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1

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

PubMed Central

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

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

2012-01-01

2

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

Microsoft Academic Search

BackgroundTransplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using

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

2012-01-01

3

Multiple Intelligences for Differentiated Learning  

ERIC Educational Resources Information Center

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

Williams, R. Bruce

2007-01-01

4

Multiple differential-aperture microscopy  

NASA Astrophysics Data System (ADS)

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.

2007-11-01

5

Immunological differentiation between neuroborreliosis and multiple sclerosis  

Microsoft Academic Search

Neuroborreliosis, a tick-borne spirochaetosis of the central nervous system, is diagnosed by the presence of intrathecally synthesized Borrelia burgdorferispecific antibodies. Multiple sclerosis and neuroborreliosis can show similarities in clinical symptoms as well as lymphocytic cell reactions and oligoclonal bands in the isoelectric focusing of cerebrospinal fluid. To differentiate between multiple sclerosis and neuroborreliosis we tested intrathecally synthesized IgM and virus

J. Heller; G. Holzer; K. Schimrigk

1990-01-01

6

MULTIPLE DIFFERENTIAL ROTARY MECHANICAL DRIVE  

DOEpatents

This patent relates to a mechanism suitable for such applications as driving two spaced-apart spools which carry a roll film strip under conditions where the film movement must be rapidly started, stopped, and reversed while maintaining a constant tension on the film. The basic drive is provided by a variable speed, reversible rnotor coupled to both spools through a first differential mechanism and driving both spools in the same direction. A second motor, providing a constant torque, is connected to the two spools through a second differential mechanism and is coupled to impart torque to one spool in a first direction anid to the other spool in the reverse direction thus applying a constant tension to the film passing over the two spools irrespective of the speed or direction of rotation thereof. (AEC)

Smits, R.G.

1964-01-28

7

Estrone potentiates myeloid cell differentiation  

Microsoft Academic Search

Hormones such as 1?,25-dihydroxy vitamin D3 (D3), all-trans retinoic acid, and 9-cis retinoic acid stimulate differentiation of myeloid progenitor cells via their interaction with specific hormone receptors. However, the sensitivity of cells to these agents is not merely governed by the expression of their receptors and the availability of ligand to bind them. Recent studies from our group suggested that

Joanne C Mountford; Christopher M Bunce; Susan V Hughes; Mark T Drayson; David Webb; Geoffery Brown; Martin Hewison

1999-01-01

8

Fever and evoked potentials in multiple sclerosis  

Microsoft Academic Search

The somatosensory evoked potentials (SEPs) and visual evoked potentials (VEPs) were studied in 19 patients with multiple sclerosis; 17 controls were studied during fever (38.0°–39.7°C) and 2–3 days following return to normal temperature. The latencies of components N20 and P114 were measured and specified as abnormal when their value exceeded the standard deviation of the controls by 2.5 times. The

A. Kazis; N. Vlaikidis; D. Xafenias; J. Papanastasiou; P. Pappa

1982-01-01

9

Bohmian Dynamics on Multiple Potential Energy Surfaces  

Microsoft Academic Search

The coupled Schrodinger equations that describe nonadiabatic dynamics on multiple potential energy surfaces are recast using the Bohm formulation of quantum mechanics. The resulting coupled Bohm equations are exact; i.e., numerical solutions are identical to those obtained from the original coupled Schrodinger equations by wave packet propagation. The classical limit of the coupled Bohm equations is derived. It corresponds to

John Burant; John Tully

2001-01-01

10

Detection of Differential Item Functioning in Multiple Groups.  

ERIC Educational Resources Information Center

|Detection of differential item functioning (DIF) is most often done between two groups of examinees under item response theory. It is sometimes important, however, to determine whether DIF is present in more than two groups. A method is presented for the detection of DIF in multiple groups. The method, the Q(sub j) statistic, is closely related…

Kim, Seock-Ho; And Others

11

Detection of Differential Item Functioning in Multiple Groups.  

ERIC Educational Resources Information Center

|A method is presented for detection of differential item functioning in multiple groups. This method is closely related to F. M. Lord's chi square for comparing vectors of item parameters estimated in two groups. An example is provided using data from 600 college students taking a mathematics test with and without calculators. (SLD)|

Kim, Seock-Ho; And Others

1995-01-01

12

Horizontal Hostility: Multiple Minority Groups and Differentiation from the Mainstream  

Microsoft Academic Search

Three studies examined minority group members' attitudes toward other, similar minority groups. We predicted that minority group members would differentiate between multiple outgroups with asymmetric horizontal hostility(White & Langer, 1999), a pattern of expressing relatively unfavorable attitudes toward an outgroup that is similar to and more mainstream than the minority ingroup. We replicated White and Langer's pattern of horizontal hostility

Judith B. White; Michael T. Schmitt; Ellen J. Langer

2006-01-01

13

In vitro Differentiation Potential of Mesenchymal Stem Cells  

Microsoft Academic Search

Summary Mesenchymal stem cells (MSCs) represent a class of multipotent progenitor cells that have been isolated from multiple tissue sites. Of these, adipose tissue and bone marrow offer advantages in terms of access, abundance, and the extent of their documentation in the literature. This review focuses on the in vitro differentiation capability of cells derived from adult human tissue. Multiple,

Jeffrey M. Gimble; Farshid Guilak; Mark E. Nuttall; Solomon Sathishkumar; Martin Vidal; Bruce A. Bunnell

2008-01-01

14

Differentiation of Self and Child Abuse Potential in Young Adulthood  

ERIC Educational Resources Information Center

|The authors examine the role of Bowen family systems theory in predicting physical child abuse potential. Relations between differentiation of self, perceptions of personal problem-solving skills, and child abuse potential were tested in a sample of 210 single young adults who were not yet parents. Greater differentiation of self that is, lower…

Skowron, Elizabeth A.; Platt, Lisa F.

2005-01-01

15

Differential cognitive impairment for diverse forms of multiple sclerosis  

Microsoft Academic Search

BACKGROUND: Cognitive impairment is a common feature in multiple sclerosis (MS) patients and occurs in 60% of all cases. Unfortunately, neurological examination does not always agree with the neuropsychological evaluation in determining the cognitive profile of the patient. On the other hand, psychophysiological techniques such as event-related potentials (ERPs) can help in evaluating cognitive impairment in different pathologies. Behavioural responses

Javier J Gonzalez-Rosa; Manuel Vazquez-Marrufo; Encarnacion Vaquero; Pablo Duque; Monica Borges; Miguel A Gamero; Carlos M Gomez; Guillermo Izquierdo

2006-01-01

16

Detection and discrimination using multiple-wavelength differential absorption lidar  

NASA Astrophysics Data System (ADS)

A methodology is presented for generalizing two-wavelength single-material differential absorption lidar to multiple wavelengths for use in simultaneous multimaterial detection and discrimination. A key role in the analysis is played by the concentration path length (CL) product covariance matrix Lambda (CL) which generalizes the CL variance. Detection statistics for a multiwavelength alarm system are computed using Lambda (CL) with a multivariate normal distribution for the estimated CL product values. Off-diagonal elements in Lambda (CL) are found to affect significantly the predicted performance of two-material detection systems.

Warren, R. E.

1985-11-01

17

Multiple Signals Converge on a Differentiation MAPK Pathway  

PubMed Central

An important emerging question in the area of signal transduction is how information from different pathways becomes integrated into a highly coordinated response. In budding yeast, multiple pathways regulate filamentous growth, a complex differentiation response that occurs under specific environmental conditions. To identify new aspects of filamentous growth regulation, we used a novel screening approach (called secretion profiling) that measures release of the extracellular domain of Msb2p, the signaling mucin which functions at the head of the filamentous growth (FG) MAPK pathway. Secretion profiling of complementary genomic collections showed that many of the pathways that regulate filamentous growth (RAS, RIM101, OPI1, and RTG) were also required for FG pathway activation. This regulation sensitized the FG pathway to multiple stimuli and synchronized it to the global signaling network. Several of the regulators were required for MSB2 expression, which identifies the MSB2 promoter as a target “hub” where multiple signals converge. Accessibility to the MSB2 promoter was further regulated by the histone deacetylase (HDAC) Rpd3p(L), which positively regulated FG pathway activity and filamentous growth. Our findings provide the first glimpse of a global regulatory hierarchy among the pathways that control filamentous growth. Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors.

Chavel, Colin A.; Dionne, Heather M.; Birkaya, Barbara; Joshi, Jyoti; Cullen, Paul J.

2010-01-01

18

Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study  

Microsoft Academic Search

BACKGROUND: Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. METHODS: Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured

Marieke de Mos; Wendy JLM Koevoet; Holger Jahr; Monique MA Verstegen; Marinus P Heijboer; Nicole Kops; Johannes PTM van Leeuwen; Harrie Weinans; Jan AN Verhaar; Gerjo JVM van Osch

2007-01-01

19

Curriculum Differentiation: Multiple Perspectives and Developments in Education  

ERIC Educational Resources Information Center

|This paper examines curriculum differentiation (i.e. streaming or ability-grouping). After placing curriculum differentiation in an international perspective, it outlines the main conclusions from empirical research on differentiation over several decades. Against this empirical background, it describes and considers the three specific…

Terwel, J.

2005-01-01

20

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

NASA Astrophysics Data System (ADS)

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

Ao, P.

2004-01-01

21

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

22

Multiple Differentiation Capacity of STRO-1+/CD146+ PDL Mesenchymal Progenitor Cells  

PubMed Central

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.

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

2009-01-01

23

[Mesenchymal stem cells: sources, phenotype, and differentiation potential].  

PubMed

Mesenchymal stem cells present in the bone marrow and some other organs are primitive pluripotent precursors of osseous, cartilaginous, adipose, and other mesenchymal tissues. The recently revealed capacity of these cells for differentiation into nonmesenchymal derivatives is of considerable theoretical and practical interest. However, many aspects of the biology of these cells remain obscure despite active research. This review considers possible sources and methods for the isolation of mesenchymal stem cells, their potential for proliferation and differentiation in different directions, and outlooks of their therapeutic application. A model of parent-progeny relationships of stromal cells is proposed, and the problems of regulation of proliferation and differentiation of mesenchymal precursors as well as their role in the maintenance of regeneration and tissue functioning are discussed. PMID:16521535

Paniushin, O V; Domaratskaia, E I; Starostin, V I

24

Computing derivatives of a gravity potential by using automatic differentiation  

NASA Astrophysics Data System (ADS)

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

Abad, Alberto; Lacruz, Elvis

2013-10-01

25

Biophysical Characteristics Reveal Neural Stem Cell Differentiation Potential  

PubMed Central

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

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

2011-01-01

26

Vestibular evoked myogenic potentials in multiple sclerosis patients  

Microsoft Academic Search

Objectives: Vestibular evoked myogenic potentials (VEMPs) are saccular responses to loud acoustic stimuli and are recordable from the sterno-cleido-mastoid muscle ipsilaterally to the stimulated ear. This study aimed to investigate VEMPs in patients suffering from multiple sclerosis (MS), and to compare these findings with both clinical and instrumental data.Methods: We recorded VEMPs from 70 MS patients, whose clinical data were

Maurizio Versino; Silvia Colnaghi; Roberto Callieco; Roberto Bergamaschi; Alfredo Romani; Vittorio Cosi

2002-01-01

27

Vascular Calcifying Progenitor Cells Possess Bidirectional Differentiation Potentials  

PubMed Central

Vascular calcification is an advanced feature of atherosclerosis for which no effective therapy is available. To investigate the modulation or reversal of calcification, we identified calcifying progenitor cells and investigated their calcifying/decalcifying potentials. Cells from the aortas of mice were sorted into four groups using Sca-1 and PDGFR? markers. Sca-1+ (Sca-1+/PDGFR?+ and Sca-1+/PDGFR??) progenitor cells exhibited greater osteoblastic differentiation potentials than Sca-1? (Sca-1?/PDGFR?+ and Sca-1?/PDGFR??) progenitor cells. Among Sca-1+ progenitor populations, Sca-1+/PDGFR?? cells possessed bidirectional differentiation potentials towards both osteoblastic and osteoclastic lineages, whereas Sca-1+/PDGFR?+ cells differentiated into an osteoblastic lineage unidirectionally. When treated with a peroxisome proliferator activated receptor ? (PPAR?) agonist, Sca-1+/PDGFR?? cells preferentially differentiated into osteoclast-like cells. Sca-1+ progenitor cells in the artery originated from the bone marrow (BM) and could be clonally expanded. Vessel-resident BM-derived Sca-1+ calcifying progenitor cells displayed nonhematopoietic, mesenchymal characteristics. To evaluate the modulation of in vivo calcification, we established models of ectopic and atherosclerotic calcification. Computed tomography indicated that Sca-1+ progenitor cells increased the volume and calcium scores of ectopic calcification. However, Sca-1+/PDGFR?? cells treated with a PPAR? agonist decreased bone formation 2-fold compared with untreated cells. Systemic infusion of Sca-1+/PDGFR?? cells into Apoe?/? mice increased the severity of calcified atherosclerotic plaques. However, Sca-1+/PDGFR?? cells in which PPAR? was activated displayed markedly decreased plaque severity. Immunofluorescent staining indicated that Sca-1+/PDGFR?? cells mainly expressed osteocalcin; however, activation of PPAR? triggered receptor activator for nuclear factor-?B (RANK) expression, indicating their bidirectional fate in vivo. These findings suggest that a subtype of BM-derived and vessel-resident progenitor cells offer a therapeutic target for the prevention of vascular calcification and that PPAR? activation may be an option to reverse calcification.

Lee, Ho-Jae; Song, Myung-Kang; Seo, Ji-Yun; Bae, Yeon-Hee; Kim, Ju-Young; Lee, Hae-Young; Lee, Whal; Koo, Bon-Kwon; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

2013-01-01

28

Engineering Spatial Control of Multiple Differentiation Fates within a Stem Cell Population  

PubMed Central

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 stem cells toward osteoblasts ‘on–pattern’ and myocytes ‘off–pattern’ simultaneously. Here this technology is extended to spatially control osteoblast, tenocyte and myocyte differentiation simultaneously. Utilizing immunofluorescence staining to identify tendon-promoting GFs, fibroblast growth factor-2 (FGF-2) was shown to upregulate the tendon marker Scleraxis (Scx) in C3H10T1/2 mesenchymal fibroblasts, C2C12 myoblasts and primary muscle-derived stem cells, while downregulating the myofibroblast marker ?-smooth muscle actin (?-SMA). Quantitative PCR studies indicated that FGF-2 may direct stem cells towards a tendon fate via the Ets family members of transcription factors such as pea3 and erm. Neighboring patterns of FGF-2 and bone morphogenetic protein-2 (BMP-2) printed onto a single fibrin-coated coverslip upregulated Scx and the osteoblast marker ALP, respectively, while non-printed regions showed spontaneous myotube differentiation. This work illustrates spatial control of multi-phenotype differentiation and may have potential in the regeneration of multi-tissue units.

Ker, Dai Fei Elmer; Chu, Bur; Phillippi, Julie A.; Gharaibeh, Burhan; Huard, Johnny; Weiss, Lee E.; Campbell, Phil G.

2011-01-01

29

MULTIPLE SOLUTIONS FOR NONRESONANCE IMPULSIVE FUNCTIONAL DIFFERENTIAL EQUATIONS  

Microsoft Academic Search

In this paper we investigate the existence of multiple solutions for first and second order impulsive functional dierential equations with bound- ary conditions. Our main tool is the Leggett and Williams fixed point theorem.

MOUFFAK BENCHOHRA; ABDELGHANI OUAHAB

2003-01-01

30

miR-206 integrates multiple components of differentiation pathways to control the transition from growth to differentiation in rhabdomyosarcoma cells  

PubMed Central

Background Similar to replicating myoblasts, many rhabdomyosarcoma cells express the myogenic determination gene MyoD. In contrast to myoblasts, rhabdomyosarcoma cells do not make the transition from a regulative growth phase to terminal differentiation. Previously we demonstrated that the forced expression of MyoD with its E-protein dimerization partner was sufficient to induce differentiation and suppress multiple growth-promoting genes, suggesting that the dimer was targeting a switch that regulated the transition from growth to differentiation. Our data also suggested that a balance between various inhibitory transcription factors and MyoD activity kept rhabdomyosarcomas trapped in a proliferative state. Methods Potential myogenic co-factors were tested for their ability to drive differentiation in rhabdomyosarcoma cell culture models, and their relation to MyoD activity determined through molecular biological experiments. Results Modulation of the transcription factors RUNX1 and ZNF238 can induce differentiation in rhabdomyosarcoma cells and their activity is integrated, at least in part, through the activation of miR-206, which acts as a genetic switch to transition the cell from a proliferative growth phase to differentiation. The inhibitory transcription factor MSC also plays a role in controlling miR-206, appearing to function by occluding a binding site for MyoD in the miR-206 promoter. Conclusions These findings support a network model composed of coupled regulatory circuits with miR-206 functioning as a switch regulating the transition from one stable state (growth) to another (differentiation).

2012-01-01

31

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

32

Potential Application of Tregitopes as Immunomodulating Agents in Multiple Sclerosis  

PubMed Central

The induction of immunologic tolerance is an important clinical goal in autoimmunity. CD4+ regulatory T (Treg) cells, defined by the expression of the transcription factor forkhead box P3 (FoxP3), play a central role in the control of autoimmune responses. Quantitative and qualitative defects of Tregs have been postulated to contribute to failed immune regulation in multiple sclerosis (MS) and other autoimmune diseases. This paper highlights the potential uses of T regulatory cell epitopes (Tregitopes), natural Treg epitopes found to be contained in human immunoglobulins, as immunomodulating agents in MS. Tregitopes expand Treg cells and induce “adaptive Tregs” resulting in immunosuppression and, therefore, are being considered as a potential therapy for autoimmune diseases. We will compare Tregitopes versus intravenous immunoglobulin (IVIg) in the treatment of EAE with emphasis on the potential applications of Tregitope for the treatment of MS.

Elyaman, Wassim; Khoury, Samia J.; Scott, David W.; De Groot, Anne S.

2011-01-01

33

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

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

Differential diagnosis of posterior fossa multiple sclerosis lesions - neuroradiological aspects  

Microsoft Academic Search

. Various infratentorial pathological conditions can mimic multiple sclerosis (MS) both clinically and radiologically. We review the inflammatory, vascular, neoplastic and metabolic conditions which show features similar to those of MS on magnetic resonance imaging (MRI). Beçet's disease, Lyme disease, progressive multifocal leukoencephalopathy, neurosarcoidosis, Whipple's disease, listeria rhombencephalitis, Bickerstaff's brainstem encephalitis, vascultis due to systemic lupus erythematosus, and acute disseminated

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

2001-01-01

36

[The differentiation potential of stem cells (the problem of plasticity)].  

PubMed

Numerous publications on the ability of adult stem cells to differentiate into the cells of various tissues, not always homodermic (stem cell flexibility), to contain serious methodic errors. The main flexibility phenomena, such as "transdifferentiation" of hemopoietic stem cells into hepatocytes, cardiomyocytes, beta-cells of islets of Langerhans, neurons etc., are caused not by a shift of the differentiation path, but by cell merging, resulting in appearance of hybrids with unusual markers of cells of non-hemopoietic origin. The second most frequent error is wrong identification of macrophages and lymphocytes, which are present in any tissue and have the donor's genotype in chimeras. Even when the cause of the error is unknown, the phenomenon of unusual cell formation is exclusively rare and never bears therapeutic potential. In general, it is at least too early to revise the main tenets of the stem cell doctrine. Embryonic stem cells are totipotent indeed; however, the time of their clinical use has not come yet. Attempts to induce their ordered differentiation keep on failing; they very often lead to formation of teratomas and, even if necessary cells such as hemopoietic stem cells are formed, they do not work after administration into an organism that has been exposed to radiation. Clinical use of embryonic stem cells do not seem possible in this decade. PMID:16320705

Chertkov, I L; Drize, N I

2005-01-01

37

Cerebellar medulloblastoma with multiple differentiation in a dog.  

PubMed

A 4-year-old female, spayed Border Collie Dog was brought to the Veterinary Medical Teaching Hospital for evaluation of a progressive head tilt and ataxia that were unresponsive to therapy. Neurologic examination localized a right-sided lesion. The owner refused additional diagnostic tests, and necropsy was performed after euthanasia. Gross findings included atrophy of the temporal muscles and a moderately well delineated, 2.5- x 1.5- x 1.0-cm, gray soft-tissue mass compressing the right cerebellar hemisphere and dorsal hindbrain, resulting in massive dilatation of the lateral, third, and fourth ventricles and hydrocephalus. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal to fusiform cells with typical morphologic characteristics of medulloblastoma and interspersed areas containing myelinated axons and cells with glial and neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with glial and neuronal differentiation. PMID:9823598

Steinberg, H; Galbreath, E J

1998-11-01

38

Differentiation potential of the fetal rat liver-derived cells.  

PubMed

Mesenchymal stem cells derived from bone marrow or several fetal tissues can be expanded and differentiated into other cell lines. The fetal liver is the source of early hematopoietic cells and also, as a fetal tissue, may be considered as a source of pluripotent stem cells. The differentiation potential of fetal rat liver cells have been examined. Freshly isolated liver cells from 14-d fetuses were cultured in Dulbecco medium supplemented with 10% FCS. The plastic-adherent cells were then passaged up to 10 times. Freshly isolated cells and cells from every passage were cultured in hematopoiesis-promoting environment that consists of methylcelulose supplemented with FCS, rat IL-3, human IL-6 and Epo. Parallely these cells were incubated in co-culture with rat muscle satellite cells (Dulbecco medium with 10% FCS and 10% HS) to examine their myogenic potential. Culture in methylcelulose resulted in a high number of GM and Mix colonies in case of freshly isolated liver cells and the number of colonies decreased according to the number of passages. In case of cells from 4th passage, there ware no hematopoietic colonies in culture. In contrast--freshly isolated cells were not able to fuse with rat satellite cells and form the myotubes. This ability appeared in plastic-adherent cells just from the second passage and increases to 5th passage. The cells from every next passage up to 10th when co-cultured with satellite cells participated in myotube formation at the same high level. This result may suggest that in the 14-d rat liver there exist at least two subpopulations of cells: the non-adherent hematopoietic cell population, and the population of plastic-adherent cells capable of differentiating into myotubes. Since the attempts to redifferentiate hematopoietic subpopulation into myopoiesis, or myopoietic subpopulation into hematopoiesis failed, it may be concluded that at least under our experimental conditions the fetal liver cells do not reveal the "plasticity" features. PMID:16382888

Machaj, Eugeniusz K; Grabowska, Iwona; Gajkowska, Agnieszka; Jastrzewska, Marzena; Oldak, Tomasz; Moraczewski, Jerzy; Pojda, Zygmunt

2005-01-01

39

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

40

Proteasome inhibition and its therapeutic potential in multiple myeloma  

PubMed Central

Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years. In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease. In this article, we briefly review the preclinical and clinical development of the drug as the underpinning for a systematic review of the large number of clinical trials that are beginning to shed some light on the full therapeutic potential of bortezomib in myeloma. We conclude with our current understanding of the mechanism of action of this agent and a discussion of the novel proteasome inhibitors under development, as it will be progress in these areas that will ultimately determine the true potential of proteasome inhibition in myeloma.

Chari, Ajai; Mazumder, Amitabha; Jagannath, Sundar

2010-01-01

41

A New Differential Logic-Compatible Multiple-Time Programmable Memory Cell  

NASA Astrophysics Data System (ADS)

This work presents a novel differential n-channel logic-compatible multiple-time programmable (MTP) memory cell. This cell features double sensing window by a differential pair of floating gates, and therefore increases the retention lifetime of the nonvolatile memory effectively. Also, a self-selective programming (SSP) method is innovated in writing one pair differential data by a single cell without increasing any design or process complexity in peripheral circuit. The differential cell is a promising MTP solution to challenge thin floating gate oxide below 70 Ĺ for 90 nm complementary metal-oxide-semiconductor (CMOS) node and beyond.

Yi-Hung Tsai,; Hsiao-Lan Yang,; Wun-Jie Lin,; Chrong Jung Lin,; Ya-Chin King,

2010-04-01

42

Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study  

PubMed Central

Background Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. Methods Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs). Results Tendon-derived cells stained D7-FIB (fibroblast-marker) positive, but ?-SMA (marker for smooth muscle cells and pericytes) negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker), and 73% positive for CD105 (mesenchymal progenitor-cell marker). In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4) and PPARG (peroxisome proliferative activated receptor ?). In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations. Conclusion This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis.

de Mos, Marieke; Koevoet, Wendy JLM; Jahr, Holger; Verstegen, Monique MA; Heijboer, Marinus P; Kops, Nicole; van Leeuwen, Johannes PTM; Weinans, Harrie; Verhaar, Jan AN; van Osch, Gerjo JVM

2007-01-01

43

Conditionally Immortalized Mouse Embryonic Fibroblasts Retain Proliferative Activity without Compromising Multipotent Differentiation Potential  

PubMed Central

Mesenchymal stem cells (MSCs) are multipotent cells which reside in many tissues and can give rise to multiple lineages including bone, cartilage and adipose. Although MSCs have attracted significant attention for basic and translational research, primary MSCs have limited life span in culture which hampers MSCs' broader applications. Here, we investigate if mouse mesenchymal progenitors can be conditionally immortalized with SV40 large T antigen and maintain long-term cell proliferation without compromising their multipotency. Using the system which expresses SV40 large T antigen flanked with Cre/loxP sites, we demonstrate that mouse embryonic fibroblasts (MEFs) can be efficiently immortalized by SV40 large T antigen. The conditionally immortalized MEFs (iMEFs) exhibit an enhanced proliferative activity and maintain long-term cell proliferation, which can be reversed by Cre recombinase. The iMEFs express most MSC markers and retain multipotency as they can differentiate into osteogenic, chondrogenic and adipogenic lineages under appropriate differentiation conditions in vitro and in vivo. The removal of SV40 large T reduces the differentiation potential of iMEFs possibly due to the decreased progenitor expansion. Furthermore, the iMEFs are apparently not tumorigenic when they are subcutaneously injected into athymic nude mice. Thus, the conditionally immortalized iMEFs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages. Our results suggest that the reversible immortalization strategy using SV40 large T antigen may be an efficient and safe approach to establishing long-term cell culture of primary mesenchymal progenitors for basic and translational research, as well as for potential clinical applications.

Huang, Enyi; Bi, Yang; Jiang, Wei; Luo, Xiaoji; Yang, Ke; Gao, Jian-Li; Gao, Yanhong; Luo, Qing; Shi, Qiong; Kim, Stephanie H.; Liu, Xing; Li, Mi; Hu, Ning; Liu, Hong; Cui, Jing; Zhang, Wenwen; Li, Ruidong; Chen, Xiang; Shen, Jikun; Kong, Yuhan; Zhang, Jiye; Wang, Jinhua; Luo, Jinyong; He, Bai-Cheng; Wang, Huicong; Reid, Russell R.; Luu, Hue H.; Haydon, Rex C.; Yang, Li; He, Tong-Chuan

2012-01-01

44

The neuroprotective potential of flavonoids: a multiplicity of effects.  

PubMed

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; Spencer, Jeremy P E

2008-12-01

45

Potential variant of multiple endocrine neoplasia in a dog.  

PubMed

This report describes multiple endocrine neoplasia in a dog, which is a rare hereditary disorder characterized by the presence of two or more neoplasms of different endocrine tissues within a patient. A 14 yr old dog was evaluated for polyuria/polydipsia, polyphagia, and abdominal enlargement. Adrenal-dependent hyperadrenocorticism with concomitant left thyroid enlargement and a presumed abdominal metastatic lesion were diagnosed by an adrenocorticotropic hormone stimulation test, ultrasonography, and computed tomography. Trilostane therapy was initiated and resolved the clinical signs for 2 yr at which time the dog presented with left testicular enlargement. The dog was euthanized and was diagnosed with adrenocortical carcinoma, thyroid carcinoma, an abdominal mass compatible with a metastatic lymph node, and bilateral interstitial cell testicular adenomas. To the authors' knowledge, this is the first report to describe the concomitant association of these types of endocrine neoplasms in a dog. The concomitant presence of these neoplasms could represent a potential variant of multiple endocrine neoplasia; however, the presence of the interstitial cell testicular adenomas may have only been an incidental finding. If any of these tumors are diagnosed, veterinarians should perform a thorough clinical assessment to evaluate for the presence of additional endocrine neoplasms or hyperplasia. PMID:22267170

Proverbio, Daniela; Spada, Eva; Perego, Roberta; Grieco, Valeria; Lodi, Matteo; Di Giancamillo, Mauro; Ferro, Elisabetta

2012-01-19

46

Auditory event-related potentials in multiple sclerosis.  

PubMed

The present study examined the effects of multiple sclerosis (MS) on the N1, P2, and P300 components of the late auditory evoked potential (LAEP). A group of 30 subjects with confirmed MS were compared with 30 control subjects who were pair-matched to the MS subjects with respect to age and gender. A standard stimulus oddball procedure was used to elicit the LAEP, in which subjects had to selectively attend to rare tones randomly interspersed among more frequently occurring tones of a different frequency. LAEPs were recorded with and without the presence of simultaneous speech competition in the nontest ear. Although the presence of speech competition produced significant latency and amplitude changes with the different components of the LAEP, the magnitude of the changes were similar for both subject groups. However, in comparison to the control group, a significantly higher proportion of MS subjects exhibited absent P300 responses on all test runs. PMID:8694124

Boose, M A; Cranford, J L

1996-01-01

47

Differential effects of alcohol on working memory: distinguishing multiple processes.  

PubMed

The authors 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 2 properties of materials to be retained in a 2-stimulus comparison procedure. Conditions included (a) spatial arrays of colors, (b) temporal sequences of colors, (c) spatial arrays of spoken digits, and (d) 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 on 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

2007-12-01

48

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.

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

2008-01-01

49

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

50

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

51

Differential Involvement of the Periaqueductal Gray in Multiple System Atrophy  

PubMed Central

The periaqueductal gray (PAG) consists of distinct columns that participate in the integrated control of autonomic function. We sought to determine whether the PAG is affected in multiple system atrophy (MSA), a disorder characterized by prominent autonomic failure. Brains were obtained at autopsy from 13 MSA patients (10 M, 3 F, age 61 ± 3 years) and 13 controls (8 M, 5 F, age 67 ± 4 years). Transverse formalin-fixed 50 ?m sections were obtained throughout the PAG and immunostained for the vesicular transporter 2 (VGLUT-2), nitric oxide synthase (NOS), or ?-synuclein and co-stained with thionin. Some sections were processed for myelin or astrocyte staining. Stereological quantitation was performed separately in the ventrolateral, lateral, dorsolateral, and dorsomedial columns of the PAG. In MSA cases, there was a decrease in the total estimated number of VGLUT-2 immunoreactive neurons in the ventrolateral, lateral, and dorsomedial and to a lesser extent dorsolateral PAG compared to controls (ventrolateral PAG: 16,299 ± 1,612 vs. 27,906 ± 2,480 respectively, p<0.01; lateral PAG: 11,004 ± 1,401 vs. 16,078 ± 1,140 respectively, p< 0.05; and dorsomedial PAG: 8,847 ± 1,052 vs. 15,412 ± 1,097 respectively, p< 0.001). The number of NOS immunoreactive neurons in the dorsolateral PAG was similar to controls. In all columns, the number of non-immunolabelled Nissl-stained cells was similar between groups. There was accumulation of glial cytoplasmic inclusions in all PAG columns in MSA. Our findings indicate involvement of the PAG columns in MSA, which may contribute to autonomic disturbances in this disorder.

Benarroch, Eduardo E.; Schmeichel, Ann M.; Low, Phillip A.; Parisi, Joseph E.

2010-01-01

52

A standard and direct method to obtain multiple soliton solutions of the nonlinear partial differential equation  

NASA Astrophysics Data System (ADS)

In this paper, we improve some key steps in the homogeneous balance method (HBM), and propose a modified homogeneous balance method (MHBM) for constructing multiple soliton solutions of the nonlinear partial differential equation (PDE) in a unified way. The method is very direct and primary; furthermore, many steps of this method can be performed by computer. Some illustrative equations are investigated by this method and multiple soliton solutions are found.

Zhao, Hong; Bai, Cheng-Lin

2006-02-01

53

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

54

A stimuli-responsive "smart probe" for selective monitoring of multiple-cations via differential analyses.  

PubMed

A dual-emissive benzimidazole-based ternary ruthenium complex containing multiple ionophores viz. carbonyl, amine, and imine exhibits discriminating behaviour for Pb(2+), Fe(2+) and Zn(2+), at parts-per-million concentrations, which leads to selective recognition of the above cations via differential responses using a single optical technique. PMID:23570037

Kumar, Anup; Singh, Alok K; Gupta, Tarkeshwar

2013-04-08

55

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

56

Identification of Differential Item Functioning in Multiple-Group Settings: A Multivariate Outlier Detection Approach  

ERIC Educational Resources Information Center

|We focus on the identification of differential item functioning (DIF) when more than two groups of examinees are considered. We propose to consider items as elements of a multivariate space, where DIF items are outlying elements. Following this approach, the situation of multiple groups is a quite natural case. A robust statistics technique is…

Magis, David; De Boeck, Paul

2011-01-01

57

Identification of Differential Item Functioning in Multiple-Group Settings: A Multivariate Outlier Detection Approach  

Microsoft Academic Search

We focus on the identification of differential item functioning (DIF) when more than two groups of examinees are considered. We propose to consider items as elements of a multivariate space, where DIF items are outlying elements. Following this approach, the situation of multiple groups is a quite natural case. A robust statistics technique is proposed to identify DIF items as

David Magis; Paul De Boeck

2011-01-01

58

Multiple Levels of Degradation Diminish Hemostatic Potential of Thawed Plasma  

PubMed Central

Background Severe bleeding after injury requires transfusion of blood products, including fresh frozen plasma (FFP). Many centers are keeping thawed plasma (TP) ready for massively transfused patients. According to the American Association of Blood Banks Standards, TP is approved for transfusion up to 5 days after thawing, when stored at 1°C to 6°C. However, there are no clinical data analyzing the effects of the approved 5-day storage on plasma. We hypothesize that the hemostatic potential (HP) of freshly thawed (FFP-0) was superior to plasma stored for 5 days (FFP-5). Methods FFP from 30 single donors were thawed at 37°C and kept at 1°C to 6°C for 5 days. HP was evaluated at day 0 and 5 by measuring kinetics of thrombin generation (TG), kinetics of clot formation by thromboelastography, clotting factors and inhibitors, and cell-derived microparticles (MPs) by flow cytometry. Results When comparing FFP-5 to FFP-0, FFP-5 exhibited only 40% of the potential of FFP-0 for TG (6.2 nM/min vs. 14.3 nM/min, p < 0.0001), a slower clotting response via thromboelastography (reaction time: 4.3 minutes vs. 3.2 minutes, p < 0.0001) and a longer delay in reaching maximum thrombus generation (5.7 minutes vs. 4.6 minutes, p < 0.01). Diminished HP was accompanied by a significant decline in multiple coagulation proteins, including FV, VII, VIII, von Willebrand factor, and free Protein S, by up to 30%, and a decrease of 50% in MP counts. Conclusion The HP and clot forming ability of TP significantly declined with storage. Hence, freshly TP may have a greater ability to restore hemostasis and correct coagulopathy compared with FFP-5. The clinical consequences for transfused patients deserve further exploration.

Matijevic, Nena; Kostousov, Vadim; Wang, Yao-Wei W.; Wade, Charles E.; Wang, Weiwei; Letourneau, Phillip; Hartwell, Elizabeth; Kozar, Rosemary; Ko, Tien; Holcomb, John B.

2011-01-01

59

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.

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

2013-01-01

60

Multiple organ failure. Pathophysiology and potential future therapy.  

PubMed Central

Multiple organ failure (MOF) has reached epidemic proportions in most intensive care units and is fast becoming the most common cause of death in the surgical intensive care unit. Furthermore, in spite of the development of successive generations of new and more powerful antibiotics and increasing sophisticated techniques of organ support, our ability to salvage patients once MOF has become established has not appreciably improved over the last two decades. Clearly, new therapeutic strategies aimed at preventing or limiting the development of the physiologic abnormalities that induce organ failure are needed to improve survival in these critically ill patients. Based on our rapidly increasing knowledge of the mechanisms of MOF and the fruits of molecular biology, a number of new therapeutic approaches are in various stages of development. To effectively use these new therapeutic options as they become available, it is necessary to have a clear understanding of the pathophysiology of MOF. Thus, the goals of this review are to integrate the vast amount of new information on the basic biology of MOF and to focus special attention on the potential therapeutic consequences of these recent advances in our understanding of this complex and perplexing syndrome.

Deitch, E A

1992-01-01

61

Visual and motor evoked potentials in the course of multiple sclerosis  

Microsoft Academic Search

Summary While evoked potentials are sensitive tools for diagnosing multiple sclerosis, little is known about their prognostic value and their role in determining the course of the disease. To validate the visual and motor evoked potentials (VEP and MEP) as measures for the course of multiple sclerosis, we examined prospectively 30 patients with relapsing-remitting or secondary progressive multiple sclerosis. The

P. Fuhr; A. Borggrefe-Chappuis; C. Schindler; L. Kappos

2001-01-01

62

Basal expression of pluripotency-associated genes can contribute to stemness property and differentiation potential.  

PubMed

Pluripotency and stemness is believed to be associated with high Oct-3/4, Nanog, and Sox-2 (ONS) expression. Similar to embryonic stem cells (ESCs), high ONS expression eventually became the measure of pluripotency in any cell. The threshold expression of ONS genes that underscores pluripotency, stemness, and differentiation potential is still unclear. Therefore, we raised a question as to whether pluripotency and stemness is a function of basal ONS gene expression. To prove this, we carried out a comparative study between basal ONS expressing NIH3T3 cells with pluripotent mouse bone marrow mesenchymal stem cells (mBMSC) and mouse ESC. Our studies on cellular, molecular, and immunological biomarkers between NIH3T3 and mBMSC demonstrated stemness property of undifferentiated NIH3T3 cells that was similar to mBMSC and somewhat close to ESC as well. In vivo teratoma formation with all three germ layer derivatives strengthen the fact that these cells in spite of basal ONS gene expression can differentiate into cells of multiple lineages without any genetic modification. Conclusively, our novel findings suggested that the phenomenon of pluripotency which imparts ability for multilineage cell differentiation is not necessarily a function of high ONS gene expression. PMID:23343006

Dadheech, Nidheesh; Srivastava, Abhay; Belani, Muskaan; Gupta, Sharad; Pal, Rajarshi; Bhonde, Ramesh R; Srivastava, Anand S; Gupta, Sarita

2013-03-08

63

Differentiation Potential of Multipotent Progenitor Cells Derived from War-Traumatized Muscle Tissue  

PubMed Central

Background: Recent military conflicts have resulted in numerous extremity injuries requiring complex orthopaedic reconstructive procedures, which begin with a thorough débridement of all contaminated and necrotic tissue in the zone of injury. The site of injury is also the site of healing, and we propose that débrided muscle tissue contains cells with robust reparative and regenerative potential. Methods: Débrided muscle from soldiers who had sustained traumatic open extremity injuries was collected during surgical débridement procedures at Walter Reed Army Medical Center. With modifications to a previously described stem-cell-isolation protocol, mesenchymal progenitor cells were harvested from traumatized muscle, enriched, expanded in culture, and exposed to induction media for osteogenesis, adipogenesis, and chondrogenesis. Results: The isolated mesenchymal progenitor cells stained positive for cell-surface markers (CD73, CD90, CD105), which are characteristic of adult human mesenchymal stem cells. Histological identification of lineage-specific markers demonstrated the potential of these cells to differentiate into multiple mesenchymal lineages. Reverse transcription-polymerase chain reaction analysis confirmed multilineage mesenchymal differentiation at the gene-expression level. Conclusions: To our knowledge, the present report provides the first description of mesenchymal progenitor cell isolation from traumatized human muscle. These cells may play an integral role in tissue repair and regeneration and merit additional investigation as they could be useful in future cell-based tissue-engineering strategies. Clinical Significance: Mesenchymal progenitor cells isolated from war-traumatized tissues have the potential for applications in cell-based tissue engineering. Elucidating the cellular mechanisms regulating their differentiation activities may lead to the development of novel treatments for musculoskeletal trauma and pathological healing responses, such as heterotopic ossification.

Nesti, Leon J.; Jackson, Wesley M.; Shanti, Rabie M.; Koehler, Steven M.; Aragon, Amber B.; Bailey, James R.; Sracic, Michael K.; Freedman, Brett A.; Giuliani, Jeffrey R.; Tuan, Rocky S.

2008-01-01

64

Sobolev quasi-periodic solutions of multidimensional wave equations with a multiplicative potential  

NASA Astrophysics Data System (ADS)

We prove the existence of quasi-periodic solutions for wave equations with a multiplicative potential on T^d , d ? 1, and finitely differentiable nonlinearities, quasi-periodically forced in time. The only external parameter is the length of the frequency vector. The solutions have Sobolev regularity both in time and space. The proof is based on a Nash-Moser iterative scheme as in [5]. The key tame estimates for the inverse linearized operators are obtained by a multiscale inductive argument, which is more difficult than for NLS due to the dispersion relation of the wave equation. We prove the ‘separation properties’ of the small divisors assuming weaker non-resonance conditions than in [11].

Berti, Massimiliano; Bolle, Philippe

2012-09-01

65

[Intrathecal immunoglobulin production in the diagnosis and differential diagnosis of multiple sclerosis].  

PubMed

The evaluation of diagnostic significance of different immunological tests for intrathecal immunoglobulin production is summarized on the historical basis of investigation of patients with inflammatory, demyelinating and other neurological disorders. The assessment of cerebrospinal fluid lost its previous significance in the 2010 revision of diagnostic criteria for multiple sclerosis. Nowadays, it is used only for the diagnosis of primary progressive multiple sclerosis. Nevertheless, the requirements of the analysis of the cerebrospinal fluid are increasing due to subtle, subclinical and atypical cases of multiple sclerosis as well as undetermined demyelinating disorders. Intrathecal humoral immune response may be pathogenic in multiple sclerosis as suggest immunological data and effectiveness of anti-B cells treatment. Based on these tests, it is useful, to differentiate subgroups of patients and to evaluate different effects of treatment in perspective. PMID:23235427

Totolian, N A; Gotovchikov, A A; Lapin, S V; Maksimov, I V; Kodzaeva, A Iu; Prakhova, L N; Il'ves, A G; Skoromets, A P; Totolian, A A; Skoromets, A A

2012-01-01

66

Multiple-scattering effect on ozone retrieval from space-based differential absorption lidar measurements.  

PubMed

Single-scattering and multiple-scattering lidar signals are calculated for a spaceborne differential absorption lidar system for global ozone measurements at the on and off wavelength pair at 305 and 315 nm. The effect of multiple scattering is found to be negligible on stratospheric and tropospheric ozone retrieval under background stratospheric aerosol. Under low-visibility conditions in the planetary boundary layer the presence of multiple scattering causes an overestimation in maritime aerosol and an underestimation in urban as well as in rural aerosol. This effect is also examined in three cirrus models. The multiple scattering does not permit accurate ozone retrieval within cirrus; however, below it the solution recovers somewhat with generally an underestimation depending on the type and density of cirrus. The effect of aerosol and Rayleigh extinction on the ozone retrieval is also discussed. PMID:18286159

Pal, S R; Bissonnette, L R

1998-09-20

67

Prognostic Factors in Patients with Multiple Recurrences of Well-Differentiated Thyroid Carcinoma  

PubMed Central

Introduction. Patients with multiple recurrences of well-differentiated thyroid carcinoma (WDTC) have markedly reduced overall survival when compared with those who have ?1 recurrence of their disease. The purpose of this investigation is to identify prognostic factors for mortality in this subgroup. Methods. Patients with multiple recurrences of WDTC were retrospectively identified from the thyroid cancer database at Mount Sinai Hospital, Toronto (1963–2000). Data on patient, tumor, and recurrence characteristics were collected, and each patient was given a MACIS score. Results. A total of 31 patients were identified (11 male, 20 female; 16–83 years). Using univariate analysis, age >45, stage III/IV disease, distant metastasis, vascular invasion, MACIS score >6, and time to recurrence of <12 months were found to be significant predictors for mortality in this subgroup. Conclusions. Patients with multiple recurrences of WDTC follow a distinct clinical course, marked with multiple treatment failures and a substantial risk of mortality.

Holler, Theresa; Theriault, Jenna; Payne, Richard J.; Clark, Jonathan; Eski, Spiro; Freeman, Jeremy L.

2009-01-01

68

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

Microsoft Academic Search

Elucidation of the mechanisms of stem cell differentiation is of great scientific interest. Increasing evidence suggests that stem cell differentiation involves changes at multiple levels of biological regulation, which together orchestrate the complex differentiation process; many related studies have been performed to investigate the various levels of regulation. The resulting valuable data, however, remain scattered. Most of the current stem

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

2012-01-01

69

Virtual reality and multiple intelligences: Potentials for higher education  

Microsoft Academic Search

IN THIS PAPER WE EXAMINE how virtual reality, an emerging computer-based technology, can promote learning that engages all\\u000a seven of the multiple intelligences proposed by Harvard educational psychologist Howard Gardner. We provides an overview of\\u000a virtual reality technologies and an overview of Gardner’s multiple intelligences. There is an extensive discussion of how\\u000a virtual reality supports learning within and across seven

Hilary McLellan

1994-01-01

70

The utility of multimodal evoked potentials in multiple sclerosis prognostication.  

PubMed

The ability to predict disability development in multiple sclerosis (MS) is limited. While abnormalities of evoked potentials (EP) have been associated with disability, the prognosticating utility of EP in MS remains to be fully elucidated. The present study assessed the utility of multimodal EP as a prognostic biomarker of disability in a cohort of clinically heterogeneous MS patients. Median and tibial nerve somatosensory, visual, and brainstem auditory EP were performed at initial assessment on 63 MS patients (53 relapsing-remitting and 10 secondary progressive) who were followed for an average of 2years. A combined EP score (CEPS) was calculated consisting of the total number of abnormal EP tests, and was correlated with the Expanded Disability Status Scale (EDSS) at baseline and follow-up. There was a significant correlation between multimodal EP and baseline and follow-up EDSS. Specifically, tibial nerve P37 latencies correlated with EDSS (RBASELINE=0.49, p<0.01; RFOLLOW-UP=0.47, p<0.01), as did the median nerve N13 (RBASELINE=0.40, p<0.01; RFOLLOW-UP=0.35, p<0.05) and N20 latencies (RBASELINE=0.43, p<0.01; RFOLLOW-UP=0.47, p<0.01), and P100 full-field (RBASELINE=0.50, p<0.001; RFOLLOW-UP=0.45, p<0.001) and central field latencies (RBASELINE=0.60, p<0.001; RFOLLOW-UP=0.50, p<0.001). In addition, there was a significant correlation between the CEPS with baseline (R=0.65, p<0.001) and follow-up (R=0.57, p<0.01) EDSS. In contrast, white matter disease burden, as measured by T2 lesion load, exhibited a weaker correlation with EDSS (RBASELINE=0.28, p<0.05). In conclusion, these findings suggest that abnormalities of EP, as quantified by the novel CEPS, may be a useful biomarker for prognosticating clinical disability in MS, and may aid in the quantification of MS disease severity and in guiding therapeutic decisions. PMID:23827173

Ramanathan, Sudarshini; Lenton, Kerry; Burke, Therese; Gomes, Lavier; Storchenegger, Karen; Yiannikas, Con; Vucic, Steve

2013-07-01

71

Multiple-Symbol Differential Unitary Space-Time Demodulation with Reduced-Complexity  

Microsoft Academic Search

We derive a new decision rule for multiple-symbol detection (MSD) of differential unitary space-time modulation (DUSTM). It is valid for both diagonal and non-diagonal con- stellations, and for quasi-static fading channels. We then present a fast algorithm based on the Extended Euclidean algorithm and bound principles for single symbol detection (SSD) with diagonal constellations. We call it bound-intersection detection (BID)

Tao Cui; Chintha Tellambura

2009-01-01

72

Multiple-symbol differential unitary space-time demodulation with reduced-complexity  

Microsoft Academic Search

We derive a new decision rule for multiple-symbol detection (MSD) of differential unitary space-time modulation (DUSTM). It is valid for both diagonal and non-diagonal constellations, and for quasi-static fading channels. We then present a fast algorithm based on the extended Euclidean algorithm and bound principles for single symbol detection (SSD) with diagonal constellations. We call it bound-intersection detection (BID) and

Tao Cui; Chintha Tellambura

2005-01-01

73

Evoked potentials and contingent negative variation during treatment of multiple sclerosis with spinal cord stimulation  

Microsoft Academic Search

Cervical somatosensory evoked potentials, brainstem evoked potentials, visual evoked potentials, and the cerebral contingent negative variation were recorded in patients with definite multiple sclerosis before, during, and after spinal cord stimulation. Improvements were seen in the cervical somatosensory and brainstem evoked potentials but neither the visual evoked potential nor the contingent negative variation changed in association with spinal cord stimulation.

E M Sedgwick; L S Illis; R C Tallis; A R Thornton; P Abraham; E El-Negamy; T B Docherty; J S Soar; S C Spencer; F M Taylor

1980-01-01

74

Equivalent system for a multiple-rational-order fractional differential system.  

PubMed

The equivalent system for a multiple-rational-order (MRO) fractional differential system is studied, where the fractional derivative is in the sense of Caputo or Riemann-Liouville. With the relationship between the Caputo derivative and the generalized fractional derivative, we can change the MRO fractional differential system with a Caputo derivative into a higher-dimensional system with the same Caputo derivative order lying in (0,1). The stability of the zero solution to the original system is studied through the analysis of its equivalent system. For the Riemann-Liouville case, we transform the MRO fractional differential system into a new one with the same order lying in (0,1), where the properties of the Riemann-Liouville derivative operator and the fractional integral operator are used. The corresponding stability is also studied. Finally, several numerical examples are provided to illustrate the derived results. PMID:23547233

Li, Changpin; Zhang, Fengrong; Kurths, Jürgen; Zeng, Fanhai

2013-04-01

75

Understanding multiple ecological responses to anthropogenic disturbance: rivers and potential flow regime change.  

PubMed

Human-induced alteration of the natural flow regime is a major threat to freshwater ecosystems and biodiversity. The effects of hydrological alteration on the structural and functional attributes of riverine communities are expected to be multiple and complex, and they may not be described easily by a single model. Based on existing knowledge of key hydrological and ecological attributes, we explored potential effects of a flow-regulation scenario on macroinvertebrate assemblage composition and diversity in two river systems in Australia's relatively undeveloped wet-dry tropics. We used a single Bayesian belief network (BBN) to model potential changes in multiple assemblage attributes within each river type during dry and wet seasons given two flow scenarios: the current, near-natural flow condition, and flow regulation. We then used multidimensional scaling (MDS) ordination to visually summarize and compare the most probable attributes of assemblages and their environment under the different scenarios. The flow-regulation scenario provided less certainty in the ecological responses of one river type during the dry season, which reduced the ability to make predictions from the BBN outputs directly. However, visualizing the BBN results in an ordination highlighted similarities and differences between the scenarios that may have been otherwise difficult to ascertain. In particular, the MDS showed that flow regulation would reduce the seasonal differentiation in hydrology and assemblage characteristics that is expected under the current low level of development. Our approach may have wider application in understanding ecosystem responses to different river management practices and should be transferred easily to other ecosystems or biotic assemblages to provide researchers, managers, and decision makers an enhanced understanding of ecological responses to potential anthropogenic disturbance. PMID:22471088

Leigh, Catherine; Stewart-Koster, Ben; Sheldon, Fran; Burford, Michele A

2012-01-01

76

Multiple solutions for elliptic problems with singular and sublinear potentials  

Microsoft Academic Search

For certain positive numbers µ and ?, we establish the multiplicity of solutions to the problem ? ?? u = µ u |x|2 + ?f (u )a .e. in ?, u =0 on??, where ? is a bounded open domain in RN (N ? 3) containing the origin with smooth boundary ??, while f : R ? R is continuous,

Alexandru Kristály; Csaba Varga

2007-01-01

77

Effect of raising body temperature on visual and somatosensory evoked potentials in patients with multiple sclerosis  

Microsoft Academic Search

The effects of raising body temperature on the visual (VEP) and somatosensory (SEP) evoked potentials were observed in normal subjects and in patients with multiple sclerosis. The amplitude of the VEP was significantly reduced to the same degree after heating in normal subjects and in patients with multiple sclerosis but there was no effect on the latency of the potential.

W B Matthews; D J Read; E Pountney

1979-01-01

78

A Search for Potential Habitable Planets in Multiple Planet Systems  

Microsoft Academic Search

Although the detection of habitable terrestrial planets around nearby stars is currently beyond our observational capabilities, carrying out dynamical studies of known extrasolar planetary systems allows us to search for potential candidates. Following from the work of Menou & Tabachnik (2003), we use a symplectic integrator to search for potential stable terrestrial planetary orbits in the habitable zones of known

S. T. Maddison; M. C. Gino; A. Munro; P. Hinds

2004-01-01

79

Potential liability of reproductive endocrinologists for high order multiple gestation  

PubMed Central

Background In light of the recent octuplet birth and the accompanying intensive media coverage, there has been much attention on high order multiple births resulting from assisted reproductive technology. Objectives The purpose of this commentary is to review 1) the relative contribution of ART to high order multiple gestation and its impact on infant morbidity, mortality, and health care dollar loss; 2) American Society of Reproductive Medicine’s guidelines for the number of embryos transferred in ART; and 3) how reproductive endocrinologists can lessen their exposure to litigation by following the ASRM guidelines for the number of embryos transferred and documenting proper informed consent in the medical records. Recommendations In situations in which the number of embryos transferred is in excess of the ASRM guidelines, justification for deviating from the ASRM guidelines should be justifiable and documented in the medical records.

Phelps, John

2010-01-01

80

Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis  

Microsoft Academic Search

BACKGROUND: This study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity. METHODS: CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC\\/MS\\/MS). Patients were stratified

Zohara Sternberg; Cassandra Hennies; Daniel Sternberg; Ping Wang; Peter Kinkel; David Hojnacki; Bianca Weinstock-Guttmann; Frederick Munschauer

2010-01-01

81

Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes.  

PubMed

Wound healing is the response of tissue to injury that results in scar formation. Tissue regeneration would be a more ideal response. Previously, we have isolated a population of cells from avian, rodent, and rabbit skeletal muscle capable of differentiating into multiple mesodermal phenotypes. The present experiments were designed to determine whether a similar population of cells exist in human skeletal muscle. Separate cell preparations from skeletal muscle on an amputated leg of a 75-year-old female and the pectoralis muscle of a 27-year-old male were enzymatically dissociated and cultured to confluence in Eagle's minimal essential medium with 10 per cent preselected horse serum, then trypsinized, filtered, and slowly frozen in 7.5 per cent dimethylsulfoxide to -80 degrees C. The cells were thawed and plated with the same media plus dexamethasone (a nonspecific differentiation agent) at 10(-10) - 10(-6) M concentrations for up to 6 weeks. Immunological and histochemical staining assays were performed. Phenotypes observed included stem cells with typical stellate morphology (control), skeletal myotubes (anti-myosin), smooth muscle (anti-a-actin), bone (von Kossa stain), cartilage (Alcec blue), and fat (Sudan black B). These experiments establish the existence of a population of mesenchymal stem cells in human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. The possibility exists of manipulating the mesenchymal stem cells to achieve appropriate regeneration of mesenchymal tissues in the injured patient. PMID:9915526

Williams, J T; Southerland, S S; Souza, J; Calcutt, A F; Cartledge, R G

1999-01-01

82

Multiple Color Stimulus Induced Steady State Visual Evoked Potentials.  

National Technical Information Service (NTIS)

Steady state visual evoked potentials (SSVEP) are of the characteristics of high SNR and effectiveness in short-term identification of evoked responses. In most of the SSVEP experiments, single high frequency stimuli are used. To characterize the complex ...

M. Cheng X. Gao S. Gao D. Xu

2001-01-01

83

Undersulfation of heparan sulfate restricts differentiation potential of mouse embryonic stem cells.  

PubMed

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

2012-02-01

84

Literature-related discovery (LRD): Potential treatments for Multiple Sclerosis  

Microsoft Academic Search

Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked (i.e., disjoint), in order to produce novel, interesting, plausible, and intelligible knowledge (i.e., potential discovery). The open discovery systems (ODS) component of LRD starts with a problem to be solved, and generates solutions to that problem through potential discovery. We have been

Ronald N. Kostoff; Michael B. Briggs; Terence J. Lyons

2008-01-01

85

The role of autonomic testing in the differentiation of Parkinson's disease from multiple system atrophy  

PubMed Central

Differentiation of idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) can be difficult. Methods devised to help distinguish the two disorders include standardized autonomic testing and cardiac imaging with iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. MSA patients had more severe adrenergic and overall autonomic dysfunction when compared to control and PD patients. Area of anhidrosis on thermoregulatory sweat testing was greater in MSA (67.4±12.42, p<0.001) versus PD patients (area of anhidrosis, 1.7±2.96). Postganglionic cardiac sympathetic innervation (iodine-123 meta-iodobenzylguanidine) expressed as heart to mediastinal ratio was significantly lower in Parkinson's disease patients (1.4±0.40, p=0.025) compared to controls (2.0±0.29), but not in multiple system atrophy (2.0±0.76). These findings indicate that autonomic dysfunction is generalized and predominantly preganglionic in multiple system atrophy, and postganglionic in Parkinson's disease. In our hands the Thermoregulatory Sweat Test provides the best distinction between MSA and PD. However further confirmatory studies using larger patient numbers are required. Currently a combination of clinical judgment and autonomic testing are recommended to help differentiate MSA and PD.

Kimpinski, Kurt; Iodice, Valeria; Burton, Duane D.; Camilleri, Michael; Mullan, Brian P.; Lipp, Axel; Sandroni, Paola; Gehrking, Tonette L.; Sletten, David M.; Ahlskog, J E.; Fealey, Robert D.; Singer, Wolfgang; Low, Phillip A.

2012-01-01

86

Doubly differential single and multiple ionization of krypton by electron impact  

SciTech Connect

Differential measurements for single and multiple ionization of Kr by 240 and 500 eV electron impact are presented. Using a pulsed extraction field, Kr{sup +}, Kr{sup 2+}, and Kr{sup 3+} ions were measured in coincidence with scattered electrons for energy losses up to 120 eV and scattering angles between 16 degree sign and 90 degree sign . Scaling properties of the doubly differential cross sections (DDCS) are investigated as a function of energy loss, scattering angle, and momentum transfer. It is shown that scaling the DDCS as outlined by Kim and Inokuti and plotting them versus a parameter consisting of the momentum transfer divided by the square root of the impact energy times 1-cos({theta}), where {theta} is the scattering angle, yielded similar curves, but with different magnitudes, for single and multiple ionization. Normalizing these curves together produced two universal curves, one appropriate for single and multiple electron emission at larger scattering angles ({theta}{>=}30 degree sign ) and one appropriate for small scattering angles ({theta}<30 degree sign )

Lucio, O. G. de; Gavin, J.; DuBois, R. D. [University of Missouri-Rolla, Rolla, Missouri 65409 (United States)

2007-05-15

87

Multiple spacecraft rendezvous maneuvers by differential drag and low thrust engines  

NASA Astrophysics Data System (ADS)

A novel two-phase hybrid controller is proposed to optimize propellant consumption during multiple spacecraft rendezvous maneuvers in Low Earth Orbit. This controller exploits generated differentials in aerodynamic drag on each involved chaser spacecraft to effect a propellant-free trajectory near to the target spacecraft during the first phase of the maneuver, and then uses a fuel optimal control strategy via continuous low-thrust engines to effect a precision dock during the second phase. In particular, by varying the imparted aerodynamic drag force on each of the chaser spacecraft, relative differential accelerations are generated between each chaser and the target spacecraft along two of the three translational degrees of freedom. In order to generate this required differential, each chaser spacecraft is assumed to include a system of rotating flat panels. Additionally, each chaser spacecraft is assumed to have continuous low-thrust capability along the three translational degrees of freedom and full-axis attitude control. Sample simulations are presented to support the validity and robustness of the proposed hybrid controller to variations in the atmospheric density along with different spacecraft masses and ballistic coefficients. Furthermore, the proposed hybrid controller is validated against a complete nonlinear orbital model to include relative navigation errors typical of carrier-phase differential GPS (CDGPS). Limitations of the proposed controller appear relative to the target spacecraft's orbit eccentricity and a general characterization of the atmospheric density. Bounds on these variables are included to provide a framework within which the proposed hybrid controller can effect an extremely low propellant rendezvous of multiple chaser spacecraft to a desired target spacecraft.

Bevilacqua, Riccardo; Hall, Jason S.; Romano, Marcello

2010-01-01

88

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.

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

2012-01-01

89

Wavelet entropy differentiations of event related potentials in dyslexia  

Microsoft Academic Search

The wavelet entropy (WE) of rest electroencephalogram (EEG) and of event-related potentials (ERP) carries information about the degree of order or disorder associated with a multi-frequency brain electrophysiological activity. In the present study, WE, relative WE and WE change were estimated for the EEG and ERP signals recorded during a working memory task, from dyslectic children and healthy subjects. The

Giorgos A. Giannakakis; Nikolaos N. Tsiaparas; Monika-filitsa S. Xenikou; Charalabos C. Papageorgiou; Konstantina S. Nikita

2008-01-01

90

Proliferation and differentiation potential of chondrocytes from osteoarthritic patients  

PubMed Central

Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained.

Tallheden, Tommi; Bengtsson, Catherine; Brantsing, Camilla; Sjogren-Jansson, Eva; Carlsson, Lars; Peterson, Lars; Brittberg, Mats; Lindahl, Anders

2005-01-01

91

Self-Adaptive Differential Evolution Based Power Economic Dispatch of Generators with Valve-Point Effects and Multiple Fuel Options  

Microsoft Academic Search

This paper presents the solution of power economic dispatch (PED) problem of generating units with valve point effects and multiple fuel options using Self-Adaptive Differential Evolution (SDE) algorithm. The global optimal solution by mathematical approaches becomes difficult for the realistic PED problem in power systems. The Differential Evolution (DE) algorithm is found to be a powerful evolutionary algorithm for global

R. Balamurugan; S. Subramanian

92

Bruton's tyrosine kinase: potential target in human multiple myeloma.  

PubMed

Bruton's tyrosine kinase (BTK), a Tec family non-receptor tyrosine kinase that is required for B cell development, is critical for the initiation and maintenance of human B-cell malignancies. However, the expression of BTK and the role that BTK plays in the pathogenesis of multiple myeloma (MM) remain seldom reported. In this study we examined the expression and screened for gene mutations of BTK in MM cells. We showed that BTK was elevated and activated in a dexamethasone-resistant cell line and in two out of nine (22.2%) patients' cells. Interestingly, patients with higher BTK expression had a poorer prognosis. In addition, a single nucleotide polymorphism (SNP) at cDNA position 2062 (T2062C) in the BTK gene was recorded in six out of eight (75%) patients and in U266 cells. This SNP in MM cells was not detected in other malignant hematopoietic cells of different lineages. These results suggest that the function of BTK warrants further investigation, and BTK expression might be used as a prognostic indicator for patients with MM. PMID:23581641

Liu, Ying; Dong, Ying; Jiang, Qian-Li; Zhang, Bo; Hu, An-Mei

2013-05-15

93

Monoclonal antibodies: potential new therapeutic treatment against multiple myeloma.  

PubMed

Despite recent treatments, such as bortezomib, thalidomide, and lenalidomide, therapy of multiple myeloma (MM) is limited, and MM remains an incurable disease associated with high mortality. The outcome of patients treated with cytotoxic therapy has not been satisfactory. Therefore, new therapies are needed for relapsed MM. A new anticancer strategy is the use of monoclonal antibodies (MoAbs) that represent the best available combination of tumor cytotoxicity, environmental signal privation, and immune system redirection. Clinical results in patients with relapsed/refractory MM suggest that MoAbs are likely to operate synergistically with traditional therapies (dexamethasone), immune modulators (thalidomide, lenalidomide), and other novel therapies (bortezomib); in addition, MoAbs have shown the ability to overcome resistance to these therapies. It remains to be defined how MoAb therapy can most fruitfully be incorporated into the current therapeutic paradigms that have achieved significant survival earnings in patients with MM. This will require careful consideration of the optimal sequence of treatments and their clinical position as either short-term induction therapy, frontline therapy in patients ineligible for ASCT, or long-term maintenance treatment. PMID:23506222

Allegra, Alessandro; Penna, Giuseppa; Alonci, Andrea; Russo, Sabina; Greve, Bruna; Innao, Vanessa; Minardi, Viviana; Musolino, Caterina

2013-04-17

94

Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis  

PubMed Central

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

2010-01-01

95

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

PubMed

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

2008-10-01

96

Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells  

PubMed Central

Background The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles. Methodology/Principal Findings to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes. Conclusions/Significance Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells.

Ballestar, Esteban; Andreu, Enrique J.; Roman-Gomez, Jose; Prieto, Ines; Martin-Subero, Jose Ignacio; Cigudosa, Juan Cruz; Siebert, Reiner; Esteller, Manel; Prosper, Felipe

2009-01-01

97

Circadian and hypothermia-induced effects on visual and auditory evoked potentials in multiple sclerosis  

Microsoft Academic Search

Objectives: Body cooling has been proposed as a symptomatic treatment for multiple sclerosis. This study aimed to assess the effects of body cooling and of circadian variations on clinical parameters and on visual and auditory evoked potential measures in multiple sclerosis patients.Methods: Clinical status was assessed and VEPs, BAEPs and MLAEPs (all with two stimulus frequencies) were recorded a total

A Romani; R Bergamaschi; M Versino; A Zilioli; R Callieco; V Cosi

2000-01-01

98

A numerical method for some stochastic differential equations with multiplicative noise [rapid communication  

NASA Astrophysics Data System (ADS)

Diffusion processes intended to model the continuous state space limit of birth death processes, chemical reactions, and other discrete particle systems often involve multiplicative noise where the diffusion vanishes near one (or more) of the state space boundaries. Standard direct numerical simulation schemes for the associated stochastic differential equations run the risk of “overshooting”, i.e., of varying outside the meaningful state space domain where simple analytic expressions for the diffusion coefficient may take on unphysical (negative or complex) values. We propose a simple scheme to overcome this problem and apply it to an exactly soluble stochastic ordinary differential equation (SODE), and to a related parabolic stochastic partial differential equation (SPDE) that admits exact analytic solution for the stationary correlation function. Armed with these analytic benchmark solutions, we demonstrate that the scheme produces approximate solutions for the SODE with distributions that display first-order convergence in the Wasserstein metric. For the SPDE, the scheme produces first order convergence for the stationary correlation function in L.

Doering, Charles R.; Sargsyan, Khachik V.; Smereka, Peter

2005-09-01

99

Performance evaluation of land mobile satellite system under vegetative shadowing using differential multiple TCM and QPSK  

NASA Astrophysics Data System (ADS)

A comparative analysis by computer simulation of the land mobile satellite system (LMSS) is presented for the uncoded quadrature phase shift keying (QPSK), rate 2/3 8-PSK trellis coded modulation (TCM), and rate 4/6 multiplicity 2 8-PSK TCM schemes. An analytical model is used for simulating the fading channel. The simulation results show that under Rayleigh fades, the TCM designed for the fading channel is superior to uncoded QPSK and to the conventional TCM optimized for the additive white Gaussian noise (AWGN) channel. The performance of differentially detected TCM under AWGN and fading is examined based on the preliminary results. Results of the uncoded QPSK with fading channel modeled with the empirical fade data are given.

Kim, Junghwan; Haschart, D.; Kwatra, S. C.; Vanderaar, Mark J.; Stevens, G. H.

100

Determination of. alpha. sub s from a differential jet multiplicity distribution at SLC and PEP  

SciTech Connect

We measure the differential jet multiplicity distribution in e{sup {plus}}e{sup {minus}} annihilation with the Mark 2 detector. This distribution is compared with the second order QCD prediction and {alpha}{sub s} is determined to be 0.123 {plus minus} 0.009 {plus minus} 0.005 at {radical}s {approximately} M{sub Z} (at SLC) and 0.149 {plus minus} 0.002 {plus minus} 0.007 at {radical}s = 29 GeV (at PEP). The running of {alpha}{sub s} between these two center of mass energies is consistent with the QCD prediction. The Q{sup 2} dependence of the {Lambda}{sub {ovr MS}} determination is also discussed. 21 refs., 3 figs.

Komamiya, Sachio.

1990-04-01

101

Slaving principle for stochastic differential equations with additive and multiplicative noise and for discrete noisy maps  

NASA Astrophysics Data System (ADS)

We first treat multidimensional nonlinear noisy maps. We assume that the variables can be split into two classes of variables u and s so that the linearized equations would give rise to growth or decay for u and s, respectively. We show how the slaved variables s can be explicitly expressed by the order parameters u by making use of the fully nonlinear equations. By taking the limit of vanishing time steps and using a Wiener process and the Îto calculus we derive the corresponding formulas for stochastic differential equations (including multiplicative noise). In this way a high-dimensional problem can be reduced to a problem of much lower dimensions described again by stochastic equations of the Îto type. A similar procedure holds for the Stratonovich calculus.

Haken, H.; Wunderlin, A.

1982-06-01

102

Evasion of multiple, intelligent pursuers in a stationary, cluttered environment using a poisson potential field  

Microsoft Academic Search

In this paper a new potential field approach is suggested for the evasive navigation of an agent that is engaging multiple pursuers in a stationary environment. Here, the gradient of a potential field that is generated by solving the Poisson equation subject to a set of mixed boundary conditions is used to generate a sequence of directions to guide the

Ahrnad A. Masoud; Saudia Arabia

2003-01-01

103

Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis  

Microsoft Academic Search

ObjectivesPatients with primary systemic (AL) amyloidosis or multiple myeloma are frequently treated with cyclic dexamethasone (DXM) courses and often require oral anticoagulants. We previously reported a strong potentiation of oral anticoagulants with intravenous methylprednisolone and observed a similar potentiation with DXM in 3 patients, which led us to prospectively investigate the interaction between DXM and oral anticoagulants.

Jérémie Sellam; Nathalie Costedoat-Chalumeau; Zahir Amoura; Guy Aymard; Sylvain Choquet; Salim Trad; Bénédicte Lebrun Vignes; Jean-Sébastien Hulot; Francis Berenbaum; Philippe Lechat; Patrice Cacoub; Annick Ankri; Xavier Mariette; Véronique Leblond; Jean-Charles Piette

2007-01-01

104

[Primary culture and multiple differentiation potency of mesenchymal stem cells from human umbilical cord].  

PubMed

Objective To establish a reliable method of isolation, culture and characterization of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and study its multiple differentiation potency. Methods HUCMSCs were isolated and cultured using Trypsin-type II collagen and hyaluronidase digestion method and tissue explant culture method, respectively. The cell growth of hUCMSCs was observed under an inverted microscope. Cell viability rate of the different passages was evaluated by trypan blue staining. The proliferation profile of hUCMSCs was analyzed by growth curve and MTT assay. Flow cytometry was used to study the cell cycle and immunophenotypage change. The differentiation potency of hUCMSCs towards the osteoblasts, adipocytes was assayed using the differentiation kits. The differentiation towards the cardiomyocytes and endothelial cells was tested by immunofluoresence staining with the specific markers. Results After 1-day culture of the enzyme digested cells, under the inverted microscope, the adherent cells were round, and 4 days later, they grew quickly and presented fusiform. Seven days later, the cells proliferated from the center to the peripheral and fused by 80% on day 10. With the tissue explant culture method, the cells started to proliferate gradually from the periphery of the tissue and grew quickly and arrayed closely in monolayer after 10 days. The cell viability in both isolation methods were more than 96% as tested by trypan blue staining. The growth curve of the third passage presented an "S" shape. MTT assay showed that the optimal cell proliferation occured on day 3 to 5. The ratios of G0/G1 phase and S+G2/M phase was 88.78% and 10.21% respectively by enzyme digestion, and 84.82% and 13.87% respectively by explant culture method. There was no significant difference in cell cycle. The positive rates of CD90, CD105, CD73 were more than 99% and the expressions of CD45, CD34, CD14, CD11b, CD79a, CD19, HLA-DR were lower than 1%. The hUCMSCs isolated by the two methods could efficiently differentiate towards the osteoblasts, lipocytes, cardiac myocytes and endothelial cells, and the positive rates were all above 90%. Conclusion The hUCMSCs can be effectively isolated by both enzyme digestion and explant culture methods. The enzyme isolation method presents a better method regarding the cell number obtained. This study showed the enzyme isolation method may be an optimal method to isolate the hUCMSCs for the cellular therapy and stem cell bioengineering. PMID:24103271

Xin, Yi; Li, Na; Huang, Yimin; Cui, Wei; Liu, Sa; Xu, Xiufang; Zhang, Zhaoguang

2013-10-01

105

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.??

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

2001-01-01

106

Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production  

Microsoft Academic Search

The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor\\u000a cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic\\u000a mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated,\\u000a non or low CEA producing cell lines were poorly metastatic to

Hans E. Wagner; Carol Ann Toth; Glenn D. Steele Jr; Peter Thomas

1992-01-01

107

Alteration, by early underfeeding, of cellular multiplication and differentiation in the inguinal fat pads of rats.  

PubMed

The effect of litter size on the incorporation of labeled thymidine (TdR) into DNA was studied in the stromal and the adipocyte fractions of the rat inguinal tissue. In experiment 1 the animal were kept in litters of 18 (UF) or 6 (control) from birth till 10 days. They were injected with [2-14C] TdR at day 3 and killed at 60 minutes, 1, 3 and 7 days post-injection. In experiment 2, the pups were raised in litters of 18 during 3 (RF3), 6 (RF6) or 10 (RF10) days, and distributed again in litters of six. They were injected with [2-14C] TdR or [14CH3]TdR at the beginning of the refeeding and killed as described previously. In all experiments the weight of the inguinal tissue was more reduced than the total body weight. In the UF, the proliferation was markedly reduced in cellular fractions as was the differentiation of stromal cells into adipocytes from six days of underfeeding. In the RF3 and the RF6 there was an attempt to recover the cell number as suggested by the recycling of the degradation products of TdR for DNA synthesis. In the RF10, cell multiplication and differentiation were strongly affected by the length of the deprivation period. PMID:7310535

Gaben-Cogneville, A M; Jahchan, T; Swierczewski, E

1981-12-01

108

Enucleated L929 Cells Support Invasion, Differentiation, and Multiplication of Trypanosoma cruzi Parasites?  

PubMed Central

Cell infection with Trypanosoma cruzi, the agent of Chagas’ disease, begins with the uptake of infective trypomastigotes within phagosomes and their release into the cytosol, where they transform into replicating amastigotes; the latter, in turn, differentiate into cytolytically released and infective trypomastigotes. We ask here if the T. cruzi infection program can develop in enucleated host cells. Monolayers of L929 cells, enucleated by centrifugation in the presence of cytochalasin B and kept at 34°C to extend the survival of cytoplasts, were infected with parasites of the CL strain. Percent infection, morphology, stage-specific markers, and numbers of parasites per cell were evaluated in nucleated and enucleated cells, both of which were present in the same preparations. Parasite uptake, differentiation and multiplication of amastigotes, development of epimastigote- and trypomastigote-like forms, and initial cytolytic release of parasites were all documented for cytoplasts and nucleated cells. Although the doubling times were similar, parasite loads at 48 and 72 h were significantly lower in the cytoplasts than in nucleated cells. Similar results were obtained with the highly virulent strain Y as well as with strains CL-14 and G, which exhibit low virulence for mice. Cytoplasts could also be infected with the CL strain 24 or 48 h after enucleation. Thus, infection of cells by T. cruzi can take place in enucleated host cells, i.e., in the absence of modulation of chromosomal and nucleolar gene transcription and of RNA modification and processing in the nucleus.

Coimbra, Vanessa C.; Yamamoto, Denise; Khusal, Ketna G.; Atayde, Vanessa Diniz; Fernandes, Maria Cecilia; Mortara, Renato A.; Yoshida, Nobuko; Alves, Maria Julia M.; Rabinovitch, Michel

2007-01-01

109

Proresolution Lipid Mediators in Multiple Sclerosis -- Differential, Disease Severity-Dependent Synthesis -- A Clinical Pilot Trial  

PubMed Central

Background The severity and longevity of inflammation is controlled by endogenous counter-regulatory signals. Among them are long-chain polyunsaturated fatty acid (PUFA)-derived lipid mediators, which promote the resolution of inflammation, an active process for returning to tissue homeostasis. Objective To determine whether endogenous production of lipid-derived resolution agonists is regulated differentially in patients with highly active and less active multiple sclerosis (MS). Design Matched-pairs study in University hospital Neurology department. Patients Based on clinical (relapse frequency) and paraclinical (MRI lesions, contrast enhancement) criteria, 10 pairs of age- and sex-matched patients with relapsing-remitting MS were assigned either to a group with highly active or less active MS. Lipid mediators were quantified in serum and cerebrospinal fluid using LC-MS/MS-based lipidomics. Results Levels of the key arachidonic (?-6) and docosahexaenoic acid (?-6)-derived mediators prostaglandins (PG), leukotrienes, hydroxyeicosatetraenoic acids (HETE) and resolution agonists lipoxin A4 (LXA4), resolvin D1 (RvD1) and neuroprotectin D1 (NPD1) were quantified. In the patient group with highly active MS, 15-HETE and PGE2 were increased, which are products of the 15-lipoxygenase and cyclooxygenase pathways. The proresolution mediator RvD1 was significantly upregulated and NPD1 was detected in the highly active group only. LXA4 levels were not increased in patients with highly active MS. Conclusions Lipid mediator pathways are regulated differentially in the cerebrospinal fluid of MS patients, depending on disease severity. Non-exhaustive or possibly ‘delayed’ resolution pathways may suggest a defective resolution program in patients with highly active MS. Longitudinal analyses are required to hetero-typify this differential resolution capacity, which may be associated with disease progression, longevity and eventual termination.

Brommer, Benedikt; Wengert, Oliver; Gronert, Karsten; Schwab, Jan M.

2013-01-01

110

Differential Regulation of Action Potentials by Inactivating and Noninactivating BK Channels in Rat Adrenal Chromaffin Cells  

PubMed Central

Abstract Large-conductance Ca2+-activated K+ (BK) channels can regulate cellular excitability in complex ways because they are able to respond independently to two distinct cellular signals, cytosolic Ca2+ and membrane potential. In rat chromaffin cells (RCC), inactivating BKi and noninactivating (BKs) channels differentially contribute to RCC action potential (AP) firing behavior. However, the basis for these differential effects has not been fully established. Here, we have simulated RCC action potential behavior, using Markovian models of BKi and BKs current and other RCC currents. The analysis shows that BK current influences both fast hyperpolarization and afterhyperpolarization of single APs and that, consistent with experimental observations, BKi current facilitates repetitive firing of APs, whereas BKs current does not. However, the key functional difference between BKi and BKs current that accounts for the differential firing is not inactivation but the more negatively shifted activation range for BKi current at a given [Ca2+].

Sun, Liang; Xiong, Yu; Zeng, Xuhui; Wu, Ying; Pan, Na; Lingle, Christopher J.; Qu, Anlian; Ding, Jiuping

2009-01-01

111

Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential  

PubMed Central

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions. Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS). Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures. Conclusions. In our experimental conditions, severe hypoxia affects the in vitro differentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.

Cicione, Claudia; Muinos-Lopez, Emma; Hermida-Gomez, Tamara; Fuentes-Boquete, Isaac; Diaz-Prado, Silvia; Blanco, Francisco J.

2013-01-01

112

Ultrafast differential transmission spectroscopy of excitonic transitions in InGaN\\/GaN multiple quantum wells  

Microsoft Academic Search

Room-temperature carrier dynamics in InGaN\\/GaN multiple quantum wells are studied by employing ultrafast pump–probe spectroscopy. Specifically, the observed differential spectral signatures are characteristic of changes in the absorption coefficient through both a reduction of the quantum-confined Stark shift due to the photoinduced in-well field screening (low carrier densities) and excitonic absorption quenching (high carrier densities). The comparison of the differential

Fei Chen; M. C. Cheung; Paul M. Sweeney; W. D. Kirkey; M. Furis; A. N. Cartwright

2003-01-01

113

Ultrafast differential transmission spectroscopy of excitonic transitions in InGaN\\/GaN multiple quantum wells  

Microsoft Academic Search

Room-temperature carrier dynamics in InGaN\\/GaN multiple quantum wells are studied by employing ultrafast pump-probe spectroscopy. Specifically, the observed differential spectral signatures are characteristic of changes in the absorption coefficient through both a reduction of the quantum-confined Stark shift due to the photoinduced in-well field screening (low carrier densities) and excitonic absorption quenching (high carrier densities). The comparison of the differential

Fei Chen; M. C. Cheung; Paul M. Sweeney; W. D. Kirkey; M. Furis; A. N. Cartwright

2003-01-01

114

Clonal analysis of the differentiation potential of human adipose-derived adult stem cells.  

PubMed

Pools of human adipose-derived adult stem (hADAS) cells can exhibit multiple differentiated phenotypes under appropriate in vitro culture conditions. Because adipose tissue is abundant and easily accessible, hADAS cells offer a promising source of cells for tissue engineering and other cell-based therapies. However, it is unclear whether individual hADAS cells can give rise to multiple differentiated phenotypes or whether each phenotype arises from a subset of committed progenitor cells that exists within a heterogeneous population. The goal of this study was to test the hypothesis that single hADAS are multipotent at a clonal level. hADAS cells were isolated from liposuction waste, and ring cloning was performed to select cells derived from a single progenitor cell. Forty-five clones were expanded through four passages and then induced for adipogenesis, osteogenesis, chondrogenesis, and neurogenesis using lineage-specific differentiation media. Quantitative differentiation criteria for each lineage were determined using histological and biochemical analyses. Eighty one percent of the hADAS cell clones differentiated into at least one of the lineages. In addition, 52% of the hADAS cell clones differentiated into two or more of the lineages. More clones expressed phenotypes of osteoblasts (48%), chondrocytes (43%), and neuron-like cells (52%) than of adipocytes (12%), possibly due to the loss of adipogenic ability after repeated subcultures. The findings are consistent with the hypothesis that hADAS cells are a type of multipotent adult stem cell and not solely a mixed population of unipotent progenitor cells. However, it is important to exercise caution in interpreting these results until they are validated using functional in vivo assays. PMID:16021633

Guilak, Farshid; Lott, Kristen E; Awad, Hani A; Cao, Qiongfang; Hicok, Kevin C; Fermor, Beverley; Gimble, Jeffrey M

2006-01-01

115

Morphology-Based Prediction of Osteogenic Differentiation Potential of Human Mesenchymal Stem Cells  

PubMed Central

Human bone marrow mesenchymal stem cells (hBMSCs) are widely used cell source for clinical bone regeneration. Achieving the greatest therapeutic effect is dependent on the osteogenic differentiation potential of the stem cells to be implanted. However, there are still no practical methods to characterize such potential non-invasively or previously. Monitoring cellular morphology is a practical and non-invasive approach for evaluating osteogenic potential. Unfortunately, such image-based approaches had been historically qualitative and requiring experienced interpretation. By combining the non-invasive attributes of microscopy with the latest technology allowing higher throughput and quantitative imaging metrics, we studied the applicability of morphometric features to quantitatively predict cellular osteogenic potential. We applied computational machine learning, combining cell morphology features with their corresponding biochemical osteogenic assay results, to develop prediction model of osteogenic differentiation. Using a dataset of 9,990 images automatically acquired by BioStation CT during osteogenic differentiation culture of hBMSCs, 666 morphometric features were extracted as parameters. Two commonly used osteogenic markers, alkaline phosphatase (ALP) activity and calcium deposition were measured experimentally, and used as the true biological differentiation status to validate the prediction accuracy. Using time-course morphological features throughout differentiation culture, the prediction results highly correlated with the experimentally defined differentiation marker values (R>0.89 for both marker predictions). The clinical applicability of our morphology-based prediction was further examined with two scenarios: one using only historical cell images and the other using both historical images together with the patient's own cell images to predict a new patient's cellular potential. The prediction accuracy was found to be greatly enhanced by incorporation of patients' own cell features in the modeling, indicating the practical strategy for clinical usage. Consequently, our results provide strong evidence for the feasibility of using a quantitative time series of phase-contrast cellular morphology for non-invasive cell quality prediction in regenerative medicine.

Agata, Hideki; Kagami, Hideaki; Shiono, Hirofumi; Kiyota, Yasujiro; Honda, Hiroyuki; Kato, Ryuji

2013-01-01

116

Morphology-based prediction of osteogenic differentiation potential of human mesenchymal stem cells.  

PubMed

Human bone marrow mesenchymal stem cells (hBMSCs) are widely used cell source for clinical bone regeneration. Achieving the greatest therapeutic effect is dependent on the osteogenic differentiation potential of the stem cells to be implanted. However, there are still no practical methods to characterize such potential non-invasively or previously. Monitoring cellular morphology is a practical and non-invasive approach for evaluating osteogenic potential. Unfortunately, such image-based approaches had been historically qualitative and requiring experienced interpretation. By combining the non-invasive attributes of microscopy with the latest technology allowing higher throughput and quantitative imaging metrics, we studied the applicability of morphometric features to quantitatively predict cellular osteogenic potential. We applied computational machine learning, combining cell morphology features with their corresponding biochemical osteogenic assay results, to develop prediction model of osteogenic differentiation. Using a dataset of 9,990 images automatically acquired by BioStation CT during osteogenic differentiation culture of hBMSCs, 666 morphometric features were extracted as parameters. Two commonly used osteogenic markers, alkaline phosphatase (ALP) activity and calcium deposition were measured experimentally, and used as the true biological differentiation status to validate the prediction accuracy. Using time-course morphological features throughout differentiation culture, the prediction results highly correlated with the experimentally defined differentiation marker values (R>0.89 for both marker predictions). The clinical applicability of our morphology-based prediction was further examined with two scenarios: one using only historical cell images and the other using both historical images together with the patient's own cell images to predict a new patient's cellular potential. The prediction accuracy was found to be greatly enhanced by incorporation of patients' own cell features in the modeling, indicating the practical strategy for clinical usage. Consequently, our results provide strong evidence for the feasibility of using a quantitative time series of phase-contrast cellular morphology for non-invasive cell quality prediction in regenerative medicine. PMID:23437049

Matsuoka, Fumiko; Takeuchi, Ichiro; Agata, Hideki; Kagami, Hideaki; Shiono, Hirofumi; Kiyota, Yasujiro; Honda, Hiroyuki; Kato, Ryuji

2013-02-21

117

Exploring the enkephalinergic differentiation potential in adult stem cells for cell therapy and drug screening implications.  

PubMed

Stem cell therapy is one of the most promising treatments in neuroregenerative medicine. Considering the role of the endogenous opioid system in controlling the pathophysiology of neurological disorders and behavioral aberrations, current studies have focused on enkephalins as a part of the opioid system. Due to high capability of unrestricted somatic stem cells (USSCs) and human mesenchymal stem cells (hMSCs) for cell therapy and transplantation; here, we examined their enkephalinergic differentiation potential through Ikaros-related pathways in order to develop in vitro models to help drug screening and stem cell therapy for the opioid-related disorders. The authenticity of the stem cells was verified by differentiation experiments along with flow cytometry for surface markers. Later, we confirmed their neurogenic differentiation with semiquantitative and quantitative transcriptional and translational evaluations of the enkephalinergic-related genes such as proenkephalin, CREBZF, Ikaros, and prodynorphin. Our findings supported the enkephalinergic differentiation of these stem cells. Noteworthy, USSCs showed higher potential for differentiating into enkephalinergic neurons under Ikaros activation than hMSCs, which makes them appropriate for neurological therapeutic applications. In conclusion, this study suggests a powerful in vitro model for neurogenesis that may help clarification of enkephalinergic differentiation and related signaling networks along with neural drug screening. Such investigations may be beneficial to ameliorate the neural-related therapeutic approaches. PMID:23054438

Hafizi, Maryam; Bakhshandeh, Behnaz; Soleimani, Masoud; Atashi, Amir

2012-10-06

118

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

PubMed

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

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

2012-06-07

119

Human Embryonic Stem Cells Develop Into Multiple Types of Cardiac Myocytes Action Potential Characterization  

Microsoft Academic Search

Human embryonic stem (hES) cells can differentiate in vitro, forming embryoid bodies (EBs) composed of derivatives of all three embryonic germ layers. Spontaneously contracting outgrowths from these EBs contain cardiomyocytes (CMs); however, the types of human CMs and their functional properties are unknown. This study characterizes the contractions and action potentials (APs) from beating EB outgrowths cultured for 40 to

Jia-Qiang He; Yue Ma; Youngsook Lee; James A. Thomson; Timothy J. Kamp

120

Clonal population of adult stem cells: life span and differentiation potential.  

PubMed

Adult stem cells derived from bone marrow, connective tissue, and solid organs can exhibit a range of differentiation potentials. Some controversy exists regarding the classification of mesenchymal stem cells as bona fide stem cells, which is in part derived from the limited ability to propagate true clonal populations of precursor cells. We isolated putative mesenchymal stem cells from the connective tissue of an adult rat (rMSC), and generated clonal populations via three rounds of dilutional cloning. The replicative potential of the clonal rMSC line far exceeded Hayflick's limit of 50-70 population doublings. The high capacity for self-renewal in vitro correlated with telomerase activity, as demonstrated by telomerase repeat amplification protocol (TRAP) assay. Exposure to nonspecific differentiation culture medium revealed multilineage differentiation potential of rMSC clones. Immunostaining confirmed the appearance of mesodermal phenotypes, including adipocytes possessing lipid-rich vacuoles, chondrocytes depositing pericellular type II collagen, and skeletal myoblasts expressing MyoD1. Importantly, the spectrum of differentiation capability was sustained through repeated passaging. Furthermore, serum-free conditions that led to high-efficiency smooth muscle differentiation were identified. rMSCs plated on collagen IV-coated surfaces and exposed to transforming growth factor-beta1 (TGF-beta1) differentiated into a homogeneous population expressing alpha-actin and calponin. Hence, clonogenic analysis confirmed the presence of a putative MSC population derived from the connective tissue of rat skeletal muscle. The ability to differentiate into a smooth muscle cell (SMC) phenotype, combined with a high proliferative capacity, make such a connective tissue-derived MSC population ideal for applications in vascular tissue construction. PMID:15129755

Seruya, Mitchel; Shah, Anup; Pedrotty, Dawn; du Laney, Tracey; Melgiri, Ryan; McKee, J Andrew; Young, Henry E; Niklason, Laura E

2004-01-01

121

Lamin A/C Haploinsufficiency Modulates the Differentiation Potential of Mouse Embryonic Stem Cells  

PubMed Central

Background Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a spectrum of genetic diseases that affect specific tissues. Most available mouse models for laminopathies recapitulate disease symptoms for muscle diseases and progerias. However, loss of human lamin A/C also has highly deleterious effects on fetal development. Hence it is important to understand the impact of lamin A/C expression levels on embryonic differentiation pathways. Methodology and Principal Findings We have investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. We initially carried out a targeted disruption of one allele of the mouse lamin A/C gene (Lmna). Undifferentiated wild-type and Lmna+/? embryonic stem cells showed similar expression of pluripotency markers and cell cycle profiles. Upon spontaneous differentiation into embryoid bodies, markers for visceral endoderm such as ?-fetoprotein were highly upregulated in haploinsufficient cells. However, neuronal markers such as ?-III tubulin and nestin were downregulated. Furthermore, we observed a reduction in the commitment of Lmna+/? cells into the myogenic lineage, but no discernible effects on cardiac, adipocyte or osteocyte lineages. In the next series of experiments, we derived embryonic stem cell clones expressing lamin A/C short hairpin RNA and examined their differentiation potential. These cells expressed pluripotency markers and, upon differentiation, the expression of lineage-specific markers was altered as observed with Lmna+/? embryonic stem cells. Conclusions We have observed significant effects on embryonic stem cell differentiation to visceral endoderm, neuronal and myogenic lineages upon depletion of lamin A/C. Hence our results implicate lamin A/C level as an important determinant of lineage-specific differentiation during embryonic development.

Sehgal, Poonam; Chaturvedi, Pankaj; Kumaran, R. Ileng; Kumar, Satish; Parnaik, Veena K.

2013-01-01

122

Clone-Forming Ability and Differentiation Potential of Migratory Neural Crest Cells  

Microsoft Academic Search

The neural crest of vertebrate embryos gives rise to a variety of differentiated cell types, including neuronal and non-neuronal cells of peripheral ganglia (sensory and autonomic), pigment cells, and mesectodermal derivatives. Neural crest cells were taken from quall embryos at the level encompassing mesencephalon and metencephalon and the developmental potentials were evaluated by culturing them as single cells on 3T3

Anne Baroffio; Elisabeth Dupin; Nicole M. Le Douarin

1988-01-01

123

DIFFERENTIAL EMISSION MEASURE ANALYSIS OF MULTIPLE STRUCTURAL COMPONENTS OF CORONAL MASS EJECTIONS IN THE INNER CORONA  

SciTech Connect

In this paper, we study the temperature and density properties of multiple structural components of coronal mass ejections (CMEs) using differential emission measure (DEM) analysis. The DEM analysis is based on the six-passband EUV observations of solar corona from the Atmospheric Imaging Assembly on board the Solar Dynamic Observatory. The structural components studied include the hot channel in the core region (presumably the magnetic flux rope of the CME), the bright loop-like leading front (LF), and coronal dimming in the wake of the CME. We find that the presumed flux rope has the highest average temperature (>8 MK) and density ({approx}1.0 Multiplication-Sign 10{sup 9} cm{sup -3}), resulting in an enhanced emission measure over a broad temperature range (3 {<=} T(MK) {<=} 20). On the other hand, the CME LF has a relatively cool temperature ({approx}2 MK) and a narrow temperature distribution similar to the pre-eruption coronal temperature (1 {<=} T(MK) {<=} 3). The density in the LF, however, is increased by 2%-32% compared with that of the pre-eruption corona, depending on the event and location. In coronal dimmings, the temperature is more broadly distributed (1 {<=} T(MK) {<=} 4), but the density decreases by {approx}35%-{approx}40%. These observational results show that: (1) CME core regions are significantly heated, presumably through magnetic reconnection; (2) CME LFs are a consequence of compression of ambient plasma caused by the expansion of the CME core region; and (3) the dimmings are largely caused by the plasma rarefaction associated with the eruption.

Cheng, X.; Ding, M. D. [School of Astronomy and Space Science, Nanjing University, Nanjing 210093 (China); Zhang, J. [School of Physics, Astronomy and Computational Sciences, George Mason University, Fairfax, VA 22030 (United States); Saar, S. H., E-mail: xincheng@nju.edu.cn, E-mail: jzhang7@gmu.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

2012-12-10

124

HMG-CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis  

Microsoft Academic Search

Impaired remyelination due to degener- ation of both postmitotic oligodendrocytes and oligo- dendrocyte progenitors (OPs) is the major hallmark of inflammatory demyelination in multiple sclerosis (MS) lesions and experimental autoimmune encephalomy- elitis (EAE). Here, we have demonstrated the poten- tial of lovastatin, a HMG-CoA reductase inhibitor, for the restoration of impaired remyelination mediated through enhanced survival and differentiation of OPs

Ajaib S. Paintlia; Manjeet K. Paintlia; Mushfiquddin Khan; Timothy Vollmer; Avtar K. Singh; Inderjit Singh

2005-01-01

125

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

ERIC Educational Resources Information Center

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

Palardy, Gregory J.

2008-01-01

126

Transcriptome analysis of differentiating trypanosomes reveals the existence of multiple post-transcriptional regulons  

PubMed Central

Background Trypanosome gene expression is regulated almost exclusively at the post-transcriptional level, with mRNA degradation playing a decisive role. When trypanosomes are transferred from the blood of a mammal to the midgut of a Tsetse fly, they transform to procyclic forms: gene expression is reprogrammed, changing the cell surface and switching the mode of energy metabolism. Within the blood, trypanosomes can pre-adapt for Tsetse transmission, becoming growth-arrested stumpy forms. We describe here the transitions in gene expression that occur during differentiation of in-vitro cultured bloodstream forms to procyclic forms. Results Some mRNAs showed changes within 30 min of cis-aconitate addition, whereas others responded 12-24 hours later. For the first 12 h after addition of cis-aconitate, cells accumulated at the G1 phase of the cell cycle, and showed decreases in mRNAs required for proliferation, mimicking the changes seen in stumpy forms: many mRNAs needed for ribosomal and flagellar biogenesis showed striking co-regulation. Other mRNAs encoding components of signal transduction pathways and potential regulators were specifically induced only during differentiation. Messenger RNAs encoding proteins required for individual metabolic pathways were often co-regulated. Conclusion Trypanosome genes form post-transcriptional regulons in which mRNAs with functions in particular pathways, or encoding components of protein complexes, show almost identical patterns of regulation.

Queiroz, Rafael; Benz, Corinna; Fellenberg, Kurt; Hoheisel, Jorg D; Clayton, Christine

2009-01-01

127

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

2013-10-09

128

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.

Bader, Joel S.; Friedmann, Theodore

2013-01-01

129

UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells  

PubMed Central

It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O2 at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F1F0 ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential.

Zhang, Jin; Khvorostov, Ivan; Hong, Jason S; Oktay, Yavuz; Vergnes, Laurent; Nuebel, Esther; Wahjudi, Paulin N; Setoguchi, Kiyoko; Wang, Geng; Do, Anna; Jung, Hea-Jin; McCaffery, J Michael; Kurland, Irwin J; Reue, Karen; Lee, Wai-Nang P; Koehler, Carla M; Teitell, Michael A

2011-01-01

130

Withania somnifera water extract as a potential candidate for differentiation based therapy of human neuroblastomas.  

PubMed

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

2013-01-31

131

Differentially regulated GPVI ectodomain shedding by multiple platelet-expressed proteinases.  

PubMed

Glycoprotein VI (GPVI) mediates platelet activation on exposed subendothelial collagens at sites of vascular injury and thereby contributes to normal hemostasis, but also to the occlusion of diseased vessels in the setting of myocardial infarction or stroke. GPVI is an attractive target for antithrombotic therapy, particularly because previous studies have shown that anti-GPVI antibodies induce irreversible down-regulation of the receptor in circulating platelets by internalization and/or ectodomain shedding. Metalloproteinases of the a disintegrin and metalloproteinase (ADAM) family have been proposed to mediate this ectodomain shedding, but direct evidence for this is lacking. Here, we studied GPVI shedding in vitro and in vivo in newly generated mice with a megakaryocyte-specific ADAM10 deficiency and in Adam17(ex/ex) mice, which lack functional ADAM17. We demonstrate that GPVI cleavage in vitro can occur independently through either ADAM10 or ADAM17 in response to distinct stimuli. In contrast, antibody (JAQ1)-induced GPVI shedding in vivo occurred in mice lacking both ADAM10/ADAM17 in their platelets, suggesting the existence of a third GPVI cleaving platelet enzyme. This was supported by in vitro studies on ADAM10/ADAM17 double-deficient platelets. These results reveal that ectodomain shedding of GPVI can be mediated through multiple differentially regulated platelet-expressed proteinases with obvious therapeutic implications. PMID:20644114

Bender, Markus; Hofmann, Sebastian; Stegner, David; Chalaris, Athena; Bösl, Michael; Braun, Attila; Scheller, Jürgen; Rose-John, Stefan; Nieswandt, Bernhard

2010-07-19

132

Multiple functions of Ldb1 required for ?-globin activation during erythroid differentiation  

PubMed Central

Ldb1 and erythroid partners SCL, GATA-1, and LMO2 form a complex that is required to establish spatial proximity between the ?-globin locus control region and gene and for transcription activation during erythroid differentiation. Here we show that Ldb1 controls gene expression at multiple levels. Ldb1 stabilizes its erythroid complex partners on ?-globin chromatin, even though it is not one of the DNA-binding components. In addition, Ldb1 is necessary for enrichment of key transcriptional components in the locus, including P-TEFb, which phosphorylates Ser2 of the RNA polymerase C-terminal domain for efficient elongation. Furthermore, reduction of Ldb1 results in the inability of the locus to migrate away from the nuclear periphery, which is necessary to achieve robust transcription of ?-globin in nuclear transcription factories. Ldb1 contributes these critical functions at both embryonic and adult stages of globin gene expression. These results implicate Ldb1 as a factor that facilitates nuclear relocation for transcription activation.

Song, Sang-Hyun; Kim, AeRi; Ragoczy, Tobias; Bender, M. A.; Groudine, Mark

2010-01-01

133

Differential sensitivity of oligodendrocytes and motor neurons to reactive nitrogen species: implications for Multiple Sclerosis  

PubMed Central

Depending on its concentration, nitric oxide (NO) has beneficial or toxic effects. In pathological conditions, NO reacts with superoxide to form peroxynitrite, which nitrates proteins forming nitrotyrosine residues (3NY), leading to loss of protein function, perturbation of signal transduction, and cell death. 3NY immunoreactivity is present in many CNS diseases, particularly Multiple Sclerosis (MS). Here, using the high flux NO donor, spermine NONOate, we report that oligodendrocytes are resistant to NO, while motor neurons are NO sensitive. Motor neuron sensitivity correlates with the NO-dependent formation of 3NY, which is significantly more pronounced in motor neurons as compared to oligodendrocytes, suggesting peroxynitrite as the toxic molecule. The heme-metabolizing enzyme, heme-oxygenase-1 (HO-1), is necessary for oligodendrocyte NO resistance, as demonstrated by loss of resistance after HO1 inhibition. Resistance is reinstated by peroxynitrite scavenging with uric acid further implicating peroxynitrite as responsible for NO sensitivity. Most importantly, differential sensitivity to NO is also present in cultures of primary oligodendrocytes and motor neurons. Finally, motor neurons cocultured with oligodendrocytes, or oligodendrocyte-conditioned media, become resistant to NO toxicity. PRELIMINARY STUDIES SUGGEST OLIGODENDROCYTES RELEASE A SOLUBLE FACTOR THAT PROTECTS MOTOR NEURONS. Our findings challenge the current paradigm that oligodendrocytes are the exclusive target of MS pathology.

Bishop, Amy; Green Hobbs, Kimberly; Eguchi, Asuka; Jeffrey, Stephanie; Smallwood, Lorraine; Pennie, Cedona; Anderson, James; Estevez, Alvaro G.

2009-01-01

134

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

SciTech Connect

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

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

2012-08-15

135

Multiple potential barriers as a possible mechanism to increase the Seebeck coefficient and electrical power factor  

Microsoft Academic Search

In this paper, a possible mechanism to increase the Seebeck coefficient of semiconductors is proposed. Multiple potential barriers are used to reduce the mean-free-path of carriers at the cold end without significantly affecting those at the hot end. This results in an increase in the Seebeck coefficient. Theoretical calculation based upon a simplified model indicates that an increase in the

D. M. Rowe; Gao Min

1994-01-01

136

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

137

Multiple Sclerosis disease distribution and potential impact of environmental air pollutants in Georgia  

Microsoft Academic Search

Multiple Sclerosis (MS) is one of the most common diseases of the central nervous system. Although the disease has been associated with some genetic and environmental factors, it has neither clear causes nor clear temporality with respect to exposure. The purpose of this study was to explore potential relationships between MS and outdoor air pollutants in GA.This study used cross-sectional

Anthony Charles Gregory; Derek G. Shendell; Ike S. Okosun; Karen E. Gieseker

2008-01-01

138

Effect of body temperature on visual evoked potential delay and visual perception in multiple sclerosis  

Microsoft Academic Search

Seven multiple sclerosis patients were cooled and four heated, but evoked potential delay changed in only five out 11 experiments. Control limits were set by cooling eight and heating four control subjects. One patient gave anomalous results in that although heating degraded perceptual delay and visual acuity, and depressed the sine wave grating MTF, double-flash resolution was improved. An explanation

D Regan; T J Murray; R Silver

1977-01-01

139

Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells.  

PubMed

Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment. Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (-/-) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (-/-) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (-/-) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages. Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy. PMID:21048850

Capo-Chichi, Callinice D; Smedberg, Jennifer L; Rula, Malgorzata; Nicolas, Emmanuelle; Yeung, Anthony T; Adamo, Richard F; Frolov, Andrey; Godwin, Andrew K; Xu, Xiang-Xi

2010-05-11

140

Mesoderm-derived stem cells: the link between the transcriptome and their differentiation potential.  

PubMed

Human adult stem cells (hASCs) have become an attractive source for autologous cell transplantation, tissue engineering, developmental biology, and the generation of human-based alternative in vitro models. Among the 3 germ cell layers, the mesoderm is the origin of today's most widely used and characterized hASC populations. A variety of isolated nonhematopoietic mesoderm-derived stem cell populations exist, and all of them show important differences in terms of function, efficacy, and differentiation potential both in vivo and in vitro. To better understand whether the intrinsic properties of these cells contribute to the overall differentiation potential of hASCs, we compared the global gene expression profiles of 4 mesoderm-derived stem cell populations: human adipose tissue-derived stromal cells, human bone marrow-derived stromal cells (hBMSCs), human (fore)skin-derived precursor cells (hSKPs), and human Wharton's jelly-derived mesenchymal stem cells (hWJs). Significant differences in gene expression profiles were detected between distinct stem cell types. hSKPs predominantly expressed genes involved in neurogenesis, skin, and bone development, whereas hWJs and, to some extent, hBMSCs showed an increased expression of genes involved in cardiovascular and liver development. Interestingly, the observed differential gene expression of distinct hASCs could be linked to existing differentiation data in which hASCs were differentiated toward specific cell types. As such, our data suggest that the intrinsic gene expression of the undifferentiated stem cells has an important impact on their overall differentiation potential as well as their application in stem cell-based research. Yet, the factors that define these intrinsic properties remain to be determined. PMID:22651824

De Kock, Joery; Najar, Mehdi; Bolleyn, Jennifer; Al Battah, Feras; Rodrigues, Robim M; Buyl, Karolien; Raicevic, Gordana; Govaere, Olivier; Branson, Steven; Meganathan, Kesavan; Gaspar, John Antonydas; Roskams, Tania; Sachinidis, Agapios; Lagneaux, Laurence; Vanhaecke, Tamara; Rogiers, Vera

2012-07-11

141

Gene Expression Profiling Reveals New Potential Players of Gonad Differentiation in the Chicken Embryo  

PubMed Central

Background In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s) involved in gonad differentiation is still incomplete. Methodology/Principal Findings With the aim of improving characterization of the molecular pathway(s) involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein) and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor ? family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. Conclusion/Significance This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors of chicken gonad differentiation and provides evidence of the preferential expression of BMPs in the developing ovary and Inhibin/Activin subunits in the developing testis.

Carre, Gwenn-Ael; Couty, Isabelle; Hennequet-Antier, Christelle; Govoroun, Marina S.

2011-01-01

142

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

PubMed

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

Oztürk, Serefnur

2010-02-19

143

Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential  

PubMed Central

Isolation of hepatic progenitor cells is a promising approach for cell replacement therapy of chronic liver disease. The winged helix transcription factor Foxl1 is a marker for progenitor cells and their descendants in the mouse liver in vivo. Here, we purify progenitor cells from Foxl1-Cre; RosaYFP mice and evaluate their proliferative and differentiation potential in vitro. Treatment of Foxl1-Cre; RosaYFP mice with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet led to an increase of the percentage of YFP-labeled Foxl1+ cells. Clonogenic assays demonstrated that up to 3.6% of Foxl1+ cells had proliferative potential. Foxl1+ cells differentiated into cholangiocytes and hepatocytes in vitro, depending on the culture condition employed. Microarray analyses indicated that Foxl1+ cells express stem cell markers such as Prom1 as well as differentiation markers such as Ck19 and Hnf4a. Thus, the Foxl1-Cre; RosaYFP model allows for easy isolation of adult hepatic progenitor cells that can be expanded and differentiated in culture.

Shin, Soona; Walton, Gabriel; Aoki, Reina; Brondell, Karrie; Schug, Jonathan; Fox, Alan; Smirnova, Olga; Dorrell, Craig; Erker, Laura; Chu, Andrew S.; Wells, Rebecca G.; Grompe, Markus; Greenbaum, Linda E.; Kaestner, Klaus H.

2011-01-01

144

Derivation of Putative Porcine Embryonic Germ Cells and Analysis of Their Multi-lineage Differentiation Potential.  

PubMed

Embryonic germ (EG) cells are cultured pluripotent stem cells derived from the primordial germ cells (PGCs) that migrate from the dorsal mesentery of the hindgut to the developing genital ridge. In this study, the morphology of the porcine genital ridge was assessed in embryos harvested on days 22-30 of pregnancy. PGCs from embryos at these stages were cultured to obtain porcine EG cell lines, and EG-like cells were derived from PGCs from embryos harvested on days 24-28 of pregnancy. The EG-like cells expressed Oct4, Sox2, Nanog, SSEA-3, SSEA-4 and alkaline phosphatase (AP). These cells were able to form embryoid bodies (EBs) in suspension culture and differentiate into cells representative of the three germ layers as verified by a-fetoprotein (AFP), ?-smooth muscle actin (?-SMA), and Nestin expression. Spontaneous differentiation from the porcine EG-like cells of delayed passage in vitro showed that they could differentiate into epithelial-like cells, mesenchymal-like cells and neuron-like cells. In vitro directed differentiation generated osteocytes, adipocytes and a variety of neural lineage cells, as demonstrated by alizarin red staining, oil red O staining, and immunofluorescence for neuronal class ? ?-tubulin (Tuj1), glial fibrillary protein (GFAP) and galactosylceramidase (GALC), respectively. These results indicate that porcine EG-like cells have the potential for multi-lineage differentiation and are useful for basic porcine stem cell research. PMID:24053947

Cong, Yimei; Ma, Jing; Sun, Ruizhen; Wang, Jianyu; Xue, Binghua; Wang, Jiaqiang; Xie, Bingteng; Wang, Juan; Hu, Kui; Liu, Zhonghua

2013-06-22

145

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

146

Differential Emission Measure Analysis of Multiple Structural Components of Coronal Mass Ejections in the Inner Corona  

NASA Astrophysics Data System (ADS)

In this paper, we study the temperature and density properties of multiple structural components of coronal mass ejections (CMEs) using differential emission measure (DEM) analysis. The DEM analysis is based on the six-passband EUV observations of solar corona from the Atmospheric Imaging Assembly on board the Solar Dynamic Observatory. The structural components studied include the hot channel in the core region (presumably the magnetic flux rope of the CME), the bright loop-like leading front (LF), and coronal dimming in the wake of the CME. We find that the presumed flux rope has the highest average temperature (>8 MK) and density (~1.0 × 109 cm-3), resulting in an enhanced emission measure over a broad temperature range (3 <= T(MK) <= 20). On the other hand, the CME LF has a relatively cool temperature (~2 MK) and a narrow temperature distribution similar to the pre-eruption coronal temperature (1 <= T(MK) <= 3). The density in the LF, however, is increased by 2%-32% compared with that of the pre-eruption corona, depending on the event and location. In coronal dimmings, the temperature is more broadly distributed (1 <= T(MK) <= 4), but the density decreases by ~35%-~40%. These observational results show that: (1) CME core regions are significantly heated, presumably through magnetic reconnection; (2) CME LFs are a consequence of compression of ambient plasma caused by the expansion of the CME core region; and (3) the dimmings are largely caused by the plasma rarefaction associated with the eruption.

Cheng, X.; Zhang, J.; Saar, S. H.; Ding, M. D.

2012-12-01

147

Full potential multiple scattering calculations of transition metals K-edges  

NASA Astrophysics Data System (ADS)

Following our recent derivation of a Real Space Full-Potential Multiple-Scattering-Theory (RSFP-MST), we calculate the low-energy part of the K-edge absorption spectra of the transition metals of the first row of the periodic table using the Hedin-Lundqvist (HL) and the Dirac-Hara (DH) complex potentials, which are often used in the literature for this kind of calculations. In both cases the complex part is taken from the HL potential. Taking advantage of the fact that in the FP-MS scheme the Schrödinger Equation is solved exactly without approximations (within the limits of the l-truncation procedure in MST), we intend to test the ab initio validity of these optical potentials in cases that are borderline between the independent particle and the weakly correlated regime. Surprisingly enough, we find better agreement with experiments with the DH potential.

Hatada, Keisuke; Hayakawa, Kuniko; Chaboy, Jesús; Natoli, Calogero R.

2009-11-01

148

Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells  

Microsoft Academic Search

We compared bona fide human induced pluripotent stem cells (iPSCs) derived from umbilical cord blood (CB) cells and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSCs and K-iPSCs were distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture did not improve

Kitai Kim; Rui Zhao; Akiko Doi; Kitwa Ng; Juli Unternaehrer; Patrick Cahan; Huo Hongguang; Yuin-Han Loh; Martin J Aryee; M William Lensch; Hu Li; James J Collins; Andrew P Feinberg; George Q Daley

2011-01-01

149

Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells  

Microsoft Academic Search

BackgroundThe therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles.Methodology\\/Principal Findingsto address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and

Pablo Aranda; Xabier Agirre; Esteban Ballestar; Enrique J. Andreu; José Román-Gómez; Inés Prieto; José Ignacio Martín-Subero; Juan Cruz Cigudosa; Reiner Siebert; Manel Esteller; Felipe Prosper

2009-01-01

150

Multiple roles of class I HDACs in proliferation, differentiation, and development.  

PubMed

Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future. PMID:22286122

Reichert, Nina; Choukrallah, Mohamed-Amin; Matthias, Patrick

2012-07-01

151

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

152

The potential role of microRNAs in regulating gonadal sex differentiation in the chicken embryo.  

PubMed

Differential gene expression regulates tissue morphogenesis. The embryonic gonad is a good example, where the developmental decision to become an ovary or testis is governed by female- or male-specific gene expression. A number of genes have now been identified that control gonadal sex differentiation. However, the potential role of microRNAs (miRNAs) in ovarian and testicular pathways is unknown. In this review, we summarise our current understanding of gonadal differentiation and the possible involvement of miRNAs, using the chicken embryo as a model system. Chickens and other birds have a ZZ/ZW sex chromosome system, in which the female, ZW, is the heterogametic sex, and the male, ZZ, is homogametic (opposite to mammals). The Z-linked DMRT1 gene is thought to direct testis differentiation during embryonic life via a dosage-based mechanism. The conserved SOX9 gene is also likely to play a key role in testis formation. No master ovary determinant has yet been defined, but the autosomal FOXL2 and Aromatase genes are considered central. No miRNAs have been definitively shown to play a role in embryonic gonadal development in chickens or any other vertebrate species. Using next generation sequencing, we carried out an expression-based screen for miRNAs expressed in embryonic chicken gonads at the time of sexual differentiation. A number of miRNAs were identified, including several that showed sexually dimorphic expression. We validated a subset of miRNAs by qRT-PCR, and prediction algorithms were used to identify potential targets. We discuss the possible roles for these miRNAs in gonadal development and how these roles might be tested in the avian model. PMID:22161018

Cutting, Andrew D; Bannister, Stephanie C; Doran, Tim J; Sinclair, Andrew H; Tizard, Mark V L; Smith, Craig A

2012-01-01

153

Generation of multiple mRNA fingerprints using fluorescence-based differential display and an automated DNA sequencer.  

PubMed

Differential display is a method for the survey, analysis and comparison of gene expression in eukaryotic cells and tissues. Differential display involves isolation of high-quality nondegraded RNA, selective reverse transcription of polyadenylated mRNA using specific anchored oligopolydeoxythymidine [oligo(dT)] primers, and the subsequent PCR amplification of the cDNA with the same oligo(dT), an arbitrary upstream primer and radioisotopes for labeling the PCR products. The radioisotopically labeled products are then separated on a sequencing gel. In this report, we describe a rapid, specific, nonradioactive fluorescent differential display methodology in which fluorescently differentially labeled anchored oligo(dT) downstream primers are used in the reaction, with subsequent analysis of fluorescently labeled PCR products on an automated sequencer. Complete gene expression profiles, containing multiple mRNA fingerprints are possible by the simultaneous comparison of the multicolored banding patterns of the fluorescently differentially labeled products from several primer combinations. This modification of the differential display technique simplifies the assay and increases the throughput of high sample volumes required for comparative gene expression studies in various clinical applications. PMID:9067034

Jones, S W; Cai, D; Weislow, O S; Esmaeli-Azad, B

1997-03-01

154

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

Microsoft Academic Search

We used Motor Evoked Potentials (MEPs), elicited by transcranial magnetic stimulation, for assessing a motor pathways dysfunction\\u000a in a selected group of Multiple Sclerosis (MS) patients, without limitation in walking. We selected 32 Relapsing Remitting\\u000a MS patients, in remission phase, with EDSS ? 3.5 and 20 healthy individuals with similar height and age distribution. We measured\\u000a the following MEP parameters: motor thresholds;

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

2007-01-01

155

Brain volume analyses and somatosensory evoked potentials in multiple system atrophy  

Microsoft Academic Search

We investigated a progression of brain atrophy and somatosensory system dysfunction in multiple system atrophy (MSA). Subjects\\u000a were 21 MSA patients [12 MSA-C (cerebellar type) and 9 MSA-P (parkinsonism type)]. The relative volumes of cerebrum, brainstem\\u000a and cerebellum to the intracranial volume were obtained from three-dimensional computed tomography (3D-CT) of the brain. The\\u000a median nerve somatosensory evoked potentials (SEPs) were

Satoko Miyatake; Hitoshi Mochizuki; Tetsuji Naka; Yoshikazu Ugawa; Hajime Tanabe; Daisuke Kuzume; Mikiya Suzuki; Katsuhisa Ogata; Mitsuru Kawai

2010-01-01

156

Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis  

Microsoft Academic Search

To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from

Violaine K. Harris; Andrew Diamanduros; Pamela Good; Elina Zakin; Varun Chalivendra; Saud A. Sadiq

2010-01-01

157

Multiple-reflection effects in hadron-nucleus scattering (I). Cluster expansion of the optical potential  

Microsoft Academic Search

A basic assumption underlying the high-energy hadron-nucleus optical potential is that no target nucleon is struck more than once. Although this condition is satisfied at high energy, such is not the case in the vicinity of medium-energy resonances, where the amplitude for the projectile to undergo multiple reflections between two target nucleons is quite large. As a remedy for this

B. D. Keister

1976-01-01

158

Hot spots of wetland vegetation reduction in relation to human accessibility: differentiating human impacts on natural ecosystems at multiple scales  

Microsoft Academic Search

Human activities have profoundly influenced natural ecosystems, especially wetlands. This study attempted to differentiate\\u000a the impact of human activities on reductions in wetland vegetation in the Lixiahe wetlands, China, at multiple spatial scales.\\u000a The reduction in wetland vegetation from 1988 to 2006 was quantified using Landsat data, and moving window analysis was used\\u000a to detect hot spots of vegetation reduction

Sheng ShengChi; Chi Xu; Shaowei Zhang; Shuqing An; Maosong Liu; Xuejiao Yang

159

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

NASA Astrophysics Data System (ADS)

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.

Wilding, Nigel B.; Sollich, Peter

2013-01-01

160

The potential of mesenchymal stromal cells as a novel cellular therapy for multiple sclerosis  

PubMed Central

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS for which only partially effective therapies exist. Intense research defining the underlying immune pathophysiology is advancing both the understanding of MS as well as revealing potential targets for disease intervention. Mesenchymal stromal cell (MSC) therapy has the potential to modulate aberrant immune responses causing demyelination and axonal injury associated with MS, as well as to repair and restore damaged CNS tissue and cells. This article reviews the pathophysiology underlying MS, as well as providing a cutting-edge perspective into the field of MSC therapy based upon the experience of authors intrinsically involved in MS and MSC basic and translational science research.

Auletta, Jeffery J; Bartholomew, Amelia M; Maziarz, Richard T; Deans, Robert J; Miller, Robert H; Lazarus, Hillard M; Cohen, Jeffrey A

2012-01-01

161

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

Microsoft Academic Search

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

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

2006-01-01

162

Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential  

SciTech Connect

The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells.

Costa-Silva, Bruno [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Alvarez-Silva, Marcio [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Calloni, Giordano Wosgrau [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Ciencias Morfologicas, Instituto de Ciencias da Saude, Universidade Federal do Rio de Janeiro - Ilha do Fundao, 21949-590, Rio de Janeiro, R.J. (Brazil); Trentin, Andrea Goncalves [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil)], E-mail: atrentin@ccb.ufsc.br

2009-04-01

163

Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially  

PubMed Central

Eosinophils are innate immune leukocytes implicated in the initiation and maintenance of type 2 immune responses, including asthma and allergy. The ability to store and rapidly secrete preformed cytokines distinguishes eosinophils from most lymphocytes, which must synthesize cytokine proteins prior to secretion and may be a factor in the apparent Th2 bias of eosinophils. Multiple studies confirm that human eosinophils from atopic or hypereosinophilic donors can secrete over 30 cytokines with a varying and often opposing immune-polarizing potential. However, it remains unclear whether all of these cytokines are constitutively preformed and available for rapid secretion from eosinophils in the circulation of healthy individuals or are restricted to eosinophils from atopic donors. Likewise, the relative concentrations of cytokines stored within eosinophils have not been studied. Here, we demonstrate that human blood eosinophils are not singularly outfitted with Th2-associated cytokines but rather, constitutively store a cache of cytokines with nominal Th1, Th2, and regulatory capacities, including IL-4, IL-13, IL-6, IL-10, IL-12, IFN-?, and TNF-?. We demonstrate further rapid and differential release of each cytokine in response to specific stimuli. As agonists, strong Th1 and inflammatory cytokines elicited release of Th2-promoting IL-4 but not Th1-inducing IL-12. Moreover, a large quantity of IFN-? was secreted in response to Th1, Th2, and inflammatory stimuli. Delineations of the multifarious nature of preformed eosinophil cytokines and the varied stimulus-dependent profiles of rapid cytokine secretion provide insights into the functions of human eosinophils in mediating inflammation and initiation of specific immunity.

Spencer, Lisa A.; Szela, Craig T.; Perez, Sandra A. C.; Kirchhoffer, Casey L.; Neves, Josiane S.; Radke, Amy L.; Weller, Peter F.

2009-01-01

164

Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma.  

PubMed

Overexpression of growth differentiation factor 15 (GDF15) by bone marrow mesenchymal stem cells occurs widely in patients with multiple myeloma, but the pathophysiologic effects of GDF15 in this setting remain undefined. GDF15 has been described in numerous solid tumors but never in hematologic malignancies. In this study, we report that GDF15 significantly increases survival of stroma-dependent multiple myeloma cells including primary multiple myeloma cells. In particular, GDF15 conferred resistance to melphalan, bortezomib, and to a lesser extent, lenalidomide in both stroma-dependent and stroma-independent multiple myeloma cells. Akt-dependent signaling was critical to mediate the effects of GDF15, whereas Src and extracellular signal-regulated kinase 1/2 signaling pathways were not involved. Given these results, we tested the clinical significance of plasma concentrations of GDF15 (pGDF15) in 131 patients with multiple myeloma and found that it correlated with disease prognosis. Specifically, patients with high levels of pGDF15 had lower probabilities of event-free and overall survival 30 months after diagnosis than patients with low pGDF15 levels. Our findings suggest that tumor microenvironment-derived GDF15 is a key survival and chemoprotective factor for multiple myeloma cells, which is pathophysiologically linked to both initial parameters of the disease as well as patient survival. PMID:22301101

Corre, Jill; Labat, Elodie; Espagnolle, Nicolas; Hébraud, Benjamin; Avet-Loiseau, Hervé; Roussel, Murielle; Huynh, Anne; Gadelorge, Mélanie; Cordelier, Pierre; Klein, Bernard; Moreau, Philippe; Facon, Thierry; Fournié, Jean-Jacques; Attal, Michel; Bourin, Philippe

2012-02-02

165

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

PubMed

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

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

2012-10-23

166

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

167

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

PubMed

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. PMID:24055981

Salamon, Achim; Jonitz-Heincke, Anika; Adam, Stefanie; Rychly, Joachim; Müller-Hilke, Brigitte; Bader, Rainer; Lochner, Katrin; Peters, Kirsten

2013-09-19

168

Multiple Dirac points and perfect transmission in graphene with a dimerlike potential  

NASA Astrophysics Data System (ADS)

In this work, we investigate electronic band structures and transport properties in dimerlike graphene superlattices (DGSLs), where the modulated potentials of square barrier A and well B on graphene are arranged as S(m) = (AB)m(BA)m. Here m is the repeated number of units. It is found that the mirror symmetry of the potential distribution on graphene can induce extra Dirac points (DPs), which originates from the dimerlike positional correlations in the system. The induced DPs, which are exactly located at the energy corresponding to zero averaged wave number, do not exist in the periodic graphene superlattices of (AB)m. The number and the position of DPs in the zero averaged wave number gap of DGSL can be manipulated. Correspondingly, multiple perfect transmissions are observed at the resonant modes. Moreover, the conductance for DGSL presents extra resonant peaks accompanying with the emergence of the induced DPs. The investigations may have potential applications in graphene-based electronic devices.

Zhang, Rui-Li; Gao, Han-Tian; Zhou, Yu; Fan, Ren-Hao; Qi, Dong-Xiang; Peng, Ru-Wen; Huang, Run-Sheng; Wang, Mu

2013-09-01

169

Multiplicity.  

National Technical Information Service (NTIS)

In federal practice, the double jeopardy protection against multiple punishment for the same offense has been described as 'one of the least understood' and 'most frequently litigated' issues. In military practice, the protection operates under the nom-de...

T. L. Herrington

1991-01-01

170

PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis.  

PubMed

PC3TIS21/BTG2 is member of a novel family of antiproliferative genes (BTG1, ANA/BTG3, PC3B, TOB, and TOB2) that play a role in cellular differentiation. We have previously shown that PC3TIS21/BTG2 is induced by nerve growth factor (NGF) at the onset of neuronal differentiation in the neural crest-derived PC12 cell line, and is a marker for neuronal birth. We now observe that PC3TIS21/BTG2 ectopically expressed in PC12 cells synergises with NGF, similarly to the cyclin-dependent kinase inhibitor p21, potentiating the induction of the neuronal markers tyrosine hydroxylase and neurofilament 160 kDa. Furthermore, PC3TIS21/BTG2 protects from apoptosis elicited by NGF deprivation in terminally differentiated PC12 cultures. Such effects might be a consequence of the arrest of cell cycle exerted by PC3TIS21/BTG2, or expression of a sensitizing (neurogenic) property of the molecule. PMID:11930152

Corrente, Giuseppina; Guardavaccaro, Daniele; Tirone, Felice

2002-03-25

171

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

PubMed

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

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

2012-03-28

172

Hematopoietic Progenitors from Early Murine Fetal Liver Possess Hepatic Differentiation Potential  

PubMed Central

Bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes during liver development. It is believed that hepatoblasts originate from endodermal tissue. Here, we provide evidence for the presence of hepatic progenitor cells in the hematopoietic compartment at an early stage of liver development. Flow cytometric analysis showed that at early stages of liver development, approximately 13% of CD45+ cells express ?-like protein-1, a marker of hepatoblasts. Furthermore, reverse transcriptase-PCR data suggest that many hepatic genes are expressed in these cells. Cell culture experiments confirmed the hepatic differentiation potential of these cells with the loss of the CD45 marker. We observed that both hematopoietic activity in ?-like protein-1+ cells and hepatic activity in CD45+ cells were high at embryonic day 10.5 and declined thereafter. Clonal analysis revealed that the hematopoietic fraction of fetal liver cells at embryonic day 10.5 gave rise to both hepatic and hematopoietic colonies. The above results suggest a common source of these two functionally distinct cell lineages. In utero transplantation experiments confirmed these results, as green fluorescent protein-expressing CD45+ cells at the same stage of development yielded functional hepatocytes and hematopoietic reconstitution. Since these cells were unable to differentiate into cytokeratin-19-expressing cholangiocytes, we distinguished them from hepatoblasts. This preliminary study provides hope to correct many liver diseases during prenatal development via transplantation of fetal liver hematopoietic cells.

Khurana, Satish; Mukhopadhyay, Asok

2008-01-01

173

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

PubMed Central

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

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

2013-01-01

174

Motor unit potential abnormalities in multiple sclerosis: further evidence for a peripheral nervous system defect.  

PubMed Central

We have recently reported abnormalities of single fibre EMG in patients with multiple sclerosis. The present study applies quantitative electrophysiological techniques to the same group of patients. The number of motor units in the extensor digitorum brevis muscle was measured and their characteristics recorded. Also the shortest distal motor latency and fastest motor conduction velocities were estimated. Abnormalities suggesting a patchy denervating/reinnervating process due to pathology in the intramuscular nerve network or at the endplate were found in a number of patients. There was a good correlation between patients with abnormal motor unit potentials and those with abnormal single fibre EMG "jitter".

Weir, A I; Hansen, S; Ballantyne, J P

1980-01-01

175

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

SciTech Connect

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 non overlapping spheres, remain valid in the case of arbitrarily shaped, non overlapping, and particularly space-filling potential cells. Specifically, it is shown that in the angular momentum representation the total scattering (transition) matrix, the Greenfunction, 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 non overlapping cells, and with respect to the choice of the cell centers. Ananalytic proof is provided for the vanishing of near-field corrections (NFC's)long conjectured to arise when the spheres bounding individual cells over lap 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 Schroedinger 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.

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

1989-07-15

176

Growth differentiation factor 15 in different stages of heart failure: potential screening implications.  

PubMed

Identification of individuals in the early stage of heart failure (HF) may allow earlier initiation of disease-modifying treatment. We evaluated concentrations of the growth differentiation factor (GDF)-15 at different stages and its potential screening value in 208 subjects. Plasma GDF-15 was measured by using an enzyme-linked immunosorbent assay. GDF-15 was positively correlated with the stages of HF (r=0.804, p<0.001). In distinguishing patients with stage B HF, the area under the curve was 0.873 (p<0.001). These findings indicate that GDF-15 concentration was elevated with the progressing stages of HF and might have potential screening implications for stage B HF. PMID:20860541

Wang, Fangfang; Guo, Yanhong; Yu, Haiyi; Zheng, Lingbing; Mi, Lin; Gao, Wei

2010-09-23

177

Functional Relationships between Genes Associated with Differentiation Potential of Aged Myogenic Progenitors  

PubMed Central

Aging is accompanied by considerable heterogeneity with possible co-expression of differentiation pathways. The present study investigates the interplay between crucial myogenic, adipogenic, and Wnt-related genes orchestrating aged myogenic progenitor differentiation (AMPD) using clonal gene expression profiling in conjunction with Bayesian structure learning (BSL) techniques. The expression of three myogenic regulatory factor genes (Myogenin, Myf-5, MyoD1), four genes involved in regulating adipogenic potential (C/EBP?, DDIT3, FoxC2, PPAR?), and two genes in the Wnt signaling pathway (Lrp5, Wnt5a) known to influence both differentiation programs were determined across 34 clones by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Three control genes were used for normalization of the clonal expression data (18S, GAPDH, and B2M). Constraint-based BSL techniques, namely (a) PC Algorithm, (b) Grow-shrink (GS) algorithm, and (c) Incremental Association Markov Blanket (IAMB) were used to model the functional relationships (FRs) in the form of acyclic networks from the clonal expression profiles. A novel resampling approach that obviates the need for a user-defined confidence threshold is proposed to identify statistically significant FRs at small sample sizes. Interestingly, the resulting acyclic network consisted of FRs corresponding to myogenic, adipogenic, Wnt-related genes and their interaction. A significant number of these FRs were robust to normalization across the three house-keeping genes and the choice of the BSL technique. The results presented elucidate the delicate balance between differentiation pathways (i.e., myogenic as well as adipogenic) and possible cross-talk between pathways in AMPD.

Nagarajan, Radhakrishnan; Datta, Sujay; Scutari, Marco; Beggs, Marjorie L.; Nolen, Greg T.; Peterson, Charlotte A.

2010-01-01

178

Functional relationships between genes associated with differentiation potential of aged myogenic progenitors.  

PubMed

Aging is accompanied by considerable heterogeneity with possible co-expression of differentiation pathways. The present study investigates the interplay between crucial myogenic, adipogenic, and Wnt-related genes orchestrating aged myogenic progenitor differentiation (AMPD) using clonal gene expression profiling in conjunction with Bayesian structure learning (BSL) techniques. The expression of three myogenic regulatory factor genes (Myogenin, Myf-5, MyoD1), four genes involved in regulating adipogenic potential (C/EBP?, DDIT3, FoxC2, PPAR?), and two genes in the Wnt signaling pathway (Lrp5, Wnt5a) known to influence both differentiation programs were determined across 34 clones by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Three control genes were used for normalization of the clonal expression data (18S, GAPDH, and B2M). Constraint-based BSL techniques, namely (a) PC Algorithm, (b) Grow-shrink (GS) algorithm, and (c) Incremental Association Markov Blanket (IAMB) were used to model the functional relationships (FRs) in the form of acyclic networks from the clonal expression profiles. A novel resampling approach that obviates the need for a user-defined confidence threshold is proposed to identify statistically significant FRs at small sample sizes. Interestingly, the resulting acyclic network consisted of FRs corresponding to myogenic, adipogenic, Wnt-related genes and their interaction. A significant number of these FRs were robust to normalization across the three house-keeping genes and the choice of the BSL technique. The results presented elucidate the delicate balance between differentiation pathways (i.e., myogenic as well as adipogenic) and possible cross-talk between pathways in AMPD. PMID:21423363

Nagarajan, Radhakrishnan; Datta, Sujay; Scutari, Marco; Beggs, Marjorie L; Nolen, Greg T; Peterson, Charlotte A

2010-09-09

179

Precancerous stem cells have the potential for both benign and malignant differentiation.  

PubMed

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, William E; Lin, Haifan; Barsky, Sanford H; Gao, Jian-Xin

2007-03-14

180

Identification of a potential tumor differentiation factor receptor candidate in prostate cancer cells.  

PubMed

Tumor differentiation factor (TDF) is a pituitary protein that is secreted into the bloodstream and has an endocrine function. TDF and TDF-P1, a 20-residue peptide selected from the ORF of TDF, induce differentiation in human breast and prostate cancer cells, but not in other cells. TDF has no known mechanism of action. In our recent study, we identified heat shock 70 kDa proteins (HSP70s) as TDF receptors (TDF-Rs) in breast cancer cells. Therefore, we sought to investigate whether TDF-R candidates from prostate cancer cells are the same as those identified in breast cancer cells. Here, we used TDF-P1 to purify the potential TDF-R candidates by affinity purification chromatography from DU145 and PC3 steroid-resistant prostate cancer cells, LNCaP steroid-responsive prostate cancer cells, and nonprostate NG108 neuroblastoma and BLK CL.4 fibroblast-like cells. We identified the purified proteins by MS, and validated them by western blotting, immunofluorescence microscopy, immunoaffinity purification chromatography, and structural biology. We identified seven candidate proteins, of which three were from the HSP70 family. These three proteins were validated as potential TDF-R candidates in LNCaP steroid-responsive and in DU145 and PC3 steroid-resistant prostate cancer cells, but not in NG108 neuroblastoma and BLK CL.4 fibroblast-like cells. Our previous study and the current study suggest that GRP78, and perhaps HSP70s, are strong TDF-R candidates, and further suggest that TDF interacts with its receptors exclusively in breast and prostate cells, inducing cell differentiation through a novel, steroid-independent pathway. PMID:22613557

Sokolowska, Izabela; Woods, Alisa G; Gawinowicz, Mary Ann; Roy, Urmi; Darie, Costel C

2012-06-14

181

Green s functions in full-potential multiple-scattering theory  

SciTech Connect

One-electron Green s functions play a central role in multiple-scattering theory (MST) based electronic- structure methods. Robust methods exist for calculating the Green s function for crystal potentials that are spherically symmetric about atomic centers. When applied to potentials of general shape, these same techniques result in pathologies in the small-r behavior of the electronic charge density because a portion of the Green s function can become singular at the origin for that case. We propose an algebraic method that eliminates the singular behavior by making use of the equivalence of two terms that involve poles in the inverse of the sine matrix. Our accurate calculations illustrate the limitations of previous methods for treating this problem that rely on extrapolating the solutions near the origin.

Rusanu, Aurelian [ORNL; Stocks, George Malcolm [ORNL; Wang, Yang [Pittsburgh Supercomputing Center; Faulkner, John Sam [Florida Atlantic University

2011-01-01

182

Potential control of multiple sclerosis by cannabis and the endocannabinoid system.  

PubMed

For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS. PMID:22583441

Pryce, Gareth; Baker, David

2012-08-01

183

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

SciTech Connect

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

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

2012-07-15

184

Calcium Currents of Olfactory Bulb Juxtaglomerular Cells: Profile and Multiple Conductance Plateau Potential Simulation  

PubMed Central

The olfactory glomerulus is the locus of information transfer between olfactory sensory neurons and output neurons of the olfactory bulb. Juxtaglomerular cells (JGCs) may influence intraglomerular processing by firing plateau potentials that support multiple spikes. It is unclear what inward currents mediate this firing pattern. In previous work, we characterized potassium currents of JGCs. We focus here on the inward currents using whole cell current clamp and voltage recording in a rat in vitro slice preparation, as well as computer simulation. We first showed that sodium current was not required to mediate plateau potentials. Voltage clamp characterization of calcium current (ICa) determined that ICa consisted of a slow activating, rapidly inactivating (?10%–90% rise 6–8ms, ?inactivation 38–77ms) component Icat1, similar to T-type currents, and a sustained (?inactivation?500ms) component Icat2, likely composed of L-type and P/Q-type currents. We used computer simulation to test their roles in plateau potential firing. We robustly modeled Icat1 and Icat2 to Hodgkin-Huxley schemes (m3h and m2, respectively) and simulated a JGC plateau potential with 6 conductances: calcium currents as above, potassium currents from our prior study (A-type Ikt1, D-type Ikt2, delayed rectifier Ikt3), and a fast sodium current (INa). We demonstrated that Icat1 was required for mediating the plateau potential, unlike INa and Icat2, and its ?inactivation determined plateau duration. We also found that Ikt1 dictated plateau potential shape more than Ikt2 and Ikt3. The influence of these two transient and opposing conductances suggests a unique mechanism of plateau potential physiology.

Masurkar, Arjun V.; Chen, Wei R.

2011-01-01

185

Potential Values of Incorporating a Multiple-Choice Question Construction in Physics Experimentation Instruction  

NASA Astrophysics Data System (ADS)

The potential value of a multiple-choice question-construction instructional strategy for the support of students’ learning of physics experiments was examined in the study. Forty-two university freshmen participated in the study for a whole semester. A constant comparison method adopted to categorize students’ qualitative data indicated that the influences of multiple-choice question construction were evident in several significant ways (promoting constructive and productive studying habits; reflecting and previewing course-related materials; increasing in-group communication and interaction; breaking passive learning style and habits, etc.), which, worked together, not only enhanced students’ comprehension and retention of the obtained knowledge, but also helped distil a sense of empowerment and learning community within the participants. Analysis with one-group t-tests, using 3 as the expected mean, on quantitative data further found that students’ satisfaction toward past learning experience, and perceptions toward this strategy’s potentials for promoting learning were statistically significant at the 0.0005 level, while learning anxiety was not statistically significant. Suggestions for incorporating question-generation activities within classroom and topics for future studies were rendered.

Yu, Fu-Yun; Liu, Yu-Hsin

2005-09-01

186

Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) expression is regulated by multiple neural differentiation signals  

PubMed Central

Neuronal differentiation requires exquisitely timed cell cycle arrest for progenitors to acquire an appropriate neuronal cell fate and is achieved by communication between soluble signals, such as growth factors and extracellular matrix molecules. Here we report that the expression of TIMP-2, a matrix metalloproteinase inhibitor, is up-regulated by signals that control proliferation (bFGF and EGF) and differentiation (retinoic acid and NGF) in neural progenitor and neuroblastoma cell lines. TIMP-2 expression coincides with the appearance of neurofilament-positive neurons, indicating that TIMP-2 may play a role in neurogenesis. The up-regulation of TIMP-2 expression by proliferative signals suggests a role in the transition from proliferation to neuronal differentiation. Live labeling experiments demonstrate TIMP-2 expression only on ?3 integrin-positive cells. Thus, TIMP-2 function may be mediated via interaction with integrin receptor(s). We propose that TIMP-2 represents a component of the neurogenic signaling cascade induced by mitogenic stimuli that may withdraw progenitor cells from the cell cycle permitting their terminal neuronal differentiation.

Jaworski, Diane M.; Perez-Martinez, Leonor

2010-01-01

187

A Generalized Logistic Regression Procedure to Detect Differential Item Functioning among Multiple Groups  

ERIC Educational Resources Information Center

|We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence…

Magis, David; Raiche, Gilles; Beland, Sebastien; Gerard, Paul

2011-01-01

188

Chaotic differential Harmony Search algorithm applied to power economic dispatch of generators with multiple fuel options  

Microsoft Academic Search

The Harmony Search (HS) algorithm was originally conceptualized using the musical improvisation process of searching for a perfect state of harmony. The HS algorithm uses a random search, which is based on random selection, memory consideration, and pitch adjusting. This paper proposes a modified HS approach combined with differential evolution and chaotic sequences to solve the economic load dispatch problem

Leandro dos Santos Coelho; Diego Luis de Andrade Bernert; Viviana Cocco Mariani

2010-01-01

189

Multiple mechanisms of interference between transformation and differentiation in thyroid cells.  

PubMed Central

Transformation of the thyroid cell line FRTL-5 results in loss or reduction of differentiation as measured by the expression of thyroglobulin and thyroperoxidase, two proteins whose genes are exclusively expressed in thyroid follicular cells. The biochemical mechanisms leading to this phenomenon were investigated in three cell lines obtained by transformation of FRTL-5 cells with Ki-ras, Ha-ras, and polyomavirus middle-T oncogenes. With the ras oncogenes, transformation leads to undetectable expression of the thyroglobulin and thyroperoxidase genes. However, the mechanisms responsible for the extinction of the differentiated phenotype seem to be different for the two ras oncogenes. In Ki-ras-transformed cells, the mRNA encoding TTF-1, a transcription factor controlling thyroglobulin and thyroperoxidase gene expression, is severely reduced. On the contrary, nearly wild-type levels of TTF-1 mRNA are detected in Ha-ras-transformed cells. Furthermore, overexpression of TTF-1 can activate transcription of the thyroglobulin promoter in Ki-ras-transformed cells, whereas it has no effect on thyroglobulin transcription in the Ha-ras-transformed line. Expression of polyoma middle-T antigen in thyroid cells leads to only a reduction of differentiation and does not severely affect either the activity or the amount of TTF-1. Another thyroid cell-specific transcription factor, TTF-2, is more sensitive to transformation, since it disappears in all three transformed lines, and probably contributes to the reduced expression of the differentiated phenotype. Images

Francis-Lang, H; Zannini, M; De Felice, M; Berlingieri, M T; Fusco, A; Di Lauro, R

1992-01-01

190

A Generalized Logistic Regression Procedure to Detect Differential Item Functioning Among Multiple Groups  

Microsoft Academic Search

We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence of uniform DIF, nonuniform

David Magis; Gilles Raîche; Sébastien Béland; Paul Gérard

2011-01-01

191

Swarm-Cell Differentiation in Salmonellaenterica Serovar Typhimurium Results in Elevated Resistance to Multiple Antibiotics  

Microsoft Academic Search

Although a wealth of knowledge exists about the molecular and biochemical mechanisms governing the swimming motility of Salmonella enterica serovar Typhimurium, its surface swarming behavior has not been extensively characterized. When inoculated onto a semisolid agar medium supplemented with appropriate nutrients, serovar Typhimurium undergoes a morphological differentiation whereby single cells hyperflagellate and elongate into nonseptate, multinucleate swarm cells. Swarm migration

Wook Kim; Teresa Killam; Vandana Sood; Michael G. Surette

2003-01-01

192

Multiple signaling pathways are involved in erythropoietin-independent differentiation of erythroid progenitors in polycythemia vera  

Microsoft Academic Search

Polycythemia vera (PV) is a myeloproliferative disorder arising in a multipotent hematopoietic stem cell. The pathogenesis of PV remains poorly understood; however, the biologic hallmark of this disease is the presence of erythropoietin (Epo)-independent colony formation (endogenous erythroid colony [EEC]) and cytokine hypersensitivity. We have developed a simple liquid culture from CD34+ cells to study PV erythroid differentiation. PV erythroid

Valérie Ugo; Christophe Marzac; Irčne Teyssandier; Frédéric Larbret; Yann Lécluse; Najet Debili; William Vainchenker; Nicole Casadevall

2004-01-01

193

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

194

Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG–SPECT  

Microsoft Academic Search

Background: Differential diagnosis between idiopathic Parkinson’s disease (PD) and multiple system atrophy (MSA) is often difficult in early disease stages. Since MSA is misdiagnosed as PD in more than 20% of the early stages, there is need for methods refining the differentiation of the two disease entities. In PD postganglionic involvement of the autonomic nervous system (ANS) predominates whereas in

A Druschky; M. J Hilz; G Platsch; M Radespiel-Tröger; K Druschky; T Kuwert; B Neundörfer

2000-01-01

195

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.

Liao, David

196

Effects of induced hyperthermia on visual evoked potentials and saccade parameters in normal subjects and multiple sclerosis patients  

Microsoft Academic Search

A convenient method for raising body temperature has been developed and used to evaluate temperature effects on visual evoked potentials and saccade reaction time and velocity in five normal subjects and five patients with multiple sclerosis.

S Bajada; F L Mastaglia; J L Black; D W Collins

1980-01-01

197

Effects of induced hyperthermia on visual evoked potentials and saccade parameters in normal subjects and multiple sclerosis patients.  

PubMed Central

A convenient method for raising body temperature has been developed and used to evaluate temperature effects on visual evoked potentials and saccade reaction time and velocity in five normal subjects and five patients with multiple sclerosis. Images

Bajada, S; Mastaglia, F L; Black, J L; Collins, D W

1980-01-01

198

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

199

Differential effects of genetic susceptibility factors in males and females with multiple sclerosis.  

PubMed

Multiple sclerosis (MS), a putative autoimmune disease, has a well documented female preponderance among patients. However, this is not the only sex effect observed in the disease. Unaffected mothers appear to be at a higher risk to transmit susceptibility (genetic, environmental or interactions thereof) compared to unaffected fathers. This maternal effect can range from intrauterine exposures to transmission of genotypes and epigenetics. PMID:23796437

Sadovnick, A Dessa

2013-05-11

200

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

201

Inhibition of Th17 Cell Differentiation as a Treatment for Multiple Sclerosis.  

National Technical Information Service (NTIS)

The goal of this project is to develop miR-326 small molecule inhibitors (SMIs) for the treatment of Multiple Sclerosis (MS). Our global approach consists of creating stable transfectants with a luciferase reporter gene and 3 target sequence for miR-326. ...

A. D'Andrea

2012-01-01

202

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

ERIC Educational Resources Information Center

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

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

2013-01-01

203

Competitive Microcredit Markets: Differentiation and ex-ante Incentives for Multiple Borrowing  

Microsoft Academic Search

We analyze an oligopolistic microcredit market characterized by asymmetric information and institutions that can offer only one type of contract. We study the effects of competition on contract choice when small entrepreneurs can borrow from more than one institution due to the absence of credit bureaus. We show that appropriate contract design can eliminate the ex-ante incentives for multiple borrowing.

Paolo Casini

2010-01-01

204

Differential reproduction in multiple-queen colonies of the fire ant Solenopsis invicta (Hymenoptera: Formicidae)  

Microsoft Academic Search

The contribution to maternity of workers and female sexuals over time by queens in six multiple-queen laboratory colonies of Solenopsis invicta was directly assessed by use of enzyme genetic markers. Queens contributed more equally to the worker pool than to the pool of sexuals in virtually all samples (Fig. 1), and individuals producing a substantial proportion of the workers often

K. G. Ross

1988-01-01

205

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

ERIC Educational Resources Information Center

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

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

2013-01-01

206

Bone Marrow-Derived Human Mesenchymal Stem Cells Express Cardiomyogenic Proteins But Do Not Exhibit Functional Cardiomyogenic Differentiation Potential  

PubMed Central

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

Siegel, Georg; Krause, Petra; Wohrle, Stefanie; Nowak, Patrick; Ayturan, Miriam; Kluba, Torsten; Brehm, Bernhard R.; Neumeister, Birgid; Kohler, David; Rosenberger, Peter; Just, Lothar; Northoff, Hinnak

2012-01-01

207

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

Microsoft Academic Search

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

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

2003-01-01

208

The HAND1 Basic Helix-Loop-Helix Transcription Factor Regulates Trophoblast Differentiation via Multiple Mechanisms  

PubMed Central

The basic helix-loop-helix (bHLH) transcription factor genes Hand1 and Mash2 are essential for placental development in mice. Hand1 promotes differentiation of trophoblast giant cells, whereas Mash2 is required for the maintenance of giant cell precursors, and its overexpression prevents giant cell differentiation. We found that Hand1 expression and Mash2 expression overlap in the ectoplacental cone and spongiotrophoblast, layers of the placenta that contain the giant cell precursors, indicating that the antagonistic activities of Hand1 and Mash2 must be coordinated. MASH2 and HAND1 both heterodimerize with E factors, bHLH proteins that are the DNA-binding partners for most class B bHLH factors and which are also expressed in the ectoplacental cone and spongiotrophoblast. In vitro, HAND1 could antagonize MASH2 function by competing for E-factor binding. However, the Hand1 mutant phenotype cannot be solely explained by ectopic activity of MASH2, as the Hand1 mutant phenotype was not altered by further mutation of Mash2. Interestingly, expression of E-factor genes (ITF2 and ALF1) was down-regulated in the trophoblast lineage prior to giant cell differentiation. Therefore, suppression of MASH2 function, required to allow giant cell differentiation, may occur in vivo by loss of its E-factor partner due to loss of its expression and/or competition from HAND1. In giant cells, where E-factor expression was not detected, HAND1 presumably associates with a different bHLH partner. This may account for the distinct functions of HAND1 in giant cells and their precursors. We conclude that development of the trophoblast lineage is regulated by the interacting functions of HAND1, MASH2, and their cofactors.

Scott, Ian C.; Anson-Cartwright, Lynn; Riley, Paul; Reda, Danny; Cross, James C.

2000-01-01

209

The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms.  

PubMed

The basic helix-loop-helix (bHLH) transcription factor genes Hand1 and Mash2 are essential for placental development in mice. Hand1 promotes differentiation of trophoblast giant cells, whereas Mash2 is required for the maintenance of giant cell precursors, and its overexpression prevents giant cell differentiation. We found that Hand1 expression and Mash2 expression overlap in the ectoplacental cone and spongiotrophoblast, layers of the placenta that contain the giant cell precursors, indicating that the antagonistic activities of Hand1 and Mash2 must be coordinated. MASH2 and HAND1 both heterodimerize with E factors, bHLH proteins that are the DNA-binding partners for most class B bHLH factors and which are also expressed in the ectoplacental cone and spongiotrophoblast. In vitro, HAND1 could antagonize MASH2 function by competing for E-factor binding. However, the Hand1 mutant phenotype cannot be solely explained by ectopic activity of MASH2, as the Hand1 mutant phenotype was not altered by further mutation of Mash2. Interestingly, expression of E-factor genes (ITF2 and ALF1) was down-regulated in the trophoblast lineage prior to giant cell differentiation. Therefore, suppression of MASH2 function, required to allow giant cell differentiation, may occur in vivo by loss of its E-factor partner due to loss of its expression and/or competition from HAND1. In giant cells, where E-factor expression was not detected, HAND1 presumably associates with a different bHLH partner. This may account for the distinct functions of HAND1 in giant cells and their precursors. We conclude that development of the trophoblast lineage is regulated by the interacting functions of HAND1, MASH2, and their cofactors. PMID:10611232

Scott, I C; Anson-Cartwright, L; Riley, P; Reda, D; Cross, J C

2000-01-01

210

Integrating Prior Knowledge in Multiple Testing under Dependence with Applications to Detecting Differential DNA Methylation  

PubMed Central

Summary DNA methylation has emerged as an important hallmark of epigenetics. Numerous platforms including tiling arrays and next generation sequencing, and experimental protocols are available for profiling DNA methylation. Similar to other tiling array data, DNA methylation data shares the characteristics of inherent correlation structure among nearby probes. However, unlike gene expression or protein DNA binding data, the varying CpG density which gives rise to CpG island, shore and shelf definition provides exogenous information in detecting differential methylation. This paper aims to introduce a robust testing and probe ranking procedure based on a non-homogeneous hidden Markov model that incorporates the above-mentioned features for detecting differential methylation. We revisit the seminal work of Sun and Cai (2009, J. R. Stat. Soc. B. 71, 393-424) and propose modeling the non-null using a non-parametric symmetric distribution in two-sided hypothesis testing. We show that this model improves probe ranking and is robust to model misspecification based on extensive simulation studies. We further illustrate that our proposed framework achieves good operating characteristics as compared to commonly used methods in real DNA methylation data that aims to detect differential methylation sites.

Kuan, Pei Fen; Chiang, Derek Y.

2012-01-01

211

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.

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

2013-01-01

212

Differential proteomics of human seminal plasma: A potential target for searching male infertility marker proteins.  

PubMed

The clinical fertility tests, available in the market, fail to define the exact cause of male infertility in almost half of the cases and point toward a crucial need of developing better ways of infertility investigations. The protein biomarkers may help us toward better understanding of unknown cases of male infertility that, in turn, can guide us to find better therapeutic solutions. Many clinical attempts have been made to identify biomarkers of male infertility in sperm proteome but only few studies have targeted seminal plasma. Human seminal plasma is a rich source of proteins that are essentially required for development of sperm and successful fertilization. This viewpoint article highlights the importance of human seminal plasma proteome in reproductive physiology and suggests that differential proteomics integrated with functional analysis may help us in searching potential biomarkers of male infertility. PMID:22532450

Tomar, Anil Kumar; Sooch, Balwinder Singh; Singh, Sarman; Yadav, Savita

2012-04-01

213

F-18 fluorodeoxyglucose: Its potential in differentiating between stress fracture and neoplasia  

SciTech Connect

F-18 fluorodeoxyglucose (FDG) accumulates into regions of enhanced glucose uptake and metabolism such as the brain, heart, and malignant tumors. The clinical usefulness of this positron-emitting radiopharmaceutical is illustrated in a case where the clinical picture and CT indicated a malignant bone lesion in the clavicle. Histologically a stress fracture was found secondary to chronic strain on the clavicle. On follow-up the lesion's course was benign. Planar imaging with F-18 FDG was performed twice during follow-up, and on both occasions there was no accumulation of radioactivity over the suspicious area, indicating normal glucose consumption. This case demonstrates the differential diagnostic potential of F-18 FDG and shows that clinically useful information may be obtained without a position emission tomograph.

Paul, R.; Ahonen, A.; Virtama, P.; Aho, A.; Ekfors, T. (University Central Hospital, Turku (Finland))

1989-12-01

214

Bacterial biosensors for evaluating potential impacts of estrogenic endocrine disrupting compounds in multiple species.  

PubMed

To study the effects and possible mechanisms of suspected endocrine disrupting compounds (EDCs), a wide variety of assays have been developed. In this work, we generated engineered Escherichia coli biosensor strains that incorporate the ligand-binding domains (LBDs) of the ?-subtype estrogen receptors (ER?) from Solea solea (sole), and Sus scrofa (pig). These strains indicate the presence of ligands for these receptors by changes in growth phenotype, and can differentiate agonist from antagonist and give a rough indication of binding affinity via dose-response curves. The resulting strains were compared with our previously reported Homo sapiens ER? biosensor strain. In initial tests, all three of the strains correctly identified estrogenic test compounds with a high degree of certainly (Z' typically greater than 0.5), including the weakly binding test compound bisphenol A (BPA) (Z' ? 0.1-0.3). The modular design of the sensing element in this strain allows quick development of new species-based biosensors by simple LBD swapping, suggesting its use in initial comparative analysis of EDC impacts across multiple species. Interestingly, the growth phenotypes of the biosensor strains indicate similar binding for highly estrogenic control compounds, but suggest differences in ligand binding for more weakly binding EDCs. PMID:21544920

Gierach, Izabela; Shapero, Kayle; Eyster, Thomas W; Wood, David W

2011-05-04

215

Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity.  

PubMed

Activators of M(1) muscarinic acetylcholine receptors (mAChRs) may provide novel treatments for schizophrenia and Alzheimer's disease. Unfortunately, the development of M(1)-active compounds has resulted in nonselective activation of the highly related M(2) to M(5) mAChR subtypes, which results in dose-limiting side effects. Using a functional screening approach, we identified several novel ligands that potentiated agonist activation of M(1) with low micromolar potencies and induced 5-fold or greater leftward shifts of the acetylcholine (ACh) concentration-response curve. These ligands did not compete for binding at the ACh binding site, indicating that they modulate receptor activity by binding to allosteric sites. The two most selective compounds, cyclopentyl 1,6-dimethyl-4-(6-nitrobenzo[d][1,3]-dioxol-5-yl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (VU0090157) and (E)-2-(4-ethoxyphenylamino)-N'-((2-hydroxynaphthalen-1-yl)methylene)acetohydrazide (VU0029767), induced progressive shifts in ACh affinity at M(1) that were consistent with their effects in a functional assay, suggesting that the mechanism for enhancement of M(1) activity by these compounds is by increasing agonist affinity. These compounds were strikingly different, however, in their ability to potentiate responses at a mutant M(1) receptor with decreased affinity for ACh and in their ability to affect responses of the allosteric M(1) agonist, 1-[1'-(2-tolyl)-1,4'-bipiperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one. Furthermore, these two compounds were distinct in their abilities to potentiate M(1)-mediated activation of phosphoinositide hydrolysis and phospholipase D. The discovery of multiple structurally distinct positive allosteric modulators of M(1) is an exciting advance in establishing the potential of allosteric modulators for selective activation of this receptor. These data also suggest that structurally diverse M(1) potentiators may act by distinct mechanisms and differentially regulate receptor coupling to downstream signaling pathways. PMID:19047481

Marlo, Joy E; Niswender, Colleen M; Days, Emily L; Bridges, Thomas M; Xiang, Yun; Rodriguez, Alice L; Shirey, Jana K; Brady, Ashley E; Nalywajko, Tasha; Luo, Qingwei; Austin, Cheryl A; Williams, Michael Baxter; Kim, Kwangho; Williams, Richard; Orton, Darren; Brown, H Alex; Lindsley, Craig W; Weaver, C David; Conn, P Jeffrey

2008-12-01

216

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(-˝)) 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

2012-02-29

217

Auditory evoked potentials in multiple sclerosis: correlation with magnetic resonance imaging.  

PubMed

The present study addresses issues regarding the location of neural sources (i.e. generators) of human auditory evoked potentials (AEPs), and the pattern of neural conduction in the auditory pathway. AEPs were recorded from fifteen patients with multiple sclerosis (MS) and compared to normals. The recordings included auditory brainstem responses (ABRs), mid-latency responses (MLRs), and long-latency responses (LLRs). AEP latency abnormalities were related to the locus of demyelinating lesions, as determined by magnetic resonance imaging (MRI) scans. The data demonstrated several anatomical patterns relating abnormal ABR wave intervals and abnormal MRI signals. From these patterns specific loci for ABR neural sources in the brainstem might be postulated. In addition, the earlier the ABR waves, the more unilateral the abnormalities appeared, suggesting bilateral sources for later waves. The MLRs were highly correlated with ABR wave V and were associated with greater abnormality in MRI signals in midbrain and forebrain regions. In general, patients with abnormal LLRs also had widespread AEP and MRI abnormalities, supporting a multiple source approach for the N1 wave of the LLRs. The observation that LLRs were only abnormal in the presence of bilateral ABR abnormalities suggests a cross wiring which would serve as a compensatory mechanism for unilateral disturbances. The AEP data showed dissociation between early and late wave abnormalities, thus supporting parallel channels for neural conduction in the central auditory system. Such a model calls for some degree of independence of AEP generators along the auditory pathway. PMID:8910140

Hendler, T; Squires, N K; Moore, J K; Coyle, P K

1996-01-01

218

Cognition in relapsing-remitting multiple sclerosis: a multichannel event-related potential (P300) study.  

PubMed

Auditory event-related potentials (AERP) were elicited in 47 patients with relapsing-remitting (RR) multiple sclerosis (MS) and 24 age-matched controls. MS patients had significantly prolonged N2 and P3 latencies as well as low P3 amplitude compared with controls. Seven of them exceeded 3 standard deviations from the control mean values. The observed N2 and P3 alterations are associated with the patients' disability status as it is defined by the Kurtzke expanded disability status scale (EDSS), but are not related to the duration of the disease. A possible cognitive decline as reflected in the observed AERP components alterations in MS patients is subsequently discussed. PMID:1546528

Triantafyllou, N I; Voumvourakis, K; Zalonis, I; Sfagos, K; Mantouvalos, V; Malliara, S; Papageorgiou, C

1992-01-01

219

Energy-harvesting potential of multiple elastic structures in tandem arrangement  

NASA Astrophysics Data System (ADS)

Vortex-induced flapping vibrations of elastic structures attached with piezoelectric materials, i.e., ``piezo-leaves'', have recently been explored for its potential application in wind energy harvesting (e.g., Li, Yuan, and Lipson, J. Appl. Phys., 2011). In this work, we explore the possibility of enhancing the structural vibration and energy harvesting performance of the generator by putting the leaves in tandem arrangement and within close range of hydrodynamic interaction. A two-dimensional model is developed, where two or more elastic plates are mounted in a cross flow. In the case of two plates, the numerical simulation shows that at a particular distance, the vibration of the downstream plate is greatly increased, and so is the energy level of the entire system. For multiple plates, we observed both synchronized and apparently chaotic vibration modes. The characteristics of the vortex interaction, plate deformation, and energetics will be presented for those coupling modes.

Yin, Bo; Luo, Haoxiang

2011-11-01

220

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.

Laxman, Sunil; Tu, Benjamin P.

2011-01-01

221

Potential impact of rate-splitting multiple access on cellular communications  

Microsoft Academic Search

The progress in the field of multiple access techniques keeps alive the hope that multiple access systems approaching the ultimate limit in terms of bandwidth efficiency are possible. The bandwidth efficiency of a spread spectrum multiple access (SSMA) system and that of an ideal multiple access technique are compared under various scenarios pertinent to cellular communications. The scenarios are: (1)

Bixio Rimoldi; Quinn Li

1996-01-01

222

Canine bone marrow cells differentiate into hepatocyte-like cells and placental hydrolysate is a potential inducer  

Microsoft Academic Search

Hepatocyte growth factor (HGF) can stimulate human and rat bone marrow (BM) cells to differentiate into hepatocytes. A human placental hydrolysate (hPH) stimulates proliferation of hepatocytes, but its role as a potential inducer of BM cells to form hepatocytes is unclear. To determine if canine BM cells stimulated with HGF or hPH differentiate into hepatocyte-like cells, BM cells were cultured

Sakurako Neo; Takefumi Ishikawa; Kikumi Ogiwara; Norio Kansaku; Miyuki Nakamura; Masashi Watanabe; Masaharu Hisasue; Ryo Tsuchiya; Takatsugu Yamada

2009-01-01

223

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

PubMed

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 ("gluten ataxia"). Patients with Whipple's disease can develop mental and psychiatric changes, supranuclear gaze palsy, upper motoneuron signs, hypothalamic dysfunction, cranial nerve abnormalities, seizures, ataxia, myorhythmia and sensory deficits. Neurological manifestations can complicate inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease) due to vascular or vasculitic mechanisms. Cases with both Crohn's disease and MS or cerebral vasculitis are described. Epilepsy, chronic inflammatory polyneuropathy, muscle involvement and myasthenia gravis are also reported. The central nervous system can be affected in patients with hepatitis C virus (HCV) infection because of vasculitis associated with HCV-related cryoglobulinemia. Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a disease caused by multiple deletions of mitochondrial DNA. It is characterized by peripheral neuropathy, ophthalmoplegia, deafness, leukoencephalopathy, and gastrointestinal symptoms due to visceral neuropathy. Neurological manifestations can be the consequence of vitamin B1, nicotinamide, vitamin B12, vitamin D, or vitamin E deficiency and from nutritional deficiency states following gastric surgery. PMID:11794474

Ghezzi, A; Zaffaroni, M

2001-11-01

224

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

PubMed Central

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

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

2010-01-01

225

Review of daclizumab and its therapeutic potential in the treatment of relapsing-remitting multiple sclerosis  

PubMed Central

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It can present in several forms, with the relapsing–remitting pattern being the most common. Since the approval of the first disease-modifying therapy and the initiation of appropriate treatments from the early stages of the disease, there seem to be positive impacts on the long-term outcomes and disability associated with MS. Currently, there are ten approved drugs for the treatment of MS, and several more are in various stages of development. These medications each have their unique profile in terms of efficacy, dose, routes of administration, tolerability, and adverse effects. Daclizumab is a humanized monoclonal antibody that is being explored for the treatment of MS. It is currently approved for use in allograft renal transplantation. Given its modulatory effects on the immune system, daclizumab’s potential for use in MS was tested in extensive Phase II trials. With continued demonstration of its efficacy, it is currently in a Phase III trial for relapsing–remitting MS. While daclizumab has demonstrated beneficial effects in controlling disease activity in MS, there were also some safety and tolerability concerns that were raised. Further information from the ongoing Phase III trial, and from open-label studies, will shed light on the benefit and risk profile of this drug and its potential for use in MS.

Reardon, Jennifer; Perumal, Jai S

2013-01-01

226

Single and multiple vibrational resonance in a quintic oscillator with monostable potentials  

NASA Astrophysics Data System (ADS)

We analyze the occurrence of vibrational resonance in a damped quintic oscillator with three cases of single well of the potential V(x)=(1)/(2)?02x2+(1)/(4)?x4+(1)/(6)?x6 driven by both low-frequency force fcos?t and high-frequency force gcos?t with ??? . We restrict our analysis to the parametric choices (i) ?02 , ? , ?>0 (single well), (ii) ?02 , ?>0 , ?<0 , ?2<4?02? (single well), and (iii) ?02>0 , ? arbitrary, ?<0 (double-hump single well). From the approximate theoretical expression of response amplitude Q at the low-frequency ? we determine the values of ? and g (denoted as ?VR and gVR ) at which vibrational resonance occurs. We show that for fixed values of the parameters of the system when ? is varied either resonance does not occur or it occurs only once. When the amplitude g is varied for the case of the potential with the parametric choice (i) at most one resonance occur while for the other two choices (ii) and (iii) multiple resonance occur. Further, gVR is found to be independent of the damping strength d while ?VR depends on d . The theoretical predictions are found to be in good agreement with the numerical result. We illustrate that the vibrational resonance can be characterized in terms of width of the orbit also.

Jeyakumari, S.; Chinnathambi, V.; Rajasekar, S.; Sanjuan, M. A. F.

2009-10-01

227

Contrasting potential of nitric oxide and peroxynitrite to mediate oligodendrocyte injury in multiple sclerosis.  

PubMed

Nitric oxide (NO) and peroxynitrite (ONOO(-)) are potential mediators of the injury and cytotoxicity occurring over time to oligodendrocytes in multiple sclerosis (MS) lesions. Our in vitro results indicate that human adult CNS-derived oligodendrocytes are relatively resistant to NO-mediated damage. In contrast, human oligodendrocytes are highly susceptible to peroxynitrite-mediated injury. In situ, we found that inducible nitric oxide synthase (iNOS) was expressed in astrocytes and macrophages in all active demyelinating and remyelinating MS lesions examined, yet no correlation was found between numbers of glial cells expressing iNOS and the extent of oligodendrocyte cell death. Nitrotyrosine groups, indicative of the presence of peroxynitrite in vivo, could be detected on astrocytes, macrophages, and oligodendrocytes in MS lesions. High numbers of nitrotyrosine-positive oligodendrocytes were found in one MS case that featured extensive oligodendrocyte cell death. Our results indicate that NO alone is unlikely to induce oligodendrocyte injury, whereas its more potent byproduct peroxynitrite is a potential mediator of injury to oligodendrocytes in MS. PMID:17437305

Jack, Carolyn; Antel, Jack; Brück, Wolfgang; Kuhlmann, Tanja

2007-07-01

228

[White matter lesions, young age, female--differential diagnosis of multiple sclerosis and juvenile stroke].  

PubMed

Fabry's disease is an X-chromosomal linked recessive lysosomal storage disease caused by a deficiency of ?-galactosidase A. Accumulation of toxic levels of sphingolipids leads to metabolic dysfunction in various cell types (endothelial cells, myocytes, fibroblasts) and organs thus causing a variety of symptoms. Neurological manifestations include recurrent strokes and polyneuropathy, many patients complain of pain or vertigo. The presentation of these polymorphic symptoms mostly at young age often leads to incorrect diagnosis and mistreatment. Here we report two cases of female patients who both were misdiagnosed and thus mistreated for many years. These case-reports aim in increasing the awareness for Fabry's disease as a differential diagnosis, especially in young women presenting with white matter lesions. PMID:23516103

Flossdorf, P; Kurschat, C; Fink, G R; Sparing, R

2013-03-20

229

The SWI/SNF chromatin remodeling complex selectively affects multiple aspects of serotonergic neuron differentiation.  

PubMed

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

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

2013-03-02

230

Breastmilk Is a Novel Source of Stem Cells with Multilineage Differentiation Potential  

PubMed Central

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self-renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self-renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self-renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient-specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. Stem Cells2012;30:2164–2174

Hassiotou, Foteini; Beltran, Adriana; Chetwynd, Ellen; Stuebe, Alison M; Twigger, Alecia-Jane; Metzger, Philipp; Trengove, Naomi; Lai, Ching Tat; Filgueira, Luis; Blancafort, Pilar; Hartmann, Peter E

2012-01-01

231

Breastmilk is a novel source of stem cells with multilineage differentiation potential.  

PubMed

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self-renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self-renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self-renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient-specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. PMID:22865647

Hassiotou, Foteini; Beltran, Adriana; Chetwynd, Ellen; Stuebe, Alison M; Twigger, Alecia-Jane; Metzger, Philipp; Trengove, Naomi; Lai, Ching Tat; Filgueira, Luis; Blancafort, Pilar; Hartmann, Peter E

2012-10-01

232

Can Vestibular-Evoked Myogenic Potentials Help Differentiate M?ni?re Disease from Vestibular Migraine?  

PubMed Central

Objectives To characterize both cervical and ocular vestibular-evoked myogenic potential (cVEMP, oVEMP) responses to air-conducted sound (ACS) and midline taps in Méničre disease (MD), vestibular migraine (VM), and controls, as well as to determine if cVEMP or oVEMP responses can differentiate MD from VM. Study Design Prospective cohort study. Setting Tertiary referral center. Subjects and Methods Unilateral definite MD patients (n = 20), VM patients (n = 21) by modified Neuhauser criteria, and age-matched controls (n = 28). cVEMP testing used ACS (clicks), and oVEMP testing used ACS (clicks and 500-Hz tone bursts) and midline tap stimuli (reflex hammer and Mini-Shaker). Outcome parameters were cVEMP peak-to-peak amplitudes and oVEMP n10 amplitudes. Results Relative to controls, MD and VM groups both showed reduced click-evoked cVEMP (P < .001) and oVEMP (P < .001) amplitudes. Only the MD group showed reduction in tone-evoked amplitudes for oVEMP. Tone-evoked oVEMPs differentiated MD from controls (P = .001) and from VM (P = .007). The oVEMPs in response to the reflex hammer and Mini-Shaker midline taps showed no differences between groups (P > .210). Conclusions Using these techniques, VM and MD behaved similarly on most of the VEMP test battery. A link in their pathophysiology may be responsible for these responses. The data suggest a difference in 500-Hz tone burst–evoked oVEMP responses between MD and MV as a group. However, no VEMP test that was investigated segregated individuals with MD from those with VM.

Zuniga, M. Geraldine; Janky, Kristen L.; Schubert, Michael C.; Carey, John P.

2013-01-01

233

Brain stem magnetic resonance imaging and evoked potential studies of symptomatic multiple sclerosis patients.  

PubMed

In this study we evaluated the sensitivity of neuroradiological and neurophysiological tests for detecting brain stem (BS) lesions in multiple sclerosis patients, since the recent introduction of the gradient motion rephasing technique has markedly increased the image quality of magnetic resonance imaging (MRI). From 50 MS patients (33 women and 17 men; mean age 35.9 +/- 8.3 years; mean duration of the disease 7.2 +/- 4.1 years) with clinical signs of BS involvement, brain MRI, BS auditory evoked potentials (BAEPs), and left and right median somatosensory evoked potentials (mSEPs) were obtained. BS MRI lesions were detected in 41 patients (82%); in 14 cases they were located in the medulla oblongata, in 55 in the pons, and in 24 in the midbrain. Single lesions were present in 20 patients, while two or more BS lesions were demonstrated in 21 patients; 30 patients had at least one lesion located close to the inner or the outer cerebrospinal fluid border. BAEPs were abnormal in 19 of the 50 patients (38%), and BS components of mSEPs were abnormal in 15 of 46 (33%). With combined use of these neurophysiological techniques, BS abnormalities were revealed in 24 patients (48%). Only 1 patient had neurophysiological BS abnormalities and normal MRI. Moreover, there was a good correlation (74%) between the clinical and MRI BS findings in the 23 patients with signs referable to focal neurological BS lesions. The concordances considering clinical and evoked potential reports were positive, but less marked.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8467844

Comi, G; Filippi, M; Martinelli, V; Scotti, G; Locatelli, T; Medaglini, S; Triulzi, F; Rovaris, M; Canal, N

1993-01-01

234

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

Microsoft Academic Search

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

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

2009-01-01

235

Multiple Intensity Differentiation for 3-D Surface Reconstruction With Mono-Vision Infrared Proximity Array Sensor  

Microsoft Academic Search

D depth sensor technologies, as manifested in several consumers' electronics products, have potential for a technological breakthrough in various application areas such as industrial, medical, and outdoor vision system. Depth sensing of human body motions can promote intuitive gesture inputs for natural HMI (Human Machine Interface) as well as HRI (Human Robot Interaction) to the next level. In today's industry,

Dugan Um; Dongseok Ryu; Myungjoon Kal

2011-01-01

236

Ionization of liquid water by fast electron impact: multiple differential cross sections for the 1B1 orbital  

NASA Astrophysics Data System (ADS)

We present a theoretical study of single ionization of water molecules in liquid phase by impact of fast electrons in a coplanar geometry. Multiple differential cross sections are obtained through a first order model obtained within the framework of an independent electron approximation in which relaxation of the target is not taken into account. The wavefunctions for a single water molecule in the liquid phase are obtained through a Wannier orbital formalism and the ejected electron is described by means of Coulomb functions. We also present averaged calculations over all molecular orientations. A comparison with previous theoretical and experimental results, the latter corresponding to water in gaz phase, shows a good agreement. The main physical features of the reaction (such as binary and recoil peaks) present in measurements for vapor are also observed in the present theoretical predictions.

Fojón, O. A.; de Sanctis, M. L.; Vuilleumier, R.; Stia, C. R.; Politis, M.-F.

2011-04-01

237

Garlic Constituent Diallyl Trisulfide Prevents Development of Poorly-Differentiated Prostate Cancer and Pulmonary Metastasis Multiplicity in TRAMP Mice  

PubMed Central

Identification of agents that are non-toxic but can delay onset and/or progression of prostate cancer, which is the second leading cause of cancer-related deaths among men in the United States, is highly desirable. We now demonstrate that oral gavage of garlic constituent diallyl trisulfide (1 and 2 mg/d, thrice/week for thirteen weeks beginning at eight weeks of age) significantly inhibits progression to poorly-differentiated prostate carcinoma and pulmonary metastasis multiplicity in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. There was a trend of a decrease in average wet weights of the urogenital tract and prostate gland in 1 and 2 mg DATS-treated mice compared with controls (?25-46% decrease in DATS-treated mice compared with controls). The incidence and the area of the dorsolateral prostate occupied by the poorly-differentiated carcinoma were significantly lower in both 1 and 2 mg DATS-treated mice compared with control mice. In addition, DATS administration resulted in a statistically significant decrease in pulmonary metastasis multiplicity compared with controls (P= 0.002). The dorsolateral prostate from DATS-treated TRAMP mice exhibited decreased cellular proliferation in association with induction of cyclinB1 and securin protein levels, and suppression of the expression of neuroendocrine marker synaptophysin. However, DATS administration did not have any appreciable effect on apoptosis induction, angiogenesis or natural killer and dendritic cell function. In conclusion, the results of the present study demonstrate, for the first time, that DATS administration prevents progression to invasive carcinoma and lung metastasis in TRAMP mice.

Singh, Shivendra V.; Powolny, Anna A.; Stan, Silvia D.; Xiao, Dong; Arlotti, Julie A.; Warin, Renaud; Hahm, Eun-Ryeong; Marynowski, Stanley W.; Bommareddy, Ajay; Potter, Douglas M.; Dhir, Rajiv

2008-01-01

238

Multiple mechanisms of selective attention: differential modulation of stimulus processing by attention to space or time  

Microsoft Academic Search

Two studies compared the modulatory effects of orienting attention to spatial locations versus temporal intervals using event-related potentials (ERPs). In both experiments subjects performed attentional orienting tasks, which used identical stimuli in both spatial and temporal orienting conditions. The first experiment (N=16) used bilateral peripheral targets (7.5° eccentricity) at two different time intervals (600, 1200ms after cue onset). During spatial

Ivan C. Griffin; Carlo Miniussi; Anna C. Nobre

2002-01-01

239

Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation  

PubMed Central

Critical events in the life cycle of malaria parasites are controlled by calcium-dependent signalling cascades, yet the molecular mechanisms of calcium release remain poorly understood. The synchronized development of Plasmodium berghei gametocytes relies on rapid calcium release from internal stores within 10 s of gametocytes being exposed to mosquito-derived xanthurenic acid (XA). Here we addressed the function of phosphoinositide-specific phospholipase C (PI-PLC) for regulating gametocyte activation. XA triggered the hydrolysis of PIP2 and the production of the secondary messenger IP3 in gametocytes. Both processes were selectively blocked by a PI-PLC inhibitor, which also reduced the early Ca2+ signal. However, microgametocyte differentiation into microgametes was blocked even when the inhibitor was added up to 5 min after activation, suggesting a requirement for PI-PLC beyond the early mobilization of calcium. In contrast, inhibitors of calcium release through ryanodine receptor channels were active only during the first minute of gametocyte activation. Biochemical determination of PI-PLC activity was confirmed using transgenic parasites expressing a fluorescent PIP2/IP3 probe that translocates from the parasite plasmalemma to the cytosol upon cell activation. Our study revealed a complex interdependency of Ca2+ and PI-PLC activity, with PI-PLC being essential throughout gamete formation, possibly explaining the irreversibility of this process.

Raabe, Andreas C; Wengelnik, Kai; Billker, Oliver; Vial, Henri J

2011-01-01

240

Differential Development of Glucose Intolerance and Pancreatic Islet Adaptation in Multiple Diet Induced Obesity Models  

PubMed Central

Background: The C57BL/6 mouse fed a high fat diet is a common and valuable model in experimental studies of obesity and type 2 diabetes (T2D). Different high fat diets are used and in order to determine which diet produces a model most accurately resembling human T2D, they need to be compared head-to-head. Methods: Four different diets, the 60% high fat diet (HFD) and the 58% high fat-high sucrose Surwit diet (HFHS) and their respective controls, were compared in C57BL/6J mice using glucose tolerance tests (IVGTT) and the euglycemic clamp. Results: Mice fed a HFD gained more weight than HFHS fed mice despite having similar energy intake. Both high fat diet models were glucose intolerant after eight weeks. Mice fed the HFD had elevated basal insulin, which was not seen in the HFHS group. The acute insulin response (AIR) was unchanged in the HFD group, but slightly increased in the HFHS diet group. The HFHS diet group had a threefold greater total insulin secretion during the IVGTT compared to its control, while no differences were seen in the HFD group. Insulin sensitivity was decreased fourfold in the HFD group, but not in the HFHS diet group. Conclusion: The HFD and HFHS diet models show differential effects on the development of insulin resistance and beta cell adaptation. These discrepancies are important to acknowledge in order to select the appropriate diet for specific studies.

Omar, Bilal; Pacini, Giovanni; Ahren, Bo

2012-01-01

241

Multiple evolutionary processes drive the patterns of genetic differentiation in a forest tree species complex  

PubMed Central

Forest trees frequently form species complexes, complicating taxonomic classification and gene pool management. This is certainly the case in Eucalyptus, and well exemplified by the Eucalyptus globulus complex. This ecologically and economically significant complex comprises four taxa (sspp. bicostata, globulus, maidenii, pseudoglobulus) that are geographically and morphologically distinct, but linked by extensive “intergrade” populations. To resolve their genetic affinities, nine microsatellites were used to genotype 1200 trees from throughout the natural range of the complex in Australia, representing 33 morphological core and intergrade populations. There was significant spatial genetic structure (FST = 0.10), but variation was continuous. High genetic diversity in southern ssp. maidenii indicates that this region is the center of origin. Genetic diversity decreases and population differentiation increases with distance from this area, suggesting that drift is a major evolutionary process. Many of the intergrade populations, along with other populations morphologically classified as ssp. pseudoglobulus or ssp. globulus, belong to a “cryptic genetic entity” that is genetically and geographically intermediate between core ssp. bicostata, ssp. maidenii, and ssp. globulus. Geography, rather than morphology, therefore, is the best predictor of overall genetic affinities within the complex and should be used to classify germplasm into management units for conservation and breeding purposes.

Jones, Rebecca C; Steane, Dorothy A; Lavery, Martyn; Vaillancourt, Rene E; Potts, Brad M

2013-01-01

242

Multiple evolutionary processes drive the patterns of genetic differentiation in a forest tree species complex.  

PubMed

Forest trees frequently form species complexes, complicating taxonomic classification and gene pool management. This is certainly the case in Eucalyptus, and well exemplified by the Eucalyptus globulus complex. This ecologically and economically significant complex comprises four taxa (sspp. bicostata, globulus, maidenii, pseudoglobulus) that are geographically and morphologically distinct, but linked by extensive "intergrade" populations. To resolve their genetic affinities, nine microsatellites were used to genotype 1200 trees from throughout the natural range of the complex in Australia, representing 33 morphological core and intergrade populations. There was significant spatial genetic structure (F(ST) = 0.10), but variation was continuous. High genetic diversity in southern ssp. maidenii indicates that this region is the center of origin. Genetic diversity decreases and population differentiation increases with distance from this area, suggesting that drift is a major evolutionary process. Many of the intergrade populations, along with other populations morphologically classified as ssp. pseudoglobulus or ssp. globulus, belong to a "cryptic genetic entity" that is genetically and geographically intermediate between core ssp. bicostata, ssp. maidenii, and ssp. globulus. Geography, rather than morphology, therefore, is the best predictor of overall genetic affinities within the complex and should be used to classify germplasm into management units for conservation and breeding purposes. PMID:23403692

Jones, Rebecca C; Steane, Dorothy A; Lavery, Martyn; Vaillancourt, René E; Potts, Brad M

2012-11-23

243

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.

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

2012-01-01

244

Moving finite element method: Applications to general partial differential equations with multiple large gradients  

SciTech Connect

The moving finite element (MFE) method has been reduced to practice in the automatic solution program DYLA for general systems of transient partial differential equations (PDEs) in 1-D. Several test examples are presented which illustrate the unique node movement and systematic control features which are intrinsic in the MFE method. Computational dilemmas of numerical diffusion, Gibbs overshooting and undershooting, zone tangling, and grid remap (or re-connection) aliasing, which occur frequently in conventional PDE methods, are essentially eliminated in the MFE mehtod. Arbitrarily large gradients (or shocks) can be solved with extremely high resolution and accuracy for non-coincident, or even counterdirected, propagating wavefronts. Boundary layers of arbitrarily small dimensions are solved with high accuracy simultaneously with the large-scale structures in reactive and non-reactive fluid calculations. The MFE method requires a small fraction of the grid nodes which are used in conventional PDE solution methods because the nodes migrate continuously and systematically to those positions where they are most needed in order to yield accurate PDE solutions on entire problem domains. Courant--Friedrichs--Lewy time-step limits are exceeded by wide margins (by factors of two to several thousand). Finally, the extension of the MFE method to 2-D is briefly discussed.

Gelinas, R.J.; Doss, S.K.; Miller, K.

1981-03-01

245

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.

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

2013-01-01

246

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

PubMed

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

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

2001-11-01

247

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

PubMed

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

Hirai, Masahiro; Hiraki, Kazuo

2007-07-04

248

In Vivo differentiation potential of epiblast stem cells revealed by chimeric embryo formation.  

PubMed

Chimera formation after blastocyst injection or morula aggregation is the principal functional assay of the developmental potential of mouse embryonic stem cells (ESCs). This property, which demonstrates functional equivalence between ESCs and the preimplantation epiblast, is not shared by epiblast stem cell (EpiSC) lines. Here, we show that EpiSCs derived either from postimplantation embryos or from ESCs in vitro readily generate chimeras when grafted to postimplantation embryos in whole embryo culture. EpiSC derivatives integrate and differentiate to derivatives of all three embryonic germ layers and primordial germ cells. In contrast, grafted ESCs seldom proliferate in postimplantation embryos, and fail to acquire the identity of their host-derived neighbors. EpiSCs do not incorporate efficiently into embryonic day 8.5 embryos, a stage by which pluripotency has been lost. Thus, chimera formation by EpiSCs requires a permissive environment, the postimplantation epiblast, and demonstrates functional equivalence between this cell type and EpiSCs. PMID:23200857

Huang, Yali; Osorno, Rodrigo; Tsakiridis, Anestis; Wilson, Valerie

2012-11-29

249

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

250

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

2013-10-02

251

Evaluation of electrospray differential mobility analysis for virus particle analysis: Potential applications for biomanufacturing.  

PubMed

The technique of electrospray differential mobility analysis (ES-DMA) was examined as a potential potency assay for routine virus particle analysis in biomanufacturing environments (e.g., evaluation of vaccines and gene delivery products for lot release) in the context of the International Committee of Harmonisation (ICH) Q2 guidelines. ES-DMA is a rapid particle sizing method capable of characterizing certain aspects of the structure (such as capsid proteins) and obtaining complete size distributions of viruses and virus-like particles. It was shown that ES-DMA can distinguish intact virus particles from degraded particles and measure the concentration of virus particles when calibrated with nanoparticles of known concentration. The technique has a measurement uncertainty of ?20%, is linear over nearly 3 orders of magnitude, and has a lower limit of detection of ?10(9)particles/mL. This quantitative assay was demonstrated for non-enveloped viruses. It is expected that ES-DMA will be a useful method for applications involving production and quality control of vaccines and gene therapy vectors for human use. PMID:21963394

Guha, Suvajyoti; Pease, Leonard F; Brorson, Kurt A; Tarlov, Michael J; Zachariah, Michael R

2011-09-22

252

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

2013-03-19

253

Fibronectin Binding Is Required for Acquisition of Mesenchymal/Endothelial Differentiation Potential in Human Circulating Monocytes  

PubMed Central

We previously reported monocyte-derived multipotential cells (MOMCs), which include progenitors capable of differentiating into a variety of mesenchymal cells and endothelial cells. In vitro generation of MOMCs from circulating CD14+ monocytes requires their binding to extracellular matrix (ECM) protein and exposure to soluble factor(s) derived from circulating CD14? cells. Here, we investigated the molecular factors involved in MOMC generation by examining the binding of monocytes to ECM proteins. We found that MOMCs were obtained on the fibronectin, but not on type I collagen, laminin, or poly-L-lysine. MOMC generation was followed by changes in the expression profiles of transcription factors and was completely inhibited by either anti-?5 integrin antibody or a synthetic peptide that competed with the RGD domain for the ?1-integrin binding site. These results indicate that acquisition of the multidifferentiation potential by circulating monocytes depends on their binding to the RGD domain of fibronectin via cell-surface ?5?1 integrin.

Seta, Noriyuki; Okazaki, Yuka; Izumi, Keisuke; Miyazaki, Hiroshi; Kato, Takashi; Kuwana, Masataka

2012-01-01

254

Multiple Sources of Striatal Inhibition Are Differentially Affected in Huntington's Disease Mouse Models  

PubMed Central

In Huntington’s disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on indirect pathway MSNs. Dual patch recordings between MSNs demonstrated reduced connectivity between MSNs in HD mice. However, while connectivity was strictly unidirectional in controls, in HD mice bidirectional connectivity occurred. Other sources of increased GABA activity in MSNs also were identified. Dual patch recordings from fast spiking (FS) interneuron–MSN pairs demonstrated greater but variable amplitude responses in MSNs. In agreement, selective optogenetic stimulation of parvalbumin-expressing, FS interneurons induced significantly larger amplitude MSN responses in HD compared with control mice. While there were no differences in responses of MSNs evoked by activating single persistent low-threshold spiking (PLTS) interneurons in recorded pairs, these interneurons fired more action potentials in both HD models, providing another source for increased frequency of spontaneous GABA synaptic activity in MSNs. Selective optogenetic stimulation of somatostatin-expressing, PLTS interneurons did not reveal any significant differences in responses of MSNs in HD mice. These findings provide strong evidence that both feedforward and to a lesser extent feedback inhibition to MSNs in HD can potentially be sources for the increased GABA synaptic activity of indirect pathway MSNs.

Cepeda, Carlos; Galvan, Laurie; Holley, Sandra M.; Rao, Shilpa P.; Andre, Veronique M.; Botelho, Elian P.; Chen, Jane Y.; Watson, Joseph B.; Deisseroth, Karl; Levine, Michael S.

2013-01-01

255

Multiple sources of striatal inhibition are differentially affected in Huntington's disease mouse models.  

PubMed

In Huntington's disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on indirect pathway MSNs. Dual patch recordings between MSNs demonstrated reduced connectivity between MSNs in HD mice. However, while connectivity was strictly unidirectional in controls, in HD mice bidirectional connectivity occurred. Other sources of increased GABA activity in MSNs also were identified. Dual patch recordings from fast spiking (FS) interneuron-MSN pairs demonstrated greater but variable amplitude responses in MSNs. In agreement, selective optogenetic stimulation of parvalbumin-expressing, FS interneurons induced significantly larger amplitude MSN responses in HD compared with control mice. While there were no differences in responses of MSNs evoked by activating single persistent low-threshold spiking (PLTS) interneurons in recorded pairs, these interneurons fired more action potentials in both HD models, providing another source for increased frequency of spontaneous GABA synaptic activity in MSNs. Selective optogenetic stimulation of somatostatin-expressing, PLTS interneurons did not reveal any significant differences in responses of MSNs in HD mice. These findings provide strong evidence that both feedforward and to a lesser extent feedback inhibition to MSNs in HD can potentially be sources for the increased GABA synaptic activity of indirect pathway MSNs. PMID:23616545

Cepeda, Carlos; Galvan, Laurie; Holley, Sandra M; Rao, Shilpa P; André, Véronique M; Botelho, Elian P; Chen, Jane Y; Watson, Joseph B; Deisseroth, Karl; Levine, Michael S

2013-04-24

256

Small Compound 6-O-Angeloylplenolin Induces Mitotic Arrest and Exhibits Therapeutic Potentials in Multiple Myeloma  

PubMed Central

Background Multiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells. Methodology/Principal Findings MM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal cells (BMSCs) were treated with 6-OAP. The effects of 6-OAP plus other drugs on MM.1S cells were evaluated. The in vivo therapeutic efficacy and pharmacokinetic features of 6-OAP were tested in nude mice bearing U266 cells and Sprague-Dawley rats, respectively. We found that 6-OAP suppressed the proliferation of dexamethasone-sensitive and dexamethasone-resistant cell lines and primary CD138+ MM cells. 6-OAP caused mitotic arrest, accompanied by activation of spindle assembly checkpoint and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. Combined use of 6-OAP and bortezomib induced potentiated cytotoxicity with inactivation of ERK1/2 and activation of JNK1/2 and Casp-8/-3. 6-OAP overcame the protective effects of IL-6 and IGF-I on MM cells through inhibition of Jak2/Stat3 and Akt, respectively. 6-OAP inhibited BMSCs-facilitated MM cell expansion and TNF-?-induced NF-?B signal. Moreover, 6-OAP exhibited potent anti-MM activity in nude mice and favorable pharmacokinetics in rats. Conclusions/Significance These results indicate that 6-OAP is a new cell cycle inhibitor which shows therapeutic potentials for MM.

Liu, Ying; Chen, Xiao-Qin; Liang, Heng-Xing; Zhang, Feng-Xiang; Zhang, Bo; Jin, Jie; Chen, Yong-Long; Cheng, Yong-Xian; Zhou, Guang-Biao

2011-01-01

257

Early abnormalities of evoked potentials and future disability in patients with multiple sclerosis.  

PubMed

Evoked potentials (EP) have a role in making the diagnosis of multiple sclerosis (MS) but their implication for predicting the future disease course in MS is under debate. EP data of 94 MS patients examined at first presentation, and after five and ten years were retrospectively analysed. Patients were divided into two groups in relation to the prior duration of disease at the time point of first examination: group 1 patients (n=44) were first examined within two years after disease onset, and group 2 patients (n=50) at later time points. As primary measures sum scores were calculated for abnormalities of single and combined EP (visual (VEP), somatosensory (SEP), magnetic motor evoked potentials (MEP)). In patients examined early after disease onset (group 1), a significant predictive value for abnormal EP was found with MEP and SEP sum scores at first presentation correlating significantly with Expanded Disability Status Scale (EDSS) values after five years, while the VEP sum score was not. The cumulative number of abnormal MEP, SEP and VEP results also indicated higher degrees of disability (EDSS > or = 3.5) after five years. Combined pathological SEP and MEP findings at first presentation best predicted clinical disability (EDSS > or = 3.5) after five years (odds ratio 11.0). EP data and EDSS at first presentation were not significantly linked suggesting that EP abnormalities at least in part represented clinically silent lesions not mirrored by EDSS. For patients in later disease phases (group 2), no significant associations between EP data at first presentation and EDSS at five and ten years were detected. Together with clinical findings and MR imaging, combined EP data may help to identify patients at high risk of long-term clinical deterioration and guide decisions as to immunomodulatory treatment. PMID:16459720

Kallmann, B A; Fackelmann, S; Toyka, K V; Rieckmann, P; Reiners, K

2006-02-01

258

Multiple mechanisms of selective attention: differential modulation of stimulus processing by attention to space or time.  

PubMed

Two studies compared the modulatory effects of orienting attention to spatial locations versus temporal intervals using event-related potentials (ERPs). In both experiments subjects performed attentional orienting tasks, which used identical stimuli in both spatial and temporal orienting conditions. The first experiment (N=16) used bilateral peripheral targets (7.5 degrees eccentricity) at two different time intervals (600, 1200 ms after cue onset). During spatial orienting a symbolic central cue predicted (75% probability) the spatial location (left, right) of the relevant target. No information was given about the probable target interval (short, long). In temporal orienting the cue predicted the target interval but not its location. Valid cueing produced significantly shorter reaction times in both the spatial and temporal orienting conditions. ERPs to identical, non-target stimulus arrays were analysed, to isolate endogenous attentional mechanisms. Spatial and temporal attention had distinct modulatory effects upon stimulus processing. Focused spatial attention affected the amplitude of early visual components. Modulation by temporal attention started later, and mainly affected potentials linked to decisions and responses. The second experiment (N=12) used unilateral target stimuli, and equated the probability of stimulus occurrence at short and long time intervals and at left or right of fixation. The results confirmed the distinct pattern of modulation of stimulus processing by spatial and temporal orienting. The optimisation of behaviour by attention can thus be achieved as a consequence of distinct modulatory processes, illustrating the flexibility of attentional functions in the human brain. PMID:12417462

Griffin, Ivan C; Miniussi, Carlo; Nobre, Anna C

2002-01-01

259

Symptomatic retrochiasmal lesions in multiple sclerosis: clinical features, visual evoked potentials, and magnetic resonance imaging.  

PubMed

We have studied 18 patients with relapsing-remitting multiple sclerosis (MS) who had symptomatic visual field defects due to retrochiasmal lesions. In 17, the lesion responsible was identified by magnetic resonance imaging (MRI), computed x-ray tomography (CT), or both. The lesion responsible involved the posterior optic radiations in eight cases, the optic tract and lateral geniculate nucleus in six, and the posterior limb of the internal capsule in three. The prognosis for recovery of the field defect was good; complete recovery occurred in 14 patients, and only two showed no recovery at all. The striking characteristic of the lesions was that most were unusually large; indeed, many were detectable on CT as well as MRI. Half-field asymmetries of either amplitude or latency of the visual evoked potentials (VEPs), consistent with a postchiasmal lesion, were present in only five out of 13 patients acutely. In only three of these did the abnormality persist at follow-up. We conclude that only large postchiasmal lesions are likely to cause symptomatic homonymous field defects in MS, usually characterized by rapid recovery. Hemifield VEPs have a low sensitivity for the detection of postchiasmal as compared with prechiasmal abnormalities. PMID:1734326

Plant, G T; Kermode, A G; Turano, G; Moseley, I F; Miller, D H; MacManus, D G; Halliday, A M; McDonald, W I

1992-01-01

260

Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.  

PubMed

To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from Bri2, were significantly associated with patients having cerebellar dysfunction and cognition impairment. Furthermore, expression levels of Bri2 were specifically decreased in the cerebellum compared to other areas of same brain in MS but not in controls, suggesting that decreased cerebellar Bri2 expression may play a role in cerebellar dysfunction. The association with cognition impairment is also of interest because Bri2 is linked to the amyloid processing pathway in the brain. CSF levels of Bri2-23 may serve as a biomarker of these functions in MS and merits further investigation. PMID:20600910

Harris, Violaine K; Diamanduros, Andrew; Good, Pamela; Zakin, Elina; Chalivendra, Varun; Sadiq, Saud A

2010-06-19

261

Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course.  

PubMed

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system (CNS) that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI) are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS). Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis. PMID:21949517

Lee, Yun Jin

2011-06-30

262

Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course  

PubMed Central

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system (CNS) that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI) are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS). Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis.

2011-01-01

263

A role of canonical transient receptor potential 5 channel in neuronal differentiation from A2B5 neural progenitor cells.  

PubMed

Store-operated Ca(2+) entry (SOCE) channels are the main pathway of Ca(2+) entry in non-excitable cells such as neural progenitor cells (NPCs). However, the role of SOCE channels has not been defined in the neuronal differentiation from NPCs. Here, we show that canonical transient receptor potential channel (TRPC) as SOCE channel influences the induction of the neuronal differentiation of A2B5(+) NPCs isolated from postnatal-12-day rat cerebrums. The amplitudes of SOCE were significantly higher in neural cells differentiated from proliferating A2B5(+) NPCs and applications of SOCE blockers, 2-aminoethoxy-diphenylborane (2-APB), and ruthenium red (RR), inhibited their rise of SOCE. Among TRPC subtypes (TRPC1-7), marked expression of TRPC5 and TRPC6 with turned-off TRPC1 expression was observed in neuronal cells differentiated from proliferating A2B5(+) NPCs. TRPC5 small interfering RNA (siRNA) blocked the neuronal differentiation from A2B5(+) NPCs and reduced the rise of SOCE. In contrast, TRPC6 siRNA had no significant effect on the neuronal differentiation from A2B5(+) NPCs. These results indicate that calcium regulation by TRPC5 would play a key role as a switch between proliferation and neuronal differentiation from NPCs. PMID:20479868

Shin, Hye Young; Hong, Yun Hwa; Jang, Sung Soo; Chae, Hong Gu; Paek, Seung Leal; Moon, Hyo Eun; Kim, Dong Gyu; Kim, Jun; Paek, Sun Ha; Kim, Sang Jeong

2010-05-07

264

A comparison of multifocal and conventional visual evoked potential techniques in patients with optic neuritis\\/multiple sclerosis  

Microsoft Academic Search

Purpose To compare conventional visual evoked potential (cVEP) and multifocal visual evoked potential (mfVEP) methods in patients\\u000a with optic neuritis\\/multiple sclerosis (ON\\/MS). Methods mfVEPs and cVEPs were obtained from eyes of the 19 patients with multiple sclerosis confirmed on MRI scans, and from eyes\\u000a of 40 normal controls. For the mfVEP, the display was a pattern-reversal dartboard array, 48° in

Larissa K. Grover; Donald C. Hood; Quraish Ghadiali; Tomas M. Grippo; Adam S. Wenick; Vivienne C. Greenstein; Myles M. Behrens; Jeffrey G. Odel

2008-01-01

265

Loss of proliferative potential during terminal differentiation coincides with the decreased abundance of a subset of heterogeneous ribonuclear proteins  

Microsoft Academic Search

The decrease in abundance of a subset of highly conserved basic nuclear proteins is established to correlate with the loss of proliferative potential in association with the process of terminal differentiation in murine mesenchymal stem cells and human ker- atinocytes. These proteins, designated P2Ps for proliferation potential proteins, have apparent molecu- lar masses of 30-40 kD, are associated with the

Parviz Minoo; William Sullivan; Larry R. Solomon; Terence E. Martin; David O. Tot; Robert E. Scott

1989-01-01

266

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

267

A case of multiple sclerosis with granulomatous uveitis in Japan—use of the antilipoarabinomannan (LAM)B test in differential diagnosis  

Microsoft Academic Search

PURPOSE: To report a patient with multiple sclerosis and associated with granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a key role in differential diagnosis.METHODS: Case report.RESULTS: A 35-year-old Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye. Ophthalmological examinations revealed granulomatous iridocyclitis in her left eye and retinal periphlebitis in

Kenji Inoue; Jiro Numaga; Satoru Joko; Shinzo Izumi; Satoshi Kato; Hidetoshi Kawashima; Yujiro Fujino

2001-01-01

268

Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells  

Microsoft Academic Search

One of the causes of erectile dysfunction (ED) is the damaged penile cavernous smooth muscle cells (SMCs) and sinus endothelial cells (ECs). To investigate the feasibility of applying immortalized human mesenchymal stem cells (MSCs) to penile cavernous ECs or SMCs repair in the treatment of ED, the in vivo potential differentiation of the immortalized human MSCs toward penile cavernous endothelial

Y S Song; H J Lee; I H Park; W K Kim; J H Ku; S U Kim; JH Ku

2007-01-01

269

Nitric oxide modulates TGF-beta-directive signals to suppress Foxp3+ regulatory T cell differentiation and potentiate Th1 development.  

PubMed

TGF-? can induce Foxp3(+) inducible regulatory T cells (Treg) and also synergize with IL-6 and IL-4 to induce Th17 and Th9 cells. We now report that NO modulates TGF-? activity away from Treg but toward the Th1 lineage. NO potentiated Th1 differentiation in the presence of TGF-? in both IL-12-independent and -dependent fashions by augmenting IFN-?-activated STAT-1 and T-bet. Differentiation into Treg, Th1, and Th17 lineages could be modulated by NO competing with other cofactors, such as IL-6 and retinoic acid. NO antagonized IL-6 to block TGF-?-directed Th17 differentiation, and together with IL-6, NO suppressed Treg development induced by TGF-? and retinoic acid. Furthermore, we show that physiologically produced NO from TNF and inducible NO synthase-producing dendritic cells can contribute to Th1 development predominating over Treg development through a synergistic activity induced when these cells cocluster with conventional dendritic cells presenting Ag to naive Th cells. This illustrates that NO is another cofactor allowing TGF-? to participate in development of multiple Th lineages and suggests a new mechanism by which NO, which is associated with protection against intracellular pathogens, might maintain effective Th1 immunity. PMID:21555530

Lee, Seung-Woo; Choi, Heonsik; Eun, So-Young; Fukuyama, Satoshi; Croft, Michael

2011-05-09

270

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.  

PubMed

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. PMID:23806280

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C

2013-06-24

271

Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting  

Microsoft Academic Search

BACKGROUND: Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt

Grace E Snow; Allison C Kasper; Alexander M Busch; Elisabeth Schwarz; Katherine E Ewings; Thomas Bee; Michael J Spinella; Ethan Dmitrovsky; Sarah J Freemantle

2009-01-01

272

A novel differential diagnostic model based on multiple biological parameters for immunoglobulin A nephropathy  

PubMed Central

Background Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis in China. An accurate diagnosis of IgAN is dependent on renal biopsies, and there is lack of non-invasive and practical classification methods for discriminating IgAN from other primary kidney diseases. The objective of this study was to develop a classification model for the auxiliary diagnosis of IgAN using multiparameter analysis with various biological parameters. Methods To establish an optimal classification model, 121 cases (58 IgAN vs. 63 non-IgAN) were recruited and statistically analyzed. The model was then validated in another 180 cases. Results Of the 57 biological parameters, there were 16 parameters that were significantly different (P?potential clinical applications in distinguishing IgAN from other primary kidney diseases.

2012-01-01

273

Selected Melanocortin 1 Receptor Single-Nucleotide Polymorphisms Differentially Alter Multiple Signaling Pathways  

PubMed Central

The melanocortin 1 receptor (MC1R) is a highly polymorphic G protein-coupled receptor, which is known to modulate pigmentation and inflammation. In the current study, we investigated the pharmacological effects of select single-nucleotide polymorphisms (SNPs) (V60L, R163Q, and F196L). After transient expression of MC1Rs in human embryonic kidney 293 cells, basal and ligand-induced cAMP signaling and mitogen-activated protein kinase (MAPK) activation were assessed by using luciferase reporter gene assays and Western blot analysis, respectively. All receptor variants showed decreased basal cAMP activity. With the V60L and F196L variants, the decrease in constitutive activity was attributable, at least in part, to a reduction in surface expression. The F196L variant also displayed a significant reduction in potency for both the peptide agonist ?-melanocyte-stimulating hormone (?-MSH) and the small-molecule agonist 1-[1-(3-methyl-l-histidyl-O-methyl-d-tyrosyl)-4-phenyl-4-piperidinyl]-1-butanone (BMS-470539). In MAPK signaling assays, the F196L variant showed decreased phospho-extracellular signal-regulated kinase levels after stimulation with either ?-MSH or BMS-470539. In contrast, the R163Q variant displayed a selective loss of ?-MSH-induced MAPK activation; whereas responsiveness to the small-molecule agonist BMS-470539 was preserved. Further assessment of MC1R variants in A549 cells, an in vitro model of inflammation, revealed an enhanced inflammatory response resulting from expression of the F196L variant (versus the wild-type MC1R). This alteration in function was restored by treatment with BMS-470539. Overall, these studies illustrate novel signaling profiles linked to distinct MC1R SNPs. Furthermore, our investigations highlight the potential for small-molecule drugs to rescue the function of MC1R variants that show reduced basal and/or ?-MSH stimulated activity.

Doyle, J. R.; Fortin, J. P.; Beinborn, M.

2012-01-01

274

Lithium as a potential adjuvant to 131I therapy of metastatic, well differentiated thyroid carcinoma.  

PubMed

As lithium inhibits the release of iodine from the thyroid but does not change iodine uptake, it may potentiate 131I therapy of thyroid cancer. The effects of lithium on the accumulation and retention of 131I in metastatic lesions and thyroid remnants were evaluated in 15 patients with differentiated thyroid carcinoma. Two 131I turnover studies were performed while the patients were hypothyroid. One was performed while the patient received lithium; the second served as a control study. From a series of gamma-camera images, it was found that lithium increased 131I retention in 24 of 31 metastatic lesions and in 6 of 7 thyroid remnants. A comparison of 131I retention during lithium with that during the control period showed that the mean increase in the biological or retention half-life was 50% in tumors and 90% in remnants. This increase occurred in at least 1 lesion in each patient and was proportionally greater in lesions with poor 131I retention. When the control biological half life was less than 3 days, lithium prolonged the effective half-life, which combines both biological turnover and isotope decay, in responding metastases by more than 50%. More 131I also accumulated during lithium therapy, probably as a consequence of its effect on iodine release. The increase in the accumulated 131I and the lengthening of the effective half-life combined to increase the estimated 131I radiation dose in metastatic tumor by 2.29 +/- 0.58 (mean +/- SEM) times. These studies suggest that lithium may be a useful adjuvant for 131I therapy of thyroid cancer, augmenting both the accumulation and retention of 131I in lesions. PMID:10084570

Koong, S S; Reynolds, J C; Movius, E G; Keenan, A M; Ain, K B; Lakshmanan, M C; Robbins, J

1999-03-01

275

The potential for a suite of isotope and chemical markers to differentiate sources of nitrate contamination: a review.  

PubMed

Nitrate is naturally found within the environment as part of the nitrogen cycle. However, anthropogenic inputs have greatly increased nitrate loads within ground and surface waters. This has had a severe impact on aquatic ecosystems and has given rise to health considerations in humans and livestock. Therefore, the identification of nitrate sources is important in preserving water quality and achieving sustainability of our water resources. Nitrate sources can be determined based on the nitrate nitrogen (N) and oxygen (O) isotopic compositions (?(15)N, ?(18)O). However, sewage and manure have overlapping ?(15)N and ?(18)O values making their differentiation on this basis problematic. The specific differentiation between sources of faecal contamination is of particular importance, because the risk to humans is usually considered higher from human faecal contamination (sewage) than from animal faecal contamination. This review summarises the current state of knowledge in using isotope tracers to differentiate various nitrate sources and identifies potential chemical tracers for differentiating sewage and manure. In particular, an in depth review of the current state of knowledge regarding the necessary considerations in using chemical markers, such as pharmaceuticals and food additives, to differentiate sewage and manure sources of nitrate contamination will be given, through an understanding of their use, occurrence and fate, in order to identify the most suitable potential chemical markers. PMID:22348997

Fenech, C; Rock, L; Nolan, K; Tobin, J; Morrissey, A

2012-02-09

276

Hepatic differentiation of mouse iPS cells and analysis of liver engraftment potential of multistage iPS progeny.  

PubMed

Hepatocyte transplantation is considered a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) are an unlimited source for the generation of functional hepatocytes. While several protocols that direct the differentiation of iPSCs into hepatocyte-like cells have already been reported, the liver engraftment potential of iPSC progeny obtained at each step of hepatic differentiation has not yet been thoroughly investigated. In this study, we present an efficient strategy to differentiate mouse iPSCs into hepatocyte-like cells and evaluate their liver engraftment potential at different time points of the protocol (5, 10, 15, and 20 days of differentiation). iPSCs were differentiated in the presence of cytokines, growth factors, and small molecules to finally generate hepatocyte-like cells. These iPSC-derived hepatocyte-like cells exhibited hepatocyte-associated functions, such as albumin secretion and urea synthesis. When we transplanted iPSC progeny into the spleen, we found that 15- and 20-day iPSC progeny engrafted into the livers and further acquired hepatocyte morphology. In contrast, 5- and 10-day iPSC progeny were also able to engraft but did not generate hepatocyte-like cells in vivo. Our data may aid in improving current protocols geared towards the use of iPSCs as a new source of liver-targeted cell therapies. PMID:23715756

Balasiddaiah, Anangi; Moreno, Daniel; Guembe, Laura; Prieto, Jesús; Aldabe, Rafael

2013-05-30

277

Potential role of soluble human leukocyte antigen-G molecules in multiple sclerosis.  

PubMed

Nonclassical human leukocyte antigen (HLA)-G antigens in soluble form (sHLA-G) have recently been suggested to have a potential role as immunomodulatory factors in multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system of unknown etiology and supposed autoimmune origin. In MS patients, sHLA-G levels were elevated in cerebrospinal fluid (CSF), intrathecally synthesized, predominantly represented by the HLA-G5 isoform and even more elevated in cases of inactive disease, as determined by magnetic resonance imaging. In MS, CSF sHLA-G concentrations were also related to the formation of an intrathecal anti-inflammatory microenvironment based on a positive correlation to CSF interleukin-10 titers and an inverse association to the levels of antiapoptotic sFas molecules in the CSF. Expression of HLA-G antigens was detected in microglia, macrophages, and endothelial cells within and around MS lesions and was enhanced in microglial cells by T-helper-1 proinflammatory cytokines. A novel subpopulation of naturally occurring CD4(+) and CD8(+) regulatory T cells expressing HLA-G1 and secreting HLA-G5 was identified in the CSF of MS patients. Taken together, these findings seem to indicate that sHLA-G antigens may be implicated in the termination of MS autoimmunity and associated with remission of the disease through their function as anti-inflammatory molecules. However, the mechanisms operating in the immunomodulatory circuit mediated by sHLA-G proteins remain to be clarified. PMID:19651179

Fainardi, Enrico; Rizzo, Roberta; Castellazzi, Massimiliano; Stignani, Marina; Granieri, Enrico; Baricordi, Olavio Roberto

2009-08-06

278

Sound lateralization, brainstem auditory evoked potentials and magnetic resonance imaging in multiple sclerosis.  

PubMed

Two tests of binaural hearing, namely intensity discrimination of alternating monaural clicks and interaural time difference (IATD) discrimination of binaural clicks, were performed in 28 patients with definite multiple sclerosis (MS) and 12 with an isolated brainstem lesion compatible with demyelination. Intensity discrimination defects were found in 53.5% and IATD defects in 82% of definite MS cases, although no overt auditory symptoms were reported and pure tone audiology was unremarkable. Corresponding figures in the isolated lesion group were 25% and 33%. Defects were manifested either by an abnormal 'bias' in favour of one ear or by a broadened 'spread' of responses (i.e., greater range of uncertainty). Brainstem auditory evoked potentials (BAEPs) were abnormal in 75% of the definite MS cases but only in 8% of the isolated lesion group. BAEP abnormalities involving component III on one or both sides were invariably associated with a defect of IATD discrimination. This is consistent with disruption of input to the superior olivary complex, the most peripheral structure where binaurally responsive units are sensitive to IATD. Lesions causing abnormality of component V alone less frequently resulted in impaired IATD discrimination, possibly because at rostral levels the IATD is encoded by the location rather than the timing of neuronal activity. In magnetic resonance imaging (MRI), abnormalities of the medulla, pons or midbrain were demonstrated in all MS patients tested and 45% of those with isolated brainstem lesions. The correlation with BAEP abnormalities was plausible in some patients but apparently anomalous in others. More severe BAEP abnormalities than would have been expected on the basis of MRI may have been due to small unresolved lesions, while the more frequent finding of normal or mildly abnormal BAEPs in conjunction with extensive MRI abnormalities may have been due to the fact that areas of abnormal signal reflect an increase in the water content of the tissue rather than demyelination per se. PMID:3208066

van der Poel, J C; Jones, S J; Miller, D H

1988-12-01

279

"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

280

Placebo controlled pilot trial to study the remyelinating potential of intravenous immunoglobulins in multiple sclerosis  

Microsoft Academic Search

Currently there is no treatment available to improve a stable deficit in multiple sclerosis. It was shown in animal models that intravenous immunoglobulins (IVIg) can enhance central nervous remyelination, and the first open trials were promising. We therefore conducted a double blind, placebo controlled pilot study to evaluate the effect of IVIg treatment in patients with multiple sclerosis with a

Martin Stangel; Friedrich Boegner; Christel H Klatt; Christoph Hofmeister; Sepp Seyfert

2000-01-01

281

Sensory impairments in spinal multiple sclerosis: A combined clinical, magnetic resonance imaging and somatosensory evoked potential study  

Microsoft Academic Search

Thirty-one cases (26 patients) of clinically definite multiple sclerosis with predominant spinal cord involvement were studied retrospectively, focusing in particular on the results of sensory testings which were compared with the findings of spinal cord magnetic resonance imaging (MRI) and somatosensory evoked potentials (SEPs). Factor analysis of the sensory impairments showed two factors corresponding to superficial (pain and light-touch) and

Toshio Fukutake; Satoshi Kuwabara; Masaru Kaneko; Shigeyuki Kojima; Takamichi Hattori

1998-01-01

282

Vestibular-evoked myogenic potentials: A method to assess vestibulo-spinal conduction in multiple sclerosis patients  

Microsoft Academic Search

Vestibular-evoked myogenic potentials (VEMPs), elicited by acoustic stimulation, have been proposed in the assessment of the vestibulo-cervical reflex pathways. The procedure has been previously validated in several otovestibular disorders. The aim of this study was to investigate patients affected by multiple sclerosis (MS) in the attempt to clarify the underlying physiopathogenetic mechanisms and the clinical utility of VEMPs in detecting

F Sartucci; F Logi

2002-01-01

283

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

284

Loss of proliferative potential during terminal differentiation coincides with the decreased abundance of a subset of heterogeneous ribonuclear proteins.  

PubMed

The decrease in abundance of a subset of highly conserved basic nuclear proteins is established to correlate with the loss of proliferative potential in association with the process of terminal differentiation in murine mesenchymal stem cells and human keratinocytes. These proteins, designated P2Ps for proliferation potential proteins, have apparent molecular masses of 30-40 kD, are associated with the 30-40S substructures of nuclear hnRNP complexes, and are recognized by antibodies made against core proteins of hnRNP particles. They also share an epitope in common with heat shock protein-90 (hsp90) and are recognized by two mAbs against hsp90. Two-dimensional electrophoretic Western blots furthermore show that P2Ps make up a subset of hnRNP proteins. Cells that possess these proteins express the potential to proliferate whether or not they are traversing the cell cycle. These include rapidly growing cells, reversibly growth-arrested cells, and nonterminally differentiated cells. In contrast, cells that have irreversibly lost their proliferative potential, such as terminally differentiated cells, show a marked reduction in the abundance of P2Ps as determined by immunodetection on Western blots. A correlation, therefore, exists between the presence of this subset of nuclear proteins and the proliferative potential in two cell types. These results raise the possibility that as a subset of hnRNP proteins, P2Ps may mediate posttranscriptional control of the processing of specific RNAs required for cell proliferation. PMID:2808514

Minoo, P; Sullivan, W; Solomon, L R; Martin, T E; Toft, D O; Scott, R E

1989-11-01

285

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

PubMed

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. PMID:23872478

Dong, Rui; Yao, Rui; Du, Juan; Wang, Songlin; Fan, Zhipeng

2013-07-18

286

Marine algae possess therapeutic potential for Ca-mineralization via osteoblastic differentiation.  

PubMed

One of the important natural product investigations from marine algae is to focus on the pharmaceutically important compounds that can be applied in bone health. Osteoporosis is one of the bone diseases caused by an imbalance between bone formation and resorption. Promotion of osteoblast differentiation is one of the best therapeutic ways to combat osteoporosis. Osteoblasts are the cells responsible for bone formation by increasing the proliferation of the osteoblastic lineage or inducing differentiation of the osteoblasts. In this review, we describe the central effects of osteoblast differentiation by various bone therapy biomaterials from marine algae. PMID:22054966

Nguyen, Minh Hong Thi; Jung, Won-Kyo; Kim, Se-Kwon

2011-01-01

287

Use of serial proton magnetic resonance spectroscopy to differentiate low grade glioma from tumefactive plaque in a patient with multiple sclerosis  

Microsoft Academic Search

We report on the use of serial proton MR spectroscopy (1H MRS) to differentiate between glioma and tumefactive plaque in a known multiple sclerosis (MS) patient who developed a symptomatic cerebral space occupying lesion. Gliomas and acute MS plaques may have indistinguishable chemical resonance spectra, whereas that of chronic plaque is distinct. In our case 1H MRS demonstrated elevated concentrations

D J A Butteriss; A ISMAIL; D W ELLISON

2003-01-01

288

Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting  

PubMed Central

Background Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency. Methods Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA) or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes. Results Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B), receptors (FZD5, FZD6, FZD10), secreted inhibitors (SFRP4, SFRP1), and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine). Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi) inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines tested including NT2/D1, NT2/D1-R1, Tera-1 and 833K cells. Conclusion During induced differentiation of human EC cells, the Wnt signalling pathway is reprogrammed and canonical Wnt signalling induced. Specific species regulating non-canonical Wnt signalling conferred growth inhibition when targeted for repression in these EC cells. Notably, FZD7 repression significantly inhibited growth of human EC cells and is a promising therapeutic target for TGCTs.

2009-01-01

289

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

PubMed Central

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.

2013-01-01

290

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

PubMed

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. PMID:24154593

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

2013-10-24

291

Differential regulation of feeding rhythms through a multiple-photoreceptor system in an avian model of blindness.  

PubMed

All organisms have evolved photodetection systems to synchronize their physiology and behavior with the external light-dark (LD) cycles. In nonmammalian vertebrates, the retina, the pineal organ, and the deep brain can be photoreceptive. Inner retinal photoreceptors transmit photic information to the brain and regulate diverse nonvisual tasks. We previously reported that even after preventing extraretinal photoreception, blind GUCY1* chickens lacking functional visual photoreceptors could perceive light that modulates physiology and behavior. Here we investigated the contribution of different photoreceptive system components (retinal/pineal and deep brain photoreceptors) to the photic entrainment of feeding rhythms. Wild-type (WT) and GUCY1* birds with head occlusion to avoid extraocular light detection synchronized their feeding rhythms to a LD cycle with light >12 lux, whereas at lower intensities blind birds free-ran with a period of >24 h. When released to constant light, both WT and blind chickens became arrhythmic; however, after head occlusion, GUCY1* birds free-ran with a 24.5-h period. In enucleated birds, brain illumination synchronized feeding rhythms, but in pinealectomized birds only responses to high-intensity light (?800 lux) were observed, revealing functional deep brain photoreceptors. In chickens, a multiple photoreceptive system, including retinal and extraretinal photoreceptors, differentially contributes to the synchronization of circadian feeding behavior. PMID:23585397

Valdez, Diego J; Nieto, Paula S; Díaz, Nicolás M; Garbarino-Pico, Eduardo; Guido, Mario E

2013-04-12

292

Socioeconomic differentials in mortality risk among men screened for the Multiple Risk Factor Intervention Trial: I. White men.  

PubMed Central

OBJECTIVES: This study examined socioeconomic differentials in risk of death from a number of specific causes in a large cohort of White men in the United States. METHODS: For 300 685 White men screened for the Multiple Risk Factor Intervention Trial between 1973 and 1975, data were collected on median income of White households in the zip code of residence, age, cigarette smoking, blood pressure, serum cholesterol, previous myocardial infarction, and drug treatment for diabetes. The 31 737 deaths that occurred over the 16-year follow-up period were grouped into specific causes and related to median White family income. RESULTS: There was an inverse association between age- adjusted all-cause mortality and median family income. There was no attenuation of this association over the follow-up period, and the association was similar for the 22 clinical centers carrying out the screening. The gradient was seen for many-but not all-of the specific causes of death. Other risk factors accounted for some of the association between income and coronary heart disease and smoking-related cancers. CONCLUSIONS: Socioeconomic position, as measured by median family income of area of residence, is an important determinant of mortality risk in White men.

Smith, G D; Neaton, J D; Wentworth, D; Stamler, R; Stamler, J

1996-01-01

293

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

PubMed Central

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

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

2007-01-01

294

Diagnosis, Prognosis and Identification of Potential Therapeutic Targets of Multiple Myeloma Based on Gene Expression Profiling.  

National Technical Information Service (NTIS)

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifing genes directly involved in disease pathogensis and clinical manifestation. The present invention used gene exp...

J. D. Shaughnessy B. Barlogie F. Zhan

2005-01-01

295

Yield potential and tuber-size distribution using EVIKA multiplication methods  

Microsoft Academic Search

A plant-multiplication technique developed at the Department of Plant Biotechnology EVIKA of the Estonian Research Institute of Agriculture involves multiplying plantlets in plastic rolls on peat before transplanting them onto the field, where the first generation of seed tubers will be grown. Four possible multiplication methods of potato meristem plants were compared from the aspect of obtaining optimal-sized, disease-free seed

Marje Särekanno; Jüri Kadaja; Katrin Kotkas; Viive Rosenberg; Virge Vasar; Triin Saue; Viacheslav Eremeev

2010-01-01

296

MHP-133, a Drug with Multiple CNS Targets: Potential for Neuroprotection and Enhanced Cognition  

Microsoft Academic Search

MHP-133 is one of a novel series of compounds designed to target multiple brain substrates expected to have synergistic actions\\u000a in the treatment of cognitive and neurodegenerative disorders such as Alzheimer’s disease. The strategy was to develop compounds\\u000a with multiple targets relevant for enhancing cognition and memory, but avoiding the serious side effects attributed to high\\u000a potency cholinergic agonists. MHP-133

Jerry J. Buccafusco; James C. Powers; Maria A. Hernandez; Mark A. Prendergast; Alvin V. Terry; Ramamohana R. Jonnala

2007-01-01

297

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

PubMed Central

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

Portaccio, Emilio

2011-01-01

298

Drug resistance in multiple myeloma: cyclosporin A analogues and their metabolites as potential chemosensitizers.  

PubMed

The malignant clone in myeloma is not eradicated by chemotherapy. Cyclosporins inhibit drug transport mechanisms, particularly the multidrug transporter p-glycoprotein 170, leading to their use as chemosensitizers. In myeloma, clonotypic blood B cells represent the major drug-resistant subset. This study compares the ability of cyclosporin A analogues and metabolites to inhibit cellular transporter(s) in myeloma and normal B cells in vitro, and evaluates their potential role in vivo. Cyclosporin A (CsA), CsG, PSC 833 or SDZ 280-446, and primary CsA and CsG metabolites, were tested for their ability to inhibit drug transport mechanisms of ex vivo malignant B cells from 81 patients with multiple myeloma as compared to B cells from normal donors, as measured by the export of the dye rhodamine 123 (Rh123) using multiparameter flow cytometry. The majority of myeloma B and normal B cells had efficient transporter function as measured by their CsA-sensitive export of Rh123. CsA and CsA analogues mediated efficient inhibition of this transport. Inhibition of dye transport by normal B cells required an approximately six-fold greater concentration of the synthetic peptolide SDZ 280-446 than was needed to optimally inhibit transport by myeloma B cells. PSC 833 and CsG were inhibitory at concentrations approximately five-fold lower than were required for CsA. Assessment of inhibitory potency in vivo indicated that the in vivo chemosensitizer levels of CsA and PSC 833 exceeded the transporter inhibitory concentration by four- and 20-fold respectively. In vivo, cyclosporins are rapidly and almost completely converted to metabolites. AM1 and AM4N, primary metabolites of CsA, mediated inhibition of transport, as did CsG metabolites GM1, GM4N and GM9. AM1 and GM9 are known to reach steady-state in vivo levels that exceed the inhibitory concentration identified here by 1.1- to 1.9-fold. Thus, cyclosporin metabolites, which accumulate in the blood during infusion of CsA and other cyclosporins, are shown here to be effective chemosensitizers for normally drug-resistant myeloma cells in vitro. Cyclosporin metabolites are considered to be less toxic than the parent drugs, suggesting that novel chemosensitization strategies designed to minimize concentrations of parent drug and maximize accumulation of primary metabolites in vivo may optimize cytotoxicity to the malignant clone in myeloma. PMID:9557608

Pilarski, L M; Yatscoff, R W; Murphy, G F; Belch, A R

1998-04-01

299

Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy.  

PubMed

Tumor-associated antigens (TAAs) trigger a TAA-specific immune response, thus they are the crux of antitumor immunosurveillance. A major advance in tumor immunology in the last 20 years was marked by the verification that CTL or B-cell epitopes rather than integral TAAs induce immunoreactivity. Previous studies on the correlation between heparanase (Hpa) expression and clinical or pathological features have generally used commercial antibodies against full-length Hpa protein rather than the functional epitopes, and the antigen determinants of such antibodies have not yet been defined. In our investigation of Hpa peptide expression in gastric cancer tissues and its association with tumor invasion, metastasis and prognosis, we analyzed Hpa expression in the tissues of 132 patients with gastric cancer using tissue microarray (TMA) technology and immunohistochemical staining. Three self-developed rabbit polyclonal antibodies against Hpa multiple antigenic peptides (MAP) and one commercial polyclonal rabbit antibody against the 50-8 kDa Hpa heterodimer were used. Clinical and pathological significance was evaluated using the Chi-square test and Kaplan-Meier survival curve analysis. The results demonstrated that the positivity rates using the antibody against MAP2 and the commercial antibody were 60.6% (80/132) and 65.2% (86/132), respectively. No expression of either MAP1 or MAP3 was noted in the cancer tissues of the 132 cases. MAP2 behaved in a similar manner to the commercial antibody in that a higher Hpa expression was observed in the cancer tissues with vessel invasion, serosal involvement, distant metastasis, poor differentiation and TNM stages III and IV. Moreover, the patients with a positive Hpa expression had a far poorer prognosis, with lower one-year and five-year survival rates. Our results demonstrate that in a similar manner to full-length Hpa proteins, MAP2 expression is closely associated with the invasion, metastasis and prognosis of gastric cancer. This finding may be of potential use in clinical therapy and in estimating the prognosis of a tumor. PMID:22807984

Zhang, Jun; Yang, Jianmin; Han, Xiaomei; Zhao, Zhongsheng; DU, Ling; Yu, Tong; Wang, Huiju

2012-05-01

300

Directed differentiation into neural lineages and therapeutic potential of porcine embryonic stem cells in rat Parkinson's disease model.  

PubMed

This study was conducted to direct porcine embryonic stem (pES) cells differentiating into neural lineages and to investigate therapeutic potential of GFP-expressing pES (pES/GFP(+)) in the rat model of Parkinson's disease (PD). Directed differentiation of pES into neural lineages was induced by suspension culture in medium containing RA, SHH, and FGF combinations without going through embryoid body formation. A high yield of nestin-expressing neural precursors was found in all treatments on day 2 after the 12-day induction. On day 6 after replating, more than 86.2 and 83.4% of the differentiated cells stained positively for NFL and MAP2, respectively. The expression of TH, ChAT, and GABA specific markers were also observed in these NFL-positive neural cells. The undifferentiated pES/GFP(+) cells and their neuronal differentiation derivatives were transplanted into the Sprague-Dawley (SD) rat's brain, and their survival and development was determined by using live animal fluorescence optical imaging system every 15 days. The results showed that fluorescent signals from the injection site of SD rats' brain could be detected through the experimental period of 3 months. The level of fluorescent signal detected in the treatment group was twofold that of the control group. The results of behavior analysis showed that PD rats exhibited stably decreased asymmetric rotations after transplantation with pES/GFP(+)-derived D18 neuronal progenitors. The dopaminergic differentiation of grafted cells in the brain was further confirmed by immunohistochemical staining with anti-TH, anti-DA, and anti-DAT antibodies. These results suggested that the differentiation approach we developed would direct pES cells to differentiate into neural lineages and benefit the development of novel therapeutics involving stem cell transplantation. PMID:20698783

Yang, Jenn-Rong; Liao, Chia-Hsin; Pang, Cheng-Yoong; Huang, Lynn Ling-Huei; Lin, Yu-Ting; Chen, Yi-Ling; Shiue, Yow-Ling; Chen, Lih-Ren

2010-08-01

301

Comparison of the neural differentiation potential of human mesenchymal stem cells from amniotic fluid and adult bone marrow.  

PubMed

Human mesenchymal stem cells (MSCs) are considered a promising tool for cell-based therapies of nervous system diseases. Bone marrow (BM) has been the traditional source of MSCs (BM-MSCs). However, there are some limitations for their clinical use, such as the decline in cell number and differentiation potential with age. Recently, amniotic fluid (AF)-derived MSCs (AF-MSCs) have been shown to express embryonic and adult stem cell markers, and can differentiate into cells of all three germ layers. In this study, we isolated AF-MSCs from second-trimester AF by limiting dilution and compared their proliferative capacity, multipotency, neural differentiation ability, and secretion of neurotrophins to those of BM-MSCs. AF-MSCs showed a higher proliferative capacity and more rapidly formed and expanded neurospheres compared to those of BM-MSCs. Both immunocytochemical and quantitative real-time PCR analyses demonstrated that AF-MSCs showed higher expression of neural stemness markers than those of BM-MSCs following neural stem cell (NSC) differentiation. Furthermore, the levels of brain-derived growth factor and nerve growth factor secreted by AF-MSCs in the culture medium were higher than those of BM-MSCs. In addition, AF-MSCs maintained a normal karyotype in long-term cultures after NSC differentiation and were not tumorigenic in vivo. Our findings suggest that AF-MSCs are a promising and safe alternative to BM-MSCs for therapy of nervous system diseases. PMID:23478940

Yan, Zhong-Jie; Hu, Yu-Qin; Zhang, Hong-Tian; Zhang, Peng; Xiao, Zong-Yu; Sun, Xin-Lin; Cai, Ying-Qian; Hu, Chang-Chen; Xu, Ru-Xiang

2013-03-12

302

Differential enantioselectivity of quizalofop ethyl and its acidic metabolite: direct enantiomeric separation and assessment of multiple toxicological endpoints.  

PubMed

Transformation products usually differ in environmental and toxicological properties compared to the parent contaminants, thus causing potential and unknown environmental risks. To elucidate differential chiral recognition of the aryloxypropanoate herbicide quizalofop ethyl (QE) and its primary product (quizalofop acid, QA), their enantiomeric separation and toxicological impacts to two freshwater algae were investigated. Addition of trace water (0.02-0.08%, v/v) to the mobile phase selectively affected retention of analyte and induced simultaneous enantio-separation for the two compounds with intrinsical water-specific resolution mechanisms, although they both possessed a chiral center in the 2-position of propionates. In algal suspensions, QE was rapidly degraded to produce the acid metabolite (QA), and the product further declined, whereas a reduction of QA as starting compound did not occur. Uptake and/or transformation of QE and QA were found a lack of enantioselectivity and isomer inversion, while cellular membrane permeability, membrane potential and algal growth showed enantioselectivity to different extents. These results suggested the presence of receptor chirality that was involved in the toxicological processes but invalid for uptake and transformation. Therefore, quizalofop acid, identified as environmentally relevant contaminant associated with application of the herbicide, participated in the toxicological processes of the parent compound, and exhibited distinct toxicological and chromatographic retention properties. PMID:21159424

Zhang, Xiaoxiang; Wang, Se; Wang, Yu; Xia, Tingting; Chen, Jingwen; Cai, Xiyun

2010-11-27

303

Neural Differentiation Potentiated by the Leukaemia Inhibitory Factor through STAT3 Signalling in Mouse Embryonal Carcinoma Cells  

Microsoft Academic Search

LIF is a cytokine playing a key role in the regulation of self-renewal and maintenance of undif- ferentiated state in mouse ES cells. The response of pluripotent cells to LIF is mediated mainly by the STAT3 and ERK signalling pathways. Recently, we have shown that LIF potentiated retinoic acid-in- duced neural differentiation of pluripotent mouse embryonal carcinoma P19 cells. Here

J. PACHERNÍK; V. HORVÁTH; L. KUBALA; P. DVO?ÁK; A. KOZUBÍK; A. HAMPL

304

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

Microsoft Academic Search

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

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

1999-01-01

305

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

SciTech Connect

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

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

2011-10-03

306

Polar agents with differentiation inducing capacity potentiate tumor necrosis factor-mediated cytotoxicity in human myeloid cell lines  

Microsoft Academic Search

Cotreatment or pretreatment of several hu- man myeloid cell lines (KG!, HL6O, U937, THP1) with the differentiation inducer DMSO was found to potenti- ate the antiproliferative and cytotoxic effects of TNF. In addition, TNF-resistant monocytic cell lines could be sen- sitized to TNF cytotoxicity by DMSO treatment. Other highly polar molecules, known to be potent differentia- tion inducers, showed similar

Stany Depraetere; Bart Vanhaesebroeckt; Walter Fierst; Jean Willems; Marcel Joniau

307

Multiple follicular hamartomas with sweat gland and sebaceous differentiation, vermiculate atrophoderma, milia, hypotrichosis, and late development of multiple basal cell carcinomas  

Microsoft Academic Search

We describe a 46-year-old woman with multiple symmetrical papulocystic lesions on the face, neck, chest, back, and upper arms since childhood. Vermiculate atrophoderma, entropion, and progressive loss of eyelashes was also noted. Since the age of 30, 12 basal cell carcinomas have developed on the face. Histopathologic examination revealed multiple anastomosing nests and strands that arose from the lower part

Ramon M. Pujol; Cristina Nadal; Xavier Matias-Guiu; Jordi Peyrí; Carlos Ferrándiz; J Palou; José M. de Moragas

1998-01-01

308

Inverse differentiation pathway by multiple mafic magma refilling in the last magmatic activity of Nisyros Volcano, Greece  

NASA Astrophysics Data System (ADS)

Based on detailed field, petrographic, chemical, and isotopic data, this paper shows that the youngest magmas of the active Nisyros volcano (South Aegean Arc, Greece) are an example of transition from rhyolitic to less evolved magmas by multiple refilling with mafic melts, triggering complex magma interaction processes. The final magmatic activity of Nisyros was characterized by sub-Plinian caldera-forming eruption (40 ka), emplacing the Upper Pumice (UP) rhyolitic deposits, followed by the extrusion of rhyodacitic post-caldera domes (about 31-10 ka). The latter are rich in magmatic enclaves with textural and compositional (basaltic-andesite to andesite) characteristics that reveal they are quenched portions of mafic magmas included in a cooler more evolved melt. Dome-lavas have different chemical, isotopic, and mineralogical characteristics from the enclaves. The latter have lower 87Sr/86Sr and higher 143Nd/144Nd values than dome-lavas. Silica contents and 87Sr/86Sr values decrease with time among dome-lavas and enclaves. Micro-scale mingling processes caused by enclave crumbling and by widespread mineral exchanges increase from the oldest to the youngest domes, together with enclave content. We demonstrate that the dome-lavas are multi-component magmas formed by progressive mingling/mixing processes between a rhyolitic component ( post-UP) and the enclave-forming mafic magmas refilling the felsic reservoir (from 15 wt.% to 40 wt.% of mafic component with time). We recognize that only the more evolved enclave magmas contribute to this process, in which recycling of cumulate plagioclase crystals is also involved. The post-UP end-member derives by fractional crystallization from the magmas leftover after the previous UP eruptions. The enclave magma differentiation develops mainly by fractional crystallization associated with multiple mixing with mafic melts changing their composition with time. A time-related picture of the relationships between dome-lavas and relative enclaves is proposed, suggesting a delay between a mafic magma input and the relative dome outpouring. We also infer that the magma viscosity reduction by re-heating allows dome extrusion without explosive activity.

Braschi, Eleonora; Francalanci, Lorella; Vougioukalakis, Georges E.

2012-07-01

309

Differentiation potential and GFP labeling of sheep bone marrow-derived mesenchymal stem cells.  

PubMed

Mesenchymal stem cells (MSCs) are an important cell population in the bone marrow microenvironment. MSCs have the capacity to differentiate in vitro into several mesenchymal tissues including bone, cartilage, fat, tendon, muscle, and marrow stroma. This study was designed to isolate, expand, and characterize the differentiation ability of sheep bone marrow-derived MSCs and to demonstrate the possibility to permanently express a reporter gene. Bone marrow was collected from the iliac crest and mononuclear cells were separated by density gradient centrifugation. Sheep MSCs cell lines were stable characterized as CD44+ and CD34- and then transfected with a green fluorescent protein (GFP) reporter gene. The GFP expression was maintained in about half (46.6%) of cloned blastocysts produced by nuclear transfer of GFP+ sheep MSCs, suggesting the possibility to establish multipotent embryonic cells' lines carrying the fluorescent tag for comparative studies on the differentiation capacity of adult stem cells (MSCs) versus embryonic stem cells. We found that sheep MSCs under appropriate culture conditions could be induced to differentiate into adipocytes, chondrocytes, and osteoblast lineages. Our results confirm the plasticity of sheep MSCs and establish the foundation for the development of a pre-clinical sheep model to test the efficiency and safety of cell replacement therapy. PMID:22886939

Czernik, Marta; Fidanza, Antonella; Sardi, Martina; Galli, Cesare; Brunetti, Dario; Malatesta, Daniela; Della Salda, Leonardo; Matsukawa, Kazutsugu; Ptak, Grazyna E; Loi, Pasqualino

2013-01-01

310

Differential scanning calorimetry: A potential tool for discrimination of olive oil commercial categories  

Microsoft Academic Search

Differential scanning calorimetry thermograms of five commercial categories of olive oils (extra virgin olive oil, olive oil, refined olive oil, olive-pomace oil and refined olive-pomace oil) were performed in both cooling and heating regimes. Overlapping transitions were resolved by deconvolution analysis and all thermal properties were related to major (triacylglycerols, total fatty acids) and minor (diacylglycerols, lipid oxidation products) chemical

Emma Chiavaro; Maria Teresa Rodriguez-Estrada; Carlo Barnaba; Elena Vittadini; Lorenzo Cerretani; Alessandra Bendini

2008-01-01

311

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression  

Microsoft Academic Search

BACKGROUND: In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing

Katrin Montzka; Nina Lassonczyk; Beate Tschöke; Sabine Neuss; Tobias Führmann; Rachelle Franzen; Ralf Smeets; Gary A Brook; Michael Wöltje

2009-01-01

312

Human Keratinocyte Growth and Differentiation on Acellular Porcine Dermal Matrix in relation to Wound Healing Potential  

PubMed Central

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7–10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing.

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Konigova, Radana; Matouskova, Eva

2012-01-01

313

Potential Sources of Differential Item Functioning in the Adaptation of Tests  

Microsoft Academic Search

This report shows a classification of differential item functioning (DIF) sources that have an effect on the adaptation of tests. This classification is based on linguistic and cultural criteria. Four general DIF sources are distinguished: cultural relevance, translation problems, morph syntactical differences, and semantic differences. The influence of these on the adaptation of tests is greater among those languages belonging

Paula Elosua; Alicia López-jaúregui

2007-01-01

314

Single-cell clones of liver cancer stem cells have the potential of differentiating into different types of tumor cells.  

PubMed

Cancer stem cells (CSCs) are believed to be a promising target for cancer therapy because these cells are responsible for tumor development, maintenance and chemotherapy resistance. Finding out the critical factors regulating CSC fate is the key for target therapy of CSCs. Just as normal stem cells are regulated by their microenvironment (niche), CSCs are also regulated by cells in the tumor microenvironment. However, whether various tumor microenvironments can induce CSCs to differentiate into different cancer cells is not clear. Here, we show that single-cell-cloned CSCs, accidentally obtained from a human liver cancer microvascular endothelial cells, express classic stem cell markers, genes associated with self-renewal and pluripotent factors and possess colony-forming ability in vitro and the ability of serial transplantation in vivo. The single-cell-cloned CSCs treated with the different tumor cell/tissue-derived conditioned culture medium, which is a mimic of carcinoma microenvironment, could differentiate into corresponding tumor cells and express specific markers of the respective type of tumor cells at the gene, protein and cell levels, respectively. Interestingly, this multilineage differentiation potential of single-cell-cloned liver CSCs sharply declined after the specific knockdown of octamer-binding transcription factor 4 (Oct4) alone, even though they were under the same induction conditions (carcinoma microenvironments). These data support the hypothesis that single-cell-cloned liver CSCs have the potential of differentiating into different types of tumor cells, and the tumor microenvironment does play a crucial role in deciding differentiation directions. Simultaneously, Oct4 in CSCs is indispensable in this process. These factors are promising targets for liver CSC-specific therapy. PMID:24136221

Liu, H; Zhang, W; Jia, Y; Yu, Q; Grau, G E; Peng, L; Ran, Y; Yang, Z; Deng, H; Lou, J

2013-10-17

315

Follicular lymphoma tumor-infiltrating T-helper (T(H)) cells have the same polyfunctional potential as normal nodal T(H) cells despite skewed differentiation.  

PubMed

The follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4(+) T-helper cells (T(H)) compared with reactive and normal lymph node (NLN) T(H) cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory T(H) cells. We further show differences in the distribution and anatomical localization of CXCR5(+) T(H) populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as T(H)2 and T(H)17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of T(H)1 and polyfunctional T(H) cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although T(H)-cell differentiation in FL is skewed compared with NLNs, FL T(H) cells should have the same intrinsic ability to elicit antitumor effector responses as NLN T(H) cells when tumor suppressive mechanisms are attenuated. PMID:21821704

Hilchey, Shannon P; Rosenberg, Alexander F; Hyrien, Ollivier; Secor-Socha, Shelley; Cochran, Matthew R; Brady, Michael T; Wang, Jyh-Chiang E; Sanz, Ińaki; Burack, W Richard; Quataert, Sally A; Bernstein, Steven H

2011-08-05

316

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

Microsoft Academic Search

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

Dimitrios Karussis; Ibrahim Kassis

2008-01-01

317

Evasion of multiple, intelligent pursuers in a stationary, cluttered environment: a harmonic potential field approach  

Microsoft Academic Search

In this paper an intelligent controller is suggested for the evasive navigation of an agent that is engaging multiple pursuers in a stationary environment. The controller is required to generate a sequence of directions to guide the motion of an evader so that it will be able to escape a group of pursuers while avoiding a set of forbidden regions

Ahmad A. Masoud; Saudia Arabia

2002-01-01

318

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

Microsoft Academic Search

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

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

2010-01-01

319

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

320

Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential  

Microsoft Academic Search

In 1890, Uhthoff studied multiple sclerosis (MS) patients who developed amblyopia following exercise, a phenomenon later discovered to be secondary to elevated body temperature from muscular activity. Six decades later, the hot bath test and various other heating reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and

Thomas C. Guthrie; Dewey A. Nelson

1995-01-01

321

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

PubMed

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

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

2010-05-23

322

Comparative proteomics of glioma stem cells and differentiated tumor cells identifies S100A9 as a potential therapeutic target.  

PubMed

Recent studies have suggested the existence of a small subset of cancer cells called cancer stem cells (CSCs), which possess the ability to initiate malignancies, promote tumor formation, drive metastasis, and evade conventional chemotherapies. Elucidation of the specific signaling pathway and mechanism underlying the action of CSCs might improve the efficacy of cancer treatments. In this study, we analyzed differentially expressed proteins between glioma stem cells and differentiated tumor cells isolated from the human glioma cell line, U251, via iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis to identify proteins correlated with specific features of CSCs. Out of a total data set of 559 identified proteins, 29 proteins were up-regulated in the glioma stem cells when compared with the differentiated cells. Interestingly, The expression level of S100A9 was fivefold higher in glioma stem cells than differentiated cells. Similar results were also observed in glioma stem cells derived from other glioma cells. More importantly, knockdown of S100A9 by RNA interference suppressed the proliferation of glioma stem cell line and decreased the growth of xenograft tumors in vivo. Taken together, these results indicate that the tumorigenesis potential of CSCs arises from highly expressed S100A9. J. Cell. Biochem. 114: 2795-2808, 2013. © 2013 Wiley Periodicals, Inc. PMID:23836528

Chen, Song; Zhao, Hongxin; Deng, Jinmu; Liao, Peng; Xu, Zhongye; Cheng, Yuan

2013-12-01

323

Naive and memory B cells respond differentially to T-dependent signaling but display an equal potential for differentiation toward the centroblast-restricted CD77/globotriaosylceramide phenotype.  

PubMed

Resting (CD38(low)) tonsillar B cells differentiate to express the centroblast-restricted CD77/globotriaosylceramide antigen on high-level engagement of CD154. As the CD38(low) population comprises both naive and memory subsets, we wished to compare the propensity of each to develop this germinal center phenotype; particularly as the capacity of memory B cells to re-enter afollicular reaction remains unclear. Resting B lymphocytes were therefore separated into CD27(-)IgA(-)IgG(-) and IgD(-) fractions to generate subsets enriched for naive and memory cells, respectively. Following stimulation via BCR and/or CD40 - surrogate signals for B cells engaged in T-dependent signaling - differences between the two subsets were seen in the kinetics and/or magnitude of responses such as entry into DNA synthesis, induction of the costimulatory molecules CD80 and CD86; up-regulation of CD23, and changes in BCL-6 mRNA expression. Nevertheless, naive and memory cells revealed a nigh identical capacity for acquiring CD77: both appeared equally sensitive in this regard, with high-level CD40 engagement via cell-bound CD154 being required for both subsets to achieve the hallmark centroblast phenotype. These findings suggest that, provided with the opportunity to encounter cell membrane CD154 in abundance, both naive and memory B cells display the potential to be diverted towards a germinal center pathway of differentiation. PMID:12811849

Gagro, Alenka; Toellner, Kai-Michael; Grafton, Gillian; Servis, Drazen; Branica, Sre?ko; Radojci?, Vedran; Kosor, Ela; Hrabak, Maja; Gordon, John

2003-07-01

324

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

PubMed

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

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

2012-04-27

325

Potential of an electronic nose for the early detection and differentiation between Streptomyces in potable water  

Microsoft Academic Search

Much attention has been focused on the production of musty-aroma compounds such as geosmin and their impact on the quality of fresh water and water-cultured raised fish and sea-food. At present, there are no efficient means of removing these off-flavours from water. Therefore, the rapid detection of geosmin-producing microorganisms, in particular the genus Streptomyces, at early stages of differentiation, is

A. Catarina Bastos; Naresh Magan

2006-01-01

326

Reduced Differentiation Potential of Primary MyoD-\\/- Myogenic Cells Derived from Adult Skeletal Muscle  

Microsoft Academic Search

To gain insight into the regeneration deficit of MyoD 2 \\/ 2 muscle, we investigated the growth and differentiation of cultured MyoD 2 \\/ 2 myogenic cells. Primary MyoD 2 \\/ 2 myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD 2

Luc A. Sabourin; Adele Girgis-Gabardo; Patrick Seale; Atsushi Asakura; Michael A. Rudnicki

1999-01-01

327

Identification of New Differentially Methylated Genes That Have Potential Functional Consequences in Prostate Cancer  

PubMed Central

Many differentially methylated genes have been identified in prostate cancer (PCa), primarily using candidate gene-based assays. Recently, several global DNA methylation profiles have been reported in PCa, however, each of these has weaknesses in terms of ability to observe global DNA methylation alterations in PCa. We hypothesize that there remains unidentified aberrant DNA methylation in PCa, which may be identified using higher resolution assay methods. We used the newly developed Illumina HumanMethylation450 BeadChip in PCa (n?=?19) and adjacent normal tissues (n?=?4) and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in PCa development and progression. We also confirmed our methylation results in an independent data set. Two aberrant DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG sites showed significant differences in DNA methylation (FDR adjusted P<0.05), defined as a mean methylation difference of at least 20% between PCa and normal samples. Furthermore, a total of 122 genes had more than one differentially methylated CpG site in their promoter region and a gene expression pattern that was inverse to the direction of change in DNA methylation (e.g. decreased expression with increased methylation, and vice-versa). Aberrant DNA methylation of two genes, AOX1 and SPON2, were confirmed via bisulfate sequencing, with most of the respective CpG sites showing significant differences between tumor samples and normal tissues. The AOX1 promoter region showed hypermethylation in 92.6% of 54 tested PCa samples in contrast to only three out of 53 tested normal tissues. This study used a new BeadChip combined with gene expression data in PCa to identify novel differentially methylated CpG sites located within genes. The newly identified differentially methylated genes may be used as biomarkers for PCa diagnosis.

Kim, Jin W.; Kim, Seong-Tae; Turner, Aubrey R.; Young, Tracey; Smith, Shelly; Liu, Wennuan; Lindberg, Johan; Egevad, Lars; Gronberg, Henrik; Isaacs, William B.; Xu, Jianfeng

2012-01-01

328

Differential scanning calorimetry: a potential tool for discrimination of olive oil commercial categories.  

PubMed

Differential scanning calorimetry thermograms of five commercial categories of olive oils (extra virgin olive oil, olive oil, refined olive oil, olive-pomace oil and refined olive-pomace oil) were performed in both cooling and heating regimes. Overlapping transitions were resolved by deconvolution analysis and all thermal properties were related to major (triacylglycerols, total fatty acids) and minor (diacylglycerols, lipid oxidation products) chemical components. All oils showed two well distinguishable exothermic events upon cooling. Crystallization enthalpies were significantly lower in olive oils due to a more ordered crystal structure, which may be related to the higher triolein content. Pomace oils exhibited a significantly higher crystallization onset temperature and a larger transition range, possibly associated to the higher amount of diacylglycerols. Heating thermograms were more complex: all oils exhibited complex exo- and endothermic transitions that could differentiate samples especially with respect to the highest temperature endotherm. These preliminary results suggest that both cooling and heating thermograms obtained by means of differential scanning calorimetry may be useful for discriminating among olive oils of different commercial categories. PMID:18724997

Chiavaro, Emma; Rodriguez-Estrada, Maria Teresa; Barnaba, Carlo; Vittadini, Elena; Cerretani, Lorenzo; Bendini, Alessandra

2008-07-29

329

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

PubMed Central

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.

Jackson, WesleyM.; Lozito, Thomas; Djouad, Farida; Kuhn, Nastaran Z.; Nesti, Leon J.; Tuan, Rocky S.

2010-01-01

330

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.

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

2012-01-01

331

A reassessment of sensory evoked potential parameters in multiple sclerosis: a discriminant analysis approach.  

PubMed Central

The sensitivity of the different parameters (absolute latency, interwave latency, latency asymmetry, amplitude) of both cervical and cerebral responses evoked by stimulation of the median nerve at the wrist was assessed in patients with multiple sclerosis by discriminant analysis. The peak latency of N13 or N20 SEP components or both was found to be more sensitive than their amplitude, provided that a preliminary covariation with the height of the subjects was performed. The measurement of latency asymmetry between the two sides increased the test's sensitivity, while amplitude asymmetry turned out to be of little diagnostic value. A linear discriminant function with four variates (that is mean amplitude, mean latency, latency asymmetry and height of the subject) was computed to summarise the information provided by the different parameters to give a rapid and exact method for the assessment of SEP abnormalities in multiple sclerosis patients.

Abbruzzese, G; Cocito, L; Ratto, S; Abbruzzese, M; Leandri, M; Favale, E

1981-01-01

332

Brain Stem Magnetic Resonance Imaging and Evoked Potential Studies of Symptomatic Multiple Sclerosis Patients  

Microsoft Academic Search

In this study we evaluated the sensitivity of neuroradiological and neurophysi-ological tests for detecting brain stem (BS) lesions in multiple sclerosis patients, since the recent introduction of the gradient motion rephasing technique has markedly increased the image quality of magnetic resonance imaging (MRI). From 50 MS patients (33 women and 17 men; mean age 35.9 ± 8.3 years; mean duration

G. Comi; M. Filippi; V. Martinelli; G. Scotti; T. Locatelli; S. Medaglini; F. Triulzi; M. Rovaris; N. Canal

1993-01-01

333

Oxidative Stress in Multiple Sclerosis Pathology and Therapeutic Potential of Nrf2 Activation  

Microsoft Academic Search

\\u000a Reactive oxygen species contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct\\u000a pathological processes. To counteract the detrimental effects of reactive oxygen species, the central nervous system is endowed\\u000a with a protective mechanism consisting of enzymatic and nonenzymatic antioxidants. Expression of most antioxidant enzymes\\u000a is regulated through the transcription factor nuclear factor-E2-related factor (Nrf2),

Helga E. de Vries; Gerty Schreibelt; Jack van Horssen

334

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

Microsoft Academic Search

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 of 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

I. Katz; M. J. Mandell

1982-01-01

335

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

NASA Astrophysics Data System (ADS)

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 of 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.

1982-06-01

336

The multiple facets of the TGF-? family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1.  

PubMed

GDF-15 (also MIC-1, NAG-1, PLAB, PTGFB) is a member of the TGF-? superfamily, which is widely distributed in mammalian tissues and has been shown to play multiple roles in various pathologies, including inflammation, cancer, cardiovascular diseases, and obesity. GDF-15 serum levels are a highly reliable predictor of disease progression. Both the anti-tumorigenic potential of GDF-15 and its capacity to promote metastasis have been documented for a large variety of cancers, yet its opposing functions, which are typical for members of the TGF-? superfamily, have only partly been resolved on the molecular level. Knowledge on physiological functions in the non-diseased organism is scarce. In the nervous system GDF-15 knockout analyses have revealed that GDF-15 is essential for the postnatal maintenance of various neuron populations. When applied exogenously GDF-15 is a powerful factor for promoting survival of developing and lesioned neurons in vitro and in vivo. Receptor activation by GDF-15 has only been partially resolved. PMID:23787157

Unsicker, Klaus; Spittau, Björn; Krieglstein, Kerstin

2013-06-18

337

Multiple effects of ? -adrenoceptor stimulation on the action potential of the rabbit atrium  

Microsoft Academic Search

Effects of ?-adrenoceptor stimulation by phenylephrine (10?7–10?4 mol\\/l) in the presence of pindolol (10?7 mol\\/l) on the action potential and force of contraction were observed in the rabbit left atrium.

Y. Miura; J. Inui

1984-01-01

338

Quality-of-service differentiation by multilength variable-weight time-and-frequency-hopping optical orthogonal codes in optical code-division multiple-access networks  

NASA Astrophysics Data System (ADS)

We consider multilength variable-weight time-and-frequency-hopping (TFH) codes for optical code-division multiple-access (CDMA) networks. To design a TFH code that can support differentiated requirements on transmission rates (TRs) and bit error rates (BERs), we propose a general construction method for two-dimensional optical CDMA code sequences with arbitrary code lengths and variable code weights. The cross-correlation peak and the autocorrelation sidelobe of the proposed code are made to be at most '1' and '0', respectively, for any pair of different-length and different-weight code sequences. We show that the ratio between signal-to-interference ratios (SIRs) of the codes with different weight and length can effectively be approximated by the ratio of the code weights, regardless of the code lengths for the proposed codes. Therefore, independent adjustment of code length and weight can differentiate TR and BER for multiple service classes, and it simplifies code design for the service differentiation. We also demonstrate BER performances under various conditions and corroborate that the proposed codes accomplish accurate and fine-tuned differentiation of TR and BER compared to the fixed-weight or fixed-length codes.

Lee, Chung-Keun; Kim, Jinsoo; Seo, Seung-Woo

2006-08-01

339

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

340

Potential of Dual Time Point FDG-PET Imaging in Differentiating Malignant from Benign Pleural Disease  

Microsoft Academic Search

Aim  The aim of this study was to assess the utility of dual time point 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging in differentiating benign from malignant pleural disease.\\u000a \\u000a \\u000a \\u000a Methods  Fifty-five consecutive patients of suspected malignant pleural mesothelioma (MPM) and recurrence of MPM who were referred\\u000a for the evaluation underwent two sequential 18F-FDG-PET scans (dual time point imaging). The average percent change in

Ayse Mavi; Sandip Basu; Tevfik F. Cermik; Muammer Urhan; Mehdi Bathaii; Dhurairaj Thiruvenkatasamy; Mohamed Houseni; Simin Dadparvar; Abass Alavi

2009-01-01

341

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

PubMed Central

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

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

2011-01-01

342

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

National Technical Information Service (NTIS)

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

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

2010-01-01

343

Multiple transcripts of the murine immunoglobulin ? membrane locus are generated by alternative splicing and differential usage of two polyadenylation sites  

Microsoft Academic Search

The human C? gene produces a number of alternatively spliced heavy chain transcripts of which some encode functional IgE isoforms. We now show that differentially processed ? mRNA variants also exist in the mouse and are generated by differential polyadenylation and alternative splicing of primary ? chain transcripts. The two poly(A) sites of the mouse membrane transcripts were identified in

Shubha Anand; Facundo D. Batista; Tatiana Tkach; Dimitar G. Efremov; Oscar R. Burrone

1997-01-01

344

Gene expression profiles in 3D tumor analogs indicate compressive strain differentially enhances metastatic potential.  

PubMed

Non-physiological mechanobiological stimuli typically occur in tumors and are considered to promote cancer spreading. Non-fluid related pressure (solid stress), which arises as tumors grow against adjacent tissues, is among the least studied endogenous stimuli due to challenges in replicating the in vivo environment. To this end, the novel devices well-pressor and the videomicroscopy-compatible optic-pressor were developed to exert precise compressive strain on cells in 3D gels in absence of other mechanical stimuli and soluble gradients. Glioblastoma (U87, HGL21) and breast cancer (MDA-MB-231) cells in 1% agarose hydrogels were exposed to 50% compressive strain for 3 h (0.25-0.05 kPa). Live imaging showed that cells elongate and deflect vertically to the load. This stimulation is shown for the first time to differentially regulate metastasis-associated genes. Furthermore, a group of differentially expressed genes was identified in all cell types, both by microarrays and confirmed by RT-PCR for select genes (caveolin-1, integrin-?1, Rac1), indicating shared response mechanisms. These genes are functionally linked and involved in decreasing cell-cell contact, increasing ECM degradation, and ultimately promoting invasion. Caveolin could orchestrate these responses while the uPA and PI3K/Akt systems could play major roles. Future work will focus on specific molecular partnerships under compression and their impact on cancer progression. PMID:20559731

Demou, Zoe N

2010-06-18

345

Evaluation of water-in-oil-in-water multiple emulsion and microemulsion as potential adjuvants for immunization with rabies antigen.  

PubMed

Water-in-oil-in-water (W/O/W) multiple emulsions and microemulsions have been studied as potential candidates to be formulated as adjuvants. In this work their application as adjuvants for rabies virus immunization was studied. The humoral response, the effective dose 50 and histology for the developed formulations were evaluated in mice and compared with those from traditional adjuvants. The microemulsion and W/O/W multiple emulsion adjuvants developed were able to induce humoral response in mice and the serum showed good in vivo protection. Compared to the other adjuvants evaluated, microemulsion was shown to be the best candidate for rabies immunization as it presented good potency against the virus and did not appear to cause any local reaction. PMID:21627989

Leclercq, Sophie Yvette; dos Santos, Roberta Márcia Marques; Macedo, Ludmila Branco; Campos, Patrícia Cota; Ferreira, Tatiane Campos; de Almeida, Joăo Gomes; Seniuk, Joăo Gabriel Toledo; Serakides, Rogéria; Silva-Cunha, Armando; Fialho, Sílvia Ligório

2011-05-24

346

The increasing incidence and prevalence of female multiple sclerosis--a critical analysis of potential environmental factors.  

PubMed

Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two women for every man with a diagnosis of MS, recent serial cross-sectional assessments provide compelling evidence for an increase of the female to male sex ratio in patients with relapsing-remitting MS over the last decades. An understanding of this phenomenon might provide key insights into the pathogenesis of the disease but also may have implications for health-care strategies and further research efforts. We review possible etiologies for the gender disparity in MS, and we discuss possible underlying causes. We determined that the biologically most plausible explanations for a disproportional increase of MS among women in some population may be the role of vitamin D in MS pathogenesis. Decreased sun exposure may be a critical factor in diminished vitamin D levels in many recent cohort studies. Vitamin D insufficiency or deficiency has been shown to affect T cell differentiation and regulation, which may affect cellular immune responses against autoantigens and pathogens that have been associated with the etiology of MS. Vitamin D also appears to impact B cell activation and differentiation, another cell type that has been implicated in the inflammatory cascade underlying CNS autoimmune disease. PMID:21354338

Sellner, Johann; Kraus, Jörg; Awad, Amer; Milo, Ron; Hemmer, Bernhard; Stüve, Olaf

2011-02-24

347

A family of fundamental solutions for elliptic quaternion coefficient differential operators and application to perturbation results for single layer potentials  

NASA Astrophysics Data System (ADS)

In this note we announce some of the results that will be presented in a forthcoming paper by the authors, and which are concerned about the construction of a family of fundamental solutions for elliptic partial differential operators with quaternion constant coefficients. The elements of such a family are functions which depend jointly real analytically on the coefficients of the operators and on the spatial variable. A detailed description of such fundamental solutions has been deduced in order to study regularity and stability properties in the frame of Schauder spaces for the corresponding layer potentials.

Dalla Riva, M.; Morais, J.; Musolino, P.

2012-11-01

348

Differential potential for envelope glycoprotein-mediated steric shielding of host cell surface proteins among filoviruses.  

PubMed

The viral envelope glycoprotein (GP) is thought to play important roles in the pathogenesis of filovirus infection. It is known that GP expressed on the cell surface forms a steric shield over host proteins such as major histocompatibility complex class I and integrin ?1, which may result in the disorder of cell-to-cell contacts and/or inhibition of the immune response. However, it is not clarified whether this phenomenon contributes to the pathogenicity of filoviruses. In this study, we found that the steric shielding efficiency differed among filovirus strains and was correlated with the difference in their relative pathogenicities. While the highly glycosylated mucin-like region of GP was indispensable, the differential shielding efficiency did not necessarily depend on the primary structure of the mucin-like region, suggesting the importance of the overall properties (e.g., flexibility and stability) of the GP molecule for efficient shielding of host proteins. PMID:24074577

Noyori, Osamu; Matsuno, Keita; Kajihara, Masahiro; Nakayama, Eri; Igarashi, Manabu; Kuroda, Makoto; Isoda, Norikazu; Yoshida, Reiko; Takada, Ayato

2013-08-28

349

A Multiple Stakeholder View of the Potential for Hoop Structures in Iowa Swine Production  

Microsoft Academic Search

A survey of Iowa farmers and nonfarmers was conducted to determine public perceptions about the potential impacts of hoop structures on Iowa swine production and support for public research on hoop structures. Stakeholder groups included hog farmers using hoop structures; hog farmers not using hoop structures, farmers not raising hogs; veterinarians, vocational agricultural teachers, and agricultural lenders; and Iowa State

C. C. Hinrichs; J. Tranquilla

1998-01-01

350

Event-related potential repetition effect in alzheimer's patients: Multiple repetition priming with pictures  

Microsoft Academic Search

The most notable symptom in probable Alzheimer's disease (PAD) is a profound deficit on direct or explicit memory tasks. In many cases these same patients show performance similar to normal controls on indirect or implicit memory tasks. During indirect testing, recent studies have shown that many PAD subjects have an intact event-related potential (ERP) repetition effect, which is thought to

Victoria A. Kazmerski; David Friedman; Sean Hewitt

1995-01-01

351

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-Muńoz, Rosa; Muńoz-Delgado, Encarnación; Rodriguez-Braun, Edith; Conesa, Ana; Pérez-Guillermo, Miguel

2012-06-28

352

Glypican-3 as a potential differential diagnosis marker for hepatocellular carcinoma: a tissue microarray-based study.  

PubMed

The differential diagnosis between hepatocellular carcinoma (HCC) and benign hepatic lesions is still difficult and new biochemical markers for HCC are required. The aim of this study was to assess the differential diagnostic value of glypican-3 (GPC3) immunostaining in HCC patients. 147 cases of surgically excised HCC tissues, 94 cases from needle biopsies, and tissue microarrays were used for this study. The tissue microarrays contained 449 specimens including: 115 HCC, 25 intrahepatic cholangiocellular carcinoma, 29 lung adenocarcinoma, 23 squamous cell lung carcinoma, 53 ovary adenocarcinoma, 44 renal cell carcinoma, 30 prostate acinar adenocarcinoma, 42 breast carcinoma, 41 gastric carcinoma and 47 colorectal carcinoma. The immunolocalization of GPC3 was measured using immunohistochemical staining. Among 147 surgically excised HCC samples, 87.1% (128/147) were GPC3 positive. No GPC3 expression, however, was observed in paracarcinomatous and cirrhotic tissues. In needle biopsy tissues, GPC3 was positively expressed in 81.9% (77/94). Among tissue microassays, HCCs showed positive GPC3 expression in 55.7% (64/115), while 9.6% (5/52) of lung carcinoma and 5.7% (3/53) of ovary adenocarcinoma also were positively stained. The other tumor types showed negative GPC3 expression. In conclusion, our results show that GPC3 is specifically overexpressed in HCC tissue and may be regarded as a potential marker for differential diagnostic hepatocellular carcinoma. PMID:22119409

Zhang, Lijie; Liu, Hui; Sun, Lin; Li, Ning; Ding, Huiguo; Zheng, Jie

2011-11-26

353

T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures.  

PubMed

The efficient generation of hematopoietic stem cells from human pluripotent stem cells is dependent on the appropriate specification of the definitive hematopoietic program during differentiation. In this study, we used T lymphocyte potential to track the onset of definitive hematopoiesis from human embryonic and induced pluripotent stem cells differentiated with specific morphogens in serum- and stromal-free cultures. We show that this program develops from a progenitor population with characteristics of hemogenic endothelium, including the expression of CD34, VE-cadherin, GATA2, LMO2, and RUNX1. Along with T cells, these progenitors display the capacity to generate myeloid and erythroid cells. Manipulation of Activin/Nodal signaling during early stages of differentiation revealed that development of the definitive hematopoietic progenitor population is not dependent on this pathway, distinguishing it from primitive hematopoiesis. Collectively, these findings demonstrate that it is possible to generate T lymphoid progenitors from pluripotent stem cells and that this lineage develops from a population whose emergence marks the onset of human definitive hematopoiesis. PMID:23219550

Kennedy, Marion; Awong, Geneve; Sturgeon, Christopher M; Ditadi, Andrea; LaMotte-Mohs, Ross; Zúńiga-Pflücker, Juan Carlos; Keller, Gordon

2012-12-07

354

Capacity to Make Medical Treatment Decisions in Multiple Sclerosis: A Potentially Remediable Deficit  

PubMed Central

Ability to make decisions about medical treatment is compromised in significant numbers of people with neurological and psychiatric illness, and this incapacity frequently corresponds with compromised neuropsychological function. Although cognitive deficits occur often in people with multiple sclerosis (MS), no research has studied decisional capacity in that disease. The present investigation examined ability to understand treatment disclosures, which is a core component of decisional capacity, in 36 people with MS and 16 normal controls. MS patients with diminished neuropsychological function showed poor understanding of treatment disclosures compared to the control group, and diminished new-learning and executive function correlated with poorer understanding. Nonetheless, with sufficient cueing, the MS patients with diminished neuropsychological function were able to display understanding that was equivalent to the control group. Implications of these results for clinical practice and medical research involving people with MS are discussed.

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

2010-01-01

355

Potential Impact of B Cells on T Cell Function in Multiple Sclerosis  

PubMed Central

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.

Ireland, Sara; Monson, Nancy

2011-01-01

356

Review of teriflunomide and its potential in the treatment of multiple sclerosis  

PubMed Central

In the light of new cases of progressive multifocal leukoencephalopathy and induced autoimmunity in multiple sclerosis (MS) patients who received treatment with upcoming disease-modifying immunosuppressant drugs with a highly specific mode of action such as natalizumab, rituximab, or alemtuzumab, alternative oral treatment options for a subgroup of less severely affected MS patients are a major focus of drug development. These agents are currently investigated in phase III clinical trials and some of them are characterized by a favorable safety profile. With an emphasis on teriflunomide, the active metabolite of an immunosuppressant approved for the treatment of rheumatoid arthritis since 1998, a number of oral treatment options for patients with MS are discussed.

Warnke, Clemens; Meyer zu Horste, Gerd; Hartung, Hans-Peter; Stuve, Olaf; Kieseier, Bernd C

2009-01-01

357

Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis.  

PubMed

Axonal damage is found in both acute and chronic lesions of multiple sclerosis. Direct axon counting in post-mortem tissue has suggested that smaller axons might have a greater susceptibility to damage, but methodological limitations have precluded unequivocal interpretation. However, as neuronal and axonal sizes are linked and neuronal changes would be expected with retrograde or transsynaptic degeneration following axon injury, we hypothesized that an alternative strategy for studying this phenomenon would be to define multiple sclerosis-associated changes in neurones. To test this hypothesis, we measured both axonal loss and neuronal size changes in the anterior optic pathway [including the optic nerve (ON), optic tract (OT) and lateral geniculate nucleus] of the brains of eight patients who died with multiple sclerosis and in eight control brains. The ONs and OTs in brains from the multiple sclerosis patients showed a trend to smaller mean cross-sectional areas (ON, multiple sclerosis = 6.84 mm(2), controls = 9.25 mm(2); and OT, multiple sclerosis = 6.45 mm(2), controls = 7.94 mm(2), P = 0.08) and had reduced axonal densities (ON, multiple sclerosis = 1.1 x 10(5)/mm(2), controls = 1.7 x 10(5)/mm(2); and OT, multiple sclerosis = 1.4 x 10(5)/mm(2), controls = 1.8 x 10(5)/mm(2), P = 0.006). Estimated total axonal counts were reduced by 32 (OT)-45% (ON) in the patients relative to controls (ON, multiple sclerosis = 8.1 x 10(5) axons, controls = 14.8 x10(5), P = 0.05; and OT, multiple sclerosis = 9.1 x 10(5), controls = 13.3 x 10(5), P = 0.02). The size distributions of the magnocellular cells in the lateral geniculate nucleus were similar for the two groups, but in multiple sclerosis brains the parvocellular cells were significantly smaller (mean sizes: multiple sclerosis = 226 microm(2), controls = 230 microm(2), P < 0.001) and had a larger variation in size, suggesting a greater proportion of atrophic neurones. Axon loss in the optic nerves of multiple sclerosis patients correlated strongly with measures of increased dispersion of cell sizes in the parvocellular layer (r = 0.8, P < 0.04). These data demonstrate that both atrophy and decreased density contribute to the substantial axonal loss in the anterior visual pathway of these patients. This appears related to a relatively selective atrophy of the smaller neurones of the parvocellular layer in the lateral geniculate nucleus, supporting the hypothesis that smaller axons may be preferentially susceptible to injury in multiple sclerosis. PMID:11522583

Evangelou, N; Konz, D; Esiri, M M; Smith, S; Palace, J; Matthews, P M

2001-09-01

358

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

Microsoft Academic Search

BACKGROUND: Recent evidence suggests that some sex differences in brain and behavior might result from direct genetic effects, and not solely the result of the organizational effects of steroid hormones. The present study examined the potential role for sex-biased gene expression during development of sexually dimorphic singing behavior and associated song nuclei in juvenile zebra finches. RESULTS: A microarray screen

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

2009-01-01

359

Differential processing of social chemosignals obtained from potential partners in regards to gender and sexual orientation.  

PubMed

On an individual level, human body odors carry information about whether a person is an eligible mate. The current studies investigate if body odors also transmit information about individuals being potential partners in more general terms, namely in regards to gender and sexual orientation. In study 1, 14 gay and 14 heterosexual men were presented with body odors obtained from potential partners (gay male and heterosexual female body odors, respectively) and heterosexual male body odor as a control. In study 2, 14 lesbian and 14 heterosexual women were presented with lesbian female and heterosexual male body odors representing body odors of potential partners, and heterosexual female body odor as a control. Central nervous processing was analyzed using chemosensory event-related potentials and current source density analysis (64-channel EEG recording). Gay and heterosexual men responded with shorter P2 latencies to the body odors of their preferred sexual partners, and lesbian women responded with shorter P2 latencies to body odors of their preferred gender. In response to heterosexual male body odors, lesbian women displayed the most pronounced P3 amplitude, and distinct neuronal activation in medial frontal and parietal neocortical areas. A similar pattern of neuronal activation was observed in gay men when presented with heterosexual male body odor. Both the early processing advantage (P2) for desirable partners' body odors as well as the enhanced evaluative processing (P3, CSD) of undesirable partners' body odors suggest that human body odors indeed carry information about individuals being potential partners in terms of gender and sexual orientation. PMID:22197679

Lübke, Katrin T; Hoenen, Matthias; Pause, Bettina M

2011-12-19

360

Lateral sinus thrombosis in the pediatric population: multiple presentations for a potentially lethal disease.  

PubMed

Lateral sinus thrombosis complicating head and neck infections is a rare but potentially life-threatening condition.We report 4 pediatric cases of lateral sinus thrombosis occurring in different settings (2 patients with acute otitis media, 1 patient with chronic otitis media, and another with acute tonsillitis) to emphasize the nonspecific clinical presentation of this complication. In all our cases, early diagnosis was missed.Keeping a high index of suspicion when dealing with these infections is a reasonable approach. PMID:19834419

Matar, Nayla E; Rassi, Simon J; Melkane, Antoine E; Haddad, Amine C

2009-10-01

361

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

PubMed

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

2013-01-17

362

Long-Term Potentiation Promotes Proliferation/Survival and Neuronal Differentiation of Neural Stem/Progenitor Cells  

PubMed Central

Neural stem cell (NSC) replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP), one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs) and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR) via systemic application of the receptor antagonist, 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP). Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF) and its consequent activation of tropomysosin receptor kinase B (TrkB) receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.

Cho, Taesup; Ryu, Jae K.; Taghibiglou, Changiz; Ge, Yuan; Chan, Allen W.; Liu, Lidong; Lu, Jie; McLarnon, James G.; Wang, Yu Tian

2013-01-01

363

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

364

Baculovirus-transduced mouse amniotic fluid-derived stem cells maintain differentiation potential  

Microsoft Academic Search

Amniotic fluid-derived stem cells have attracted considerable attention in the field of regenerative medicine. Approach of\\u000a genetic modification probably enhances their regenerative potential. In this work, we wanted to determine whether baculovirus\\u000a as a new gene vector could efficiently and safely transduce mouse amniotic fluid-derived stem cells (mAFSs). Cells were isolated\\u000a from mouse amniotic fluid and cultured in vitro. These

Zheng-Shan Liu; Yong-Feng Xu; Shan-Wei Feng; Yong Li; Xiao-Li Yao; Xi-Lin Lu; Cheng Zhang

2009-01-01

365

Diagnostic potential of near-infrared Raman spectroscopy in the colon: Differentiating adenomatous from hyperplastic polyps  

Microsoft Academic Search

Background: Near-infrared Raman spectroscopy is a promising optical technique for GI tissue diagnosis. This study assessed the diagnostic potential of near-infrared Raman spectroscopy in the colon by evaluating its ability to distinguish between adenomatous and hyperplastic polyps. Methods: Ex vivo and in vivo Raman spectra of colon polyps were collected by using a custom-built, fiber-optic, near-infrared Raman spectroscopic system. Multivariate

Andrea Molckovsky; Louis-Michel Wong Kee Song; Martin G. Shim; Norman E. Marcon; Brian C. Wilson

2003-01-01

366

SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases.  

PubMed

SRPK1 (serine-arginine protein kinase 1) is a protein kinase that specifically phosphorylates proteins containing serine-arginine-rich domains. Its substrates include a family of SR proteins that are key regulators of mRNA AS (alternative splicing). VEGF (vascular endothelial growth factor), a principal angiogenesis factor contains an alternative 3' splice site in the terminal exon that defines a family of isoforms with a different amino acid sequence at the C-terminal end, resulting in anti-angiogenic activity in the context of VEGF165-driven neovascularization. It has been shown recently in our laboratories that SRPK1 regulates the choice of this splice site through phosphorylation of the splicing factor SRSF1 (serine/arginine-rich splicing factor 1). The present review summarizes progress that has been made to understand how SRPK1 inhibition may be used to manipulate the balance of pro- and anti-angiogenic VEGF isoforms in animal models in vivo and therefore control abnormal angiogenesis and other pathophysiological processes in multiple disease states. PMID:22817743

Oltean, Sebastian; Gammons, Melissa; Hulse, Richard; Hamdollah-Zadeh, Maryam; Mavrou, Athina; Donaldson, Lucy; Salmon, Andrew H; Harper, Steve J; Ladomery, Michael R; Bates, David O

2012-08-01

367

Chemokines and chemokine receptors in multiple sclerosis. Potential targets for new therapies.  

PubMed

Multiple sclerosis (MS) is a chronic demyelinating disease of the human central nervous system of a still unknown etiology. The autoimmune inflammatory process is believed to be essential for the development of the disease. Several different studies have shown that chemokines and chemokine receptors are involved in the pathogenesis of MS. Chemokines can mediate the trafficking of immune cells across the blood-brain barrier, and regulate their transfer to lesion sites. Chemokines were detected in actively demyelinating lesions and were found to be elevated in the cerebrospinal fluid of patients with MS during relapse. Different pairs of chemokine receptors and their ligands seem to play a pathogenic role in MS (e.g., CXCR3 and CXCL9, CXCL10; CCR1 and CCL3, CCL4, CCL5; CCR2 and CCL2; CCR5 and CCL3, CCL4, CCL5). Interfering with the chemokine system may be an effective therapeutic approach in MS. In this review we briefly summarize the results of the previous studies and identify the most important findings in the field. PMID:17295707

Szczuci?ski, Adam; Losy, Jacek

2007-03-01

368

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism.  

PubMed

Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2? is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor ? (PPAR?). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS. PMID:22924648

Gonzalo, Hugo; Brieva, Luis; Tatzber, Franz; Jové, Mariona; Cacabelos, Daniel; Cassanyé, Anna; Lanau-Angulo, Lucia; Boada, Jordi; Serrano, José C E; González, Cristina; Hernández, Lourdes; Peralta, Sílvia; Pamplona, Reinald; Portero-Otin, Manuel

2012-09-28

369

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.

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

2013-01-01

370

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

2013-09-10

371

Success and failure of evoked potentials in detecting clinical and subclinical lesions in multiple sclerosis patients.  

PubMed

The value of visual, brain stem auditory and somatosensory potentials in detecting clinical and subclinical lesions as compared to the routine neurological, ophthalmological and vestibular examinations was investigated in 100 M.S. patients. It would appear that the VEP and SEP are far superior to the routine techniques in demonstrating lesions. On the other hand, the BAEP is inferior to the clinical and vestibular test as an indicator of brain stem lesions. All clinically manifest posterior column lesions are associated with abnormal SEP. However a substantial proportion of clinically evident lesions in the visual pathways or the midbrain and pons are not detectable by the VEP and BAEP. PMID:6282514

van Buggenhout, E; Ketelaer, P; Carton, H

1982-01-01

372

Novel Differentiation Therapy Approach to Reduce the Metastatic Potential of Basal, Highly Metastatic, Triple-Negative Breast Cancers.  

National Technical Information Service (NTIS)

Low-grade breast cancer is associated with increased differentiation and reduced metastases, suggesting that reprogramming tumor cells to a more differentiated state could improve outcome. Utilizing a novel differentiation therapy approach, We have reprog...

I. M. Chu

2011-01-01

373

Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients.  

PubMed

Interferon beta (IFNbeta) is a first-line therapy for multiple sclerosis (MS). However, some patients experience a decline in efficacy with continued therapy due to the development of anti-IFNbeta neutralizing antibodies (NAb). We investigated the frequency of NAb cross-sectionally in 846 MS patients who were receiving IFNbeta-1b, IFNbeta-1a im, or IFNbeta-1a sc. The frequency of NAb in patients receiving IFNbeta-1a im was lower (5%) than in patients treated with any other form of IFNbeta (22-35%) (P < 0.0001). Binding antibodies (BAb) were measured in 808 patients. The frequency differed significantly between treatment groups, ranging from 45% (IFNbeta-1a im) to 88% (IFNbeta-1b). The proportion of NAb-positive patients within the BAb-positive group differed significantly among treatment groups, ranging between 12% (IFNbeta-1a im) and 51% (IFNbeta-1a sc). The median NAb titer from all IFNbeta-1a-treated patients was higher than from IFNbeta-1b-treated patients (446 versus 171 NU/ mL, P = 0.04). Among NAb-positive patients, the frequency of NAb titers > 100 NU/mL was 71% for IFNbeta-1a compared with 58% for IFNbeta-1b (P = 0.04). Except for conflicting data regarding IFNbeta-1a sc, the results are generally consistent with the literature and together with the differing proportion of NAb-positive patients within the BAb-positive group, provide further insight into the immunogenicity of the IFNbeta preparations. PMID:17263000

Gneiss, C; Tripp, P; Reichartseder, F; Egg, R; Ehling, R; Lutterotti, A; Khalil, M; Kuenz, B; Mayringer, I; Reindl, M; Berger, T; Deisenhammer, F

2006-12-01

374

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

PubMed Central

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

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

2011-01-01

375

Identification of new potential vaccine candidates against Chlamydia pneumoniae by multiple screenings.  

PubMed

Chlamydia are intracellular bacteria associated to serious human disease. A vaccine has proved difficult to obtain so far, and current opinions agree that multi-antigen combinations may be required to induce optimal protective responses. In order to identify new potential vaccine candidates, we recently screened the Chlamydia pneumoniae (Cpn) genome and described 53 recombinant proteins which elicited antibodies binding to purified Cpn cells. We now report that six proteins in this group can also induce in vitro neutralizing antibodies. Antibody specificity for the corresponding antigens was assessed by immunoblot analysis of 2DE Cpn protein maps. Furthermore, four of the six in vitro neutralizing antigens (Pmp2, Pmp10, OmpH-like and enolase) could inhibit Cpn dissemination in a hamster model. The results show that these Cpn proteins are immunoaccessible in infectious EBs, and recommend further investigation on their value as vaccine components. PMID:15629361

Finco, Oretta; Bonci, Alessandra; Agnusdei, Mauro; Scarselli, Maria; Petracca, Roberto; Norais, Nathalie; Ferrari, Germano; Garaguso, Ignazio; Donati, Manuela; Sambri, Vittorio; Cevenini, Roberto; Ratti, Giulio; Grandi, Guido

2005-01-19

376

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

PubMed

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

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

2006-01-01

377

Differentiation potential of a basal epithelial cell line established from human bronchial explant.  

PubMed

Due to the cellular complexity of the airway epithelium, it is important to carefully define bronchial cell lines that capture the phenotypic traits of a particular cell type. We describe the characterization of a human bronchial epithelial cell line, VA10. It was established by transfection of primary bronchial epithelial cells with retroviral constructs containing the E6 and E7 oncogenes from HPV16. The cell line has been cultured for over 2 yr, a total of 60 passages. Although prolonged culture resulted in increased chromosomal instability, no major phenotypic drift in marker expression was observed. The cells expressed cytokeratins 5, 13, 14, and 17 suggesting a basal-like phenotype. This was further supported by the expression of alpha6beta4 integrins and the basal cell-associated transcription factor p63. The VA10 cell line generated high transepithelial electrical resistance in suspended and air-liquid interface culture, indicating functionally active tight junction (TJ) complexes. Immunocytochemistry showed the typical reticular structures of occludin and TJ-associated F-actin. VA10 produced pseudostratified layer in air-liquid interface culture with expression of p63 restricted to the basal layer. Furthermore, VA10 produced round colonies when cultured in laminin-rich reconstituted basement membrane, and immunostaining of claudin-1 and the basolateral marker beta4 integrin revealed colonies that generated polarization as expected in vivo. These data indicate that VA10 epithelia have the potential to model the bronchial epithelium in vivo and may be useful to study epithelial regeneration and repair and the effect of chemicals and potential drug candidates on TJ molecules in airway epithelia. PMID:17876679

Halldorsson, Skarphedinn; Asgrimsson, Valthor; Axelsson, Ivar; Gudmundsson, Gudmundur Hrafn; Steinarsdottir, Margret; Baldursson, Olafur; Gudjonsson, Thorarinn

2007-09-18

378

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

NASA Astrophysics Data System (ADS)

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

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

2010-12-01

379

Selectively multiple-valued memory design using negative differential resistance circuits implemented by standard SiGe BiCMOS process  

Microsoft Academic Search

A novel multiple-valued memory circuit design using negative differential resistance (NDR) circuit based on standard 0.35 mum SiGe process is demonstrated. The NDR circuit is made of metal-oxide-semiconductor field-effect-transistor (MOS) and heterojunction-bipolar-transistor (HBT) devices, but it can show the NDR characteristic in its current-voltage curve by suitably designing the MOS widths\\/lengths parameters. The memory circuit use three-peak MOS-HBT-NDR circuit as

Dong-Shong Liang; Cheng-Chi Tai; Kwang-Jow Gan; Yi-Zhi Lin

2008-01-01

380

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

381

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

PubMed Central

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

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

2013-01-01

382

Planetary surface dating from crater size-frequency distribution measurements: Multiple resurfacing episodes and differential isochron fitting  

NASA Astrophysics Data System (ADS)

The analysis of crater size-frequency distributions and absolute densities forms the basis of current approaches for estimating the absolute and relative ages of planetary surfaces. Users of the Neukum system of crater dating have conventionally used a cumulative presentation of the data, but because of the recent proliferation of interest in identifying resurfacing ages, it is worth emphasising the utility of the differential presentation of crater data in identifying resurfacing events and, particularly, in distinguishing the signature of short-lived events, such as volcanic flows, from long-acting processes, such as aeolian erosion. The work describes some additional considerations for making isochron fits to differentially plotted crater populations with respect to the removal of a binning bias for incrementally/differentially plotted data. The Hartmann approach has not typically employed the fitting of isochrons, but differential fitting would be a natural choice for this system, and is implemented in the Craterstats software. A revised calculation of the martian epoch boundary times in both chronology systems is provided.

Michael, G. G.

2013-09-01

383

Novel immortalized human fetal liver cell line, cBAL111, has the potential to differentiate into functional hepatocytes  

PubMed Central

Background A clonal cell line that combines both stable hepatic function and proliferation capacity is desirable for in vitro applications that depend on hepatic function, such as pharmacological or toxicological assays and bioartificial liver systems. Here we describe the generation and characterization of a clonal human cell line for in vitro hepatocyte applications. Results Cell clones derived from human fetal liver cells were immortalized by over-expression of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed hepatic functionality similar to the parental cells prior to immortalization, and did not grow in soft agar. Cell line cBAL111 expressed markers of immature hepatocytes, like glutathione S transferase and cytokeratin 19, as well as progenitor cell marker CD146 and was negative for lidocaine elimination. On the other hand, the cBAL111 cells produced urea, albumin and cytokeratin 18 and eliminated galactose. In contrast to hepatic cell lines NKNT-3 and HepG2, all hepatic functions were expressed in cBAL111, although there was considerable variation in their levels compared with primary mature hepatocytes. When transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the liver and partly differentiated into hepatocytes showing expression of human albumin and carbamoylphosphate synthetase without signs of cell fusion. Conclusion This novel liver cell line has the potential to differentiate into mature hepatocytes to be used for in vitro hepatocyte applications.

Deurholt, Tanja; van Til, Niek P; Chhatta, Aniska A; ten Bloemendaal, Lysbeth; Schwartlander, Ruth; Payne, Catherine; Plevris, John N; Sauer, Igor M; Chamuleau, Robert AFM; Elferink, Ronald PJ Oude; Seppen, Jurgen; Hoekstra, Ruurdtje

2009-01-01

384

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

PubMed

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

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

2013-08-13

385

Single-walled carbon nanotubes: differential genotoxic potential associated with physico-chemical properties.  

PubMed

Single-walled carbon nanotubes (SWCNTs) have recently attracted great attention because of their fibrous structure and high aspect ratio. Here the genotoxic potential of 400-800 nm, 1-3 ?m and 5-30 ?m SWCNT with respect to their geometry and surface characteristics was studied. Following thorough physico-chemical characterisation, human bronchial epithelial (BEAS-2B) and lymphoblastoid (MCL-5) cells were treated with SWCNT for 24 or 48 h. This showed significant increases in micronucleus frequency in a time- and dose-dependent manner in both cell types in the absence of cytotoxicity. Over the same dose range, only 1-3 ?m SWCNT gave rise to significant increases in hprt point mutations at doses ?25 ?g/ml. Cellular 2,7-dichlorodihydrofluoresceindiacetate (DCFH-DA) fluorescence assay and RT-PCR for oxidative pathway gene profiling revealed a possible oxidative mechanism for the genotoxicity observed in the 1-3 ?m SWCNT. Consequently, this study has demonstrated that SWCNT genotoxicity is dependent on its secondary structure under experimental conditions and oxidative stress alone cannot account for the observed damage. PMID:22263934

Manshian, Bella B; Jenkins, Gareth Js; Williams, Paul M; Wright, Chris; Barron, Andrew R; Brown, Andrew P; Hondow, Nicole; Dunstan, Peter R; Rickman, Rob; Brady, Ken; Doak, Shareen H

2012-01-20

386

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

SciTech Connect

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

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

2012-07-13

387

Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination.  

PubMed

A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing-remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses. PMID:18566024

Hebb, A L O; Moore, C S; Bhan, V; Campbell, T; Fisk, J D; Robertson, H A; Thorne, M; Lacasse, E; Holcik, M; Gillard, J; Crocker, S J; Robertson, G S

2008-06-01

388

Diffuse Iodine-131 lung uptake in bronchiectasis: a potential pitfall in the follow up of differentiated thyroid carcinoma.  

PubMed

Background. I-131 total body scintigraphy is a commonly used post thyroidectomy imaging procedure in the management of differentiated thyroid cancer, in particular in patients with intermediate or high risk of persistent or recurrent disease, in combination with serum thyroglobulin determinations and ultrasound of the neck. It can show the persistence of residual thyroid tissue after thyroidectomy and local and distant metastases. Although this is a highly sensitive method for detecting normal and pathologic thyroid tissue, especially when performed after a radio-ablative dose, false-positive scans (i.e. uptake in the absence of residual thyroid tissue or metastases) can occur in different situations. Patient Findings. We report a case of a 42-yr-old woman with recurrent chest infections and bronchiectasis, who had a total thyroidectomy and I-131 treatment because of a papillary thyroid carcinoma. She presented with marked bilateral I-131 uptake in the lungs mimicking metastatic involvement of the lungs by thyroid cancer but interpreted as nonspecific bilateral uptake by her bronchiectatic bronchial tree. Summary. Our case, as well as others reported in the literature, calls attention to the fact that radioiodine lung uptake may be related to chronic inflammatory lung disease, thus representing a potential diagnostic pitfall in patients with differentiated thyroid cancer. Conclusions. I-131 uptake should be interpreted on the bases of clinical context, imaging and laboratory findings (serum Tg). Recognition of potential false-positive I-131 scans is critical to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine with possible side effects and even worsening of lung disease itself. PMID:22876778

Triggiani, Vincenzo; Moschetta, Marco; Giagulli, Vito Angelo; Licchelli, Brunella; Guastamacchia, Edoardo

2012-08-01

389

Comparison of proliferation and differentiation potential between mouse primary hepatocytes and embryonic hepatic progenitor cells in vitro.  

PubMed

Cell therapy may be a novel and effective treatment strategy for liver diseases, replacing liver transplantation. The potential of two alternative cell types (hepatic progenitor/stem cells and mature hepatocytes) has not yet been fully assessed; the issues of low amplification efficiency and recovery function remain to be resolved. In this study, we investigated the proliferation, differentiation and function of primary mouse mature hepatocytes and embryonic hepatic progenitor cells. Primary cells were obtained from the livers of mouse embryos at 14.5 days post coitus [hepatic progenitor 14.5d (HP14.5d) cells], as well as from the livers of 3-month-old mice [liver cells 3m (LC3m)]. Using trypan blue staining and crystal violet staining to detect cell viability, we found that compared with the limited growth capability of primary LC3m cells, primary HP14.5d cells exhibited an active cell proliferation; however, proliferative ability of passaged HP14.5d cells significantly decreased. After the HP14.5d cells were treated in hepatic induction medium, the expression of progenitor cell markers decreased and that of mature hepatic markers increased, to levels similar to those of LC3m cells. On day 12 of induction, the HP14.5d cells showed comparable indocyanine green (ICG) uptake and glycogen storage to that of the LC3m cells. Therefore, our study demonstrates that primary hepatic progenitor cells have a stronger proliferation capacity and differentiation potential, supporting their clinical application in liver cell transplantation. PMID:23756629

He, Yun; Zhou, Jian-Wu; Xu, Lei; Gong, Meng-Jia; He, Tong-Chuan; Bi, Yang

2013-06-11

390

Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.  

PubMed

Neural stem cell (NSC) replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP), one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs) and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR) via systemic application of the receptor antagonist, 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP). Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF) and its consequent activation of tropomysosin receptor kinase B (TrkB) receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases. PMID:24146937

Cho, Taesup; Ryu, Jae K; Taghibiglou, Changiz; Ge, Yuan; Chan, Allen W; Liu, Lidong; Lu, Jie; McLarnon, James G; Wang, Yu Tian

2013-10-17

391

Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis  

PubMed Central

Expression of PAX2 (Paired-box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax-2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes—clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma—but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax-2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT-PCR. PAX2 promoter methylation status was assessed by methylation-specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax-2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut-off, Pax-2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax-2 immunoexpression. We concluded that Pax-2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax-2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC.

Patricio, Patricia; Ramalho-Carvalho, Joao; Costa-Pinheiro, Pedro; Almeida, Mafalda; Barros-Silva, Joao Diogo; Vieira, Joana; Dias, Paula Cristina; Lobo, Francisco; Oliveira, Jorge; Teixeira, Manuel R; Henrique, Rui; Jeronimo, Carmen

2013-01-01

392

Differential expression and localization of transient receptor potential vanilloid 1 in rabbit and human eyes.  

PubMed

Introduction: The superfamily of transient receptor potential (TRP) cation channels is involved in nociception. Members of this family, such as the vanilloid receptor type 1 (TRPV1) channel, are activated by a wide range of stimuli including heat (?43°C), low pH (?6.5), hypoxia, and hypertonicity. Here we report TRPV1 expression in rabbit and human eyes. Material and methods: We analyzed the expression of TRPV1 mRNA by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and protein by immunohistochemistry in eyes of New Zealand White rabbits and humans. Results: In rabbit and human eyes, TRPV1 protein was present in all layers of the corneal epithelium, but only in the basal layer of the conjunctiva. It was also in the ciliary and lens epithelia of both species as well as in the secretory cells of the rabbit lacrimal gland. The retinal pigment epithelium was positive for this protein in both species. TRPV1 was also present in rabbit Müller cells, where it had a similar pattern of expression to vimentin intermediate filaments. Analysis by qRT-PCR showed that TRPV1 mRNA was found in all of the structures where the protein was present. The highest level was in the lens and the lowest in the retina. Conclusion: TRPV1 is expressed in cells that are particularly active in Ca˛? exchange as well as in cells with significant water transport activity. Because TRPV1 is a Ca˛? channel, it probably functions in the regulation of both water and Ca˛? movements in ocular tissues. PMID:23709255

Martínez-García, M Carmen; Martínez, Tamara; Pańeda, Covadonga; Gallego, Patricia; Jimenez, Ana I; Merayo, Jesus

2013-05-27

393

Potential of two-dimensional electro-fluid-dynamic devices for continuous purification of multiple components from complex samples.  

PubMed

Two-dimensional electro-fluid-dynamic (EFD) devices, in which both electric field and hydrodynamic pressure are used to drive the analyte and fluid migration, enable two-dimensional channel networks to be used for chemical separation instead of one-dimensional column separation systems. Investigation of the theory of mass transfer in symmetrical Y-shaped EFD devices shows that the magnitude of pressure-induced velocity in lateral channels at critical boundary conditions between different steady state migration paths is independent of the channel cross-sectional area ratio. Therefore, the analyte has four possible mass transfer pathways according to the electric field and pressure setup in all symmetrical Y-shaped 2-D EFD devices, and such devices with any cross-sectional area ratio have the capacity to continuously purify two analytes from a mixture simultaneously. In addition, a new format of multiple-branched 2-D EFD devices is introduced to process multiple analytes. A "proof-reading" mechanism based on the infinite resolution conditions ensures the purity of the components collected. The separation processes are simulated by COMSOL Multiphysics, and the migration behavior of the analytes was monitored using fluorescent dyes to verify the flow behavior of different analytes in individual channels. These 2-D EFD devices offer the potential of continuous fractionation and purification of analytes from complex sample mixtures. PMID:21923103

Liu, Chang; Luo, Yong; Maxwell, E Jane; Fang, Ning; Chen, David D Y

2011-10-04

394

Differential effects of peripheral vibration on motor-evoked potentials in acute stages of stroke.  

PubMed

Objective:? The excitability of sensorimotor cortex and spinal motoneurones can be modulated by afferent signals arising from the periphery. Low- and high-frequency vibrations activate separate classes of afferent units in the periphery. Low-frequency vibrations (2-100?Hz) activate the type I fast adapting afferent units (FA-I), whereas high-frequency vibrations (60-1000?Hz) preferentially activate the type II units (FA-II). Muscle spindles are also sensitive to high-frequency mechanical vibrations. Motor-evoked potentials (MEP) generated in response to transcranial magnetic stimulation (TMS) can be modulated by afferent signals. However, it is not clear whether these interactions take place at cortical or spinal cord levels. Methods:? Cerebrovascular attacks resulting in stroke generally affect both sensory and motor systems. In eight stroke patients with partial motor deficit in the first two weeks of the incident we studies the effects of low- (30?Hz) and high- (130?Hz) frequency mechanical vibrations on the MEPs obtained in response to TMS. Recordings from the abductor digiti minimi muscle were carried out by TMS of both lesioned and intact hemispheres. Six patients were tested again four to eight weeks after the initial assessment. The results also were compared with data obtained from eight control subjects. MEPs were evoked by 50% above threshold intensities and for each testing condition initially five control MEPs were recorded. This was followed by consecutive MEPs obtained during vibration (N= 5) and between vibrations (N= 5), and the traces were averaged and analyzed. Results:? In normal subjects both low- (30?Hz) and high- (130?Hz) frequency vibration resulted in shortening of MEP latencies. In patients, there was a similar effect on the affected side with 30?Hz, but not with 130?Hz. Stimulation of the intact hemisphere during high-frequency vibration in the second test revealed a latency shortening, which could be due to central reorganization. The amplitude of MEPs showed a stronger facilitation in the presence of low-frequency vibration in the early stage of stroke compared with normal subjects. However, in the second test the level of facilitation was reduced, indicating an effect at the cortical level. Conclusions:? The results suggest that a cerebrovascular accident influences the modulatory effects of afferent inputs at both spinal and cortical levels, and in time, as reorganization takes place, these altered influences settle towards normal levels. PMID:21992838

Tarlaci, Sultan; Turman, Bulent; Uludag, Burhanettin; Ertekin, Cumhur

2010-07-01

395

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

PubMed

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

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

2012-09-24

396

Transcriptional control of flavonoid biosynthesis: a complex network of conserved regulators involved in multiple aspects of differentiation in Arabidopsis.  

PubMed

Secondary metabolism is not only a protective mechanism against biotic and abiotic stresses but also part of the molecular programs that contribute to normal plant growth and development. In this context, secondary metabolism is intimately linked with other aspects of plant differentiation in which transcription factors play a key coordinating role. Recent findings illustrate the complexity of regulatory networks that control flavonoid biosynthesis in Arabidopsis and other species. They also underline the close relationship between secondary metabolism and epidermal and seed differentiation in Arabidopsis, and the central role played by conserved WD40 domain proteins in regulating these processes. This review highlights recent advances in this field and describes how they help our understanding of the molecular regulation of plant secondary metabolism. PMID:15860424

Broun, Pierre

2005-06-01

397

Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways  

Microsoft Academic Search

This study sought to assess the role of several signaling pathways in the fluid flow shear stress-induced proliferation and differentiation of normal human osteoblasts. We evaluated the effects of an effective dose of selective inhibitors of the extracellular signal-regulated kinases (ERK) pathway (PD98059 and U0126), the nitric oxide synthase pathway (N?-nitro-l-arginine methyl ester), the cyclo-oxygenase pathway (indomethacin), or the Gi\\/o

Sonia Kapur; David J Baylink; K.-H William Lau

2003-01-01

398

Mitochondrial gene expression is regulated at multiple levels and differentially in the heart and liver by thyroid hormones  

Microsoft Academic Search

Biogenesis of the oxidative phosphorylation system (OXPHOS) requires the coordinated expression of the nuclear and the mitochondrial\\u000a genomes. Thyroid hormones play an important role in cell growth and differentiation and are one of the main effectors in mitochondrial\\u000a biogenesis. To determine how mtDNA expression is regulated, we have investigated the response of two different tissues, the\\u000a heart and liver, to

Erika Fernández-Vizarra; José A. Enriquez; Acisclo Pérez-Martos; Julio Montoya; Patricio Fernández-Silva

2008-01-01

399

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

PubMed Central

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

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

2013-01-01

400

hTERT gene immortalized human adipose-derived stem cells and its multiple differentiations: a preliminary investigation.  

PubMed

Human adipose-derived adult stem cells (hADSCs) can express human telomerase reverse transcriptase phenotypes under an appropriate culture condition. Because adipose tissue is abundant and easily accessible, hADSCs offer a promising source of stem cells for tissue engineering application and other cell-based therapies. However, the shortage of cells number and the difficulty to proliferate, known as the "Hayflick limit" in vitro, limit their further clinical application. Here, hADSCs were transfected with human telomerase reverse transcriptase (hTERT) gene by the lentiviral vector to prolong the lifespan of stem cells and even immortalize them. Following to this, the cellular properties and functionalities of the transfected cell lines were assayed. The results demonstrated that hADSCs had been successfully transfected with hTERT gene (hTERT-ADSCs). Then, hTERT-ADSCs were initially selected by G418 and subsequently expanded over 20 passages in vitro. Moreover, the qualitative and quantitative differentiation criteria for 20 passages of hTERT-ADSCs also demonstrated that hTERT-ADSCs could differentiate into osteogenesis, chondrogenesis, and adipogenesis phenotypes in lineage-specific differentiation media. These findings confirmed that this transfection could prolong the lifespan of hADSCs. PMID:23322249

Wang, L; Song, K; Qu, X; Wang, H; Zhu, H; Xu, X; Zhang, M; Tang, Y; Yang, X

2013-01-16

401

Determination of ionized hydrogen plus Cs\\/6s\\/ potential from differential cross section measurements at energies 13.4-24.2 eV  

Microsoft Academic Search

Measurements of the elastic differential cross section for the scattering of ionized hydrogen by Cs in the energy range from 13.4 to 24.2 eV are presented. A best Morse potential for the state Cs(6s) plus ionized hydrogen is