contrast, postmitotic neural retina leucine zipper (NRL)+ rod precursors, located interior to the cone precursors, did not appear until E65. At E50, before NRL+ rod precursors are evident, transplanted cells gave rise almost exclusively to cones. At, E57, transplanted cells gave rise to equal numbers of rods and cones, but by E65, transplanted cells gave rise almost exclusively to rods. Transplantation of cells at E85 or E105, as precursors initiate opsin expression, led to few integrated cells. Conclusions. Consistent with their sequential appearances in embryonic retina, these results demonstrate sequential and surprisingly narrow developmental windows for integration/differentiation of cone and rod precursors following transplantation. PMID:24327609

Wang, Wei; Zhou, Liang; Lee, Sang Joon; Liu, Yongqing; Fernandez de Castro, Juan; Emery, Douglas; Vukmanic, Eric; Kaplan, Henry J.; Dean, Douglas C.

2014-01-01

231

Differentiation of porcine mesenchymal stem cells into epithelial cells as a potential therapeutic application to facilitate epithelial regeneration.  

PubMed

Epithelial denudation is one of the characteristics of chronic asthma. To restore its functions, the airway epithelium has to rapidly repair the injuries and regenerate its structure and integrity. Mesenchymal stem cells (MSCs) have the ability to differentiate into many cell lineages. However, the differentiation of MSCs into epithelial cells has not been fully studied. Here, we examined the differentiation of MSCs into epithelial cells using three different media compositions with various growth supplementations. The MSCs were isolated from porcine bone marrow by density gradient centrifugation. The isolated MSCs were CD11(-) CD34(-) CD45(-) CD44(+) CD90(+) and CD105(+) by immunostaining and flow cytometry. MSCs were stimulated with EpiGRO (Millipore), BEpiCM (ScienCell) and AECGM (PromoCell) media for 5 and 10?days, and epithelial differentiation was assessed by qPCR (keratin 14, 18 and EpCAM), fluorometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM), western blot analysis (pancytokeratin, EpCAM) and flow cytometry (cytokeratin 7-8, cytokeratin 14-15-16-19 and EpCAM). The functional marker MUC1 was also assessed after 10?days of air-liquid interface (ALI) culture in optimized media. Cells cultured in BEpiCM containing fibroblast growth factor and prostaglandin E2 showed the highest expression of the epithelial markers: CK7-8 (85.90%); CK-14-15-16-19 (10.14%); and EpCAM (64.61%). The cells also expressed functional marker MUC1 after ALI culture. The differentiated MSCs when cultured in BEpiCM medium ex vivo in a bioreactor on a decellularized trachea for 10?days retained the epithelial-like phenotype. In conclusion, porcine bone marrow-derived MSCs demonstrate commitment to the epithelial lineage and might be a potential therapy for facilitating the repair of denuded airway epithelium. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23696537

Kokubun, Kelsey; Pankajakshan, Divya; Kim, Min-Jung; Agrawal, Devendra K

2013-05-21

232

Differential charging of high-voltage spacecraft - The equilibrium potential of insulated surfaces  

NASA Technical Reports Server (NTRS)

A theory is presented for the steady-state potential of insulated surfaces near exposed high voltages. The term 'insulated surfaces' is used to mean either dielectric surfaces or electrically isolated metallic surfaces. The potential is bounded below by the zero of the material's I-V curve assuming total suppression of secondary electrons, and above by assuming total extraction of secondaries. Within these bounds, the material's surface potential is determined consistently with the solution to Poisson's equation external to the vehicle. The theory is compared with rocket experiments and with SCATHA satellite data. Also, an explanation is suggested for the observed 'snapover' of solar cell coverslips from near plasma ground potential to near the potential of positively biased interconnects with increasing bias voltage.

Katz, I.; Mandell, M. J.

1982-01-01

233

Measurements of jet multiplicity and differential production cross sections of Z+jets events in proton-proton collisions at sqrt(s)=7 TeV  

E-print Network

Measurements of differential cross sections are presented for the production of a Z boson and at least one hadronic jet in proton-proton collisions at sqrt(s) = 7 TeV, recorded by the CMS detector, using a data sample corresponding to an integrated luminosity of 4.9 inverse femtobarns. The jet multiplicity distribution is measured for up to six jets. The differential cross sections are measured as a function of jet transverse momentum and pseudorapidity for the four highest transverse momentum jets. The distribution of the scalar sum of jet transverse momenta is also measured as a function of the jet multiplicity. The measurements are compared with theoretical predictions at leading and next-to-leading order in perturbative QCD.

CMS Collaboration

2014-08-19

234

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

235

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

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

2012-01-01

236

Downregulation of H19 improves the differentiation potential of mouse parthenogenetic embryonic stem cells.  

PubMed

Parthenogenetic embryonic stem cells (P-ESCs) offer an alternative source of pluripotent cells, which hold great promise for autologous transplantation and regenerative medicine. P-ESCs have been successfully derived from blastocysts of several mammalian species. However, compared with biparental embryonic stem cells (B-ESCs), P-ESCs are limited in their ability to fully differentiate into all 3 germ layers. For example, it has been observed that there is a differentiation bias toward ectoderm derivatives at the expense of endoderm and mesoderm derivatives-muscle in particular-in chimeric embryos, teratomas, and embryoid bodies. In the present study we found that H19 expression was highly upregulated in P-ESCs with more than 6-fold overexpression compared with B-ESCs. Thus, we hypothesized that manipulation of the H19 gene in P-ESCs would alleviate their limitations and allow them to function like B-ESCs. To test this hypothesis we employed a small hairpin RNA approach to reduce the amount of H19 transcripts in mouse P-ESCs. We found that downregulation of H19 led to an increase of mesoderm-derived muscle and endoderm in P-ESCs teratomas similar to that observed in B-ESCs teratomas. This phenomenon coincided with upregulation of mesoderm-specific genes such as Myf5, Myf6, and MyoD. Moreover, H19 downregulated P-ESCs differentiated into a higher percentage of beating cardiomyocytes compared with control P-ESCs. Collectively, these results suggest that P-ESCs are amenable to molecular modifications that bring them functionally closer to true ESCs. PMID:21793658

Ragina, Neli P; Schlosser, Karianne; Knott, Jason G; Senagore, Patricia K; Swiatek, Pamela J; Chang, Eun Ah; Fakhouri, Walid D; Schutte, Brian C; Kiupel, Matti; Cibelli, Jose B

2012-05-01

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

In vivo differentiation potential of buffalo (Bubalus bubalis) embryonic stem cell.  

PubMed

Embryonic stem cells (ESCs) derived from inner cell mass (ICM) of mammalian blastocyst are having indefinite proliferation and differentiation capability for any type of cell lineages. In the present study, ICMs of in vitro-derived buffalo blastocysts were cultured into two different culture systems using buffalo fetal fibroblast as somatic cell support and Matrigel as synthetic support to obtain pluripotent buffalo embryonic stem cell (buESC) colonies. Pluripotency of the ESCs were characterised through pluripotency markers whereas, their differentiation capability was assessed by teratoma assay using immuno-compromised mice. Cumulus ooccyte complexes from slaughter house-derived ovaries were subjected to in vitro maturation, in vitro fertilization and in vitro culture to generate blastocysts. Total 262 blastocysts were derived through IVEP with 11.83 % (31/262) hatching rate. To generate buESCs, 15 ICMs from hatched blastocysts were cultured on mitomycin-C-treated homologous fetal fibroblast feeder layer, whereas the leftover 16 ICMs were cultured on extra-cellular matrix (Matrigel). No significant differences were observed for primary ESCs colony formation between two culture systems. Primary colonies as well as passaged ESCs were characterised by alkaline phosphatase staining, karyotyping and expression of transcription-based stem cell markers, OCT-4 and cell surface antigens SSEA-4 and TRA-1-60. Batch of ESCs found positive for pluripotency markers and showing normal karyotype after fifteenth passage were inoculated into eight immuno-compromised mice through subcutaneous and intramuscular route. Subcutaneous route of inoculation was found to be better than intramuscular route. Developed teratomas were excised surgically and subjected to histological analysis. Histological findings revealed presence of all the three germinal layer derivatives in teratoma sections. Presence of germinal layer derivatives were further confirmed by reverse transcriptase-polymerase chain reaction for the presence of differentiation markers like nerve cell adhesion molecule, fetal liver kinase-1 and alpha-feto protein for ectoderm, mesoderm and endoderm, respectively. PMID:22678753

Verma, Om Prakash; Kumar, Rajesh; Nath, Amar; Sharma, Manjinder; Dubey, Pawan Kumar; Kumar, G Sai; Sharma, G Taru

2012-06-01

239

Investigation of potential of differential absorption Lidar techniques for remote sensing of atmospheric pollutants  

NASA Technical Reports Server (NTRS)

The NASA multipurpose differential absorption lidar (DIAL) system uses two high conversion efficiency dye lasers which are optically pumped by two frequency-doubled Nd:YAG lasers mounted rigidly on a supporting structure that also contains the transmitter, receiver, and data system. The DIAL system hardware design and data acquisition system are described. Timing diagrams, logic diagrams, and schematics, and the theory of operation of the control electronics are presented. Success in obtaining remote measurements of ozone profiles with an airborne systems is reported and results are analyzed.

Butler, C. F.; Shipley, S. T.; Allen, R. J.

1981-01-01

240

Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist  

PubMed Central

Multiple myeloma is a common plasma cell neoplasm that is incurable with conventional therapy. The treatment paradigm of multiple myeloma is not standardized and is evolving. The advent of novel drugs, including the proteasome inhibitor bortezomib and the immunomodulatory agents, has resulted in increased median survival. Unfortunately, all patients eventually relapse and require further therapy. Pomalidomide is the newest immunomodulatory drug, created by chemical modification of thalidomide with the intention of increasing therapeutic activity while limiting toxicity. Its mechanism of action is incompletely understood but involves anti-angiogenic effects, immunomodulation, an effect on the myeloma tumor microenvironment, and the protein cereblon. It is more potent than thalidomide and lenalidomide. In phase II studies, it has shown significant activity in patients with relapsed and refractory multiple myeloma, including patients who are heavily pretreated, have disease refractory to lenalidomide and bortezomib, and those with high-risk cytogenetic or molecular markers. It is generally well tolerated, with adverse effects including fatigue, neutropenia, neuropathy, and thromboembolic disease. Pomalidomide is a promising new agent in the expanding arsenal of antimyeloma drugs. In this review, we discuss the clinical experience to date with pomalidomide in multiple myeloma. PMID:23730498

Lacy, Martha Q.

2013-01-01

241

DISTRIBUTED COOPERATIVE CONTROL OF MULTIPLE VEHICLE FORMATIONS USING STRUCTURAL POTENTIAL FUNCTIONS 1  

Microsoft Academic Search

In this paper, we propose a framework for formation stabilization of multiple autonomous vehicles in a distributed fashion. Each vehicle is assumed to have simple dynamics, i.e. a double-integrator, with a directed (or an undirected) information flow over the formation graph of the vehicles. Our goal is to find a distributed control law (with an ecient computational cost) for each

Reza Olfati-Saber; Richard M. Murray

242

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

243

A case of multiple macronodular hepatic tuberculosis difficult to differentiate from hepatocellular carcinoma with intrahepatic metastasis: CT-guided fine needle aspiration biopsy confirmed the diagnosis  

PubMed Central

Multiple macronodular hepatic tuberculosis is difficult to be differentiated from hepatocellular carcinoma with intrahepatic metastasis in clinical practice, especially when hepatitis B with or without liver cirrhosis coexists with it. Herein, we report a 30-year-old man with a 10-year history of hepatitis B and a family medical history of hepatocellular carcinoma related with hepatitis B that was finally diagnosed as multiple macronodular hepatic tuberculosis. Abdominal B-mode ultrasonography (US) and plain computed tomography (CT) revealed multiple unequal-sized nodules in the liver. CT-guided fine needle aspiration biopsy (FNAB) of the liver demonstrated a caseating granuloma with lymphocytes, multinucleate giant cells and epithelioid cells compatible with the diagnosis of tuberculosis and no hepatoma cells were detected. Thus, the diagnosis of hepatic tuberculosis was confirmed and hepatocellular carcinoma with intrahepatic metastasis was excluded. PMID:25550879

Zhang, Lei; Yang, Nai-Bin; Ni, Shun-Lan; Zhang, Sai-Nan; Shen, Chen-Bo; Lu, Ming-Qin

2014-01-01

244

A DELAY DIFFERENTIAL MODEL FOR EL NINO/SOUTHERN OSCILLATION (ENSO): PULLBACK ATTRACTORS, PHASE LOCKING, AND MULTIPLE SOLUTIONS  

NASA Astrophysics Data System (ADS)

We consider a highly idealized model for El Nino/Southern Oscillation (ENSO) variability, previously studied by two of the co-authors. The model is governed by a delay differential equation for sea surface temperature T in the Tropical Pacific, and it combines two key mechanisms that participate in ENSO dynamics: delayed negative feedback and seasonal forcing. We perform a theoretical and numerical study of the model in the three-dimensional space of its physically relevant parameters: strength of seasonal forcing, atmosphere-ocean coupling, and propagation period of oceanic waves across the Tropical Pacific. Phase locking of model solutions to the periodic forcing is prevalent: the local maxima and minima of the solutions tend to occur at the same position within the seasonal cycle. Such phase locking is a key feature of the observed El Nino (warm) and La Nina (cold) events. The phasing of the extrema within the seasonal cycle depends sensitively on model parameters when forcing is weak. We also study co-existence of multiple solutions for fixed model parameters and describe the basins of attraction of the stable solutions within a one-dimensional manifold of constant initial model histories. We study next a two-dimensional manifold of solutions, given by initial histories that are piecewise constant, with a jump from T = a to T = 0 that occurs at time t = -b. To do so, we apply the concept of pullback attractor (PBA) in order to study the model dynamics in the model-parameter region where sensitivity to parameter values is high. Computation of the model's PBAs clearly demonstrates that its dynamics --- whether periodic or quasi-periodic --- occurs on a two-dimensional torus, within the three-dimensional space generated by the "product" of the two-dimensional manifold parameterized by (a,b) with the model variable T. This behavior reflects the competition between two oscillatory mechanisms: an external one due to the seasonal forsing and an internal one due to the delayed feedbacks. Such an interpretation is much harder to obtain from the complex, parameter-sensitive dynamics of the model using more traditional, theoretical and numerical, approaches.

Chekroun, M. D.; Zaliapin, I.; Ghil, M.

2009-12-01

245

Interatomic potentials for PuC by Chen-Möbius multiple lattice inversion  

NASA Astrophysics Data System (ADS)

The atomic interactions of PuC with B1 structure were described by Chen-Möbius lattice inversion combined with first-principle calculations. In order to obtain the inversion potential parameters of PuC, three different structures including two virtual crystals were built and the Morse function plus a modified term was adopted to fit the pair-potential curves. The reliability of the inversion potential was tested by checking the stability of the transition of PuC from disordered to ordered state and comparing the calculated and experimental physical and thermal properties of PuC. All the results show that the inversion potential could give a stable and accurate description of the atomic interactions in PuC and the physical and thermal properties of PuC are well reproduced by the potential.

Huang, H.; Meng, D. Q.; Lai, X. C.; Li, G.; Long, Y.

2013-11-01

246

Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma.  

PubMed

Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown that SAC has a poorer prognosis and has different molecular and immunohistochemical features compared with conventional carcinoma (CC) but, to date, only one previous study has analyzed its mRNA expression profile by microarray. Using a different microarray platform, we have studied the molecular signature of 11 SACs and compared it with that of 15 matched CC with the aim of discerning the functions which characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a validation set of 70 SACs and 70 CCs to assess their diagnostic and prognostic values. Microarray data showed a higher representation of morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related functions and also an overexpression of fascin1 (actin-bundling protein associated with invasion) and the antiapoptotic gene hippocalcin in SAC all of which were validated both by quantitative real-time PCR (qPCR) and immunohistochemistry. Fascin1 expression was statistically associated with KRAS mutation with 88.6% sensitivity and 85.7% specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity = 100%). Evaluation of these markers in CRCs showing histological and molecular characteristics of high-level microsatellite instability (MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular profiling demonstrates that SAC shows activation of distinct signaling pathways and that immunohistochemical fascin1 and hippocalcin expression can be reliably used for its differentiation from other CRC subtypes. PMID:22696308

Conesa-Zamora, Pablo; García-Solano, José; García-García, Francisco; Turpin, María Del Carmen; Trujillo-Santos, Javier; Torres-Moreno, Daniel; Oviedo-Ramírez, Isabel; Carbonell-Muñoz, Rosa; Muñoz-Delgado, Encarnación; Rodriguez-Braun, Edith; Conesa, Ana; Pérez-Guillermo, Miguel

2013-01-15

247

Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor  

PubMed Central

Background Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs. Case Report We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT. Discussion Our case demonstrates multiple possible causes of cerebellar ataxia in a patient, including hypothyroidism, HT, chronic ET, and bilateral thalamic DBS. Counseling of patients may be appropriate when multiple risk factors for cerebellar ataxia coexist in one individual. PMID:23439792

Shneyder, Natalya; Lyons, Mark K.; Driver-dunckley, Erika; Evidente, Virgilio Gerald H.

2012-01-01

248

Effect of pulsed electromagnetic field on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells.  

PubMed

Pulsed electromagnetic fields (PEMFs) have been used clinically to slow down osteoporosis and accelerate the healing of bone fractures for many years. The aim of this study is to investigate the effect of PEMFs on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells (BMMSC). PEMF stimulus was administered to BMMSCs for 8 h per day during culture period. The PEMF applied consisted of 4.5 ms bursts repeating at 15 Hz, and each burst contained 20 pulses. Results showed that about 59% and 40% more viable BMMSC cells were obtained in the PEMF-exposed cultures at 24 h after plating for the seeding density of 1000 and 3000 cells/cm2, respectively. Although, based on the kinetic analysis, the growth rates of BMMSC during the exponential growth phase were not significantly affected, 20-60% higher cell densities were achieved during the exponentially expanding stage. Many newly divided cells appeared from 12 to 16 h after the PEMF treatment as revealed by the cell cycle analysis. These results suggest that PEMF exposure could enhance the BMMSC cell proliferation during the exponential phase and it possibly resulted from the shortening of the lag phase. In addition, according to the cytochemical and immunofluorescence analysis performed, the PEMF-exposed BMMSC showed multi-lineage differentiation potential similar to the control group. PMID:19204973

Sun, Li-Yi; Hsieh, Dean-Kuo; Yu, Tzai-Chiu; Chiu, Hsien-Tai; Lu, Sheng-Fen; Luo, Geng-Hong; Kuo, Tom K; Lee, Oscar K; Chiou, Tzyy-Wen

2009-05-01

249

In vitro proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells from ovariectomized rats.  

PubMed

Bone marrow-derived mesenchymal stem cells (BMMSCs) from the patients suffering from age-related osteoporosis were found to have numerous degeneration, such as decreased growth rate, impaired capacity of differentiating into local tissue, and repressed telomerase activity. However, it is not clear whether post-menopausal osteoporotic bone is either subject to such decline in cellular function. In the present study, bone marrow cells were harvested from ovariectomized (OVX) and Sham rats and cultured in vitro at 3 months post-surgery. MTT assay indicated that the proliferation potential of (OVX)BMMSCs was always higher than that of (Sham)BMMSCs, no matter cultured in basic, osteoblastic or adipogenic medium. Alkaline phosphatase activity assay, Alizarin red S staining, Oil red O staining and real-time RT-PCR analysis further demonstrated that bilateral ovariectomization positively influenced the osteoblastic and adipogenic differentiation potential of BMMSCs, this action may be partly mediated through up-regulation of osteoblastic special markers core binding factor a1, collagen type I and low-density lipoprotein receptor-related protein 5, as well as adipogenic special markers peroxisome proliferators activated receptor gamma, CCAAT/enhancer binding protein alpha and adipocyte lipid-binding protein 2. These results may hold great promise for using post-menopausal osteoporotic bone as an attractive autologous marrow source for tissue engineering and cell-based therapies. PMID:25257163

Gao, Ying; Jiao, Yanjun; Nie, Wei; Lian, Bo; Wang, Binquan

2014-12-01

250

The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation  

PubMed Central

Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The MET receptor has an important role in the biology of RMS, and its overexpression and hyperactivation correlate with the metastatic ability of RMS. Consequently, interfering with MET expression or functionality may constitute a sound strategy for reducing the progression and metastatic potential of RMS. Our study reveals that downregulation of the MET receptor leads to changes in the morphology of ARMS cell in vivo. Tumors acquire a spindle shape that is characteristic of muscle fibers. Inhibition of MET expression or function leads to (i) a decreased expression of the early myogenic marker MyoD, (ii) a decreased ability of ARMS cells to metastasize to bone marrow cavities, (iii) downregulation of CXCR4 receptor expression and (iv) a decreased migration of MET-depleted cells towards gradients of HGF and SDF-1. Finally, we demonstrate that in vitro differentiation of alveolar RMS cells decreases their metastatic behavior by reducing both the expression of the MET and CXCR4 receptors and their migratory response to HGF and SDF-1. These findings suggest that blockers of MET receptor function and inducers of RMS cells differentiation may be clinically useful for reducing the aggressiveness and metastatic potential of RMS and may have significant implications for its treatment. PMID:23328666

Miekus, K; Lukasiewicz, E; Jarocha, D; Sekula, M; Drabik, G; Majka, M

2013-01-01

251

Bone Marrow Angiogenesis and Plasma Cell Angiogenic and Invasive Potential in Patients with Active Multiple Myeloma  

Microsoft Academic Search

Factor VIII-related antigen-positive microvessel areas were measured by both immunohistochemistry and computerized image analysis in patients with active multiple myeloma (MM), nonactive MM and monoclonal gammopathies of undetermined significance (MGUS). A 5- to 6-fold larger area was found in patients with active MM compared to the other two groups. The conditioned medium (CM) of their bone marrow plasma cells stimulated

Angelo Vacca; Domenico Ribatti; Aldo M. Roccaro; Roberto Ria; Loredana Palermo; Franco Dammacco

2001-01-01

252

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

253

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.

254

Four Cultivars of Japanese Barberry Demonstrate Differential Reproductive Potential under Landscape Conditions  

Microsoft Academic Search

While japanese barberry (Berberis thunbergii DC.) is an acknowledged inva- sive plant naturalized throughout the eastern and northern U.S., the danger posed by its popular horticultural forms is unknown and controversial. This work analyzed the reproductive potential and seedling growth of four ornamental genotypes important to the nursery industry. Fruit and seed production was quantified in 2001, 2002, and 2003

Jonathan M. Lehrer; Mark H. Brand; Jessica D. Lubell

2006-01-01

255

The normal matrix model with a monomial potential, a vector equilibrium problem, and multiple orthogonal polynomials on a star  

NASA Astrophysics Data System (ADS)

We investigate the asymptotic behaviour of a family of multiple orthogonal polynomials that is naturally linked with the normal matrix model with a monomial potential of arbitrary degree d + 1. The polynomials that we investigate are multiple orthogonal with respect to a system of d analytic weights defined on a symmetric (d + 1)-star centred at the origin. In the first part we analyse in detail a vector equilibrium problem involving a system of d interacting measures (?1, …, ?d) supported on star-like sets in the plane. We show that in the subcritical regime, the first component ?1* of the solution to this problem is the asymptotic zero distribution of the multiple orthogonal polynomials. It also characterizes the domain where the eigenvalues in the normal matrix model accumulate, in the sense that the Schwarz function associated with the boundary of this domain can be expressed explicitly in terms of ?1* . The second part of the paper is devoted to the asymptotic analysis of the multiple orthogonal polynomials. The asymptotic results are obtained again in the subcritical regime, and they follow from the Deift/Zhou steepest descent analysis of a Riemann–Hilbert problem of size (d + 1) × (d + 1). The vector equilibrium problem and the Riemann–Hilbert problem that we investigate are generalizations of those studied recently by Bleher–Kuijlaars in the case d = 2.

Kuijlaars, Arno B. J.; López-García, Abey

2015-02-01

256

Differential potentiation of GABAA receptor function by two stereoisomers of diimidazoquinazoline analogues.  

PubMed Central

1. U-84935, diimidazo[1,5-a;1',2'-C]quinazoline,5-(5-cyclopropyl-1,2,4-oxid iazol-3yl)- 2,3-dihydro, is a ligand of high affinity for the benzodiazepine site of the GABAA receptor composed of alpha 1 beta 2 gamma 2 subunits. 2. The efficacy of its analogues was measured with their ability to potentiate GABA-mediated Cl- currents in the whole cell configuration of the patch clamp techniques in human kidney cells (A293 cells) expressing the subtype of the GABAA receptor. 3. The analogues displayed various levels of efficacy including agonists, partial agonists and antagonists without marked changes in their affinity for the receptors. 4. The major determinant of their efficacy was the spacial configuration of a methyl substituent of the C2 atom of the rigid and planar diimidazoquinazoline ring: U-90167, containing the methyl substituent projected below the plane of the ring, markedly enhanced the GABA current with a maximal potentiation of 220 +/- 25%, while its stereoisomer, U-90168, marginally increased the GABA response with a maximal potentiation of 45 +/- 10%, to which its methyl group appeared to contribute very little. 5. U-90167 potentiated the GABA response with an EC50 of 8.1 nM and a Hill coefficient of 1.1 and did not alter the reversal potential for the Cl- current. 6. From computational modelling, the sensitive methyl group of U-90167 could be assigned to the general region for the 5-phenyl group of diazepam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1330189

Im, H. K.; Im, W. B.; Pregenzer, J. F.; Petke, J. D.; Hamilton, B. J.; Carter, D. B.; Von Voigtlander, P. F.; Hansen, H. C.; Kristiansen, M.

1992-01-01

257

Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells.  

PubMed

NK-cells undergo a "licensing" process as they develop into fully-functional cells capable of efficiently killing targets. NK-cell differentiation is accompanied by an increased surface expression of inhibitory killer immunoglobulin-like receptor (KIR) molecules, which is positively associated with cytotoxicity against the HLA-deficient K562 cell line. NK-cells are rapidly redeployed between the blood and tissues in response to acute exercise, but it is not known if exercise evokes a preferential trafficking of differentiated NK-cells or impacts NK-cell cytotoxic activity (NKCA) against HLA-expressing target cells. Sixteen healthy cyclists performed three 30-min bouts of cycling exercise at -5%, +5%, and +15% of lactate threshold. Blood samples obtained before, immediately after, and 1h after exercise were used to enumerate NK-cells and their subsets, and determine NKCA and degranulating subsets (CD107+) against cell lines of multiple myeloma (U266 and RPMI-8226), lymphoma (721.221 and 221 AEH), and leukemia (K562) origin by 4 and 10-color flow cytometry, respectively. Exercise evoked a stepwise redeployment of NK-cell subsets in accordance with differentiation status [highly-differentiated (KIR+/NKG2A-) >medium-differentiated (KIR+/NKG2A+)>low-differentiated (KIR-/NKG2A+)] that was consistent across all exercise intensities. NKCA per cell increased ?1.6-fold against U266 and 221 AEH targets 1h post-exercise and was associated with a decreased proportion of NK-cells expressing the inhibitory receptor CD158b and increased proportion of NK-cells expressing the activating receptor NKG2C, respectively. We conclude that exercise evokes a preferential redeployment of NK-cell subsets with a high differentiation phenotype and augments cytotoxicity against HLA-expressing target cells. Exercise may serve as a simple strategy to enrich the blood compartment of highly cytotoxic NK-cell subsets that can be harvested for clinical use. PMID:24200514

Bigley, Austin B; Rezvani, Katayoun; Chew, Claude; Sekine, Takuya; Pistillo, Mira; Crucian, Brian; Bollard, Catherine M; Simpson, Richard J

2014-07-01

258

Toll-like receptors as potential therapeutic targets for multiple diseases  

Microsoft Academic Search

The family of Toll-like receptors (TLRs) is receiving considerable attention as potential regulators and controllers of the immune response through their ability to recognize pathogen-associated molecular patterns. The discovery that endogenous ligands, as well as microbial components, are recognized by TLRs, and that small-molecular-mass synthetic compounds activate TLRs, raised interest in these receptors as potential targets for the development of

Claudia Zuany-Amorim; John Hastewell; Christoph Walker

2002-01-01

259

Differential Potentiation of Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples  

Microsoft Academic Search

Numerous studies have demonstrated that diesel exhaust particles (DEP) potentiate allergic immune responses, however the chemical components associated with this effect, and the underlying mechanisms are not well understood. This study characterized the composition of three chemically distinct DEP samples (N, C, and A-DEP), and compared post-sensitization and post-challenge inflammatory allergic phenotypes in BALB\\/c mice. Mice were instilled intranasally with

Tina Stevens; Seung-Hyun Cho; William P. Linak; M. Ian Gilmour

2009-01-01

260

Nuclear Reprogramming Strategy Modulates Differentiation Potential of Induced Pluripotent Stem Cells  

Microsoft Academic Search

Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stem cell-like\\u000a properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the\\u000a process of nuclear reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited\\u000a potential to expand progenitor pools. Molecular dissection of nuclear

Almudena Martinez-Fernandez; Timothy J. Nelson; Andre Terzic

2011-01-01

261

Adult stem cells and their trans-differentiation potential—perspectives and therapeutic applications  

Microsoft Academic Search

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given\\u000a time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem\\u000a cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader\\u000a to

Sabine Hombach-Klonisch; Soumya Panigrahi; Anja Seifert; Esteban Alberti; Paola Pocar; Maciej Kurpisz; Klaus Schulze-Osthoff; Andrzej Mackiewicz; Marek Los

2008-01-01

262

Differential effects of thioridazine enantiomers on action potential duration in rabbit papillary muscle.  

PubMed

The antipsychotic drug thioridazine has potential for treatment of multidrug-resistant microbes including tuberculosis but also causes cardiotoxic QT interval prolongation. Both thioridazine enantiomers have potent antimicrobial effects, but the neuroleptic effect primarily resides with (+)-thioridazine. In this study we for the first time investigate the cardiotoxicity of the isolated thioridazine enantiomers and show their effects on ventricular repolarization. The effects of (+)-thioridazine, (-)-thioridazine, and racemate on the rabbit ventricular action potential duration (APD) were investigated in a randomized controlled blinded experiment. Action potentials were measured in papillary muscles isolated from 21 female rabbits, and the drug effect on 90% APD in comparison with control (??-APD90) was evaluated. Increasing concentrations of (+)-thioridazine and the racemate caused significant dose-dependent ??-APD90 prolongation, while (-)-thioridazine did not. At 0.5 and 2Hz pacing, (+)-thioridazine caused 19.5% and 20.1% ??-APD90 prolongation, the racemate caused 8.0% and 12.9%, and (-)-thioridazine caused 1.5% and 1.1%. The effect of (-)-thioridazine on APD90 was significantly less than that of the other drugs at both pacing rates (P<0.01 in all cases), and there was no significant difference between (-)-thioridazine and control. The results of this study indicate that the APD prolonging effect of thioridazine is primarily due to the (+)-thioridazine enantiomer. If these results are valid in humans, (-)-thioridazine may be a safer drug for treatment of multidrug-resistant tuberculosis and other microbes. PMID:25449032

Jensen, Ask Schou; Pennisi, Cristian Pablo; Sevcencu, Cristian; Christensen, Jørn Bolstad; Kristiansen, Jette Elisabeth; Struijk, Johannes Jan

2015-01-15

263

Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection  

PubMed Central

Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. PMID:25054025

DING, HONGMEI; LIU, JIANHUA; XUE, RONG; ZHAO, PENG; QIN, YI; ZHENG, FANG; SUN, XUGUO

2014-01-01

264

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; Balandrán, Juan Carlos; Arriaga-Pizano, Lourdes; Purizaca, Jessica; Huerta-Yepez, Sara; Jiménez, Elva; Aguilera, Wendy; Medina-Sanson, Aurora; Mayani, Héctor

2013-01-01

265

TLR stimulation of bone marrow lymphoid precursors from childhood acute leukemia modifies their differentiation potentials.  

PubMed

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; Vadillo, Eduardo; Contreras-Quiroz, Adriana; Balandrán, Juan Carlos; Arriaga-Pizano, Lourdes; Purizaca, Jessica; Huerta-Yepez, Sara; Jiménez, Elva; Aguilera, Wendy; Medina-Sanson, Aurora; Mayani, Héctor; Pelayo, Rosana

2013-01-01

266

A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential.  

PubMed

The Sox2 transcription factor must be robustly transcribed in embryonic stem (ES) cells to maintain pluripotency. Two gene-proximal enhancers, Sox2 regulatory region 1 (SRR1) and SRR2, display activity in reporter assays, but deleting SRR1 has no effect on pluripotency. We identified and functionally validated the sequences required for Sox2 transcription based on a computational model that predicted transcriptional enhancer elements within 130 kb of Sox2. Our reporter assays revealed three novel enhancers-SRR18, SRR107, and SRR111-that, through the formation of chromatin loops, form a chromatin complex with the Sox2 promoter in ES cells. Using the CRISPR/Cas9 system and F1 ES cells (Mus musculus(129) × Mus castaneus), we generated heterozygous deletions of each enhancer region, revealing that only the distal cluster containing SRR107 and SRR111, located >100 kb downstream from Sox2, is required for cis-regulation of Sox2 in ES cells. Furthermore, homozygous deletion of this distal Sox2 control region (SCR) caused significant reduction in Sox2 mRNA and protein levels, loss of ES cell colony morphology, genome-wide changes in gene expression, and impaired neuroectodermal formation upon spontaneous differentiation to embryoid bodies. Together, these data identify a distal control region essential for Sox2 transcription in ES cells. PMID:25512558

Zhou, Harry Y; Katsman, Yulia; Dhaliwal, Navroop K; Davidson, Scott; Macpherson, Neil N; Sakthidevi, Moorthy; Collura, Felicia; Mitchell, Jennifer A

2014-12-15

267

Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome.  

PubMed

Children with Down syndrome have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B-cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here we compared B-cell populations of 19 children with Down syndrome with those in healthy age-matched controls. We found that all steps of peripheral B-cell development are altered in Down syndrome, with a more severe defect during the later stages of B-cell development. Transitional and mature-naïve B-cell numbers are reduced by 50% whereas switched memory B cells represent 10-15% of the numbers in age-matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with Down syndrome have an increased ability to differentiate into antibody-forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in Down syndrome. This article is protected by copyright. All rights reserved. PMID:25472482

Carsetti, Rita; Valentini, Diletta; Marcellini, Valentina; Scarsella, Marco; Marasco, Emiliano; Giustini, Ferruccio; Bartuli, Andrea; Villani, Alberto; Ugazio, Alberto G

2014-12-01

268

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

269

Potential application of hydrolyzed fish collagen for inducing the multidirectional differentiation of rat bone marrow mesenchymal stem cells.  

PubMed

Hydrolyzed fish collagen (HFC) has recently attracted considerable attention because of its outstanding bioactivity. However, few studies have been performed to determine the biological effects of HFC on bone marrow mesenchymal stem cells (BMSCs), which are often used in regenerative medicine. In this study, the molecular weight, amino acid composition, and contact angle of HFC were measured. The influence of HFC on cell viability and the multidirectional differentiation of BMSCs into osteogenic, endothelial, adipogenic, chondrogenic, and neural lineages were also assessed. Furthermore, the mechanism by which HFC promotes osteogenesis was investigated at the protein level. The molecular weight of HFC ranged from 700 to 1300 Da, the contact angle of HFC was approximately 26°, and HFC was found to be composed of various amino acids, including glycine, proline, and hydroxyproline. At a concentration of 0.2 mg/mL, HFC promoted cell viability, and significantly up-regulated the expression of osteogenic markers (RUNX2, ALP, OPN, and OCN), as well as endothelial markers (CD31, VE-cadherin, and VEGFR2). Western blot results indicated that treatment of BMSCs with 0.2 mg/mL HFC could activate the MAPK/ERK signaling pathway and then increase the protein level of RUNX2, while treatment with PD98059, a specific inhibitor of ERK1/2, could significantly inhibit the expression of P-ERK and RUNX2. Interestingly, real-time PCR demonstrated that HFC inhibited the expression of adipogenic markers (LPL and ADFP) and chondrogenic markers (aggrecan and COLII), whereas it had no effect on neural differentiation markers (MAP2 and ?3-tubulin). In summary, this study suggests that without the use of any additional inducing reagent, HFC has the potential to actively promote osteogenic and endothelial differentiation because of its high hydrophilicity and the optimal extracellular microenvironment supplied by its amino acids. This research also revealed that HFC inhibited adipogenic and chondrogenic differentiation, but it had no influence on the neural differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). PMID:24359018

Liu, Chao; Sun, Jiao

2014-01-13

270

Evoked response study tool: a portable, rugged system for single and multiple auditory evoked potential measurements.  

PubMed

Although the potential of using portable auditory evoked potential systems for field testing of stranded cetaceans has been long recognized, commercial systems for evoked potential measurements generally do not possess the bandwidth required for testing odontocete cetaceans and are not suitable for field use. As a result, there have been a number of efforts to develop portable evoked potential systems for field testing of cetaceans. This paper presents another such system, called the evoked response study tool (EVREST). EVREST is a Windows-based hardware/software system designed for calibrating sound stimuli and recording and analyzing transient and steady-state evoked potentials. The EVREST software features a graphical user interface, real-time analysis and visualization of recorded data, a variety of stimulus options, and a high level of automation. The system hardware is portable, rugged, battery-powered, and possesses a bandwidth that encompasses the audible range of echolocating odontocetes, making the system suitable for field testing of stranded or rehabilitating cetaceans. PMID:19603907

Finneran, James J

2009-07-01

271

Differentiation between cortical and subcortical lesions following focal ischemia in cats by multimodality evoked potentials.  

PubMed

Regional ischemia was induced in cats by occluding the middle cerebral artery. Evoked and spontaneous electrical activity as well as regional cerebral blood flow (rCBF) were recorded with platinum depth macroelectrodes in three primary cortical areas: the auditory cortex (A, middle ectosylvian gyrus) and the front and hind limb somatosensory cortex (SF and SH, lateral and medial posterior sigmoid gyrus). To distinguish among the various evoked potentials after click, median or tibial nerve stimulation, electrical field interactions had to be eliminated using a multiplex stimulation and analysis system. Spontaneous electrocortical activity was evaluated by power spectral analysis. In all areas, evoked potentials were abolished 10 min after arterial occlusion. However, rCBF behaved differently in these regions: it was severely reduced in A, decreased moderately in SF and remained unchanged in SH. The graded reduction of rCBF in the three cortical areas was related to changes in electrophysiological activity during the first minutes of ischemia. In A, auditory potentials were abolished within 3 min after occlusion, whereas in SH, the decrease of somatosensory responses started after about 5 min. In SF, two components of the EP changes were found: an early decrease immediately and a later decrease about 5 min after occlusion. The different rates of EP impairment possibly correspond to two types of ischemia. The fast EP abolishment seems to be caused by local cortical damage whereas the delayed EP decrease probably reflects impairment of subcortical white matter structures. Thus, this method may be useful for distinguishing between gray and white matter ischemia. PMID:3612168

Kataoka, K; Graf, R; Rosner, G; Radermacher, B; Heiss, W D

1987-06-01

272

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

273

Differential effects of endogenous lithium on neurobehavioural functioning: a study on auditory evoked potentials.  

PubMed

Lithium occurs naturally in food and water. Low environmental concentrations in drinking water are associated with mental illnesses and behavioural offences, and at therapeutic dosages it is used to treat psychiatric (especially affective) disorders, partly by facilitating serotonergic (5-HT) neurotransmission. As little is known about the psychophysiological role of nutritional lithium in the general population, endogenous lithium concentrations were hypothesised to be associated with measurable effects on emotional liability and the loudness dependence (LD) that is proposed as one of the most valid indicators of 5-HT neurotransmission. Auditory evoked potentials of healthy volunteers [N=36] with high (>2.5 microg/l) or low (<1.5 microg/l) lithium serum concentrations were recorded. Emotional liability was assessed using the Brief Symptom Inventory (BSI). Low-lithium levels correlated with Somatisation while correlations between lithium and LD were not significant. Still, LD correlated positively with Paranoid Ideation, negatively with Anxiety and, in the high-lithium group, inversely with further aspects of emotional liability (Depression, Psychological Distress). In conclusion, the effects of low levels of endogenous lithium are associated with emotional liability, and high levels with some protective effects, although findings remain inconclusive regarding LD. Potential benefits of endogenous lithium on neurobehavioural functioning, especially in high-risk individuals, would have public health implications. PMID:20452041

Norra, Christine; Feilhauer, Johanna; Wiesmüller, Gerhard Andreas; Kunert, Hanns Jürgen

2010-06-30

274

The potential of using robotics in data acquisition from multiple sensors  

Microsoft Academic Search

This paper shows the potential of using robotics for data acquisition within full-scale field trials. Robotics ensured simultaneously measurements from several sensors from GPS targeted sampling points. This was demonstrated by supporting a project developing methods to measure gap fraction and canopy structure in cereals. The project required measurements from ordinary barley canopy areas using a high- dynamic-range RGB camera,

Rasmus N. Jørgensen; Claus G. Sørensen; Hans Jacobsen; Kristian Kirk; Hans Jørgen Andersen; Del Nantt

2005-01-01

275

Potential nosocomial acquisition of epidemic Listeria monocytogenes presenting as multiple brain abscesses resembling nocardiosis.  

PubMed

Listerial brain abscesses are rare, and are found mostly in patients with underlying hematological malignancies or solid-organ transplants. A case of a patient with Crohn's disease and multiple brain abscesses involving the left cerebellum and right sylvian fissure is described. The Gram stain and histopathology of the cerebellar abscess revealed Gram-positive, beaded rods suggestive of Nocardia. However, on culture, Listeria monocytogenes was identified. Listeria may appear Gram-variable and has been misidentified as streptococci, enterococci and diphtheroids. The present case is the first reported case of L monocytogenes resembling Nocardia on both microbiological and histopathological assessment. Reported cases of listerial brain abscesses are sporadic, while the current case was part of a nationwide listerial outbreak linked to consumption of contaminated deli meats. Broad antimicrobial therapy (including antilisterial coverage) in immunosuppressed patients presenting with brain abscess is crucial, until cultures confirm the identification of the organism. PMID:21358887

Stefanovic, Aleksandra; Reid, James; Nadon, A Celine; Grant, Jennifer

2010-01-01

276

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; Bagalà, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

2014-01-01

277

Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.  

PubMed

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; Bagalà, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

2014-01-01

278

Contribution of Vestibular-Evoked Myogenic Potential (VEMP) testing in the assessment and the differential diagnosis of otosclerosis  

PubMed Central

Background The aim of this prospective clinical study was to evaluate the clinical importance of Vestibular-Evoked Myogenic Potentials (VEMPs) in the assessment and differential diagnosis of otosclerosis and otologic diseases characterized by “pseudo-conductive” components. We also investigated the clinical appearance of balance disorders in patients with otosclerosis by correlating VEMP results with the findings of caloric testing and pure tone audiometry(PTA). Material/Methods Air-conducted(AC) 4-PTA, bone-conducted(BC) 4-PTA, air-bone Gap(ABG), AC, BC tone burst evoked VEMP, and calorics were measured preoperatively in 126 otosclerotic ears. Results The response rate of the AC-VEMPs and BC-VEMPs was 29.36% and 44.03%, respectively. Statistical differences were found between the means of ABG, AC 4-PTA, and BC 4-PTA in the otosclerotic ears in relation to AC-VEMP elicitability. About one-third of patients presented with disequilibrium. A statistically significant interaction was found between calorics and dizziness in relation to PTA thresholds. No relationship was found between calorics and dizziness with VEMPs responses. Conclusions AC and BC VEMPs can be elicited in ears with otosclerosis. AC-VEMP is more vulnerable to conductive hearing loss. Evaluation of AC-VEMP thresholds can be added in the diagnostic work-up of otosclerosis in case of doubt, enhancing differential diagnosis in patients with air-bone gaps. Otosclerosis is not a cause of canal paresis or vertigo. PMID:24509900

Tramontani, Ourania; Gkoritsa, Eleni; Ferekidis, Eleftherios; Korres, Stavros G.

2014-01-01

279

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

280

Overexpression of the skNAC gene in human rhabdomyosarcoma cells enhances their differentiation potential and inhibits tumor cell growth and spreading.  

PubMed

Skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide complex (skNAC) is exclusively present in striated muscle cells. During skeletal muscle cell differentiation, skNAC expression is strongly induced, suggesting that the protein might be a regulator of the differentiation process. Rhabdomyosarcoma is a tumor of skeletal muscle origin. Since there is a strong inverse correlation between rhabdomyosarcoma cell differentiation status and metastatic potential, we analyzed skNAC expression patterns in a set of rhabdomyosarcoma cell lines: Whereas RD/12 and RD/18 cells showed a marked induction of skNAC gene expression upon the induction of differentiation-similarly as the one seen in nontransformed myoblasts-skNAC was not induced in CCA or Rh30 cells. Overexpressing skNAC in CCA and Rh30 cells led to a reduction in cell cycle progression and cell proliferation accompanied by an upregulation of specific myogenic differentiation markers, such as Myogenin or Myosin Heavy Chain. Furthermore, in contrast to vector-transfected controls, a high percentage of the cells formed long, Myosin Heavy Chain-positive, multinucleate myotubes. Consistently, soft agar assays revealed a drop in the metastatic potential of skNAC-overexpressing cells. Taken together, these data indicate that reconstitution of skNAC expression can enhance the differentiation potential of rhabdomyosarcoma cells and reduces their metastatic potential, a finding which might have important therapeutic implications. PMID:25209525

Berkholz, Janine; Kuzyniak, Weronika; Hoepfner, Michael; Munz, Barbara

2014-12-01

281

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 Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

2012-01-01

282

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

283

Multiple sources of positive- and negative-priming effects: An event-related potential study  

Microsoft Academic Search

Event-related potential correlates of positive priming (PP) and negative priming (NP) were investigated in order to further\\u000a elucidate the cognitive mechanisms involved. Thirty-six participants performed both an identity- and a location-based priming\\u000a task. Repeating the target stimulus\\/location from the immediately preceding display produced behavioral PP. With localization,\\u000a but not with identification, behavioral NP was observed when the target stimulus\\/location matched

Henning Gibbons; Thomas H. Rammsayer; Jutta Stahl

2006-01-01

284

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

285

Adult stem cells and their trans-differentiation potential--perspectives and therapeutic applications.  

PubMed

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader to the basic information about the field. We describe selected stem cell isolation techniques and stem cell markers for various stem cell populations. These include makers for endothelial progenitor cells (CD146/MCAM/MUC18/S-endo-1, CD34, CD133/prominin, Tie-2, Flk1/KD/VEGFR2), hematopoietic stem cells (CD34, CD117/c-Kit, Sca1), mesenchymal stem cells (CD146/MCAM/MUC18/S-endo-1, STRO-1, Thy-1), neural stem cells (CD133/prominin, nestin, NCAM), mammary stem cells (CD24, CD29, Sca1), and intestinal stem cells (NCAM, CD34, Thy-1, CD117/c-Kit, Flt-3). Separate section provides a concise summary of recent clinical trials involving stem cells directed towards improvement of a damaged myocardium. In the last part of the review, we reflect on the field and on future developments. PMID:18629466

Hombach-Klonisch, Sabine; Panigrahi, Soumya; Rashedi, Iran; Seifert, Anja; Alberti, Esteban; Pocar, Paola; Kurpisz, Maciej; Schulze-Osthoff, Klaus; Mackiewicz, Andrzej; Los, Marek

2008-12-01

286

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

Microsoft Academic Search

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 alphas is determined to be 0.123+\\/-0.009+\\/-0.005 at &surd;s~=MZ (at the SLAC Linear Collider) and 0.149+\\/-0.002+\\/-0.007 at &surd;s=29 GeV (at the SLAC storage ring PEP). The running of alphas between these two center-of-mass energies is consistent with

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

1990-01-01

287

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

288

GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target  

PubMed Central

Multiple myeloma (MM) is an incurable haematological malignancy characterised by the proliferation of mature antibody-secreting plasma B cells in the bone marrow. MM can arise from initiating translocations, of which the musculoaponeurotic fibrosarcoma (MAF) family is implicated in ?5%. MMs bearing Maf translocations are of poor prognosis. These translocations are associated with elevated Maf expression, including c-MAF, MAFB and MAFA, and with t(14;16) and t(14;20) translocations, involving c-MAF and MAFB, respectively. c-MAF is also overexpressed in MM through MEK/ERK activation, bringing the number of MMs driven by the deregulation of a Maf gene close to 50%. Here we demonstrate that MAFB and c-MAF are phosphorylated by the Ser/Thr kinase GSK3 in human MM cell lines. We show that LiCl-induced GSK3 inhibition targets these phosphorylations and specifically decreases proliferation and colony formation of Maf-expressing MM cell lines. Interestingly, bortezomib induced stabilisation of Maf phosphorylation, an observation that could explain, at least partially, the low efficacy of bortezomib for patients carrying Maf translocations. Thus, GSK3 inhibition could represent a new therapeutic approach for these patients. PMID:24442204

Herath, N I; Rocques, N; Garancher, A; Eychène, A; Pouponnot, C

2014-01-01

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

Evolution of antibody structure during the immune response. The differentiative potential of a single B lymphocyte  

PubMed Central

Changes in the structure and function of antibodies occur during the course of an immune response due to variable (V) region gene somatic mutation and isotype switch recombination. While the end products of both these processes are now well documented, their mechanisms, timing, and regulation during clonal expansion remain unclear. Here I describe the characterization of antibodies expressed by a large number of hybridomas derived from single B cell clones at an intermediate stage of an immune response. These data provide new insights into the mechanism, relative timing, and potential of V gene mutation and isotype switching. The data suggest that somatic mutation and isotype switching are completely independent processes that may, but need not, occur simultaneously during clonal expansion. In addition, the results of this analysis demonstrate that individual B cell clones are far more efficient than previously imagined at generating and fixing particular V region somatic mutations that result in increased affinity for the eliciting epitope. Models to account for this high efficiency are discussed. Taken together with previous data, the results of this analysis also suggest that the "somatic evolution" of V region structure to a single epitope takes place in two stages; the first in which particular mutations are sustained and fixed by antigen selection in the CDR regions of the V region genes expressed in a clone over a short period of clonal expansion, and the second in which these selected CDR mutations are maintained in the growing clone, deleterious mutations are lost, and selectively neutral mutations accumulate throughout the length of V genes over long periods of clonal expansion. PMID:2507726

1989-01-01

291

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

292

Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma.  

PubMed

The adaptive immune system is clearly capable of recognizing and attacking malignant plasma cells in patients with multiple myeloma (MM). However, MM patients evidence severe defects of humoral and cellular immunity, and it is likely that the profound immune dysregulation typical for this malignancy contributes to its eventual escape from natural immune control. One of the factors responsible for the immune dysfunction in MM might be the programmed death 1 (PD-1) protein. The physiological role of PD-1 is to guarantee T-cell homeostasis by limiting T-cell activation and proliferation. Accordingly, binding of the ligand PD-L1 to PD-1 expressed on the surface of activated T cells delivers an inhibitory signal, reducing cytokine production and proliferation. Using the same mechanism, PD-L1/PD-1 interactions have been shown in a number of animal models to confer tumor escape from immune control. Recently, clinical trials have suggested a significant therapeutic impact of PD-1/PD-L inhibition on a variety of solid tumors-for example, by the application of monoclonal antibodies. We show here that based on (1) the broad expression of PD-1 and its ligands in the microenvironment of myeloma, (2) data indicating an important role of the PD-1 pathway in the immune evasion by MM cells and (3) preclinical results providing a strong rationale for therapeutic PD-1/PD-L inhibition in this malignancy, MM may be very well suited for immunotherapy, for example, a monoclonal antibody, targeting PD-1 and/or its ligands. PMID:24153012

Atanackovic, D; Luetkens, T; Kröger, N

2014-05-01

293

Immature muscular tissue differentiation into bone-like tissue by bone morphogenetic proteins in vitro, with ossification potential in vivo.  

PubMed

The objective of this study was to induce bone formation from immature muscular tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition, cultured IMTs were implanted subcutaneously into Sprague-Dawley (SD) rats to determine their in vivo ossification potential. BMPs, extracted from bovine cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks culture on ePTFE scaffolds. Osteoblast-like cells and osteoid tissues were partially identified by hematoxylin-eosin staining 2 weeks after culture. Collagen type I (Col-I), osteopontin (OP), and osteocalcin (OC) were detected in the osteoid tissues by immunohistochemical staining. OC gene expression remained low, but OP and Col-I were upregulated during the culture period. In vivo implanted IMTs showed slight radiopacity 1 week after implantation and strong radiopacity 2 and 3 weeks after implantation. One week after implantation, migration of numerous capillaries was observed and ossification was detected after 2 weeks by histological observation. These results suggest that IMTs are able to differentiate into bone-like tissue in vitro, with an ossification potential after implantation in vivo. PMID:24115406

Hayashi, Tatsuhide; Kobayashi, Syuichiro; Asakura, Masaki; Kawase, Mayu; Ueno, Atsuko; Uematsu, Yasuaki; Kawai, Tatsushi

2014-09-01

294

Laser-Based Propagation of Human iPS and ES Cells Generates Reproducible Cultures with Enhanced Differentiation Potential  

PubMed Central

Proper maintenance of stem cells is essential for successful utilization of ESCs/iPSCs as tools in developmental and drug discovery studies and in regenerative medicine. Standardization is critical for all future applications of stem cells and necessary to fully understand their potential. This study reports a novel approach for the efficient, consistent expansion of human ESCs and iPSCs using laser sectioning, instead of mechanical devices or enzymes, to divide cultures into defined size clumps for propagation. Laser-mediated propagation maintained the pluripotency, quality, and genetic stability of ESCs/iPSCs and led to enhanced differentiation potential. This approach removes the variability associated with ESC/iPSC propagation, significantly reduces the expertise, labor, and time associated with manual passaging techniques and provides the basis for scalable delivery of standardized ESC/iPSC lines. Adoption of standardized protocols would allow researchers to understand the role of genetics, environment, and/or procedural effects on stem cells and would ensure reproducible production of stem cell cultures for use in clinical/therapeutic applications. PMID:22701128

Hohenstein Elliott, Kristi A.; Peterson, Cory; Soundararajan, Anuradha; Kan, Natalia; Nelson, Brandon; Spiering, Sean; Mercola, Mark; Bright, Gary R.

2012-01-01

295

Differential effects of exogenous estrogen versus a estrogen-progesterone combination on auditory evoked potentials in menopausal women.  

PubMed

The study was undertaken to determine the differential effects of estrogen and progestin on auditory evoked responses in postmenopausal women receiving hormone replacement therapy (HRT). Forty-seven women between 45 and 70 years of age attending menopause and HRT clinic were divided into two groups. Group I included 32 women who attained natural menopause and receiving combined estrogen progestin therapy. While group II included 15 surgically menopausal women receiving only estrogen. Evoked potentials were recorded in form of auditory brainstem response (ABR), middle latency response (MLR) & slow vertex response (SVR). There was improvement of conduction in auditory pathways at the level of brainstem and thalamocortical projections as indicated by the decrease in latencies of most of the waves of ABR and/MLR after 6 months of HRT in both the groups. The conduction in association areas, as indicated by SVR, did not show a significant change. The intergroup comparison after therapy revealed a decrease in latency of wave V and I-V interpeak latency in group II indicating that only estrogen users are benefited more. Thus HRT facilitates the process of sensory conduction, which may form one of the mechanisms of improved neuropsychological functions in menopausal women on HRT. The addition of progestin to estrogen does not have a negative or potentiating effect on it. PMID:16440855

Khaliq, Farah; Tandon, Om Prakash; Goel, Neerja

2005-01-01

296

HEB-Deficient T-Cell Precursors Lose T-Cell Potential and Adopt an Alternative Pathway of Differentiation? †  

PubMed Central

Early thymocytes possess multilineage potential, which is progressively restricted as cells transit through the double-negative stages of T-cell development. DN1 cells retain the ability to become natural killer cells, dendritic cells, B cells, and myeloid cells as well as T cells, but these options are lost by the DN3 stage. The Notch1 signaling pathway is indispensable for initiation of the T-cell lineage and inhibitory for the B-cell lineage, but the regulatory mechanisms by which the T-cell fate is locked in are largely undefined. Previously, we discovered that the E-protein transcription factor HEBAlt promoted T-cell specification. Here, we report that HEB?/? T-cell precursors have compromised Notch1 function and lose T-cell potential. Moreover, reconstituting HEB?/? precursors with Notch1 activity enforced fidelity to the T-cell fate. However, instead of becoming B cells, HEB?/? DN3 cells adopted a DN1-like phenotype and could be induced to differentiate into thymic NK cells. HEB?/? DN1-like cells retained GATA3 and Id2 expression but had lower levels of the Bcl11b gene, a Notch target gene. Therefore, our studies have revealed a new set of interactions between HEB, Notch1, and GATA3 that regulate the T-cell fate choice in developing thymocytes. PMID:21189289

Braunstein, Marsela; Anderson, Michele K.

2011-01-01

297

Electrospun scaffolds for multiple tissues regeneration in vivo through topography dependent induction of lineage specific differentiation.  

PubMed

Physical topographic cues from various substrata have been shown to exert profound effects on the growth and differentiation of stem cells due to their niche-mimicking features. However, the biological function of different topographic materials utilized as bio-scaffolds in vivo have not been rigorously characterized. This study investigated the divergent differentiation pathways of mesenchymal stem cells (MSCs) and neo-tissue formation trigged by aligned and randomly-oriented fibrous scaffolds, both in vitro and in vivo. The aligned group was observed to form more mature tendon-like tissue in the Achilles tendon injury model, as evidenced by histological scoring and collagen I immunohistochemical staining data. In contrast, the randomly-oriented group exhibited much chondrogenesis and subsequent bone tissue formation through ossification. Additionally, X-ray imaging and osteocalcin immunohistochemical staining also demonstrated that osteogenesis in vivo is driven by randomly oriented topography. Furthermore, MSCs on the aligned substrate exhibited tenocyte-like morphology and enhanced tenogenic differentiation compared to cells grown on randomly-oriented scaffold. qRT-PCR analysis of osteogenic marker genes and alkaline phosphatase (ALP) staining demonstrated that MSCs cultured on randomly-oriented fiber scaffolds displayed enhanced osteogenic differentiation compared with cells cultured on aligned fiber scaffolds. Finally, it was demonstrated that cytoskeletal tension release abrogated the divergent differentiation pathways on different substrate topography. Collectively, these findings illustrate the relationship between topographic cues of the scaffold and their inductive role in tissue regeneration; thus providing an insight into future development of smart functionalized bio-scaffold design and its application in tissue engineering. PMID:25617136

Yin, Zi; Chen, Xiao; Song, Hai-Xin; Hu, Jia-Jie; Tang, Qiao-Mei; Zhu, Ting; Shen, Wei-Liang; Chen, Jia-Lin; Liu, Huanhuan; Heng, Boon Chin; Ouyang, Hong-Wei

2015-03-01

298

Multiplicity of layered solutions for Allen-Cahn systems with symmetric double well potential  

NASA Astrophysics Data System (ADS)

We study the existence of solutions u:R3?R2 for the semilinear elliptic systems -?u(x,y,z)+?W(u(x,y,z))=0, where W:R2?R is a double well symmetric potential. We use variational methods to show, under generic non-degenerate properties of the set of one dimensional heteroclinic connections between the two minima a± of W, that (0.1) has infinitely many geometrically distinct solutions u?C2(R3,R2) which satisfy u(x,y,z)?a± as x?±? uniformly with respect to (y,z)?R2 and which exhibit dihedral symmetries with respect to the variables y and z. We also characterize the asymptotic behavior of these solutions as |(y,z)|?+?.

Alessio, Francesca; Montecchiari, Piero

2014-12-01

299

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

300

Differential metabolomic analysis of the potential antiproliferative mechanism of olive leaf extract on the JIMT-1 breast cancer cell line.  

PubMed

A new differential metabolomic approach has been developed to identify the phenolic cellular metabolites derived from breast cancer cells treated with a supercritical fluid extracted (SFE) olive leaf extract. The SFE extract was previously shown to have significant antiproliferative activity relative to several other olive leaf extracts examined in the same model. Upon SFE extract incubation of JIMT-1 human breast cancer cells, major metabolites were identified by using HPLC coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF-MS). After treatment, diosmetin was the most abundant intracellular metabolite, and it was accompanied by minor quantities of apigenin and luteolin. To identify the putative antiproliferative mechanism, the major metabolites and the complete extract were assayed for cell cycle, MAPK and PI3K proliferation pathways modulation. Incubation with only luteolin showed a significant effect in cell survival. Luteolin induced apoptosis, whereas the whole olive leaf extract incubation led to a significant cell cycle arrest at the G1 phase. The antiproliferative activity of both pure luteolin and olive leaf extract was mediated by the inactivation of the MAPK-proliferation pathway at the extracellular signal-related kinase (ERK1/2). However, the flavone concentration of the olive leaf extract did not fully explain the strong antiproliferative activity of the extract. Therefore, the effects of other compounds in the extract, probably at the membrane level, must be considered. The potential synergistic effects of the extract also deserve further attention. Our differential metabolomics approach identified the putative intracellular metabolites from a botanical extract that have antiproliferative effects, and this metabolomics approach can be expanded to other herbal extracts or pharmacological complex mixtures. PMID:25560707

Barrajón-Catalán, Enrique; Taamalli, Amani; Quirantes-Piné, Rosa; Roldan-Segura, Cristina; Arráez-Román, David; Segura-Carretero, Antonio; Micol, Vicente; Zarrouk, Mokhtar

2015-02-01

301

Dolphin and sea lion auditory evoked potentials in response to single and multiple swept amplitude tones.  

PubMed

Measurement of the auditory steady-state response (ASSR) is increasingly used to assess marine mammal hearing. These tests normally entail measuring the ASSR to a sequence of sinusoidally amplitude modulated tones, so that the ASSR amplitude function can be defined and the auditory threshold estimated. In this study, an alternative method was employed, where the ASSR was elicited by an amplitude modulated stimulus whose sound pressure level was slowly varied, or "swept," over a range of levels believed to bracket the threshold. The ASSR amplitude function was obtained by analyzing the resulting grand average evoked potential using a short-time Fourier transform. The suitability of this technique for hearing assessment of bottlenose dolphins and California sea lions was evaluated by comparing ASSR amplitude functions and thresholds obtained with swept amplitude and discrete, constant amplitude stimuli. When factors such as the number of simultaneous tones, the number of averages, and the frequency analysis window length were taken into account, the performance and time required for the swept-amplitude and discrete stimulus techniques were similar. The decision to use one technique over another depends on the relative importance of obtaining suprathreshold information versus the lowest possible thresholds. PMID:21877816

Finneran, James J; Mulsow, Jason; Schlundt, Carolyn E; Houser, Dorian S

2011-08-01

302

Culex gelidus: An emerging mosquito vector with potential to transmit multiple virus infections.  

PubMed

Culex gelidus Theobald has emerged as a major vector of Japanese encephalitis virus (JEV) in India, Southeast Asian countries and Australia. The species has expanded its geographic distribution from the Indian subcontinent to Japan, China, other Southeast Asian countries, Island nations in Australasian region and Australia. In recent years, a sudden increase in its population especially in the urban and sub-urban areas has been observed in several countries, thus, becoming a dominant mosquito species. The virus has been repeatedly isolated from from different geographical locations making it one of the most important vectors of JEV. Apart from JEV, other viruses of public health importance, viz. Getah, Ross River (RRV), Sindbis and Tembusu have been isolated from the mosquito. Experimental studies have shown that the mosquito Cx. qelidus is highly competent to transmit West Nile, Kunjin and Murray valley encephalitis viruses with infection and transmission rates of >80 and >50%, respectively for each virus. The species is also found competent to transmit RRV, but at a lower rate. Experimental studies have shown that the species is susceptible to chikungunya, Chandipura and Chittoor (Batai) viruses. Development of resistance to DDT and malathion has also been detected in the species recently. The invasive nature, ability to breed both in fresh and dirty waters, development of resistance to insecticides, high anthropophily and its potential to transmit important human viruses pose an increased threat of viral encephalitis in India and Oriental region especially in the light of explosive increase in its population. PMID:25540955

Sudeep, A B

2014-01-01

303

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

304

Protective effects of bioactive phytochemicals from Mentha piperita with multiple health potentials  

PubMed Central

Mentha piperita essential oil was bactericidal in order of E. coli> S. aureus > Pseudomonas aeruginosa > S. faecalis > Klebsiella pneumoniae. The oil with total phenolics of 89.43 ± 0.58 µg GAE/mg had 63.82 ± 0.05% DPPH inhibition activity with an IC 50 = 3.9 µg/ml. Lipid peroxidation inhibition was comparable to BHT and BHA. A 127% hike was noted in serum ferric-reducing antioxidant power. There was 38.3% decrease in WBCs count, while platelet count showed increased levels of 214.12%. Significant decrease in uric acid level and cholesterol/HDL and LDL/HDL ratios were recorded. The volatile oil displayed high cytotoxic action toward the human tumor cell line. The results of this study deserve attention with regard to antioxidative and possible anti-neoplastic chemotherapy that form a basis for future research. The essential oil of mint may be exploited as a natural source of bioactive phytopchemicals bearing antimicrobial and antioxidant potentials that could be supplemented for both nutritional purposes and preservation of foods. PMID:20931070

Sharafi, Seyedeh Maryam; Rasooli, Iraj; Owlia, Parviz; Taghizadeh, Massoud; Astaneh, Shakiba Darvish Alipoor

2010-01-01

305

The bone marrow stromal compartment in multiple myeloma patients retains capability for osteogenic differentiation in vitro: defining the stromal defect in myeloma.  

PubMed

Defects in bone repair contribute to multiple myeloma (MM) bone disease. It is unknown whether this reflects failure of osteogenic differentiation from mesenchymal stromal cells (MSC), inherent stromal defects or mature cell dysfunction. We quantified the number of fibroblast colony-forming units (CFU-f) and osteoblast colony-forming units (CFU-ob) in freshly isolated bone marrow (BM) from healthy individuals (N = 10) and MM patients (N = 54). CFU-f and CFU-ob were present in MM BM, at comparable frequency to normal subjects, irrespective of disease stage, and the presence of bone disease. Adherent cultures from MM BM are able to differentiate into osteoblasts, as indicated by the early upregulation of RUNX2, SP7, AXIN2 and DLX5, and the production of alkaline phosphatase and calcium. Coculture with MM cells failed to prevent osteogenic differentiation of adult human MSC. On the other hand, MM cells induced cell cycle progression in resting MSC in a cell contact dependent manner. This effect was confirmed using both primary CD138+ cells and MM cell lines, and was not seen with B or T cell lines. Our data confirm the presence of osteoblast progenitors and the preservation of osteogenic function in MM, however dysregulation of cell cycle control may contribute to the loss of normal bone homeostasis that ultimately results in osteolytic bone loss. PMID:25079197

Kassen, Deepika; Moore, Sally; Percy, Laura; Herledan, Gaelle; Bounds, Danton; Rodriguez-Justo, Manuel; Croucher, Peter; Yong, Kwee

2014-10-01

306

Humin as an electron donor for enhancement of multiple microbial reduction reactions with different redox potentials in a consortium.  

PubMed

A solid-phase humin, acting as an electron donor, was able to enhance multiple reductive biotransformations, including dechlorination of pentachlorophenol (PCP), dissimilatory reduction of amorphous Fe (III) oxide (FeOOH), and reduction of nitrate, in a consortium. Humin that was chemically reduced by NaBH4 served as an electron donor for these microbial reducing reactions, with electron donating capacities of 0.013 mmol e(-)/g for PCP dechlorination, 0.15 mmol e(-)/g for iron reduction, and 0.30 mmol e(-)/g for nitrate reduction. Two pairs of oxidation and reduction peaks within the humin were detected by cyclic voltammetry analysis. 16S rRNA gene sequencing-based microbial community analysis of the consortium incubated with different terminal electron acceptors, suggested that Dehalobacter sp., Bacteroides sp., and Sulfurospirillum sp. were involved in the PCP dechlorination, dissimilatory iron reduction, and nitrate reduction, respectively. These findings suggested that humin functioned as a versatile redox mediator, donating electrons for multiple respiration reactions with different redox potentials. PMID:25176636

Zhang, Dongdong; Zhang, Chunfang; Xiao, Zhixing; Suzuki, Daisuke; Katayama, Arata

2015-02-01

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. PMID:25228354

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

2014-12-01

308

Potential of a simple lab-on-a-tube for point-of-care measurements of multiple analytes.  

PubMed

This technical note presents a simple and disposable lab-on-a-tube (LOT) for point-of-care measurements of multiple analytes. LOT is a one-step device that can perform both sample collection and multi-sensing on-site. Sample collection is conducted by taking advantage of its inherent micro/macro channel structure while multi-sensing is conducted by integrated microsensors. This approach ensures reliable transportation of various samples into the testing area by either passive capillary force or active suction force, thus avoiding the need for a pump or injection components as used in lab-on-a-chip systems. The developed LOT (Diameter = 1 mm, Sensing length = 4.5 mm, Required sample volume = 3.5 microl) is capable of simultaneously quantifying the concentrations of glucose, lactate and oxygen in human serum samples. The result suggests the LOT hold great potential for many point-of-care applications. PMID:20480114

Li, Chunyan; Shutter, Lori A; Wu, Pei-Ming; Ahn, Chong H; Narayan, Raj K

2010-06-01

309

Microbial Monitoring of Pathogens by Comparing Multiple Real-Time PCR Platforms for Potential Space Applications  

NASA Technical Reports Server (NTRS)

The International Space Station (ISS) is a closed environment wih rotations of crew and equipment each introducing their own microbial flora making it necessary to monitor the air, surfaces, and water for microbial contamination. Current microbial monitoring includes labor and time intensive methods to enumerate total bacterial and fungal cells with limited characterization during in-flight testing. Although this culture-based method has been sufficient for monitoring the ISS, future long duration missions will need to perform more comprehensive characterization in-flight, since sample return and ground characterization may not be available. A workshop was held in 2011 at the Johnson Space Center to discuss alternative methodologies and technologies suitable for microbial monitoring for these longterm exploration missions where molecular-based methodologies, such as polymerase chain reaction (PCR), were recommended. In response, a multi-center (Marshall Space Flight Center, Johnson Space Center, Jet Propulsion Laboratory, and Kennedy Space Center) collaborative research effort was initiated to explore novel commercial-off-the-shelf hardware options for spaceflight environmental monitoring. The goal was to evaluate quantitative/semi-quantitative PCR approaches to space applications for low cost in-flight rapid identification of microorganisms affecting crew safety. The initial phase of this project identified commercially available platforms that could be minimally modified to perform nominally in microgravity followed by proof-of-concept testing on the highest qualifying candidates with a universally available test organism, Salmonella enterica. The platforms evaluated during proof-of-concept testing included the iCubate 2.0(TradeMark) (iCubate, Huntsville, AL), RAZOR EX (BioFire Diagnostics; Salt Lake City, Utah) and SmartCycler(TradeMark) (Cepheid; Sunnyvale, CA). The analysis identified two potential technologies (iCubate 2.0 and RAZOR EX) that were able to perform sample-to-answer testing with cell sample concentrations between SO to 400 cells. In addition, the commercial systems were evaluated for initial flight safety and readiness, sample concentration needs were reviewed, and a competitive procurement of commercially available platforms was initiated.

Birmele, Michele

2012-01-01

310

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

311

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization*  

PubMed Central

Multiple Ca2+-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca2+, although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys155, both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli. PMID:24174527

Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y.; Chung, Man-Kyo

2013-01-01

312

Quantum Dots Do Not Alter the Differentiation Potential of Pancreatic Stem Cells and Are Distributed Randomly among Daughter Cells  

PubMed Central

With the increasing relevance of cell-based therapies, there is a demand for cell-labeling techniques for in vitro and in vivo studies. For the reasonable tracking of transplanted stem cells in animal models, the usage of quantum dots (QDs) for sensitive cellular imaging has major advances. QDs could be delivered to the cytoplasm of the cells providing intense and stable fluorescence. Although QDs are emerging as favourable nanoparticles for bioimaging, substantial investigations are still required to consider their application for adult stem cells. Therefore, rat pancreatic stem cells (PSCs) were labeled with different concentrations of CdSe quantum dots (Qtracker 605 nanocrystals). The QD labeled PSCs showed normal proliferation and their usual spontaneous differentiation potential in vitro. The labeling of the cell population was concentration dependent, with increasing cell load from 5?nM QDs to 20?nM QDs. With time-lapse microscopy, we observed that the transmission of the QD particles during cell divisions was random, appearing as equal or unequal transmission to daughter cells. We report here that QDs offered an efficient and nontoxic way to label pancreatic stem cells without genetic modifications. In summary, QD nanocrystals are a promising tool for stem cell labeling and facilitate tracking of transplanted cells in animal models. PMID:23997768

Danner, S.; Benzin, H.; Vollbrandt, T.; Oder, J.; Richter, A.; Kruse, C.

2013-01-01

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

Population differentiation and species formation in the deep sea: the potential role of environmental gradients and depth.  

PubMed

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

315

Differential sensitivity of osteoblasts and bacterial pathogens to 405-nm light highlighting potential for decontamination applications in orthopedic surgery  

NASA Astrophysics Data System (ADS)

Healthcare associated infections pose a major threat to patients admitted to hospitals and infection rates following orthopedic arthroplasty surgery are as high as 4%. A 405-nm high-intensity narrow spectrum light has been proven to reduce environmental contamination in hospital isolation rooms, and there is potential to develop this technology for application in arthroplasty surgery. Cultured rat osteoblasts were exposed to varying light intensities and it was found that exposures of up to a dose of 36 J/cm2 had no significant effect on cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay], function (alkaline phosphatase activity), and proliferation rate (BrdU cell proliferation assay). High irradiance exposures (54 J/cm2) significantly affected the cell viability indicating that the effects of 405-nm light on osteoblasts are dose dependent. Additionally, exposure of a variety of clinically related bacteria to a dose of 36 J/cm2 resulted in up to 100% kill. These results demonstrating the differential sensitivity of osteoblasts and bacteria to 405-nm light are an essential step toward developing the technique for decontamination in orthopedic surgery.

Ramakrishnan, Praveen; Maclean, Michelle; MacGregor, Scott J.; Anderson, John G.; Grant, M. Helen

2014-10-01

316

Please cite this article in press as: M. Schiavon, et al., Transcriptome profiling of genes differentially modulated by sulfur and chromium identifies potential targets for phytoremediation and reveals a complex SCr interplay on sulfate transport regulati  

E-print Network

differentially modulated by sulfur and chromium identifies potential targets for phytoremediation and reveals differentially modulated by sulfur and chromium identifies potential targets for phytoremediation and reveals in the short-time response of plants to Cr exposure. I Potential gene targets for Cr phytoremediation have been

317

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

318

Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro  

PubMed Central

Aim: Glutamate receptors are expressed in osteoblastic cells. The present study was undertaken to investigate the mechanisms underlying the stimulation of osteoblast differentiation by N-methyl-D-aspartate (NMDA) receptor activation in vitro. Methods: Primary culture of osteoblasts was prepared from SD rats. Microarray was used to detect the changes of gene expression. The effect of NMDA receptor agonist or antagonist on individual gene was examined using RT-PCR. The activity of alkaloid phosphotase (ALP) was assessed using a commercial ALP staining kit. Results: Microarray analyses revealed that 10 genes were up-regulated by NMDA (0.5 mmol/L) and down-regulated by MK801 (100 ?mol/L), while 13 genes down-regulated by NMDA (0.5 mmol/L) and up-regulated by MK801 (100 ?mol/L). Pretreatment of osteoblasts with the specific PKC inhibitor Calphostin C (0.05 ?mol/L), the PKA inhibitor H-89 (20 nmol/L), or the PI3K inhibitor wortmannin (100 nmol/L) blocked the ALP activity increase caused by NMDA (0.5 mmol/L). Furthermore, NMDA (0.5 mmol/L) rapidly increased PI3K phosphorylation, which could be blocked by pretreatment of wortmannin (100 nmol/L). Conclusion: The results suggest that activation of NMDA receptors stimulates osteoblasts differentiation through PKA, PKC, and PI3K signaling pathways, which is a new role for glutamate in regulating bone remodeling. PMID:21685927

Li, Jie-li; Zhao, Lin; Cui, Bin; Deng, Lian-fu; Ning, Guang; Liu, Jian-min

2011-01-01

319

Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes  

PubMed Central

Pathway specificity is poorly understood for mitogen-activated protein kinase (MAPK) cascades that control different outputs in response to different stimuli. In yeast, it is not known how the same MAPK cascade activates Kss1 MAPK to promote invasive growth (IG) and proliferation, and both Fus3 and Kss1 MAPKs to promote mating. Previous work has suggested that the Kss1 MAPK cascade is activated independently of the mating G protein (Ste4)–scaffold (Ste5) system during IG. Here we demonstrate that Ste4 and Ste5 activate Kss1 during IG and in response to multiple stimuli including butanol. Ste5 activates Kss1 by generating a pool of active MAPKKK (Ste11), whereas additional scaffolding is needed to activate Fus3. Scaffold-independent activation of Kss1 can occur at multiple steps in the pathway, whereas Fus3 is strictly dependent on the scaffold. Pathway specificity is linked to Kss1 immunity to a MAPK phosphatase that constitutively inhibits basal activation of Fus3 and blocks activation of the mating pathway. These findings reveal the versatility of scaffolds and how a single MAPK cascade mediates different outputs. PMID:15192700

Andersson, Jessica; Simpson, David M; Qi, Maosong; Wang, Yunmei; Elion, Elaine A

2004-01-01

320

Development of a PCR-based strategy for CYP2D6 genotyping including gene multiplication of worldwide potential use.  

PubMed

There is growing consensus on the potential use of pharmacogenetics in clinical practice, and hopes have been expressed for application to the improvement of global health. However, two major challenges may lead to widening the "biotechnological gap" between the developing and the industrial world; first the unaffordability of some current technologies for poorer countries, and second the necessity of analyzing all described alleles for every clinical case due to the inability to predict the ethnic group of a given patient. Because of its role in the metabolism of a number of drugs, cytochrome P450 2D6 (CYP2D6) is an excellent candidate for use in the optimization of drug therapy. CYP2D6 is a highly polymorphic gene locus with more than 50 variant alleles, and subjects can be classified as poor metabolizers (PM), extensive metabolizers (EM), or ultrarapid metabolizers (UM) of a given CYP2D6 substrate. Several strategies and methods for CYP2D6 genotyping exist. Some, however, are expensive and laborious. The aim of this study was to design a PCR-based genotyping methodology to allow rapid, straightforward, and inexpensive identification of 90%-95% of CYP2D6 PM or UM genotypes for routine clinical use, independent of the individual's ethnic group. CYP2D6 is amplified in initial extra long PCRs (XL-PCRs), which subsequently undergo fragment-length polymorphism analysis for the determination of carriers of CYP2D6 allelic variants. The same XL-PCRs are also used for the determination of CYP2D6 multiplication and 2D6*5 allele (abolished activity). The application of this new strategy for the detection of CYP2D6 mutated alleles and multiplications to routine clinical analysis will enable the PM and UM phenotypes to be predicted and identified at a reasonable cost in a large number of individuals at most locations. PMID:18957039

Dorado, Pedro; Cáceres, Macarena; Pozo-Guisado, Eulalia; Wong, Ma-Li; Licinio, Julio; Llerena, Adrián

2005-10-01

321

Multiple techniques for mineral identification on Mars:. a study of hydrothermal rocks as potential analogues for astrobiology sites on Mars  

NASA Astrophysics Data System (ADS)

Spectroscopic studies of Mars analog materials combining multiple spectral ranges and techniques are necessary in order to obtain ground truth information for interpretation of rocks and soils on Mars. Two hydrothermal rocks from Yellowstone National Park, Wyoming, were characterized here because they contain minerals requiring water for formation and they provide a possible niche for some of the earliest organisms on Earth. If related rocks formed in hydrothermal sites on Mars, identification of these would be important for understanding the geology of the planet and potential habitability for life. XRD, thermal properties, VNIR, mid-IR, and Raman spectroscopy were employed to identify the mineralogy of the samples in this study. The rocks studied here include a travertine from Mammoth Formation that contains primarily calcite with some aragonite and gypsum and a siliceous sinter from Octopus Spring that contains a variety of poorly crystalline to amorphous silicate minerals. Calcite was detected readily in the travertine rock using any one of the techniques studied. The small amount of gypsum was uniquely identified using XRD, VNIR, and mid-IR, while the aragonite was uniquely identified using XRD and Raman. The siliceous sinter sample was more difficult to characterize using each of these techniques and a combination of all techniques was more useful than any single technique. Although XRD is the historical standard for mineral identification, it presents some challenges for remote investigations. Thermal properties are most useful for minerals with discrete thermal transitions. Raman spectroscopy is most effective for detecting polarized species such as CO 3, OH, and CH, and exhibits sharp bands for most highly crystalline minerals when abundant. Mid-IR spectroscopy is most useful in characterizing Si-O (and metal-O) bonds and also has the advantage that remote information about sample texture (e.g., particle size) can be determined. Mid-IR spectroscopy is also sensitive to structural OH, CO 3, and SO 4 bonds when abundant. VNIR spectroscopy is best for characterizing metal excitational bands and water, and is also a good technique for identification of structural OH, CO 3, SO 4, or CH bonds. Combining multiple techniques provides the most comprehensive information about mineralogy because of the different selection rules and particle size sensitivities, in addition to maximum coverage of excitational and vibrational bands at all wavelengths. This study of hydrothermal rocks from Yellowstone provides insights on how to combine information from multiple instruments to identify mineralogy and hence evidence of water on Mars.

Bishop, Janice L.; Murad, Enver; Lane, Melissa D.; Mancinelli, Rocco L.

2004-06-01

322

Low-Complexity Near-Optimum Multiple-Symbol Differential Detection of DAPSK Based on Iterative Amplitude/Phase Processing  

E-print Network

resilience against the typical high-Doppler-induced performance degradation of DAPSK and/or enhance it is robust against the phase ambiguities induced by rapid fading, while dispensing with channel estimation bit. As a potential complexity reduction technique, the well- known tree-search-based sphere detection

Southampton, University of

323

Urinary Metabolite Profiling Offers Potential for Differentiation of Liver-Kidney Yin Deficiency and Dampness-Heat Internal Smoldering Syndromes in Posthepatitis B Cirrhosis Patients  

PubMed Central

Zheng is the basic theory and essence of traditional Chinese medicine (TCM) in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX)” or “Dampness-Heat Internal Smoldering (SR)” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification.

Wang, Xiaoyan; Zhou, Mingmei; Yu, Huan; Lin, Yan; Du, Guangli; Luo, Guoan

2015-01-01

324

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

325

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

326

Poly(Epsilon-lysine) dendrons tethered with phosphoserine increase mesenchymal stem cell differentiation potential of calcium phosphate gels.  

PubMed

Calcium phosphates (CaP) are considered as biomaterials of choice for the treatment of critical-sized bone defects. Novel injectable CaP materials integrating poly(epsilon-lysine) generation 3 dendrons tethered with phosphoserine were obtained by sol-gel synthesis. This type of dendron was integrated to mimic the biochemical structure of noncollagenous proteins present in the forming osteoids during bone repair. Sol-gel synthesis was coupled with a dialysis process able to equilibrate the materials at a physiological pH value. Fourier transform infrared spectroscopy (FTIR) showed the successful retention of the dendrons after gel dialysis, whereas X-ray diffraction analysis demonstrated both the pH-tuned formation of a hydroxyapatite crystalline phase within the gel and the complete removal of ammonium nitrate deriving from the sol-gel reaction solvent. Scanning electron microscopy images confirmed the presence of crystalline domains in gels synthesized at pH 9.0. Injectability tests showed that the optimized formulations fulfilled the rheological properties required to minimally invasive surgical procedures. Cytotoxicity tests on osteoblast-like MG-63 cells as well as morphology and viability studies showed that the dendrons induced a significantly higher level of cell proliferation at early incubation time. Differentiation of the cell was also clearly enhanced at longer incubation time as demonstrated by both alkaline phosphatase activity and expression of typical markers. Altogether, the data from this work indicate the clinical potential of the osteoid-mimicking CaP cements in minimally invasive bone surgery. PMID:24229073

Raucci, Maria Grazia; Alvarez-Perez, Marco Antonio; Meikle, Steven; Ambrosio, Luigi; Santin, Matteo

2014-02-01

327

p-CREB expression in human gliomas: potential use in the differential diagnosis between astrocytoma and oligodendroglioma.  

PubMed

Phosphorylated cyclic-AMP responsive element binding protein (p-CREB) is a transcription factor that is involved in gliomagenesis. For this reason, it was recently proposed as a potential therapeutic target in gliomas; however, gliomas comprise tumors with different biomolecular profile, clinical behavior, and response to chemotherapy. In the present study, we aimed to investigate whether p-CREB expression varies in the 2 main types of gliomas, astrocytomas and oligodendrogliomas. Thus, we analyzed the expression of p-CREB in a series of astrocytomas and oligodendrogliomas of different histologic grades by immunohistochemistry and Western blot analysis. p53 overexpression and the Ki-67 labeling index were also assessed in all the tumors. p-CREB immunohistochemical expression was present in 100% of the astrocytic tumors, but in only 46% of oligodendrogliomas (P = .0033 for grade II; P = .0041 for grade III tumors). Absence of p-CREB immunohistochemical expression was significantly associated with 1p/19q codeletion (P < .0001) and identified 1p/19q codeleted tumors, with 70% sensitivity and 100% specificity (area under the curve = 0.85; P < .0001). In addition, p-CREB expression correlated with higher Ki-67 labeling index (P = .049) and p53 overexpression (P < .0001) as well as with the histologic grade of astrocytomas (P = .044). Immunohistochemical results were further confirmed by Western blot analysis. Our findings demonstrate that astrocytomas and oligodendrogliomas are characterized by distinctive patterns of p-CREB expression. These distinct expression patterns might provide insight into the mechanism of tumorigenesis of glial tumors and represent a useful tool for the differential diagnosis of astrocytoma and oligodendroglioma. PMID:25476123

Barresi, Valeria; Mondello, Stefania; Branca, Giovanni; Rajan, Thangavelu Soundara; Vitarelli, Enrica; Tuccari, Giovanni

2015-02-01

328

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

329

A composite enhancer regulates p63 gene expression in epidermal morphogenesis and in keratinocyte differentiation by multiple mechanisms.  

PubMed

p63 is a crucial regulator of epidermal development, but its transcriptional control has remained elusive. Here, we report the identification of a long-range enhancer (p63LRE) that is composed of two evolutionary conserved modules (C38 and C40), acting in concert to control tissue- and layer-specific expression of the p63 gene. Both modules are in an open and active chromatin state in human and mouse keratinocytes and in embryonic epidermis, and are strongly bound by p63. p63LRE activity is dependent on p63 expression in embryonic skin, and also in the commitment of human induced pluripotent stem cells toward an epithelial cell fate. A search for other transcription factors involved in p63LRE regulation revealed that the CAAT enhancer binding proteins Cebpa and Cebpb and the POU domain-containing protein Pou3f1 repress p63 expression during keratinocyte differentiation by binding the p63LRE enhancer. Collectively, our data indicate that p63LRE is composed of additive and partly redundant enhancer modules that act to direct robust p63 expression selectively in the basal layer of the epidermis. PMID:25567987

Antonini, Dario; Sirico, Anna; Aberdam, Edith; Ambrosio, Raffaele; Campanile, Carmen; Fagoonee, Sharmila; Altruda, Fiorella; Aberdam, Daniel; Brissette, Janice L; Missero, Caterina

2015-01-30

330

Mutations in the Arabidopsis Peroxisomal ABC Transporter COMATOSE Allow Differentiation between Multiple Functions In Planta: Insights from an Allelic Series  

PubMed Central

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal ?-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; Lousa, Carine De Marcos; Baldwin, Jocelyn M.; Baldwin, Stephen A.; Baker, Alison; Holdsworth, Michael J.

2009-01-01

331

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

332

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni  

PubMed Central

Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

2015-01-01

333

potential of Visible-Near Infrared Spectroscopy for mapping of multiple soil properties using real-time soil sensor  

NASA Astrophysics Data System (ADS)

Over the past few decades, scientists have understood the needs for the exploitation of optical means particularly Vis-NIR spectroscopy to measure agriculture soil properties in real-time. The objective of this study is therefore to investigate the potential of Vis-NIR spectroscopy for mapping of multiple (19) soil properties using the optical-based real-time soil sensor (RTSS). For this purpose, Vis-NIR soil reflectance spectra (from 310 to 1700nm) were acquired using a tractor-mounted RTSS at 2 fields of a commercial farm in Hokkaido, Japan. The RTSS consists of a halogen lamp, fiber optics, two spectrophotometers, computer, DGPS receiver, and CCD camera. A total of 262 soil samples were collected subsequently for laboratory chemical analysis. PLSR coupled with full-cross validation was used to establish the relationship between the pre-treated Vis-NIR spectra with the value of soil properties obtained by chemical analysis. From this analysis, it was found that the accuracy of the calibration models ranged from Rval2 of 0.65 to 0.86 and RPD from 1.7 to 2.7, meaning that the accuracy some of the models were excellent and others were almost good. Moreover, the predicted maps of 19 soil properties were comparable with the measured map. This shows that the RTSS by means of Vis-NIR spectroscopy can be used for mapping the 19 soil properties.

Aliah, B. S. N.; Kodaira, M.; Shibusawa, S.

2013-05-01

334

Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.  

PubMed

In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

2015-04-01

335

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; Dessì, Maria A.; Rescigno, Antonio

2013-01-01

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

Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells.  

PubMed

Methotrexate (MTX), as a chemotherapeutic drug, is widely used in the therapy of several cancer types. The efficiency of drug treatment is compromised by the appearance of multidrug resistance (MDR), and the underlying molecular mechanisms remain incompletely understood. We investigated the mechanism of MDR in the MTX-induced breast cancer MCF-7 cells (MCF-7/MTX) using proteomic analysis. MCF-7 drug-sensitive cells (MCF-7/S) were exposed in progressively increasing concentrations of MTX to establish the drug-resistant cell line MCF-7/MTX. The biological characteristics of the cells were analyzed by MTT, flow cytometry, quantitative PCR, western blotting and the global protein profiles of MCF-7/MTX and MCF-7/S were compared using a proteomic approach. The resistance factor of MCF-7/MTX cells was 64, and it possessed significant MDR. Seventeen differentially expressed proteins between MCF-7/MTX and MCF-7/S cells were identified, seven proteins were upregulated and 10 proteins were downregulated in MCF-7/MTX cells. We verified that the protein levels of nucleophosmin (NPM), ?-enolase (ENO1) and vimentin (VIM) were upregulated, and heterogeneous nuclear ribonucleoprotein (hnRNP C1/C2), phosphoglycerate mutase 1 (PGAM1) and proteasome subunit ? type-2 (PSMA2) were downregulated in MCF-7/MTX cells. The mRNA levels of NPM, VIM, hnRNP C1/C2, PGAM1 and PSMA2 were consistent with the protein expressions, but the gene expression of ENO1 was slightly downregulated. Surprisingly, knockdown of NPM by siRNA sensitized MCF-7/MTX cells to MTX and attenuated the multidrug resistance. The proteins identified, particularly NPM provides new insights into the mechanism of MDR and is expected to become a crucial molecular target for breast cancer treatment. PMID:24736981

Chen, Siying; Cai, Jiangxia; Zhang, Weipeng; Zheng, Xiaowei; Hu, Sasa; Lu, Jun; Xing, Jianfeng; Dong, Yalin

2014-07-01

338

Development of real-time PCR assay for differential detection and quantification for multiple Babesia microti-genotypes.  

PubMed

We have developed a real-time PCR assay that can rapidly and differentially detect and quantify four genotypes of small subunit ribosomal RNA gene (SSUrDNA) of Babesia microti (Kobe-, Otsu-, Nagano- and US-types). In this assay, four genotype-specific pairs of primers targeted on internal transcribed spacer (ITS) 1 or 2 sequences were used and amplicons by each pair of primers were quantitatively detected by fluorescent SYBR Green I. The four genotype-specific pairs of primers displayed the high specificity for homologous genotype DNA. The standard curves of cycle threshold (Ct) values versus amount of target DNA per reaction (log) for all four genotypes were linear and the correlation coefficient (Rsq) values for the curves were from 0.970 to 0.997. The standard curves were almost identical even in the presence of heterologous genotype DNA. This assay could detect 10-30 fg purified DNA (equivalent to the amount of 1-5 parasite DNA) of each genotype B. microti. This assay could also detect each genotype B. microti infection in blood with 3×10(-6)%-1×10(-5)% parasitemia. This assay was applicable to field rodent and tick samples to reveal mixed infection in several samples, for which a single genotype of B. microti had been detected by direct sequencing analyses in our previous studies. This assay also seemed to be applicable to clinical human samples, showing Kobe-type positive results for the first Japanese babesiosis patient and the asymptomatic donor, both infected with Kobe-type B. microti. PMID:21723958

Ohmori, Shiho; Kawai, Atsuko; Takada, Nobuhiro; Saito-Ito, Atsuko

2011-12-01

339

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, François-X; Vanderheyden, Nancy; Brucato, Nicolas; Waelkens, Marc; Decorte, Ronny

2011-01-01

340

Carfilzomib promotes the osteogenic differentiation potential of mesenchymal stem cells derived from myeloma patients by inhibiting notch1 activity in vitro.  

PubMed

Notch1 signaling plays a key role in the differentiation of mesenchymal stem cells (MSCs). Carfilzomib (CFZ), a second-generation proteasome inhibitor, has potent cytotoxicity against myeloma cells. In this study, we investigated the effects of CFZ on the osteogenic differentiation potential of MSCs derived from myeloma patients (MM-MSCs) in vitro. MM-MSCs showed decreased osteogenic differentiation ability, together with an impairment of notch1 deactivation. The notch1 inhibitor DAPT and the downregulation of notch1 by shRNA promoted osteogenesis in MM-MSCs. Additionally, CFZ treatment resulted in notch1 inhibition and enhanced osteogenesis in MM-MSCs. These findings suggest that CFZ stimulates osteogenesis via notch1 inhibition. PMID:24939218

Li, Yali; Li, Jun; Zhuang, Wenzhuo; Wang, Qian; Ge, Xueping; Zhang, Xiaohui; Chen, Ping; Fu, Jinxiang; Li, Bingzong

2014-08-01

341

Catalase potentiates retinoic acid-induced THP1 monocyte differentiation into macrophage through inhibition of peroxisome proliferator-activated receptor  

Microsoft Academic Search

Macrophage differentiation plays a piv- otal role in cardiovascular diseases and many other physiological processes. However, the role of re- action oxygen species in macrophage differentia- tion has not been elucidated. Here, we report func- tional characterization of catalase, an enzyme that degrades hydrogen peroxide (H2O2), in THP-1 monocyte differentiation. Treatment of THP-1 cells with catalase was able to synergize

Qiurong Ding; Ting Jin; Zhenzhen Wang; Yan Chen

2007-01-01

342

Mesenchymal stem cell secretion of chemokines during differentiation into osteoblasts, and their potential role in mediating interactions with breast cancer cells.  

PubMed

Over 70% of patients with advanced breast cancer will develop bone metastases for which there is no cure. Mesenchymal Stem Cells (MSCs) and their derivative osteoblasts are subpopulations of cells within the bone marrow environment, postulated as potential interacting targets for disseminating cancer cells because of their ability to secrete a range of chemokines. This study aimed to investigate chemokine secretion throughout MSC differentiation into osteoblasts and their effect on the breast cancer cells. Primary MSCs and osteoblast progenitors were cultured in appropriate conditions to induce differentiation into mature osteoblasts. Chemokines secreted throughout differentiation were detected using ChemiArray and ELISA. Migration of breast cancer cells in response to the bone-derived cells was quantified using Transwell inserts. Breast cancer cells were cocultured with MSCs, retrieved using magnetic beads, and changes in CCL2 expression were analyzed. MSCs secreted a range of factors including IL-6, TIMP-1 and CCL2, the range and level of which changed throughout differentiation. CCL2 secretion by MSCs increased significantly above control cells as they differentiated into mature osteoblasts (p<0.05). The bone-derived cells stimulated migration of breast cancer cells, and this was inhibited (21-50%) in the presence of a CCL2 antibody. CCL2 gene expression in breast cancer cells was upregulated following direct coculture with MSCs. The varying levels of chemokines secreted throughout MSC differentiation may play an important role in supporting tumor cell homing and progression. These results further highlight the distinct effect MSCs have on breast cancer cells and their potential importance in supporting development of metastases. PMID:19003962

Molloy, Alan P; Martin, Fiachra T; Dwyer, Roisin M; Griffin, Tomas P; Murphy, Mary; Barry, Frank P; O'Brien, Timothy; Kerin, Michael J

2009-01-15

343

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

344

Differential neuroprotective potential of CRMP2 peptide aptamers conjugated to cationic, hydrophobic, and amphipathic cell penetrating peptides  

PubMed Central

The microtubule-associated axonal specification collapsin response mediator protein 2 (CRMP2) is a novel target for neuroprotection. A CRMP2 peptide (TAT-CBD3) conjugated to the HIV transactivator of transcription (TAT) protein’s cationic cell penetrating peptide (CPP) motif protected neurons in the face of toxic levels of Ca2+ influx leaked in via N-methyl-D-aspartate receptor (NMDAR) hyperactivation. Here we tested whether replacing the hydrophilic TAT motif with alternative cationic (nona-arginine (R9)), hydrophobic (membrane transport sequence (MTS) of k-fibroblast growth factor) or amphipathic (model amphipathic peptide (MAP)) CPPs could be superior to the neuroprotection bestowed by TAT-CBD3. In giant plasma membrane vesicles (GPMVs) derived from cortical neurons, the peptides translocated across plasma membranes with similar efficiencies. Cortical neurons, acutely treated with peptides prior to a toxic glutamate challenge, demonstrated enhanced efflux of R9-CBD3 compared to others. R9-CBD3 inhibited N-methyl-D-aspartate (NMDA)-evoked Ca2+ influx to a similar extent as TAT-CBD3 while MTS-CBD3 was ineffective which correlated with the ability of R9- and TAT-CBD3, but not MTS-CBD3, to block NMDAR interaction with CRMP2. Unrestricted Ca2+ influx through NMDARs leading to delayed calcium dysregulation and neuronal cell death was blocked by all peptides but MAP-CBD3. When applied acutely for 10 min, R9-CBD3 was more effective than TAT-CBD3 at neuroprotection while MTS- and MAP-CBD3 were ineffective. In contrast, long-term (>24 h) treatment with MTS-CBD3 conferred neuroprotection where TAT-CBD3 failed. Neither peptide altered surface trafficking of NMDARs. Neuroprotection conferred by MTS-CBD3 peptide is likely due to its increased uptake coupled with decreased efflux when compared to TAT-CBD3. Overall, our results demonstrate that altering CPPs can bestow differential neuroprotective potential onto the CBD3 cargo.

Moutal, Aubin; François-Moutal, Liberty; Brittain, Joel M.; Khanna, May; Khanna, Rajesh

2015-01-01

345

Assessment of the therapeutic potential of cytokines, cytotoxic drugs and effector cell populations for the treatment of multiple myeloma using the 5T33 murine myeloma model  

Microsoft Academic Search

The therapeutic potential of six cytokines, eight cytotoxic drugs and two effector cell populations for the treatment of multiple myeloma was assessed in vitro using the 5T33 murine myeloma model. The efficacy of combination IFN-? and melphalan therapy was also evaluated in vitro and in vivo. Of the cytokines tested in vitro using the MTT assay, only IFN-? demonstrated significant

Linda S Manning; Narelle L Chamberlain; Michael F Leahy; Frank T Cordingley

1995-01-01

346

Differentiation Potential of O Bombay Human-Induced Pluripotent Stem Cells and Human Embryonic Stem Cells into Fetal Erythroid-Like Cells  

PubMed Central

Objective There is constant difficulty in obtaining adequate supplies of blood components, as well as disappointing performance of "universal" red blood cells. Advances in somatic cell reprogramming of human-induced pluripotent stem cells (hiPSCs) have provided a valuable alternative source to differentiate into any desired cell type as a therapeutic promise to cure many human disease. Materials and Methods In this experimental study, we examined the erythroid differentiation potential of normal Bombay hiPSCs (B-hiPSCs) and compared results to human embryonic stem cell (hESC) lines. Because of lacking ABO blood group expression in B-hiPSCs, it has been highlighted as a valuable source to produce any cell type in vitro. Results Similar to hESC lines, hemangioblasts derived from B-hiPSCs expressed approximately 9% KDR+CD31+ and approximately 5% CD31+CD34+. In semisolid media, iPSC and hESC-derived hemangioblast formed mixed type of hematopoietic colony. In mixed colonies, erythroid progenitors were capable to express CD71+GPA+HbF+ and accompanied by endothelial cells differentiation. Conclusion Finally, iPS and ES cells have been directly induced to erythropoiesis without hemangioblast formation that produced CD71+HbF+ erythroid cells. Although we observed some variations in the efficiency of hematopoietic differentiation between iPSC and ES cells, the pattern of differentiation was similar among all three tested lines.

Ganji, Fatemeh; Abroun, Saeid; Baharvand, Hossein; Aghdami, Nasser; Ebrahimi, Marzieh

2015-01-01

347

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

348

Demonstration of differential quantitative requirements for NSF among multiple vesicle fusion pathways of GLUT4 using a dominant-negative ATPase-deficient NSF  

SciTech Connect

In this study, we investigated the relative participation of N-ethylmaleimide-sensitive factor (NSF) in vivo in a complex multistep vesicle trafficking system, the translocation response of GLUT4 to insulin in rat adipose cells. Transfections of rat adipose cells demonstrate that over-expression of wild-type NSF has no effect on total, or basal and insulin-stimulated cell-surface expression of HA-tagged GLUT4. In contrast, a dominant-negative NSF (NSF-D1EQ) can be expressed at a low enough level that it has little effect on total HA-GLUT4, but does reduce both basal and insulin-stimulated cell-surface HA-GLUT4 by {approx}50% without affecting the GLUT4 fold-translocation response to insulin. However, high expression levels of NSF-D1EQ decrease total HA-GLUT4. The inhibitory effect of NSF-D1EQ on cell-surface HA-GLUT4 is reversed when endocytosis is inhibited by co-expression of a dominant-negative dynamin (dynamin-K44A). Moreover, NSF-D1EQ does not affect cell-surface levels of constitutively recycling GLUT1 and TfR, suggesting a predominant effect of low-level NSF-D1EQ on the trafficking of GLUT4 from the endocytic recycling compared to the intracellular GLUT4-specific compartment. Thus, our data demonstrate that the multiple fusion steps in GLUT4 trafficking have differential quantitative requirements for NSF activity. This indicates that the rates of plasma and intracellular membrane fusion reactions vary, leading to differential needs for the turnover of the SNARE proteins.

Chen Xiaoli [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Matsumoto, Hideko [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Hinck, Cynthia S. [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Al-Hasani, Hadi [Institute of Biochemistry, University of Cologne, Cologne (Germany); St-Denis, Jean-Francois [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Whiteheart, Sidney W. [Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY (United States); Cushman, Samuel W. [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States)]. E-mail: sam_cushman@nih.gov

2005-07-22

349

From broadscale patterns to fine-scale processes: habitat structure influences genetic differentiation in the pitcher plant midge across multiple spatial scales.  

PubMed

The spatial scale at which samples are collected and analysed influences the inferences that can be drawn from landscape genetic studies. We examined genetic structure and its landscape correlates in the pitcher plant midge, Metriocnemus knabi, an inhabitant of the purple pitcher plant, Sarracenia purpurea, across several spatial scales that are naturally delimited by the midge's habitat (leaf, plant, cluster of plants, bog and system of bogs). We analysed 11 microsatellite loci in 710 M. knabi larvae from two systems of bogs in Algonquin Provincial Park (Canada) and tested the hypotheses that variables related to habitat structure are associated with genetic differentiation in this midge. Up to 54% of variation in individual-based genetic distances at several scales was explained by broadscale landscape variables of bog size, pitcher plant density within bogs and connectivity of pitcher plant clusters. Our results indicate that oviposition behaviour of females at fine scales, as inferred from the spatial locations of full-sib larvae, and spatially limited gene flow at broad scales represent the important processes underlying observed genetic patterns in M. knabi. Broadscale landscape features (bog size and plant density) appear to influence oviposition behaviour of midges, which in turn influences the patterns of genetic differentiation observed at both fine and broad scales. Thus, we inferred linkages among genetic patterns, landscape patterns and ecological processes across spatial scales in M. knabi. Our results reinforce the value of exploring such links simultaneously across multiple spatial scales and landscapes when investigating genetic diversity within a species. PMID:21929541

Rasic, Gordana; Keyghobadi, Nusha

2012-01-01

350

Validity of approximate methods in molecular scattering. III - Effective potential and coupled states approximations for differential and gas kinetic cross sections  

NASA Technical Reports Server (NTRS)

Two dimensionality-reducing approximations, the j sub z-conserving coupled states (sometimes called the centrifugal decoupling) method and the effective potential method, were applied to collision calculations of He with CO and with HCl. The coupled states method was found to be sensitive to the interpretation of the centrifugal angular momentum quantum number in the body-fixed frame, but the choice leading to the original McGuire-Kouri expression for the scattering amplitude - and to the simplest formulas - proved to be quite successful in reproducing differential and gas kinetic cross sections. The computationally cheaper effective potential method was much less accurate.

Monchick, L.; Green, S.

1977-01-01

351

Potential role of heat shock proteins in neural differentiation of murine embryonal carcinoma stem cells (P19).  

PubMed

HSPs (heat shock proteins) have been recognized to maintain cellular homoeostasis during changes in microenvironment. The present study aimed to investigate the HSPs expression pattern in hierarchical neural differentiation stages from mouse embryonal carcinoma stem cells (P19) and its role in heat stressed exposed cells. For induction of HSPs, cells were heated at 42°C for 30 min and recovered at 37°C in different time points. For neural differentiation, EBs (embryoid bodies) were formed by plating P19 cells in bacterial dishes in the presence of 1 mM RA (retinoic acid) and 5% FBS (fetal bovine serum). Then, on the sixth day, EBs were trypsinized and plated in differentiation medium containing neurobasal medium, B27, N2 and 5% FBS and for an extra 4 days. The expression of HSPs and neural cell markers were evaluated by Western blot, flow cytometry and immunocytochemistry in different stages. Our results indicate that HSC (heat shock constant)70 and HSP60 expressions decreased following RA treatment, EB formation and in mature neural cells derived from heat-stressed single cells and not heat-treated EBs. While the level of HSP90 increased six times following maturation process, HSP25 was expressed constantly during neural differentiation; however, its level was enhanced with heat stress. Accordingly, heat shock 12 h before the initiation of differentiation did not affect the expression of neuroectodermal and neural markers, nestin and ?-tubulin III, respectively. However, both markers increased when heat shock was induced after treatment and when EBs were formed. In conclusion, our results raise the possibility that HSPs could regulate cell differentiation and proliferation under both physiological and pathological conditions. PMID:21355853

Afzal, Elahe; Ebrahimi, Marzieh; Najafi, S Mahmoud Arab; Daryadel, Arezoo; Baharvand, Hossein

2011-07-01

352

Differential analysis of N-glycoproteome between hepatocellular carcinoma and normal human liver tissues by combination of multiple protease digestion and solid phase based labeling  

PubMed Central

Background Dysregulation of glycoproteins is closely related with many diseases. Quantitative proteomics methods are powerful tools for the detection of glycoprotein alterations. However, in almost all quantitative glycoproteomics studies, trypsin is used as the only protease to digest proteins. This conventional method is unable to quantify N-glycosites in very short or long tryptic peptides and so comprehensive glycoproteomics analysis cannot be achieved. Methods In this study, a comprehensive analysis of the difference of N-glycoproteome between hepatocellular carcinoma (HCC) and normal human liver tissues was performed by an integrated workflow combining the multiple protease digestion and solid phase based labeling. The quantified N-glycoproteins were analyzed by GoMiner to obtain a comparative view of cellular component, biological process and molecular function. Results/conclusions An integrated workflow was developed which enabled the processes of glycoprotein coupling, protease digestion and stable isotope labeling to be performed in one reaction vessel. This workflow was firstly evaluated by analyzing two aliquots of the same protein extract from normal human liver tissue. It was demonstrated that the multiple protease digestion improved the glycoproteome coverage and the quantification accuracy. This workflow was further applied to the differential analysis of N-glycoproteome of normal human liver tissue and that with hepatocellular carcinoma. A total of 2,329 N-glycosites on 1,052 N-glycoproteins were quantified. Among them, 858 N-glycosites were quantified from more than one digestion strategy with over 99% confidence and 1,104 N-glycosites were quantified from only one digestion strategy with over 95% confidence. By comparing the GoMiner results of the N-glycoproteins with and without significant changes, the percentage of membrane and secreted proteins and their featured biological processes were found to be significant different revealing that protein glycosylation may play the vital role in the development of HCC. PMID:25097464

2014-01-01

353

Differentiation modulates the balance of positive and negative Jun/AP-1 DNA binding activities to regulate cellular proliferative potential: different effects in nontransformed and transformed cells  

PubMed Central

Differentiation of 3T3T cells into adipocytes results in the progressive repression of growth factor responsiveness. This is associated with the transcriptional repression of the inducibility of c- jun and junB expression by serum. In contrast, differentiation of SV-40 large T antigen-transformed 3T3T cells (CSV3-1) does not repress growth factor responsiveness nor c-jun or junB inducibility even though CSV3-1 cells can differentiate into adipocytes. To better explain these observations, we have studied compositional changes in AP-1 DNA binding activity attributed to c-Jun, JunB, and JunD during the differentiation process in 3T3T and CSV3-1 cells. The results show that in nontransformed 3T3T cells, differentiation represses AP-1 DNA binding activity via a proportionate downregulation of c-Jun, JunB, and JunD. In contrast, in CSV3-1 cells, AP-1 DNA binding activity increases twofold during differentiation, which is accounted for by an increase in JunD with no change in c-Jun and JunB. If c-Jun and JunB serve as positive regulators and JunD serves as a negative regulator for cell proliferation as suggested by previous studies, the repression of JunD expression in differentiating CSV3-1 cells should be mitogenic because decreasing JunD/AP-1 DNA binding activity would allow c-Jun/AP-1 and JunB/AP-1 DNA binding activities to be dominant. The results confirm this prediction showing that antisense junD oligodeoxyribonucleotides are mitogenic for differentiating CSV3-1 cells whereas antisense c-jun and junB inhibit mitogenesis. These data support the conclusion that differentiation can regulate cellular proliferative potential by modulating the balance of positive and negative Jun/AP-1 DNA binding activities in distinct ways in nontransformed and transformed cells. PMID:8922393

1996-01-01

354

Comparative analysis of multilineage properties of mesenchymal stromal cells derived from fetal sources shows an advantage of mesenchymal stromal cells isolated from cord blood in chondrogenic differentiation potential  

PubMed Central

Background aims Cord blood (CB) and amniotic fluid (AF) could represent new and attractive mesenchymal stromal cell (MSC) sources, but their potential therapeutic applications are still limited by lack of standardized protocols for isolation and differentiation. In particular, chondrogenic differentiation has never been deeply investigated. Methods MSCs were obtained from CB and AF samples collected during cesarean sections at term and compared for their biological and differentiation properties, with particular interest in cartilage differentiation, in which quantitative real-time polymerase chain reaction and immunohistochemical analyses were performed to evaluate the expression of type 2 collagen, type 10 collagen, SRY-box9 and aggrecan. Results We were able to isolate MSCs from 12 of 30 (40%) and 5 of 20 (25%) CB and AF units, respectively. Fluorescence in situ hybridization analysis indicated the fetal origin of isolated MSC strains. Both populations expressed mesenchymal but not endothelial and hematopoietic markers, even though we observed a lower expression of human leukocyte antigen (HLA) I in CB-MSCs. No differences in proliferation rate and cell cycle analysis could be detected. After osteogenic induction, both populations showed matrix mineralization and typical marker expression. Under chondrogenic conditions, pellets derived from CB-MSCs, in contrast with AF-MSCs pellets, were significantly larger, showed cartilage-like morphology and resulted positive for chondrocyte-associated markers, such as type 2 collagen, type 10 collagen, SRY-box9 and aggrecan. Conclusions Our results show that CB-MSCs and AF-MSCs collected at term differ from each other in their biological and differentiation properties. In particular, only CB-MSCs showed a clear chondrogenic potential and thus could represent an ideal candidate for cartilage-tissue engineering. PMID:24794181

Pievani, Alice; Scagliotti, Valeria; Russo, Francesca Maria; Azario, Isabella; Rambaldi, Benedetta; Sacchetti, Benedetto; Marzorati, Simona; Erba, Eugenio; Giudici, Giovanni; Riminucci, Mara; Biondi, Andrea; Vergani, Patrizia; Serafini, Marta

2014-01-01

355

Differential mesengenic potential and expression of stem cell-fate modulators in mesenchymal stromal cells from human-term placenta and bone marrow.  

PubMed

Placenta has attracted increasing attention over the past decade as a stem cell source for regenerative medicine. In particular, the amniochorionic membrane has been shown to harbor populations of mesenchymal stromal cells (MSCs). In this study, we have characterized ex vivo expanded MSCs from the human amniotic (hAMSCs) and chorionic (hCMSCs) membranes of human full-term placentas and adult bone marrow (hBMSCs). Our results show that hAMSCs, hCMSCs, and hBMSCs express typical mesenchymal (CD73, CD90, CD105, CD44, CD146, CD166) and pluripotent (Oct-4, Sox2, Nanog, Lin28, and Klf4) markers but not hematopoietic markers (CD45, CD34). Ex vivo expanded hAMSCs were found to be of fetal origin, while hCMSCs cultures contained only maternal cells. Cell proliferation was significantly higher in hCMSCs, compared to hAMSCs and hBMSCs. Integrin profiling revealed marked differences in the expression of ? subunits between the three cell sources. Cadherin receptors were consistently expressed on a subset of progenitors (ranging from 1% to 60%), while N-CAM (CD56) was only expressed in hAMSCs and hCMSCs but not in hBMSCs. When induced to differentiate, hAMSCs and hCMSCs displayed strong chondrogenic and osteogenic differentiation potential but very limited capacity for adipogenic conversion. In contrast, hBMSCs showed strong differentiation potential along the three lineages. These results illustrate how MSCs from different ontological sources display differential expression of cell-fate mediators and mesodermal differentiation capacity. PMID:22105866

Jaramillo-Ferrada, Pamela A; Wolvetang, Ernst J; Cooper-White, Justin J

2012-09-01

356

Differential Relationships between WISC-IV and WIAT-II Scales: An Evaluation of Potentially Moderating Child Demographics  

ERIC Educational Resources Information Center

Considerable debate exists regarding the accuracy of intelligence tests with members of different groups. This study investigated differential predictive validity of the "Wechsler Intelligence Scale for Children-Fourth Edition". Participants from the WISC-IV--WIAT-II standardization linking sample (N = 550) ranged in age from 6 through 16 years (M…

Konold, Timothy R.; Canivez, Gary L.

2010-01-01

357

Multiple Classes of Transcription Factors Regulate the Expression of VASCULAR-RELATED NAC-DOMAIN7, a Master Switch of Xylem Vessel Differentiation.  

PubMed

The secondary cell walls of xylem cells, including vessel elements, provide mechanical strength and contribute to the conduction of water and minerals. VASCULAR-RELATED NAC-DOMAIN7 (VND7) is a NAC-domain transcription factor that regulates the expression of genes required for xylem vessel element formation. Transient expression assays using 68 transcription factors that are expressed during xylem vessel differentiation showed that 14 transcription factors, including VND1-VND7, are putative positive regulators of VND7 expression. Electrophoretic mobility shift assays revealed that all seven VND proteins bound to the VND7 promoter region at its SMBE/TERE motif, indicating that VND7 is a direct target of all of the VND transcription factors. Overexpression of VND1-VND5, GATA12 and ANAC075, newly identified transcription factors that function upstream of VND7, resulted in ectopic xylem vessel element formation. These data suggest that VND7 transcription is a regulatory target of multiple classes of transcription factors. PMID:25265867

Endo, Hitoshi; Yamaguchi, Masatoshi; Tamura, Taizo; Nakano, Yoshimi; Nishikubo, Nobuyuki; Yoneda, Arata; Kato, Ko; Kubo, Minoru; Kajita, Shinya; Katayama, Yoshihiro; Ohtani, Misato; Demura, Taku

2014-09-29

358

Targeted Quantitation of Site-Specific Cysteine Oxidation in Endogenous Proteins Using a Differential Alkylation and Multiple Reaction Monitoring Mass Spectrometry Approach  

PubMed Central

Reactive oxygen species (ROS) are both physiological intermediates in cellular signaling and mediators of oxidative stress. The cysteine-specific redox-sensitivity of proteins can shed light on how ROS are regulated and function, but low sensitivity has limited quantification of the redox state of many fundamental cellular regulators in a cellular context. Here we describe a highly sensitive and reproducible oxidation analysis approach (OxMRM) that combines protein purification, differential alkylation with stable isotopes, and multiple reaction monitoring mass spectrometry that can be applied in a targeted manner to virtually any cysteine or protein. Using this approach, we quantified the site-specific cysteine oxidation status of endogenous p53 for the first time and found that Cys182 at the dimerization interface of the DNA binding domain is particularly susceptible to diamide oxidation intracellularly. OxMRM enables analysis of sulfinic and sulfonic acid oxidation levels, which we validate by assessing the oxidation of the catalytic Cys215 of protein tyrosine phosphatase-1B under numerous oxidant conditions. OxMRM also complements unbiased redox proteomics discovery studies as a verification tool through its high sensitivity, accuracy, precision, and throughput. PMID:20233844

Held, Jason M.; Danielson, Steven R.; Behring, Jessica B.; Atsriku, Christian; Britton, David J.; Puckett, Rachel L.; Schilling, Birgit; Campisi, Judith; Benz, Christopher C.; Gibson, Bradford W.

2010-01-01

359

Assessment of pluripotency and multilineage differentiation potential of NTERA-2 cells as a model for studying human embryonic stem cells.  

PubMed

Embryonal carcinoma cells are pluripotent stem cells derived from teratocarcinomas and are considered to be the malignant counterparts of human embryonic stem cells. As there are few reliable experimental systems available to study the molecular mechanisms governing normal embryogenesis, well-characterized human embryonal carcinoma stem cell lines may provide a robust and simple model to study certain aspects of pluripotency and cellular differentiation. Here, we have analysed NTERA-2 cL.D1 cells at molecular and cellular levels during expansion and differentiation, via formation of cell aggregates similar to embryoid bodies in embryonic stem cells. Thus, human embryonal carcinoma cells may provide a valuable insight into cell fate determination, into the embryonic ectoderm, mesoderm and endoderm and their downstream derivatives. PMID:17109641

Pal, Rajarshi; Ravindran, Geeta

2006-12-01

360

Differential transcript regulation in Arabidopsis thaliana and the halotolerant Lobularia maritima indicates genes with potential function in plant salt adaptation.  

PubMed

Salt stress is an environmental factor that severely impairs plant growth and productivity. Salinity-induced transcript accumulation was monitored in the salt-sensitive Arabidopsis thaliana and the related salt-tolerant Lobularia maritima using cDNA-arrays with expressed sequence tags derived from a cDNA subtraction library of salt-stressed L. maritima. The expression profiles revealed differences of the steady state transcript regulation in A. thaliana and L. maritima in response to salt stress. The differentially expressed transcripts include those involved in the control of gene expression as a transcription factor II homologue as well as signal transduction elements such as a serine/threonine protein kinase, a SNF1-related protein kinase AKIN10 homologue, and protein phosphatase 2C. Other ESTs with differential regulation patterns included transcripts encoding proteins with function in general stress responses and defense and included a peroxidase, dehydrins, enzymes of lipid and nitrogen metabolism, and functionally unclassified proteins. In a more detailed analysis the basic leucine zipper transcription factor AtbZIP24 showed differential transcript abundance in A. thaliana and L. maritima in response to salt stress. Transgenic AtbZIP24-RNAi lines showed improved growth and development under salt stress that was correlated with changed Cl(-) accumulation. The data indicate that AtbZIP24 functions as a transcriptional repressor in salt-stressed A. thaliana that negatively regulates growth and development under salinity in context of controlling Cl(-) homeostasis. Monitoring the differential and tissue specific global regulation of gene expression during adaptation to salinity in salt-sensitive and halotolerant plants is a promising and powerful approach to identify novel elements of plant salt stress adaptation. PMID:18703123

Popova, Olga V; Yang, Oksoon; Dietz, Karl-Josef; Golldack, Dortje

2008-11-01

361

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

362

Structure-based and multiple potential three-dimensional quantitative structure-activity relationship (SB-MP-3D-QSAR) for inhibitor design.  

PubMed

The inhibitions of enzymes (proteins) are determined by the binding interactions between ligands and targeting proteins. However, traditional QSAR (quantitative structure-activity relationship) is a one-side technique, only considering the structures and physicochemical properties of inhibitors. In this study, the structure-based and multiple potential three-dimensional quantitative structure-activity relationship (SB-MP-3D-QSAR) is presented, in which the structural information of host protein is involved in the QSAR calculations. The SB-MP-3D-QSAR actually is a combinational method of docking approach and QSAR technique. Multiple docking calculations are performed first between the host protein and ligand molecules in a training set. In the targeting protein, the functional residues are selected, which make the major contribution to the binding free energy. The binding free energy between ligand and targeting protein is the summation of multiple potential energies, including van der Waals energy, electrostatic energy, hydrophobic energy, and hydrogen-bond energy, and may include nonthermodynamic factors. In the foundational QSAR equation, two sets of weighting coefficients {aj} and {bp} are assigned to the potential energy terms and to the functional residues, respectively. The two coefficient sets are solved by using iterative double least-squares (IDLS) technique in the training set. Then, the two sets of weighting coefficients are used to predict the bioactivities of inquired ligands. In an application example, the new developed method obtained much better results than that of docking calculations. PMID:22480344

Du, Qi-Shi; Gao, Jing; Wei, Yu-Tuo; Du, Li-Qin; Wang, Shu-Qing; Huang, Ri-Bo

2012-04-23

363

Epigenetic Marks Define the Lineage and Differentiation Potential of Two Distinct Neural Crest-Derived Intermediate Odontogenic Progenitor Populations  

PubMed Central

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

2013-01-01

364

Dominant role of the ERAP1 polymorphism R528K in shaping the HLA-B27 peptidome through differential processing determined by multiple peptide residues.  

PubMed

Objective. To characterize the alterations, and their mechanism, induced in the HLA-B27-bound peptidome expressed in live cells by the natural ERAP1 polymorphisms predisposing to ankylosing spondylitis: R528K and N575D/Q725R. Methods. HLA-B*27:05-bound peptides were isolated from 3 human lymphoid cell lines expressing distinct ERAP1 variants differing at residues 528 and/or 575/725. The HPLC-fractionated peptide pools were compared by mass spectrometry based on identity in molecular mass and chromatographic retention time. The relative amounts of each shared peptide in any given cell line pair were estimated from the respective ion peak intensities. Peptide sequencing was also carried out by mass spectrometry. Results. HLA-B27-bound ligands predominant in the context of the ERAP1 variant with K528 collectively showed higher molecular mass, higher frequency of N-terminal residues resistant to ERAP1 and bulkier residues downstream the N-terminus, relative to peptides predominant in the R528 context. None of these differences were observed with ERAP1 variants differing at positions 575/725, but not at residue 528. Neither R528K nor N575D/Q725R altered the mean length of B*27:05-bound ligands. Conclusion. The R528K, but not the N575D/Q725R polymorphism, alters the expression levels of many HLA-B*27:05-bound peptides, depending on the susceptibility of their N-terminal residues to trimming and the size of amino acid side chains at multiple positions downstream the N-terminus. The significant alterations in the B*27:05 peptidome and the structural features of the peptides that determine their differential expression in distinct ERAP1 contexts can explain the association of the R528K polymorphism with ankylosing spondylitis. This article is protected by copyright. All rights reserved. PMID:25469497

Sanz-Bravo, Alejandro; Campos, José; Mazariegos, Marina S; LópezdeCastro, José A

2014-12-01

365

Multiple Structurally Distinct ER? mRNA Variants in Zebrafish are Differentially Expressed by Tissue Type, Stage of Development and Estrogen Exposure  

PubMed Central

It is well established that estrogen-like environmental chemicals interact with the ligand-binding site of estrogen receptors (ER) to disrupt transcriptional control of estrogen responsive targets. Here we investigate the possibility that estrogens also impact splicing decisions on estrogen responsive genes, such as that encoding ER? itself. Targeted PCR cloning was applied to identify six ER? mRNA variants in zebrafish. Sequencing revealed alternate use of transcription and translation start sites, multiple exon deletions, intron retention and alternate polyadenylation. As determined by quantitative (q)PCR, N-terminal mRNA variants predicting long (ER?L) and short (ER?S) isoforms were differentially expressed by tissue-type, sex, stage of development and estrogen exposure. Whereas ER?L mRNA was diffusely distributed in liver, brain, heart, eye, and gonads, ER?S mRNA was preferentially expressed in liver (female > male) and ovary. Neither ER?L nor ER?S transcripts varied significantly during development, but 17?-estradiol selectively increased accumulation of ER?S mRNA (~170-fold by 120 hpf), an effect mimicked by bisphenol-A and diethylstilbestrol. Significantly, a C-truncated variant (ER?S-Cx) lacking most of the ligand binding and AF-2 domains was transcribed exclusively from the short isoform promoter and was similar to ER?S in its tissue-, stage- and estrogen inducible expression. These results support the idea that promoter choice and alternative splicing of the esr1 gene of zebrafish are part of the autoregulatory mechanism by which estrogen modulates subsequent ER? expression, and further suggest that environmental estrogens could exert some of their toxic effects by altering the relative abundance of structurally and functionally distinct ER? isoforms. PMID:24090614

Cotter, Kellie A.; Yershov, Anya; Novillo, Apolonia; Callard, Gloria V.

2013-01-01

366

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

367

Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations  

Microsoft Academic Search

BackgroundRecently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction

Nermin Serbecic; Fahmy Aboul-Enein; Sven C. Beutelspacher; Martin Graf; Karl Kircher; Wolfgang Geitzenauer; Werner Brannath; Priska Lang; Wolfgang Kristoferitsch; Hans Lassmann; Andreas Reitner; Ursula Schmidt-Erfurth; Christoph Kleinschnitz

2010-01-01

368

Comparative genomics of multiple strains of Pseudomonas cannabina pv. alisalensis, a potential model pathogen of both Monocots and Dicots  

Technology Transfer Automated Retrieval System (TEKTRAN)

Comparative genomics of closely related pathogens that differ in host range can provide insights into mechanisms of host-pathogen interactions and host adaptation. Sequencing multiple strains of the same pathogen further reveals information concerning pathogen diversity and the molecular basis of vi...

369

Influence of Low Intensity Laser Irradiation on Isolated Human Adipose Derived Stem Cells Over 72 Hours and Their Differentiation Potential into Smooth Muscle Cells Using Retinoic Acid  

Microsoft Academic Search

Introduction  Human adipose derived stem cells (hADSCs), with their impressive differentiation potential, may be used in autologous cell\\u000a therapy or grafting to replace damaged tissues. Low intensity laser irradiation (LILI) has been shown to influence the behaviour\\u000a of various cells, including stem cells.\\u000a \\u000a \\u000a \\u000a \\u000a Aims  This study aimed to investigate the effect of LILI on hADSCs 24, 48 or 72 h post-irradiation and

Jennifer Anne de Villiers; Nicolette Nadene Houreld; Heidi Abrahamse

370

Thrombin and thrombin-derived peptides promote proliferation of cardiac progenitor cells in the form of cardiospheres without affecting their differentiation potential.  

PubMed

Many studies demonstrated that human adult cardiac progenitor cells in the form of cardiospheres (CSps) could represent a powerful candidate for cardiac cell therapy. To achieve the clinical translation of this biotechnological product, the development of well-defined culture conditions is required to optimize their proliferation and differentiation. Thrombin, a serine protease acting through the protease-activated receptor 1 (PAR-1) signalling to modulate many cellular functions such as proliferation and differentiation in several cell types, is one of the factors included in the CSps medium. Therefore, the assessment of the effective dependence of the thrombin related cellular effects from PAR-signalling is strategic both for understanding the biological potential of these cells and for the GMP translation of the medium formulation, using synthesised analogs. In this study the effects of thrombin on human CSps and their potential relationship with the specific proteolytic activation of PAR-1 have been investigated in different culture conditions, including thrombin inhibitor hirudin and PAR-1 agonist/ antagonist peptides TFLLR and MUMB2. In this study we show that, in the presence of thrombin and TFLLR, CSps, in which PAR-1 expression was evidenced by immunofluorescence and western blot analysis, increase their proliferation activity (BrdU assay). Such increased proliferative rate was consistently associated with a higher phosphorylation level of the cell cycle inhibitor GSK3. Concerning the assessment of the potential effects of thrombin and its agonist on differentiation, both western blot and real-time PCR analysis for stemness, cardiac and vascular markers (such as cKit, cx43 and KDR) showed that CSps commitment was substantially unaffected, except for GATA4 mRNA, whose transcription was down-regulated in the presence of the natural protease, but not after treatment with TFLLR. In conclusion, activation of PAR-1-dependent signalling is important to support CSps proliferative potential, keeping unaltered or at best stable their differentiation properties. The availability of thrombin agonists, such as TFLLR, able to guarantee the required growth effect without affecting CSps lineage commitment, could represent a technological improvement for cost-effective, easy-to-handle and GMPtranslatable synthetic media. PMID:22051170

Fabrizi, C; Angelini, F; Chimenti, I; Pompili, E; Somma, F; Gaetani, R; Messina, E; Fumagalli, L; Giacomello, A; Frati, G

2011-01-01

371

Identification of differentially expressed genes potentially involved in the tolerance of Lotus tenuis to long-term alkaline stress.  

PubMed

Soil alkalinity is one of the most serious agricultural problems limiting crop yields. The legume Lotus tenuis is an important forage acknowledged by its ability to naturally grow in alkaline soils. To gain insight into the molecular responses that are activated by alkalinity in L. tenuis plants, subtractive cDNA libraries were generated from leaves and roots of these plants. Total RNAs of non-stressed plants (pH 5.8; E.C. 1.2), and plants stressed by the addition of 10 mM of NaHCO3 (pH 9.0; E.C. 1.9), were used as source of the driver and the tester samples, respectively. RNA samples were collected after 14 and 28 days of treatment. A total of 158 unigenes from leaves and 92 unigenes from roots were obtained and classified into 11 functional categories. Unigenes from these categories (4 for leaves and 8 for roots), that were related with nutrient metabolism and oxidative stress relief were selected, and their differential expression analyzed by qRT-PCR. These genes were found to be differentially expressed in a time dependent manner in L. tenuis during the alkaline stress application. Data generated from this study will contribute to the understanding of the general molecular mechanisms associated to plant tolerance under long-term alkaline stress in plants. PMID:25025825

Paz, Rosalía Cristina; Rocco, Rubén Anibal; Jiménez-Bremont, Juan Francisco; Rodríguez-Kessler, Margarita; Becerra-Flora, Alicia; Menéndez, Ana Bernardina; Ruíz, Oscar Adolfo

2014-09-01

372

Identification of differentially expressed microRNAs in Culex pipiens and their potential roles in pyrethroid resistance.  

PubMed

Pyrethroids are the major class of insecticides used for mosquito control. Excessive and improper use of insecticides, however, has resulted in pyrethroid resistance, which has become a major obstacle for mosquito control. The development of pyrethroid resistance is a complex process involving many genes, and information on post-transcription regulation of pyrethroid resistance is lacking. In this study, we extracted RNA from mosquitoes in various life stages (fourth-instar larvae, pupae, male and female adult mosquitoes) from deltamethrin-sensitive (DS) and resistant (DR) strains. Using illumina sequencing, we obtained 13760296 and 12355472 reads for DS-strains and DR-strains, respectively. We identified 100 conserved miRNAs and 42 novel miRNAs derived from 21 miRNA precursors in Culex pipiens. After normalization, we identified 28 differentially expressed miRNAs between the two strains. Additionally, we found that cpp-miR-71 was significant down regulated in female adults from the DR-strain. Based on microinjection and CDC Bottle Bioassay data, we found that cpp-miR-71 may play a contributing role in deltamethrin resistance. The present study provides the firstly large-scale characterization of miRNAs in Cu. pipiens and provides evidence of post-transcription regulation. The differentially expressed miRNAs between the two strains are expected to contribute to the development of pyrethroid resistance. PMID:25446390

Hong, Shanchao; Guo, Qin; Wang, Weijie; Hu, Shengli; Fang, Fujin; Lv, Yuan; Yu, Jing; Zou, Feifei; Lei, Zhentao; Ma, Kai; Ma, Lei; Zhou, Dan; Sun, Yan; Zhang, Donghui; Shen, Bo; Zhu, Changliang

2014-11-01

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

Investigation of low-level laser therapy potentiality on proliferation and differentiation of human osteoblast-like cells in the absence/presence of osteogenic factors  

NASA Astrophysics Data System (ADS)

Several studies have shown that low-level laser irradiation (LLLI) has beneficial effects on bone regeneration. The objective of this study was to examine the in vitro effects of LLLI on proliferation and differentiation of a human osteoblast-like cell line (Saos-2 cell line). Cultured cells were exposed to different doses of LLLI with a semiconductor diode laser (659 nm 10 mW power output). The effects of laser on proliferation were assessed daily up to seven days of culture in cells irradiated once or for three consecutive days with laser doses of 1 or 3 J/cm2. The obtained results showed that laser stimulation enhances the proliferation potential of Saos-2 cells without changing their telomerase pattern or morphological characteristics. The effects on cell differentiation were assessed after three consecutive laser irradiation treatments in the presence or absence of osteo-inductive factors on day 14. Enhanced secretion of proteins specific for differentiation toward bone as well as calcium deposition and alkaline phosphatase activity were observed in irradiated cells cultured in a medium not supplemented with osteogenic factors. Taken together these findings indicate that laser treatment enhances the in vitro proliferation of Saos-2 cells, and also influences their osteogenic maturation, which suggest it is a helpful application for bone tissue regeneration.

Bloise, Nora; Ceccarelli, Gabriele; Minzioni, Paolo; Vercellino, Marco; Benedetti, Laura; De Angelis, Maria Gabriella Cusella; Imbriani, Marcello; Visai, Livia

2013-12-01

375

Native nucleus pulposus tissue matrix promotes notochordal differentiation of human induced pluripotent stem cells with potential for treating intervertebral disc degeneration.  

PubMed

Native porcine nucleus pulposus (NP) tissue harbors a number of notochordal cells (NCs). Whether the native NP matrix supports the homeostasis of notochordal cells is poorly understood. We hypothesized the NP matrix alone may contain sufficient regulatory factors and can serve as stimuli to generate notochordal cells (NCs) from human pluripotent stem cells. NCs are a promising cell sources for cell-based therapy to treat some types of intervertebral disc (IVD) degeneration. One major limitation of this emerging technique is the lack of available NCs as a potential therapeutic cell source. Human pluripotent stem cells derived from reprogramming or somatic cell nuclear transfer technique may yield stable and unlimited source for therapeutic use. We devised a new method to use porcine NP matrix to direct notochordal differentiation of human induced pluripotent stem cells (hiPSCs). The results showed that hiPSCs successfully differentiated into NC-like cells under the influence of devitalized porcine NP matrix. The NC-like cells expressed typical notochordal marker genes including brachyury (T), cytokeratin-8 (CK-8) and cytokeratin-18 (CK-18), and they displayed the ability to generate NP-like tissue in vitro, which was rich in aggrecan and collagen type II. These findings demonstrated the proof of concept for using native NP matrix to direct notochordal differentiation of hiPSCs. It provides a foundation for further understanding the biology of NCs, and eventually towards regenerative therapies for disc degeneration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014. PMID:24889905

Liu, Yongxing; Fu, Susan; Rahaman, Mohamed N; Mao, Jeremy J; Bal, B Sonny

2014-06-01

376

The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer DNA glycosylases OGG1 and NEIL3 are required for neural stem cell state. Black-Right-Pointing-Pointer No effect on cell viability by OGG1 or NEIL3 knockdown in neural stem cells. Black-Right-Pointing-Pointer OGG1 or NEIL3 RNA knockdown result in decreased proliferation and differentiation. Black-Right-Pointing-Pointer Increased HP1{gamma} immunoreactivity after NEIL3 knockdown suggests premature senescence. -- Abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1{gamma} immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.

Reis, Amilcar [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)] [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)] [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)

2012-07-13

377

Kinetic Analysis of Dynamic 11C-Acetate PET/CT Imaging as a Potential Method for Differentiation of Hepatocellular Carcinoma and Benign Liver Lesions  

PubMed Central

Objective: The kinetic analysis of 11C-acetate PET provides more information than routine one time-point static imaging. This study aims to investigate the potential of dynamic 11C-acetate hepatic PET imaging to improve the diagnosis of hepatocellular carcinoma (HCC) and benign liver lesions by using compartmental kinetic modeling and discriminant analysis. Methods: Twenty-two patients were enrolled in this study, 6 cases were with well-differentiated HCCs, 7 with poorly-differentiated HCCs and 9 with benign pathologies. Following the CT scan, all patients underwent 11C-acetate dynamic PET imaging. A three-compartment irreversible dual-input model was applied to the lesion time activity curves (TACs) to estimate the kinetic rate constants K1-k3, vascular fraction (VB) and the coefficient ? representing the relative hepatic artery (HA) contribution to the hepatic blood supply on lesions and non-lesion liver tissue. The parameter Ki (=K1×k3/(k2 + k3)) was calculated to evaluate the local hepatic metabolic rate of acetate (LHMAct). The lesions were further classified by discriminant analysis with all the above parameters. Results: K1 and lesion to non-lesion standardized uptake value (SUV) ratio (T/L) were found to be the parameters best characterizing the differences among well-differentiated HCC, poorly-differentiated HCC and benign lesions in stepwise discriminant analysis. With discriminant functions consisting of these two parameters, the accuracy of lesion prediction was 87.5% for well-differentiated HCC, 50% for poorly-differentiated HCC and 66.7% for benign lesions. The classification was much better than that with SUV and T/L, where the corresponding classification accuracy of the three kinds of lesions was 57.1%, 33.3% and 44.4%. Conclusion: 11C-acetate kinetic parameter K1 could improve the identification of HCC from benign lesions in combination with T/L in discriminant analysis. The discriminant analysis using static and kinetic parameters appears to be a very helpful method for clinical liver masses diagnosis and staging.

Huo, Li; Guo, Jinxia; Dang, Yonghong; Lv, Jinqiao; Zheng, Youjing; Li, Fang; Xie, Qingguo; Chen, Xiaoyuan

2015-01-01

378

CD98 is a potential target for ablating B cell clonal expansion and autoantibody in multiple sclerosis.  

PubMed

Current B cell-directed therapies for multiple sclerosis impact multiple B cell functions. CD98hc enables B cell clonal expansion and antibody production. I probed the relative importance of autoantibody secretion vs. other B cell functions in MS and targeted CD98hc as a possible therapeutic strategy. I report that the loss of CD98hc function in B cells largely prevents autoantibody production while preserving antigen-presenting and T cell-directing capacities. Mice lacking CD98hc in B cells are protected from EAE; importantly this is overcome with autoantibody-containing plasma. Thus CD98hc blockade is a possible avenue to treat MS by inhibiting clonal expansion and autoantibody. PMID:25002078

Cantor, Joseph M

2014-09-15

379

341 feline embryonic stem-like cells derived from in vitro-produced blastocysts retain in vitro differentiation potential.  

PubMed

Embryonic stem (ES) cells are pluripotent cells that can differentiate into all 3 germ layers, including endoderm, mesoderm, and ectoderm. Embryonic stem cells are generally divided into 2 types, naïve and primed-state, depending on their signaling pathways. Domestic cat is a useful animal model for the study of human diseases because many genetic and infectious diseases in the cat are analogous with similar aetiology to human diseases. The cat can also be used as a research model for reproductive physiology and conservation of wild felids. Until recently, information on establishment of feline ES cells is limited. The objectives of this study were to isolate cat ES cells from in vitro-produced blastocysts and to examine the effect of different concentrations of basic fibroblast growth factor (bFGF) on the expression of pluripotent genes. Inner cell masses (ICM) from cat blastocysts (n=40, Day 7 after in vitro fertilization) that were matured, fertilized, and cultured entirely in vitro, were isolated by immunosurgery and plated on mitmycin-treated mouse embryonic fibroblasts. The ICM (n=20) were then cultured in embryonic stem cell medium containing 1000IUmL(-1) of leukemia inhibitory factor (LIF) and different bFGF concentrations (0, 4, 10, and 20ngmL(-1)). The ICM outgrowths at 7 days postplating were collected and analysed for expression of pluripotent genes (SOX-2, OCT-4, and NANOG). Results showed that transcription levels of all 3 pluripotent genes were higher in ICM outgrowths cultured in 20ngmL(-1) of bFGF compared with the lower concentrations. For isolation of ES cells, ICM (n=20) were cultured in embryonic stem cell medium supplemented with 1000IUmL(-1) of LIF and 20ngmL(-1) of bFGF due to the results obtained from the above experiment. Established ES cells were characterised by detecting alkaline phosphatase (AP) activity and expression of ES markers (SOX-2, OCT-4, SSEA-4) at protein level, and karyotyped at passage 20 and 40. In vitro differentiation into embryoid bodies (EB) was induced by the hanging drop technique, and EB samples (n=5 for each time point) were tested for the expression of TTR, AFP, T (Bracyury), NKX2.5, MAP-2, and NESTIN genes at 0, 7, and 14 days of culture. A total of 3 ES-like cell lines were established with a typical ES morphology, such as a well-defined colony, a large nucleus to cytoplasm ratio with 1 to 2 prominent nucleoli. The 3 ES-like cell lines were passaged up to 40 times with a normal diploid karyotype (n=38). They were strongly positive for AP, SOX-2, OCT-4, and SSEA-4. Following EB culture, cell aggregation and cystic-like structure were observed. The EB samples also expressed all differentiation markers. This study reports that feline ES-like cell lines can be generated from in vitro-produced feline blastocysts. The ES cell lines can be repeatedly passaged indicating self-renewal ability, and gene expression of the EB demonstrates cellular differentiation into all 3 germ layers. PMID:25472389

Tharasanit, T; Tiptanavattana, N; Phakdeedindan, P; Techakumphu, M

2014-12-01

380

Potential Usefulness of Multiple-Mammographic Views in Computer-Aided Diagnosis Scheme for Identifying Histological Classification of Clustered Microcalcification  

Microsoft Academic Search

The purpose of this study was to investigate the usefulness of multiple-view mammograms in the computerized scheme for identifying\\u000a histological classifications. Our database consisted of mediolateral oblique (MLO) and craniocaudal (CC) magnification mammograms\\u000a obtained from 77 patients, which included 14 invasive carcinomas, 17 noninvasive carcinomas of comedo type, 17 noninvasive\\u000a carcinomas of noncomedo type, 14 mastopathies, and 15 fibroadenomas. Five

Ryohei Nakayama; Ryoji Watanabe; Kiyoshi Namba; Koji Yamamoto; Kan Takeda; Shigehiko Katsuragawa; Kunio Doi

2006-01-01

381

Transcriptional profiling and co-expression network analysis identifies potential biomarkers to differentiate chronic hepatitis B and the caused cirrhosis.  

PubMed

Liver cirrhosis is one of the most common non-neoplastic causes of mortality worldwide. Chronic hepatitis B (CHB) is a major cause of liver cirrhosis in China. To find biomarkers for the diagnosis of CHB caused cirrhosis (HBC), we examined the transcriptional profiling of CHB and HBC. The leukocyte samples of CHB (n = 5) and HBC (n = 5) were analyzed by microarray. The results showed that 2128 mapped genes were differentially expressed between CHB and HBC (fold change ? 2.0, p < 0.05). Gene ontology (GO) analysis indicated that these 2128 differentially expressed genes (DEGs) were enriched for immune response and cell formation functions mostly. Moreover, co-expression networks using the k-core algorithm were established to determine the core genes, which may play important roles in the progression of CHB to HBC. There were markedly different gene co-expression patterns in CHB and HBC. We validated the five core genes, CASP1, TGFBI, IFI30, HLA-DMA and PAG1 in CHB (n = 60) and HBC (n = 60) by quantitative RT-PCR. The expression of the five genes were consistent with microarray, and there were statistically significant co-expression patterns of TGF?1, PAG1 and HLA-DMA mRNA (Pearson correlation coefficient >0.6). Furthermore, we constructed an mRNA panel of TGFBI, IFI30, HLA-DMA and PAG1 (TIPH HBCtest) by means of a logistic regression model, and evaluated the TIPH HBCtest for HBC diagnosis by area under the receiver operating characteristic curve (AUC) analysis, which showed a higher accuracy (AUC = 0.903). This study suggested that there are particular transcriptional profiles, gene co-expression patterns and core genes in CHB and HBC. The TIPH HBC test may be useful in the diagnosis of HBC from CHB. PMID:24599568

Lu, Yi-Yu; Chen, Qi-Long; Guan, Yan; Guo, Zhi-Zhong; Zhang, Hui; Zhang, Wei; Hu, Yi-Yang; Su, Shi-Bing

2014-05-01

382

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 therapeuti