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Sample records for satellite cells resident

  1. Satellite cells: the architects of skeletal muscle.

    Science.gov (United States)

    Chang, Natasha C; Rudnicki, Michael A

    2014-01-01

    The outstanding regenerative capacity of skeletal muscle is attributed to the resident muscle stem cell termed satellite cell. Satellite cells are essential for skeletal muscle regeneration as they ultimately provide the myogenic precursors that rebuild damaged muscle tissue. Satellite cells characteristically are a heterogeneous population of stem cells and committed progenitor cells. Delineation of cellular hierarchy and understanding how lineage fate choices are determined within the satellite cell population will be invaluable for the advancement of muscle regenerative therapies.

  2. Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis.

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    Tierney, Matthew T; Sacco, Alessandra

    2016-06-01

    The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity.

  3. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

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    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  4. Muscle Satellite Cell Heterogeneity and Self-Renewal

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    Norio eMotohashi

    2014-01-01

    Full Text Available Adult skeletal muscle possesses extraordinary regeneration capacities. After muscle injury or exercise, large numbers of newly formed muscle fibers are generated within a week as a result of expansion and differentiation of a self-renewing pool of muscle stem cells termed muscle satellite cells. Normally, satellite cells are mitotically quiescent and reside beneath the basal lamina of muscle fibers. Upon regeneration, satellite cells are activated, and give rise to daughter myogenic precursor cells. After several rounds of proliferation, these myogenic precursor cells contribute to the formation of new muscle fibers. During cell division, a minor population of myogenic precursor cells returns to quiescent satellite cells as a self-renewal process. Currently, accumulating evidence has revealed the essential roles of satellite cells in muscle regeneration and the regulatory mechanisms, while it still remains to be elucidated how satellite cell self-renewal is molecularly regulated and how satellite cells are important in aging and diseased muscle. The number of satellite cells is decreased due to the changing niche during ageing, resulting in attenuation of muscle regeneration capacity. Additionally, in Duchenne muscular dystrophy (DMD patients, the loss of satellite cell regenerative capacity and decreased satellite cell number due to continuous needs for satellite cells lead to progressive muscle weakness with chronic degeneration. Thus, it is necessary to replenish muscle satellite cells continuously. This review outlines recent findings regarding satellite cell heterogeneity, asymmetric division and molecular mechanisms in satellite cell self-renewal which is crucial for maintenance of satellite cells as a muscle stem cell pool throughout life. In addition, we discuss roles in the stem cell niche for satellite cell maintenance, as well as related cell therapies for approaching treatment of DMD.

  5. Satellite cells from dystrophic muscle retain regenerative capacity

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    Luisa Boldrin

    2015-01-01

    Full Text Available Duchenne muscular dystrophy is an inherited disorder that is characterized by progressive skeletal muscle weakness and wasting, with a failure of muscle maintenance/repair mediated by satellite cells (muscle stem cells. The function of skeletal muscle stem cells resident in dystrophic muscle may be perturbed by being in an increasing pathogenic environment, coupled with constant demands for repairing muscle. To investigate the contribution of satellite cell exhaustion to this process, we tested the functionality of satellite cells isolated from the mdx mouse model of Duchenne muscular dystrophy. We found that satellite cells derived from young mdx mice contributed efficiently to muscle regeneration within our in vivo mouse model. To then test the effects of long-term residence in a dystrophic environment, satellite cells were isolated from aged mdx muscle. Surprisingly, they were as functional as those derived from young or aged wild type donors. Removing satellite cells from a dystrophic milieu reveals that their regenerative capacity remains both intact and similar to satellite cells derived from healthy muscle, indicating that the host environment is critical for controlling satellite cell function.

  6. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    -damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role...... damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains...

  7. The role of satellite cells in muscle hypertrophy.

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    Blaauw, Bert; Reggiani, Carlo

    2014-02-01

    The role of satellite cells in muscle hypertrophy has long been a debated issue. In the late 1980s it was shown that proteins remain close to the myonucleus responsible for its synthesis, giving rise to the idea of a nuclear domain. This, together with the observation that during various models of muscle hypertrophy there is an activation of the muscle stem cells, i.e. satellite cells, lead to the idea that satellite cell activation is required for muscle hypertrophy. Thus, satellite cells are not only responsible for muscle repair and regeneration, but also for hypertrophic growth. Further support for this line of thinking was obtained after studies showing that irradiation of skeletal muscle, and therefore elimination of all satellite cells, completely prevented overload-induced hypertrophy. Recently however, using different transgenic approaches, it has become clear that muscle hypertrophy can occur without a contribution of satellite cells, even though in most situations of muscle hypertrophy satellite cells are activated. In this review we will discuss the contribution of satellite cells, and other muscle-resident stem cells, to muscle hypertrophy both in mice as well as in humans.

  8. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

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    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  9. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

    Science.gov (United States)

    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  10. Satellite cells in human skeletal muscle plasticity.

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    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  11. Muscle Satellite Cells: Exploring the Basic Biology to Rule Them.

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    Almeida, Camila F; Fernandes, Stephanie A; Ribeiro Junior, Antonio F; Keith Okamoto, Oswaldo; Vainzof, Mariz

    2016-01-01

    Adult skeletal muscle is a postmitotic tissue with an enormous capacity to regenerate upon injury. This is accomplished by resident stem cells, named satellite cells, which were identified more than 50 years ago. Since their discovery, many researchers have been concentrating efforts to answer questions about their origin and role in muscle development, the way they contribute to muscle regeneration, and their potential to cell-based therapies. Satellite cells are maintained in a quiescent state and upon requirement are activated, proliferating, and fusing with other cells to form or repair myofibers. In addition, they are able to self-renew and replenish the stem pool. Every phase of satellite cell activity is highly regulated and orchestrated by many molecules and signaling pathways; the elucidation of players and mechanisms involved in satellite cell biology is of extreme importance, being the first step to expose the crucial points that could be modulated to extract the optimal response from these cells in therapeutic strategies. Here, we review the basic aspects about satellite cells biology and briefly discuss recent findings about therapeutic attempts, trying to raise questions about how basic biology could provide a solid scaffold to more successful use of these cells in clinics.

  12. RBP-J (Rbpsuh) is essential to maintain muscle progenitor cells and to generate satellite cells

    OpenAIRE

    Vasyutina, Elena; Lenhard, Diana C.; Wende, Hagen; Erdmann, Bettina; Epstein, Jonathan A.; Birchmeier, Carmen

    2007-01-01

    In the developing muscle, a pool of myogenic progenitor cells is formed and maintained. These resident progenitors provide a source of cells for muscle growth in development and generate satellite cells in the perinatal period. By the use of conditional mutagenesis in mice, we demonstrate here that the major mediator of Notch signaling, the transcription factor RBP-J, is essential to maintain this pool of progenitor cells in an undifferentiated state. In the absence of RBP-J, these cells unde...

  13. PRMT7 Preserves Satellite Cell Regenerative Capacity.

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    Blanc, Roméo Sébastien; Vogel, Gillian; Chen, Taiping; Crist, Colin; Richard, Stéphane

    2016-02-16

    Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7(-/-) adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.

  14. PRMT7 Preserves Satellite Cell Regenerative Capacity

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    Roméo Sébastien Blanc

    2016-02-01

    Full Text Available Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells, which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.

  15. Regulation of satellite cell function in sarcopenia

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    Stephen E Alway

    2014-09-01

    Full Text Available The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell function that is impacted by the environment (niche of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia, and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration. While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function.

  16. RBP-J (Rbpsuh) is essential to maintain muscle progenitor cells and to generate satellite cells.

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    Vasyutina, Elena; Lenhard, Diana C; Wende, Hagen; Erdmann, Bettina; Epstein, Jonathan A; Birchmeier, Carmen

    2007-03-13

    In the developing muscle, a pool of myogenic progenitor cells is formed and maintained. These resident progenitors provide a source of cells for muscle growth in development and generate satellite cells in the perinatal period. By the use of conditional mutagenesis in mice, we demonstrate here that the major mediator of Notch signaling, the transcription factor RBP-J, is essential to maintain this pool of progenitor cells in an undifferentiated state. In the absence of RBP-J, these cells undergo uncontrolled myogenic differentiation, leading to a depletion of the progenitor pool. This results in a lack of muscle growth in development and severe muscle hypotrophy. In addition, satellite cells are not formed late in fetal development in conditional RBP-J mutant mice. We conclude that RBP-J is required in the developing muscle to set aside proliferating progenitors and satellite cells.

  17. Muscle Interstitial Cells: A Brief Field Guide to Non-satellite Cell Populations in Skeletal Muscle.

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    Tedesco, Francesco Saverio; Moyle, Louise A; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle regeneration is mainly enabled by a population of adult stem cells known as satellite cells. Satellite cells have been shown to be indispensable for adult skeletal muscle repair and regeneration. In the last two decades, other stem/progenitor cell populations resident in the skeletal muscle interstitium have been identified as "collaborators" of satellite cells during regeneration. They also appear to have a key role in replacing skeletal muscle with adipose, fibrous, or bone tissue in pathological conditions. Here, we review the role and known functions of these different interstitial skeletal muscle cell types and discuss their role in skeletal muscle tissue homeostasis, regeneration, and disease, including their therapeutic potential for cell transplantation protocols.

  18. A role for RNA post-transcriptional regulation in satellite cell activation

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    Farina Nicholas H

    2012-10-01

    Full Text Available Abstract Background Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood. Methods Satellite cells isolated by FACS from uninjured skeletal muscle and 12 h post-muscle injury from wild type and Syndecan-4 null mice were probed using Affymetrix 430v2 gene chips and analyzed by Spotfiretm and Ingenuity Pathway analysis to identify gene expression changes and networks associated with satellite cell activation, respectively. Additional analyses of target genes identify miRNAs exhibiting dynamic changes in expression during satellite cell activation. The function of the miRNAs was assessed using miRIDIAN hairpin inhibitors. Results An unbiased gene expression screen identified over 4,000 genes differentially expressed in satellite cells in vivo within 12 h following muscle damage and more than 50% of these decrease dramatically. RNA binding proteins and genes involved in post-transcriptional regulation were significantly over-represented whereas splicing factors were preferentially downregulated and mRNA stability genes preferentially upregulated. Furthermore, six computationally identified miRNAs demonstrated novel expression through muscle regeneration and in satellite cells. Three of the six miRNAs were found to regulate satellite cell fate. Conclusions The quiescent satellite cell is actively maintained in a state poised to activate in response to external signals. Satellite cell activation appears to be regulated by post-transcriptional gene regulation.

  19. Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin.

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    Guardiola, Ombretta; Lafuste, Peggy; Brunelli, Silvia; Iaconis, Salvatore; Touvier, Thierry; Mourikis, Philippos; De Bock, Katrien; Lonardo, Enza; Andolfi, Gennaro; Bouché, Ann; Liguori, Giovanna L; Shen, Michael M; Tajbakhsh, Shahragim; Cossu, Giulio; Carmeliet, Peter; Minchiotti, Gabriella

    2012-11-20

    Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. However, our understanding of the molecular mechanisms underlying satellite cell activation is still largely undefined. Here, we show that Cripto, a regulator of early embryogenesis, is a novel regulator of muscle regeneration and satellite cell progression toward the myogenic lineage. Conditional inactivation of cripto in adult satellite cells compromises skeletal muscle regeneration, whereas gain of function of Cripto accelerates regeneration, leading to muscle hypertrophy. Moreover, we provide evidence that Cripto modulates myogenic cell determination and promotes proliferation by antagonizing the TGF-β ligand myostatin. Our data provide unique insights into the molecular and cellular basis of Cripto activity in skeletal muscle regeneration and raise previously undescribed implications for stem cell biology and regenerative medicine.

  20. Globular adiponectin activates motility and regenerative traits of muscle satellite cells.

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    Tania Fiaschi

    Full Text Available Regeneration of adult injured skeletal muscle is due to activation of satellite cells, a population of stem cells resident beneath the basal lamina. Thus, information on soluble factors affecting satellite cell activation, as well as migration towards injury and fusion into new myofibers are essential. Here, we show that globular adiponectin (gAd, positively affects several features of muscle satellite cells. gAd activates satellite cells to exit quiescence and increases their recruitment towards myotubes. gAd elicits in satellite cells a specific motility program, involving activation of the small GTPase Rac1, as well as expression of Snail and Twist transcription factors driving a proteolytic motility, useful to reach the site of injury. We show that satellite cells produce autocrine full length adiponectin (fAd, which is converted to gAd by activated macrophages. In turns, gAd concurs to attract to the site of injury both satellite cells and macrophages and induces myogenesis in muscle satellite cells. Thus, these findings add a further role for gAd in skeletal muscle, including the hormone among factors participating in muscle regeneration.

  1. Skeletal Muscle Satellite Cell Activation Following Cutaneous Burn in Rats

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    2013-12-01

    Satellite cell isolation and culture Satellite cells were isolated similar as described by Allen et al. [30]. Following euthanasia , muscles were...satellite cell cultures. Methods Cell Biol 1997;52:155–76. [31] Tatsumi R, Liu X, Pulido A, Morales M, Sakata T, Dial S, Hattori A, Ikeuchi Y, Allen RE

  2. Isolation and Culture of Satellite Cells from Mouse Skeletal Muscle.

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    Musarò, Antonio; Carosio, Silvia

    2017-01-01

    Skeletal muscle tissue is characterized by a population of quiescent mononucleated myoblasts, localized between the basal lamina and sarcolemma of myofibers, known as satellite cells. Satellite cells play a pivotal role in muscle homeostasis and are the major source of myogenic precursors in mammalian muscle regeneration.This chapter describes protocols for isolation and culturing satellite cells isolated from mouse skeletal muscles. The classical procedure, which will be discussed extensively in this chapter, involves the enzymatic dissociation of skeletal muscles, while the alternative method involves isolation of satellite cells from isolated myofibers in which the satellite cells remain in their in situ position underneath the myofiber basal lamina.In particular, we discuss the technical aspect of satellite cell isolation, the methods necessary to enrich the satellite cell fraction and the culture conditions that optimize proliferation and myotube formation of mouse satellite cells.

  3. Proliferation conditions for human satellite cells. The fractional content of satellite cells

    DEFF Research Database (Denmark)

    Gaster, M; Beck-Nielsen, H; Schrøder, H D

    2001-01-01

    the fraction of Sc in culture. Evaluation of different culture conditions allowed us to find proliferation conditions preferentially for Sc: a) Sc should be cultured on surfaces coated with ECM-gel. b) Primary cell culture should be inoculated in DMEM supplemented with 10% fetal calf serum to increase cell......Primary satellite cell cultures have become an important tool as a model system for skeletal muscles. A common problem in human satellite cell culturing is fibroblast overgrowth. We combined N-CAM (Leu19) immunocytochemical staining of satellite cells (Sc) with stereological methods to estimate...... adherence. c) Change of media to DMEM supplemented with 2% Ultroser-G and 2% FCS after 24 h.d) Before subcultivation, cells should be preplated for 30 min. The fractional content of Sc in passage four when applying this method of cultivation was 0.82 +/- 0.07 (mean +/- SE, N = 10). Our method enabled us...

  4. Memory NK cells: why do they reside in the liver?

    OpenAIRE

    Jiang, Xiaojun; Chen, Yonglin; Peng, Hui; Tian, Zhigang

    2013-01-01

    Immune memory is the hallmark of adaptive immunity. However, recent studies have shown that natural killer (NK) cells, key components of the innate immune system, also mediate memory responses in mice and humans. Strikingly, memory NK cells were liver-resident in some models, raising the question as to whether the liver is a special organ for the acquisition of NK cell memory. Here, we review the characteristics of NK cell memory by summarizing recent progress and discuss how the liver may ge...

  5. Satellite Cells in Muscular Dystrophy - Lost in Polarity.

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    Chang, Natasha C; Chevalier, Fabien P; Rudnicki, Michael A

    2016-06-01

    Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem-cell divisions, and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review we highlight recent research advances in DMD and discuss the current state of treatment and, importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD.

  6. Myogenic skeletal muscle satellite cells communicate by tunnelling nanotubes.

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    Tavi, Pasi; Korhonen, Topi; Hänninen, Sandra L; Bruton, Joseph D; Lööf, Sara; Simon, Andras; Westerblad, Håkan

    2010-05-01

    Quiescent satellite cells sit on the surface of the muscle fibres under the basal lamina and are activated by a variety of stimuli to disengage, divide and differentiate into myoblasts that can regenerate or repair muscle fibres. Satellite cells adopt their parent's fibre type and must have some means of communication with the parent fibre. The mechanisms behind this communication are not known. We show here that satellite cells form dynamic connections with muscle fibres and other satellite cells by F-actin based tunnelling nanotubes (TNTs). Our results show that TNTs readily develop between satellite cells and muscle fibres. Once developed, TNTs permit transport of intracellular material, and even cellular organelles such as mitochondria between the muscle fibre and satellite cells. The onset of satellite cell differentiation markers Pax-7 and MyoD expression was slower in satellite cells cultured in the absence than in the presence of muscle cells. Furthermore physical contact between myofibre and satellite cell progeny is required to maintain subtype identity. Our data establish that TNTs constitute an integral part of myogenic cell communication and that physical cellular interaction control myogenic cell fate determination.

  7. Conditional Cripto overexpression in satellite cells promotes myogenic commitment and enhances early regeneration.

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    Prezioso, Carolina; Iaconis, Salvatore; Andolfi, Gennaro; Zentilin, Lorena; Iavarone, Francescopaolo; Guardiola, Ombretta; Minchiotti, Gabriella

    2015-01-01

    Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. Despite extensive studies, knowledge of the molecular mechanisms underlying the early events associated with satellite cell activation and myogenic commitment in muscle regeneration remains still incomplete. Cripto is a novel regulator of postnatal skeletal muscle regeneration and a promising target for future therapy. Indeed, Cripto is expressed both in myogenic and inflammatory cells in skeletal muscle after acute injury and it is required in the satellite cell compartment to achieve effective muscle regeneration. A critical requirement to further explore the in vivo cellular contribution of Cripto in regulating skeletal muscle regeneration is the possibility to overexpress Cripto in its endogenous configuration and in a cell and time-specific manner. Here we report the generation and the functional characterization of a novel mouse model for conditional expression of Cripto, i.e., the Tg:DsRed (loxP/loxP) Cripto-eGFP mice. Moreover, by using a satellite cell specific Cre-driver line we investigated the biological effect of Cripto overexpression in vivo, and provided evidence that overexpression of Cripto in the adult satellite cell compartment promotes myogenic commitment and differentiation, and enhances early regeneration in a mouse model of acute injury.

  8. Reduced satellite cell population may lead to contractures in children with cerebral palsy.

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    Smith, Lucas R; Chambers, Henry G; Lieber, Richard L

    2013-03-01

    Satellite cells are the stem cells residing in muscle responsible for skeletal muscle growth and repair. Skeletal muscle in cerebral palsy (CP) has impaired longitudinal growth that results in muscle contractures. We hypothesized that the satellite cell population would be reduced in contractured muscle. We compared the satellite cell populations in hamstring muscles from participants with CP contracture (n=8; six males, two females; age range 6-15y; Gross Motor Function Classification System [GMFCS] levels II-V; 4 with hemiplegia, 4 with diplegia) and from typically developing participants (n=8; six males, two females, age range 15-18y). Muscle biopsies were extracted from the gracilis and semitendinosus muscles and mononuclear cells were isolated. Cell surface markers were stained with fluorescently conjugated antibodies to label satellite cells (neural cell adhesion molecule) and inflammatory and endothelial cells (CD34 and CD4 respectively). Cells were analyzed using flow cytometry to determine cell populations. After gating for intact cells a mean of 12.8% (SD 2.8%) were determined to be satellite cells in typically developing children, but only 5.3% (SD 2.3%; p0.05) suggesting the isolation procedure was valid. A reduced satellite cell population may account for the decreased longitudinal growth of muscles in CP that develop into fixed contractures or the decreased ability to strengthen muscle in CP. This suggests a unique musculoskeletal disease mechanism and provides a potential therapeutic target for debilitating muscle contractures. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

  9. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

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    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  10. Isolation, Culture and Identification of Porcine Skeletal Muscle Satellite Cells

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    Bo-jiang Li

    2015-08-01

    Full Text Available The objective of this study was to establish the optimum protocol for the isolation and culture of porcine muscle satellite cells. Mononuclear muscle satellite cells are a kind of adult stem cell, which is located between the basal lamina and sarcolemma of muscle fibers and is the primary source of myogenic precursor cells in postnatal muscle. Muscle satellite cells are a useful model to investigate the mechanisms of muscle growth and development. Although the isolation and culture protocols of muscle satellite cells in some species (e.g. mouse have been established successfully, the culture system for porcine muscle satellite cells is very limited. In this study, we optimized the isolation procedure of porcine muscle satellite cells and elaborated the isolation and culture process in detail. Furthermore, we characterized the porcine muscle satellite cells using the immunofluorecence. Our study provides a reference for the isolation of porcine muscle satellite cells and will be useful for studying the molecular mechanisms in these cells.

  11. A global downregulation of microRNAs occurs in human quiescent satellite cells during myogenesis

    NARCIS (Netherlands)

    Koning, Merel; Werker, Paul M N; van Luyn, Marja J A; Krenning, Guido; Harmsen, Martin C

    2012-01-01

    During myogenesis, human satellite cells differentiate and form multinucleated myotubes, while a fraction of the human satellite cells enter quiescence. These quiescent satellite cells are able to activate, proliferate and contribute to muscle regeneration. Post-transcriptional regulation of

  12. Use of Advanced Solar Cells for Commercial Communication Satellites

    Science.gov (United States)

    Bailey, Sheila G.; Landis, Geoffrey A.

    1995-01-01

    The current generation of communications satellites are located primarily in geosynchronous Earth orbit (GEO). Over the next decade, however, a new generation of communications satellites will be built and launched, designed to provide a world-wide interconnection of portable telephones. For this mission, the satellites must be positioned in lower polar and near-polar orbits. To provide complete coverage, large numbers of satellites will be required. Because the required number of satellites decreases as the orbital altitude is increased, fewer satellites would be required if the orbit chosen were raised from low to intermediate orbit. However, in intermediate orbits, satellites encounter significant radiation due to trapped electrons and protons. Radiation tolerant solar cells may be necessary to make such satellites feasible. We analyze the amount of radiation encountered in low and intermediate polar orbits at altitudes of interest to next-generation communication satellites, calculate the expected degradation for silicon, GaAs, and InP solar cells, and show that the lifetimes can be significantly increased by use of advanced solar cells.

  13. Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

    2014-08-01

    Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermal growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and its

  14. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle.

    Science.gov (United States)

    McCarthy, John J; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B; Srikuea, Ratchakrit; Lawson, Benjamin A; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S; Esser, Karyn A; Dupont-Versteegden, Esther E; Peterson, Charlotte A

    2011-09-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca(2+) sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.

  15. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

    Science.gov (United States)

    McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

    2011-01-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

  16. M-cadherin-mediated intercellular interactions activate satellite cell division.

    Science.gov (United States)

    Marti, Merce; Montserrat, Núria; Pardo, Cristina; Mulero, Lola; Miquel-Serra, Laia; Rodrigues, Alexandre Miguel Cavaco; Andrés Vaquero, José; Kuebler, Bernd; Morera, Cristina; Barrero, María José; Izpisua Belmonte, Juan Carlos

    2013-11-15

    Adult muscle stem cells and their committed myogenic precursors, commonly referred to as the satellite cell population, are involved in both muscle growth after birth and regeneration after damage. It has been previously proposed that, under these circumstances, satellite cells first become activated, divide and differentiate, and only later fuse to the existing myofiber through M-cadherin-mediated intercellular interactions. Our data show that satellite cells fuse with the myofiber concomitantly to cell division, and only when the nuclei of the daughter cells are inside the myofiber, do they complete the process of differentiation. Here we demonstrate that M-cadherin plays an important role in cell-to-cell recognition and fusion, and is crucial for cell division activation. Treatment of satellite cells with M-cadherin in vitro stimulates cell division, whereas addition of anti-M-cadherin antibodies reduces the cell division rate. Our results suggest an alternative model for the contribution of satellite cells to muscle development, which might be useful in understanding muscle regeneration, as well as muscle-related dystrophies.

  17. Memory regulatory T cells reside in human skin.

    Science.gov (United States)

    Sanchez Rodriguez, Robert; Pauli, Mariela L; Neuhaus, Isaac M; Yu, Siegrid S; Arron, Sarah T; Harris, Hobart W; Yang, Sara Hsin-Yi; Anthony, Bryan A; Sverdrup, Francis M; Krow-Lucal, Elisabeth; MacKenzie, Tippi C; Johnson, David S; Meyer, Everett H; Löhr, Andrea; Hsu, Andro; Koo, John; Liao, Wilson; Gupta, Rishu; Debbaneh, Maya G; Butler, Daniel; Huynh, Monica; Levin, Ethan C; Leon, Argentina; Hoffman, William Y; McGrath, Mary H; Alvarado, Michael D; Ludwig, Connor H; Truong, Hong-An; Maurano, Megan M; Gratz, Iris K; Abbas, Abul K; Rosenblum, Michael D

    2014-03-01

    Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.

  18. Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    Xiaoti Xu

    2015-09-01

    Full Text Available Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.

  19. Resident cardiac progenitor cells: at the heart of regeneration.

    Science.gov (United States)

    Bollini, Sveva; Smart, Nicola; Riley, Paul R

    2011-02-01

    Stem cell therapy has recently emerged as an innovative strategy over conventional cardiovascular treatments to restore cardiac function in patients affected by ischemic heart disease. Various stem cell populations have been tested and their potential for cardiac repair has been analyzed. Embryonic stem cells retain the greatest differentiation potential, but concerns persist with regard to their immunogenic and teratogenic effects. Although adult somatic stem cells are not tumourigenic and easier to use in an autologous setting, they exist in small numbers and possess reduced differentiation potential. Traditionally the heart was considered to be a post-mitotic organ; however, this dogma has recently been challenged with the identification of a reservoir of resident stem cells, defined as cardiac progenitor cells (CPCs). These endogenous progenitors may represent the best candidates for cardiovascular cell therapy, as they are tissue-specific, often pre-committed to a cardiac fate, and display a greater propensity to differentiate towards cardiovascular lineages. This review will focus on current research into the biology of CPCs and their regenerative potential. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  20. How do resident stem cells repair the damagedmyocardium?

    Institute of Scientific and Technical Information of China (English)

    Emiko Hayashi; Toru Hosoda

    2015-01-01

    It has been a decade since the monumental discoveryof resident stem cells in the mammalian heart, and thefollowing studies witnessed the continuous turnoverof cardiomyocytes and vascular cells, maintaining thehomeostasis of the organ. Recently, the autologousadministration of c-kit-positive cardiac stem cells inpatients with ischemic heart failure has led to an incredibleoutcome; the left ventricular ejection fraction of the celltreatedgroup improved from 30% at the baseline to 38%after one year and to 42% after two years of cell injection.The potential underlying mechanisms, before and aftercell infusion, are explored and discussed in this article.Some of them are related to the intrinsic property of theresident stem cells, such as direct differentiation, paracrineaction, and immunomodulatory function, whereas othersinvolve environmental factors, leading to cellular reverseremodeling and to the natural selection of "juvenile" cells.It has now been demonstrated that cardiac stem cells fortherapeutic purposes can be prepared from tiny biopsiedspecimens of the failing heart as well as from frozentissues, which may remarkably expand the repertoireof the strategy against various cardiovascular disorders,including non-ischemic cardiomyopathy and congenitalheart diseases. Further translational investigations areneeded to explore these possibilities.

  1. [Molecular mechanism maintaining muscle satellite cells and the roles in sarcopenia.

    Science.gov (United States)

    Takemoto, Yusei; Fukada, So-Ichiro

    2017-01-01

    Skeletal muscle has its stem cell named satellite cell. The absence of satellite cells does not allow muscle regeneration, it is unquestionable that satellite cell is indispensable for muscle regeneration processes. A certain number of satellite cells appear to be necessary for the successful muscle regeneration, meaning the maintenance of the satellite cells is essential for the functional homeostasis of skeletal muscle. Recent studies have revealed the molecular mechanism underlying satellite cell maintenance in a steady state. A loss of those molecules responsible for the maintenance often results in decreased satellite cell pool and reduced regeneration ability. On the other hand, the contribution of satellite cells to muscle hypertrophy or aged-related atrophy(sarcopenia)is controversial. In this review, we will introduce the molecules that regulate satellite cells homeostasis in the dormant state and then further discuss the recent results on the roles of satellite cell in sarcopenia.

  2. Interleukin-8 derived from local tissue-resident stromal cells promotes tumor cell invasion.

    Science.gov (United States)

    Welte, Gabriel; Alt, Eckhard; Devarajan, Eswaran; Krishnappa, Srinivasalu; Jotzu, Constantin; Song, Yao-Hua

    2012-11-01

    The aim of this study is to evaluate the role of adipose tissue resident stromal cells on tumor cell invasion. Our data show that a subpopulation of adipose tissue derived stromal cells expressing Nestin, NG2, α-smooth muscle actin and PDGFR-α migrate toward the cancer cells. Microarray analysis revealed the upregulation of IL-8 in the migrated cells. We demonstrated that stromal cell derived IL-8 promote the invasion and the anchorage-independent growth of cancer cells. We conclude that human breast cancer cells attract a subpopulation of stromal cells that secrete IL-8 to promote tumor cell invasion in a paracrine fashion.

  3. Wave characterization for mammalian cell culture: residence time distribution.

    Science.gov (United States)

    Rodrigues, Maria Elisa; Costa, Ana Rita; Henriques, Mariana; Azeredo, Joana; Oliveira, Rosário

    2012-02-15

    The high dose requirements of biopharmaceutical products led to the development of mammalian cell culture technologies that increase biomanufacturing capacity. The disposable Wave bioreactor is one of the most promising technologies, providing ease of operation and no cross-contamination, and using an innovative undulation movement that ensures good mixing and oxygen transfer without cell damage. However, its recentness demands further characterization. This study evaluated the residence time distribution (RTD) in Wave, allowing the characterization of mixing and flow and the comparison with ideal models and a Stirred tank reactor (STR) used for mammalian cell culture. RTD was determined using methylene blue with pulse input methodology, at three flow rates common in mammalian cell culture (3.3×10(-5)m(3)/h, 7.9×10(-5)m(3)/h, and 1.25×10(-4)m(3)/h) and one typical of microbial culture (5×10(-3)m(3)/h). Samples were taken periodically and the absorbance read at 660nm. It was observed that Wave behavior diverted from ideal models, but was similar to STR. Therefore, the deviations are not related to the particular Wave rocking mechanism, but could be associated with the inadequacy of these reactors to operate in continuous mode or to a possible inability of the theoretical models to properly describe the behavior of reactors designed for mammalian cell culture. Thus, the development of new theoretical models could better characterize the performance of these reactors.

  4. Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martín A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2016-01-01

    Accumulation of oxidized proteins is a hallmark of cellular and organismal aging. Adult muscle stem cell (or satellite cell) replication and differentiation is compromised with age contributing to sarcopenia. However, the molecular events related to satellite cell dysfunction during aging...

  5. Satellite glial cells in sensory ganglia: its role in pain

    Directory of Open Access Journals (Sweden)

    Filipa Alexandra Leite Costa

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: Satellite glial cells in sensory ganglia are a recent subject of research in the field of pain and a possible therapeutic target in the future. Therefore, the aim of this study was to summarize some of the important physiological and morphological characteristics of these cells and gather the most relevant scientific evidence about its possible role in the development of chronic pain. CONTENT: In the sensory ganglia, each neuronal body is surrounded by satellite glial cells forming distinct functional units. This close relationship enables bidirectional communication via a paracrine signaling between those two cell types. There is a growing body of evidence that glial satellite cells undergo structural and biochemical changes after nerve injury, which influence neuronal excitability and consequently the development and/or maintenance of pain in different animal models of chronic pain. CONCLUSIONS: Satellite glial cells are important in the establishment of physiological pain, in addition to being a potential target for the development of new pain treatments.

  6. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle.

    Science.gov (United States)

    Egner, Ingrid M; Bruusgaard, Jo C; Gundersen, Kristian

    2016-08-15

    The largest mammalian cells are the muscle fibers, and they have multiple nuclei to support their large cytoplasmic volumes. During hypertrophic growth, new myonuclei are recruited from satellite stem cells into the fiber syncytia, but it was recently suggested that such recruitment is not obligatory: overload hypertrophy after synergist ablation of the plantaris muscle appeared normal in transgenic mice in which most of the satellite cells were abolished. When we essentially repeated these experiments analyzing the muscles by immunohistochemistry and in vivo and ex vivo imaging, we found that overload hypertrophy was prevented in the satellite cell-deficient mice, in both the plantaris and the extensor digitorum longus muscles. We attribute the previous findings to a reliance on muscle mass as a proxy for fiber hypertrophy, and to the inclusion of a significant number of regenerating fibers in the analysis. We discuss that there is currently no model in which functional, sustainable hypertrophy has been unequivocally demonstrated in the absence of satellite cells; an exception is re-growth, which can occur using previously recruited myonuclei without addition of new myonuclei. © 2016. Published by The Company of Biologists Ltd.

  7. Neonatal Satellite Cells Form Small Myotubes in Vitro

    NARCIS (Netherlands)

    Carvajal Monroy, P.L.; Grefte, S.; Kuijpers-Jagtman, A.M.; Den Hoff, Von J.W.; Wagener, F.A.D.T.G.

    2017-01-01

    Although palatal muscle reconstruction in patients with cleft palate takes place during early childhood, normal speech development is often not achieved. We hypothesized that the intrinsic properties of head satellite cells (SCs) and the young age of these patients contribute to the poor muscle

  8. Label-free screening of niche-to-niche variation in satellite stem cells using functionalized pores

    Science.gov (United States)

    Chapman, Matthew R.; Balakrishnan, Karthik; Conboy, Michael J.; Mohanty, Swomitra; Jabart, Eric; Huang, Haiyan; Hack, James; Conboy, Irina M.; Sohn, Lydia L.

    2012-02-01

    Combinations of surface markers are currently used to identify muscle satellite cells. Using pores functionalized with specific antibodies and measuring the transit time of cells passing through these pores, we discovered remarkable heterogeneity in the expression of these markers in muscle (satellite) stem cells that reside in different single myofibers. Microniche-specific variation in stem cells of the same organ has not been previously described, as bulk analysis does not discriminate between separate myofibers or even separate hind-leg muscle groups. We found a significant population of Sca-1+ satellite cells that form myotubes, thereby demonstrating the myogenic potential of Sca-1+ cells, which are currently excluded in bulk sorting. Finally, using our label-free pore screening technique, we have been able to quantify directly surface expression of Notch1 without activation of the Notch pathway. We show for the first time Notch1-expression heterogeneity in unactivated satellite cells. The discovery of fiber-to-fiber variations prompts new research into the reasons for such diversity in muscle stem cells.

  9. Substrate elasticity affects bovine satellite cell activation kinetics in vitro.

    Science.gov (United States)

    Lapin, M R; Gonzalez, J M; Johnson, S E

    2013-05-01

    Satellite cells support efficient postnatal skeletal muscle hypertrophy through fusion into the adjacent muscle fiber. Nuclear contribution allows for maintenance of the fiber myonuclear domain and proficient transcription of myogenic genes. Niche growth factors affect satellite cell biology; however, the interplay between fiber elasticity and microenvironment proteins remains largely unknown. The objective of the experiment was to examine the effects of hepatocyte growth factor (HGF) and surface elasticity on bovine satellite cell (BSC) activation kinetics in vitro. Young's elastic modulus was calculated for the semimembranosus (SM) and LM muscles of young bulls (5 d; n = 8) and adult cows (27 mo; n = 4) cattle. Results indicate that LM elasticity decreased (P Young's modulus for the SM was noted. Bovine satellite cells were seeded atop polyacrylamide bioscaffolds with surface elasticities that mimic young bull and adult cow LM or traditional cultureware. Cells were maintained in low-serum media supplemented with 5 ng/mL HGF or vehicle only for 24 or 48 h. Activation was evaluated by proliferating cell nuclear antigen (PCNA) immunocytochemistry. Results indicate that BSC maintained on rigid surfaces were activated at 24 h and refractive to HGF supplementation. By contrast, fewer (P young bull (8.1 ± 1.7 kPa) or adult cow (14.6 ± 1.6 kPa) LM. Supplementation with HGF promoted activation of BSC cultured on bioscaffolds as measured by an increase (P muscle stem cells (P > 0.05). However, with increasing surface elasticity, an increase (P muscle progenitors was observed. These results confirm that biophysical and biochemical signals regulate BSC activation.

  10. Defining a role for non-satellite stem cells in the regulation of muscle repair following exercise

    Directory of Open Access Journals (Sweden)

    Marni D. Boppart

    2013-11-01

    Full Text Available Skeletal muscle repair is essential for effective remodeling, tissue maintenance, and initiation of beneficial adaptations post-eccentric exercise. A series of well characterized events, such as recruitment of immune cells and activation of satellite cells, constitute the basis for muscle regeneration. However, details regarding the fine-tuned regulation of this process in response to different types of injury are open for investigation. Muscle-resident non-myogenic, non-satellite stem cells expressing conventional mesenchymal stem cell (MSC markers, have the potential to significantly contribute to regeneration given the role for bone marrow-derived MSCs in whole body tissue repair in response to injury and disease. The purpose of this mini-review is to highlight a regulatory role for non-satellite stem cells in the process of skeletal muscle healing post-eccentric exercise. The non-myogenic, non-satellite stem cell fraction will be defined, its role in tissue repair will be briefly reviewed, and recent studies demonstrating a contribution to eccentric exercise-induced regeneration will be presented.  

  11. Cell therapy for ischaemic heart disease: focus on the role of resident cardiac stem cells.

    Science.gov (United States)

    Chamuleau, S A J; Vrijsen, K R; Rokosh, D G; Tang, X L; Piek, J J; Bolli, R

    2009-05-01

    Myocardial infarction results in loss of cardiomyocytes, scar formation, ventricular remodelling, and eventually heart failure. In recent years, cell therapy has emerged as a potential new strategy for patients with ischaemic heart disease. This includes embryonic and bone marrow derived stem cells. Recent clinical studies showed ostensibly conflicting results of intracoronary infusion of autologous bone marrow derived stem cells in patients with acute or chronic myocardial infarction. Anyway, these results have stimulated additional clinical and pre-clinical studies to further enhance the beneficial effects of stem cell therapy. Recently, the existence of cardiac stem cells that reside in the heart itself was demonstrated. Their discovery has sparked intense hope for myocardial regeneration with cells that are obtained from the heart itself and are thereby inherently programmed to reconstitute cardiac tissue. These cells can be detected by several surface markers (e.g. c-kit, Sca-1, MDR1, Isl-1). Both in vitro and in vivo differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells has been demonstrated, and animal studies showed promising results on improvement of left ventricular function. This review will discuss current views regarding the feasibility of cardiac repair, and focus on the potential role of the resident cardiac stem and progenitor cells. (Neth Heart J 2009;17:199-207.).

  12. Lung-resident γδ T cells and their roles in lung diseases.

    Science.gov (United States)

    Cheng, Min; Hu, Shilian

    2017-08-01

    γδ T cells are greatly enriched in mucosal and epithelial sites, such as the skin, respiratory, digestive and reproductive tracts, and they are defined as tissue-resident immune cells. In these tissues, the characteristics and biological roles of γδ T cells are distinguished from each other. The lungs represent the most challenging immunological dilemma for the host, and they have their own effective immune system. The abundance of γδ T cells, an estimated 8-20% of resident pulmonary lymphocytes in the lung, maintains lung tissue homeostasis. In this review, we summarize the recent research progress regarding lung-resident γδ T cells, including their development, residency and immune characteristics, and discuss the involvement of γδ T cells in infectious diseases of the lung, including bacterial, viral and fungal infections; lung allergic disease; lung inflammation and fibrosis; and lung cancer. © 2017 John Wiley & Sons Ltd.

  13. Hepatic Stellate Cells Support Hematopoiesis and are Liver-Resident Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Claus Kordes

    2013-02-01

    Full Text Available Background/Aims: Hematopoiesis can occur in the liver, when the bone marrow fails to provide an adequate environment for hematopoietic stem cells. Hepatic stellate cells possess characteristics of stem/progenitor cells, but their contribution to hematopoiesis is not known thus far. Methods: Isolated hepatic stellate cells from rats were characterized with respect to molecular markers of bone marrow mesenchymal stem cells (MSC and treated with adipocyte or osteocyte differentiation media. Stellate cells of rats were further co-cultured with murine stem cell antigen-1+ hematopoietic stem cells selected by magnetic cell sorting. The expression of murine hematopoietic stem cell markers was analyzed by mouse specific quantitative PCR during co-culture. Hepatic stellate cells from eGFP+ rats were transplanted into lethally irradiated wild type rats. Results: Desmin-expressing stellate cells were associated with hematopoietic sites in the fetal rat liver. Hepatic stellate cells expressed MSC markers and were able to differentiate into adipocytes and osteocytes in vitro. Stellate cells supported hematopoietic stem/progenitor cells during co-culture similar to bone marrow MSC, but failed to differentiate into blood cell lineages after transplantation. Conclusion: Hepatic stellate cells are liver-resident MSC and can fulfill typical functions of bone marrow MSC such as the differentiation into adipocytes or osteocytes and support of hematopoiesis.

  14. Satellite cell activity is differentially affected by contraction mode in human muscle following a work-matched bout of exercise

    Directory of Open Access Journals (Sweden)

    Robert D Hyldahl

    2014-12-01

    Full Text Available Optimal repair and adaptation of skeletal muscle is facilitated by resident stem cells (satellite cells. To understand how different exercise modes influence satellite cell dynamics, we measured satellite cell activity in conjunction with markers of muscle damage and inflammation in human skeletal muscle following a single work- and intensity-matched bout of eccentric (ECC or concentric contractions (CON. Participants completed a single bout of ECC (n=7 or CON (n=7 of the knee extensors. A muscle biopsy was obtained before and 24 h after exercise. Functional measures and immunohistochemical analyses were used to determine the extent of muscle damage and indices of satellite cell activity. Cytokine concentrations were measured using a multiplexed magnetic bead assay. Isokinetic peak torque decreased following ECC (p<0.05 but not CON. Greater histological staining of the damage marker Xin was observed in muscle samples of ECC vs CON. Tenasin C immunoreactivity increased 15 fold (P<0.01 following ECC and was unchanged following CON. The inflammatory cytokines interferon gamma-induced protein 10 (IP-10 and monocyte chemotactic protein 1 (MCP-1 increased pre- to post-ECC (4.26 ± 1.4 vs. 10.49 ± 5.8 pg/ml, and 3.06 ± 0.7 vs. 6.25 ± 4.6 pg/ml, respectively; p<0.05. There was no change in any cytokine post-CON. Satellite cell content increased 27% pre- to post-ECC (0.10 ± 0.031 vs. 0.127 ± 0.041, respectively; p<0.05. There was no change in satellite cell number in CON (0.099 ± 0.027 vs. 0.102 ± 0.029, respectively. There was no fiber type-specific satellite cell response following either exercise mode. ECC but not CON resulted in an increase in MyoD positive nuclei per myofiber pre- to post-exercise (p<0.05, but there was no change in MyoD DNA binding activity in either condition. In conclusion, ECC but not CON results in functional and histological evidence of muscle damage that is accompanied by increased satellite cell activity 24 h post-exercise.

  15. The satellite cell in male and female, developing and adult mouse muscle: distinct stem cells for growth and regeneration.

    Directory of Open Access Journals (Sweden)

    Alice Neal

    Full Text Available Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration.

  16. Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.

    Science.gov (United States)

    Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M; Franklin, Ruth A; Luo, Chong T; Oh, Soyoung A; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S; Li, Ming O

    2016-01-28

    Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αβ, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a, and CD103, these cells share a gene-expression signature distinct from those of conventional NK cells, T cells, and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type-1-like innate lymphoid cells and type 1 innate-like T cells.

  17. RESIDENT PROGENITOR CARDIAC CELLS IN PATIENTS WITH DILATED CARDIOMYOPATHY AND CONGESTIVE HEART FAILURE

    Directory of Open Access Journals (Sweden)

    T. G. Kulikova

    2014-01-01

    Full Text Available Aim. To study content of resident progenitor cardiomyocytes in endomyocardial biopsy samples of patients with dilated cardiomyopathy (DCM and heart failure (HF at different disease stages and relate it to patient clinical characteristics.Material and methods. Resident progenitor cardiomyocytes were studied in endomyocardial biopsy samples from 14 patients (age from 26 to 52 years old with DCM and HF by immunofluorescence method. Results were analyzed individually for each patient.Results. Resident progenitor cardiomyocytes expressing simultaneously stem cell markers c-kit, MDR-1 and early cardiomyocyte differentiation markers GATA-4 and Nkx2.5 were found in endomyocardial biopsy samples from patients with DCM and HF. Resident progenitor cardiomyocytes detected by these cell markers were found in all patients at all disease stages.Conclusion. Results show that the myocardial regenerative processes exist at all stages of the disease progression.

  18. RESIDENT PROGENITOR CARDIAC CELLS IN PATIENTS WITH DILATED CARDIOMYOPATHY AND CONGESTIVE HEART FAILURE

    Directory of Open Access Journals (Sweden)

    T. G. Kulikova

    2015-09-01

    Full Text Available Aim. To study content of resident progenitor cardiomyocytes in endomyocardial biopsy samples of patients with dilated cardiomyopathy (DCM and heart failure (HF at different disease stages and relate it to patient clinical characteristics.Material and methods. Resident progenitor cardiomyocytes were studied in endomyocardial biopsy samples from 14 patients (age from 26 to 52 years old with DCM and HF by immunofluorescence method. Results were analyzed individually for each patient.Results. Resident progenitor cardiomyocytes expressing simultaneously stem cell markers c-kit, MDR-1 and early cardiomyocyte differentiation markers GATA-4 and Nkx2.5 were found in endomyocardial biopsy samples from patients with DCM and HF. Resident progenitor cardiomyocytes detected by these cell markers were found in all patients at all disease stages.Conclusion. Results show that the myocardial regenerative processes exist at all stages of the disease progression.

  19. Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair.

    Science.gov (United States)

    MacLeod, Amanda S; Rudolph, Ross; Corriden, Ross; Ye, Ivan; Garijo, Olivia; Havran, Wendy L

    2014-06-15

    Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, but their role in UV radiation (UVR)-mediated skin injury and subsequent tissue regeneration is less clear. In this study, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermal γδ T cells (DETCs) in mice through mechanisms involving the release of ATP from keratinocytes. Following UVR, extracellular ATP leads to an increase in CD69 expression, proliferation, and IL-17 production, and to changes in DETC morphology. Furthermore, we find that the purinergic receptor P2X7 and caspase-1 are necessary for UVR-induced IL-1 production in keratinocytes, which increases IL-17 secretion by DETCs. IL-17, in turn, induces epidermal TNF-related weak inducer of apoptosis and growth arrest and DNA damage-associated gene 45, two molecules linked to the DNA repair response. Finally, we demonstrate that DETCs and human skin-resident T cells limit DNA damage in keratinocytes. Taken together, our findings establish a novel role for skin-resident T cells in the UVR-associated DNA repair response and underscore the importance of skin-resident T cells to overall skin regeneration.

  20. Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martín A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2016-01-01

    Accumulation of oxidized proteins is a hallmark of cellular and organismal aging. Adult muscle stem cell (or satellite cell) replication and differentiation is compromised with age contributing to sarcopenia. However, the molecular events related to satellite cell dysfunction during aging are not...

  1. Resident macrophages influence stem cell activity in the mammary gland

    NARCIS (Netherlands)

    Gyorki, D.E.; Asselin-Labat, M.L.; Rooijen, van N.; Lindeman, G.J.; Visvader, J.E.

    2009-01-01

    Introduction Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells

  2. Discovery of Novel Small Molecules that Activate Satellite Cell Proliferation and Enhance Repair of Damaged Muscle.

    Science.gov (United States)

    Billin, Andrew N; Bantscheff, Marcus; Drewes, Gerard; Ghidelli-Disse, Sonja; Holt, Jason A; Kramer, Henning F; McDougal, Alan J; Smalley, Terry L; Wells, Carrow I; Zuercher, William J; Henke, Brad R

    2016-02-19

    Skeletal muscle progenitor stem cells (referred to as satellite cells) represent the primary pool of stem cells in adult skeletal muscle responsible for the generation of new skeletal muscle in response to injury. Satellite cells derived from aged muscle display a significant reduction in regenerative capacity to form functional muscle. This decrease in functional recovery has been attributed to a decrease in proliferative capacity of satellite cells. Hence, agents that enhance the proliferative abilities of satellite cells may hold promise as therapies for a variety of pathological settings, including repair of injured muscle and age- or disease-associated muscle wasting. Through phenotypic screening of isolated murine satellite cells, we identified a series of 2,4-diaminopyrimidines (e.g., 2) that increased satellite cell proliferation. Importantly, compound 2 was effective in accelerating repair of damaged skeletal muscle in an in vivo mouse model of skeletal muscle injury. While these compounds were originally prepared as c-Jun N-terminal kinase 1 (JNK-1) inhibitors, structure-activity analyses indicated JNK-1 inhibition does not correlate with satellite cell activity. Screening against a broad panel of kinases did not result in identification of an obvious molecular target, so we conducted cell-based proteomics experiments in an attempt to identify the molecular target(s) responsible for the potentiation of the satellite cell proliferation. These data provide the foundation for future efforts to design improved small molecules as potential therapeutics for muscle repair and regeneration.

  3. Iron acquisition by Mycobacterium tuberculosis residing within myeloid dendritic cells.

    Science.gov (United States)

    Olakanmi, Oyebode; Kesavalu, Banurekha; Abdalla, Maher Y; Britigan, Bradley E

    2013-12-01

    The pathophysiology of Mycobacterium tuberculosis (M.tb) infection is linked to the ability of the organism to grow within macrophages. Lung myeloid dendritic cells are a newly recognized reservoir of M.tb during infection. Iron (Fe) acquisition is critical for M.tb growth. In vivo, extracellular Fe is chelated to transferrin (TF) and lactoferrin (LF). We previously reported that M.tb replicating in human monocyte-dervied macrophages (MDM) can acquire Fe bound to TF, LF, and citrate, as well as from the MDM cytoplasm. Access of M.tb to Fe may influence its growth in macrophages and dendritic cells. In the present work we confirmed the ability of different strains of M.tb to grow in human myeloid dendritic cells in vitro. Fe acquired by M.tb replicating within dendritic cells from externally added Fe chelates varied with the Fe chelate present in the external media: Fe-citrate > Fe-LF > Fe-TF. Fe acquisition rates from each chelate did not vary over 7 days. M.tb within dendritic cells also acquired Fe from the dendritic cell cytoplasm, with the efficiency of Fe acquisition greater from cytoplasmic Fe sources, regardless of the initial Fe chelate from which that cytoplasmic Fe was derived. Growth and Fe acquisition results with human MDM were similar to those with dendritic cells. M.tb grow and replicate within myeloid dendritic cells in vitro. Fe metabolism of M.tb growing in either MDM or dendritic cells in vitro is influenced by the nature of Fe available and the organism appears to preferentially access cytoplasmic rather than extracellular Fe sources. Whether these in vitro data extend to in vivo conditions should be examined in future studies.

  4. Rb1 gene inactivation expands satellite cell and postnatal myoblast pools.

    Science.gov (United States)

    Hosoyama, Tohru; Nishijo, Koichi; Prajapati, Suresh I; Li, Guangheng; Keller, Charles

    2011-06-03

    Satellite cells are well known as a postnatal skeletal muscle stem cell reservoir that under injury conditions participate in repair. However, mechanisms controlling satellite cell quiescence and activation are the topic of ongoing inquiry by many laboratories. In this study, we investigated whether loss of the cell cycle regulatory factor, pRb, is associated with the re-entry of quiescent satellite cells into replication and subsequent stem cell expansion. By ablation of Rb1 using a Pax7CreER,Rb1 conditional mouse line, satellite cell number was increased 5-fold over 6 months. Furthermore, myoblasts originating from satellite cells lacking Rb1 were also increased 3-fold over 6 months, while terminal differentiation was greatly diminished. Similarly, Pax7CreER,Rb1 mice exhibited muscle fiber hypotrophy in vivo under steady state conditions as well as a delay of muscle regeneration following cardiotoxin-mediated injury. These results suggest that cell cycle re-entry of quiescent satellite cells is accelerated by lack of Rb1, resulting in the expansion of both satellite cells and their progeny in adolescent muscle. Conversely, that sustained Rb1 loss in the satellite cell lineage causes a deficit of muscle fiber formation. However, we also show that pharmacological inhibition of protein phosphatase 1 activity, which will result in pRb inactivation accelerates satellite cell activation and/or expansion in a transient manner. Together, our results raise the possibility that reversible pRb inactivation in satellite cells and inhibition of protein phosphorylation may provide a new therapeutic tool for muscle atrophy by short term expansion of the muscle stem cells and myoblast pool.

  5. Isolation, culture and biological characteristics of multipotent porcine skeletal muscle satellite cells.

    Science.gov (United States)

    Yang, Jinjuan; Liu, Hao; Wang, Kunfu; Li, Lu; Yuan, Hongyi; Liu, Xueting; Liu, Yingjie; Guan, Weijun

    2017-03-02

    Skeletal muscle has a huge regenerative potential for postnatal muscle growth and repair, which mainly depends on a kind of muscle progenitor cell population, called satellite cell. Nowadays, the majority of satellite cells were obtained from human, mouse, rat and other animals but rarely from pig. In this article, the porcine skeletal muscle satellite cells were isolated and cultured in vitro. The expression of surface markers of satellite cells was detected by immunofluorescence and RT-PCR assays. The differentiation capacity was assessed by inducing satellite cells into adipocytes, myoblasts and osteoblasts. The results showed that satellite cells isolated from porcine tibialis anterior were subcultured up to 12 passages and were positive for Pax7, Myod, c-Met, desmin, PCNA and NANOG but were negative for Myogenin. Satellite cells were also induced to differentiate into adipocytes, osteoblasts and myoblasts, respectively. These findings indicated that porcine satellite cells possess similar biological characteristics of stem cells, which may provide theoretical basis and experimental evidence for potential therapeutic application in the treatment of dystrophic muscle and other muscle injuries.

  6. Feasibility Analysis on the Utilization of the Iridium Satellite Communications Network for Resident Space Objects in Low Earth Orbit

    Science.gov (United States)

    2013-03-21

    equatorial speed. Ideally, the GEO satellite remains directly overhead in the absence of perturbing forces. Of course , perturbing forces exist and cause a...respectively. Assuming a mean Earth radius of 6371 km, the Earth- central angles and can be found from trigonometry using the footprint

  7. Satellite Cells Contribution to Exercise Mediated Muscle Hypertrophy and Repair

    Science.gov (United States)

    Bazgir, Behzad; Fathi, Rouhollah; Rezazadeh Valojerdi, Mojtaba; Mozdziak, Paul; Asgari, Alireza

    2017-01-01

    Satellite cells (SCs) are the most abundant skeletal muscle stem cells. They are widely recognized for their contributions to maintenance of muscle mass, regeneration and hypertrophy during the human life span. These cells are good candidates for cell therapy due to their self-renewal capabilities and presence in an undifferentiated form. Presently, a significant gap exists between our knowledge of SCs behavior and their application as a means for human skeletal muscle tissue repair and regeneration. Both physiological and pathological stimuli potentially affect SCs activation, proliferation, and terminal differentiation the former category being the focus of this article. Activation of SCs occurs following exercise, post-training micro-injuries, and electrical stimulation. Exercise, as a potent and natural stimulus, is at the center of numerous studies on SC activation and relevant fields. According to research, different exercise modalities end with various effects. This review article attempts to picture the state of the art of the SCs life span and their engagement in muscle regeneration and hypertrophy in exercise. PMID:28042532

  8. Satellite Cells Contribution to Exercise Mediated Muscle Hypertrophy and Repair

    Directory of Open Access Journals (Sweden)

    Behzad Bazgir

    2016-10-01

    Full Text Available Satellite cells (SCs are the most abundant skeletal muscle stem cells. They are widely recognized for their contributions to maintenance of muscle mass, regeneration and hypertrophy during the human life span. These cells are good candidates for cell therapy due to their self-renewal capabilities and presence in an undifferentiated form. Presently, a significant gap exists between our knowledge of SCs behavior and their application as a means for human skeletal muscle tissue repair and regeneration. Both physiological and pathological stimuli potentially affect SCs activation, proliferation, and terminal differentiation - the former category being the focus of this article. Activation of SCs occurs following exercise, post-training micro-injuries, and electrical stimulation. Exercise, as a potent and natural stimulus, is at the center of numerous studies on SC activation and relevant fields. According to research, different exercise modalities end with various effects. This review article attempts to picture the state of the art of the SCs life span and their engagement in muscle regeneration and hypertrophy in exercise.

  9. An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage.

    Science.gov (United States)

    Southcombe, J H; Mounce, G; McGee, K; Elghajiji, A; Brosens, J; Quenby, S; Child, T; Granne, I

    2017-01-23

    When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress. We demonstrate that unexplained recurrent miscarriage is associated with significantly decreased expression of the T-cell co-receptor CD8 and tissue residency marker CD69. These cells differ from those found in control women, with less expression of CD127 indicating a lack of homeostatic cell control through IL-7 signalling. Nevertheless this population is resident in the endometrium of women who have RM, more than three months after the last miscarriage, indicating that the memory CD8-T cell population is altered in RM patients. This is the first evidence of a differing pre-pregnancy phenotype in endometrial immune cells in RM.

  10. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

    Science.gov (United States)

    Sojka, Dorothy K; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A; Artyomov, Maxim N; Ivanova, Yulia; Zhong, Chao; Chase, Julie M; Rothman, Paul B; Yu, Jenny; Riley, Joan K; Zhu, Jinfang; Tian, Zhigang; Yokoyama, Wayne M

    2014-01-01

    Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001 PMID:24714492

  11. Differential satellite cell density of type I and II fibres with lifelong endurance running in old men

    DEFF Research Database (Denmark)

    Mackey, Abigail; Karlsen, A; Couppé, C

    2014-01-01

    between these variables were determined. RESULTS: In O-Un and O-Tr, type II fibres were smaller and contained fewer satellite cells than type I fibres. However, when expressed relative to fibre area, the difference in satellite cell content between fibre types was eliminated in O-Tr, but not O...... the satellite cell pool and (ii) is associated with a similar density of satellite cells in type I and II fibres despite a failure to preserve the equal fibre type distribution of satellite cells observed in young individuals. Taken together, these data reveal a differential regulation of satellite cell content...

  12. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  13. Assessment of satellite cell number and activity status in human skeletal muscle biopsies

    DEFF Research Database (Denmark)

    Mackey, Abigail; Kjaer, Michael; Charifi, Nadia;

    2009-01-01

    The primary aim of our study was to validate the assessment of myonuclear and satellite cell number in biopsies from human skeletal muscle. We found that 25 type I and 25 type II fibers are sufficient to estimate the mean number of myonuclei per fiber. In contrast, the assessment of satellite cells...

  14. Isolation and characterization of satellite cells from rat head branchiomeric muscles

    NARCIS (Netherlands)

    Carvajal Monroy, P.L.; Yablonka-Reuveni, Z.; Grefte, Sander; Kuijpers-Jagtman, Anne Marie; Wagener, F.A.D.T.G.; Hoff, Von den J.W.

    2015-01-01

    This protocol describes the isolation of satellite cells from branchiomeric head muscles of a 9 week-old rat. The muscles originate from different branchial arches. Subsequently, the satellite cells are cultured on a spot coating of millimeter size to study their differentiation. This approach avoid

  15. A myogenic precursor cell that could contribute to regeneration in zebrafish and its similarity to the satellite cell.

    Science.gov (United States)

    Siegel, Ashley L; Gurevich, David B; Currie, Peter D

    2013-09-01

    The cellular basis for mammalian muscle regeneration has been an area of intense investigation over recent decades. The consensus is that a specialized self-renewing stem cell, termed the satellite cell, plays a major role during the process of regeneration in amniotes. How broadly this mechanism is deployed within the vertebrate phylogeny remains an open question. A lack of information on the role of cells analogous to the satellite cell in other vertebrate systems is even more unexpected given the fact that satellite cells were first designated in frogs. An intriguing aspect of this debate is that a number of amphibia and many fish species exhibit epimorphic regenerative processes in specific tissues, whereby regeneration occurs by the dedifferentiation of the damaged tissue, without deploying specialized stem cell populations analogous to satellite cells. Hence, it is feasible that a cellular process completely distinct from that deployed during mammalian muscle regeneration could operate in species capable of epimorphic regeneration. In this minireview, we examine the evidence for the broad phylogenetic distribution of satellite cells. We conclude that, in the vertebrates examined so far, epimorphosis does not appear to be deployed during muscle regeneration, and that analogous cells expressing similar marker genes to satellite cells appear to be deployed during the regenerative process. However, the functional definition of these cells as self-renewing muscle stem cells remains a final hurdle to the definition of the satellite cell as a generic vertebrate cell type.

  16. Adult Vascular Wall Resident Multipotent Vascular Stem Cells, Matrix Metalloproteinases, and Arterial Aneurysms

    Directory of Open Access Journals (Sweden)

    Bruno Amato

    2015-01-01

    Full Text Available Evidences have shown the presence of multipotent stem cells (SCs at sites of arterial aneurysms: they can differentiate into smooth muscle cells (SMCs and are activated after residing in a quiescent state in the vascular wall. Recent studies have implicated the role of matrix metalloproteinases in the pathogenesis of arterial aneurysms: in fact the increased synthesis of MMPs by arterial SMCs is thought to be a pivotal mechanism in aneurysm formation. The factors and signaling pathways involved in regulating wall resident SC recruitment, survival, proliferation, growth factor production, and differentiation may be also related to selective expression of different MMPs. This review explores the relationship between adult vascular wall resident multipotent vascular SCs, MMPs, and arterial aneurysms.

  17. Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site.

    Directory of Open Access Journals (Sweden)

    Kutlu G Elpek

    Full Text Available Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions.

  18. The Potential for Resident Lung Mesenchymal Stem Cells to Promote Functional Tissue Regeneration: Understanding Microenvironmental Cues

    Directory of Open Access Journals (Sweden)

    Susan M. Majka

    2012-10-01

    Full Text Available Tissue resident mesenchymal stem cells (MSCs are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs and endothelial progenitor cells (EPC are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH, pulmonary fibrosis (PF, chronic obstructive pulmonary disease (COPD/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases.

  19. The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: understanding microenvironmental cues.

    Science.gov (United States)

    Foronjy, Robert F; Majka, Susan M

    2012-12-01

    Tissue resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs) and endothelial progenitor cells (EPC) are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH), pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD)/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases.

  20. Notch Signaling Rescues Loss of Satellite Cells Lacking Pax7 and Promotes Brown Adipogenic Differentiation.

    Science.gov (United States)

    Pasut, Alessandra; Chang, Natasha C; Rodriguez, Uxia Gurriaran; Faulkes, Sharlene; Yin, Hang; Lacaria, Melanie; Ming, Hong; Rudnicki, Michael A

    2016-07-12

    Pax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) rescues the loss of Pax7-deficient satellite cells and restores their proliferative potential. Strikingly NICD1-expressing satellite cells do not undergo myogenic differentiation and instead acquire a brown adipogenic fate both in vivo and in vitro. NICD-expressing Pax7(-/-) satellite cells fail to upregulate MyoD and instead express the brown adipogenic marker PRDM16. Overall, these results show that Notch1 activation compensates for the loss of Pax7 in the quiescent state and acts as a molecular switch to promote brown adipogenesis in adult skeletal muscle.

  1. Methods for Observing and Quantifying Muscle Satellite Cell Motility and Invasion In Vitro.

    Science.gov (United States)

    Lund, Dane K; McAnulty, Patrick; Siegel, Ashley L; Cornelison, Ddw

    2017-01-01

    Motility and/or chemotaxis of satellite cells has been suggested or observed in multiple in vitro and in vivo contexts. Satellite cell motility also affects the efficiency of muscle regeneration, particularly in the context of engrafted exogenous cells. Consequently, there is keen interest in determining what cell-autonomous and environmental factors influence satellite cell motility and chemotaxis in vitro and in vivo. In addition, the ability of activated satellite cells to relocate in vivo would suggest that they must be able to invade and transit through the extracellular matrix (ECM), which is supported by studies in which alteration or addition of matrix metalloprotease (MMP) activity enhanced the spread of engrafted satellite cells. However, despite its potential importance, analysis of satellite cell motility or invasion quantitatively even in an in vitro setting can be difficult; one of the most powerful techniques for overcoming these difficulties is timelapse microscopy. Identification and longitudinal evaluation of individual cells over time permits not only quantification of variations in motility due to intrinsic or extrinsic factors, it permits observation and analysis of other (frequently unsuspected) cellular activities as well. We describe here three protocols developed in our group for quantitatively analyzing satellite cell motility over time in two dimensions on purified ECM substrates, in three dimensions on a living myofiber, and in three dimensions through an artificial matrix.

  2. Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population.

    Science.gov (United States)

    Morrison, Jamie I; Lööf, Sara; He, Pingping; Simon, András

    2006-01-30

    In contrast to mammals, salamanders can regenerate complex structures after injury, including entire limbs. A central question is whether the generation of progenitor cells during limb regeneration and mammalian tissue repair occur via separate or overlapping mechanisms. Limb regeneration depends on the formation of a blastema, from which the new appendage develops. Dedifferentiation of stump tissues, such as skeletal muscle, precedes blastema formation, but it was not known whether dedifferentiation involves stem cell activation. We describe a multipotent Pax7+ satellite cell population located within the skeletal muscle of the salamander limb. We demonstrate that skeletal muscle dedifferentiation involves satellite cell activation and that these cells can contribute to new limb tissues. Activation of salamander satellite cells occurs in an analogous manner to how the mammalian myofiber mobilizes stem cells during skeletal muscle tissue repair. Thus, limb regeneration and mammalian tissue repair share common cellular and molecular programs. Our findings also identify satellite cells as potential targets in promoting mammalian blastema formation.

  3. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance.

    Science.gov (United States)

    Soroosh, Pejman; Doherty, Taylor A; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H; Croft, Michael

    2013-04-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iTreg cells is unclear. Here, we show that lung-resident tissue MØs coexpress TGF-β and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) Treg cells. Treg cell induction in this model depended on both TGF-β and retinoic acid. Transfer of the antigen-pulsed tissue MØs into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue MØs to allergens suppressed their ability to generate iTreg cells coincident with blocking airway tolerance. Suppression of Treg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue MØs have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma.

  4. Epicardial Origin of Resident Mesenchymal Stem Cells in the Adult Mammalian Heart

    Directory of Open Access Journals (Sweden)

    Naisana S. Asli

    2014-04-01

    Full Text Available The discovery of stem and progenitor cells in the adult mammalian heart has added a vital dimension to the field of cardiac regeneration. Cardiac-resident stem cells are likely sequestered as reserve cells within myocardial niches during the course of embryonic cardiogenesis, although they may also be recruited from external sources, such as bone marrow. As we begin to understand the nature of cardiac-resident stem and progenitor cells using a variety of approaches, it is evident that they possess an identity embedded within their gene regulatory networks that favours cardiovascular lineage potential. In addition to contributing lineage descendants, cardiac stem cells may also be stress sensors, offering trophic cues to other cell types, including cardiomyocytes and vasculature cells, and likely other stem cells and immune cells, during adaptation and repair. This presents numerous possibilities for endogenous cardiac stem and progenitor cells to be used in cell therapies or as targets in heart rejuvenation. In this review, we focus on the epicardium as an endogenous source of multi-potential mesenchymal progenitor cells in development and as a latent source of such progenitors in the adult. We track the origin and plasticity of the epicardium in embryos and adults in both homeostasis and disease. In this context, we ask whether directed activation of epicardium-derived progenitor cells might have therapeutic application.

  5. Karyopherin Alpha 1 Regulates Satellite Cell Proliferation and Survival by Modulating Nuclear Import.

    Science.gov (United States)

    Choo, Hyo-Jung; Cutler, Alicia; Pavlath, Grace K

    2016-07-19

    Satellite cells are stem cells with an essential role in skeletal muscle repair. Precise regulation of gene expression is critical for proper satellite cell quiescence, proliferation, differentiation and self-renewal. Nuclear proteins required for gene expression are dependent on the nucleocytoplasmic transport machinery to access to nucleus, however little is known about regulation of nuclear transport in satellite cells. The best characterized nuclear import pathway is classical nuclear import which depends on a classical nuclear localization signal (cNLS) in a cargo protein and the heterodimeric import receptors, karyopherin alpha (KPNA) and beta (KPNB). Multiple KPNA1 paralogs exist and can differ in importing specific cNLS proteins required for cell differentiation and function. We show that transcripts for six Kpna paralogs underwent distinct changes in mouse satellite cells during muscle regeneration accompanied by changes in cNLS proteins in nuclei. Depletion of KPNA1, the most dramatically altered KPNA, caused satellite cells in uninjured muscle to prematurely activate, proliferate and undergo apoptosis leading to satellite cell exhaustion with age. Increased proliferation of satellite cells led to enhanced muscle regeneration at early stages of regeneration. In addition, we observed impaired nuclear localization of two key KPNA1 cargo proteins: p27, a cyclin-dependent kinase inhibitor associated with cell cycle control and lymphoid enhancer factor 1, a critical cotranscription factor for β-catenin. These results indicate that regulated nuclear import of proteins by KPNA1 is critical for satellite cell proliferation and survival and establish classical nuclear import as a novel regulatory mechanism for controlling satellite cell fate. Stem Cells 2016.

  6. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem

  7. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem cel

  8. Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish.

    Science.gov (United States)

    Berberoglu, Michael A; Gallagher, Thomas L; Morrow, Zachary T; Talbot, Jared C; Hromowyk, Kimberly J; Tenente, Inês M; Langenau, David M; Amacher, Sharon L

    2017-04-15

    Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle. Here, we show that adult zebrafish skeletal muscle contains cells similar to mammalian satellite cells. Adult zebrafish satellite-like cells have dense heterochromatin, express Pax7 and Pax3, proliferate in response to injury, and show peak myogenic responses 4-5 days post-injury (dpi). Furthermore, using a pax7a-driven GFP reporter, we present evidence implicating satellite-like cells as a possible source of new muscle. In lieu of central nucleation, which distinguishes regenerating myofibers in mammals, we describe several characteristics that robustly identify newly-forming myofibers from surrounding fibers in injured adult zebrafish muscle. These characteristics include partially overlapping expression in satellite-like cells and regenerating myofibers of two RNA-binding proteins Rbfox2 and Rbfoxl1, known to regulate embryonic muscle development and function. Finally, by analyzing pax7a; pax7b double mutant zebrafish, we show that Pax7 is required for adult skeletal muscle repair, as it is in the mouse.

  9. Comparison and analysis of Wuding and avian chicken skeletal muscle satellite cells.

    Science.gov (United States)

    Tong, H Q; Jiang, Z Q; Dou, T F; Li, Q H; Xu, Z Q; Liu, L X; Gu, D H; Rong, H; Huang, Y; Chen, X B; Jois, M; Te Pas, M F W; Ge, C R; Jia, J J

    2016-10-05

    Chicken skeletal muscle satellite cells are located between the basement membrane and the sarcolemma of mature muscle fibers. Avian broilers have been genetically selected based on their high growth velocity and large muscle mass. The Wuding chicken is a famous local chicken in Yunnan Province that undergoes non-selection breeding and is slow growing. In this study, we aimed to explore differences in the proliferation and differentiation properties of satellite cells isolated from the two chicken breeds. Using immunofluorescence, hematoxylin-eosin staining and real-time polymerase chain reaction analysis, we analyzed the in vitro characteristics of proliferating and differentiating satellite cells isolated from the two chicken breeds. The growth curve of satellite cells was S-shaped, and cells from Wuding chickens entered the logarithmic phase and plateau phase 1 day later than those from Avian chicken. The results also showed that the two skeletal muscle satellite cell lines were positive for Pax7, MyoD and IGF-1. The expression of Pax7 followed a downward trend, whereas that of MyoD and IGF-1 first increased and subsequently decreased in cells isolated from the two chickens. These data indicated that the skeletal muscle satellite cells of Avian chicken grow and differentiate faster than did those of Wuding chickens. We suggest that the methods of breeding selection applied to these breeds regulate the characteristics of skeletal muscle satellite cells to influence muscle growth.

  10. Phenotypic changes in satellite glial cells in cultured trigeminal ganglia.

    Science.gov (United States)

    Belzer, Vitali; Shraer, Nathanael; Hanani, Menachem

    2010-11-01

    Satellite glial cells (SGCs) are specialized cells that form a tight sheath around neurons in sensory ganglia. In recent years, there is increasing interest in SGCs and they have been studied in both intact ganglia and in tissue culture. Here we studied phenotypic changes in SGCs in cultured trigeminal ganglia from adult mice, containing both neurons and SGCs, using phase optics, immunohistochemistry and time-lapse photography. Cultures were followed for up to 14 days. After isolation virtually every sensory neuron is ensheathed by SGCs, as in the intact ganglia. After one day in culture, SGCs begin to migrate away from their parent neurons, but in most cases the neurons still retain an intact glial cover. At later times in culture, there is a massive migration of SGCs away from the neurons and they undergo clear morphological changes, and at 7 days they become spindle-shaped. At one day in culture SGCs express the glial marker glutamine synthetase, and also the purinergic receptor P2X7. From day 2 in culture the glutamine synthetase expression is greatly diminished, whereas that of P2X7 is largely unchanged. We conclude that SGCs retain most of their characteristics for about 24 h after culturing, but undergo major phenotypic changes at later times.

  11. Replication of the resident Marek's Disease virus genome in synchronized nonproducer MKT-1 cells.

    Science.gov (United States)

    Lau, R Y; Nonoyama, M

    1980-02-01

    MKT-1, a virus nonproducer lymphoblastoid cell line established from a Marek's disease tumor, was synchronized by double thymidine block to determine the sequence of events in the synthesis of cellular and latent marek's disease virus DNA. Cellular DNA synthesis was measured by incorporation of [3H]thymidine, whereas viral DNA synthesis was determined by DNA-DNA reassociation kinetics. The results of these studies indicate that the resident Marek's disease viral DNA in MKT-1 cells replicates during the early S phase of the cell cycle, before the onset of active cellular DNA synthesis. This observation is similar to that seen in the replication of resident Epstein-Barr virus DNA in synchronized Raji cells.

  12. LOCAL IMMUNITY BY TISSUE-RESIDENT CD8+ MEMORY T CELLS

    Directory of Open Access Journals (Sweden)

    Thomas eGebhardt

    2012-11-01

    Full Text Available Microbial infection primes a CD8+ cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8+ T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103+ memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Here, we review evolving concepts regarding the generation and long-term persistence of these tissue-resident memory T cells (TRM in epithelial and neuronal tissues. We further discuss the role of TRM cells in local infection control and their contribution to localized immune phenomena, in both mice and humans.

  13. Tissue-Resident Memory T Cells and Fixed Immune Surveillance in Nonlymphoid Organs.

    Science.gov (United States)

    Carbone, Francis R

    2015-07-01

    T cell immunity is often defined in terms of memory lymphocytes that use the blood to access a range of organs. T cells are involved in two patterns of recirculation. In one, the cells shuttle back and forth between blood and secondary lymphoid organs, whereas in the second, memory cells recirculate between blood and nonlymphoid tissues. The latter is a means by which blood T cells control peripheral infection. It is now clear that there exists a distinct memory T cell subset that is absent from blood but found within nonlymphoid tissues. These nonrecirculating tissue-resident memory T (TRM) cells develop within peripheral compartments and never spread beyond their point of lodgement. This review examines fixed immune surveillance by TRM cells, highlighting features that make them potent controllers of infection in nonlymphoid tissues. These features provide clues about TRM cell specialization, such as their ability to deal with sequestered, persisting infections confined to peripheral compartments.

  14. The effect of temperature on proliferation and differentiation of chicken skeletal muscle satellite cells isolated from different muscle types.

    Science.gov (United States)

    Harding, Rachel L; Halevy, Orna; Yahav, Shlomo; Velleman, Sandra G

    2016-04-01

    Skeletal muscle satellite cells are a muscle stem cell population that mediate posthatch muscle growth and repair. Satellite cells respond differentially to environmental stimuli based upon their fiber-type of origin. The objective of this study was to determine how temperatures below and above the in vitro control of 38°C affected the proliferation and differentiation of satellite cells isolated from the chicken anaerobic pectoralis major (p. major) or mixed fiber biceps femoris (b.femoris) muscles. The satellite cells isolated from the p. major muscle were more sensitive to both cold and hot temperatures compared to the b.femoris satellite cells during both proliferation and differentiation. The expressions of myogenic regulatory transcription factors were also different between satellite cells from different fiber types. MyoD expression, which partially regulates proliferation, was generally expressed at higher levels in p. major satellite cells compared to the b.femoris satellite cells from 33 to 43°C during proliferation and differentiation. Similarly, myogenin expression, which is required for differentiation, was also expressed at higher levels in p. major satellite cells in response to both cold and hot temperatures during proliferation and differentiation than b. femoris satellite cells. These data demonstrate that satellite cells from the anaerobic p. major muscle are more sensitive than satellite cells from the aerobic b. femoris muscle to both hot and cold thermal stress during myogenic proliferation and differentiation.

  15. A Comparative Study on Rat Intestinal Epithelial Cells and Resident Gut Bacteria (ii) Effect of Arsenite

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to use facultative gut bacteria as an alternate to animals for the initial gastrointestinal toxicity screening of heavy metals, a comparative study on rat intestinal epithelial cells and resident gut bacteria was undertaken.Methods in vitro growth rate of four gut bacteria, dehydrogenase (DHA) and esterase (EA) activity test, intestinal epithelial and bacterial cell membrane enzymes and in situ effect of arsenite were analysed. Results Growth profile of mixed resident population of gut bacteria and pure isolates of Escherichia coli, Pseudomonas sp., Lactobacillus sp., and Staphylococcus sp.revealed an arsenite (2-20 ppm) concentration-dependent inhibition. The viability pattern of epithelial cells also showed similar changes. DHA and EA tests revealed significant inhibition (40%-72%) with arsenite exposure of 5 and 10 ppm in isolated gut bacteria and epithelial cells. Decrease in membrane alkaline phosphatase and Ca2+-Mg2+-ATPase activities was in the range of 33%-55% in four bacteria at the arsenite exposure of 10 ppm, whereas it was 60%-65% in intestinal epithelial villus cells. in situ incubation of arsenite using intestinal loops also showed more or less similar changes in membrane enzymes of resident gut bacterial population and epithelial cells. Conclusion The results indicate that facultative gut bacteria can be used as suitable in vitro model for the preliminary screening of arsenical gastrointestinal cytotoxic effects.

  16. Spatial partitioning of secretory cargo from Golgi resident proteins in live cells

    Directory of Open Access Journals (Sweden)

    White Jamie

    2001-10-01

    Full Text Available Abstract Background To maintain organelle integrity, resident proteins must segregate from itinerant cargo during secretory transport. However, Golgi resident enzymes must have intimate access to secretory cargo in order to carry out glycosylation reactions. The amount of cargo and associated membrane may be significant compared to the amount of Golgi membrane and resident protein, but upon Golgi exit, cargo and resident are efficiently sorted. How this occurs in live cells is not known. Results We observed partitioning of the fluorescent Golgi resident T2-CFP and fluorescent cargo proteins VSVG3-YFP or VSVG3-SP-YFP upon Golgi exit after a synchronous pulse of cargo was released from the ER. Golgi elements remained stable in overall size, shape and relative position as cargo emptied. Cargo segregated from resident rapidly by blebbing into micron-sized domains that contained little or no detectable resident protein and that appeared to be continuous with the parent Golgi element. Post-Golgi transport carriers (TCs exited repeatedly from these domains. Alternatively, entire cargo domains exited Golgi elements, forming large TCs that fused directly with the plasma membrane. However, domain formation did not appear to be an absolute prerequisite for TC exit, since TCs also exited directly from Golgi elements in the absence of large domains. Quantitative cargo-specific photobleaching experiments revealed transfer of cargo between Golgi regions, but no discrete intra-Golgi TCs were observed. Conclusions Our results establish domain formation via rapid lateral partitioning as a general cellular strategy for segregating different transmembrane proteins along the secretory pathway and provide a framework for consideration of molecular mechanisms of secretory transport.

  17. New insights into the epigenetic control of satellite cells

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Epigenetics finely tunes gene expression at a functionallevel without modifying the DNA sequence, therebycontributing to the complexity of genomic regulation.Satellite cells (SCs) are adult muscle stem cells thatare important for skeletal post-natal muscle growth,homeostasis and repair. The understanding of theepigenome of SCs at different stages and of themultiple layers of the post-transcriptional regulationof gene expression is constantly expanding. Dynamicinteractions between different epigenetic mechanismsregulate the appropriate timing of muscle-specific geneexpression and influence the lineage fate of SCs. Inthis review, we report and discuss the recent literatureabout the epigenetic control of SCs during the myogenicprocess from activation to proliferation and from theircommitment to a muscle cell fate to their differentiationand fusion to myotubes. We describe how the coordinatedactivities of the histone methyltransferasefamilies Polycomb group (PcG), which represses theexpression of developmentally regulated genes, andTrithorax group, which antagonizes the repressive activityof the PcG, regulate myogenesis by restricting geneexpression in a time-dependent manner during eachstep of the process. We discuss how histone acetylationand deacetylation occurs in specific loci throughoutSC differentiation to enable the time-dependent transcriptionof specific genes. Moreover, we describe themultiple roles of microRNA, an additional epigeneticmechanism, in regulating gene expression in SCs, byrepressing or enhancing gene transcription or translationduring each step of myogenesis. The importance ofthese epigenetic pathways in modulating SC activationand differentiation renders them as promising targetsfor disease interventions. Understanding the mostrecent findings regarding the epigenetic mechanismsthat regulate SC behavior is useful from the perspectiveof pharmacological manipulation for improving muscleregeneration and for promoting muscle homeostasisunder

  18. Enobosarm (GTx-024) Modulates Adult Skeletal Muscle Mass Independently of the Androgen Receptor in the Satellite Cell Lineage.

    Science.gov (United States)

    Dubois, Vanessa; Simitsidellis, Ioannis; Laurent, Michaël R; Jardi, Ferran; Saunders, Philippa T K; Vanderschueren, Dirk; Claessens, Frank

    2015-12-01

    Androgens increase skeletal muscle mass, but their clinical use is hampered by a lack of tissue selectivity and subsequent side effects. Selective androgen receptor modulators elicit muscle-anabolic effects while only sparingly affecting reproductive tissues. The selective androgen receptor modulator, GTx-024 (enobosarm), is being investigated for cancer cachexia, sarcopenia, and muscle wasting diseases. Here we investigate the role of muscle androgen receptor (AR) in the anabolic effect of GTx-024. In mice lacking AR in the satellite cell lineage (satARKO), the weight of the androgen-sensitive levator ani muscle was lower but was decreased further upon orchidectomy. GTx-024 was as effective as DHT in restoring levator ani weights to sham levels. Expression of the muscle-specific, androgen-responsive genes S-adenosylmethionine decarboxylase and myostatin was decreased by orchidectomy and restored by GTx-024 and DHT in control mice, whereas the expression was low and unaffected by androgen status in satARKO. In contrast, insulin-like growth factor 1Ea expression was not different between satARKO and control muscle, decreased upon castration, and was restored by DHT and GTx-024 in both genotypes. These data indicate that GTx-024 does not selectively modulate AR in the satellite cell lineage and that cells outside this lineage remain androgen responsive in satARKO muscle. Indeed, residual AR-positive cells were present in satARKO muscle, coexpressing the fibroblast-lineage marker vimentin. AR positive, muscle-resident fibroblasts could therefore be involved in the indirect effects of androgens on muscle. In conclusion, both DHT and GTx-024 target AR pathways in the satellite cell lineage, but cells outside this lineage also contribute to the anabolic effects of androgens.

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  4. File list: Unc.Myo.10.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Oth.Myo.20.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Unc.Myo.50.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: InP.Myo.50.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: InP.Myo.05.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: DNS.Myo.20.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: His.Myo.10.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. A simplified but robust method for the isolation of avian and mammalian muscle satellite cells

    Directory of Open Access Journals (Sweden)

    Baquero-Perez Belinda

    2012-06-01

    Full Text Available Abstract Background Current methods of isolation of muscle satellite cells from different animal species are highly variable making inter-species comparisons problematic. This variation mainly stems from the use of different proteolytic enzymes to release the satellite cells from the muscle tissue (sometimes a single enzyme is used but often a combination of enzymes is preferred and the different extracellular matrix proteins used to coat culture ware. In addition, isolation of satellite cells is frequently laborious and sometimes may require pre-plating of the cell preparation on uncoated flasks or Percoll centrifugation to remove contaminating fibroblasts. The methodology employed to isolate and culture satellite cells in vitro can critically determine the fusion of myoblasts into multi-nucleated myotubes. These terminally differentiated myotubes resemble mature myofibres in the muscle tissue in vivo, therefore optimal fusion is a keystone of in vitro muscle culture. Hence, a simple method of muscle satellite cell isolation and culture of different vertebrate species that can result in a high fusion rate is highly desirable. Results We demonstrate here a relatively simple and rapid method of isolating highly enriched muscle satellite cells from different avian and mammalian species. In brief, muscle tissue was mechanically dissociated, digested with a single enzyme (pronase, triturated with a 10-ml pipette, filtered and directly plated onto collagen coated flasks. Following this method and after optimization of the cell culture conditions, excellent fusion rates were achieved in the duck, chicken, horse and cow (with more than 50% cell fusion, and to a lesser extent pig, pointing to pronase as a highly suitable enzyme to release satellite cells from muscle tissue. Conclusions Our simplified method presents a quick and simple alternative to isolating highly enriched muscle satellite cell cultures which can subsequently rapidly differentiate

  12. The behaviour of satellite cells in response to exercise: what have we learned from human studies?

    DEFF Research Database (Denmark)

    Kadi, Fawzi; Olsen, Steen Schytte

    2005-01-01

    Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the underst......Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards...... the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei...... and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation...

  13. Autoantibodies and Resident Renal Cells in the Pathogenesis of Lupus Nephritis: Getting to Know the Unknown

    Directory of Open Access Journals (Sweden)

    Susan Yung

    2012-01-01

    Full Text Available Systemic lupus erythematosus is characterized by a breakdown of self-tolerance and production of autoantibodies. Kidney involvement (i.e., lupus nephritis is both common and severe and can result in permanent damage within the glomerular, vascular, and tubulo-interstitial compartments of the kidney, leading to acute or chronic renal failure. Accumulating evidence shows that anti-dsDNA antibodies play a critical role in the pathogenesis of lupus nephritis through their binding to cell surface proteins of resident kidney cells, thereby triggering the downstream activation of signaling pathways and the release of mediators of inflammation and fibrosis. This paper describes the mechanisms through which autoantibodies interact with resident renal cells and how this interaction plays a part in disease pathogenesis that ultimately leads to structural and functional alterations in lupus nephritis.

  14. Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jun-ichi Kawabe

    2014-01-01

    Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

  15. Satellited 4q identified in amniotic fluid cells

    Energy Technology Data Exchange (ETDEWEB)

    Miller, I.; Hsieh, C.L.; Songster, G. [Stanford Univ. Medical Center, Stanford, CA (United States)] [and others

    1995-01-16

    Extra material was identified on the distal long arm of a chromosome 4 in an amniotic fluid specimen sampled at 16.6 weeks of gestational age. There was no visible loss of material from chromosome 4, and no evidence for a balanced rearrangement. The primary counseling issue in this case was advanced maternal age. Ultrasound findings were normal, and family history was unremarkable. The identical 4qs chromosome was observed in cells from a paternal peripheral blood specimen and appeared to be an unbalanced rearrangement. This extra material was NOR positive in lymphocytes from the father, but was negative in the fetal amniocytes. Father`s relatives were studied to verify the familial origin of this anomaly. In situ hybridization with both exon and intron sequences of ribosomal DNA demonstrated that ribosomal DNA is present at the terminus of the 4qs chromosome in the fetus, father, and paternal grandmother. This satellited 4q might have been derived from a translocation event that resulted in very little or no loss from the 4q and no specific phenotype. This derivative chromosome 4 has been inherited through at least 3 generations of phenotypically normal individuals. 8 refs., 3 figs.

  16. Satellite cell activity, without expansion, after nonhypertrophic stimuli.

    Science.gov (United States)

    Joanisse, Sophie; McKay, Bryon R; Nederveen, Joshua P; Scribbans, Trisha D; Gurd, Brendon J; Gillen, Jenna B; Gibala, Martin J; Tarnopolsky, Mark; Parise, Gianni

    2015-11-01

    The purpose of the present studies was to determine the effect of various nonhypertrophic exercise stimuli on satellite cell (SC) pool activity in human skeletal muscle. Previously untrained men and women (men: 29 ± 9 yr and women: 29 ± 2 yr, n = 7 each) completed 6 wk of very low-volume high-intensity sprint interval training. In a separate study, recreationally active men (n = 16) and women (n = 3) completed 6 wk of either traditional moderate-intensity continuous exercise (n = 9, 21 ± 4 yr) or low-volume sprint interval training (n = 10, 21 ± 2 yr). Muscle biopsies were obtained from the vastus lateralis before and after training. The fiber type-specific SC response to training was determined, as was the activity of the SC pool using immunofluorescent microscopy of muscle cross sections. Training did not induce hypertrophy, as assessed by muscle cross-sectional area, nor did the SC pool expand in any group. However, there was an increase in the number of active SCs after each intervention. Specifically, the number of activated (Pax7(+)/MyoD(+), P ≤ 0.05) and differentiating (Pax7(-)/MyoD(+), P ≤ 0.05) SCs increased after each training intervention. Here, we report evidence of activated and cycling SCs that may or may not contribute to exercise-induced adaptations while the SC pool remains constant after three nonhypertrophic exercise training protocols.

  17. Innate Response Activator (IRA) B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.

    Science.gov (United States)

    Chiappini, Nico; Cantisani, Rocco; Pancotto, Laura; Ruggiero, Paolo; Rosa, Domenico; Manetti, Andrea; Romano, Antonio; Montagnani, Francesca; Bertholet, Sylvie; Castellino, Flora; Del Giudice, Giuseppe

    2015-01-01

    Innate response activator (IRA) B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA) B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

  18. Innate Response Activator (IRA B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.

    Directory of Open Access Journals (Sweden)

    Nico Chiappini

    Full Text Available Innate response activator (IRA B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

  19. Theoretical Investigation of Laser-Radiation Effects on Satellite Solar Cells

    Science.gov (United States)

    Abdel-Hadi, Yasser; El-Hameed, Afaf; Hamdy, Ola

    This research concerns with the studying of laser-powered solar panels for space applications. A model describing the laser effects on satellite solar cell has been developed. These effects are studied theoretically in order to determine the performance limits of the solar cells when they are powered by laser radiation during the satellite eclipse. A comparison between some different common types of the solar cells used for these purpose is considered in this study. The obtained results are reported to optimize the use of laser-powered satellites.

  20. Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms.

    Science.gov (United States)

    Yang, Shoufeng; Hay, Iain D; Cameron, David R; Speir, Mary; Cui, Bintao; Su, Feifei; Peleg, Anton Y; Lithgow, Trevor; Deighton, Margaret A; Qu, Yue

    2015-12-21

    Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBCbiofilm). Two populations of "persister cells" were observed: bacteria that survived antibiotics at MBCbiofilm for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics.

  1. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy.

    Science.gov (United States)

    Fry, Christopher S; Lee, Jonah D; Jackson, Janna R; Kirby, Tyler J; Stasko, Shawn A; Liu, Honglu; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2014-04-01

    Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.

  2. Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise

    DEFF Research Database (Denmark)

    Mikkelsen, U R; Langberg, H; Helmark, I C

    2009-01-01

    exercise in vivo in human skeletal muscle. Eight young healthy males performed 200 maximal eccentric contractions with each leg. An NSAID was infused via a microdialysis catheter into the vastus lateralis muscle of one leg (NSAID leg) before, during, and for 4.5 h after exercise, with the other leg working...... of satellite cells 8 days after exercise. These results suggest that NSAIDs negatively affect satellite cell activity after unaccustomed eccentric exercise.......Despite the widespread consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), the influence of these drugs on muscle satellite cells is not fully understood. The aim of the present study was to investigate the effect of a local NSAID infusion on satellite cells after unaccustomed eccentric...

  3. The quasi-parallel lives of satellite cells and atrophying muscle

    Directory of Open Access Journals (Sweden)

    Stefano eBiressi

    2015-07-01

    Full Text Available Skeletal muscle atrophy or wasting accompanies various chronic illnesses and the aging process, thereby reducing muscle function. One of the most important components contributing to effective muscle repair in postnatal organisms, the satellite cells, have recently become the focus of several studies examining factors participating in the atrophic process. We critically examine here the experimental evidence linking satellite cell function with muscle loss in connection with various diseases as well as aging, and in the subsequent recovery process. Several recent reports have investigated the changes in satellite cells in terms of their differentiation and proliferative capacity in response to various atrophic stimuli. In this regard, we review the molecular changes within satellite cells that contribute to their dysfunctional status in atrophy, with the intention of shedding light on novel potential pharmacological targets to counteract the loss of muscle mass.

  4. Gap junctional communication between the satellite cells of rat dorsal root ganglia.

    Science.gov (United States)

    Sakuma, E; Wang, H J; Asai, Y; Tamaki, D; Amano, K; Mabuchi, Y; Herbert, D C; Soji, T

    2001-06-01

    Many studies have described the ultrastructure of the dorsal root ganglia in various embryonic and adult animals, but in spite of the efforts of many investigators the functional role of the satellite cells in this tissue is not clearly understood. In this study, we discuss the function of this cell type based on the concept of cell-to-cell interaction through gap junctions. Five male 60 day-old Wistar strain rats were used. All animals were anesthetized with pentobarbital and perfused with glutaraldehyde fixative, then the dorsal root ganglia in levels L4, L5 and L6 were taken from each rat. After postosmication, the specimens were prepared for observation by transmission electron microscopy. All nerve cells were completely surrounded by satellite cell cytoplasmic expansions. The boundaries between adjacent nerve cells and satellite cells were complicated due to the presence of perikaryal projections of nerve cells. Gap junctions which showed the typical trilamellar structure of plasma membranes were found mainly between satellite cell processes belonging to the same nerve cell. On the other hand, some gap junctions were found between the satellite cell projections belonging to different nerve cells. The size of the gap junctions ranged from 300 to 400 nm. No gap junctions were associated with the plasma membrane of any nerve cell. In conclusion, only satellite cells can share free transcellular exchange of cytoplasmic molecules such as ions, amino acids, sugars and several second messengers including cAMP and inositol 1,4,5-triphosphate by way of gap junctions in dorsal root ganglia.

  5. The effect of space microgravity on the physiological activity of mammalian resident cardiac stem cells

    Science.gov (United States)

    Belostotskaya, Galina; Zakharov, Eugeny

    Prolonged exposure to weightlessness during space flights is known to cause depression of heart function in mammals. The decrease in heart weight and its remodeling under the influence of prolonged weightlessness (or space microgravity) is assumed to be due to both morphological changes of working cardiomyocytes and their progressive loss, as well as to possible depletion of resident cardiac stem cells (CSCs) population, or their inability to self-renewal and regeneration of muscle tissue under conditions of weightlessness. We have previously shown that the presence of different maturity clones formed by resident CSCs not only in culture but also in the mammalian myocardium can be used as an indicator of the regenerative activity of myocardial cells [Belostotskaya, et al., 2013: 2014]. In this study, we were interested to investigate whether the 30-day near-Earth space flight on the spacecraft BION-M1 affects the regenerative potential of resident CSCs. Immediately after landing of the spacecraft, we had examined the presence of resident c-kit+, Sca-1+ and Isl1+ CSCs and their development in suspension of freshly isolated myocardial cells of C57BL mice in comparison to controls. Cardiac cell suspension was obtained by enzymatic digestion of the heart [Belostotskaya and Golovanova, 2014]. Immunocytochemically stained preparations of fixed cells were analyzed with confocal microscope Leica TCS SP5 (Germany) in the Resource Center of St-Petersburg State University. CSCs were labeled with appropriate antibodies. CSCs differentiation into mature cardiomyocytes was verified using antibodies to Sarcomeric α-Actinin and Cardiac Troponin T. Antibodies to Connexin43 were used to detect cell-cell contacts. All antibodies were conjugated with Alexa fluorochromes (488, 532, 546, 568, 594 and/or 647 nm), according to Zenon-technology (Invitrogen). It has been shown that, under identical conditions of cell isolation, more complete digestion of heart muscle was observed in

  6. The majority of human memory B cells recognizing RhD and tetanus resides in IgM+ B cells.

    Science.gov (United States)

    Della Valle, Luciana; Dohmen, Serge E; Verhagen, Onno J H M; Berkowska, Magdalena A; Vidarsson, Gestur; Ellen van der Schoot, C

    2014-08-01

    B cell memory to T cell-dependent (TD) Ags are considered to largely reside in class-switched CD27(+) cells. However, we previously observed that anti-RhD (D) Igs cloned from two donors, hyperimmunized with D(+) erythrocytes, were predominantly of the IgM isotype. We therefore analyzed in this study the phenotype and frequency of D- and tetanus toxoid-specific B cells by culturing B cells in limiting dilution upon irradiated CD40L-expressing EL4.B5 cells and testing the culture supernatant. Most Ag-specific B cells for both TD Ags were found to reside in the IgM-expressing B cells, including CD27(-) B cells, in both hyperimmunized donors and nonhyperimmunized volunteers. Only shortly after immunization a sharp increase in Ag-specific CD27(+)IgG(+) B cells was observed. Next, B cells were enriched with D(+) erythrocyte ghosts and sorted as single cells. Sequencing of IGHV, IGLV, IGKV, and BCL6 genes from these D-specific B cell clones demonstrated that both CD27(-)IgM(+) and CD27(+)IgM(+) B cells harbored somatic mutations, documenting their Ag-selected nature. Furthermore, sequencing revealed a clonal relationship between the CD27(-)IgM(+), CD27(+)IgM(+), and CD27(+)IgG(+) B cell subsets. These data strongly support the recently described multiple layers of memory B cells to TD Ags in mice, where IgM(+) B cells represent a memory reservoir which can re-enter the germinal center and ensure replenishment of class-switched memory CD27(+) B cells from Ag-experienced precursors.

  7. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    Directory of Open Access Journals (Sweden)

    Matthew Emerson Randolph

    2015-10-01

    Full Text Available The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies, such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some muscular dystrophies. The biology of muscle stem cells varies depending on their embryologic origins and the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease.

  8. TCR-pMHC encounter differentially regulates transcriptomes of(-) tissue-resident CD8 T cells.

    Science.gov (United States)

    Yoshikawa, Akihiro; Bi, Kevin; Keskin, Derin B; Zhang, Guanglang; Reinhold, Bruce; Reinherz, Ellis L

    2017-09-05

    To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (TR ) differentiation, polyclonal responses were compared against NP366-374 /D(b) and PA224-233 /D(b) , two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103+ and CD103- CD8 TR generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherence junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGFβ signaling pathways and memory signatures among PA224-233 /D(b) T cells consistent with T resident memory (TRM ) status. In contrast, NP366-374 /D(b) T cells exhibit enrichment of effector signatures, upregulating pro-inflammatory mediators even among TRM . While NP366-374 /D(b) T cells manifest transcripts linked to canonical exhaustion pathways, PA224-233 /D(b) T cells exploit P2xr7 purinoreceptor attenuation. The NP366-374 /D(b) CD103+ subset expresses the antimicrobial lactotransferrin whereas PA224-233 /D(b) CD103+ utilizes pore-forming mpeg-1, with T cell biology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. mTOR is necessary for proper satellite cell activity and skeletal muscle regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Liang, Xinrong; Shan, Tizhong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Jiang, Qinyang [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); College of Animal Science and Technology, Guangxi University, Nanning 530004 (China); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Zheng, Rong, E-mail: zhengrong@mail.hzau.edu.cn [Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2015-07-17

    The serine/threonine kinase mammalian target of rapamycin (mTOR) is a key regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive deletion of Mtor gene results in embryonic lethality, the function of mTOR in muscle stem cells (satellite cells) and skeletal muscle regeneration remains to be determined. In this study, we established a satellite cell specific Mtor conditional knockout (cKO) mouse model by crossing Pax7{sup CreER} and Mtor{sup flox/flox} mice. Skeletal muscle regeneration after injury was severely compromised in the absence of Mtor, indicated by increased number of necrotic myofibers infiltrated by Evans blue dye, and reduced number and size of regenerated myofibers in the Mtor cKO mice compared to wild type (WT) littermates. To dissect the cellular mechanism, we analyzed satellite cell-derived primary myoblasts grown on single myofibers or adhered to culture plates. The Mtor cKO myoblasts exhibited defective proliferation and differentiation kinetics when compared to myoblasts derived from WT littermates. At the mRNA and protein levels, the Mtor cKO myoblasts expressed lower levels of key myogenic determinant genes Pax7, Myf5, Myod, Myog than did the WT myoblasts. These results suggest that mTOR is essential for satellite cell function and skeletal muscle regeneration through controlling the expression of myogenic genes. - Highlights: • Pax7{sup CreER} was used to delete Mtor gene in satellite cells. • Satellite cell specific deletion of Mtor impairs muscle regeneration. • mTOR is necessary for satellite cell proliferation and differentiation. • Deletion of Mtor leads to reduced expression of key myogenic genes.

  10. Embryonic Hematopoietic Progenitor Cells Reside in Muscle before Bone Marrow Hematopoiesis.

    Directory of Open Access Journals (Sweden)

    Yuka Tanaka

    Full Text Available In mice, hematopoietic cells home to bone marrow from fetal liver prenatally. To elucidate mechanisms underlying homing, we performed immunohistochemistry with the hematopoietic cell marker c-Kit, and observed c-Kit(+ cells localized inside muscle surrounding bone after 14.5 days post coitum. Flow cytometric analysis showed that CD45(+ c-Kit(+ hematopoietic cells were more abundant in muscle than in bone marrow between 14.5 and 17.5 days post coitum, peaking at 16.5 days post coitum. CD45(+ c-Kit(+ cells in muscle at 16.5 days post coitum exhibited higher expression of Gata2, among several hematopoietic genes, than did fetal liver or bone marrow cells. Colony formation assays revealed that muscle hematopoietic cells possess hematopoietic progenitor activity. Furthermore, exo utero transplantation revealed that fetal liver hematopoietic progenitor cells home to muscle and then to BM. Our findings demonstrate that hematopoietic progenitor cell homing occurs earlier than previously reported and that hematopoietic progenitor cells reside in muscle tissue before bone marrow hematopoiesis occurs during mouse embryogenesis.

  11. Multiple receptor-ligand interactions direct tissue resident gamma delta T cell activation

    Directory of Open Access Journals (Sweden)

    Deborah A. Witherden

    2014-11-01

    Full Text Available Gamma delta T cells represent a major T cell population in epithelial tissues, such as skin, intestine, and lung, where they function in maintenance of the epithelium and provide a crucial first line defense against environmental and pathogenic insults. Despite their importance, the molecular mechanisms directing their activation and function have remained elusive. Epithelial resident gamma delta T cells function through constant communication with neighboring cells, either via direct cell-to-cell contact or cell-to-matrix interactions. These intimate relationships allow gamma delta T cells to facilitate the maintenance of epithelial homeostasis, tissue repair following injury, inflammation, and protection from malignancy. Recent studies have identified a number of molecules involved in these complex interactions, under both homeostatic conditions, as well as following perturbation of these barrier tissues. These interactions are crucial to the timely production of cytokines, chemokines, growth factors and extracellular matrix proteins for restoration of homeostasis. In this review, we discuss recent advances in understanding the mechanisms directing epithelial-T cell crosstalk and the distinct roles played by individual receptor-ligand pairs of cell surface molecules in this process.

  12. Function of Membrane-Associated Proteoglycans in the Regulation of Satellite Cell Growth.

    Science.gov (United States)

    Song, Yan

    2016-01-01

    Muscle growth can be divided into embryonic and postnatal periods. During the embryonic period, mesenchymal stem cells proliferate and differentiate to form muscle fibers. Postnatal muscle growth (hypertrophy) is characterized by the enlargement of existing muscle fiber size. Satellite cells (also known as adult myoblasts) are responsible for hypertrophy. The activity of satellite cells can be regulated by their extracellular matrix (ECM). The ECM is composed of collagens, proteoglycans, non-collagenous glycoproteins, cytokines and growth factors. Proteoglycans contain a central core protein with covalently attached glycosaminoglycans (GAGs: chondroitin sulfate, keratan sulfate, dermatan sulfate, and heparan sulfate) and N- or O-linked glycosylation chains. Membrane-associated proteoglycans attach to the cell membrane either through a glycosylphosphatidylinositol anchor or transmembrane domain. The GAGs can bind proteins including cytokines and growth factors. Both cytokines and growth factors play important roles in regulating satellite cell growth and development. Cytokines are generally associated with immune cells. However, cytokines can also affect muscle cell development. For instance, interleukin-6, tumor necrosis factor-α, and leukemia inhibitory factor have been reported to affect the proliferation and differentiation of satellite cells and myoblasts. Growth factors are potent stimulators or inhibitors of satellite cell proliferation and differentiation. The proper function of some cytokines and growth factors requires an interaction with the cell membrane-associated proteoglycans to enhance the affinity to bind to their primary receptors to initiate downstream signal transduction. This chapter is focused on the interaction of membrane-associated proteoglycans with cytokines and growth factors, and their role in satellite cell growth and development.

  13. Use of fuel cells in residences and commercial establishments; Uso de celulas combustiveis em residencias e estabelecimentos comerciais

    Energy Technology Data Exchange (ETDEWEB)

    Serra, Eduardo T. [Centro de Pesquisas de Energia Eletrica, Rio de Janeiro, RJ (Brazil)

    2003-05-01

    This paper analyses the present technological stage and the economical feasibility of the application of low power fuel cells for meeting of the residence and small commercial units electric power consumption needs.

  14. Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease

    National Research Council Canada - National Science Library

    Tanima Bose; Ryan Lee; Aihua Hou; Louis Tong; K George Chandy

    2017-01-01

    Non-recirculating resident memory (TRM ) and recirculating T cells mount vigorous immune responses to both self and foreign antigens in barrier tissues like the skin, lung and gastrointestinal tract...

  15. Proton irradiation effects of amorphous silicon solar cell for solar power satellite

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Yousuke; Oshima, Takeshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Sasaki, Susumu; Kuroda, Hideo; Ushirokawa, Akio

    1997-03-01

    Flexible amorphous silicon(fa-Si) solar cell module, a thin film type, is regarded as a realistic power generator for solar power satellite. The radiation resistance of fa-Si cells was investigated by the irradiations of 3,4 and 10 MeV protons. The hydrogen gas treatment of the irradiated fa-Si cells was also studied. The fa-Si cell shows high radiation resistance for proton irradiations, compared with a crystalline silicon solar cell. (author)

  16. Proliferating resident microglia express the stem cell antigen CD34 in response to acute neural injury

    DEFF Research Database (Denmark)

    Ladeby, Rune; Wirenfeldt, Martin; Dalmau, Ishar

    2005-01-01

    following transection of the entorhino-dentate perforant path projection. To investigate the possible link between microglia and hematopoietic precursors, we analyzed the expression of the stem cell marker CD34 by lesion-reactive microglia in conjunction with the proliferation marker bromodeoxyuridine (Brd......U) and the use of radiation bone marrow (BM) chimeric mice. We found that CD34 is upregulated on early-activated resident microglia, rather than by infiltrating bone marrow-derived cells. The number of CD34(+) microglia peaked at day 3 when 67% of the resident CD11b/Mac-1(+) microglia co-expressed CD34, and all...... CD34(+) cells co-expressed Mac-1, and decreased sharply toward day 5, unlike Mac-1, which was maximally expressed at day 5. Approximately 80% of the CD34(+) cells in the denervated dentate gyrus had incorporated BrdU into their nuclei at day 3. We also showed that CD34 is upregulated on early...

  17. Original and regenerating lizard tail cartilage contain putative resident stem/progenitor cells.

    Science.gov (United States)

    Alibardi, Lorenzo

    2015-11-01

    Regeneration of cartilaginous tissues is limited in mammals but it occurs with variable extension in lizards (reptiles), including in their vertebrae. The ability of lizard vertebrae to regenerate cartilaginous tissue that is later replaced with bone has been analyzed using tritiated thymidine autoradiography and 5BrdU immunocytochemistry after single pulse or prolonged-pulse and chase experiments. The massive cartilage regeneration that can restore broad vertebral regions and gives rise to a long cartilaginous tube in the regenerating tail, depends from the permanence of some chondrogenic cells within adult vertebrae. Few cells that retain tritiated thymidine or 5-bromodeoxy-uridine for over 35 days are mainly localized in the inter-vertebral cartilage and in sparse chondrogenic regions of the neural arch of the vertebrae, suggesting that they are putative resident stem/progenitor cells. The study supports previous hypothesis indicating that the massive regeneration of the cartilaginous tissue in damaged vertebrae and in the regenerating tail of lizards derive from resident stem cells mainly present in the cartilaginous areas of the vertebrae including in the perichondrium that are retained in adult lizards as growing centers for most of their lifetime.

  18. Leishmania infantum antigens modulate memory cell subsets of liver resident T lymphocyte.

    Science.gov (United States)

    Rodrigues, A; Claro, M; Alexandre-Pires, G; Santos-Mateus, D; Martins, C; Valério-Bolas, A; Rafael-Fernandes, M; Pereira, M A; Pereira da Fonseca, I; Tomás, A M; Santos-Gomes, G

    2017-02-01

    In the recent years, the liver has been recognized as an important immune organ with major regulatory functions and immune memory, adding to the well-described vital metabolic functions. There are evidences from experimental infections performed with visceral Leishmania species that immune responses to parasite infection can be organ-specific. The liver is the compartment of acute resolving infection, with minimal tissue damage and resistance to reinfection, whereas the spleen is the compartment of parasite persistence. Control of hepatic infection in mice requires a coordinated immune response that involves the development of inflammatory granulomas. It is also described that the liver harbors populations of resident lymphocytes, which may exhibit memory characteristics. Therefore, the present study aims to address the role of the liver as an immune memory organ in the context of Leishmania infantum infection, by characterizing phenotypically resident liver T lymphocytes. The dynamics of memory T cells in L. infantum infected BALB/c mice and the effect of anti-leishmanial treatment in the differentiation of memory cell subsets were analyzed. The potential of recognition, differentiation and selection of memory lymphocytes by three L. infantum recombinant proteins were also explored. L. infantum infection generates effector and central memory T cells, but the cells did not expand when recalled, demonstrating a possible parasite silencing effect. The treatment with a leishmanicidal drug (antimoniate meglumine) increases the levels of memory and effector T cells, eliciting a more robust hepatic immune response. L. infantum parasites with a decreased sensitivity to the leishmanicidal drug favor the expansion of memory CD8(+) T cell subset, but inhibit the proliferation of CD8(+) T effector cells, possibly assuring their own survival. The recombinant proteins LirCyp1 and LirSOD are strongly recognized by memory cells of treated mice, indicating that these proteins

  19. Temperature effect on proliferation and differentiation of satellite cells from turkeys with different growth rates.

    Science.gov (United States)

    Clark, D L; Coy, C S; Strasburg, G M; Reed, K M; Velleman, S G

    2016-04-01

    Poultry selected for growth have an inefficient thermoregulatory system and are more sensitive to temperature extremes. Satellite cells are precursors to skeletal muscle and mediate all posthatch muscle growth. Their physiological functions are affected by temperature. The objective of the current study was to determine how temperature affects satellite cells isolated from the pectoralis major (p. major) muscle (breast muscle) of turkeys selected for increased 16 wk body weight (F line) in comparison to a randombred control line (RBC2) from which the F line originated. Pectoralis major muscle satellite cells were thermally challenged by culturing between 33°C and 43°C to analyze the effects of cold and heat on proliferation and differentiation as compared to control temperature of 38°C. Expression levels of myogenic regulatory factors: myogenic differentiation factor 1 (MYOD1) and myogenin (MYOG) were quantified by quantitative polymerase chain reaction (qPCR). At all sampling times, proliferation increased at a linear rate across temperature in both the RBC2 and F lines. Differentiation also increased at a linear rate across temperature from 33 to 41°C at all sampling times in both the F and RBC2 lines. Satellite cells isolated from F line turkeys were more sensitive to both hot and cold temperatures as proliferation and differentiation increased to a greater extent across temperature (33 to 43°C) when compared with the RBC2 line. Expression of MYOD1 and MYOG increased as temperatures increased from 33 to 41°C at all sampling times in both the F and RBC2 lines. These results demonstrate that satellite cell function is sensitive to both cold and hot temperatures and p. major muscle satellite cells from F line turkeys are more sensitive to temperature extremes than RBC2 satellite cells.

  20. Adipose progenitor cells reside among the mature adipocytes: morphological research using an organotypic culture system.

    Science.gov (United States)

    Anayama, Hisashi; Fukuda, Ryo; Yamate, Jyoji

    2015-11-01

    The precise localization and biological characteristics of the adipose progenitor cells are still a focus of debate. In this study, the localization of the adipose progenitor cells was determined using an organotypic culture system of adipose tissue slices. The tissue slices of subcutaneous white adipose tissue from rats were placed on a porous membrane and cultured at the interface between air and the culture medium for up to 5 days with or without adipogenic stimulation. The structure of adipose tissue components was sufficiently preserved during the culture and, following adipogenic stimulation with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine, numerous multilocular adipocytes appeared in the interstitium among the mature adipocytes. Histomorphological 3-D observation using confocal laser microscopy revealed the presence of small mesenchymal cells containing little or no fat residing in the perivascular region and on the mature adipocytes and differentiation from the pre-existing mesenchymal cells to multilocular adipocytes. Immunohistochemistry demonstrated that these cells were initially present within the fibronectin-positive extracellular matrix (ECM). The adipose differentiation of the mesenchymal cells was confirmed by the enhanced expression of C/EBP-β suggesting adipose differentiation and the concurrent advent of CD105-expressing mesenchymal cells within the interstitium of the mature adipocytes. Based on the above, the mesenchymal cells embedded in the ECM around the mature adipocytes were confirmed to be responsible for adipogenesis because the transition of the mesenchymal cells to the stem state contributed to the increase in the number of adipocytes in rat adipose tissue.

  1. Influence of skeletal muscle satellite cells implanted into infarcted myocardium on remnant myocyte volumes

    Institute of Scientific and Technical Information of China (English)

    钟竑; 朱洪生; 卫洪超; 张臻

    2003-01-01

    Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes.Methods Thirty-six adult mongrel canines were divided randomly into implantation group and control group. In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4', 6-diamidino-2-phenylindone (DAPI) in vitro. In both groups, a model of acute myocardial infarction was established in every dog. In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells. The dogs in the control group received M199 solution without skeletal muscle satellite cells. The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time). Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope. Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS. A P<0.05 was considered significant.Results A portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs. Cross-sectional area and cell volume were increased in normal myocardium. Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross-sectional area, cell area and cell volume differed significantly from those of the control group (P< 0.05). Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged. Conclusion Skeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium.

  2. Tissue-Resident T Cells as the Central Paradigm of Chlamydia Immunity.

    Science.gov (United States)

    Johnson, Raymond M; Brunham, Robert C

    2016-04-01

    For almost 2 decades, results from Chlamydia pathogenesis investigations have been conceptualized using a cytokine polarization narrative. Recent viral immunity studies identifying protective tissue-resident memory T cells (Trm) suggest an alternative paradigm based on localized immune networks. As Chlamydia vaccines enter the preclinical pipeline and, in the case of an attenuated trachoma vaccine, are given to human subjects, it may be useful to ask whether cytokine polarization is the appropriate framework for understanding and evaluating vaccine efficacy. In this review, we revisit C. trachomatis pathogenesis data from mice and humans using a Trm narrative and note a comfortable concordance with the Chlamydia pathogenesis literature.

  3. Lens stem cells may reside outside the lens capsule: an hypothesis

    Directory of Open Access Journals (Sweden)

    Meyer Rita A

    2007-06-01

    Full Text Available Abstract In this paper, we consider the ocular lens in the context of contemporary developments in biological ideas. We attempt to reconcile lens biology with stem cell concepts and a dearth of lens tumors. Historically, the lens has been viewed as a closed system, in which cells at the periphery of the lens epithelium differentiate into fiber cells. Theoretical considerations led us to question whether the intracapsular lens is indeed self-contained. Since stem cells generate tumors and the lens does not naturally develop tumors, we reasoned that lens stem cells may not be present within the capsule. We hypothesize that lens stem cells reside outside the lens capsule, in the nearby ciliary body. Our ideas challenge the existing lens biology paradigm. We begin our discussion with lens background information, in order to describe our lens stem cell hypothesis in the context of published data. Then we present the ciliary body as a possible source for lens stem cells, and conclude by comparing the ocular lens with the corneal epithelium.

  4. Enhanced satellite cell proliferation with resistance training in elderly men and women

    DEFF Research Database (Denmark)

    Mackey, Abigail; Esmarck, B; Kadi, F

    2007-01-01

    In addition to the well-documented loss of muscle mass and strength associated with aging, there is evidence for the attenuating effects of aging on the number of satellite cells in human skeletal muscle. The aim of this study was to investigate the response of satellite cells in elderly men...... and women to 12 weeks of resistance training. Biopsies were collected from the m. vastus lateralis of 13 healthy elderly men and 16 healthy elderly women (mean age 76+/-SD 3 years) before and after the training period. Satellite cells were visualized by immunohistochemical staining of muscle cross......-sections with a monoclonal antibody against neural cell adhesion molecule (NCAM) and counterstaining with Mayer's hematoxylin. Compared with the pre-training values, there was a significant increase (Pcells per fiber post-training in males (from 0.11+/-0.03 to 0...

  5. CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

    DEFF Research Database (Denmark)

    Cheuk, Stanley; Schlums, Heinrich; Sérézal, Irène Gallais

    2017-01-01

    Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced...

  6. THE ROLE OF SATELLITE CELLS IN CRUSH INJURY OF RAT SKELETON MUSCLE

    Directory of Open Access Journals (Sweden)

    DilekBURUKOĞLU

    2013-02-01

    Full Text Available The crush type of injury in rat skeletal muscle is often used in tissue degeneration and regeneration. After crush injury muscle tissue begins to regenerate. In this process, it is accepted that satellite cells play an important role which are very sensitive to muscle injury. The aim of this microscopic study was to examine role of satellite cells in muscle regeneration in crush injury. This research was done the department of Histology&Embryology in Eskişehir Osmangazi University in 2008. Ethic approval of this study has been received. During the study, the whole essential and ethics conditionshave been done. In the study 36 Spraque-Dawley rats were used. The rats were separated into 5 groups as test and control groups. Crush type of injury has been applied on muscles of right hind extremitiesof testing group rats by applying 3.5 kg of weight for 6 hours. In according to testing periods rats were anaesthetized intraperitoneally with ketamine 30mg/kg + xylazine 10mg/kg and sacrificied 3, 7, 14 and 21-day intervals. After crush injury, increased satellite cells were particularly observed on day 7. Alsosignificant increased of satellite cells and regenerated myofibrils were detected on day 14. However, satellite cells were seen on day-21 were similar to control group. In crush injuries, number of satellitecells were markedly increased and actively involved into regeneration process of the skeleton muscle.

  7. Characterisation of equine satellite cell transcriptomic profile response to β-hydroxy-β-methylbutyrate (HMB).

    Science.gov (United States)

    Szcześniak, Katarzyna A; Ciecierska, Anna; Ostaszewski, Piotr; Sadkowski, Tomasz

    2016-10-01

    β-Hydroxy-β-methylbutyrate (HMB) is a popular ergogenic aid used by human athletes and as a supplement to sport horses, because of its ability to aid muscle recovery, improve performance and body composition. Recent findings suggest that HMB may stimulate satellite cells and affect expressions of genes regulating skeletal muscle cell growth. Despite the scientific data showing benefits of HMB supplementation in horses, no previous study has explained the mechanism of action of HMB in this species. The aim of this study was to reveal the molecular background of HMB action on equine skeletal muscle by investigating the transcriptomic profile changes induced by HMB in equine satellite cells in vitro. Upon isolation from the semitendinosus muscle, equine satellite cells were cultured until the 2nd day of differentiation. Differentiating cells were incubated with HMB for 24 h. Total cellular RNA was isolated, amplified, labelled and hybridised to microarray slides. Microarray data validation was performed with real-time quantitative PCR. HMB induced differential expressions of 361 genes. Functional analysis revealed that the main biological processes influenced by HMB in equine satellite cells were related to muscle organ development, protein metabolism, energy homoeostasis and lipid metabolism. In conclusion, this study demonstrated for the first time that HMB has the potential to influence equine satellite cells by controlling global gene expression. Genes and biological processes targeted by HMB in equine satellite cells may support HMB utility in improving growth and regeneration of equine skeletal muscle; however, the overall role of HMB in horses remains equivocal and requires further proteomic, biochemical and pharmacokinetic studies.

  8. IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.

    Science.gov (United States)

    Ding, Xiaoli; Cao, Fang; Cui, Langjun; Ciric, Bogoljub; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-12-01

    Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling.

  9. Restricted maternal nutrition alters myogenic regulatory factor expression in satellite cells of ovine offspring.

    Science.gov (United States)

    Raja, J S; Hoffman, M L; Govoni, K E; Zinn, S A; Reed, S A

    2016-07-01

    Poor maternal nutrition inhibits muscle development and postnatal muscle growth. Satellite cells are myogenic precursor cells that contribute to postnatal muscle growth, and their activity can be evaluated by the expression of several transcription factors. Paired-box (Pax)7 is expressed in quiescent and active satellite cells. MyoD is expressed in activated and proliferating satellite cells and myogenin is expressed in terminally differentiating cells. Disruption in the expression pattern or timing of expression of myogenic regulatory factors negatively affects muscle development and growth. We hypothesized that poor maternal nutrition during gestation would alter the in vitro temporal expression of MyoD and myogenin in satellite cells from offspring at birth and 3 months of age. Ewes were fed 100% or 60% of NRC requirements from day 31±1.3 of gestation. Lambs from control-fed (CON) or restricted-fed (RES) ewes were euthanized within 24 h of birth (birth; n=5) or were fed a control diet until 3 months of age (n=5). Satellite cells isolated from the semitendinosus muscle were used for gene expression analysis or cultured for 24, 48 or 72 h and immunostained for Pax7, MyoD or myogenin. Fusion index was calculated from a subset of cells allowed to differentiate. Compared with CON, temporal expression of MyoD and myogenin was altered in cultured satellite cells isolated from RES lambs at birth. The percent of cells expressing MyoD was greater in RES than CON (P=0.03) after 24 h in culture. After 48 h of culture, there was a greater percent of cells expressing myogenin in RES compared with CON (P0.05). In satellite cells from RES lambs at 3 months of age, the percent of cells expressing MyoD and myogenin were greater than CON after 72 h in culture (Psatellite cells of the offspring, which may reduce the pool of myoblasts, decrease myoblast fusion and contribute to the poor postnatal muscle growth previously observed in these animals.

  10. IL-27 Regulates IL-18 binding protein in skin resident cells.

    Directory of Open Access Journals (Sweden)

    Miriam Wittmann

    Full Text Available IL-18 is an important mediator involved in chronic inflammatory conditions such as cutaneous lupus erythematosus, psoriasis and chronic eczema. An imbalance between IL-18 and its endogenous antagonist IL-18 binding protein (BP may account for increased IL-18 activity. IL-27 is a cytokine with dual function displaying pro- and anti-inflammatory properties. Here we provide evidence for a yet not described anti-inflammatory mode of action on skin resident cells. Human keratinocytes and surprisingly also fibroblasts (which do not produce any IL-18 show a robust, dose-dependent and highly inducible mRNA expression and secretion of IL-18BP upon IL-27 stimulation. Other IL-12 family members failed to induce IL-18BP. The production of IL-18BP peaked between 48-72 h after stimulation and was sustained for up to 96 h. Investigation of the signalling pathway showed that IL-27 activates STAT1 in human keratinocytes and that a proximal GAS site at the IL-18BP promoter is of importance for the functional activity of IL-27. The data are in support of a significant anti-inflammatory effect of IL-27 on skin resident cells. An important novel property of IL-27 in skin pathobiology may be to counter-regulate IL-18 activities by acting on keratinocytes and importantly also on dermal fibroblasts.

  11. IMPROVING METHODOLOGICAL STRATEGIES FOR SATELLITE CELLS COUNTING IN HUMAN MUSCLE DURING AGEING

    Directory of Open Access Journals (Sweden)

    Špela Sajko

    2011-05-01

    Full Text Available Stereological methods, based on the optical disector principle and fluorescent staining, were developed for estimating frequency of satellite cells in skeletal muscles. The parameter NL(sc, fib (number of satellite cells per fibre length was compared with the parameter NN(sc, nucl (the percentage of satellite cell nuclei in all muscle nuclei, most often published in the literature, by applying unbiased sampling and counting procedures and using a confocal microscope. The methods were tested in autopsy samples of four young vs. four old human vastus lateralis muscles. Both parameters NL(sc, fib and NN(sc, nucl declined during ageing. However, it appears that the two parameters cannot be substituted one by the other because the number of nuclei per fibre length tends to be increased during aging. Using the introduced methods, it is more straightforward to estimate NL(sc, fib than NN(sc, nucl.

  12. Arterial calcification: Finger-pointing at resident and circulating stem cells

    Institute of Scientific and Technical Information of China (English)

    Francesco; Vasuri; Silvia; Fittipaldi; Gianandrea; Pasquinelli

    2014-01-01

    The term "Stammzelle"(stem cells) originally appeared in 1868 in the works of Ernst Haeckel who used it to describe the ancestor unicellular organism from which he presumed all multicellular organisms evolved. Since then stem cells have been studied in a wide spectrum of normal and pathological conditions; it is remarkable to note that ectopic arterial calcification was considered a passive deposit of calcium since its original discovering in 1877; in the last decades, resident and circulating stem cells were imaged to drive arterial calcification through chondro-osteogenic differentiation thus opening the idea that an active mechanism could be at the basis of the process that clinically shows a Janus effect: calcifications either lead to the stabilization or rupture of the atherosclerotic plaques. A review of the literature underlines that 130 years after stem cell discovery, antigenic markers of stem cells are still debated and the identification of the osteoprogenitor phenotype is even more elusive due to tissue degradation occurring at processing and manipulation. It is necessary to find a consensus to perform comparable studies that implies phenotypic recognition of stem cells antigens. A hypothesis is based on the singular morphology and amitotic mechanism of division of osteoclasts: it constitutes the opening to a new approach on osteoprogenitors markers and recognition. Our aim was to highlight all the present evidences of the active calcification process, summarize the different cellular types involved, and discuss a novel approach to discover osteoprogenitor phenotypes in arterial wall.

  13. Arterial calcification: Finger-pointing at resident and circulating stem cells.

    Science.gov (United States)

    Vasuri, Francesco; Fittipaldi, Silvia; Pasquinelli, Gianandrea

    2014-11-26

    The term ''Stammzelle'' (stem cells) originally appeared in 1868 in the works of Ernst Haeckel who used it to describe the ancestor unicellular organism from which he presumed all multicellular organisms evolved. Since then stem cells have been studied in a wide spectrum of normal and pathological conditions; it is remarkable to note that ectopic arterial calcification was considered a passive deposit of calcium since its original discovering in 1877; in the last decades, resident and circulating stem cells were imaged to drive arterial calcification through chondro-osteogenic differentiation thus opening the idea that an active mechanism could be at the basis of the process that clinically shows a Janus effect: calcifications either lead to the stabilization or rupture of the atherosclerotic plaques. A review of the literature underlines that 130 years after stem cell discovery, antigenic markers of stem cells are still debated and the identification of the osteoprogenitor phenotype is even more elusive due to tissue degradation occurring at processing and manipulation. It is necessary to find a consensus to perform comparable studies that implies phenotypic recognition of stem cells antigens. A hypothesis is based on the singular morphology and amitotic mechanism of division of osteoclasts: it constitutes the opening to a new approach on osteoprogenitors markers and recognition. Our aim was to highlight all the present evidences of the active calcification process, summarize the different cellular types involved, and discuss a novel approach to discover osteoprogenitor phenotypes in arterial wall.

  14. Target engagement and drug residence time can be observed in living cells with BRET.

    Science.gov (United States)

    Robers, Matthew B; Dart, Melanie L; Woodroofe, Carolyn C; Zimprich, Chad A; Kirkland, Thomas A; Machleidt, Thomas; Kupcho, Kevin R; Levin, Sergiy; Hartnett, James R; Zimmerman, Kristopher; Niles, Andrew L; Ohana, Rachel Friedman; Daniels, Danette L; Slater, Michael; Wood, Monika G; Cong, Mei; Cheng, Yi-Qiang; Wood, Keith V

    2015-12-03

    The therapeutic action of drugs is predicated on their physical engagement with cellular targets. Here we describe a broadly applicable method using bioluminescence resonance energy transfer (BRET) to reveal the binding characteristics of a drug with selected targets within intact cells. Cell-permeable fluorescent tracers are used in a competitive binding format to quantify drug engagement with the target proteins fused to Nanoluc luciferase. The approach enabled us to profile isozyme-specific engagement and binding kinetics for a panel of histone deacetylase (HDAC) inhibitors. Our analysis was directed particularly to the clinically approved prodrug FK228 (Istodax/Romidepsin) because of its unique and largely unexplained mechanism of sustained intracellular action. Analysis of the binding kinetics by BRET revealed remarkably long intracellular residence times for FK228 at HDAC1, explaining the protracted intracellular behaviour of this prodrug. Our results demonstrate a novel application of BRET for assessing target engagement within the complex milieu of the intracellular environment.

  15. Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.

    Science.gov (United States)

    Kostallari, Enis; Baba-Amer, Yasmine; Alonso-Martin, Sonia; Ngoh, Pamela; Relaix, Frederic; Lafuste, Peggy; Gherardi, Romain K

    2015-04-01

    The satellite cells, which serve as adult muscle stem cells, are both located beneath myofiber basement membranes and closely associated with capillary endothelial cells. We observed that 90% of capillaries were associated with pericytes in adult mouse and human muscle. During post-natal growth, newly formed vessels with their neuroglial 2 proteoglycan (NG2)-positive pericytes became progressively associated with the post-natal muscle stem cells, as myofibers increased in size and satellite cells entered into quiescence. In vitro, human muscle-derived pericytes promoted myogenic cell differentiation through insulin-like growth factor 1 (IGF1) and myogenic cell quiescence through angiopoietin 1 (ANGPT1). Diphtheria toxin-induced ablation of muscle pericytes in growing mice led both to myofiber hypotrophy and to impaired establishment of stem cells quiescence. Similar effects were observed following conditional in vivo deletion of pericyte Igf1 and Angpt1 genes, respectively. Our data therefore demonstrate that, by promoting post-natal myogenesis and stem cell quiescence, pericytes play a key role in the microvascular niche of satellite cells. © 2015. Published by The Company of Biologists Ltd.

  16. Direct and indirect effects of immune and central nervous system-resident cells on human oligodendrocyte progenitor cell differentiation.

    Science.gov (United States)

    Moore, Craig S; Cui, Qiao-Ling; Warsi, Nebras M; Durafourt, Bryce A; Zorko, Nika; Owen, David R; Antel, Jack P; Bar-Or, Amit

    2015-01-15

    In multiple sclerosis, successful remyelination within the injured CNS is largely dependent on the survival and differentiation of oligodendrocyte progenitor cells. During inflammatory injury, oligodendrocytes and oligodendrocyte progenitor cells within lesion sites are exposed to secreted products derived from both infiltrating immune cell subsets and CNS-resident cells. Such products may be considered either proinflammatory or anti-inflammatory and have the potential to contribute to both injury and repair processes. Within the CNS, astrocytes also contribute significantly to oligodendrocyte biology during development and following inflammatory injury. The overall objective of the current study was to determine how functionally distinct proinflammatory and anti-inflammatory human immune cell subsets, implicated in multiple sclerosis, can directly and/or indirectly (via astrocytes) impact human oligodendrocyte progenitor cell survival and differentiation. Proinflammatory T cell (Th1/Th17) and M1-polarized myeloid cell supernatants had a direct cytotoxic effect on human A2B5(+) neural progenitors, resulting in decreased O4(+) and GalC(+) oligodendrocyte lineage cells. Astrocyte-conditioned media collected from astrocytes pre-exposed to the same proinflammatory supernatants also resulted in decreased oligodendrocyte progenitor cell differentiation without an apparent increase in cell death and was mediated through astrocyte-derived CXCL10, yet this decrease in differentiation was not observed in the more differentiated oligodendrocytes. Th2 and M2 macrophage or microglia supernatants had neither a direct nor an indirect impact on oligodendrocyte progenitor cell differentiation. We conclude that proinflammatory immune cell responses can directly and indirectly (through astrocytes) impact the fate of immature oligodendrocyte-lineage cells, with oligodendrocyte progenitor cells more vulnerable to injury compared with mature oligodendrocytes.

  17. Poised Regeneration of Zebrafish Melanocytes Involves Direct Differentiation and Concurrent Replenishment of Tissue-Resident Progenitor Cells.

    Science.gov (United States)

    Iyengar, Sharanya; Kasheta, Melissa; Ceol, Craig J

    2015-06-22

    Efficient regeneration following injury is critical for maintaining tissue function and enabling organismal survival. Cells reconstituting damaged tissue are often generated from resident stem or progenitor cells or from cells that have dedifferentiated and become proliferative. While lineage-tracing studies have defined cellular sources of regeneration in many tissues, the process by which these cells execute the regenerative process is largely obscure. Here, we have identified tissue-resident progenitor cells that mediate regeneration of zebrafish stripe melanocytes and defined how these cells reconstitute pigmentation. Nearly all regeneration melanocytes arise through direct differentiation of progenitor cells. Wnt signaling is activated prior to differentiation, and inhibition of Wnt signaling impairs regeneration. Additional progenitors divide symmetrically to sustain the pool of progenitor cells. Combining direct differentiation with symmetric progenitor divisions may serve as a means to rapidly repair injured tissue while preserving the capacity to regenerate.

  18. THE IMPROVEMENT OF INFARCTED MYOCARDIAL CONTRACTILE FORCE AFTER AUTOLOGOUS SKELETAL MUSCLE SATELLITE CELL IMPLANTATION

    Institute of Scientific and Technical Information of China (English)

    钟竑; 朱洪生; 张臻

    2002-01-01

    Objective To study the improvement of infarcted myocardial contractile force after autologous skeletal muscle satellite cell implantation via intracoronary arterial perfusion. Methods Skeletal muscle cells were harvested from gluteus max of adult mongrel dogs and the cells were cultured and expanded before being labeled with DAPI (4, 6-diamidino-2-phenylindone). The labeled cells were then implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) coronary artery. Specimens were taken at 2nd, 4th, 8th week after myoblast implantation for histologic and contractile force evaluation, respectively. Results The satellite cells with fluorescence had been observed in the infarct site and also in papi-llary muscle with consistent oriented direction of host myocardium. A portion of the implanted cells had differen-tiated into muscle fibers. Two weeks after implantation, the myocardial contractile force showed no significant difference between the cell implant group and control group. At 4 and 8 week, the contractile force in the cell implant group was better than that in control group. Conclusion The skeletal muscle satellite cells, implanted into infarct myocardium by intracoronary arterial perfusion, could disseminate through the entire infarcted zone with myocardial regeneration and improve the contractile function of the infarcted myocardium.

  19. Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells.

    Science.gov (United States)

    Tanaka, Tomohiro; Obana, Masanori; Mohri, Tomomi; Ebara, Masaki; Otani, Yuta; Maeda, Makiko; Fujio, Yasushi

    2015-10-01

    Cytokines play important roles in cardiac repair and regeneration. Recently, we demonstrated that interleukin (IL)-6 family cytokines induce the endothelial differentiation of Sca-1+ cardiac resident stem cells through STAT3/Pim-1 signaling pathway. In contrast, the biological functions of IL-12 family cytokines in heart remain to be elucidated, though they show structural homology with IL-6. In the present study, we examined the effects of IL-12 family cytokines on the transdifferentiation of cardiac Sca-1+ cells into cardiac cells. RT-PCR analyses revealed that IL-27 receptor α (IL-27Rα), but not IL-12R or IL-23R, was expressed in cardiac Sca-1+ cells. The transcript expression of IL-27 was elevated in murine hearts in cardiac injury models. Intriguingly, IL-27 stimulation for 14 days induced the endothelial cell (EC) marker genes, such as CD-31 and VE-cadherin. Immunoblot analyses clarified that IL-27 treatment rapidly phosphorylated STAT3. IL-27 upregulated the expression of Pim-1, but the overexpression of dominant negative STAT3 abrogated the induction of Pim-1 by IL-27. Finally, adenoviral transfection of dominant negative Pim-1 inhibited IL-27-induced EC differentiation of cardiac Sca-1+ cells. These findings demonstrated that IL-27 promoted the commitment of cardiac stem cells into the EC lineage, possibly leading to neovascularization as a novel biological function. IL-27 could not only regulate the inflammation but also contribute to the maintenance of the tissue homeostasis through stem cell differentiation at inflammatory sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise

    DEFF Research Database (Denmark)

    Crameri, Regina M; Langberg, Henning; Magnusson, Peter

    2004-01-01

    desmin or dystrophin, were not observed, and hence did not appear to induce the expression of either N-CAM or FA1. We therefore propose that satellite cells can be induced to re-enter the cell growth cycle after a single bout of unaccustomed high intensity exercise. However, a single bout of exercise......No studies to date have reported activation of satellite cells in vivo in human muscle after a single bout of high intensity exercise. In this investigation, eight individuals performed a single bout of high intensity exercise with one leg, the contralateral leg being the control. A significant...... increase in mononuclear cells staining for the neural cell adhesion molecule (N-CAM) and fetal antigen 1 (FA1) were observed within the exercised human vastus lateralis muscle on days 4 and 8 post exercise. In addition, a significant increase in the concentration of the FA1 protein was determined...

  1. Muse cells, newly found non-tumorigenic pluripotent stem cells, reside in human mesenchymal tissues.

    Science.gov (United States)

    Wakao, Shohei; Akashi, Hideo; Kushida, Yoshihiro; Dezawa, Mari

    2014-01-01

    Mesenchymal stem cells (MSCs) have been presumed to include a subpopulation of pluripotent-like cells as they differentiate not only into the same mesodermal-lineage cells but also into ectodermal- and endodermal-lineage cells and exert tissue regenerative effects in a wide variety of tissues. A novel type of pluripotent stem cell, Multilineage-differentiating stress enduring (Muse) cells, was recently discovered in mesenchymal tissues such as the bone marrow, adipose tissue, dermis and connective tissue of organs, as well as in cultured fibroblasts and bone marrow-MSCs. Muse cells are able to differentiate into all three germ layers from a single cell and to self-renew, and yet exhibit non-tumorigenic and low telomerase activities. They can migrate to and target damaged sites in vivo, spontaneously differentiate into cells compatible with the targeted tissue, and contribute to tissue repair. Thus, Muse cells may account for the wide variety of differentiation abilities and tissue repair effects that have been observed in MSCs. Muse cells are unique in that they are pluripotent stem cells that belong in the living body, and are thus assumed to play an important role in 'regenerative homeostasis' in vivo.

  2. Pax3-induced expansion enables the genetic correction of dystrophic satellite cells.

    Science.gov (United States)

    Filareto, Antonio; Rinaldi, Fabrizio; Arpke, Robert W; Darabi, Radbod; Belanto, Joseph J; Toso, Erik A; Miller, Auston Z; Ervasti, James M; McIvor, R Scott; Kyba, Michael; Perlingeiro, Rita Cr

    2015-01-01

    Satellite cells (SCs) are indispensable for muscle regeneration and repair; however, due to low frequency in primary muscle and loss of engraftment potential after ex vivo expansion, their use in cell therapy is currently unfeasible. To date, an alternative to this limitation has been the transplantation of SC-derived myogenic progenitor cells (MPCs), although these do not hold the same attractive properties of stem cells, such as self-renewal and long-term regenerative potential. We develop a method to expand wild-type and dystrophic fresh isolated satellite cells using transient expression of Pax3. This approach can be combined with genetic correction of dystrophic satellite cells and utilized to promote muscle regeneration when transplanted into dystrophic mice. Here, we show that SCs from wild-type and dystrophic mice can be expanded in culture through transient expression of Pax3, and these expanded activated SCs can regenerate the muscle. We test this approach in a gene therapy model by correcting dystrophic SCs from a mouse lacking dystrophin using a Sleeping Beauty transposon carrying the human μDYSTROPHIN gene. Transplantation of these expanded corrected cells into immune-deficient, dystrophin-deficient mice generated large numbers of dystrophin-expressing myofibers and improved contractile strength. Importantly, in vitro expanded SCs engrafted the SC compartment and could regenerate muscle after secondary injury. These results demonstrate that Pax3 is able to promote the ex vivo expansion of SCs while maintaining their stem cell regenerative properties.

  3. Every breath you take: The impact of environment on resident memory CD8 T cells in the lung

    Directory of Open Access Journals (Sweden)

    Hillary eShane

    2014-07-01

    Full Text Available Resident memory T cells (TRM are broadly defined as a population of T cells which persist in non-lymphoid sites long term, do not re-enter the circulation, and are distinct from central memory T cells (TCM and circulating effector memory T cells (TEM. Recent studies have described populations of TRM cells in the skin, gut, lungs and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.

  4. Comparison and analysis of Wuding and avian chicken skeletal muscle satellite cells

    NARCIS (Netherlands)

    Tong, H.Q.; Jiang, Z.Q.; Dou, T.F.; Li, Q.H.; Xu, Z.Q.; Liu, L.X.; Gu, D.H.; Rong, H.; Huang, Y.; Chen, X.B.; Jois, M.; Pas, te M.F.W.; Ge, C.R.; Jia, J.J.

    2016-01-01

    Chicken skeletal muscle satellite cells are located between the basement membrane and the sarcolemma of mature muscle fibers. Avian broilers have been genetically selected based on their high growth velocity and large muscle mass. The Wuding chicken is a famous local chicken in Yunnan Province th

  5. Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise

    DEFF Research Database (Denmark)

    Farup, Jean; Rahbek, Stine Klejs; Knudsen, Inge Skovgaard

    2014-01-01

    Human skeletal muscle satellite cells (SCs) are essential for muscle regeneration and remodeling processes in healthy and clinical conditions involving muscle breakdown. However, the potential influence of protein supplementation on post-exercise SC regulation in human skeletal muscle has not bee...

  6. Reduced satellite cell numbers with spinal cord injury and aging in humans

    NARCIS (Netherlands)

    Verdijk, L.B.; Dirks, M.L.; Snijders, T.; Prompers, J.J.; Beelen, M.; Jonkers, R.A.; Thijssen, D.H.J.; Hopman, M.T.E.; Loon, L.J. van

    2012-01-01

    INTRODUCTION: Both sarcopenia and spinal cord injury (SCI) are characterized by the loss of skeletal muscle mass and function. Despite obvious similarities in atrophy between both models, differences in muscle fiber size and satellite cell content may exist on a muscle fiber type-specific level.

  7. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  8. Alkaline regenerative fuel cell energy storage system for manned orbital satellites

    Science.gov (United States)

    Martin, R. E.; Gitlow, B.; Sheibley, D. W.

    1982-01-01

    It is pointed out that the alkaline regenerative fuel cell system represents a highly efficient, lightweight, reliable approach for providing energy storage in an orbiting satellite. In addition to its energy storage function, the system can supply hydrogen and oxygen for attitude control of the satellite and for life support. A summary is presented of the results to date obtained in connection with the NASA-sponsored fuel cell technology advancement program, giving particular attention to the requirements of the alkaline regenerative fuel cell and the low-earth mission. Attention is given to system design guidelines, weight considerations, gold-platinum cathode cell performance, matrix development, the electrolyte reservoir plate, and the cyclical load profile tests.

  9. Cycle training modulates satellite cell and transcriptional responses to a bout of resistance exercise.

    Science.gov (United States)

    Murach, Kevin A; Walton, R Grace; Fry, Christopher S; Michaelis, Sami L; Groshong, Jason S; Finlin, Brian S; Kern, Philip A; Peterson, Charlotte A

    2016-09-01

    This investigation evaluated whether moderate-intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle-aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle-aged women (56 ± 5 years, BMI 26 ± 1, VO2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I- and II-associated satellite cell density and cross-sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle-remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training (P = 0.052). MyHC I satellite cell density increased 29% in response to acute resistance exercise before endurance training and 50% with endurance training (P training, MyHC I satellite cell density decreased by 13% in response to acute resistance exercise (acute resistance × training interaction, P trained state in response to resistance exercise. Similar satellite cell and gene expression response patterns indicate coordinated regulation of the muscle environment to promote adaptation. Moderate-intensity endurance cycle training modulates the response to acute resistance exercise, potentially conditioning the muscle for more intense concentric/eccentric activity. These results suggest that cycle training is an effective endurance exercise modality for promoting growth in middle-aged women, who are susceptible to muscle mass loss with progressing age.

  10. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Somik [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yin, Hongshan [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei (China); Nam, Deokhwa [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Li, Yong [Department of Pediatric Surgery, Center for Stem Cell Research and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Ma, Ke, E-mail: kma@houstonmethodist.org [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States)

    2015-02-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

  11. Cell therapy for ischaemic heart disease: focus on the role of resident cardiac stem cells

    NARCIS (Netherlands)

    S.A.J. Chamuleau; K.R. Vrijsen; D.G. Rokosh; X.L. Tang; J.J. Piek; R. Bolli

    2009-01-01

    Myocardial infarction results in loss of cardiomyocytes, scar formation, ventricular remodelling, and eventually heart failure. In recent years, cell therapy has emerged as a potential new strategy for patients with ischaemic heart disease. This includes embryonic and bone marrow derived stem cells.

  12. Resident adult neural stem cells in Parkinson's disease--the brain's own repair system?

    Science.gov (United States)

    van den Berge, Simone A; van Strien, Miriam E; Hol, Elly M

    2013-11-05

    One important pathological process in the brain of Parkinson disease (PD) patients is the degeneration of the dopaminergic neurons in the substantia nigra, which leads to a decline in striatal dopamine levels and motor dysfunction. A major clinical problem is that this degenerative process currently cannot be stopped or reversed. Expectations from the restorative capacity of neural stem cells (NSCs) are high, as these cells can potentially replace the degenerating neurons. The discovery of the presence of NSCs in the adult human brain has instigated research into the potential of these cells as a resource to promote brain repair in neurodegenerative diseases. Neural stem and progenitor cells reside in the subventricular zone (SVZ), which is closely situated to the striatum, which is affected in PD. Therefore, restoring the dopamine levels in the striatum of PD patients through stimulating endogenous NSCs in the nearby SVZ to migrate into the striatum and differentiate into dopaminergic neurons might thus be an attractive future therapeutic approach. We will review the reported changes in NSCs in the SVZ of PD animal models and PD patients, which are due to a lack of striatal dopamine. Furthermore, we will summarise the reports that describe efforts to stimulate NSCs to replace dopaminergic cells in the SN and restore striatal dopamine levels. In our opinion, mobilizing the endogenous SVZ NSCs to replenish striatal dopamine is an attractive approach to alleviate the motor symptoms in PD patients, without the ethical and immunological challenges of transplantation of NSCs and foetal brain tissue. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Ectopic development of skeletal muscle induced by subcutaneous transplant of rat satellite cells

    Directory of Open Access Journals (Sweden)

    M.G. Fukushima

    2005-03-01

    Full Text Available The present study analyzes the ectopic development of the rat skeletal muscle originated from transplanted satellite cells. Satellite cells (10(6 cells obtained from hindlimb muscles of newborn female 2BAW Wistar rats were injected subcutaneously into the dorsal area of adult male rats. After 3, 7, and 14 days, the transplanted tissues (N = 4-5 were processed for histochemical analysis of peripheral nerves, inactive X-chromosome and acetylcholinesterase. Nicotinic acetylcholine receptors (nAChRs were also labeled with tetramethylrhodamine-labeled alpha-bungarotoxin. The development of ectopic muscles was successful in 86% of the implantation sites. By day 3, the transplanted cells were organized as multinucleated fibers containing multiple clusters of nAChRs (N = 2-4, resembling those from non-innervated cultured skeletal muscle fibers. After 7 days, the transplanted cells appeared as a highly vascularized tissue formed by bundles of fibers containing peripheral nuclei. The presence of X chromatin body indicated that subcutaneously developed fibers originated from female donor satellite cells. Differently from the extensor digitorum longus muscle of adult male rat (87.9 ± 1.0 µm; N = 213, the diameter of ectopic fibers (59.1 µm; N = 213 did not obey a Gaussian distribution and had a higher coefficient of variation. After 7 and 14 days, the organization of the nAChR clusters was similar to that of clusters from adult innervated extensor digitorum longus muscle. These findings indicate the histocompatibility of rats from 2BAW colony and that satellite cells transplanted into the subcutaneous space of adult animals are able to develop and fuse to form differentiated skeletal muscle fibers.

  14. Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections.

    Science.gov (United States)

    Conti, Heather R; Peterson, Alanna C; Brane, Lucas; Huppler, Anna R; Hernández-Santos, Nydiaris; Whibley, Natasha; Garg, Abhishek V; Simpson-Abelson, Michelle R; Gibson, Gregory A; Mamo, Anna J; Osborne, Lisa C; Bishu, Shrinivas; Ghilardi, Nico; Siebenlist, Ulrich; Watkins, Simon C; Artis, David; McGeachy, Mandy J; Gaffen, Sarah L

    2014-09-22

    Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα(-/-), and Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1-2 d by tongue-resident populations of γδ T cells and CD3(+)CD4(+)CD44(hi)TCRβ(+)CCR6(+) natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β(-/-) and TCR-δ(-/-) mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1(-/-), IL-7Rα(-/-), and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens.

  15. CD161 Expression Defines a Th1/Th17 Polyfunctional Subset of Resident Memory T Lymphocytes in Bronchoalveolar Cells.

    Directory of Open Access Journals (Sweden)

    Yolanda Gonzalez

    Full Text Available Alveolar resident memory T cells (T(RM comprise a currently uncharacterized mixture of cell subpopulations. The CD3(+CD161(+ T cell subpopulation resides in the liver, intestine and skin, but it has the capacity for tissue migration; however, the presence of resident CD3(+CD161(+ T cells in the bronchoalveolar space under normal conditions has not been reported. Bronchoalveolar cells (BACs from healthy volunteers were evaluated and found that 8.6% (range 2.5%-21% of these cells were CD3(+ T lymphocytes. Within the CD3(+ population, 4.6% of the cells (2.1-11.3 expressed CD161 on the cell surface, and 74.2% of the CD161(+CD3(+ T cells expressed CD45RO. The number of CD3(+CD161(+ T cells was significantly lower in the bronchoalveolar space than in the blood (4.6% of BACs vs 8.4% of peripheral blood mononuclear cells (PBMCs; P<0.05. We also found that 2.17% of CD4(+ T lymphocytes and 1.52% of CD8(+ T lymphocytes expressed CD161. Twenty-two percent of the alveolar CD3(+CD161(+ T lymphocytes produced cytokines upon stimulation by PMA plus ionomycin, and significantly more interferon gamma (IFN-γ was produced compared with other cytokines (P = 0.05. Most alveolar CD3(+CD161(+ T cells produced interleukin-17 (IL-17 and IFN-γ simultaneously, and the percentage of these cells was significantly higher than the percentage of CD3(+CD161- T cells. Moreover, the percentage of alveolar CD3(+CD161(+ T lymphocytes that produced IFN-γ/IL-17 was significantly higher than those in the peripheral blood (p<0.05. In conclusion, Th1/Th17-CD3(+CD161(+ TRM could contribute to compartment-specific immune responses in the lung.

  16. Regulation of turkey myogenic satellite cell migration by MicroRNAs miR-128 and miR-24.

    Science.gov (United States)

    Velleman, S G; Harding, R L

    2016-12-05

    Myogenic satellite cells are an adult stem cell responsible for all post-hatch muscle growth in poultry. As a stem cell population, satellite cells are highly heterogeneous, but the origin of this heterogeneity remains unclear. Heterogeneity is, in part, regulated by gene expression. One method of endogenous gene regulation that may contribute to heterogeneity is microRNAs (miRNAs). Two miRNAs previously shown to regulate poultry myogenic satellite cell proliferation and differentiation, miR-128 and miR-24, were studied to determine if they also affected satellite cell migration. Satellite cell migration is an essential step for both proliferation and differentiation. During proliferation, satellite cells will migrate and align to form new myofibers or donate their nuclei to existing myofibers leading to muscle fiber hypertrophy or regeneration. Transient transfection of miRNA specific mimics to each miRNA reduced migration of satellite cells following a cell culture scratch at 72 h of proliferation when the cultures were 90 to 100% confluent. However, only the migration in cells transfected with miR-24 mimics at 24 and 30 h following the scratch was significantly reduced (P ≤ 0.05) to around 70% of the distance migrated by controls. Alternately, transfection with inhibitors specific to miR-128 or miR-24 significantly (P ≤ 0.05) increased migration between 147 and 252% compared to their controls between 24 and 48 h following the scratch. These data demonstrate that miR-128 and miR-24 play a role in myogenic satellite cell migration, which will impact muscle development and growth.

  17. Critical amino acids in syndecan-4 cytoplasmic domain modulation of turkey satellite cell growth and development.

    Science.gov (United States)

    Song, Yan; McFarland, Douglas C; Velleman, Sandra G

    2012-02-01

    Syndecan-4 is composed of a core protein and covalently attached glycosaminoglycan (GAG) and N-linked glycosylated (N-glycosylated) chains. The core protein is divided into extracellular, transmembrane, and cytoplasmic domains. The cytoplasmic domain has two conserved regions and a variable region in the middle. The Ser residue in the conserved region 1 and the Tyr residue in the variable region are important in regulating protein kinase C alpha (PKCα) membrane localization and focal adhesion formation. The objective of the current study was to investigate the role of syndecan-4 Ser and Tyr residues in combination with the GAG and N-glycosylated chains in turkey satellite cell proliferation, differentiation, fibroblast growth factor 2 (FGF2) responsiveness, and PKCα membrane localization. Site-directed mutagenesis was used to generate Ser and Tyr mutants with or without GAG and N-glycosylated chains. The wild type and mutant syndecan-4 constructs were transfected into turkey satellite cells. The over-expression of Ser and Tyr mutants increased cell proliferation and differentiation and decreased membrane localization of PKCα. Furthermore, Ser mutants enhanced cellular responsiveness to FGF2. The results from this study are the first demonstration of a role of syndecan-4 cytoplasmic domain Ser and Tyr residues in regulating satellite cell proliferation, differentiation, and the modulation of cellular responsiveness to FGF2.

  18. Nestin- and Doublecortin-Positive Cells Reside in Adult Spinal Cord Meninges and Participate in Injury-Induced Parenchymal Reaction

    OpenAIRE

    2011-01-01

    Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of...

  19. Plasticity and recovery of skeletal muscle satellite cells during limb regeneration.

    Science.gov (United States)

    Morrison, Jamie I; Borg, Paula; Simon, András

    2010-03-01

    Salamander limb regeneration depends on local progenitors whose progeny are recruited to the new limb. We previously identified a Pax7(+) cell population in skeletal muscle whose progeny have the potential to contribute to the regenerating limb. However, the plasticity of individual Pax7(+) cells, as well as their recovery within the new limb, was unclear. Here, we show that Pax7(+) cells remain present after multiple rounds of limb amputation/regeneration. Pax7(+) cells are found exclusively within skeletal muscle in the regenerating limb and proliferate where the myofibers are growing. Pax7 is rapidly down-regulated in the blastema, and analyses of clonal derivatives show that Pax7(+) cell progeny are not restricted to skeletal muscle during limb regeneration. Our data suggest that the newt regeneration blastema is not entirely a composite of lineage-restricted progenitors. The results demonstrate that except for a transient and subsequently blunted increase, skeletal muscle satellite cells constitute a stable pool of reserve cells for multiple limb regeneration events.-Morrison, J. I., Borg, P., Simon, A. Plasticity and recovery of skeletal muscle satellite cells during limb regeneration.

  20. T cell memory. Skin-resident memory CD8⁺ T cells trigger a state of tissue-wide pathogen alert.

    Science.gov (United States)

    Ariotti, Silvia; Hogenbirk, Marc A; Dijkgraaf, Feline E; Visser, Lindy L; Hoekstra, Mirjam E; Song, Ji-Ying; Jacobs, Heinz; Haanen, John B; Schumacher, Ton N

    2014-10-03

    After an infection, pathogen-specific tissue-resident memory T cells (T(RM) cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create T(RM) cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how T(RM) cells provide such pathogen protection. Here, we demonstrate that activated T(RM) cells in mouse skin profoundly alter the local tissue environment by inducing a number of broadly active antiviral and antibacterial genes. This "pathogen alert" allows skin T(RM) cells to protect against an antigenically unrelated virus. These data describe a mechanism by which tissue-resident memory CD8(+) T cells protect previously infected sites that is rapid, amplifies the activation of a small number of cells into an organ-wide response, and has the capacity to control escape variants.

  1. Satellite cell response to erythropoietin treatment and endurance training in healthy young men

    DEFF Research Database (Denmark)

    Hoedt, Andrea; Christensen, Britt; Nellemann, Birgitte

    2016-01-01

    KEY POINT: Erythropoietin (Epo) treatment may induce myogenic differentiation factor (MyoD) expression and prevent apoptosis in satellite cells (SCs) in murine and in vitro models. Endurance training stimulates SC proliferation in vivo in murine and human skeletal muscle. In the present study, we...... show, in human skeletal muscle, that treatment with an Epo-stimulating agent (darbepoetin-α) in vivo increases the content of MyoD(+) SCs in healthy young men. Moreover, we report that Epo receptor mRNA is expressed in adult human SCs, suggesting that Epo may directly target SCs through ligand......-term Epo treatment during disease conditions involving anaemia may impact SCs and warrants further investigation. Satellite cell (SC) proliferation is observed following erythropoitin treatment in vitro in murine myoblasts and endurance training in vivo in human skeletal muscle. The present study aimed...

  2. Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes.

    Science.gov (United States)

    Morena, Deborah; Maestro, Nicola; Bersani, Francesca; Forni, Paolo Emanuele; Lingua, Marcello Francesco; Foglizzo, Valentina; Šćepanović, Petar; Miretti, Silvia; Morotti, Alessandro; Shern, Jack F; Khan, Javed; Ala, Ugo; Provero, Paolo; Sala, Valentina; Crepaldi, Tiziana; Gasparini, Patrizia; Casanova, Michela; Ferrari, Andrea; Sozzi, Gabriella; Chiarle, Roberto; Ponzetto, Carola; Taulli, Riccardo

    2016-03-17

    Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity.

  3. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...... control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we...

  4. Blood groups and red cell acid phosphatase types in a Mixteca population resident in Mexico City.

    Science.gov (United States)

    Buentello, L.; García, P.; Lisker, R.; Salamanca, F.; Peñaloza, R.

    1999-01-01

    Several blood groups, ABO, Rh, Ss, Fy, Jk, and red cell acid phosphatase (ACP) types were studied in a native Mixteca population that has resided in Mexico City since 1950. Gene frequencies were obtained and used to establish admixture estimates with blacks and whites. The subjects came from three different geographical areas: High Mixteca, Low Mixteca, and Coast Mixteca. All frequencies were in Hardy-Weinberg equilibrium. The difference in the ABO frequencies was statistically significant when subjects from the three areas were compared simultaneously. Rh frequencies differed only between the High and the Low Mixteca populations. The ACP frequencies were similar between the Low Mixteca population and a previously reported Mestizo population. However, there were significant differences between the High Mixteca group and a Mestizo population, all the subjects being from Oaxaca. This is the first report of Ss, Fy, Jk, and ACP frequencies in a Mixteca population. Am. J. Hum. Biol. 11:525-529, 1999. Copyright 1999 Wiley-Liss, Inc.

  5. The effect of nutritional status and myogenic satellite cell age on turkey satellite cell proliferation, differentiation, and expression of myogenic transcriptional regulatory factors and heparan sulfate proteoglycans syndecan-4 and glypican-1.

    Science.gov (United States)

    Harthan, Laura B; McFarland, Douglas C; Velleman, Sandra G

    2014-01-01

    Posthatch satellite cell mitotic activity is a critical component of muscle development and growth. Satellite cells are myogenic stem cells that can be induced by nutrition to follow other cellular developmental pathways, and whose mitotic activity declines with age. The objective of the current study was to determine the effect of restricting protein synthesis on the proliferation and differentiation, expression of myogenic transcriptional regulatory factors myogenic determination factor 1, myogenin, and myogenic regulatory factor 4, and expression of the heparan sulfate proteoglycans syndecan-4 and glypican-1 in satellite cells isolated from 1-d-, 7-wk-, and 16-wk-old turkey pectoralis major muscle (1 d, 7 wk, and 16 wk cells, respectively) by using variable concentrations of Met and Cys. Four Met concentrations-30 (control), 7.5, 3, or 0 mg/L with 3.2 mg/L of Cys per 1 mg/L of Met-were used for culture of satellite cells to determine the effect of nutrition and age on satellite cell behavior during proliferation and differentiation. Proliferation was reduced by lower Met and Cys concentrations in all ages at 96 h of proliferation. Differentiation was increased in the 1 d Met-restricted cells, whereas the 7 wk cells treated with 3 mg/L of Met had decreased differentiation. Reduced Met and Cys levels from the control did not significantly affect the 16 wk cells at 72 h of differentiation. However, medium with no Met or Cys suppressed differentiation at all ages. The expression of myogenic determination factor 1, myogenin, myogenic regulatory factor 4, syndecan-4, and glypican-1 was differentially affected by age and Met or Cys treatment. These data demonstrate the age-specific manner in which turkey pectoralis major muscle satellite cells respond to nutritional availability and the importance of defining optimal nutrition to maximize satellite cell proliferation and differentiation for subsequent muscle mass accretion.

  6. Effects of Massage on Satellite Cells of Acute Contusive Skeletal Muscles

    Institute of Scientific and Technical Information of China (English)

    胡军; 张喜林; 严隽陶

    2007-01-01

    Objective: To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods: Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by early Tuina and routine Tuina. The number of satellite cells of skeletal muscles was observed. Results: The number of the satellite cells continued to grow in both groups, and it began to increase significantly 3-5 days after Tuina treatment. Early Tuina treatment produces larger number of satellite cells than routine Tuina treatment.Conclusion: Early Tuina treatment is helpful to the marked recovery of skeletal muscles by increasing the number of satellite cell.%目的:探讨推拿治疗骨骼肌损伤的机理.方法:以重物打击方式造成腓肠肌急性挫伤模型,施以早期推拿治疗和常规推拿治疗,观察骨骼肌卫星细胞数量变化.结果:各组卫星细胞数量均呈持续上升趋势,常规治疗组和早期手法组的卫星细胞数量在3~5 d时就开始有大幅度上升.早期手法组卫星细胞数量多于常规治疗组.结论:早期手法对卫星细胞数增加作用明显有助于骨骼肌功能恢复.

  7. Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

    OpenAIRE

    Pietrangelo, Tiziana; Puglielli, Cristina; Mancinelli, Rosa; Beccafico, Sara; Fanò, Giorgio; Fulle, Stefania

    2009-01-01

    Abstract Sarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage ...

  8. Effects of voluntary wheel running on satellite cells in the rat plantaris muscle

    OpenAIRE

    Atsushi Kojima; Mitsutoshi Kurosaka; Yuji Ogura; Hisashi Naito; Shizuo Katamoto; Katsumasa Goto

    2009-01-01

    This study investigated the effects of voluntary wheel running on satellite cells in the rat plantaris muscle. Seventeen 5-week-old male Wistar rats were assigned to a control (n = 5) or training (n = 12) group. Each rat in the training group ran voluntarily in a running-wheel cage for 8 weeks. After the training period, the animals were anesthetized, and the plantaris muscles were removed, weighed, and analyzed immunohistochemically and biochemically. Although there were no significant diffe...

  9. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen.

    Science.gov (United States)

    Ariotti, Silvia; Beltman, Joost B; Chodaczek, Grzegorz; Hoekstra, Mirjam E; van Beek, Anna E; Gomez-Eerland, Raquel; Ritsma, Laila; van Rheenen, Jacco; Marée, Athanasius F M; Zal, Tomasz; de Boer, Rob J; Haanen, John B A G; Schumacher, Ton N

    2012-11-27

    Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they encounter newly infected target cells. Here we demonstrate that antigen-specific CD8(+) T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. Furthermore, we provide direct evidence for the identification of rare antigen-expressing epithelial cells by skin-patrolling memory T cells in vivo. These data demonstrate the existence of skin patrol by memory T cells and reveal the value of this patrol in the rapid detection of renewed infections at a previously infected site.

  10. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

    Science.gov (United States)

    Lee, Eun Ju; Jan, Arif Tasleem; Baig, Mohammad Hassan; Ashraf, Jalaluddin Mohammad; Nahm, Sang-Soep; Kim, Yong-Woon; Park, So-Young; Choi, Inho

    2016-08-01

    Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin (FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.-Lee, E. J., Jan, A. T., Baig, M. H., Ashraf, J. M., Nahm, S.-S., Kim, Y.-W., Park, S.-Y., Choi, I. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

  11. Satellite SAR observation of the sea surface wind field caused by rain cells

    Institute of Scientific and Technical Information of China (English)

    YE Xiaomin; LIN Mingsen; YUAN Xinzhe; DING Jing; XIE Xuetong; ZHANG Yi; XU Ying

    2016-01-01

    Rain cells or convective rain, the dominant form of rain in the tropics and subtropics, can be easy detected by satellite Synthetic Aperture Radar (SAR) images with high horizontal resolution. The footprints of rain cells on SAR images are caused by the scattering and attenuation of the rain drops, as well as the downward airflow. In this study, we extract sea surface wind field and its structure caused by rain cells by using a RADARSAT-2 SAR image with a spatial resolution of 100 m for case study. We extract the sea surface wind speeds from SAR image by using CMOD4 geophysical model function with outside wind directions of NCEP final operational global analysis data, Advance Scatterometer (ASCAT) onboard European MetOp-A satellite and microwave scatterometer onboard Chinese HY-2 satellite, respectively. The root-mean-square errors (RMSE) of these SAR wind speeds, validated against NCEP, ASCAT and HY-2, are 1.48 m/s, 1.64 m/s and 2.14 m/s, respectively. Circular signature patterns with brighter on one side and darker on the opposite side on SAR image are interpreted as the sea surface wind speed (or sea surface roughness) variety caused by downdraft associated with rain cells. The wind speeds taken from the transect profile which superposes to the wind ambient vectors and goes through the center of the circular footprint of rain cell can be fitted as a cosine or sine curve in high linear correlation with the values of no less than 0.80. The background wind speed, the wind speed caused by rain cell and the diameter of footprint of the rain cell with kilometers or tens of kilometers can be acquired by fitting curve. Eight cases interpreted and analyzed in this study all show the same conclusion.

  12. Rainbow trout (Oncorhynchus mykiss) muscle satellite cells are targets of salmonid alphavirus infection.

    Science.gov (United States)

    Biacchesi, Stéphane; Jouvion, Grégory; Mérour, Emilie; Boukadiri, Abdelhak; Desdouits, Marion; Ozden, Simona; Huerre, Michel; Ceccaldi, Pierre-Emmanuel; Brémont, Michel

    2016-01-08

    Sleeping disease in rainbow trout is characterized by an abnormal swimming behaviour of the fish which stay on their side at the bottom of the tanks. This sign is due to extensive necrosis and atrophy of red skeletal muscle induced by the sleeping disease virus (SDV), also called salmonid alphavirus 2. Infections of humans with arthritogenic alphaviruses, such as Chikungunya virus (CHIKV), are global causes of debilitating musculoskeletal diseases. The mechanisms by which the virus causes these pathologies are poorly understood due to the restrictive availability of animal models capable of reproducing the full spectrum of the disease. Nevertheless, it has been shown that CHIKV exhibits a particular tropism for muscle stem cells also known as satellite cells. Thus, SDV and its host constitute a relevant model to study in details the virus-induced muscle atrophy, the pathophysiological consequences of the infection of a particular cell-type in the skeletal muscle, and the regeneration of the muscle tissue in survivors together with the possible virus persistence. To study a putative SDV tropism for that particular cell type, we established an in vivo and ex vivo rainbow trout model of SDV-induced atrophy of the skeletal muscle. This experimental model allows reproducing the full panel of clinical signs observed during a natural infection since the transmission of the virus is arthropod-borne independent. The virus tropism in the muscle tissue was studied by immunohistochemistry together with the kinetics of the muscle atrophy, and the muscle regeneration post-infection was observed. In parallel, an ex vivo model of SDV infection of rainbow trout satellite cells was developed and virus replication and persistence in that particular cell type was followed up to 73 days post-infection. These results constitute the first observation of a specific SDV tropism for the muscle satellite cells.

  13. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

    Science.gov (United States)

    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  14. New Insights into Regulatory T Cells: Exosome- and Non-Coding RNA-Mediated Regulation of Homeostasis and Resident Treg Cells.

    Science.gov (United States)

    Li, Peiyao; Liu, Changhong; Yu, Zhibin; Wu, Minghua

    2016-01-01

    Regulatory T (Treg) cells are a group of cells that are heterogeneous in origin and in functional activity. Treg cells comprise a necessary balance to adaptive immune responses. As key regulators of self-tolerance, Treg cells have been involved in a series of pathologic processes and considered as therapeutic targets. Here, we summarize recent research regarding Treg cell origins and their functional classification, highlight the role of exosomes and non-coding RNA in modulating Treg cell homeostasis, and discuss the current understanding of resident Treg cells.

  15. New Insights into Regulatory T Cells: Exosome- and Non-Coding RNA-Mediated Regulation of Homeostasis and Resident Treg Cells

    Science.gov (United States)

    Li, Peiyao; Liu, Changhong; Yu, Zhibin; Wu, Minghua

    2016-01-01

    Regulatory T (Treg) cells are a group of cells that are heterogeneous in origin and in functional activity. Treg cells comprise a necessary balance to adaptive immune responses. As key regulators of self-tolerance, Treg cells have been involved in a series of pathologic processes and considered as therapeutic targets. Here, we summarize recent research regarding Treg cell origins and their functional classification, highlight the role of exosomes and non-coding RNA in modulating Treg cell homeostasis, and discuss the current understanding of resident Treg cells. PMID:27999575

  16. On spatial distribution of proton radiation belt from solar cell degradation of Akebono satellite

    Science.gov (United States)

    Miyake, W.; Miyoshi, Y.; Matsuoka, A.

    2013-12-01

    Solar cells on any satellite degrade gradually due to severe space radiation environment. We found a fair correlation between the decrease rate of solar cell output current of Akebono satellite orbiting in the inner magnetosphere and trapped proton flux from AP8 model between 1989 and 1992. After 1993, presumably as a result of long-term degradation, variation of solar cell output seems more susceptible to other causes such as high temperature effect, and simple monthly averaged data show no significant relation between them. One of possible causes for the temperature variation of the solar cells is terrestrial heat radiation with changing orientation of solar cell panels towards the earth and another is solar radiation varied with eccentric earth's orbit around the sun. In order to remove the possible temperature effect, we sort the data expected to be least affected by the terrestrial heat radiation from the orbit conditions, and also analyze difference of the output current for a month from that for the same month in the previous year. The analysis method leads us to successfully track a continuous correlation between the decease rate of solar cell output and energetic trapped proton flux up to 1996. We also discuss the best-fitted spatial distribution of energetic protons from comparison with model calculations.

  17. Commitment of Satellite Cells Expressing the Calcium Channel α2δ1 Subunit to the Muscle Lineage

    Directory of Open Access Journals (Sweden)

    Tammy Tamayo

    2012-01-01

    Full Text Available Satellite cells can maintain or repair muscle because they possess stem cell properties, making them a valuable option for cell therapy. However, cell transplants into skeletal muscle of patients with muscular dystrophy are limited by donor cell attachment, migration, and survival in the host tissue. Cells used for therapy are selected based on specific markers present in the plasma membrane. Although many markers have been identified, there is a need to find a marker that is expressed at different states in satellite cells, activated, quiescent, or differentiated cell. Furthermore, the marker has to be present in human tissue. Recently we reported that the plasma membrane α2δ1 protein is involved in cell attachment and migration in myoblasts. The α2δ1 subunit forms a part of the L-type voltage-dependent calcium channel in adult skeletal muscle. We found that the α2δ1 subunit is expressed in the majority of newly isolated satellite cells and that it appears earlier than the α1 subunits and at higher levels than the β or γ subunits. We also found that those cells that expressed α2δ1 would differentiate into muscle cells. This evidence indicates that the α2δ1 may be used as a marker of satellite cells that will differentiate into muscle.

  18. Antibiotic prophylaxis for children with sickle cell disease: a survey of pediatric dentistry residency program directors and pediatric hematologists.

    Science.gov (United States)

    Tate, Anupama Rao; Norris, Chelita Kaye; Minniti, Caterina P

    2006-01-01

    The purposes of this study were to: (1) investigate the current clinical practice regarding the use of antibiotic prophylaxis by pediatric dentistry residency program directors and pediatric hematologists for children with sickle cell disease (SCD) requiring dental treatment; and (2) evaluate the perceived relative risk of bacteremia following specific dental procedures, as defined by pediatric dentistry residency program directors and pediatric hematologists. A written survey depicting various clinical scenarios of SCD children requiring common dental procedures was mailed to directors of pediatric dental advanced education programs and distributed to pediatric hematologists attending the 2003 Annual Sickle Cell Disease Association of America conference in Washington, DC. Surveys were returned by 60% (N=34/57) of the pediatric dentistry residency program directors. The surveys were obtained from 51% of pediatric hematologists at the meeting (N=72/140). At least 50% of all respondents recommended prophylaxis for the following clinical situations: dental extractions, treatment under general anesthesia, and status post splenectomy. The perceived risk of infectious complication was highest for extractions, followed by restorative treatment and tooth polishing. Dental residency program directors were more likely (71%, N=24/34) to recommend additional antibiotic therapy for patients taking penicillin prophylaxis if they required an invasive oral surgical procedure. Conversely, only 38% (N=25/66) of pediatric hematologists recommended additional antibiotic therapy (P=.001). Eighty-six percent of dental residency program directors (N=25/29) chose amoxicillin for prophylaxis whereas only 62% of pediatric hematologists (N=36/58) recommended amoxicillin. (P<.05). There is a lack of consensus on the appropriate use of antibiotic prophylaxis in SCD children undergoing dental treatments. Further research and risk/benefit assessment is needed to create a unified approach.

  19. Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy.

    Science.gov (United States)

    Spranger, Stefani; Dai, Daisy; Horton, Brendan; Gajewski, Thomas F

    2017-05-08

    Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103(+) dendritic cells (DCs) in T cell-inflamed tumors. Our data indicate that lack of CD103(+) DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.

    Directory of Open Access Journals (Sweden)

    Jutta Schröder-Braunstein

    Full Text Available Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.

  1. Reduced satellite cell number in situ in muscular contractures from children with cerebral palsy.

    Science.gov (United States)

    Dayanidhi, Sudarshan; Dykstra, Peter B; Lyubasyuk, Vera; McKay, Bryon R; Chambers, Henry G; Lieber, Richard L

    2015-07-01

    Satellite cells (SC) are quiescent adult muscle stem cells critical for postnatal development. Children with cerebral palsy have impaired muscular growth and develop contractures. While flow cytometry previously demonstrated a reduced SC population, extracellular matrix abnormalities may influence the cell isolation methods used, systematically isolating fewer cells from CP muscle and creating a biased result. Consequently, the purpose of this study was to use immunohistochemistry on serial muscle sections to quantify SC in situ. Serial cross-sections from human gracilis muscle biopsies (n = 11) were labeled with fluorescent antibodies for Pax7 (SC transcriptional marker), laminin (basal lamina), and 4',6-diamidino-2-phenylindole (nuclei). Fluorescence microscopy under high magnification was used to identify SC based on labeling and location. Mean SC/100 myofibers was reduced by ∼70% (p muscle growth and apparent decreased responsiveness of CP muscle to exercise. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  2. The vascular endothelial growth factor expression and vascular regeneration in infarcted myocardium by skeletal muscle satellite cells

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss and provides a new strategy for infarct therapy. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that VEGF expression and vascular regeneration increased in infarcted myocardium by skeletal muscle satellite cells, which can promote vascular producing and improve survival environment in infarcted myocardium.Methods The skeletal muscle satellite cells were implanted into the infarcted myocardium in a model through ligated left anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying the expression of VEGF and the density of vascular by immunochemical method at two weeks after implantation. Results The proliferation and differentiation of the skeletal muscle satellite cell was very well. The expression of VEGF was higher in the implanted group (146.83±2.49) than that in the control group (134.26±6.84) (P<0.05). The vascular density in the implanted group (13.00±1.51) was also higher than that in the control (10.68±1.79) (P<0.05). Conclusion The implanted satellite cell could excrete growth factor that would induce angiogenesis and improve cell survival environment in infarcted myocardium.

  3. Multidimensional fractionation is a requirement for quantitation of Golgi-resident glycosylation enzymes from cultured human cells.

    Science.gov (United States)

    Lin, Chi-Hung; Chik, Jenny H L; Packer, Nicolle H; Molloy, Mark P

    2015-02-06

    Glycosylation results from the concerted action of glycosylation enzymes in the secretory pathway. In general, gene expression serves as the primary control mechanism, but post-translational fine-tuning of glycosylation enzyme functions is often necessary for efficient synthesis of specific glycan epitopes. While the field of glycomics has rapidly advanced, there lacks routine proteomic methods to measure expression of specific glycosylation enzymes needed to fill the gap between mRNA expression and the glycomic profile in a "reverse genomics" workflow. Toward developing this workflow we enriched Golgi membranes from two human colon cancer cell lines by sucrose density centrifugation and further mass-based fractionation by SDS-PAGE. We then applied mass spectrometry to demonstrate a doubling in the number of Golgi resident proteins identified, compared to the unenriched, low speed centrifuged supernatant of lysed cells. A total of 35 Golgi-resident glycosylation enzymes, of which 23 were glycosyltransferases, were identified making this the largest protein database so far of Golgi resident glycosylation enzymes experimentally identified in cultured human cells. We developed targeted mass spectrometry assays for specific quantitation of many of these glycosylation enzymes. Our results show that alterations in abundance of glycosylation enzymes at the protein level were generally consistent with the resultant glycomic profiles, but not necessarily with the corresponding glycosyltransferase mRNA expression as exemplified by the case of O-glycan core 1 T synthase.

  4. The long, the short, and the micro: a polyA tale of Pax3 in satellite cells.

    Science.gov (United States)

    Pasut, Alessandra; Rudnicki, Michael A

    2012-03-02

    The use of alternative polyadenylation sites is emerging as an important regulator of gene expression. In this issue of Cell Stem Cell, Boutet et al. (2012) report that alternative 3'UTRs of the Pax3 transcript restrict its expression to axial satellite cells through miR-mediated targeting of one of the isoforms. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    Science.gov (United States)

    Woon, Heng Giap; Braun, Asolina; Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G; Khanna, Rajiv; Elliot, Michael; Bell, Andrew; Hislop, Andrew D; Tangye, Stuart G; Rickinson, Alan B; Gebhardt, Thomas; Britton, Warwick J; Palendira, Umaimainthan

    2016-08-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

  6. Brain derived neurotrophic factor contributes to the cardiogenic potential of adult resident progenitor cells in failing murine heart.

    Directory of Open Access Journals (Sweden)

    Rasmita Samal

    Full Text Available Resident cardiac progenitor cells show homing properties when injected into the injured but not to the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain derived neurotrophic factor (BDNF moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium.Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up regulated 5-fold during heart failure which was verified by qRT-PCR and confirmed at protein level. The migratory capacity of Sca-1 cells from transgenic hearts was improved by 15% in the presence of 25 ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC proteomics approach. After BDNF treatment significant differences between newly synthesized proteins in Sca-1 cells from control and transgenic hearts were observed for CDK1, SRRT, HDGF, and MAP2K3 which are known to regulate cell cycle, survival and differentiation. Moreover BDNF repressed the proliferation of Sca-1 cells from transgenic hearts.Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii repressed the cell cycle progression suggesting its potency to ameliorate heart failure.

  7. Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Manuel Scimeca

    2015-01-01

    Full Text Available Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed by in situ molecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology.

  8. Satellite cell activation induced by aerobic muscle adaptation in response to endurance exercise in humans and rodents.

    Science.gov (United States)

    Abreu, Phablo; Mendes, Sávio Victor Diógenes; Ceccatto, Vânia Marilande; Hirabara, Sandro Massao

    2017-02-01

    Although the requirement of satellite cells activation and expansion following injury, mechanical load or growth stimulus provoked by resistance exercise has been well established, their function in response to aerobic exercise adaptation remains unclear. A clear relationship between satellite cell expansion in fiber-type specific myosin heavy chain and aerobic performance has been related, independent of myonuclear accretion or muscle growth. However, the trigger for this activation process is not fully understood yet and it seems to be a multi-faceted and well-orchestrated process. Emerging in vitro studies suggest a role for metabolic pathways and oxygen availability for satellite cell activation, modulating the self-renewal potential and cell fate control. The goal of this review is to describe and discuss the current knowledge about the satellite cell activation and expansion in response to aerobic exercise adaptation in human and rodent models. Additionally, findings about the in vitro metabolic control, which seems be involved in the satellite cell activation and cell fate control, are presented and discussed.

  9. Candidate solar cell materials for photovoltaic conversion in a solar power satellite /SPS/

    Science.gov (United States)

    Glaser, P. E.; Almgren, D. W.

    1978-01-01

    In recognition of the obstacles to solar-generated baseload power on earth, proposals have been made to locate solar power satellites in geosynchronous earth orbit (GEO), where solar energy would be available 24 hours a day during most of the time of the year. In an SPS, the electricity produced by solar energy conversion will be fed to microwave generators forming part of a planar phase-array transmitting antenna. The antenna is designed to precisely direct a microwave beam of very low intensity to one or more receiving antennas at desired locations on earth. At the receiving antenna, the microwave energy will be safely and efficiently reconverted to electricity and then be transmitted to consumers. An SPS system will include a number of satellites in GEO. Attention is given to the photovoltaic option for solar energy conversion in GEO, solar cell requirements, the availability of materials, the implication of large production volumes, requirements for high-volume manufacture of solar cell arrays, and the effects of concentration ratio on solar cell array area.

  10. Transcription of Satellite III non-coding RNAs is a general stress response in human cells

    Science.gov (United States)

    Valgardsdottir, Rut; Chiodi, Ilaria; Giordano, Manuela; Rossi, Antonio; Bazzini, Silvia; Ghigna, Claudia; Riva, Silvano; Biamonti, Giuseppe

    2008-01-01

    In heat-shocked human cells, heat shock factor 1 activates transcription of tandem arrays of repetitive Satellite III (SatIII) DNA in pericentromeric heterochromatin. Satellite III RNAs remain associated with sites of transcription in nuclear stress bodies (nSBs). Here we use real-time RT-PCR to study the expression of these genomic regions. Transcription is highly asymmetrical and most of the transcripts contain the G-rich strand of the repeat. A low level of G-rich RNAs is detectable in unstressed cells and a 104-fold induction occurs after heat shock. G-rich RNAs are induced by a wide range of stress treatments including heavy metals, UV-C, oxidative and hyper-osmotic stress. Differences exist among stressing agents both for the kinetics and the extent of induction (>100- to 80.000-fold). In all cases, G-rich transcripts are associated with nSBs. On the contrary, C-rich transcripts are almost undetectable in unstressed cells and modestly increase after stress. Production of SatIII RNAs after hyper-osmotic stress depends on the Tonicity Element Binding Protein indicating that activation of the arrays is triggered by different transcription factors. This is the first example of a non-coding RNA whose transcription is controlled by different transcription factors under different growth conditions. PMID:18039709

  11. Space satellite power system. [conversion of solar energy by photovoltaic solar cell arrays

    Science.gov (United States)

    Glaser, P. E.

    1974-01-01

    The concept of a satellite solar power station was studied. It is shown that it offers the potential to meet a significant portion of future energy needs, is pollution free, and is sparing of irreplaceable earth resources. Solar energy is converted by photovoltaic solar cell arrays to dc energy which in turn is converted into microwave energy in a large active phased array. The microwave energy is beamed to earth with little attenuation and is converted back to dc energy on the earth. Economic factors are considered.

  12. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.

    Science.gov (United States)

    Stegmann, Kerstin A; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R; Kennedy, Patrick; Maini, Mala K

    2016-05-23

    Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p hi)Eomes(lo)(CXCR6-) and T-bet(lo)Eomes(hi)(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bet(hi)Eomes(lo), suggesting its lineage was closer to CXCR6- peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-bet(lo)Eomes(hi) NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.

  13. Analyses of the differentiation potential of satellite cells from myoD-/-, mdx, and PMP22 C22 mice

    Directory of Open Access Journals (Sweden)

    Huxley Clare

    2005-03-01

    Full Text Available Abstract Background Sporadic and sometimes contradictory studies have indicated changes in satellite cell behaviour associated with the progressive nature of human Duchenne muscular dystrophy (DMD. Satellite cell proliferation and number are reportedly altered in DMD and the mdx mouse model. We recently found that satellite cells in MSVski transgenic mice, a muscle hypertrophy model showing progressive muscle degeneration, display a severe ageing-related differentiation defect in vitro. We tested the hypothesis that similar changes contribute to the gradual loss of muscle function with age in mdx and PMP22 mice, a model of human motor and sensory neuropathy type 1A (HMSN1A. Methods Single extensor digitorum longus muscle fibres were cultured from mdx and PMP22 mice and age- and genetic background-matched controls. Mice at several ages were compared with regard to the differentiation of satellite cells, assayed as the proportion of desmin-expressing cells that accumulated sarcomeric myosin heavy chain. Results Satellite cells of 2 month, 6 month, and 12 month old mdx mice were capable of differentiating to a similar extent to age-matched wild type control animals in an in vitro proliferation/differentiation model. Strikingly, differentiation efficiency in individual 6 month and 12 month old mdx animals varies to a much higher extent than in age-matched controls, younger mdx animals, or PMP22 mice. In contrast, differentiation of myoblasts from all myoD null mice assayed was severely impaired in this assay system. The defect in satellite cell differentiation that occurs in some mdx animals arises from a delay in differentiation that is not overcome by IGF-1 treatment at any phase of cultivation. Conclusion Overall, a defect in satellite cell differentiation above that arising through normal ageing does not occur in mdx or PMP22 mouse models of human disease. Nonetheless, the impaired differentiation of satellite cells from some mdx animals

  14. In vivo transfer of intracellular labels from locally implanted bone marrow stromal cells to resident tissue macrophages.

    Directory of Open Access Journals (Sweden)

    Edyta Pawelczyk

    Full Text Available Intracellular labels such as dextran coated superparamagnetic iron oxide nanoparticles (SPION, bromodeoxyuridine (BrdU or green fluorescent protein (GFP are frequently used to study the fate of transplanted cells by in vivo magnetic resonance imaging or fluorescent microscopy. Bystander uptake of labeled cells by resident tissue macrophages (TM can confound the interpretation of the presence of intracellular labels especially during direct implantation of cells, which can result in more than 70% cell death. In this study we determined the percentages of TM that took up SPION, BrdU or GFP from labeled bone marrow stromal cells (BMSCs that were placed into areas of angiogenesis and inflammation in a mouse model known as Matrigel plaque perfusion assay. Cells recovered from digested plaques at various time points were analyzed by fluorescence microscopy and flow cytometry. The analysis of harvested plaques revealed 5% of BrdU(+, 5-10% of GFP(+ and 5-15% of dextran(+ macrophages. The transfer of the label was not dependent on cell dose or viability. Collectively, this study suggests that care should be taken to validate donor origin of cells using an independent marker by histology and to assess transplanted cells for TM markers prior to drawing conclusions about the in vivo behavior of transplanted cells.

  15. Resident resistance.

    Science.gov (United States)

    Price, J L; Cleary, B

    1999-01-01

    Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident.

  16. Satellite cells senescence in limb muscle of severe patients with COPD.

    Directory of Open Access Journals (Sweden)

    Marie-Eve Thériault

    Full Text Available RATIONALE: The maintenance of peripheral muscle mass may be compromised in chronic obstructive pulmonary disease (COPD due to premature cellular senescence and exhaustion of the regenerative potential of the muscles. METHODS: Vastus lateralis biopsies were obtained from patients with COPD (n = 16 and healthy subjects (n = 7. Satellite cell number and the proportion of central nuclei, as a marker of muscle regenerative events, were assessed on cryosections. Telomere lengths, used as a marker of cellular senescence, were determined using Southern blot analyses. RESULTS: Central nuclei proportion was significantly higher in patients with COPD with a preserved muscle mass compared to controls and patients with COPD with muscle atrophy (p<0.001. In COPD, maximal telomere length was significantly decreased compared to controls (p<0.05. Similarly, minimal telomere length was significantly reduced in GOLD III-IV patients with muscle atrophy compared to controls (p<0.005. Minimal, mean and maximum telomere lengths correlated with mid-thigh muscle cross-sectional area (MTCSA (R = 0.523, p = 0.005; R = 0.435, p = 0.019 and R = 0.491, p = 0.009, respectively. CONCLUSIONS: Evidence of increased regenerative events was seen in GOLD III-IV patients with preserved muscle mass. Shortening of telomeres in GOLD III-IV patients with muscle atrophy is consistent with an increased number of senescent satellite cells and an exhausted muscle regenerative capacity, compromising the maintenance of muscle mass in these individuals.

  17. Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.

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    Thomas B Thornley

    Full Text Available The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.

  18. Circularly Polarized Transparent Microstrip Patch Reflectarray Integrated with Solar Cell for Satellite Applications

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    S. H. Zainud-Deen

    2016-01-01

    Full Text Available Circularly polarized (CP transparent microstrip reflectarray antenna is integrated with solar cell for small satellite applications at 10 GHz. The reflectarray unit cell consists of a perfect electric conductor (PEC square patch printed on an optically transparent substrate with the PEC ground plane. A comparison between using transparent conducting polymers and using the PEC in unit-cell construction has been introduced. The waveguide simulator is used to calculate the required compensation phase of each unit cell in the reflectarray. The radiation characteristics of 13 × 13 CP transparent reflectarray antenna are investigated. A circularly polarized horn antenna is used to feed the reflectarray. The solar cell is incorporated with the transparent reflectarray on the same area. The solar-cell integration with the reflectarray reduces the maximum gain by about 0.5 dB due to the increase in the magnitude of the reflection coefficient. The results are calculated using the finite integral technique (FIT.

  19. Study on Cell Error Rate of a Satellite ATM System Based on CDMA

    Institute of Scientific and Technical Information of China (English)

    赵彤宇; 张乃通

    2003-01-01

    In this paper, the cell error rate (CER) of a CDMA-based satellite ATM system is analyzed. Two fading models, i.e. the partial fading model and the total fading model are presented according to multi-path propagation fading and shadow effect. Based on the total shadow model, the relation of CER vs. the number of subscribers at various elevations under 2D-RAKE receiving and non-diversity receiving is got. The impact on cell error rate with pseudo noise (PN) code length is also considered. The result that the maximum likelihood combination of multi-path signal would not improve the system performance when multiple access interference (MAI) is small, on the contrary the performance may be even worse is abtained.

  20. Potential Role of Omega-3 Fatty Acids on the Myogenic Program of Satellite Cells.

    Science.gov (United States)

    Bhullar, Amritpal S; Putman, Charles T; Mazurak, Vera C

    2016-01-01

    Skeletal muscle loss is associated with aging as well as pathological conditions. Satellite cells (SCs) play an important role in muscle regeneration. Omega-3 fatty acids are widely studied in a variety of muscle wasting diseases; however, little is known about their impact on skeletal muscle regeneration. The aim of this review is to evaluate studies examining the effect of omega-3 fatty acids, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on the regulation of SC proliferation and differentiation. This review highlights mechanisms by which omega-3 fatty acids may modulate the myogenic program of the stem cell population within skeletal muscles and identifies considerations for future studies. It is proposed that minimally three myogenic transcriptional regulatory factors, paired box 7 (Pax7), myogenic differentiation 1 protein, and myogenin, should be measured to confirm the stage of SCs within the myogenic program affected by omega-3 fatty acids.

  1. Communication between neuronal somata and satellite glial cells in sensory ganglia.

    Science.gov (United States)

    Huang, Li-Yen M; Gu, Yanping; Chen, Yong

    2013-10-01

    Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. "What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia?" and "how do tissue or nerve injuries affect the communication?" are the main questions addressed in this review. Copyright © 2013 Wiley Periodicals, Inc.

  2. Optimized High Temperature PEM Fuel Cell & High Pressure PEM Electrolyser for Regenerative Fuel Cell Systems in GEO Telecommunication Satellites

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    Farnes Jarle

    2017-01-01

    Full Text Available Next generation telecommunication satellites will demand increasingly more power. Power levels up to 50 kW are foreseen for the next decades. Battery technology that can sustain up to 50 kW for eclipse lengths of up to 72 minutes will represent a major impact on the total mass of the satellite, even with new Li-ion battery technologies. Regenerative fuel cell systems (RFCS were identified years ago as a possible alternative to rechargeable batteries. CMR Prototech has investigated this technology in a series of projects initiated by ESA focusing on both the essential fuel cell technology, demonstration of cycle performance of a RFCS, corresponding to 15 years in orbit, as well as the very important reactants storage systems. In the last two years the development has been focused towards optimising the key elements of the RFCS; the HTPEM fuel cell and the High Pressure PEM electrolyser. In these ESA activities the main target has been to optimise the design by reducing the mass and at the same time improve the performance, thus increasing the specific energy. This paper will present the latest development, including the main results, showing that significant steps have been taken to increase TRL on these key components.

  3. Satellite cell heterogeneity revealed by G-Tool, an open algorithm to quantify myogenesis through colony-forming assays

    Directory of Open Access Journals (Sweden)

    Ippolito Joseph

    2012-06-01

    Full Text Available Abstract Background Muscle growth and repair is accomplished by the satellite cell pool, a self-renewing population of myogenic progenitors. Functional heterogeneity within the satellite cell compartment and changes in potential with experimental intervention can be revealed by in vitro colony-forming cell (CFC assays, however large numbers of colonies need to be assayed to give meaningful data, and manually quantifying nuclei and scoring markers of differentiation is experimentally limiting. Methods We present G-Tool, a multiplatform (Java open-source algorithm that analyzes an ensemble of fluorescent micrographs of satellite cell-derived colonies to provide quantitative and statistically meaningful metrics of myogenic potential, including proliferation capacity and propensity to differentiate. Results We demonstrate the utility of G-Tool in two applications: first, we quantify the response of satellite cells to oxygen concentration. Compared to 3% oxygen which approximates tissue levels, we find that 21% oxygen, the ambient level, markedly limits the proliferative potential of transit amplifying progeny but at the same time inhibits the rate of terminal myogenic differentiation. We also test whether satellite cells from different muscles have intrinsic differences that can be read out in vitro. Compared to masseter, dorsi, forelimb and hindlimb muscles, we find that the diaphragm satellite cells have significantly increased proliferative potential and a reduced propensity to spontaneously differentiate. These features may be related to the unique always-active status of the diaphragm. Conclusions G-Tool facilitates consistent and reproducible CFC analysis between experiments and individuals. It is released under an open-source license that enables further development by interested members of the community.

  4. Development of a nitric oxide-releasing analogue of the muscle relaxant guaifenesin for skeletal muscle satellite cell myogenesis.

    Science.gov (United States)

    Wang, Guqi; Burczynski, Frank J; Hasinoff, Brian B; Zhang, Kaidong; Lu, Qilong; Anderson, Judy E

    2009-01-01

    Nitric oxide (NO) mediates activation of satellite precursor cells to enter the cell cycle. This provides new precursor cells for skeletal muscle growth and muscle repair from injury or disease. Targeting a new drug that specifically delivers NO to muscle has the potential to promote normal function and treat neuromuscular disease, and would also help to avoid side effects of NO from other treatment modalities. In this research, we examined the effectiveness of the NO donor, iosorbide dinitrate (ISDN), and a muscle relaxant, methocarbamol, in promoting satellite cell activation assayed by muscle cell DNA synthesis in normal adult mice. The work led to the development of guaifenesin dinitrate (GDN) as a new NO donor for delivering nitric oxide to muscle. The results revealed that there was a strong increase in muscle satellite cell activation and proliferation, demonstrated by a significant 38% rise in DNA synthesis after a single transdermal treatment with the new compound for 24 h. Western blot and immunohistochemistry analyses showed that the markers of satellite cell myogenesis, expression of myf5, myogenin, and follistatin, were increased after 24 h oral administration of the compound in adult mice. This research extends our understanding of the outcomes of NO-based treatments aimed at promoting muscle regeneration in normal tissue. The potential use of such treatment for conditions such as muscle atrophy in disuse and aging, and for the promotion of muscle tissue repair as required after injury or in neuromuscular diseases such as muscular dystrophy, is highlighted.

  5. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training

    DEFF Research Database (Denmark)

    Olsen, Steen Schytte

    2006-01-01

    The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded design 32 healthy, male subjects (19–26 years) were assigned...... in the control group (CON). In conclusion, the present study demonstrates for the first time that creatine supplementation in combination with strength training amplifies the training-induced increase in satellite cell number and myonuclei concentration in human skeletal muscle fibres, thereby allowing......). Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry. Muscle mean fibre (MFA) area was determined after...

  6. MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

    DEFF Research Database (Denmark)

    Yin, Hang; Pasut, Alessandra; Soleimani, Vahab D

    2013-01-01

    (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism...... are downregulated in mice exposed to cold, resulting in de novo generation of satellite cell-derived brown adipocytes. Therefore, microRNA-133 represents an important therapeutic target for the treatment of obesity....... of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels...

  7. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8(+) T cells

    DEFF Research Database (Denmark)

    Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D;

    2016-01-01

    BACKGROUND: Skin-resident memory T (TRM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore......, the mechanisms whereby TRM cells induce rapid recall responses need further investigation. OBJECTIVES: To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. METHODS: To address these questions, we analysed responses......, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8(+) TRM cells....

  8. A Distinct Lung-Interstitium-Resident Memory CD8+ T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection

    Directory of Open Access Journals (Sweden)

    Pavlo Gilchuk

    2016-08-01

    Full Text Available The nature and anatomic location of the protective memory CD8+ T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8+ T cells and their role in lower airway infections. Memory CD8+ T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8+ T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3LO resident memory CD8+ T (Trm cell population that preferentially localizes to the pulmonary interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8+ T cells into the lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce lung interstitial Trm cells may confer better protection against respiratory pathogens.

  9. Characterization of Cardiac-Resident Progenitor Cells Expressing High Aldehyde Dehydrogenase Activity

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    Marc-Estienne Roehrich

    2013-01-01

    Full Text Available High aldehyde dehydrogenase (ALDH activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDHbr cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDHbr cells in the heart has not been evaluated so far. We have characterized ALDHbr cells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDHbr. ALDHvery-br cells were more frequent in neonatal hearts than adult. ALDHbr cells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDHvery-br cells, intermediate in ALDHbr cells, and lowest in ALDHdim cells. ALDH1A2 expression was highest in ALDHvery-br cells, intermediate in ALDHdim cells, and lowest in ALDHbr cells. ALDH1A3 and ALDH2 expression was detectable in ALDHvery-br and ALDHbr cells, unlike ALDHdim cells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDHbr cells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDHbr cells, unlike ALDHdim cells, could be grown in culture for more than 40 passages. They expressed sarcomeric α-actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDHbr cells declined with cell passage. In conclusion, the cardiac-derived ALDHbr population is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDHbr cells remains to be evaluated.

  10. Molecular and functional heterogeneity of early postnatal porcine satellite cell populations is associated with bioenergetic profile

    Science.gov (United States)

    Miersch, Claudia; Stange, Katja; Hering, Silvio; Kolisek, Martin; Viergutz, Torsten; Röntgen, Monika

    2017-01-01

    During postnatal development, hyperplastic and hypertrophic processes of skeletal muscle growth depend on the activation, proliferation, differentiation, and fusion of satellite cells (SC). Therefore, molecular and functional SC heterogeneity is an important component of muscle plasticity and will greatly affect long-term growth performance and muscle health. However, its regulation by cell intrinsic and extrinsic factors is far from clear. In particular, there is only minor information on the early postnatal period which is critical for muscle maturation and the establishment of adult SC pools. Here, we separated two SC subpopulations (P40/50, P50/70) from muscle of 4-day-old piglets. Our results characterize P40/50 as homogeneous population of committed (high expression of Myf5), fast-proliferating muscle progenitors. P50/70 constituted a slow-proliferating phenotype and contains high numbers of differentiated SC progeny. During culture, P50/70 is transformed to a population with lower differentiation potential that contains 40% Pax7-positive cells. A reversible state of low mitochondrial activity that results from active down-regulation of ATP-synthase is associated with the transition of some of the P50/70 cells to this more primitive fate typical for a reserve cell population. We assume that P40/50 and P50/70 subpopulations contribute unequally in the processes of myofiber growth and maintenance of the SC pool. PMID:28344332

  11. Adapted physical exercise enhances activation and differentiation potential of satellite cells in the skeletal muscle of old mice.

    Science.gov (United States)

    Cisterna, Barbara; Giagnacovo, Marzia; Costanzo, Manuela; Fattoretti, Patrizia; Zancanaro, Carlo; Pellicciari, Carlo; Malatesta, Manuela

    2016-05-01

    During ageing, a progressive loss of skeletal muscle mass and a decrease in muscle strength and endurance take place, in the condition termed sarcopenia. The mechanisms of sarcopenia are complex and still unclear; however, it is known that muscle atrophy is associated with a decline in the number and/or efficiency of satellite cells, the main contributors to muscle regeneration. Physical exercise proved beneficial in sarcopenia; however, knowledge of the effect of adapted physical exercise on the myogenic properties of satellite cells in aged muscles is limited. In this study the amount and activation state of satellite cells as well as their proliferation and differentiation potential were assessed in situ by morphology, morphometry and immunocytochemistry at light and transmission electron microscopy on 28-month-old mice submitted to adapted aerobic physical exercise on a treadmill. Sedentary age-matched mice served as controls, and sedentary adult mice were used as a reference for an unperturbed control at an age when the capability of muscle regeneration is still high. The effect of physical exercise in aged muscles was further analysed by comparing the myogenic potential of satellite cells isolated from old running and old sedentary mice using an in vitro system that allows observation of the differentiation process under controlled experimental conditions. The results of this ex vivo and in vitro study demonstrated that adapted physical exercise increases the number and activation of satellite cells as well as their capability to differentiate into structurally and functionally correct myotubes (even though the age-related impairment in myotube formation is not fully reversed): this evidence further supports adapted physical exercise as a powerful, non-pharmacological approach to counteract sarcopenia and the age-related deterioration of satellite cell capabilities even at very advanced age.

  12. Satellite cell activation in stretched skeletal muscle and the role of nitric oxide and hepatocyte growth factor.

    Science.gov (United States)

    Tatsumi, Ryuichi; Liu, Xiaosong; Pulido, Antonio; Morales, Mark; Sakata, Tomowa; Dial, Sharon; Hattori, Akihito; Ikeuchi, Yoshihide; Allen, Ronald E

    2006-06-01

    In the present study, we examined the roles of hepatocyte growth factor (HGF) and nitric oxide (NO) in the activation of satellite cells in passively stretched rat skeletal muscle. A hindlimb suspension model was developed in which the vastus, adductor, and gracilis muscles were subjected to stretch for 1 h. Satellite cells were activated by stretch determined on the basis of 5-bromo-2'-deoxyuridine (BrdU) incorporation in vivo. Extracts from stretched muscles stimulated BrdU incorporation in freshly isolated control rat satellite cells in a concentration-dependent manner. Extracts from stretched muscles contained the active form of HGF, and the satellite cell-activating activity could be neutralized by incubation with anti-HGF antibody. The involvement of NO was investigated by administering nitro-L-arginine methyl ester (L-NAME) or the inactive enantiomer N(G)-nitro-D-arginine methyl ester HCl (D-NAME) before stretch treatment. In vivo activation of satellite cells in stretched muscle was not inhibited by D-NAME but was inhibited by L-NAME. The activity of stretched muscle extract was abolished by L-NAME treatment but could be restored by the addition of HGF, indicating that the extract was not inhibitory. Finally, NO synthase activity in stretched and unstretched muscles was assayed in muscle extracts immediately after 2-h stretch treatment and was found to be elevated in stretched muscle but not in stretched muscle from L-NAME-treated rats. The results of these experiments demonstrate that stretching muscle liberates HGF in a NO-dependent manner, which can activate satellite cells.

  13. Identification and Characterization of Lineage(-)CD45(-)Sca-1(+) VSEL Phenotypic Cells Residing in Adult Mouse Bone Tissue.

    Science.gov (United States)

    Nakatsuka, Ryusuke; Iwaki, Ryuji; Matsuoka, Yoshikazu; Sumide, Keisuke; Kawamura, Hiroshi; Fujioka, Tatsuya; Sasaki, Yutaka; Uemura, Yasushi; Asano, Hiroaki; Kwon, A-Hon; Sonoda, Yoshiaki

    2016-01-01

    Murine bone marrow (BM)-derived very small embryonic-like stem cells (BM VSELs), defined by a lineage-negative (Lin(-)), CD45-negative (CD45(-)), Sca-1-positive (Sca-1(+)) immunophenotype, were previously reported as postnatal pluripotent stem cells (SCs). We developed a highly efficient method for isolating Lin(-)CD45(-)Sca-1(+) small cells using enzymatic treatment of murine bone. We designated these cells as bone-derived VSELs (BD VSELs). The incidences of BM VSELs in the BM-derived nucleated cells and that of BD VSELs in bone-derived nucleated cells were 0.002% and 0.15%, respectively. These BD VSELs expressed a variety of hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and endothelial cell markers. The gene expression profile of the BD VSELs was clearly distinct from those of HSCs, MSCs, and ES cells. In the steady state, the BD VSELs proliferated slowly, however, the number of BD VSELs significantly increased in the bone after acute liver injury. Moreover, green fluorescent protein-mouse derived BD VSELs transplanted via tail vein injection after acute liver injury were detected in the liver parenchyma of recipient mice. Immunohistological analyses suggested that these BD VSELs might transdifferentiate into hepatocytes. This study demonstrated that the majority of the Lin(-)CD45(-)Sca-1(+) VSEL phenotypic cells reside in the bone rather than the BM. However, the immunophenotype and the gene expression profile of BD VSELs were clearly different from those of other types of SCs, including BM VSELs, MSCs, HSCs, and ES cells. Further studies will therefore be required to elucidate their cellular and/or SC characteristics and the potential relationship between BD VSELs and BM VSELs.

  14. Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy.

    Science.gov (United States)

    Oishi, Yoshimi; Tsukamoto, Hayato; Yokokawa, Takumi; Hirotsu, Keisuke; Shimazu, Mariko; Uchida, Kenji; Tomi, Hironori; Higashida, Kazuhiko; Iwanaka, Nobumasa; Hashimoto, Takeshi

    2015-03-15

    We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals. Copyright © 2015 the American Physiological Society.

  15. Liver-Resident Memory CD8(+) T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.

    Science.gov (United States)

    Fernandez-Ruiz, Daniel; Ng, Wei Yi; Holz, Lauren E; Ma, Joel Z; Zaid, Ali; Wong, Yik Chun; Lau, Lei Shong; Mollard, Vanessa; Cozijnsen, Anton; Collins, Nicholas; Li, Jessica; Davey, Gayle M; Kato, Yu; Devi, Sapna; Skandari, Roghieh; Pauley, Michael; Manton, Jonathan H; Godfrey, Dale I; Braun, Asolina; Tay, Szun Szun; Tan, Peck Szee; Bowen, David G; Koch-Nolte, Friedrich; Rissiek, Björn; Carbone, Francis R; Crabb, Brendan S; Lahoud, Mireille; Cockburn, Ian A; Mueller, Scott N; Bertolino, Patrick; McFadden, Geoffrey I; Caminschi, Irina; Heath, William R

    2016-10-18

    In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8(+) T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids. Exploring the requirements for liver Trm cell induction, we showed that by combining dendritic cell-targeted priming with liver inflammation and antigen recognition on hepatocytes, high frequencies of Trm cells could be induced and these cells were essential for protection against malaria sporozoite challenge. Our study highlights the immune potential of liver Trm cells and provides approaches for their selective transfer, expansion, or depletion, which may be harnessed to control liver infections or autoimmunity. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

    Science.gov (United States)

    Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

    2011-12-01

    Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury.

  17. Histamine from Brain Resident MAST Cells Promotes Wakefulness and Modulates Behavioral States

    OpenAIRE

    Sachiko Chikahisa; Tohru Kodama; Atsushi Soya; Yohei Sagawa; Yuji Ishimaru; Hiroyoshi Séi; Seiji Nishino

    2013-01-01

    Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing espec...

  18. The microbiota maintain homeostasis of liver-resident γδT-17 cells in a lipid antigen/CD1d-dependent manner

    Science.gov (United States)

    Li, Fenglei; Hao, Xiaolei; Chen, Yongyan; Bai, Li; Gao, Xiang; Lian, Zhexiong; Wei, Haiming; Sun, Rui; Tian, Zhigang

    2017-01-01

    The microbiota control regional immunity using mechanisms such as inducing IL-17A-producing γδ T (γδT-17) cells in various tissues. However, little is known regarding hepatic γδT cells that are constantly stimulated by gut commensal microbes. Here we show hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. The global commensal quantity affects the number of liver-resident γδT-17 cells; indeed, E. coli alone can generate γδT-17 cells in a dose-dependent manner. Liver-resident γδT-17 cell homeostasis depends on hepatocyte-expressed CD1d, that present lipid antigen, but not Toll-like receptors or IL-1/IL-23 receptor signalling. Supplementing mice in vivo or loading hepatocytes in vitro with exogenous commensal lipid antigens augments the hepatic γδT-17 cell number. Moreover, the microbiota accelerate nonalcoholic fatty liver disease through hepatic γδT-17 cells. Thus, our work describes a unique liver-resident γδT-17 cell subset maintained by gut commensal microbes through CD1d/lipid antigens. PMID:28067223

  19. MicroRNA-128 regulates the proliferation and differentiation of bovine skeletal muscle satellite cells by repressing Sp1.

    Science.gov (United States)

    Dai, Yang; Zhang, Wei Ran; Wang, Yi Min; Liu, Xin Feng; Li, Xin; Ding, Xiang Bin; Guo, Hong

    2016-03-01

    MicroRNAs (miRNAs) play essential roles in muscle cell proliferation and differentiation. The muscle-specific miRNAs miR-1 and miR-206 have been shown to regulate muscle development and promote myogenic differentiation; however, it is likely that a number of other miRNAs play important roles in regulating myogenesis as well. microRNA-128 (miR-128) has been reported to be highly expressed in brain and skeletal muscle, and we found that miR-128 is also up-regulated during bovine skeletal muscle satellite cell differentiation using microarray analysis and qRT-PCR. However, little is known about the functions of miR-128 in bovine skeletal muscle satellite cell development. In this study, we investigated the biological functions of miR-128 in bovine skeletal muscle cell development. Using a dual-luciferase reporter assay, we confirmed that miR-128 regulates the Sp1 gene. Over-expression of miR-128 reduced Sp1 protein levels and inhibited muscle satellite cell proliferation and differentiation. Inhibition of miR-128 increased Sp1 protein levels and promoted muscle satellite cell differentiation but also suppressed proliferation. Changes in miR-128 and Sp1 expression levels also affected the protein levels of MyoD and CDKN1A. Sp1, an activator of MyoD and a suppressor of CDKN1A, plays an important role in bovine muscle cell proliferation and differentiation. The results of our study reveal a mechanism by which miR-128 regulates bovine skeletal muscle satellite cell proliferation and myogenic differentiation via Sp1.

  20. Micro space power system using MEMS fuel cell for nano-satellites

    Science.gov (United States)

    Lee, Jongkwang; Kim, Taegyu

    2014-08-01

    A micro space power system using micro fuel cell was developed for nano-satellites. The power system was fabricated using microelectromechanical system (MEMS) fabrication technologies. Polymer electrolyte membrane (PEM) fuel cell was selected in consideration of space environment. Sodium borohydride (NaBH4) was selected as a hydrogen source while hydrogen peroxide (H2O2) was selected as an oxygen source. The power system consists of a micro fuel cell, micro-reactor, micro-pump, and fuel cartridges. The micro fuel cell was fabricated on a light-weight and corrosion-resistant glass plates. The micro-reactor was used to generate hydrogen from NaBH4 alkaline solution via a catalytic hydrolysis reaction. All components such as micro-pump, fuel cartridges, and auxiliary battery were integrated for a complete power system. The storability of NaBH4 solution was evaluated at -25 °C and the performance of the micro power system was measured at various operating conditions. The power output of micro power system reasonably followed up the given electric load conditions.

  1. The differential proliferative ability of satellite cells in Lantang and Landrace pigs.

    Science.gov (United States)

    Wang, Xiu-qi; Yang, Wei-jun; Yang, Zhou; Shu, Gang; Wang, Song-bo; Jiang, Qing-yan; Yuan, Li; Wu, Tong-shan

    2012-01-01

    Here, for the first time, we evaluate the hypothesis that the proliferative abilities of satellite cells (SCs) isolated from Lantang (indigenous Chinese pigs) and Landrace pigs, which differ in muscle characteristics, are different. SCs were isolated from the longissimus dorsi muscle of neonatal Lantang and Landrace pigs. Proliferative ability was estimated by the count and proliferative activity of viable cells using a hemocytometer and MTT assay at different time points after seeding, respectively. Cell cycle information was detected by flow cytometry. Results showed that there was a greater (PLandrace pigs after 72 h of culture. The percentage of cell population in S phase and G(2)/M phases in Lantang pigs were higher (PLandrace pigs. The mRNA abundances of MyoD, Myf5, myogenin and Pax7 in SCs from Lantang pigs were higher (PLandrace pigs. Protein levels of MyoD, myogenin, myostatin, S6K, phosphorylated mTOR and phosphorylated eIF4E were consistent with the corresponding mRNA abundance. Collectively, these findings suggested that SCs in the two breeds present different proliferative abilities, and the proliferative potential of SCs in Lantang pigs is higher than in Landrace pigs.

  2. Skeletal muscle satellite cells: mediators of muscle growth during development and implications for developmental disorders.

    Science.gov (United States)

    Dayanidhi, Sudarshan; Lieber, Richard L

    2014-11-01

    Satellite cells (SCs) are the muscle stem cells responsible for longitudinal and cross-sectional postnatal growth and repair after injury and which provide new myonuclei when needed. We review their morphology and contribution to development and their role in sarcomere and myonuclear addition. SCs, similar to other tissue stem cells, cycle through different states, such as quiescence, activation, and self-renewal, and thus we consider the signaling mechanisms involved in maintenance of these states. The role of the SC niche and their interactions with other cells, such as fibroblasts and the extracellular matrix, are all emerging as major factors that affect aging and disease. Interestingly, children with cerebral palsy appear to have a reduced SC number, which could play a role in their reduced muscular development and even in muscular contracture formation. Finally, we review the current information on SC dysfunction in children with muscular dystrophy and emerging therapies that target promotion of myogenesis and reduction of fibrosis. © 2014 Wiley Periodicals, Inc.

  3. Plane of nutrition affects growth rate, organ size and skeletal muscle satellite cell activity in newborn calves.

    Science.gov (United States)

    MacGhee, M E; Bradley, J S; McCoski, S R; Reeg, A M; Ealy, A D; Johnson, S E

    2016-11-18

    Plane of nutrition effects on body, tissue and cellular growth in the neonatal calf are poorly understood. The hypothesis that a low plane of nutrition (LPN) would limit skeletal muscle size by reducing fibre growth and muscle progenitor cell activity was tested. At birth, calves were randomly assigned to either a LPN (20% CP, 20% fat; GE=1.9 Mcal/days) or a high plane of nutrition (HPN; 27% CP, 10% fat, GE = 3.8 Mcal/days) in a 2 × 3 factorial design to test the impact of diet on neonatal calf growth, organ weight and skeletal muscle morphometry with time. Groups of calves (n = 4 or 5) were euthanised at 2, 4 and 8 week of age and organ and empty carcass weights were recorded. Body composition was measured by DXA. Longissimus muscle (LM) fibre cross-sectional area (CSA), fibre/mm(2) and Pax7 were measured by immunohistology. Satellite cells were isolated at each time point and proliferation rates were measured by EdU incorporation. Calves fed a HPN had greater (p satellite cells per fibre. Proliferation rates of satellite cells isolated from HPN fed calves were greater (p satellite cell activity.

  4. Muscle Fiber Characteristics, Satellite Cells and Soccer Performance in Young Athletes

    Directory of Open Access Journals (Sweden)

    Thomas I. Metaxas, Athanasios Mandroukas, Efstratios Vamvakoudis, Kostas Kotoglou, Björn Ekblom, Konstantinos Mandroukas

    2014-09-01

    Full Text Available This study is aimed to examine the muscle fiber type, composition and satellite cells in young male soccer players and to correlate them to cardiorespiratory indices and muscle strength. The participants formed three Groups: Group A (n = 13, 11.2 ± 0.4yrs, Group B (n=10, 13.1 ± 0.5yrs and Group C (n = 9, 15.2 ± 0.6yrs. Muscle biopsies were obtained from the vastus lateralis. Peak torque values of the quadriceps and hamstrings were recorded and VO2max was measured on the treadmill. Group C had lower type I percentage distribution compared to A by 21.3% (p < 0.01, while the type IIA relative percentage was higher by 18.1% and 18.4% than in Groups A and B (p < 0.05. Groups B and C had higher cross-sectional area (CSA values in all fiber types than in Group A (0.05 < p < 0.001. The number of satellite cells did not differ between the groups. Groups B and C had higher peak torque at all angular velocities and absolute VO2max in terms of ml·min-1 than Group A (0.05 < p < 0.001. It is concluded that the increased percentage of type IIA muscle fibers noticed in Group C in comparison to the Groups A and B should be mainly attributed to the different workload exercise and training programs. The alteration of myosin heavy chain (MHC isoforms composition even in children is an important mechanism for skeletal muscle characteristics. Finally, CSA, isokinetic muscle strength and VO2max values seems to be expressed according to age.

  5. Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro.

    Science.gov (United States)

    Chal, Jérome; Al Tanoury, Ziad; Hestin, Marie; Gobert, Bénédicte; Aivio, Suvi; Hick, Aurore; Cherrier, Thomas; Nesmith, Alexander P; Parker, Kevin K; Pourquié, Olivier

    2016-10-01

    Progress toward finding a cure for muscle diseases has been slow because of the absence of relevant cellular models and the lack of a reliable source of muscle progenitors for biomedical investigation. Here we report an optimized serum-free differentiation protocol to efficiently produce striated, millimeter-long muscle fibers together with satellite-like cells from human pluripotent stem cells (hPSCs) in vitro. By mimicking key signaling events leading to muscle formation in the embryo, in particular the dual modulation of Wnt and bone morphogenetic protein (BMP) pathway signaling, this directed differentiation protocol avoids the requirement for genetic modifications or cell sorting. Robust myogenesis can be achieved in vitro within 1 month by personnel experienced in hPSC culture. The differentiating culture can be subcultured to produce large amounts of myogenic progenitors amenable to numerous downstream applications. Beyond the study of myogenesis, this differentiation method offers an attractive platform for the development of relevant in vitro models of muscle dystrophies and drug screening strategies, as well as providing a source of cells for tissue engineering and cell therapy approaches.

  6. In vivo generation of decidual natural killer cells from resident hematopoietic progenitors.

    Science.gov (United States)

    Chiossone, Laura; Vacca, Paola; Orecchia, Paola; Croxatto, Daniele; Damonte, Patrizia; Astigiano, Simonetta; Barbieri, Ottavia; Bottino, Cristina; Moretta, Lorenzo; Mingari, Maria Cristina

    2014-03-01

    Decidual natural killer cells accumulate at the fetal-maternal interface and play a key role in a successful pregnancy. However, their origin is still unknown. Do they derive from peripheral natural killer cells recruited in decidua or do they represent a distinct population that originates in situ? Here, we identified natural killer precursors in decidua and uterus of pregnant mice. These precursors underwent rapid in situ differentiation and large proportions of proliferating immature natural killer cells were present in decidua and uterus as early as gestation day 4.5. Here, we investigated the origin of decidua- and uterus-natural killer cells by performing transfer experiments of peripheral mature natural killer cells or precursors from EGFP(+) mice. Results showed that mature natural killer cells did not migrate into decidua and uterus, while precursors were recruited in these organs and differentiated towards natural killer cells. Moreover, decidua- and uterus-natural killer cells displayed unique phenotypic and functional features. They expressed high levels of the activating Ly49D receptor in spite of their immature phenotype. In addition, decidua- and uterus-natural killer cells were poorly cytolytic and produced low amounts of IFN-γ, while they released factors (GM-CSF, VEGF, IP-10) involved in neo-angiogenesis and tissue remodeling. Our data reveal in situ generation of decidual natural killer cells and provide an important correlation between mouse and human decidual natural killer cells, allowing further studies to be carried out on their role in pregnancy-related diseases.

  7. Analytical study of pulsed laser irradiation on some materials used for photovoltaic cells on satellites

    Directory of Open Access Journals (Sweden)

    Afaf M. Abd El-Hameed

    2015-12-01

    Full Text Available The present research concerns on the study of laser-powered solar panels used for space applications. A mathematical model representing the laser effects on semiconductors has been developed. The temperature behavior and heat flow on the surface and through a slab has been studied after exposed to nano-second pulsed laser. The model is applied on two different types of common active semiconductor materials that used for photovoltaic cells fabrication as silicon (Si, and gallium arsenide (GaAs. These materials are used for receivers’ manufacture for laser beamed power in space. Various values of time are estimated to clarify the heat flow through the material sample and generated under the effects of pulsed laser irradiation. These effects are theoretically studied in order to determine the performance limits of the solar cells when they are powered by laser radiation during the satellite eclipse. Moreover, the obtained results are carried out to optimize conversion efficiency of photovoltaic cells and may be helpful to give more explanation for layout of the light-electricity space systems.

  8. Skeletal muscle satellite cells, mitochondria and microRNAs: their involvement in the pathogenesis of ALS

    Directory of Open Access Journals (Sweden)

    Stavroula Tsitkanou

    2016-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS, also known as motor neurone disease (MND, is a fatal motor neurone disorder. It results in progressive degeneration and death of upper and lower motor neurones, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between two to five years from the onset of symptoms. ALS manifests as either familial ALS (FALS (~10% of cases or sporadic ALS (SALS, (~90% of cases. Mutations in the copper/zinc (CuZn superoxide dismutase (SOD1 gene account for ~20% of FALS cases and the mutant SOD1 mouse model has been used extensively to help understand the ALS pathology. As the precise mechanisms causing ALS are not well understood there is presently no cure. Recent evidence suggests that motor neuron degradation may involve a cell non-autonomous phenomenon involving numerous cell types within various tissues. Skeletal muscle is now considered as an important tissue involved in the pathogenesis of ALS by activating a retrograde signalling cascade that degrades motor neurons. Skeletal muscle heath and function are regulated by numerous factors including satellite cells, mitochondria and microRNAs. Studies demonstrate that in ALS these factors show various levels of dysregulation within the skeletal muscle. This review provides an overview of their dysregulation in various ALS models as well as how they may contribute individually and/or synergistically to the ALS pathogenesis.

  9. Analytical study of pulsed laser irradiation on some materials used for photovoltaic cells on satellites

    Science.gov (United States)

    Abd El-Hameed, Afaf M.

    2015-12-01

    The present research concerns on the study of laser-powered solar panels used for space applications. A mathematical model representing the laser effects on semiconductors has been developed. The temperature behavior and heat flow on the surface and through a slab has been studied after exposed to nano-second pulsed laser. The model is applied on two different types of common active semiconductor materials that used for photovoltaic cells fabrication as silicon (Si), and gallium arsenide (GaAs). These materials are used for receivers' manufacture for laser beamed power in space. Various values of time are estimated to clarify the heat flow through the material sample and generated under the effects of pulsed laser irradiation. These effects are theoretically studied in order to determine the performance limits of the solar cells when they are powered by laser radiation during the satellite eclipse. Moreover, the obtained results are carried out to optimize conversion efficiency of photovoltaic cells and may be helpful to give more explanation for layout of the light-electricity space systems.

  10. Injury-induced neurogenesis: consideration of resident microglia as supportive of neural progenitor cells.

    Science.gov (United States)

    McPherson, Christopher A; Kraft, Andrew D; Harry, G Jean

    2011-02-01

    The induction of neurogenesis in the adult subgranular zone (SGZ) by injury is often accompanied by changes in the extracellular environment that can have significant impacts on neural progenitor cells (NPCs). We examined the induction of neurogenesis in the SGZ at 72 h following an injection of the hippocampal toxicant, trimethyltin (TMT; 2 mg/kg, ip) inducing apoptosis in dentate granule neurons. BrdU+ incorporation during the active period of neuronal death indicated NPC proliferation and migration of newly generated cells into the granule cell layer (GCL). BrdU+ cells were transiently in contact with process bearing microglia within the inner SGZ layer. Contact with GFAP+ astrocyte processes occurred once cells were within the GCL. A small percentage of the BrdU+ cells within the SGZ region showed immunoreactivity for tumor necrosis factor (TNF) p75 receptor (TNFp75R). In mice deficient for TNFp75R, TMT injection produced an equivalent level of dentate granule cell death however; BrdU+ cells were localized at the SGZ as compared to the presence of cells within the GCL in the WT mice dosed with TMT. These data suggest that cells generated by NPCs in the SGZ induced with a focal lesion to the dentate granule neurons of adolescent mice maintain the capacity to utilize the neuroinflammation and microglia responses within their environment for migration into the GCL.

  11. Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells.

    Science.gov (United States)

    Puelles, Victor G; Douglas-Denton, Rebecca N; Cullen-McEwen, Luise A; Li, Jinhua; Hughson, Michael D; Hoy, Wendy E; Kerr, Peter G; Bertram, John F

    2015-09-01

    Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335-502), 389 NECs (IQR=265-498), and 146 PECs (IQR=111-206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431-746; Pnumber of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology.

  12. Delay in post-ovariectomy estrogen replacement negates estrogen-induced augmentation of post-exercise muscle satellite cell proliferation.

    Science.gov (United States)

    Mangan, Gary; Iqbal, Sobia; Hubbard, Andrew; Hamilton, Victoria; Bombardier, Eric; Tiidus, Peter M

    2015-11-01

    This study examined the effects of a delay in post-ovariectomy replacement of 17β-estradiol (estrogen) on the post-exercise proliferation of muscle satellite cells. Nine-week-old, ovariectomized, female Sprague-Dawley rats (n = 64) were distributed among 8 groups based on estrogen status (0.25 mg estrogen pellet or sham), exercise status (90 min run at 17 m·min(-1) and a grade of -13.5° or unexercised), and estrogen replacement ("proximal", estrogen replacement within 2 weeks; or "delayed", estrogen replacement at 11 weeks following ovariectomy). Significant increases in satellite cells were found in the soleus and white gastrocnemius muscle (immunofluorescent colocalization of nuclei with Pax7) 72 h following eccentric exercise (p exercised groups. Proximal E2 replacement resulted in a further augmentation of muscle satellite cells in exercised rats (p estrogen replacement group. Expression of PI3K was unaltered and phosphorylation of Akt relative to total Akt increased following estrogen supplementation and exercise. Exercise alone did not alter the expression levels of Akt. An 11 week delay in post-ovariectomy estrogen replacement negated the augmenting influence seen with proximal (2 week delay) post-ovariectomy estrogen replacement on post-exercise muscle satellite cell proliferation. This effect appears to be independent of the PI3K-Akt signaling pathway.

  13. Mesenchymal stem cells in human placental chorionic villi reside in a vascular Niche

    NARCIS (Netherlands)

    Castrechini, N. M.; Murthi, P.; Gude, N. M.; Erwich, J. J. H. M.; Gronthos, S.; Zannettino, A.; Brennecke, S. R.; Kalionis, B.; Brennecke, S.P.

    2010-01-01

    The chorionic villi of human term placentae are a rich source of mesenchymal stem cells (PMSCs) The stem cell "niche" within the chorionic villi regulates how PMSCs participate in placental tissue generation, maintenance and repair, but the anatomic location of the niche has not been defined A numbe

  14. The regenerating antler blastema: the derivative of stem cells resident in a pedicle stump.

    Science.gov (United States)

    Li, Chunyi; Chu, Wenhui

    2016-01-01

    Antlers of the deer are the only mammalian organs that can fully grow back once lost from their pedicles, hence offer the only opportunity to learn how nature has bestowed mammalian epimorphic regeneration. Investigations have demonstrated that it is the proliferation and differentiation of pedicle periosteal cells (PPCs), but not dedifferentiation of the local differentiated cells, that give rise to the antler blastema. PPCs express key embryonic stem cell markers and can be induced to differentiate into multiple cell lineages, so are termed antler stem cells. Further research has found that PPCs can initiate antler regeneration only when they have interacted with cells of the pedicle skin. Histologically, the process of early antler regeneration resembles that of healing of a mouse leg stump wound. However what sets these two apart is the difference in proliferation potential between the PPCs and the periosteal cells of the long bone. We believe that if we can impart a greater proliferation potential to the long bone periosteal cells, we might be able to achieve the dream of regenerating limbs in mammals.

  15. Skin-resident antigen-presenting cells: Instruction manual for vaccine development

    Directory of Open Access Journals (Sweden)

    Cynthia M. Fehres

    2013-06-01

    Full Text Available The induction of antigen-specific effector T cells is driven by proper antigen presentation and co-stimulation by dendritic cells (DCs. For this reason strategies have been developed to instruct DCs for the induction of CD4+ and CD8+ T cell responses. Since DCs are localized, amongst other locations, in peripheral tissues such as the skin, new vaccines are aiming at targeting antigens to DCs in situ. Optimal skin-DC targeting in combination with adequate adjuvant delivery facilitates DC maturation and migration to draining lymph nodes and enhances antigen cross-presentation and T cell priming. In this review we describe what DC subsets populate the human skin, as well as current vaccination strategies based on targeting strategies and alternative administration for the induction of robust long-lived anti-cancer effector T cells.

  16. Dynamic T cell migration program provides resident memory within intestinal epithelium

    Science.gov (United States)

    Choo, Daniel; Vezys, Vaiva; Wherry, E. John; Duraiswamy, Jaikumar; Akondy, Rama; Wang, Jun; Casey, Kerry A.; Barber, Daniel L.; Kawamura, Kim S.; Fraser, Kathryn A.; Webby, Richard J.; Brinkmann, Volker; Butcher, Eugene C.; Newell, Kenneth A.

    2010-01-01

    Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of intestinal homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult to reconcile with reports of intestinal T cell responses after alternative routes of immunization. We reconcile this discrepancy by demonstrating that activation within spleen results in intermediate induction of homing potential to the intestinal mucosa. We further demonstrate that memory T cells within small intestine epithelium do not routinely recirculate with memory T cells in other tissues, and we provide evidence that homing is similarly dynamic in humans after subcutaneous live yellow fever vaccine immunization. These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation. PMID:20156972

  17. A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

    OpenAIRE

    Matthew Emerson Randolph; Pavlath, Grace K.

    2015-01-01

    The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies, such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in t...

  18. Endothelial protein C receptor-expressing hematopoietic stem cells reside in the perisinusoidal niche in fetal liver.

    Science.gov (United States)

    Iwasaki, Hiroko; Arai, Fumio; Kubota, Yoshiaki; Dahl, Maria; Suda, Toshio

    2010-07-29

    Hematopoietic stem cells (HSCs) are maintained in specialized niches in adult bone marrow. However, niche and HSC maintenance mechanism in fetal liver (FL) still remains unclear. Here, we investigated the niche and the molecular mechanism of HSC maintenance in mouse FL using HSCs expressing endothelial protein C receptor (EPCR). The antiapoptotic effect of activated protein C (APC) on EPCR(+) HSCs and the expression of protease-activated receptor 1 (Par-1) mRNA in these cells suggested the involvement of the cytoprotective APC/EPCR/Par-1 pathway in HSC maintenance. Immunohistochemistry revealed that EPCR(+) cells were localized adjacent to, or integrated in, the Lyve-1(+) sinusoidal network, where APC and extracellular matrix (ECM) are abundant, suggesting that HSCs in FL were maintained in the APC- and ECM-rich perisinusoidal niche. EPCR(+) HSCs were in a relatively slow cycling state, consistent with their high expression levels of p57 and p18. Furthermore, the long-term reconstitution activity of EPCR(+) HSCs decreased significantly after short culture but not when cocultured with feeder layer of FL-derived Lyve-1(+) cells, which suggests that the maintenance of the self-renewal activity of FL HSCs largely depended on the interaction with the perisinusoidal niche. In conclusion, EPCR(+) HSCs resided in the perisinusoidal niche in mouse FL.

  19. Fibroblast Growth Factor-10 (FGF-10) Mobilizes Lung-resident Mesenchymal Stem Cells and Protects Against Acute Lung Injury.

    Science.gov (United States)

    Tong, Lin; Zhou, Jian; Rong, Linyi; Seeley, Eric J; Pan, Jue; Zhu, Xiaodan; Liu, Jie; Wang, Qin; Tang, Xinjun; Qu, Jieming; Bai, Chunxue; Song, Yuanlin

    2016-02-12

    FGF-10 can prevent or reduce lung specific inflammation due to traumatic or infectious lung injury. However, the exact mechanisms are poorly characterized. Additionally, the effect of FGF-10 on lung-resident mesenchymal stem cells (LR-MSCs) has not been studied. To better characterize the effect of FGF-10 on LR-MSCs, FGF-10 was intratracheally delivered into the lungs of rats. Three days after instillation, bronchoalveolar lavage was performed and plastic-adherent cells were cultured, characterized and then delivered therapeutically to rats after LPS intratracheal instillation. Immunophenotyping analysis of FGF-10 mobilized and cultured cells revealed expression of the MSC markers CD29, CD73, CD90, and CD105, and the absence of the hematopoietic lineage markers CD34 and CD45. Multipotency of these cells was demonstrated by their capacity to differentiate into osteocytes, adipocytes, and chondrocytes. Delivery of LR-MSCs into the lungs after LPS injury reduced the inflammatory response as evidenced by decreased wet-to-dry ratio, reduced neutrophil and leukocyte recruitment and decreased inflammatory cytokines compared to control rats. Lastly, direct delivery of FGF-10 in the lungs of rats led to an increase of LR-MSCs in the treated lungs, suggesting that the protective effect of FGF-10 might be mediated, in part, by the mobilization of LR-MSCs in lungs.

  20. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    Directory of Open Access Journals (Sweden)

    Sachiko Chikahisa

    Full Text Available Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS. Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v mice. No significant difference was found in the basal amount of sleep/wake between W/W(v mice and their wild-type littermates (WT, although W/W(v mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v mice. Injection of H1 antagonists (triprolidine and mepyramine significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v mice. W/W(v mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  1. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    Science.gov (United States)

    Chikahisa, Sachiko; Kodama, Tohru; Soya, Atsushi; Sagawa, Yohei; Ishimaru, Yuji; Séi, Hiroyoshi; Nishino, Seiji

    2013-01-01

    Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v)) mice. No significant difference was found in the basal amount of sleep/wake between W/W(v) mice and their wild-type littermates (WT), although W/W(v) mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v) mice. Injection of H1 antagonists (triprolidine and mepyramine) significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v) mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v) mice. W/W(v) mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  2. Effect of MSTN Propeptide and shRNA Co-expression Vector on Proliferation of Skeletal Muscle Satellite Cells

    Institute of Scientific and Technical Information of China (English)

    Feng Lin-he; Wang Xin; Lu Ming; Tong Hui-li; Li Shu-feng; Yan Yun-qin

    2014-01-01

    Myostatin (MSTN) is a negative regulator of skeletal muscle growth, in order to study the effect of inhibition MSTN expression on the proliferation of bovine skeletal muscle satellite cells, we constructed co-expression vector pcDNA3.1-Pro-MSTNshRNA, transfected it into muscle satellite cells by Liposome 2000, and detected cell proliferation changes by CCK-8 method and flow cytometry after 48 h. The expressions of P21 and CDK2 were detected by Western blot and real-time PCR. The results showed that the cell vitality of experimental groups significantly increased than that of the negative control, and cells in S phase also increased significantly (P<0.05). After knocked down MSTN gene, P21 expression decreased (P<0.05), but CDK2 gene expression increased (P<0.05). These results indicated that MSTN gene expression was associated with P21 and CDK2, the proliferation of skeletal muscle satellite cells could be promoted while MSTN was inhibited, which provided a theoretical basis for the study on transgenic cattle.

  3. Satellite glial cells can promote the extension of neuronal axons in vitro

    Institute of Scientific and Technical Information of China (English)

    Jiu-Hong Zhao; Yi-Di Huang; Xi-Nan Yi; Quan-Peng Zhang; Xian-Fang Zhang; Xu Dong; Gang Luo; Hai-Ying Zhang; Kun-Ju Wang; Mei-Li Lao

    2015-01-01

    Objective: To study the influence of satellite glial cells (SGCs) on the outgrowth of neuronal neurite and the role of Slit1 protein and the contact with neurons in this process, in vitro. Methods: Neurons culture and SGC-neuron co-culture were used as the cell models. The length of axons and dendrites were measured via immunofluorescence to observe the influence of SGCs on the outgrowth of neuronal neurite. The Slit1 protein was added into SGC-neuron co-culture model. The length of dendrites was measured via immunofluorescence at different point times. Result: The anatomical relationship between neurons and SGCs changed as culture period expand. At 12 h after culture, SGCs all surrounded neurons; by 72 h after culture, SGCs were all off neurons. SGCs can promote the growth of neuronal axos, but inhibit the growth of its dendrites; when SGCs closely contact with neurons, the effect of Slit1 on promoting the dendritic growth is not obvious, but when SGCs were off neurons, the effect of Slit1 on promoting the dendritic growth is significant. Conclusion: SGCs can promote the growth of neuronal axos, but inhibit the growth of its dendrites; Slit- Robo signaling pathways and contact with neurons play a role in this process.

  4. The differential proliferative ability of satellite cells in Lantang and Landrace pigs.

    Directory of Open Access Journals (Sweden)

    Xiu-qi Wang

    Full Text Available Here, for the first time, we evaluate the hypothesis that the proliferative abilities of satellite cells (SCs isolated from Lantang (indigenous Chinese pigs and Landrace pigs, which differ in muscle characteristics, are different. SCs were isolated from the longissimus dorsi muscle of neonatal Lantang and Landrace pigs. Proliferative ability was estimated by the count and proliferative activity of viable cells using a hemocytometer and MTT assay at different time points after seeding, respectively. Cell cycle information was detected by flow cytometry. Results showed that there was a greater (P<0.05 number of SCs in Lantang pigs compared with Landrace pigs after 72 h of culture. The percentage of cell population in S phase and G(2/M phases in Lantang pigs were higher (P<0.05, while in G(0/G(1 phase was lower (P<0.05 in comparison with the Landrace pigs. The mRNA abundances of MyoD, Myf5, myogenin and Pax7 in SCs from Lantang pigs were higher (P<0.05, while those of myostatin, Smad3 and genes in the mammalian target of rapamycin (mTOR pathway (with the exception of 4EBP1 were lower (P<0.05 than the Landrace pigs. Protein levels of MyoD, myogenin, myostatin, S6K, phosphorylated mTOR and phosphorylated eIF4E were consistent with the corresponding mRNA abundance. Collectively, these findings suggested that SCs in the two breeds present different proliferative abilities, and the proliferative potential of SCs in Lantang pigs is higher than in Landrace pigs.

  5. Dnmt3a Regulates Proliferation of Muscle Satellite Cells via p57Kip2

    Science.gov (United States)

    Naito, Masashi; Mori, Masaki; Inagawa, Masayo; Miyata, Kohei; Hashimoto, Naohiro; Tanaka, Sakae; Asahara, Hiroshi

    2016-01-01

    Cell differentiation status is defined by the gene expression profile, which is coordinately controlled by epigenetic mechanisms. Cell type-specific DNA methylation patterns are established by chromatin modifiers including de novo DNA methyltransferases, such as Dnmt3a and Dnmt3b. Since the discovery of the myogenic master gene MyoD, myogenic differentiation has been utilized as a model system to study tissue differentiation. Although knowledge about myogenic gene networks is accumulating, there is only a limited understanding of how DNA methylation controls the myogenic gene program. With an aim to elucidate the role of DNA methylation in muscle development and regeneration, we investigate the consequences of mutating Dnmt3a in muscle precursor cells in mice. Pax3 promoter-driven Dnmt3a-conditional knockout (cKO) mice exhibit decreased organ mass in the skeletal muscles, and attenuated regeneration after cardiotoxin-induced muscle injury. In addition, Dnmt3a-null satellite cells (SCs) exhibit a striking loss of proliferation in culture. Transcriptome analysis reveals dysregulated expression of p57Kip2, a member of the Cip/Kip family of cyclin-dependent kinase inhibitors (CDKIs), in the Dnmt3a-KO SCs. Moreover, RNAi-mediated depletion of p57Kip2 replenishes the proliferation activity of the SCs, thus establishing a role for the Dnmt3a-p57Kip2 axis in the regulation of SC proliferation. Consistent with these findings, Dnmt3a-cKO muscles exhibit fewer Pax7+ SCs, which show increased expression of p57Kip2 protein. Thus, Dnmt3a is found to maintain muscle homeostasis by epigenetically regulating the proliferation of SCs through p57Kip2. PMID:27415617

  6. Dnmt3a Regulates Proliferation of Muscle Satellite Cells via p57Kip2.

    Directory of Open Access Journals (Sweden)

    Masashi Naito

    2016-07-01

    Full Text Available Cell differentiation status is defined by the gene expression profile, which is coordinately controlled by epigenetic mechanisms. Cell type-specific DNA methylation patterns are established by chromatin modifiers including de novo DNA methyltransferases, such as Dnmt3a and Dnmt3b. Since the discovery of the myogenic master gene MyoD, myogenic differentiation has been utilized as a model system to study tissue differentiation. Although knowledge about myogenic gene networks is accumulating, there is only a limited understanding of how DNA methylation controls the myogenic gene program. With an aim to elucidate the role of DNA methylation in muscle development and regeneration, we investigate the consequences of mutating Dnmt3a in muscle precursor cells in mice. Pax3 promoter-driven Dnmt3a-conditional knockout (cKO mice exhibit decreased organ mass in the skeletal muscles, and attenuated regeneration after cardiotoxin-induced muscle injury. In addition, Dnmt3a-null satellite cells (SCs exhibit a striking loss of proliferation in culture. Transcriptome analysis reveals dysregulated expression of p57Kip2, a member of the Cip/Kip family of cyclin-dependent kinase inhibitors (CDKIs, in the Dnmt3a-KO SCs. Moreover, RNAi-mediated depletion of p57Kip2 replenishes the proliferation activity of the SCs, thus establishing a role for the Dnmt3a-p57Kip2 axis in the regulation of SC proliferation. Consistent with these findings, Dnmt3a-cKO muscles exhibit fewer Pax7+ SCs, which show increased expression of p57Kip2 protein. Thus, Dnmt3a is found to maintain muscle homeostasis by epigenetically regulating the proliferation of SCs through p57Kip2.

  7. The effect of nutritional status and muscle fiber type on myogenic satellite cell fate and apoptosis.

    Science.gov (United States)

    Powell, D J; McFarland, D C; Cowieson, A J; Muir, W I; Velleman, S G

    2014-01-01

    Satellite cells (SC) are multipotential stem cells that can be induced by nutrition to alter their cellular developmental fate, which may vary depending on their fiber type origin. The objective of the current study was to determine the effect of restricting protein synthesis on inducing adipogenic transdifferentiation and apoptosis of SC originating from fibers of the fast glycolytic pectoralis major (p. major) and fast oxidative and glycolytic biceps femoris (b. femoris) muscles of the chicken. The availability of the essential sulfur amino acids Met and Cys was restricted to regulate protein synthesis during SC proliferation and differentiation. The SC were cultured and treated with 1 of 6 Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3/9.6, 1/3.2, or 0/0 mg/L. Reductions in Met/Cys concentrations from the control level resulted in increased lipid staining and expression of the adipogenic marker genes peroxisome proliferator-activated receptor gamma and stearoyl-CoA desaturase during differentiation in the p. major SC. Although b. femoris SC had increased lipid staining at lower Met/Cys concentrations, there was no increase in expression of either adipogenic gene. For both muscle types, SC Met/Cys, concentration above the control increased the expression of peroxisome proliferator-activated receptor gamma and stearoyl-CoA desaturase during differentiation. As Met/Cys concentration was decreased during proliferation, a dose-dependent decline in all apoptotic cells occurred except for early apoptotic cells in the p. major, which had no treatment effect (P nutrition on SC transdifferentiation to an adipogenic lineage and apoptosis, and the effect of fiber type on this response in an in vitro context.

  8. New insights into Regulatory T cells:exosome and non-coding RNA mediated regulation of homeostasis, and resident regulatory T cells

    Directory of Open Access Journals (Sweden)

    Peiyao Li

    2016-12-01

    Full Text Available Regulatory T (Treg cells are a population of cells that are heterogeneous in origin and in functional activity. Treg cells constitute an essential counterbalance to adaptive immune responses. As key regulators of self-tolerance, Treg cells have been implicated in a number of pathologic processes and considered as therapeutic targets. Here, we summarize recent research regarding Treg cell origins and their functional classification, highlight the role of exosomes and non-coding RNA in modulating Treg cell homeostasis, and discuss the current understanding of resident Treg cells.

  9. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Lorenzo Alibardi

    2015-09-01

    Full Text Available The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage.

  10. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells.

    Science.gov (United States)

    Alibardi, Lorenzo

    2015-09-01

    The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage.

  11. Oval cell response is attenuated by depletion of liver resident macrophages in the 2-AAF/partial hepatectomy rat.

    Directory of Open Access Journals (Sweden)

    Shuai Xiang

    Full Text Available BACKGROUND/AIMS: Macrophages are known to play an important role in hepatocyte mediated liver regeneration by secreting inflammatory mediators. However, there is little information available on the role of resident macrophages in oval cell mediated liver regeneration. In the present study we aimed to investigate the role of macrophages in oval cell expansion induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH in rats. METHODOLOGY/PRINCIPAL FINDINGS: We depleted macrophages in the liver of 2-AAF/PH treated rats by injecting liposome encapsulated clodronate 48 hours before PH. Regeneration of remnant liver mass, as well as proliferation and differentiation of oval cells were measured. We found that macrophage-depleted rats suffered higher mortality and liver transaminase levels. We also showed that depletion of macrophages yielded a significant decrease of EPCAM and PCK positive oval cells in immunohistochemical stained liver sections 9 days after PH. Meanwhile, oval cell differentiation was also attenuated as a result of macrophage depletion, as large foci of small basophilic hepatocytes were observed by day 9 following hepatectomy in control rats whereas they were almost absent in macrophage depleted rats. Accordingly, real-time polymerase chain reaction analysis showed lower expression of albumin mRNA in macrophage depleted livers. Then we assessed whether macrophage depletion may affect hepatic production of stimulating cytokines for liver regeneration. We showed that macrophage-depletion significantly inhibited hepatic expression of tumor necrosis factor-α and interleukin-6, along with a lack of signal transducer and activator of transcription 3 phosphorylation during the early period following hepatectomy. CONCLUSIONS: These data indicate that macrophages play an important role in oval cell mediated liver regeneration in the 2-AAF/PH model.

  12. Aged Muscle Demonstrates Fiber-Type Adaptations in Response to Mechanical Overload, in the Absence of Myofiber Hypertrophy, Independent of Satellite Cell Abundance.

    Science.gov (United States)

    Lee, Jonah D; Fry, Christopher S; Mula, Jyothi; Kirby, Tyler J; Jackson, Janna R; Liu, Fujun; Yang, Lin; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2016-04-01

    Although sarcopenia, age-associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7(CreER)-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle-treated mice mounted a regenerative response, not apparent in tamoxifen-treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber-type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response. © The Author 2015. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels

    DEFF Research Database (Denmark)

    Kvorning, T; Kadi, F; Schjerling, P

    2015-01-01

    AIM: To investigate how suppression of endogenous testosterone during an 8-week strength training period influences the activity of satellite cells and myonuclei. METHODS: Twenty-two moderately trained young men participated in this randomized, placebo-controlled, and double-blinded intervention...... from the mid-portion of the vastus lateralis muscle. RESULTS: Testosterone resting level in goserelin was 10-20 times lower compared with placebo, and the training-induced increase in the level of testosterone was abolished in goserelin. Training increased satellite cells number in type II fibres by 20......% in placebo and by 52% in goserelin (P cells and myonuclei were seen in type I fibres in either group. Data from the microarray analysis...

  14. Effects of Chronic Blood-Flow Restriction Exercise on Skeletal Muscle Size and Myogenic Satellite Cell Expression

    DEFF Research Database (Denmark)

    Aagaard, Per; Jacobsen, Mikkel; Jensen, Kasper Yde

    2016-01-01

    of continued sports activity, resulting in visible hypertrophy of his left leg. AIM: To study the effect of chronic blood-flow restricted (BFR) exercise conditions on skeletal muscle size and myogenic satellite cell (SC) expression in an arterio-venous shunt patient. METHODS: Muscle biopsies were obtained from......-regulation in myogenic satellite cell activity within all stages of the cell cycle, which was accompanied by substantial muscle hypertrophy. Specifically, muscle fiber cross-sectional area (40%) and myonuclei number (15%) were elevated in the affected leg, together with an elevated myonuclear domain (20%). This single......-case study confirms previous result from our Lab demonstrating that blood-flow restricted muscle exercise leads to a marked activation of myogenic SCs, upregulated myonuclei number and marked myofiber hypertrophy....

  15. Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin

    NARCIS (Netherlands)

    Chong, James J. H.; Chandrakanthan, Vashe; Xaymardan, Munira; Asli, Naisana S.; Li, Joan; Ahmed, Ishtiaq; Heffernan, Corey; Menon, Mary K.; Scarlett, Christopher J.; Rashidianfar, Amirsalar; Biben, Christine; Zoellner, Hans; Colvin, Emily K.; Pimanda, John E.; Biankin, Andrew V.; Zhou, Bin; Pu, William T.; Prall, Owen W. J.; Harvey, Richard P.

    2011-01-01

    Colony-forming units fibroblast (CFU-Fs), analogous to those giving rise to bone marrow (BM) mesenchymal stem cells (MSCs), are present in many organs, although the relationship between BM and organ-specific CFU-Fs in homeostasis and tissue repair is unknown. Here we describe a population of adult c

  16. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.

    Science.gov (United States)

    Cantaluppi, Vincenzo; Gatti, Stefano; Medica, Davide; Figliolini, Federico; Bruno, Stefania; Deregibus, Maria C; Sordi, Andrea; Biancone, Luigi; Tetta, Ciro; Camussi, Giovanni

    2012-08-01

    Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We previously found that microvesicles released from these progenitor cells activate an angiogenic program in endothelial cells by horizontal mRNA transfer. Here, we tested whether these microvesicles prevent acute kidney injury in a rat model of ischemia-reperfusion injury. The RNA content of microvesicles was enriched in microRNAs (miRNAs) that modulate proliferation, angiogenesis, and apoptosis. After intravenous injection following ischemia-reperfusion, the microvesicles were localized within peritubular capillaries and tubular cells. This conferred functional and morphologic protection from acute kidney injury by enhanced tubular cell proliferation, reduced apoptosis, and leukocyte infiltration. Microvesicles also protected against progression of chronic kidney damage by inhibiting capillary rarefaction, glomerulosclerosis, and tubulointerstitial fibrosis. The renoprotective effect of microvesicles was lost after treatment with RNase, nonspecific miRNA depletion of microvesicles by Dicer knock-down in the progenitor cells, or depletion of pro-angiogenic miR-126 and miR-296 by transfection with specific miR-antagomirs. Thus, microvesicles derived from endothelial progenitor cells protect the kidney from ischemic acute injury by delivering their RNA content, the miRNA cargo of which contributes to reprogramming hypoxic resident renal cells to a regenerative program.

  17. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population

    Directory of Open Access Journals (Sweden)

    Walker Peter A

    2012-09-01

    Full Text Available Abstract Introduction We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. Methods C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4+/CD25+/FOXP3+ T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86+ M1 and CD206+ M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. Results Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. Conclusions The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC

  18. Muscle Stem Cell Fate Is Controlled by the Cell-Polarity Protein Scrib

    Directory of Open Access Journals (Sweden)

    Yusuke Ono

    2015-02-01

    Full Text Available Satellite cells are resident skeletal muscle stem cells that supply myonuclei for homeostasis, hypertrophy, and repair in adult muscle. Scrib is one of the major cell-polarity proteins, acting as a potent tumor suppressor in epithelial cells. Here, we show that Scrib also controls satellite-cell-fate decisions in adult mice. Scrib is undetectable in quiescent cells but becomes expressed during activation. Scrib is asymmetrically distributed in dividing daughter cells, with robust accumulation in cells committed to myogenic differentiation. Low Scrib expression is associated with the proliferative state and preventing self-renewal, whereas high Scrib levels reduce satellite cell proliferation. Satellite-cell-specific knockout of Scrib in mice causes a drastic and insurmountable defect in muscle regeneration. Thus, Scrib is a regulator of tissue stem cells, controlling population expansion and self-renewal with Scrib expression dynamics directing satellite cell fate.

  19. Age-specific functional epigenetic changes in p21 and p16 in injury-activated satellite cells.

    Science.gov (United States)

    Li, Ju; Han, Suhyoun; Cousin, Wendy; Conboy, Irina M

    2015-03-01

    The regenerative capacity of muscle dramatically decreases with age because old muscle stem cells fail to proliferate in response to tissue damage. Here, we uncover key age-specific differences underlying this proliferative decline: namely, the genetic loci of cyclin/cyclin-dependent kinase (CDK) inhibitors (CDKIs) p21 and p16 are more epigenetically silenced in young muscle stem cells, as compared to old, both in quiescent cells and those responding to tissue injury. Interestingly, phosphorylated ERK (pERK) induced in these cells by ectopic FGF2 is found in association with p21 and p16 promoters, and moreover, only in the old cells. Importantly, in the old satellite cells, FGF2/pERK silences p21 epigenetically and transcriptionally, which leads to reduced p21 protein levels and enhanced cell proliferation. In agreement with the epigenetic silencing of the loci, young muscle stem cells do not depend as much as old on ectopic FGF/pERK for their myogenic proliferation. In addition, other CDKIs, such asp15(INK4B) and p27(KIP1) , become elevated in satellite cells with age, confirming and explaining the profound regenerative defect of old muscle. This work enhances our understanding of tissue aging, promoting strategies for combating age-imposed tissue degeneration.

  20. IGF-1,bFGF EXPRESSION AND VASCULAR REGENERATION IN ACUTE INFARCTED CANINE MYOCARDIUM AFTER AUTOLOGUS SKELETAL MUSCLE SATELLITE CELL IMPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱洪生; 钟竑; 张臻

    2003-01-01

    Objective To study the cell growth factor secretion and vascular regeneration in acute infarcted myocardium after autologous skeletal muscle satellite cell implantation.MethodsAutologous skeletal muscle satellite cells from adult mongrel canine were implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) artery. Specimens were harvested at 2, 4, 8 weeks after implantation for the expression of insulin like growth factor-1 (IGF-1), basic fibroblast growth factor (Bfgf) and the vascular density.ResultsThe expression of IGF-1, Bfgf and the vascular density in skeletal muscle satellite cell implant group were higher than that in the control group.ConclusionThe skeletal muscle satellite cells, after being implanted into the acute myocardial infarction, not only showed myocardial regeneration, but also showed the ability to secrete the cell factors, hence representing a positive effect on the regeneration of the infarcted myocardium.

  1. Fiber Type-Specific Satellite Cell Content in Cyclists Following Heavy Training with Carbohydrate and Carbohydrate-Protein Supplementation

    Science.gov (United States)

    McKenzie, Alec I.; D'Lugos, Andrew C.; Saunders, Michael J.; Gworek, Keith D.; Luden, Nicholas D.

    2016-01-01

    The central purpose of this study was to evaluate the fiber type-specific satellite cell and myonuclear responses of endurance-trained cyclists to a block of intensified training, when supplementing with carbohydrate (CHO) vs. carbohydrate-protein (PRO). In a crossover design, endurance-trained cyclists (n = 8) performed two consecutive training periods, once supplementing with CHO (de facto “control” condition) and the other with PRO. Each training period consisted of 10 days of intensified cycle training (ICT–120% increase in average training duration) followed by 10 days of recovery (RVT–reduced volume training; 33% volume reduction vs. normal training). Skeletal muscle biopsies were obtained from the vastus lateralis before and after ICT and again following RVT. Immunofluorescent microscopy was used to quantify SCs (Pax7+), myonuclei (DAPI+), and myosin heavy chain I (MyHC I). Data are expressed as percent change ± 90% confidence limits. The 10-day block of ICTCHO increased MyHC I SC content (35 ± 28%) and myonuclear density (16 ± 6%), which remained elevated following RVTCHO (SC = 69 ± 50% vs. PRE; Nuclei = 17 ± 15% vs. PRE). MyHC II SC and myonuclei were not different following ICTCHO, but were higher following RVTCHO (SC = +33 ± 31% vs. PRE; Nuclei = 15 ± 14% vs. PRE), indicating a delayed response compared to MyHC I fibers. The MyHC I SC pool increased following ICTPRO (37 ± 37%), but without a concomitant increase in myonuclei. There were no changes in MyHC II SC or myonuclei following ICTPRO. Collectively, these trained endurance cyclists possessed a relatively large pool of SCs that facilitated rapid (MyHC I) and delayed (MyHC II) satellite cell proliferation and myonuclear accretion under carbohydrate conditions. The current findings strengthen the growing body of evidence demonstrating alterations in satellite cell number in the absence of hypertrophy. Satellite cell pool expansion is typically viewed as an advantageous response to

  2. Growth hormone responsive neural precursor cells reside within the adult mammalian brain

    OpenAIRE

    Blackmore, Daniel G.; Brent A. Reynolds; Golmohammadi, Mohammad G.; Large, Beatrice; Aguilar, Roberto M.; Haro, Luis; Waters, Michael J.; Rietze, Rodney L.

    2012-01-01

    The detection of growth hormone (GH) and its receptor in germinal regions of the mammalian brain prompted our investigation of GH and its role in the regulation of endogenous neural precursor cell activity. Here we report that the addition of exogenous GH significantly increased the expansion rate in long-term neurosphere cultures derived from wild-type mice, while neurospheres derived from GH null mice exhibited a reduced expansion rate. We also detected a doubling in the frequency of large ...

  3. Effect of eccentric contraction on satellite cell activation in human vastus lateralis muscle.

    Science.gov (United States)

    Imaoka, Yoko; Kawai, Minako; Mori, Futoshi; Miyata, Hirofumi

    2015-09-01

    We compared the time-course of satellite cell (SC) activation between eccentric and concentric contractions in the vastus lateralis (VL) muscle after step exercise. Young adults participated in a 30-min step up/down exercise which mainly involved concentric contractions with the right VL muscle and eccentric contractions with the left VL muscle. The concentric and eccentric contraction phases of the VL muscles were identified by changes in the electromyogram (EMG) and knee joint angle. Biopsy samples were taken from both VL muscles at three time periods: before the exercise and 2 and 5 days after the exercise. We found that the numbers of SCs were significantly increased in the type IIa fibers of the left VL at 2 and 5 days after the exercise. The expression of both hepatocyte growth factor (HGF) and myogenic differentiation 1 (MyoD) mRNA had significantly increased in the left VL at 2 and 5 days after the exercise and in the right VL at 5 days after the exercise. The expression of transient receptor potential canonical (TRPC) 1 mRNA also increased in the left VL at 2 days after exercise. These results indicate that eccentric contraction can effectively activate SC proliferation for up to 5 days after exercise. Similar changes in HGF, MyoD and TRPC1 mRNA expression suggest that HGF/c-Met signal activation through cation influx has a major impact on skeletal muscle SC activation in response to eccentric exercise.

  4. Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts

    Institute of Scientific and Technical Information of China (English)

    Xiaojia Ge; Ravi Kambadur; Craig McFarlane; Anuradha Vajjala; Sudarsanareddy Lokireddy; Zhi Hui Ng; Chek Kun Tan; Nguan Soon Tan; Walter Wahli; Mridula Sharma

    2011-01-01

    TGF-β and myostatin are the two most important regulators of muscle growth.Both growth factors have been shown to signal through a Smad3-dependent pathway.However to date,the role of Smad3 in muscle growth and differentiation is not investigated.Here,we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy.Consistent with this,we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice.Loss of Smad3 also led to defective satellite cell (SC) functionality.Smad3-null SCs showed reduced propensity for self-renewal,which may lead to a progressive loss of SC number.Indeed,decreased SC number was observed in skeletal muscle from Smad3- null mice showing signs of severe muscle wasting.Further in vitro analysis of primary myoblast cultures identified that Smad3-nuil myoblasts exhibit impaired proliferation,differentiation and fusion,resulting in the formation of atrophied myotubes.A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts.Given that myostatin is a negative regulator,we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice.Consistent with this theory,inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype.

  5. Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise.

    Science.gov (United States)

    Farup, Jean; Rahbek, Stine Klejs; Knudsen, Inge Skovgaard; de Paoli, Frank; Mackey, Abigail L; Vissing, Kristian

    2014-11-01

    Human skeletal muscle satellite cells (SCs) are essential for muscle regeneration and remodeling processes in healthy and clinical conditions involving muscle breakdown. However, the potential influence of protein supplementation on post-exercise SC regulation in human skeletal muscle has not been well investigated. In a comparative human study, we investigated the effect of hydrolyzed whey protein supplementation following eccentric exercise on fiber type-specific SC accumulation. Twenty-four young healthy subjects received either hydrolyzed whey protein + carbohydrate (whey, n = 12) or iso-caloric carbohydrate (placebo, n = 12) during post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior to and 24, 48 and 168 h post-exercise, muscle biopsies were obtained from the exercise leg and analyzed for fiber type-specific SC content. Maximal voluntary contraction (MVC) and serum creatine kinase (CK) were evaluated as indices of recovery from muscle damage. In type II fiber-associated SCs, the whey group increased SCs/fiber from 0.05 [0.02; 0.07] to 0.09 [0.06; 0.12] (p eccentric exercise.

  6. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

    Science.gov (United States)

    Dubois, Vanessa; Laurent, Michaël R; Sinnesael, Mieke; Cielen, Nele; Helsen, Christine; Clinckemalie, Liesbeth; Spans, Lien; Gayan-Ramirez, Ghislaine; Deldicque, Louise; Hespel, Peter; Carmeliet, Geert; Vanderschueren, Dirk; Claessens, Frank

    2014-07-01

    Androgens have well-established anabolic actions on skeletal muscle, although the direct effects of the androgen receptor (AR) in muscle remain unclear. We generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is selectively ablated in satellite cells, the muscle precursor cells. Total-limb maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles containing ∼10% more type I fibers and 10% less type IIa fibers than the corresponding control littermates. The weight of the perineal levator ani muscle is markedly reduced (-52%). Thus, muscle AR is involved in fiber-type distribution and force production of the limb muscles, while it is a major determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes (6-fold reduction in satARKO) through direct transcription activation by the AR. Consequently, muscle hypertrophy in response to androgens is augmented in Mstn-knockout mice. Our finding that androgens induce Mstn signaling to restrain their own anabolic actions has implications for the treatment of muscle wasting disorders.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C., Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P., Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

  7. Permanent resident.

    Science.gov (United States)

    Fisher, John F

    2016-01-01

    The training of physicians in the past century was based primarily on responsibility and the chain-of-command. Those with the bulk of that responsibility in the fields of pediatrics and internal medicine were residents. Residents trained the medical students and supervised them carefully in caring for patients. Most attending physicians supervised their teams at arm's length, primarily serving as teachers of the finer points of diagnosis and treatment during set periods of the day or week with a perfunctory signature on write-ups or progress notes. Residents endeavored to protect the attending physician from being heavily involved unless they were unsure about a clinical problem. Before contacting the attending physician, a more senior resident would be called. Responsibility was the ultimate teacher. The introduction of diagnosis-related groups by the federal government dramatically changed the health care delivery system, placing greater emphasis on attending physician visibility in the medical record, ultimately resulting in more attending physician involvement in day-to-day care of patients in academic institutions. Without specified content in attending notes, hospital revenues would decline. Although always in charge technically, attending physicians increasingly have assumed the role once dominated by the resident. Using biographical experiences of more than 40 years, the author acknowledges and praises the educational role of responsibility in his own training and laments its declining role in today's students and house staff.

  8. Permanent resident

    Directory of Open Access Journals (Sweden)

    John F. Fisher

    2016-05-01

    Full Text Available The training of physicians in the past century was based primarily on responsibility and the chain-of-command. Those with the bulk of that responsibility in the fields of pediatrics and internal medicine were residents. Residents trained the medical students and supervised them carefully in caring for patients. Most attending physicians supervised their teams at arm's length, primarily serving as teachers of the finer points of diagnosis and treatment during set periods of the day or week with a perfunctory signature on write-ups or progress notes. Residents endeavored to protect the attending physician from being heavily involved unless they were unsure about a clinical problem. Before contacting the attending physician, a more senior resident would be called. Responsibility was the ultimate teacher. The introduction of diagnosis-related groups by the federal government dramatically changed the health care delivery system, placing greater emphasis on attending physician visibility in the medical record, ultimately resulting in more attending physician involvement in day-to-day care of patients in academic institutions. Without specified content in attending notes, hospital revenues would decline. Although always in charge technically, attending physicians increasingly have assumed the role once dominated by the resident. Using biographical experiences of more than 40 years, the author acknowledges and praises the educational role of responsibility in his own training and laments its declining role in today's students and house staff.

  9. The closely related CD103+ dendritic cells (DCs) and lymphoid-resident CD8+ DCs differ in their inflammatory functions.

    Science.gov (United States)

    Jiao, Zhijun; Bedoui, Sammy; Brady, Jamie L; Walter, Anne; Chopin, Michael; Carrington, Emma M; Sutherland, Robyn M; Nutt, Stephen L; Zhang, Yuxia; Ko, Hyun-Ja; Wu, Li; Lew, Andrew M; Zhan, Yifan

    2014-01-01

    Migratory CD103+ and lymphoid-resident CD8+ dendritic cells (DCs) share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+ DCs. This superior capacity to drive Th17 responses was also evident in CD103+ DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103+ DCs compared with CD8+ DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103+ DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103+ DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs.

  10. The closely related CD103+ dendritic cells (DCs and lymphoid-resident CD8+ DCs differ in their inflammatory functions.

    Directory of Open Access Journals (Sweden)

    Zhijun Jiao

    Full Text Available Migratory CD103+ and lymphoid-resident CD8+ dendritic cells (DCs share many attributes, such as dependence on the same transcription factors, cross-presenting ability and expression of certain surface molecules, such that it has been proposed they belong to a common sub-lineage. The functional diversity of the two DC types is nevertheless incompletely understood. Here we reveal that upon skin infection with herpes simplex virus, migratory CD103+ DCs from draining lymph nodes were more potent at inducing Th17 cytokine production by CD4+ T cells than CD8+ DCs. This superior capacity to drive Th17 responses was also evident in CD103+ DCs from uninfected mice. Their differential potency to induce Th17 differentiation was reflected by higher production of IL-1β and IL-6 by CD103+ DCs compared with CD8+ DCs upon stimulation. The two types of DCs from isolated lymph nodes also differ in expression of certain pattern recognition receptors. Furthermore, elevated levels of GM-CSF, typical of those found in inflammation, substantially increased the pool size of CD103+ DCs in lymph nodes and skin. We argue that varied levels of GM-CSF may explain the contrasting reports regarding the positive role of GM-CSF in regulating development of CD103+ DCs. Together, we find that these two developmentally closely-related DC subsets display functional differences and that GM-CSF has differential effect on the two types of DCs.

  11. Real-time imaging of resident T cells in human lung and ovarian carcinomas reveals how different tumor microenvironments control T lymphocyte migration

    Directory of Open Access Journals (Sweden)

    Houcine eBougherara

    2015-10-01

    Full Text Available T cells play a key role in the battle against cancer. To perform their antitumor activities, T cells need to adequately respond to tumor antigens by establishing contact with either malignant cells or antigen-presenting cells. These latter functions rely on a series of migratory steps that go from entry of T cells into the tumor followed by their locomotion in the tumor stroma. Our knowledge of how T cells migrate within tumors mainly comes from experiments performed in mouse models. Whereas such systems have greatly advanced our understanding, they do not always faithfully recapitulate the disease observed in cancer patients. We previously described a technique based on tissue slices that enables to track with real-time imaging microscopy the motile behavior of fluorescent T cells plated onto fresh sections of human lung tumors. We have now refined this approach to monitor the locomotion of resident tumor-infiltrating CD8 T cells labeled with fluorescently-coupled antibodies. Using this approach, our findings reveal that CD8 T cells accumulate in the stroma of ovarian and lung carcinomas but move slowly in this compartment. Conversely, even though less populated, tumors islets were found to be zones of faster migration for resident CD8 T cells. We also confirm the key role played by collagen fibers which, by their orientation, spacing and density, control the distribution and migration of resident CD8 T cells within the tumor stroma. We have subsequently demonstrated that under some physical tissue constraints CD8 T cells exhibited a mode of migration characterized by alternate forward and backward movements. In sum, using an ex vivo assay to track CD8 T cells in fresh human tumor tissues, we have identified the extracellular matrix as a major stromal component in influencing T cell migration, thereby impacting control of tumor growth. This approach will aid in the development and testing of novel immunotherapy strategies to promote T cell

  12. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth.

    Science.gov (United States)

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon; Vendelbo, Mikkel Holm; Paoli, Frank de; Vissing, Kristian

    2014-10-15

    Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type-specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P hypertrophy correlated with whole muscle hypertrophy exclusively following Conc training (P eccentric resistance training while type II fiber hypertrophy was accentuated when combining concentric resistance training with whey protein supplementation.

  13. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training

    DEFF Research Database (Denmark)

    Olsen, Steen; Aagaard, Per; Kadi, Fawzi

    2006-01-01

    ). Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry. Muscle mean fibre (MFA) area was determined after...... histochemical analysis. All training regimes were found to increase the proportion of satellite cells, but significantly greater enhancements were observed with creatine supplementation at week 4 (compared to STR-CON) and at week 8 (compared to STR-PRO and STR-CON) (P... number was no longer elevated in STR-CRE, while it remained elevated in STR-PRO and STR-CON. Furthermore, creatine supplementation resulted in an increased number of myonuclei per fibre and increases of 14-17% in MFA at week 4, 8 and 16 (Pincrease in MFA only...

  14. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth

    DEFF Research Database (Denmark)

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon

    2014-01-01

    -specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose......Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type......) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P

  15. Charge efficiency of Ni/H2 cells during transfer orbit of Telstar 4 satellites

    Science.gov (United States)

    Fang, W. C.; Maurer, Dean W.; Vyas, B.; Thomas, M. N.

    1994-02-01

    The TELSTAR 4 communication satellites being manufactured by Martin Marietta Astro Space (Astro Space) for AT&T are three axis stabilized spacecraft scheduled to be launched on expendable vehicles such as the Atlas or Ariane rockets. Typically, these spacecraft consist of a box that holds the electronics and supports the antenna reflectors and the solar array wings. The wings and reflectors are folded against the sides of the box during launch and the spacecraft is spun for attitude control in that phase; they are then deployed after achieving the final orbit. The launch phase and transfer orbits required to achieve the final geosynchronous orbit typically take 4 to 5 days during which time the power required for command, telemetry, attitude control, heaters, etc., is provided by two 50 AH nickel hydrogen batteries augmented by the exposed outboard solar panels. In the past, this situation has presented no problem since there was a considerable excess of power available from the array. In the case of large high powered spacecraft such as TELSTAR 4, however, the design power levels in transfer orbit approach the time-averaged power available from the exposed surface area of the solar arrays, resulting in a very tight power margin. To compound the difficulty, the array output of the spinning spacecraft in transfer orbit is shaped like a full wave rectified sine function and provides very low charging rates to the batteries during portions of the rotation. In view of the typically low charging efficiency of alkaline nickel batteries at low rates, it was decided to measure the efficiency during a simulation of the TELSTAR 4 conditions at the expected power levels and temperatures on three nickel hydrogen cells of similar design. The unique feature of nickel hydrogen cells that makes the continuous measurement of efficiency possible is that hydrogen is one of the active materials and thus, cell pressure is a direct measure of the state of charge or available capacity

  16. Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential.

    Science.gov (United States)

    Swaims-Kohlmeier, Alison; Haaland, Richard E; Haddad, Lisa B; Sheth, Anandi N; Evans-Strickfaden, Tammy; Lupo, L Davis; Cordes, Sarah; Aguirre, Alfredo J; Lupoli, Kathryn A; Chen, Cheng-Yen; Ofotukun, Igho; Hart, Clyde E; Kohlmeier, Jacob E

    2016-07-01

    The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7(hi), consistent with a central memory or recirculating memory T cell phenotype. In addition, roughly half of these CCR7(hi) CD4 T cells expressed CD69, consistent with resident memory T cells, whereas the remaining CCR7(hi) CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7(hi) CD4 T cells compared with blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7(hi) memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7(hi) memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7(hi) FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle, and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7(hi) CD4 T cells, and progesterone levels predict opportunities for HIV to access these novel target cells.

  17. The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

    Science.gov (United States)

    Chakravarthy, M. V.; Booth, F. W.; Spangenburg, E. E.

    2001-01-01

    Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

  18. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration

    OpenAIRE

    Alessandra Castiglioni; Gianfranca Corna; Elena Rigamonti; Veronica Basso; Michela Vezzoli; Antonella Monno; Almada, Albert E; Anna Mondino; Wagers, Amy J.; Angelo A. Manfredi; Patrizia Rovere-Querini

    2015-01-01

    Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the musc...

  19. Broad-Spectrum Antimicrobial Star Polycarbonates Functionalized with Mannose for Targeting Bacteria Residing inside Immune Cells.

    Science.gov (United States)

    Yang, Chuan; Krishnamurthy, Sangeetha; Liu, Jie; Liu, Shaoqiong; Lu, Xiaohua; Coady, Daniel J; Cheng, Wei; De Libero, Gennaro; Singhal, Amit; Hedrick, James L; Yang, Yi Yan

    2016-06-01

    In this study, a series of star-shaped polycarbonates are synthesized by metal-free organocatalytic ring-opening polymerization of benzyl chloride (BnCl) and mannose-functionalized cyclic carbonate monomers (MTC-BnCl and MTC-ipman) with heptakis-(2,3-di-O-acetyl)-β-cyclodextrin (DA-β-CD) as macroinitiator. The distributions and compositions of pendent benzyl chloride and protected mannose group (ipman) units are facilely modulated by varying the polymerization sequence and feed ratio of the monomers, allowing precise control over the molecular composition, and the resulting polymers have narrow molecular weight distribution. After deprotection of ipman groups and quaternization with various N,N-dimethylalkylamines, these star polymers with optimized compositions of cationic and mannose groups in block and random forms exhibit strong bactericidal activity and low hemolysis. Furthermore, the optimal mannose-functionalized polymer demonstrates mannose receptor-mediated intracellular bactericidal activity against BCG mycobacteria without inducing cytotoxicity on mammalian cells at the effective dose. Taken together, the materials designed in this study have potential use as antimicrobial agents against diseases such as tuberculosis, which is caused by intracellular bacteria.

  20. GPI-anchored proteins do not reside in ordered domains in the live cell plasma membrane

    Science.gov (United States)

    Sevcsik, Eva; Brameshuber, Mario; Fölser, Martin; Weghuber, Julian; Honigmann, Alf; Schütz, Gerhard J.

    2015-04-01

    The organization of proteins and lipids in the plasma membrane has been the subject of a long-lasting debate. Membrane rafts of higher lipid chain order were proposed to mediate protein interactions, but have thus far not been directly observed. Here we use protein micropatterning combined with single-molecule tracking to put current models to the test: we rearranged lipid-anchored raft proteins (glycosylphosphatidylinositol(GPI)-anchored-mGFP) directly in the live cell plasma membrane and measured the effect on the local membrane environment. Intriguingly, this treatment does neither nucleate the formation of an ordered membrane phase nor result in any enrichment of nanoscopic-ordered domains within the micropatterned regions. In contrast, we find that immobilized mGFP-GPIs behave as inert obstacles to the diffusion of other membrane constituents without influencing their membrane environment over distances beyond their physical size. Our results indicate that phase partitioning is not a fundamental element of protein organization in the plasma membrane.

  1. Distinct Upstream Role of Type I IFN Signaling in Hematopoietic Stem Cell-Derived and Epithelial Resident Cells for Concerted Recruitment of Ly-6Chi Monocytes and NK Cells via CCL2-CCL3 Cascade.

    Directory of Open Access Journals (Sweden)

    Erdenebileg Uyangaa

    Full Text Available Type I interferon (IFN-I-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV. However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-γ/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-I-dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I-dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident-to-hematopoietic-to-resident cells that drives cytokine-to-chemokine-to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues.

  2. Myogenic-specific ablation of Fgfr1 impairs FGF2-mediated proliferation of satellite cells at the myofiber niche but does not abolish the capacity for muscle regeneration

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    Zipora eYablonka-Reuveni

    2015-05-01

    Full Text Available Skeletal muscle satellite cells (SCs are Pax7+ myogenic stem cells that reside between the basal lamina and the plasmalemma of the myofiber. In mature muscles, SCs are typically quiescent, but can be activated in response to muscle injury. Depending on the magnitude of tissue trauma, SCs may divide minimally to repair subtle damage within individual myofibers or produce a larger progeny pool that forms new myofibers in cases of overt muscle injury. SC transition through proliferation, differentiation and renewal is governed by the molecular blueprint of the cells as well as by the extracellular milieu at the SC niche. In particular, the role of the fibroblast growth factor (FGF family in regulating SCs during growth and aging is well recognized. Of the several FGFs shown to affect SCs, FGF1, FGF2 and FGF6 proteins have been documented in adult skeletal muscle. These prototypic paracrine FGFs transmit their mitogenic effect through the FGFRs, which are transmembrane tyrosine kinase receptors. Using the mouse model, we show here that of the four FGFRs, only Fgfr1 and Fgfr4 are expressed at relatively high levels in quiescent SCs and their proliferating progeny. To further investigate the role of FGFR1 in adult myogenesis, we have employed a genetic (Cre/loxP approach for myogenic-specific (MyoDCre-driven ablation of Fgfr1. Neither muscle histology nor muscle regeneration following cardiotoxin-induced injury were overtly affected in Fgfr1-ablated mice. This suggests that FGFR1 is not obligatory for SC performance in this acute muscle trauma model, where compensatory growth factor/cytokine regulatory cascades may exist. However, the SC mitogenic response to FGF2 is drastically repressed in isolated myofibers prepared from Fgfr1-ablated mice. Collectively, our study indicates that FGFR1 is important for FGF-mediated proliferation of SCs and its mitogenic role is not compensated by FGFR4 that is also highly expressed in SCs.

  3. Mycobacterium ulcerans infections cause progressive muscle atrophy and dysfunction, and mycolactone impairs satellite cell proliferation.

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    Houngbédji, Germain Mabèrou; Bouchard, Patrice; Frenette, Jérôme

    2011-03-01

    Clinical observations from Buruli ulcer (BU) patients in West Africa suggest that severe Mycobacterium ulcerans infections can cause skeletal muscle contracture and atrophy leading to significant impairment in function. In the present study, male mice C57BL/6 were subcutaneously injected with M. ulcerans in proximity to the right biceps muscle, avoiding direct physical contact between the infectious agent and the skeletal muscle. The histological, morphological, and functional properties of the muscles were assessed at different times after the injection. On day 42 postinjection, the isometric tetanic force and the cross-sectional area of the myofibers were reduced by 31% and 29%, respectively, in the proximate-infected muscles relative to the control muscles. The necrotic areas of the proximate-infected muscles had spread to 7% of the total area by day 42 postinjection. However, the number of central nucleated fibers and myogenic regulatory factors (MyoD and myogenin) remained stable and low. Furthermore, Pax-7 expression did not increase significantly in mycolactone-injected muscles, indicating that the satellite cell proliferation is abrogated by the toxin. In addition, the fibrotic area increased progressively during the infection. Lastly, muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (atrogin-1/MAFbx), two muscle-specific E3 ubiquitin ligases, were upregulated in the presence of M. ulcerans. These findings confirmed that skeletal muscle is affected in our model of subcutaneous infection with M. ulcerans and that a better understanding of muscle contractures and weakness is essential to develop a therapy to minimize loss of function and promote the autonomy of BU patients.

  4. Reduced masticatory function is related to lower satellite cell numbers in masseter muscle.

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    Kuijpers, M A R; Grefte, S; Bronkhorst, E M; Carels, C E L; Kiliaridis, S; Von den Hoff, J W

    2014-06-01

    The physiology of masseter muscles is known to change in response to functional demands, but the effect on the satellite cell (SC) population is not known. In this study, the hypothesis is tested that a decreased functional demand of the masseter muscle causes a reduction of SCs. To this end, twelve 5-week-old male Sprague-Dawley rats were put on a soft diet (SD, n = 6) or a hard diet (HD, n = 6) and sacrificed after 14 days. Paraffin sections of the superficial masseter and the m. digastricus (control muscle) were stained with haematoxylin and eosin for tissue survey and with anti-myosin heavy chain (MHC) for slow and fast fibres. Frozen sections of both muscles were double-stained for collagen type IV and Pax7. Slow MHC fibres were equally distributed in the m. digastricus but only localized in a small area of the m. masseter. No differences between HD or SD for the m. digastricus were found. The m. masseter had more SCs per fibre in HD than in SD (0.093 ± 0.007 and 0.081 ± 0.008, respectively; P = 0.027). The m. masseter had more fibres per surface area than the m. digastricus in rats with an SD group (758.1 ± 101.6 and 568.4 ± 85.6, P = 0.047) and a HD group (737.7 ± 32.6 and 592.2 ± 82.2; P = 0.007). The m. digastricus had more SCs per fibre than the m. masseter in the SD group (0.094 ± 0.01 and 0.081 ± 0.008; P = 0.039). These results suggest that reduced masseter muscle function is related to a lower number of SCs. Reduced muscle function might decrease microdamage and hence the requirement of SCs in the muscle fibres.

  5. Akirin2 regulates proliferation and differentiation of porcine skeletal muscle satellite cells via ERK1/2 and NFATc1 signaling pathways

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    Chen, Xiaoling; Luo, Yanliu; Huang, Zhiqing; Jia, Gang; Liu, Guangmang; Zhao, Hua

    2017-01-01

    Akirin2, a novel nuclear factor, plays an important role in myogenesis. To investigate the role of Akirin2 in proliferation and differentiation of porcine skeletal muscle satellite cells, Akirin2 overexpression and Akirin2 silence technologies were employed. Our results showed that overexpression of Akirin2 markedly enhanced the proliferation and differentiation of porcine skeletal muscle satellite cells, whereas silencing of Akirin2 got the opposite results. Furthermore, our results showed that Akirin2 affected proliferation and differentiation of porcine skeletal muscle satellite cells through extracellular-signal regulated kinase-1/2 (ERK1/2) and NFATc1 signaling pathways. These results indicate that Akirin2 can effectively promote skeletal muscle satellite cells proliferation and differentiation, acting through ERK1/2- and NFATc1-dependent mechanisms. PMID:28327665

  6. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    OpenAIRE

    Mari Dezawa; Taeko Shigemoto; Fumitaka Ogura; Shohei Wakao; Yasumasa Kuroda

    2012-01-01

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have no...

  7. Leucocytes, cytokines and satellite cells: what role do they play in muscle damage and regeneration following eccentric exercise?

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    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls; Peake, Jonathan M

    2012-01-01

    Exercise-induced muscle damage is an important topic in exercise physiology. However several aspects of our understanding of how muscles respond to highly stressful exercise remain unclear In the first section of this review we address the evidence that exercise can cause muscle damage and inflammation in otherwise healthy human skeletal muscles. We approach this concept by comparing changes in muscle function (i.e., the force-generating capacity) with the degree of leucocyte accumulation in muscle following exercise. In the second section, we explore the cytokine response to 'muscle-damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role of the cyclooxygenase enzymes (COX1 and 2). In summary, we propose that muscle damage as evaluated by changes in muscle function is related to leucocyte accumulation in the exercised muscles. 'Extreme' exercise protocols, encompassing unaccustomed maximal eccentric exercise across a large range of motion, generally inflict severe muscle damage, inflammation and prolonged recovery (> 1 week). By contrast, exercise resembling regular athletic training (resistance exercise and downhill running) typically causes mild muscle damage (myofibrillar disruptions) and full recovery normally occurs within a few days. Large variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to

  8. Satellite Communication.

    Science.gov (United States)

    Technology Teacher, 1985

    1985-01-01

    Presents a discussion of communication satellites: explains the principles of satellite communication, describes examples of how governments and industries are currently applying communication satellites, analyzes issues confronting satellite communication, links mathematics and science to the study of satellite communication, and applies…

  9. 负荷运动对人体骨骼肌卫星细胞的影响%Affect Human Skeletal Muscle Satellite Cells Analysis of the Load Movement

    Institute of Scientific and Technical Information of China (English)

    余群; 王丽平; 翁锡全

    2014-01-01

    骨骼肌在运动损伤、发育和重建等过程中卫星细胞具有重要的生理作用。适宜的运动训练可以激活肌卫星细胞,使之增殖并向成肌的肌卫星细胞转化。文章阐述了骨骼肌卫星细胞的特征、负荷运动对肌卫星细胞的影响,以及运动对卫星细胞的激活与增殖的作用机制;并对人体衰老过程中肌卫星细胞的变化规律进行分析与探讨。%Skeletal muscle satellite cells in skeletal muscle growth and development ,physiology and pathology of skeletal mus‐cle damage repair and remodeling process plays an important role .Appropriate exercise training can activate satellite cells ,satellite cells proliferate and promote myoblast differentiation .In addition ,skeletal muscle satellite cells are generally in a resting state ,it will not participate in the synthesis of gene expression and protein .But it can be activated in sports injuries ,mechanical traction or weight training and other specialized stress during differentiation and fusion into myotubes able to participate in the repair of skele ‐tal muscle .In this paper ,the origins of skeletal muscle satellite cells ,morphological characteristics and different exercise training on human skeletal muscle satellite cells as well as the impact of exercise training on skeletal muscle satellite cell activation ,prolif‐eration and changes of the aging process of skeletal muscle satellite cells were analyzed and discussion .

  10. PPARγ and MyoD are differentially regulated by myostatin in adipose-derived stem cells and muscle satellite cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Feng [Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 (China); Deng, Bing [Wuhan Institute of Animal Science and Veterinary Medicine, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208 (China); Wen, Jianghui [Wu Han University of Technology, Wuhan 430074 (China); Chen, Kun [Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 (China); Liu, Wu; Ye, Shengqiang; Huang, Haijun [Wuhan Institute of Animal Science and Veterinary Medicine, Wuhan Academy of Agricultural Science and Technology, Wuhan, Hubei, 430208 (China); Jiang, Siwen, E-mail: jiangsiwen@mail.hzau.edu.cn [Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 (China); Xiong, Yuanzhu, E-mail: xiongyzhu@163.com [Key Laboratory of Swine Genetics and Breeding of the Agricultural Ministry and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070 (China)

    2015-03-06

    Myostatin (MSTN) is a secreted protein belonging to the transforming growth factor-β (TGF-β) family that is primarily expressed in skeletal muscle and also functions in adipocyte maturation. Studies have shown that MSTN can inhibit adipogenesis in muscle satellite cells (MSCs) but not in adipose-derived stem cells (ADSCs). However, the mechanism by which MSTN differently regulates adipogenesis in these two cell types remains unknown. Peroxisome proliferator-activated receptor-γ (PPARγ) and myogenic differentiation factor (MyoD) are two key transcription factors in fat and muscle cell development that influence adipogenesis. To investigate whether MSTN differentially regulates PPARγ and MyoD, we analyzed PPARγ and MyoD expression by assessing mRNA, protein and methylation levels in ADSCs and MSCs after treatment with 100 ng/mL MSTN for 0, 24, and 48 h. PPARγ mRNA levels were downregulated after 24 h and upregulated after 48 h of treatment in ADSCs, whereas in MSCs, PPARγ levels were downregulated at both time points. MyoD expression was significantly increased in ADSCs and decreased in MSCs. PPARγ and MyoD protein levels were upregulated in ADSCs and downregulated in MSCs. The CpG methylation levels of the PPARγ and MyoD promoters were decreased in ADSCs and increased in MSCs. Therefore, this study demonstrated that the different regulatory adipogenic roles of MSTN in ADSCs and MSCs act by differentially regulating PPARγ and MyoD expression. - Highlights: • PPARγ and MyoD mRNA and protein levels are upregulated by myostatin in ADSCs. • PPARγ and MyoD mRNA and protein levels are downregulated by myostatin in MSCs. • PPARγ exhibited different methylation levels in myostatin-treated ADSCs and MSCs. • MyoD exhibited different methylation levels in myostatin-treated ADSCs and MSCs. • PPARγ and MyoD are differentially regulated by myostatin in ADSCs and MSCs.

  11. Isolation, Culture, and Immunostaining of Skeletal Muscle Myofibers from Wildtype and Nestin-GFP Mice as a Means to Analyze Satellite Cell.

    Science.gov (United States)

    Stuelsatz, Pascal; Keire, Paul; Yablonka-Reuveni, Zipora

    2017-01-01

    Multinucleated myofibers, the functional contractile units of adult skeletal muscle, harbor mononuclear Pax7(+) myogenic progenitors on their surface between the myofiber basal lamina and plasmalemma. These progenitors, known as satellite cells, are the primary myogenic stem cells in adult muscle. This chapter describes our laboratory protocols for isolating, culturing, and immunostaining intact myofibers from mouse skeletal muscle as a means for studying satellite cell dynamics. The first protocol discusses myofiber isolation from the flexor digitorum brevis (FDB) muscle. These short myofibers are plated in dishes coated with PureCol collagen (formerly known as Vitrogen) and maintained in a mitogen-poor medium (± supplemental growth factors). Employing such conditions, satellite cells remain at the surface of the parent myofiber while synchronously undergoing a limited number of proliferative cycles and rapidly differentiate. The second protocol discusses the isolation of longer myofibers from the extensor digitorum longus (EDL) muscle. These EDL myofibers are routinely plated individually as adherent myofibers in wells coated with Matrigel and maintained in a mitogen-rich medium, conditions in which satellite cells migrate away from the parent myofiber, proliferate extensively, and generate numerous differentiating progeny. Alternatively, these EDL myofibers can be plated as non-adherent myofibers in uncoated wells and maintained in a mitogen-poor medium (± supplemental growth factors), conditions that retain satellite cell progeny at the myofiber niche similar to the FDB myofiber cultures. However, the adherent myofiber format is our preferred choice for monitoring satellite cells in freshly isolated (Time 0) myofibers. We conclude this chapter by promoting the Nestin-GFP transgenic mouse as an efficient tool for direct analysis of satellite cells in isolated myofibers. While satellite cells have been often detected by their expression of the Pax7 protein or

  12. The acute satellite cell response and skeletal muscle hypertrophy following resistance training.

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    Leeann M Bellamy

    Full Text Available The extent of skeletal muscle hypertrophy in response to resistance training is highly variable in humans. The main objective of this study was to explain the nature of this variability. More specifically, we focused on the myogenic stem cell population, the satellite cell (SC as a potential mediator of hypertrophy. Twenty-three males (aged 18-35 yrs participated in 16 wk of progressive, whole body resistance training, resulting in changes of 7.9±1.6% (range of -1.9-24.7% and 21.0±4.0% (range of -7.0 to 51.7% in quadriceps volume and myofibre cross-sectional area (CSA, respectively. The SC response to a single bout of resistance exercise (80% 1RM, analyzed via immunofluorescent staining resulted in an expansion of type II fibre associated SC 72 h following exercise (pre: 11.3±0.9; 72 h: 14.8±1.4 SC/type II fibre; p<0.05. Training resulted in an expansion of the SC pool associated with type I (pre: 10.7±1.1; post: 12.1±1.2 SC/type I fibre; p<0.05 and type II fibres (pre: 11.3±0.9; post: 13.0±1.2 SC/type II fibre; p<0.05. Analysis of individual SC responses revealed a correlation between the relative change in type I associated SC 24 to 72 hours following an acute bout of resistance exercise and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.566, p = 0.012 and the relative change in type II associated SC following 16 weeks of resistance training and the percentage increase in quadriceps lean tissue mass assessed by MRI (r2 = 0.493, p = 0.027. Our results suggest that the SC response to resistance exercise is related to the extent of muscular hypertrophy induced by training.

  13. Diminished CD103 (αEβ7) Expression on Resident T Cells from the Female Genital Tract of HIV-Positive Women

    Science.gov (United States)

    Moylan, David C.; Goepfert, Paul A.; Kempf, Mirjam-Colette; Saag, Michael S.; Richter, Holly E.; Mestecky, Jiri; Sabbaj, Steffanie

    2017-01-01

    Background Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT). Methods Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L−CCR7−CD103+CD69+ CD4+ and CD8+ T cells in mucosa-derived T cells from healthy and HIV-positive women. Results We demonstrate that TrM are present in the FGT of healthy and HIV-positive women. The expression of the mucosal retention receptor, CD103, from HIV-positive women was reduced compared to healthy women and was lowest in women with CD4 counts < 500 cells/mm3. Furthermore, CD103 expression on mucosa-derived CD8+ T cells correlated with antigen-specific IFN-γ production by mucosal CD4+ T cells and was inversely correlated with T-bet from CD8+CD103+ mucosa-derived T cells. Conclusions These data suggest that CD4+ T cells, known to be impaired during HIV-1 infection and necessary for the expression of CD103 in murine models, may play a role in the expression of CD103 on resident T cells from the human FGT. PMID:28164171

  14. The nanofibrous PAN-PANi scaffold as an efficient substrate for skeletal muscle differentiation using satellite cells.

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    Hosseinzadeh, Simzar; Mahmoudifard, Matin; Mohamadyar-Toupkanlou, Farzaneh; Dodel, Masomeh; Hajarizadeh, Atena; Adabi, Mahdi; Soleimani, Masoud

    2016-07-01

    Among polymers, polyaniline (PANi) has been introduced as a good candidate for muscle regeneration due to high conductivity and also biocompatibility. Herein, for the first time, we report the use of electrospun nanofibrous membrane of PAN-PANi as efficient scaffold for muscle regeneration. The prepared PAN-PANi electrospun nanofibrous membrane was characterized by scanning electron microscopy (SEM), Attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) and tensile examination. The softer scaffolds of non-composite electrospun nanofibrous PAN govern a higher rate of cell growth in spite of lower differentiation value. On the other hand, PAN-PANi electrospun nanofibrous membrane exposed high cell proliferation and also differentiation value. Thank to the conductive property and higher Young's modulus of composite type due to the employment of PANi, satellite cells were induced into more matured form as analyzed by Real-Time PCR. On the other hand, grafting of composite nanofibrous electrospun scaffold with gelatin increased the surface stiffness directing satellite cells into lower cell proliferation and highest value of differentiation. Our results for first time showed the significant role of combination between conductivity, mechanical property and surface modification of PAN-PANi electrospun nanofibers and provid new insights into most biocompatible scaffolds for muscle tissue engineering. The schematic figure conveys the effective combination of conductive and surface stiffness on muscle tissue engineering.

  15. Multi-Grid-Cell Validation of Satellite Aerosol Property Retrievals in INTEX/ITCT/ICARTT 2004

    Science.gov (United States)

    Russell, P. B.; Livingston, J. M.; Redemann, J.; Schmid, B.; Ramirez, S. A.; Eilers, J.; Kahn, R.; Chu, D. A.; Remer, L.; Quinn, P. K.; Rood, M. J.; Wang, W.

    2007-01-01

    Aerosol transport off the US Northeast coast during the Summer 2004 International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) Intercontinental Chemical Transport Experiment (INTEX) and Intercontinental Transport and Chemical Transformation (ITCT) experiments produced a wide range of aerosol types and aerosol optical depth (AOD) values, often with strong horizontal AOD gradients. In these conditions we flew the 14-channel NASA Ames Airborne Tracking Sun photometer (AATS) on a Jetstream 31 (J31) aircraft. Legs flown at low altitude (usually less than 100 m ASL) provided comparisons of AATS AOD spectra to retrievals for 90 grid cells of the satellite radiometers MODIS-Terra, MODIS-Aqua, and MISR, all over the ocean. Characterization of the retrieval environment was aided by using vertical profiles by the J31 (showing aerosol vertical structure) and, on occasion, shipboard measurements of light scattering and absorption. AATS provides AOD at 13 wavelengths lambda from 354 to 2138 nm, spanning the range of aerosol retrieval wavelengths for MODIS over ocean (466-2119 nm) and MISR (446-866 nm). Midvisible AOD on low-altitude J31 legs in satellite grid cells ranged from 0.05 to 0.9, with horizontal gradients often in the range 0.05 to 0.13 per 10 km. When possible, we used ship measurements of humidified aerosol scattering and absorption to estimate AOD below the J31. In these cases, which had J31 altitudes 60-110 m ASL (typical of J31 low-altitude transects), estimated midvisible AOD below the J31 ranged from 0.003 to 0.013, with mean 0.009 and standard deviation 0.003. These values averaged 6 percent of AOD above the 53 1. MISR-AATS comparisons on 29 July 2004 in 8 grid cells (each -17.6 km x 17.6 km) show that MISR versions 15 and 16 captured the AATS-measured AOD gradient (correlation coefficient R2 = 0.87 to 0.92), but the MISR gradient was somewhat weaker than the AATS gradient. The large AOD (midvisible values up to -0.9) and

  16. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells.

    Science.gov (United States)

    Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari

    2012-11-08

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  17. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    Directory of Open Access Journals (Sweden)

    Mari Dezawa

    2012-11-01

    Full Text Available Mesenchymal stem cells (MSCs are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  18. Early-age feed restriction affects viability and gene expression of satellite cells isolated from the gastrocnemius muscle of broiler chicks

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    Li Yue

    2012-11-01

    Full Text Available Abstract Background Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0–14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. However, how satellite cells respond to such nutritional insult has not been adequately elucidated. Results One-day-old broiler chicks were allocated to control (Con, ad libitum feeding, intermittent feeding (IF, feed provided on alternate days and re-feeding (RF, 2 days ad libitum feeding after 12 days of intermittent feeding groups. Chickens were killed on Day 15 and satellite cells were isolated. When cultured, satellite cells from the IF group demonstrated significant retardation in proliferation and differentiation potential, while RF partly restored the proliferation rate and differentiation potential of the satellite cells. Significant up-regulation of insulin like growth factor I receptor (IGF-IR (P0.05 and thyroid hormone receptor α (TRα (P0.05, and down-regulation of growth hormone receptor (GHR (P0.01 and IGF-I (P0.01 mRNA expression was observed in freshly isolated IF satellite cells when compared with Con cells. In RF cells, the mRNA expression of IGF-I was higher (P0.05 and of TRα was lower (P0.01 than in IF cells, suggesting that RF restored the mRNA expression of TRα and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio tended to increase in the IF group, which was reversed in the RF group (P0.05, indicating that RF reduced the pro-apoptotic influence of IF. Moreover, no significant effect of T3 was detected on cell survival in IF cells compared with Con (PP0.05 cells. Conclusions These data suggest that early-age feed restriction inhibits the proliferation and differentiation of satellite cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone receptors in satellite cells, as well as blunted sensitivity of satellite cells to T3, and that RF partially reverses these effects. Thus

  19. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration

    Science.gov (United States)

    Castiglioni, Alessandra; Basso, Veronica; Vezzoli, Michela; Monno, Antonella; Almada, Albert E.; Mondino, Anna; Wagers, Amy J.; Manfredi, Angelo A.; Rovere-Querini, Patrizia

    2015-01-01

    Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue. PMID:26039259

  20. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration.

    Directory of Open Access Journals (Sweden)

    Alessandra Castiglioni

    Full Text Available Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue.

  1. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration.

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    Castiglioni, Alessandra; Corna, Gianfranca; Rigamonti, Elena; Basso, Veronica; Vezzoli, Michela; Monno, Antonella; Almada, Albert E; Mondino, Anna; Wagers, Amy J; Manfredi, Angelo A; Rovere-Querini, Patrizia

    2015-01-01

    Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue.

  2. Retention of Ag-specific memory CD4(+) T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

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    Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

    2017-03-15

    Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4(+) T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4(+) T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4(+) T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4(+) T-cell populations are generated in peripheral lymph nodes following immunisation.

  3. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8+ T Cells, Facilitating Protection from Local Cytomegalovirus Infection

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    Jenny Tosca Thom

    2015-11-01

    Full Text Available Tissue-resident memory T cells (TRM reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG most-effectively induces CD8+ and CD4+ TRM cells against murine cytomegalovirus (MCMV, which persists in and spreads from this organ. TRM generation depended on local antigen for CD4+, but not CD8+, TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8+ T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8+ T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8+ T cells in protecting mucosal tissues against CMV infection.

  4. The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection.

    Science.gov (United States)

    Thom, Jenny Tosca; Weber, Thomas Christian; Walton, Senta Maria; Torti, Nicole; Oxenius, Annette

    2015-11-10

    Tissue-resident memory T cells (TRM) reside in barrier tissues and provide local immediate protective immunity. Here, we show that the salivary gland (SG) most-effectively induces CD8(+) and CD4(+) TRM cells against murine cytomegalovirus (MCMV), which persists in and spreads from this organ. TRM generation depended on local antigen for CD4(+), but not CD8(+), TRM cells, highlighting major differences in T cell subset-specific demands for TRM development. CMV-specific CD8(+) T cells fail to control virus replication upon primary infection in the SG due to CMV-induced MHC I downregulation in glandular epithelial cells. Using intraglandular infection, we challenge this notion and demonstrate that memory CD8(+) T cells confer immediate protection against locally introduced MCMV despite active viral immune evasion, owing to early viral tropism to cells that largely withstand MHC I downregulation. Thus, we unravel a yet-unappreciated role for memory CD8(+) T cells in protecting mucosal tissues against CMV infection.

  5. Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.

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    Charlotte J Green

    Full Text Available BACKGROUND: Glucagon like peptide-1 (GLP-1 stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the glucose-dependency of its extra-pancreatic effects has not been examined. METHODS: Skeletal muscle satellite cells isolated from young (22.5 ± 0.97 yr, lean (BMI 22.5 ± 0.6 kg/m(2, healthy males were differentiated in media containing either 22.5 mM (high or 5 mM (normal glucose for 7 days in the absence or presence of insulin and/or various GLP-1 concentrations. Myocellular effects of GLP-1, insulin and glucose were assessed by western-blot, glucose uptake and glycogen synthesis. RESULTS: We firstly show that the GLP-1 receptor protein is expressed in differentiated human muscle satellite cells (myocytes. Secondly, we show that in 5 mM glucose media, exposure of myocytes to GLP-1 results in a dose dependent increase in glucose uptake, GLUT4 amount and subsequently glycogen synthesis in a PI3K dependent manner, independent of the insulin signaling cascade. Importantly, we provide evidence that differentiation of human satellite cells in hyperglycemic (22.5 mM glucose conditions increases GLUT1 expression, and renders the cells insulin resistant and interestingly GLP-1 resistant in terms of glucose uptake and glycogen synthesis. Hyperglycemic conditions did not affect the ability of insulin to phosphorylate downstream targets, PKB or GSK3. Interestingly we show that at 5 mM glucose, GLP-1 increases GLUT4 protein levels and that this effect is abolished by hyperglycemia. CONCLUSIONS: GLP-1 increases glucose uptake and glycogen synthesis into fully-differentiated human satellite cells in a PI3-K dependent mechanism potentially through increased GLUT4 protein levels. The latter occurs independently of the insulin signaling pathway. Attenuation

  6. Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells

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    Shan, Qiang; Xue, Hai-Hui; Harty, John T.

    2017-01-01

    Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM) provide robust protection in a variety of infectious models. TRM rapidly ‘sense’ infection in non-lymphoid tissues and ‘alarm’ the host by enhancing immune cell recruitment to the site of the infection to accelerate pathogen clearance. Here, we show that compared to pathogen-specific TCIRCM, sepsis does not invoke significant numerical decline of Vaccinia virus induced skin-TRM keeping their effector functions (e.g., Ag-dependent IFN-γ production) intact. IFN-γ-mediated recruitment of immune cells to the site of localized infection was, however, reduced in CLP hosts despite TRM maintaining their ‘sensing and alarming’ functions. The capacity of memory CD8 T-cells in the septic environment to respond to inflammatory cues and arrive to the site of secondary infection/antigen exposure remained normal suggesting T-cell-extrinsic factors contributed to the observed lesion. Mechanistically, we showed that IFN-γ produced rapidly during sepsis-induced cytokine storm leads to reduced IFN-γR1 expression on vascular endothelium. As a consequence, decreased expression of adhesion molecules and/or chemokines (VCAM1 and CXCL9) on skin endothelial cells in response to TRM-derived IFN-γ was observed, leading to sub-optimal bystander-recruitment of effector cells and increased susceptibility to pathogen re-encounter. Importantly, as visualized by intravital 2-photon microscopy, exogenous administration of CXCL9/10 was sufficient to correct sepsis-induced impairments in recruitment of effector cells at the localized site of TRM

  7. Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Derek B Danahy

    2017-09-01

    Full Text Available Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM provide robust protection in a variety of infectious models. TRM rapidly 'sense' infection in non-lymphoid tissues and 'alarm' the host by enhancing immune cell recruitment to the site of the infection to accelerate pathogen clearance. Here, we show that compared to pathogen-specific TCIRCM, sepsis does not invoke significant numerical decline of Vaccinia virus induced skin-TRM keeping their effector functions (e.g., Ag-dependent IFN-γ production intact. IFN-γ-mediated recruitment of immune cells to the site of localized infection was, however, reduced in CLP hosts despite TRM maintaining their 'sensing and alarming' functions. The capacity of memory CD8 T-cells in the septic environment to respond to inflammatory cues and arrive to the site of secondary infection/antigen exposure remained normal suggesting T-cell-extrinsic factors contributed to the observed lesion. Mechanistically, we showed that IFN-γ produced rapidly during sepsis-induced cytokine storm leads to reduced IFN-γR1 expression on vascular endothelium. As a consequence, decreased expression of adhesion molecules and/or chemokines (VCAM1 and CXCL9 on skin endothelial cells in response to TRM-derived IFN-γ was observed, leading to sub-optimal bystander-recruitment of effector cells and increased susceptibility to pathogen re-encounter. Importantly, as visualized by intravital 2-photon microscopy, exogenous administration of CXCL9/10 was sufficient to correct sepsis-induced impairments in recruitment of effector cells at the localized site of TRM

  8. Expression of CCAAT/Enhancer Binding Protein Beta in Muscle Satellite Cells Inhibits Myogenesis in Cancer Cachexia.

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    Marchildon, François; Lamarche, Émilie; Lala-Tabbert, Neena; St-Louis, Catherine; Wiper-Bergeron, Nadine

    2015-01-01

    Cancer cachexia is a paraneoplastic syndrome that causes profound weight loss and muscle mass atrophy and is estimated to be the cause of up to 30% of cancer deaths. Though the exact cause is unknown, patients with cancer cachexia have increased muscle protein catabolism. In healthy muscle, injury activates skeletal muscle stem cells, called satellite cells, to differentiate and promote regeneration. Here, we provide evidence that this mechanism is inhibited in cancer cachexia due to persistent expression of CCAAT/Enhancer Binding Protein beta (C/EBPβ) in muscle myoblasts. C/EBPβ is a bzip transcription factor that is expressed in muscle satellite cells and is normally downregulated upon differentiation. However, in myoblasts exposed to a cachectic milieu, C/EBPβ expression remains elevated, despite activation to differentiate, resulting in the inhibition of myogenin expression and myogenesis. In vivo, cancer cachexia results in increased number of Pax7+ cells that also express C/EBPβ and the inhibition of normal repair mechanisms. Loss of C/EBPβ expression in primary myoblasts rescues differentiation under cachectic conditions without restoring myotube size, indicating that C/EBPβ is an important inhibitor of myogenesis in cancer cachexia.

  9. Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells

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    Arutyunyan Anna

    2012-08-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs. Results We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the presence of drug-treated ALL cells. These mitotically inactivated MEFs showed few changes in gene expression, but a family of sequences of which transcription is significantly increased was identified. A sequence related to this family, which we named cassini, was selected for further characterization. We found that cassini was highly upregulated in drug-treated ALL cells. Analysis of RNAs from different normal mouse tissues showed that cassini expression is highest in spleen and thymus, and can be further enhanced in these organs by exposure of mice to bacterial endotoxin. Heat shock, but not other types of stress, significantly induced the transcription of this locus in ALL cells. Transient overexpression of cassini in human 293 embryonic kidney cells did not increase the cytotoxic or cytostatic effects of chemotherapeutic drugs but provided some protection. Database searches revealed that sequences highly homologous to cassini are present in rodents, apicomplexans, flatworms and primates, indicating that they are conserved in evolution. Moreover, CASSINI RNA was induced in human ALL cells treated with vincristine. Surprisingly, cassini belongs to the previously reported murine family of γ-satellite/major satellite DNA sequences, which were not known to be present in other species. Conclusions Our results show that the transcription of at least one member of these sequences is regulated, suggesting that this has a function in normal and transformed immune cells. Expression of these sequences may protect cells when they are exposed to specific stress stimuli.

  10. Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.

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    Arutyunyan, Anna; Stoddart, Sonia; Yi, Sun-ju; Fei, Fei; Lim, Min; Groffen, Paula; Feldhahn, Niklas; Groffen, John; Heisterkamp, Nora

    2012-08-23

    Acute lymphoblastic leukemia (ALL) cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs). We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the presence of drug-treated ALL cells. These mitotically inactivated MEFs showed few changes in gene expression, but a family of sequences of which transcription is significantly increased was identified. A sequence related to this family, which we named cassini, was selected for further characterization. We found that cassini was highly upregulated in drug-treated ALL cells. Analysis of RNAs from different normal mouse tissues showed that cassini expression is highest in spleen and thymus, and can be further enhanced in these organs by exposure of mice to bacterial endotoxin. Heat shock, but not other types of stress, significantly induced the transcription of this locus in ALL cells. Transient overexpression of cassini in human 293 embryonic kidney cells did not increase the cytotoxic or cytostatic effects of chemotherapeutic drugs but provided some protection. Database searches revealed that sequences highly homologous to cassini are present in rodents, apicomplexans, flatworms and primates, indicating that they are conserved in evolution. Moreover, CASSINI RNA was induced in human ALL cells treated with vincristine. Surprisingly, cassini belongs to the previously reported murine family of γ-satellite/major satellite DNA sequences, which were not known to be present in other species. Our results show that the transcription of at least one member of these sequences is regulated, suggesting that this has a function in normal and transformed immune cells. Expression of these sequences may protect cells when they are exposed to specific stress stimuli.

  11. Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats

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    H. Shen

    2016-01-01

    Full Text Available This study evaluated the effect of muscle satellite cells (MSCs overexpressing myogenin (MyoG on denervated muscle atrophy. Rat MSCs were isolated and transfected with the MyoG-EGFP plasmid vector GV143. MyoG-transfected MSCs (MTMs were transplanted into rat gastrocnemius muscles at 1 week after surgical denervation. Controls included injections of untransfected MSCs or the vehicle only. Muscles were harvested and analyzed at 2, 4, and 24 weeks post-transplantation. Immunofluorescence confirmed MyoG overexpression in MTMs. The muscle wet weight ratio was significantly reduced at 2 weeks after MTM injection (67.17±6.79 compared with muscles injected with MSCs (58.83±5.31 or the vehicle (53.00±7.67; t=2.37, P=0.04 and t=3.39, P=0.007, respectively. The muscle fiber cross-sectional area was also larger at 2 weeks after MTM injection (2.63×103±0.39×103 compared with MSC injection (1.99×103±0.58×103 or the vehicle only (1.57×103±0.47×103; t=2.24, P=0.049 and t=4.22, P=0.002, respectively. At 4 and 24 weeks post-injection, the muscle mass and fiber cross-sectional area were similar across all three experimental groups. Immunohistochemistry showed that the MTM group had larger MyoG-positive fibers. The MTM group (3.18±1.13 also had higher expression of MyoG mRNA than other groups (1.41±0.65 and 1.03±0.19 at 2 weeks after injection (t=2.72, P=0.04. Transplanted MTMs delayed short-term atrophy of denervated muscles. This approach can be optimized as a novel stand-alone therapy or as a bridge to surgical re-innervation of damaged muscles.

  12. Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats.

    Science.gov (United States)

    Shen, H; Lv, Y; Shen, X Q; Xu, J H; Lu, H; Fu, L C; Duan, T

    2016-02-01

    This study evaluated the effect of muscle satellite cells (MSCs) overexpressing myogenin (MyoG) on denervated muscle atrophy. Rat MSCs were isolated and transfected with the MyoG-EGFP plasmid vector GV143. MyoG-transfected MSCs (MTMs) were transplanted into rat gastrocnemius muscles at 1 week after surgical denervation. Controls included injections of untransfected MSCs or the vehicle only. Muscles were harvested and analyzed at 2, 4, and 24 weeks post-transplantation. Immunofluorescence confirmed MyoG overexpression in MTMs. The muscle wet weight ratio was significantly reduced at 2 weeks after MTM injection (67.17±6.79) compared with muscles injected with MSCs (58.83±5.31) or the vehicle (53.00±7.67; t=2.37, P=0.04 and t=3.39, P=0.007, respectively). The muscle fiber cross-sectional area was also larger at 2 weeks after MTM injection (2.63×10³±0.39×10³) compared with MSC injection (1.99×10³±0.58×10³) or the vehicle only (1.57×10³±0.47×10³; t=2.24, P=0.049 and t=4.22, P=0.002, respectively). At 4 and 24 weeks post-injection, the muscle mass and fiber cross-sectional area were similar across all three experimental groups. Immunohistochemistry showed that the MTM group had larger MyoG-positive fibers. The MTM group (3.18±1.13) also had higher expression of MyoG mRNA than other groups (1.41±0.65 and 1.03±0.19) at 2 weeks after injection (t=2.72, P=0.04). Transplanted MTMs delayed short-term atrophy of denervated muscles. This approach can be optimized as a novel stand-alone therapy or as a bridge to surgical re-innervation of damaged muscles.

  13. Nitric oxide synthase inhibition delays low-frequency stimulation-induced satellite cell activation in rat fast-twitch muscle.

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    Martins, Karen J B; MacLean, Ian; Murdoch, Gordon K; Dixon, Walter T; Putman, Charles T

    2011-12-01

    This study examined the effect of nitric oxide synthase (NOS) inhibition via N(ω)-nitro-l-arginine methyl ester (l-NAME) administration on low-frequency stimulation-induced satellite cell (SC) activation in rat skeletal muscle. l-NAME only delayed stimulation-induced increases in SC activity. Also, stimulation-induced increases in hepatocyte growth factor (HGF) mRNA and protein expression were only abrogated at the mRNA level in l-NAME-treated animals. Therefore, early stimulation-induced SC activation appears to be NOS-dependent, while continued activation may involve NOS-independent HGF translational control mechanisms.

  14. Deficiency of lymph node-resident dendritic cells (DCs) and dysregulation of DC chemoattractants in a malnourished mouse model of Leishmania donovani infection.

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    Ibrahim, Marwa K; Barnes, Jeffrey L; Osorio, E Yaneth; Anstead, Gregory M; Jimenez, Fabio; Osterholzer, John J; Travi, Bruno L; Ahuja, Seema S; White, A Clinton; Melby, Peter C

    2014-08-01

    Malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan Leishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of L. donovani. In the present study, we found reduced numbers of resident dendritic cells (conventional and monocyte derived) but not migratory dermal dendritic cells in the skin-draining lymph nodes of L. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in the lymph nodes of infected malnourished mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node and CCR7 was increased in lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination of L. donovani is related to insufficient numbers of lymph node-resident but not migratory dermal dendritic cells. This is likely driven by the altered activity of the CCR2 and CCR7 chemoattractant pathways.

  15. Perineuronal satellite neuroglia in the telencephalon of New Caledonian crows and other Passeriformes: evidence of satellite glial cells in the central nervous system of healthy birds?

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    Medina, Felipe S; Hunt, Gavin R; Gray, Russell D; Wild, J Martin; Kubke, M Fabiana

    2013-01-01

    Glia have been implicated in a variety of functions in the central nervous system, including the control of the neuronal extracellular space, synaptic plasticity and transmission, development and adult neurogenesis. Perineuronal glia forming groups around neurons are associated with both normal and pathological nervous tissue. Recent studies have linked reduction in the number of perineuronal oligodendrocytes in the prefrontal cortex with human schizophrenia and other psychiatric disorders. Therefore, perineuronal glia may play a decisive role in homeostasis and normal activity of the human nervous system. Here we report on the discovery of novel cell clusters in the telencephala of five healthy Passeriforme, one Psittaciform and one Charadriiforme bird species, which we refer to as Perineuronal Glial Clusters (PGCs). The aim of this study is to describe the structure and distribution of the PGCs in a number of avian species. PGCs were identified with the use of standard histological procedures. Heterochromatin masses visible inside the nuclei of these satellite glia suggest that they may correspond to oligodendrocytes. PGCs were found in the brains of nine New Caledonian crows, two Japanese jungle crows, two Australian magpies, two Indian mynah, three zebra finches (all Passeriformes), one Southern lapwing (Charadriiformes) and one monk parakeet (Psittaciformes). Microscopic survey of the brain tissue suggests that the largest PGCs are located in the hyperpallium densocellulare and mesopallium. No clusters were found in brain sections from one Gruiform (purple swamphen), one Strigiform (barn owl), one Trochiliform (green-backed firecrown), one Falconiform (chimango caracara), one Columbiform (pigeon) and one Galliform (chick). Our observations suggest that PGCs in Aves are brain region- and taxon-specific and that the presence of perineuronal glia in healthy human brains and the similar PGCs in avian gray matter is the result of convergent evolution. The discovery

  16. CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes.

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    Dee, Christopher T; Nagaraju, Raghavendar T; Athanasiadis, Emmanouil I; Gray, Caroline; Fernandez Del Ama, Laura; Johnston, Simon A; Secombes, Christopher J; Cvejic, Ana; Hurlstone, Adam F L

    2016-11-01

    CD4(+) T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4(+) T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4(+) cells allowing us to scrutinize the development and specialization of teleost CD4(+) leukocytes in vivo. We provide further evidence that CD4(+) macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4(+) T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4(+) T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b-expressing Th2-like cells, which do not coexpress il-4/13a Additionally, we identify a contrasting population of regulatory T cell-like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4(+) T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity.

  17. TLR4 Expression by Liver Resident Cells Mediates the Development of Glucose Intolerance and Insulin Resistance in Experimental Periodontitis.

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    Vladimir Ilievski

    developed GI/IR despite similar degrees of gingival inflammation, circulating cytokine levels, and LPS concentrations. We conclude that LPS from periodontitis sites has a pivotal role in triggering the development of GI/IR through a mechanism that involves TLR4 expression by resident macrophages/Kupffer cells in the liver.

  18. Solar photovoltaic research and development program of the Air Force Aero Propulsion Laboratory. [silicon solar cell applicable to satellite power systems

    Science.gov (United States)

    Wise, J.

    1979-01-01

    Progress is reported in the following areas: laser weapon effects, solar silicon solar cell concepts, and high voltage hardened, high power system technology. Emphasis is placed on solar cells with increased energy conversion efficiency and radiation resistance characteristics for application to satellite power systems.

  19. Perineuronal satellite neuroglia in the telencephalon of New Caledonian crows and other Passeriformes: evidence of satellite glial cells in the central nervous system of healthy birds?

    Directory of Open Access Journals (Sweden)

    Felipe S. Medina

    2013-07-01

    Full Text Available Glia have been implicated in a variety of functions in the central nervous system, including the control of the neuronal extracellular space, synaptic plasticity and transmission, development and adult neurogenesis. Perineuronal glia forming groups around neurons are associated with both normal and pathological nervous tissue. Recent studies have linked reduction in the number of perineuronal oligodendrocytes in the prefrontal cortex with human schizophrenia and other psychiatric disorders. Therefore, perineuronal glia may play a decisive role in homeostasis and normal activity of the human nervous system.Here we report on the discovery of novel cell clusters in the telencephala of five healthy Passeriforme, one Psittaciform and one Charadriiforme bird species, which we refer to as Perineuronal Glial Clusters (PGCs. The aim of this study is to describe the structure and distribution of the PGCs in a number of avian species.PGCs were identified with the use of standard histological procedures. Heterochromatin masses visible inside the nuclei of these satellite glia suggest that they may correspond to oligodendrocytes. PGCs were found in the brains of nine New Caledonian crows, two Japanese jungle crows, two Australian magpies, two Indian mynah, three zebra finches (all Passeriformes, one Southern lapwing (Charadriiformes and one monk parakeet (Psittaciformes. Microscopic survey of the brain tissue suggests that the largest PGCs are located in the hyperpallium densocellulare and mesopallium. No clusters were found in brain sections from one Gruiform (purple swamphen, one Strigiform (barn owl, one Trochiliform (green-backed firecrown, one Falconiform (chimango caracara, one Columbiform (pigeon and one Galliform (chick.Our observations suggest that PGCs in Aves are brain region- and taxon-specific and that the presence of perineuronal glia in healthy human brains and the similar PGCs in avian gray matter is the result of convergent evolution. The

  20. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

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    Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

    2000-01-01

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  1. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

    Science.gov (United States)

    Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

    2000-01-01

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  2. Epidermis–dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Junko, E-mail: jokano@belle.shiga-med.ac.jp [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan); Kojima, Hideto; Katagi, Miwako [Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga (Japan); Nakae, Yuki [Department of Internal Medicine, Shiga University of Medical Science, Shiga (Japan); Terashima, Tomoya [Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga (Japan); Nakagawa, Takahiko [TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto (Japan); Kurakane, Takeshi; Okamoto, Naoki; Morohashi, Keita [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan); Maegawa, Hiroshi [Department of Internal Medicine, Shiga University of Medical Science, Shiga (Japan); Udagawa, Jun [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan)

    2015-06-12

    Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP{sup +}) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP{sup +} cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR. - Highlights: • Bone marrow-derived cells (BMDCs) migrate in the epidermis due to ionizing radiation (IR). • BMDCs dissociate from the epidermis-dermis junction in preparing epidermal sheets. • The doses of IR determine the location and the number of migrating BMDCs in the skin.

  3. Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency

    Science.gov (United States)

    Southard, Sheryl; Kim, Ju-Ryoung; Low, SiewHui; Tsika, Richard W; Lepper, Christoph

    2016-01-01

    When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic ‘scaling’ of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.e. satellite cells, SCs) but surprisingly without affecting muscle tissue size. Super-numeral SCs attain a ‘normal’ quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts. In dystrophic muscle, the TEAD1 transgene also ameliorated the pathology. We further demonstrate that hyperplastic SCs accumulate non-cell-autonomously via signal(s) from the TEAD1-expressing myofiber, suggesting that myofiber-specific TEAD1 overexpression activates a physiological signaling pathway(s) that determines initial and homeostatic SC pool size. We propose that TEAD1 and its downstream effectors are medically relevant targets for enhancing muscle regeneration and ameliorating muscle pathology. DOI: http://dx.doi.org/10.7554/eLife.15461.001 PMID:27725085

  4. Short-term ursolic acid promotes skeletal muscle rejuvenation through enhancing of SIRT1 expression and satellite cells proliferation.

    Science.gov (United States)

    Bakhtiari, Nuredin; Hosseinkhani, Saman; Soleimani, Masoud; Hemmati, Roohullah; Noori-Zadeh, Ali; Javan, Mohammad; Tashakor, Amin

    2016-03-01

    Ursolic acid (UA) is a triterpenoid compound, which exerts its influences on the skeletal muscles. However, the mechanisms underlying these effects are still unclear. In this study, muscle satellite cells were isolated and purified by high-throughput pre-plating method (∼>60%) from 10 days old mice skeletal muscles. Evaluation of paired-box 7 (Pax7) expressions then confirmed the purification. Treatment of the cells with UA showed that UA up-regulated SIRT1 (∼35 folds) and overexpressed PGC-1α (∼175 folds) gene significantly. Moreover, the number of muscle satellite cells, which accompanied by initiation of neomyogenesis in the animal skeletal muscles, was increased (∼3.4 times). We also evaluated UA-mediated changes in the cellular energy status in the skeletal muscles. The results revealed that in the UA-treated mice, ATP and ADP contents in the various skeletal muscle tissue types, including: Gastrocnemius (Gas), Tibialis Anterior (Tib) and Gluteus Maximus (Glu) have been significantly decreased (P≤0.001); 2.2, 3.2, 2 times for ATP, and 9.6, 35.7, 11.6 times for ADP, respectively; however to compensate this process mitochondrial biogenesis occurred (12.33%±1.5 times). Furthermore, a rise in ATP/ADP ratio was observed 2.5, 4.5, 2.05 times for Gas, Tib and Glu muscles, respectively (P≤0.001). Alternatively, UA enhanced the expression of myoglobin (∼2 folds) in concert with remodeling of glycolytic muscle fibers to mainly fast IIA (∼30%) and slow-twitch (∼4%) types as well. Finally, our study indicated that UA indirectly mimicked beneficial effects of short-term calorie restriction and exercise (fast-oxidative) by directing the skeletal muscle composition toward oxidative metabolism.

  5. Epidermis-dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation.

    Science.gov (United States)

    Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakae, Yuki; Terashima, Tomoya; Nakagawa, Takahiko; Kurakane, Takeshi; Okamoto, Naoki; Morohashi, Keita; Maegawa, Hiroshi; Udagawa, Jun

    2015-06-12

    Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP(+)) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP(+) cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR.

  6. Testosterone inhibits transforming growth factor-β signaling during myogenic differentiation and proliferation of mouse satellite cells: potential role of follistatin in mediating testosterone action.

    Science.gov (United States)

    Braga, Melissa; Bhasin, Shalender; Jasuja, Ravi; Pervin, Shehla; Singh, Rajan

    2012-03-05

    Testosterone (T) administration is associated with increased satellite cell number and skeletal muscle hypertrophy, although there is considerable heterogeneity in the response of different skeletal muscle groups to T in vivo. We investigated the effects of T on the growth and differentiation of satellite cells isolated from levator ani (LA) and gastrocnemius (gastroc) muscles. T up regulated follistatin (Fst) expression, but down regulated the mRNA and protein expression of a number of genes in the transforming growth factor-beta (TGF-β)-signaling pathway. Inhibition of Fst expression by small interfering RNA (siRNA) inhibited myogenic differentiation and blocked the pro-myogenic effects of T. Treatment of satellite cells with T or Fst up regulated the expression of Pax7 and PCNA, and increased their proliferation. T and Fst blocked TGF-β induced inhibition of growth and myogenic differentiation and down regulated TGF-β-dependent transcriptome in both LA and gastroc cells. We conclude that T stimulation of satellite cell proliferation and myogenic differentiation are associated with up regulation of Fst and inhibition of TGF-β-signaling.

  7. The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle Satellite Cells

    Directory of Open Access Journals (Sweden)

    Swapna Kollu

    2015-06-01

    Full Text Available To ensure accurate genomic segregation, cells evolved the spindle assembly checkpoint (SAC, whose role in adult stem cells remains unknown. Inducible perturbation of a SAC kinase, Mps1, and its downstream effector, Mad2, in skeletal muscle stem cells shows the SAC to be critical for normal muscle growth, repair, and self-renewal of the stem cell pool. SAC-deficient muscle stem cells arrest in G1 phase of the cell cycle with elevated aneuploidy, resisting differentiation even under inductive conditions. p21CIP1 is responsible for these SAC-deficient phenotypes. Despite aneuploidy’s correlation with aging, we find that aged proliferating muscle stem cells display robust SAC activity without elevated aneuploidy. Thus, muscle stem cells have a two-step mechanism to safeguard their genomic integrity. The SAC prevents chromosome missegregation and, if it fails, p21CIP1-dependent G1 arrest limits cellular propagation and tissue integration. These mechanisms ensure that muscle stem cells with compromised genomes do not contribute to tissue homeostasis.

  8. VL51ES (Generation 6 Li-Ion Cell for Satellites

    Directory of Open Access Journals (Sweden)

    Defer M.

    2017-01-01

    Full Text Available This paper presents the design of Saft’s VL51ES (Generation 6 Li-Ion cell, the main challenges in the course of the development, the main BOL characteristics and performances achieved during the development program. Finally, it also describes how this cell fits in Saft’s battery range and the benefits of it.

  9. Residency Allocation Database

    Data.gov (United States)

    Department of Veterans Affairs — The Residency Allocation Database is used to determine allocation of funds for residency programs offered by Veterans Affairs Medical Centers (VAMCs). Information...

  10. MicroRNA-1 and MicroRNA-206 Improve Differentiation Potential of Human Satellite Cells : A Novel Approach for Tissue Engineering of Skeletal Muscle

    NARCIS (Netherlands)

    Koning, Merel; Werker, Paul M. N.; van der Schaft, Daisy W. J.; Bank, Ruud A.; Harmsen, Martin C.

    2012-01-01

    Innovative strategies based on regenerative medicine, in particular tissue engineering of skeletal muscle, are promising for treatment of patients with skeletal muscle damage. However, the efficiency of satellite cell differentiation in vitro is suboptimal. MicroRNAs are involved in the regulation o

  11. Satellite RNAs and Satellite Viruses.

    Science.gov (United States)

    Palukaitis, Peter

    2016-03-01

    Satellite RNAs and satellite viruses are extraviral components that can affect either the pathogenicity, the accumulation, or both of their associated viruses while themselves being dependent on the associated viruses as helper viruses for their infection. Most of these satellite RNAs are noncoding RNAs, and in many cases, have been shown to alter the interaction of their helper viruses with their hosts. In only a few cases have the functions of these satellite RNAs in such interactions been studied in detail. In particular, work on the satellite RNAs of Cucumber mosaic virus and Turnip crinkle virus have provided novel insights into RNAs functioning as noncoding RNAs. These effects are described and potential roles for satellite RNAs in the processes involved in symptom intensification or attenuation are discussed. In most cases, models describing these roles involve some aspect of RNA silencing or its suppression, either directly or indirectly involving the particular satellite RNA.

  12. IL-17A-producing resident memory γδ T cells orchestrate the innate immune response to secondary oral Listeria monocytogenes infection.

    Science.gov (United States)

    Romagnoli, Pablo A; Sheridan, Brian S; Pham, Quynh-Mai; Lefrançois, Leo; Khanna, Kamal M

    2016-07-26

    Memory γδ T cells are important for the clearance of Listeria monocytogenes infection in the intestinal mucosa. However, the mechanisms by which memory γδ T cells provide protection against secondary oral infection are poorly understood. Here we used a recombinant strain of L. monocytogenes that efficiently invades the intestinal epithelium to show that Vγ4(+) memory γδ T cells represent a resident memory (Trm) population in the mesenteric lymph nodes (MLNs). The γδ Trm exhibited a remarkably static pattern of migration that radically changed following secondary oral L. monocytogenes infection. The γδ Trms produced IL-17A early after rechallenge and formed organized clusters with myeloid cells surrounding L. monocytogenes replication foci only after a secondary oral infection. Antibody blocking studies showed that in addition to IL-17A, the chemokine receptor C-X-C chemokine receptor 3 (CXCR3) is also important to enable the local redistribution of γδ Trm cells and myeloid cells specifically near the sites of L. monocytogenes replication within the MLN to restrict bacterial growth and spread. Our findings support a role for γδ Trms in orchestrating protective immune responses against intestinal pathogens.

  13. Satellite Cell Functional Alterations Following Cutaneous Burn in rats Include an Increase in Their Osteogenic Potential

    Science.gov (United States)

    2013-10-07

    skeletal muscle hypertrophy and atrophy. Nat Cell Biol 2003;5:87. [6] Brack AS, Rando TA. Intrinsic changes and extrinsic influences of myogenic stem...Skeletal muscle Muscle precursor cell Thermal injury Atrophy Heterotopic ossification a b s t r a c t Background: Significant consequences of severe burn...include skeletal muscle atrophy and heterotopic ossification (HO). The cellular mechanisms underlying either of these condi- tions are not known

  14. Centriolar satellites

    DEFF Research Database (Denmark)

    Tollenaere, Maxim A X; Mailand, Niels; Bekker-Jensen, Simon

    2015-01-01

    Centriolar satellites are small, microscopically visible granules that cluster around centrosomes. These structures, which contain numerous proteins directly involved in centrosome maintenance, ciliogenesis, and neurogenesis, have traditionally been viewed as vehicles for protein trafficking...... highlight newly discovered regulatory mechanisms targeting centriolar satellites and their functional status, and we discuss how defects in centriolar satellite components are intimately linked to a wide spectrum of human diseases....

  15. Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

    Directory of Open Access Journals (Sweden)

    Maciej Lech

    2012-01-01

    Full Text Available Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries.

  16. In situ hybridization of the feline major satellite DNA FA-SAT in feline fibrosarcoma cell lines and feline fibrosarcoma tissue sections

    OpenAIRE

    Alfaro Alarcón, Alejandro

    2009-01-01

    Feline fibrosarcomas are the most common skin tumors of cats. Despite this high frequency and the publication of different hypotheses for their pathogenesis by several authors, the alterations accompanying the development of this tumor are still not completely understood. We studied the feline major satellite DNA (FA-SAT) hybridization pattern by FISH in four fibrosarcoma cell lines and one normal embryonic fibroblastic cell line as well as in 30 fibrosarcomas from 28 cats. Of the latter, ...

  17. Satellite theory

    Science.gov (United States)

    Kozai, Y.

    1981-04-01

    The dynamical characteristics of the natural satellite of Mars, Jupiter, Saturn, Uranus and Neptune are analyzed on the basis of the solar tidal perturbation factor and the oblateness factor of the primary planet for each satellite. For the inner satellites, for which the value of the solar tidal factor is much smaller than the planetary oblateness factor, it is shown that the eccentricity and inclination of satellite orbits are generally very small and almost constant; several pairs of inner satellites are also found to exhibit commensurable mean motions, or secular accelerations in mean longitude. In the case of the outer satellites, for which solar perturbations are dominant, secular perturbations and long-period perturbations may be derived by the solution of equations of motion reduced to one degree of freedom. The existence of a few satellites, termed intermediary satellites, for which the solar tidal perturbation is on the order of the planetary oblateness factor, is also observed, and the pole of the orbital plane of the satellite is noted to execute a complex motion around the pole of the planet or the orbital plane of the planet.

  18. Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes

    Directory of Open Access Journals (Sweden)

    Angela Maria Cozzolino

    2016-01-01

    Full Text Available In many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance of differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness of extracellular matrix that, in vivo, characterizes their correspondent organ and tissue. In the liver, the stromal rigidity is essential to obtain the correct organ physiology whereas any alteration causes liver cell dysfunctions. The rigidity of the substrate is an element no longer negligible for the cultivation of several cell types, so that many data so far obtained, where cells have been cultured on plastic, could be revised. Regarding liver cells, standard culture conditions lead to the dedifferentiation of primary hepatocytes, transdifferentiation of stellate cells into myofibroblasts, and loss of fenestration of sinusoidal endothelium. Furthermore, standard cultivation of liver stem/precursor cells impedes an efficient execution of the epithelial/hepatocyte differentiation program, leading to the expansion of a cell population expressing only partially liver functions and products. Overcoming these limitations is mandatory for any approach of liver tissue engineering. Here we propose cell lines as in vitro models of liver stem cells and hepatocytes and an innovative culture method that takes into account the substrate stiffness to obtain, respectively, a rapid and efficient differentiation process and the maintenance of the fully differentiated phenotype.

  19. Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Kenneth C Loh

    Full Text Available Sphingosine-1-phosphate (S1P activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD, were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3, a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD.

  20. Community effect triggers terminal differentiation of myogenic cells derived from muscle satellite cells by quenching Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yanagisawa, Michiko [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Aging Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 (Japan); Mukai, Atsushi; Shiomi, Kosuke [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Song, Si-Yong [Institute of Neuroscience, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki-shi, Kagawa 769-2193 (Japan); Hashimoto, Naohiro, E-mail: nao@ncgg.go.jp [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan)

    2011-01-15

    A high concentration of bone morphogenetic proteins (BMPs) stimulates myogenic progenitor cells to undergo heterotopic osteogenic differentiation. However, the physiological role of the Smad signaling pathway during terminal muscle differentiation has not been resolved. We report here that Smad1/5/8 was phosphorylated and activated in undifferentiated growing mouse myogenic progenitor Ric10 cells without exposure to any exogenous BMPs. The amount of phosphorylated Smad1/5/8 was severely reduced during precocious myogenic differentiation under the high cell density culture condition even in growth medium supplemented with a high concentration of serum. Inhibition of the Smad signaling pathway by dorsomorphin, an inhibitor of Smad activation, or noggin, a specific antagonist of BMP, induced precocious terminal differentiation of myogenic progenitor cells in a cell density-dependent fashion even in growth medium. In addition, Smad1/5/8 was transiently activated in proliferating myogenic progenitor cells during muscle regeneration in rats. The present results indicate that the Smad signaling pathway is involved in a critical switch between growth and differentiation of myogenic progenitor cells both in vitro and in vivo. Furthermore, precocious cell density-dependent myogenic differentiation suggests that a community effect triggers the terminal muscle differentiation of myogenic cells by quenching the Smad signaling.

  1. Temporal changes in glycogenolytic enzyme mRNAs during myogenesis of primary porcine satellite cells

    DEFF Research Database (Denmark)

    Henckel, Poul; Theil, Peter Kappel; Sørensen, Inge Lise

    2007-01-01

    , phosphorylase kinase, phosphorylase and glycogen debranching enzyme, and no alterations of the transporter molecule GLUT4, clearly indicate that glycogenolytic enzymes of potential importance to meat quality development are regulated at the gene level during myogenesis, and are heavily involved in muscle cell...... and muscle fibre development. The genes, however, are not influenced by insulin, and the lack of response to insulin of expression of gene-encoding enzymes involved in the formation and degradation of glycogen may question the applicability of porcine cell culture systems, like the one applied, as a model...

  2. Extracellular Vesicles: Satellites of Information Transfer in Cancer and Stem Cell Biology.

    Science.gov (United States)

    Desrochers, Laura M; Antonyak, Marc A; Cerione, Richard A

    2016-05-23

    The generation and shedding of extracellular vesicles (EVs), including exosomes and microvesicles (MVs), by cells has emerged as a form of intercellular communication with important roles in several physiological processes and diseases such as cancer. These membrane-enclosed packets can transfer specific proteins, RNA transcripts, microRNAs, and even DNA to target cells, thereby altering their function. Despite the exponential growth of the EV field, a great deal remains unclear about the mechanisms that regulate exosome and MV biogenesis, as well as about how to isolate different classes of EVs and how to best take advantage of them for clinical applications.

  3. Identification of genes differentially expressed in myogenin knock-down bovine muscle satellite cells during differentiation through RNA sequencing analysis.

    Directory of Open Access Journals (Sweden)

    Eun Ju Lee

    Full Text Available BACKGROUND: The expression of myogenic regulatory factors (MRFs consisting of MyoD, Myf5, myogenin (MyoG and MRF4 characterizes various phases of skeletal muscle development including myoblast proliferation, cell-cycle exit, cell fusion and the maturation of myotubes to form myofibers. Although it is well known that the function of MyoG cannot be compensated for other MRFs, the molecular mechanism by which MyoG controls muscle cell differentiation is still unclear. Therefore, in this study, RNA-Seq technology was applied to profile changes in gene expression in response to MyoG knock-down (MyoGkd in primary bovine muscle satellite cells (MSCs. RESULTS: About 61-64% of the reads of over 42 million total reads were mapped to more than 13,000 genes in the reference bovine genome. RNA-Seq analysis identified 8,469 unique genes that were differentially expressed in MyoGkd. Among these genes, 230 were up-regulated and 224 were down-regulated by at least four-fold. DAVID Functional Annotation Cluster (FAC and pathway analysis of all up- and down-regulated genes identified overrepresentation for cell cycle and division, DNA replication, mitosis, organelle lumen, nucleoplasm and cytosol, phosphate metabolic process, phosphoprotein phosphatase activity, cytoskeleton and cell morphogenesis, signifying the functional implication of these processes and pathways during skeletal muscle development. The RNA-Seq data was validated by real time RT-PCR analysis for eight out of ten genes as well as five marker genes investigated. CONCLUSIONS: This study is the first RNA-Seq based gene expression analysis of MyoGkd undertaken in primary bovine MSCs. Computational analysis of the differentially expressed genes has identified the significance of genes such as SAP30-like (SAP30L, Protein lyl-1 (LYL1, various matrix metalloproteinases, and several glycogenes in myogenesis. The results of the present study widen our knowledge of the molecular basis of skeletal muscle

  4. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina;

    2014-01-01

    leading to increased mobilization of non-carbohydrate substrates as branched chain amino acids or long chain fatty acids was observed in senescent cells. In addition, phospho-and glycerolipids metabolism was altered. Increased levels of acyl-carnitines indicated augmented turnover of storage and membrane...

  5. Residence-time dependent cell wall deformation of different Staphylococcus aureus strains on gold measured using surface-enhanced-fluorescence

    NARCIS (Netherlands)

    Li, Jiuyi; Busscher, Henk J.; Swartjes, Jan J. T. M.; Chen, Yun; Harapanahalli, Akshay K.; Norde, Willem; van der Mei, Henny C.; Sjollema, Jelmer

    2014-01-01

    Bacterial adhesion to surfaces is accompanied by cell wall deformation that may extend to the lipid membrane with an impact on the antimicrobial susceptibility of the organisms. Nanoscale cell wall deformation upon adhesion is difficult to measure, except for Delta pbp4 mutants, deficient in peptido

  6. "The preadipocyte factor" DLK1 marks adult mouse adipose tissue residing vascular cells that lack in vitro adipogenic differentiation potential

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Jensen, Line; Schrøder, Henrik Daa

    2009-01-01

    Delta-like 1 (Dlk1) is expressed in 3T3-L1 preadipocytes and has frequently been referred to as "the" preadipocyte marker, yet the phenotype of DLK1(+) cells in adipose tissue remains undetermined. Herein, we demonstrate that DLK1(+) cells encompass around 1-2% of the adult mouse adipose stromal...

  7. Sphingosylphosphorylcholine promotes the differentiation of resident Sca-1 positive cardiac stem cells to cardiomyocytes through lipid raft/JNK/STAT3 and β-catenin signaling pathways.

    Science.gov (United States)

    Li, Wenjing; Liu, Honghong; Liu, Pingping; Yin, Deling; Zhang, Shangli; Zhao, Jing

    2016-07-01

    Resident cardiac Sca-1-positive (+) stem cells may differentiate into cardiomyocytes to improve the function of damaged hearts. However, little is known about the inducers and molecular mechanisms underlying the myogenic conversion of Sca-1(+) stem cells. Here we report that sphingosylphosphorylcholine (SPC), a naturally occurring bioactive lipid, induces the myogenic conversion of Sca-1(+) stem cells, as evidenced by the increased expression of cardiac transcription factors (Nkx2.5 and GATA4), structural proteins (cardiac Troponin T), transcriptional enhancer (Mef2c) and GATA4 nucleus translocation. First, SPC activated JNK and STAT3, and the JNK inhibitor SP600125 or STAT3 inhibitor stattic impaired the SPC-induced expression of cardiac transcription factors and GATA4 nucleus translocation, which suggests that JNK and STAT3 participated in SPC-promoted cardiac differentiation. Moreover, STAT3 activation was inhibited by SP600125, whereas JNK was inhibited by β-cyclodextrin as a lipid raft breaker, which indicates a lipid raft/JNK/STAT3 pathway involved in SPC-induced myogenic transition. β-Catenin, degraded by activated GSK3β, was inhibited by SPC. Furthermore, GSK3β inhibitors weakened but the β-catenin inhibitor promoted SPC-induced differentiation. We found no crosstalk between the lipid raft/JNK/STAT3 and β-catenin pathway. Our study describes a lipid, SPC, as an endogenic inducer of myogenic conversion in Sca-1(+) stem cells with low toxicity and high efficiency for uptake.

  8. Injection of duck recombinant follistatin fusion protein into duck muscle tissues stimulates satellite cell proliferation and muscle fiber hypertrophy.

    Science.gov (United States)

    Liu, He-he; Wang, Ji-wen; Yu, Hai-yue; Zhang, Rong-ping; Chen, Xi; Jin, Hai-bo; Dai, Fei; Li, Liang; Xu, Feng

    2012-06-01

    Follistatin (FST) can inhibit the expression of myostatin, which is a predominant inhibitor of muscle development. The potential application of myostatin-based technology has been prompted in different ways in agriculture. We previously constructed an expression vector of duck FST and isolated the FST fusion protein. After the protein was purified and refolded, it was added to the medium of duck myoblasts cultured in vitro. The results show that the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide value of the myoblasts in the duck FST treatment group is higher than that in the control group, which indicates that the duck FST fusion protein exhibits the biological activities that can accelerate myoblast proliferation. To further investigate the roles of duck FST on muscle development, we injected the protein into the duck muscle tissues in vivo. The results show that both the duck muscle fiber cross-sectional area and the satellite cell activation frequency are influenced more in the FST treatment group than they are in the control group. In addition to these phenomena, expression of MyoD and Myf5 were increased, and the expression of myostatin was decreased. Together, these results suggest the potential for using duck FST fusion protein to inhibit myostatin activity and subsequently to enhance muscle growth in vivo. The mechanism by which FST regulates muscle development in the duck is similar to that in mammals and fishes.

  9. Effects of Dexamethasone on Satellite Cells and Tissue Engineered Skeletal Muscle Units.

    Science.gov (United States)

    Syverud, Brian C; VanDusen, Keith W; Larkin, Lisa M

    2016-03-01

    Tissue engineered skeletal muscle has potential for application as a graft source for repairing soft tissue injuries, a model for testing pharmaceuticals, and a biomechanical actuator system for soft robots. However, engineered muscle to date has not produced forces comparable to native muscle, limiting its potential for repair and for use as an in vitro model for pharmaceutical testing. In this study, we examined the trophic effects of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation and fusion into myotubes, on our tissue engineered three-dimensional skeletal muscle units (SMUs). Using our established SMU fabrication protocol, muscle isolates were cultured with three experimental DEX concentrations (5, 10, and 25 nM) and compared to untreated controls. Following seeding onto a laminin-coated Sylgard substrate, the administration of DEX was initiated on day 0 or day 6 in growth medium or on day 9 after the switch to differentiation medium and was sustained until the completion of SMU fabrication. During this process, total cell proliferation was measured with a BrdU assay, and myogenesis and structural advancement of muscle cells were observed through immunostaining for MyoD, myogenin, desmin, and α-actinin. After SMU formation, isometric tetanic force production was measured to quantify function. The histological and functional assessment of the SMU showed that the administration of 10 nM DEX beginning on either day 0 or day 6 yielded optimal SMUs. These optimized SMUs exhibited formation of advanced sarcomeric structure and significant increases in myotube diameter and myotube fusion index, compared with untreated controls. Additionally, the optimized SMUs matured functionally, as indicated by a fivefold rise in force production. In conclusion, we have demonstrated that the addition of DEX to our process of engineering skeletal muscle tissue improves myogenesis, advances muscle structure, and increases force production in the

  10. Satellite Communications

    CERN Document Server

    Pelton, Joseph N

    2012-01-01

    The field of satellite communications represents the world's largest space industry. Those who are interested in space need to understand the fundamentals of satellite communications, its technology, operation, business, economic, and regulatory aspects. This book explains all this along with key insights into the field's future growth trends and current strategic challenges. Fundamentals of Satellite Communications is a concise book that gives all of the key facts and figures as well as a strategic view of where this dynamic industry is going. Author Joseph N. Pelton, PhD, former Dean of the International Space University and former Director of Strategic Policy at Intelstat, presents a r

  11. Results of the 2005-2008 Association of Residents in Radiation Oncology Survey of Chief Residents in the United States: Clinical Training and Resident Working Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Gondi, Vinai, E-mail: gondi@humonc.wisc.edu [Department of Radiation Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (United States); Bernard, Johnny Ray [Mayo Clinic Jacksonville, Jacksonville, Florida (United States); Jabbari, Siavash [University of California San Francisco, San Francisco, California (United States); Keam, Jennifer [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Amorim Bernstein, Karen L. de [Albert Einstein College of Medicine, Bronx, New York (United States); Dad, Luqman K. [SUNY Roswell Park Cancer Institute, Buffalo, New York (United States); Li, Linna [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Poppe, Matthew M. [University of Utah Huntsman Cancer Hospital (United States); Strauss, Jonathan B. [Northwestern University Feinberg School of Medicine, Chicago, Illinois (United States); Chollet, Casey T. [Loyola University Medical Center, Maywood, Illinois (United States)

    2011-11-15

    Purpose: To document clinical training and resident working conditions reported by chief residents during their residency. Methods and Materials: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistics were used to assess changes in clinical training and resident working conditions over time. Results: Surveys were completed by representatives from 55 programs (response rate, 71.4%) in 2005 to 2006, 60 programs (75.9%) in 2006 to 2007, and 74 programs (93.7%) in 2007 to 2008. Nearly all chief residents reported receiving adequate clinical experience in commonly treated disease sites, such as breast and genitourinary malignancies; and commonly performed procedures, such as three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Clinical experience in extracranial stereotactic radiotherapy increased over time (p < 0.001), whereas clinical experience in endovascular brachytherapy (p <0.001) decreased over time. The distribution of gynecologic and prostate brachytherapy cases remained stable, while clinical case load in breast brachytherapy increased (p = 0.006). A small but significant percentage of residents reported receiving inadequate clinical experience in pediatrics, seeing 10 or fewer pediatric cases during the course of residency. Procedures involving higher capital costs, such as particle beam therapy and intraoperative radiotherapy, and infrequent clinical use, such as head and neck brachytherapy, were limited to a minority of institutions. Most residency programs associated with at least one satellite facility have incorporated resident rotations into their clinical training, and the majority of residents at these programs find them valuable experiences. The majority of residents reported working 60 or fewer hours per week on required clinical duties

  12. Relationship between skeletal muscle satellite cells and exercise%骨骼肌卫星细胞生长因子与运动训练的关系

    Institute of Scientific and Technical Information of China (English)

    谢永涛; 蓝岚

    2011-01-01

    BACKGROUND: High intensity of exercise can lead to injury to fine structure of skeletal muscle tissue, and the activation,proliferation and differentiation of skeletal muscle satellite cells are closely related to muscle tissue injury.OBJECTIVE: Based on the thinking that training can cause muscle structural damage and repair is needed, this study proposed a dependent relationship between repair of skeletal muscle structure and skeletal muscle satellite cells.METHODS: A computer-based retrieval was performed by the first author to search manuscripts in CNKI and Medline database published between 2000 and 2010 with the key words “skeletal muscle satellite cells, growth factor, exercise, and skeletal muscle ultrastructure” in English and Chinese languages. A total of 97 manuscripts were retrieved. Following inclusion and exclusion criteria, 23 manuscripts were included in the final analysis. The mechanism underlying skeletal tissue repair and skeletal muscle satellite cell activation was summarized, and the relationship between these two was analyzed.RESULTS AND CONCLUSION: High intensity of exercise can result in injury to skeletal muscle tissue, satellite cells are the key toskeletal muscle repair and the growth factors of satellite cells are also related to exercise methods. At present, the relationship between skeletal muscle satellite cells growth factors and exercise lacks of sufficient recognition and research.%背景:大运动量训练可以导致骨骼肌组织微细结构的损伤性变化,而骨骼肌卫星细胞的激活、增殖与分化和肌肉组织损伤的修复有密切关系.目的:文章从训练导致肌肉组织结构性损伤需要修复的客观实际出发,提出运动后骨骼肌结构的修复与骨骼肌卫星细胞生长因子之间存在某种依赖关系.方法:由第一作者通过计算机网络检索中国期刊全文数据库(CNKI)和Medline数据库(2000/2010),检索词分别为"骨骼肌卫星细胞,生长因子,运动训

  13. Satellite Geomagnetism

    DEFF Research Database (Denmark)

    Olsen, Nils; Stolle, Claudia

    2012-01-01

    Observations of Earth’s magnetic field from space began more than 50 years ago. A continuous monitoring of the field using low Earth orbit (LEO) satellites, however, started only in 1999, and three satellites have taken highprecision measurements of the geomagnetic field during the past decade...... ability to characterize and understand the many sources that contribute to Earth’s magnetic field. In this review, we summarize investigations of Earth’s interior and environment that have been possible through the analysis of high-precision magnetic field observations taken by LEO satellites........ The unprecedented time-space coverage of their data opened revolutionary new possibilities for monitoring, understanding, and exploring Earth’s magnetic field. In the near future, the three-satellite constellation Swarm will ensure continuity of such measurement and provide enhanced possibilities to improve our...

  14. Cryptic chemotactic activity of fibronectin for human monocytes resides in the 120-kDa fibroblastic cell-binding fragment.

    Science.gov (United States)

    Clark, R A; Wikner, N E; Doherty, D E; Norris, D A

    1988-08-25

    Monocytes and lymphocytes form a second wave of infiltrating blood leukocytes in areas of tissue injury. The mechanisms for monocyte accumulation at these sites are not completely understood. Recently, however, fragments from extracellular matrix proteins including collagen, elastin, and fibronectin have been shown to induce monocyte chemotaxis. In this report we demonstrate that chemotactic activity for human monocytes is expressed when a 120-kDa fragment containing the RGDS cell-binding peptide is released from intact fibronectin or from larger fibronectin fragments. Monocytes, either from mononuclear cell Ficoll-Hypaque preparations (10-20% monocytes, 89-90% lymphocytes) or from elutriation preparations (95% monocytes, 5% lymphocytes), but not lymphocytes, migrated toward 120-kDa fragment preparations (10(-7) M) in blind-end chambers when the cells were separated from the chemoattractant by a 5-micron pore polycarbonate filter either alone or overlying a 0.45-micron pore nitrocellulose filter. Neutrophils migrated toward zymosan-activated serum but not toward 10(-5)-10(-8) M concentrations of the 120-kDa fragment. Intact fibronectin had no chemotactic activity for human monocytes. Fibronectin was isolated from citrated human plasma by sequential gelatin-Sepharose affinity and DEAE ion-exchange chromatography in the presence of buffers containing 1 mM phenylmethylsulfonyl fluoride to prevent fragmentation. Controlled enzymatic digestion with thermolysin cleaved fibronectin into 30 kDa fibrin, 45 kDa collagen, and 150/160-kDa cell and heparin domains. Upon prolonged digestion, purified 150/160-kDa fragments were cleaved into 120-kDa cell and 30/40-kDa heparin-binding fragments. Even though the intact fibronectin molecule, the 150/160-kDa fragments, and the 120-kDa fragment, have cell binding activity for Chinese hamster ovary fibroblasts, only the 120-kDa fragment expressed chemotactic activity for human monocytes. Thus, the 120-kDa fibroblastic cell

  15. Resident Characteristics Report

    Data.gov (United States)

    Department of Housing and Urban Development — The Resident Characteristics Report summarizes general information about households who reside in Public Housing, or who receive Section 8 assistance. The report...

  16. Role of the mTORC1 Complex in Satellite Cell Activation by RNA-Induced Mitochondrial Restoration: Dual Control of Cyclin D1 through MicroRNAs

    OpenAIRE

    Jash, Sukanta; Dhar, Gunjan; Ghosh, Utpalendu; Adhya, Samit

    2014-01-01

    During myogenesis, satellite stem cells (SCs) are induced to proliferate and differentiate to myogenic precursors. The role of energy sensors such as the AMP-activated protein kinase (AMPK) and the mammalian Target of Rapamycin (mTOR) in SC activation is unclear. We previously observed that upregulation of ATP through RNA-mediated mitochondrial restoration (MR) accelerates SC activation following skeletal muscle injury. We show here that during regeneration, the AMPK-CRTC2-CREB and Raptor-mTO...

  17. Satellite (Natural)

    Science.gov (United States)

    Murdin, P.

    2000-11-01

    In its most general sense, any celestial object in orbit around a similar larger object. Thus, for example, the Magellanic Clouds are satellite galaxies of our own Milky Way galaxy. Without qualification, the term is used to mean a body in orbit around a planet; an alternative term is moon. The term natural satellite distinguishes these bodies from artificial satellites—spacecraft placed in orbi...

  18. The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny

    Science.gov (United States)

    Shafi, Raheel; Iyer, Sai Prasad N.; Ellies, Lesley G.; O'Donnell, Niall; Marek, Kurt W.; Chui, Daniel; Hart, Gerald W.; Marth, Jamey D.

    2000-01-01

    Nuclear and cytoplasmic protein glycosylation is a widespread and reversible posttranslational modification in eukaryotic cells. Intracellular glycosylation by the addition of N-acetylglucosamine (GlcNAc) to serine and threonine is catalyzed by the O-GlcNAc transferase (OGT). This “O-GlcNAcylation” of intracellular proteins can occur on phosphorylation sites, and has been implicated in controlling gene transcription, neurofilament assembly, and the emergence of diabetes and neurologic disease. To study OGT function in vivo, we have used gene-targeting approaches in male embryonic stem cells. We find that OGT mutagenesis requires a strategy that retains an intact OGT gene as accomplished by using Cre-loxP recombination, because a deletion in the OGT gene results in loss of embryonic stem cell viability. A single copy of the OGT gene is present in the male genome and resides on the X chromosome near the centromere in region D in the mouse spanning markers DxMit41 and DxMit95, and in humans at Xq13, a region associated with neurologic disease. OGT RNA expression in mice is comparably high among most cell types, with lower levels in the pancreas. Segregation of OGT alleles in the mouse germ line with ZP3-Cre recombination in oocytes reveals that intact OGT alleles are required for completion of embryogenesis. These studies illustrate the necessity of conditional gene-targeting approaches in the mutagenesis and study of essential sex-linked genes, and indicate that OGT participation in intracellular glycosylation is essential for embryonic stem cell viability and for mouse ontogeny. PMID:10801981

  19. Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle.

    Science.gov (United States)

    Dalbo, V J; Roberts, M D; Mobley, C B; Ballmann, C; Kephart, W C; Fox, C D; Santucci, V A; Conover, C F; Beggs, L A; Balaez, A; Hoerr, F J; Yarrow, J F; Borst, S E; Beck, D T

    2017-04-01

    The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week(-1) ) or ORX + trenbolone (TREN; 1.0 mg week(-1) ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p TREN compared to ORX (p TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.

  20. Dynamic Imaging of Marrow-Resident Granulocytes Interacting with Human Mesenchymal Stem Cells upon Systemic Lipopolysaccharide Challenge

    Directory of Open Access Journals (Sweden)

    Jay T. Myers

    2013-01-01

    Full Text Available Human mesenchymal stem cells (hMSCs have gained intense research interest due to their immune-modulatory, tissue differentiating, and homing properties to sites of inflammation. Despite evidence demonstrating the biodistribution of infused hMSCs in target organs using static fluorescence imaging or whole-body imaging techniques, surprisingly little is known about how hMSCs behave dynamically within host tissues on a single-cell level in vivo. Here, we infused fluorescently labeled clinical-grade hMSCs into immune-competent mice in which neutrophils and monocytes express a second fluorescent marker under the lysozyme M (LysM promoter. Using intravital two-photon microscopy (TPM, we were able for the first time to capture dynamic interactions between hMSCs and LysM+ granulocytes in the calvarium bone marrow of recipient mice during systemic LPS challenge in real time. Interestingly, many of the infused hMSCs remained intact despite repeated cellular contacts with host neutrophils. However, we were able to observe the destruction and subsequent phagocytosis of some hMSCs by surrounding granulocytes. Thus, our imaging platform provides opportunities to gain insight into the biology and therapeutic mechanisms of hMSCs in vivo at a single-cell level within live hosts.

  1. The Ideal Resident Doctor: Á Resident's Perspective

    African Journals Online (AJOL)

    trainer relationship can only then be imagined. ... like these lend themselves to personal and cultural ... An ideal resident's clinical options .... of humanistic and professional values, the lack of .... graduate medical education should do more in mak-.

  2. Lecithin:Cholesterol Acyltransferase (LCAT) Deficiency Promotes Differentiation of Satellite Cells to Brown Adipocytes in a Cholesterol-dependent Manner.

    Science.gov (United States)

    Nesan, Dinushan; Tavallaee, Ghazaleh; Koh, Deborah; Bashiri, Amir; Abdin, Rawand; Ng, Dominic S

    2015-12-18

    Our laboratory previously reported that lecithin:cholesterol acyltransferase (LCAT) and LDL receptor double knock-out mice (Ldlr(-/-)xLcat(-/-) or DKO) spontaneously develop functioning ectopic brown adipose tissue (BAT) in skeletal muscle, putatively contributing to protection from the diet-induced obesity phenotype. Here we further investigated their developmental origin and the mechanistic role of LCAT deficiency. Gene profiling of skeletal muscle in DKO newborns and adults revealed a classical lineage. Primary quiescent satellite cells (SC) from chow-fed DKO mice, not in Ldlr(-/-)xLcat(+/+) single-knock-out (SKO) or C57BL/6 wild type, were found to (i) express exclusively classical BAT-selective genes, (ii) be primed to express key functional BAT genes, and (iii) exhibit markedly increased ex vivo adipogenic differentiation into brown adipocytes. This gene priming effect was abrogated upon feeding the mice a 2% high cholesterol diet in association with accumulation of excess intracellular cholesterol. Ex vivo cholesterol loading of chow-fed DKO SC recapitulated the effect, indicating that cellular cholesterol is a key regulator of SC-to-BAT differentiation. Comparing adipogenicity of Ldlr(+/+)xLcat(-/-) (LCAT-KO) SC with DKO SC identified a role for LCAT deficiency in priming SC to express BAT genes. Additionally, we found that reduced cellular cholesterol is important for adipogenic differentiation, evidenced by increased induction of adipogenesis in cholesterol-depleted SC from both LCAT-KO and SKO mice. Taken together, we conclude that ectopic BAT in DKO mice is classical in origin, and its development begins in utero. We further showed complementary roles of LCAT deficiency and cellular cholesterol reduction in the SC-to-BAT adipogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Stand-up exercise training facilitates muscle recovery from disuse atrophy by stimulating myogenic satellite cell proliferation in mice.

    Science.gov (United States)

    Itoh, Yuta; Hayakawa, Kimihide; Mori, Tomohiro; Agata, Nobuhide; Inoue-Miyazu, Masumi; Murakami, Taro; Sokabe, Masahiro; Kawakami, Keisuke

    2014-11-01

    Determining the cellular and molecular recovery processes in inactivity - or unloading -induced atrophied muscles should improve rehabilitation strategies. We assessed the effects of stand-up exercise (SE) training on the recovery of atrophied skeletal muscles in male mice. Mice were trained to stand up and press an elevated lever in response to a light-tone cue preceding an electric foot shock and then subjected to tail suspension (TS) for 2 weeks to induce disuse atrophy in hind limb muscles. After release from TS, mice were divided into SE-trained (SE cues: 25 times per set, two sets per day) and non-SE-trained groups. Seven days after the training, average myofiber cross-sectional area (CSA) of the soleus muscle was significantly greater in the SE-trained group than in the non-SE-trained group (1843 ± 194 μm(2) vs. 1315 ± 153 μm(2)). Mean soleus muscle CSA in the SE trained group was not different from that in the CON group subjected to neither TS nor SE training (2005 ± 196 μm(2)), indicating that SE training caused nearly complete recovery from muscle atrophy. The number of myonuclei per myofiber was increased by ~60% in the SE-trained group compared with the non-SE-trained and CON groups (0.92 ± 0.03 vs. 0.57 ± 0.03 and 0.56 ± 0.11, respectively). The number of proliferating myonuclei, identified by 5-ethynyl-2'-deoxyuridine staining, increased within the first few days of SE training. Thus, it is highly likely that myogenic satellite cells proliferated rapidly in atrophied muscles in response to SE training and fused with existing myofibers to reestablish muscle mass.

  4. In Situ Proximity Ligation Assay (PLA) Analysis of Protein Complexes Formed Between Golgi-Resident, Glycosylation-Related Transporters and Transferases in Adherent Mammalian Cell Cultures.

    Science.gov (United States)

    Maszczak-Seneczko, Dorota; Sosicka, Paulina; Olczak, Teresa; Olczak, Mariusz

    2016-01-01

    In situ proximity ligation assay (PLA) is a novel, revolutionary technique that can be employed to visualize protein complexes in fixed cells and tissues. This approach enables demonstration of close (i.e., up to 40 nm) proximity between any two proteins of interest that can be detected using a pair of specific antibodies that have been raised in distinct species. Primary antibodies bound to the target proteins are subsequently recognized by two PLA probes, i.e., secondary antibodies conjugated with oligonucleotides that anneal when brought into close proximity in the presence of two connector oligonucleotides and a DNA ligase forming a circular DNA molecule. In the next step, the resulting circular DNA is amplified by a rolling circle polymerase. Finally, fluorescent oligonucleotide probes hybridize to complementary fragments of the amplified DNA molecule, forming a typical, spot-like pattern of PLA signal that reflects subcellular localization of protein complexes. Here we describe the use of in situ PLA in adherent cultures of mammalian cells in order to visualize interactions between Golgi-resident, functionally related glycosyltransferases and nucleotide sugar transporters relevant to N-glycan biosynthesis.

  5. AMPKα, C/EBPβ, CPT1β, GPR43, PPARγ, and SCD Gene Expression in Single- and Co-cultured Bovine Satellite Cells and Intramuscular Preadipocytes Treated with Palmitic, Stearic, Oleic, and Linoleic Acid

    OpenAIRE

    Choi, S H; Park, S. K.; B. J. Johnson; Chung, K. Y.; Choi, C. W.; Kim, K. H.; Kim, W. Y.; Smith, B.

    2015-01-01

    We previously demonstrated that bovine subcutaneous preadipocytes promote adipogenic gene expression in muscle satellite cells in a co-culture system. Herein we hypothesize that saturated fatty acids would promote adipogenic/lipogenic gene expression, whereas mono- and polyunsaturated fatty acids would have the opposite effect. Bovine semimembranosus satellite cells (BSC) and intramuscular preadipocytes (IPA) were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS)/D...

  6. Airborne Cladosporium and other fungi in damp versus reference residences

    Science.gov (United States)

    Pasanen, A.-L.; Niininen, M.; Kalliokoski, P.; Nevalainen, A.; Jantunen, M. J.

    Our previous study (Nevalainen et al., 1991, Envir. Int.17, 299-302) showed that airborne counts of total viable fungal spores in damp residences did not remarkably differ from those in reference residences. The results of the present study confirmed this finding. Indoor air spore counts varied considerably from residence to residence and even within the same residence. Thus, the counts were only occasionally high in the damp residences. Counts of airborne Cladosporium spp. spores and yeast cells were significantly higher in the damp residences than in the reference ones. The difference of yeast cell counts between the residence groups was explained by the difference in outdoor air, whereas Cladosporium spp. spores were mainly derived from indoors. Prevalence of Aspergillus spp. spores was also slightly higher in the damp residences than in the reference ones.

  7. Lymph node and circulating T cell characteristics are strongly correlated in end-stage renal disease patients, but highly differentiated T cells reside within the circulation.

    Science.gov (United States)

    Dedeoglu, B; de Weerd, A E; Huang, L; Langerak, A W; Dor, F J; Klepper, M; Verschoor, W; Reijerkerk, D; Baan, C C; Litjens, N H R; Betjes, M G H

    2017-05-01

    Ageing is associated with changes in the peripheral T cell immune system, which can be influenced significantly by latent cytomegalovirus (CMV) infection. To what extent changes in circulating T cell populations correlate with T cell composition of the lymph node (LN) is unclear, but is crucial for a comprehensive understanding of the T cell system. T cells from peripheral blood (PB) and LN of end-stage renal disease patients were analysed for frequency of recent thymic emigrants using CD31 expression and T cell receptor excision circle content, relative telomere length and expression of differentiation markers. Compared with PB, LN contained relatively more CD4(+) than CD8(+) T cells (P T cells and thymic output parameters showed a strong linear correlation between PB and LN. Highly differentiated CD28(null) T cells, being CD27(-) , CD57(+) or programmed death 1 (PD-1(+) ), were found almost exclusively in the circulation but not in LN. An age-related decline in naive CD4(+) and CD8(+) T cell frequency was observed (P = 0·035 and P = 0·002, respectively) within LN, concomitant with an increase in central memory CD8(+) T cells (P = 0·033). Latent CMV infection increased dramatically the frequency of circulating terminally differentiated T cells, but did not alter T cell composition and ageing parameters of LN significantly. Overall T cell composition and measures of thymic function in PB and LN are correlated strongly. However, highly differentiated CD28(null) T cells, which may comprise a large part of circulating T cells in CMV-seropositive individuals, are found almost exclusively within the circulation.

  8. High-sensitive bioorthogonal SERS tag for live cancer cell imaging by self-assembling core-satellites structure gold-silver nanocomposite.

    Science.gov (United States)

    Chen, Meng; Zhang, Ling; Gao, Mingxia; Zhang, Xiangmin

    2017-09-01

    A novel, high-sensitivity, biocompatible SERS tag with core-shell structure based on gold nanoparticles containing alkynyl molecule core -silver nanoparticle satellites shell was fabricated for the first time to be used for live cancer cells Surface enhanced Raman scattering (SERS) imaging. (E)-2-((4-(phenylethynyl)benzylidene) amino) ethanethiol (PBAT) synthesized facilely in our lab is the Raman-silence region reporter which is advantage for bioorthogonal SERS cell imaging. In order to enhance the intensity of the Raman tags for live cancer cell imaging, a series of news measures have been adopted. Firstly, reporter molecules of the PBAT were added twice, which is embedded in the gold core with the reduction of tetrachloroaurate and then PBAT is conjugated again on disperse gold nanoparticles (PBAT-Au). Furthermore, numerous Ag nanoparticles self-assembly were densely arranged around PBAT-Au core surface (PBAT- Au@Ag), just like a circle of satellites cluster, which produce obvious "hot spots" effects enhancing the signal of the Raman tags enormously. Finally, Bovine serum albumin (BSA) and polydopamine (PDA) coated on the PBAT- Au@Ag successively, defined as (PBAT-Au@Ag@BSA@PDA), which make as-synthesized nanocomposites own features of bio-compatibility and facilitates antibody modification. Compared with Au@PBAT@PDA, PBAT-Au@Ag@BSA@PDA with core-shell satellites structure showed 10-fold increase in the Raman signals intensity. Moreover, PBAT-Au@Ag@BSA@PDA nanocomposites were successfully applied in the Raman imaging of human glioma cells (U251) by the recognition of the anti-epidermal growth factor receptor (EGFR). All experimental results demonstrated that the nanocomposites have high value and huge potential application in the live cancer cells imaging and biomedical diagnostics in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Tungsten Promotes Sex-Specific Adipogenesis in the Bone by Altering Differentiation of Bone Marrow-Resident Mesenchymal Stromal Cells.

    Science.gov (United States)

    Bolt, Alicia M; Grant, Michael P; Wu, Ting Hua; Flores Molina, Manuel; Plourde, Dany; Kelly, Alexander D R; Negro Silva, Luis Fernando; Lemaire, Maryse; Schlezinger, Jennifer J; Mwale, Fackson; Mann, Koren K

    2016-04-01

    Tungsten is a naturally occurring metal that increasingly is being incorporated into industrial goods and medical devices, and is recognized as an emerging contaminant. Tungsten preferentially and rapidly accumulates in murine bone in a concentration-dependent manner; however the effect of tungsten deposition on bone biology is unknown. Other metals alter bone homeostasis by targeting bone marrow-derived mesenchymal stromal cell (MSC) differentiation, thus, we investigated the effects of tungsten on MSCsin vitroandin vivoIn vitro, tungsten shifted the balance of MSC differentiation by enhancing rosiglitazone-induced adipogenesis, which correlated with an increase in adipocyte content in the bone of tungsten-exposed, young, male mice. Conversely, tungsten inhibited osteogenesis of MSCsin vitro; however, we found no evidence that tungsten inhibited osteogenesisin vivo Interestingly, two factors known to influence adipogenesis are sex and age of mice. Both female and older mice have enhanced adipogenesis. We extended our study and exposed young female and adult (9-month) male and female mice to tungsten for 4 weeks. Although tungsten accumulated to a similar extent in young female mice, it did not promote adipogenesis. Interestingly, tungsten did not accumulate in the bone of older mice; it was undetectable in adult male mice, and just above the limit of detect in adult female mice. Surprisingly, tungsten enhanced adipogenesis in adult female mice. In summary, we found that tungsten alters bone homeostasis by altering differentiation of MSCs, which could have significant implications for bone quality, but is highly dependent upon sex and age.

  10. Scientific Satellites

    Science.gov (United States)

    1967-01-01

    followed Hale’s into orbit. In 1879, Jules Verne wrote about launching small satellites with a gun possessing a muzzle velocity of 10 000 m/sec (ref. 3...was activated in 1950.11 It was located only a few tens of miles from the spot where Jules Verne had his Baltimore Gun Club fire a manned projectile to...principle, satellites can be launched by a single impulse applied at the Earth’s surface-say, with a large cannon, & la Jules Verne (sec. 8-3). In

  11. Correlated NOS-Imu and myf5 expression by satellite cells in mdx mouse muscle regeneration during NOS manipulation and deflazacort treatment.

    Science.gov (United States)

    Anderson, Judy E; Vargas, Cinthya

    2003-06-01

    Satellite cells, muscle precursor cells in skeletal muscle, are normally quiescent and become activated by disease or injury. A lack of dystrophin and changes in the expression or activity of neuronal nitric oxide synthase (NOS-I) affect the timing of activation in vivo. Nitric oxide synthase inhibition delays muscle repair in normal mice, and worsens muscular dystrophy in the mdx mouse, a genetic homologue of Duchenne muscular dystrophy. However, the potential role of activation and repair events mediated by nitric oxide in determining the outcome of steroid or other treatments for muscular dystrophy is not clear. We tested the hypothesis that the extent of repair in dystrophic muscles of mdx mice is partly dependent on NOS-Imu expression and activity. Myotube formation in regenerating muscle was promoted by deflazacort treatment of mdx dystrophic mice (PImu mRNA expression and activity were present in satellite cells and very new myotubes of regenerating and dystrophic muscle. Deflazacort treatment resulted in increased NOS-Imu expression in regenerating muscles in a strong and specific correlation with myf5 expression (r=0.95, PImu and myf5 expression in the diaphragm without affecting the diameter of non-regenerating fibres. These in vivo studies suggest that gains in NOS-Imu expression and nitric oxide synthase activity in satellite cells can increase the extent and speed of repair, even in the absence of dystrophin in muscle fibres. NOS-Imu may be a useful therapeutic target to augment the effects of steroidal or other treatments of muscular dystrophy.

  12. [Burnout in nursing residents].

    Science.gov (United States)

    Franco, Gianfábio Pimentel; de Barros, Alba Lúcia Bottura Leite; Nogueira-Martins, Luiz Antônio; Zeitoun, Sandra Salloum

    2011-03-01

    Nursing residents may experience physical and emotional exhaustion from the daily life of attending the Program. The aim of this study was to determine the Burnout incidence among Nursing Residents. An investigative, descriptive, analytical, longitudinal-prospective study was conducted with 16 Residents over two years. The Maslach Burnout Inventory was used, translated and validated for Brazil, as well as a sociodemographic/occupational data tool. Of all residents, 17.2% showed high rates in Emotional Exhaustion and Depersonalization; 18.8% showed impaired commitment in Personal Accomplishment, 75% of which belonged to specialty areas, such as Emergency Nursing, Adult and Pediatric Intensive Care. Age and specialty area were positively correlated with Personal Accomplishment. One of the Residents was identified with changes in three subscales of the Maslach Burnout Inventory, thus characterized as a Burnout Syndrome patient. Nursing Residents have profiles of disease. Knowing these factors can minimize health risks of these workers.

  13. Residents in difficulty

    DEFF Research Database (Denmark)

    Christensen, Mette K.; O'Neill, Lotte Dyhrberg; Hansen, Dorthe H.;

    2016-01-01

    Background The majority of studies on prevalence and characteristics of residents in difficulty have been conducted in English-speaking countries and the existing literature may not reflect the prevalence and characteristics of residents in difficulty in other parts of the world such as the Scand......Background The majority of studies on prevalence and characteristics of residents in difficulty have been conducted in English-speaking countries and the existing literature may not reflect the prevalence and characteristics of residents in difficulty in other parts of the world...... of the topic. Methods We performed a mixed methods study. All regional residency program directors (N = 157) were invited to participate in an e-survey about residents in difficulty. Survey data were combined with database data on demographical characteristics of the background population (N = 2399...

  14. Effect of mean cell residence time on transmembrane flux, mixed-liquor characteristics and overall performance of a submerged anaerobic membrane bioreactor.

    Science.gov (United States)

    Pacheco-Ruiz, Santiago; Heaven, Sonia; Banks, Charles J

    2017-05-01

    Kinetic control of Mean Cell Residence Time (MCRT) was shown to have a significant impact on membrane flux under steady-state conditions. Two laboratory-scale flat-plate submerged anaerobic membrane bioreactors were operated for 245 days on a low-to-intermediate strength substrate with high suspended solids. Transmembrane pressure was maintained at 2.2 kPa throughout four experimental phases, while MCRT in one reactor was progressively reduced. This allowed very accurate measurement of sustainable membrane flux rates at different MCRTs, and hence the degree of membrane fouling. Performance data were gathered on chemical oxygen demand (COD) removal efficiency, and a COD mass balance was constructed accounting for carbon converted into new biomass and that lost in the effluent as dissolved methane. Measurements of growth yield at each MCRT were made, with physical characterisation of each mixed liquor based on capillary suction time. The results showed membrane flux and MLSS filterability was highest at short MCRT, although specific methane production (SMP) was lower since a proportion of COD removal was accounted for by higher biomass yield. There was no advantage in operating at an MCRT <25 days. When considering the most suitable MCRT there is thus a trade-off between membrane performance, SMP and waste sludge yield.

  15. A MULTICENTER, LONGITUDINAL, INTERVENTIONAL, DOUBLE BLIND RANDOMIZED CLINICAL TRIAL IN HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS RESIDING IN REMOTE AREAS: LESSONS LEARNED FROM THE LATE CYTOMEGALOVIRUS PREVENTION TRIAL.

    Science.gov (United States)

    Kimball, Louise E; Stevens-Ayers, Terry; Green, Margaret L; Xie, Hu; Flowers, Mary E D; Jerome, Keith R; LeBlanc, Renee; Dahlgren, Christi; Nichols, W Garrett; Chemaly, Roy F; Papanicolaou, G; Boeckh, Michael

    2016-12-15

    The logistics of conducting double-blinded phase III clinical trials with participants residing in remote locations are complex. Here we describe the implementation of an interventional trial for the prevention of late cytomegalovirus (CMV) disease in hematopoietic cell transplantation (HCT) subjects in a long-term follow-up environment. A total of 184 subjects at risk for late CMV disease surviving 80 days following allogeneic HCT were randomized to receive six months of valganciclovir or placebo. Subjects were followed through day 270 post-transplant at their local physician's office within the United States. Anti-viral treatment interventions were based on CMV DNAemia as measured by polymerase chain reaction (PCR) (>1000 copies/mL) and granulocyte colony stimulating factor (G-CSF) was prescribed for neutropenia (absolute neutrophil count (ANC <1.0 × 10(9) cells/L). Blood samples for viral testing and safety monitoring were shipped to a central laboratory by overnight carrier. Real-time communication was established between the coordinating center and study sites, primary care physicians, and study participants to facilitate starting, stopping and dose adjustments of antiviral drugs and G-CSF. The time required to make these interventions was analyzed. Of the 4169 scheduled blood specimens, 3832 (92%) were received and analyzed; the majority (97%) arriving at the central site within 2 days. Among subjects with positive CMV DNAemia (N=46), over 50% received open label antiviral medication within one day. The median time to start G-CSF for neutropenia was <1 day after posting of laboratory results (range 0-6; N=38). Study drug dose adjustments for abnormal renal function were implemented 203 times; within one day for 48% of cases and within 2 days for 80% of cases. Complex randomized, double-blind, multicenter interventional trials with treatment decisions made at a central coordinating site can be conducted safely and effectively according to Good Clinical

  16. Neonatal Phosphate Nutrition Alters in Vivo and in Vitro Satellite Cell Activity in Pigs

    Directory of Open Access Journals (Sweden)

    Chad H. Stahl

    2012-05-01

    Full Text Available Satellite cell activity is necessary for postnatal skeletal muscle growth. Severe phosphate (PO4 deficiency can alter satellite cell activity, however the role of neonatal PO4 nutrition on satellite cell biology remains obscure. Twenty-one piglets (1 day of age, 1.8 ± 0.2 kg BW were pair-fed liquid diets that were either PO4 adequate (0.9% total P, supra-adequate (1.2% total P in PO4 requirement or deficient (0.7% total P in PO4 content for 12 days. Body weight was recorded daily and blood samples collected every 6 days. At day 12, pigs were orally dosed with BrdU and 12 h later, satellite cells were isolated. Satellite cells were also cultured in vitro for 7 days to determine if PO4 nutrition alters their ability to proceed through their myogenic lineage. Dietary PO4 deficiency resulted in reduced (P < 0.05 sera PO4 and parathyroid hormone (PTH concentrations, while supra-adequate dietary PO4 improved (P < 0.05 feed conversion efficiency as compared to the PO4 adequate group. In vivo satellite cell proliferation was reduced (P < 0.05 among the PO4 deficient pigs, and these cells had altered in vitro expression of markers of myogenic progression. Further work to better understand early nutritional programming of satellite cells and the potential benefits of emphasizing early PO4 nutrition for future lean growth potential is warranted.

  17. Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells.

    Science.gov (United States)

    Weinstein, Jason S; Delano, Matthew J; Xu, Yuan; Kelly-Scumpia, Kindra M; Nacionales, Dina C; Li, Yi; Lee, Pui Y; Scumpia, Philip O; Yang, Lijun; Sobel, Eric; Moldawer, Lyle L; Reeves, Westley H

    2013-04-15

    Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (lipogranuloma) formation. A novel transplantation model was used to show that transplanted lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4(+) T cells were not required for autoantibody production from the transplanted lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell-dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.

  18. The assessment of cytotoxic T cell and natural killer cells activity in residents of high and ordinary background radiation areas of Ramsar-Iran

    Directory of Open Access Journals (Sweden)

    Sajad Borzoueisileh

    2013-01-01

    Full Text Available The effective radiation dose of human from natural sources is about 2.4 mSv/y and the dose limit for radiation workers is 20 mSv/y. Ramsar, a city in Iran, has been the subject of concern in the last forty years for a high level of radiation measured in some spots as high as 260 mSv/y. Carcinogenesis is one of the most studied effects of radiation especially in high doses. Recent studies showed that the high level of natural radiation received by inhabitants of this area, paradoxically don′t have significant health effect. Natural killer (NK cells and cytotoxic T cells are the most important cells in tumor immune surveillance and CD107a is a widely expressed intracellular protein located in the lysosomal/endosomal membrane. CD107a transiently located on the cell membrane can be used as a marker of CD8 + T cell degranulation following stimulation. It is also expressed, to a lower extent, on activated NK cells. In this study, 60 healthy people were selected randomly and their consent obtained and confounding factors such as sex, age, life-styles was matched then the count of activated NK and CD8 + cells was compared in high and normal background radiation areas inhabitants of Ramsar. After filling the questionnaire and measurement of background radiation, blood samples of 30 healthy people from each region were analyzed immediately by means of flowcytometry. The leukocytes and their subsets were not significantly different between two groups and the count of active cells was higher in control group. The result shows that the changes in immune system occur due to radiation and maybe it is as a result of higher radiosensitivity of activated cells.

  19. Stimulation with monochromatic green light during incubation alters satellite cell mitotic activity and gene expression in relation to embryonic and posthatch muscle growth of broiler chickens.

    Science.gov (United States)

    Zhang, L; Zhang, H J; Wang, J; Wu, S G; Qiao, X; Yue, H Y; Yao, J H; Qi, G H

    2014-01-01

    Previous studies showed that monochromatic green light stimuli during embryogenesis accelerated posthatch body weight (BW) and pectoral muscle growth of broilers. In this experiment, we further investigated the morphological and molecular basis of this phenomenon. Fertile broiler eggs (Arbor Acres, n=880) were pre-weighed and randomly assigned to 1 of the 2 incubation treatment groups: (1) dark condition (control group), and (2) monochromatic green light group (560 nm). The monochromatic lighting systems sourced from light-emitting diode lamps and were equalized at the intensity of 15 lx at eggshell level. The dark condition was set as a commercial control from day 1 until hatching. After hatch, 120 male 1-day-old chicks from each group were housed under incandescent white light with an intensity of 30 lx at bird-head level. No effects of light stimuli during embryogenesis on hatching time, hatchability, hatching weight and bird mortality during the feeding trial period were observed in the present study. Compared with the dark condition, the BW, pectoral muscle weight and myofiber cross-sectional areas were significantly greater on 7-day-old chicks incubated under green light. Green light also increased the satellite cell mitotic activity of pectoral muscle on 1- and 3-day-old birds. In addition, green light upregulated MyoD, myogenin and myostatin mRNA expression in late embryos and/ or newly hatched chicks. These data suggest that stimulation with monochromatic green light during incubation promote muscle growth by enhancing proliferation and differentiation of satellite cells in late embryonic and newly hatched stages. Higher expression of myostatin may ultimately help prevent excessive proliferation and differentiation of satellite cells in birds incubated under green light.

  20. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication

    DEFF Research Database (Denmark)

    Mackey, Abigail L; Rasmussen, Lotte K; Kadi, Fawzi;

    2016-01-01

    muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared...... proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch...

  1. Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons

    OpenAIRE

    Chen, Yong; Zhang, Xiaofei; Wang, Congying; Li, Guangwen; Gu, Yanping; Huang, Li-Yen Mae

    2008-01-01

    Purinergic ionotropic P2X7 receptors (P2X7Rs) are closely associated with excitotoxicity and nociception. Inhibition of P2X7R activation has been considered as a potentially useful strategy to improve recovery from spinal cord injury and reduce inflammatory damage to trauma. The physiological functions of P2X7Rs, however, are poorly understood, even though such information is essential for making the P2X7R an effective therapeutic target. We show here that P2X7Rs in satellite cells of dorsal ...

  2. Strength training increases the size of the satellite cell pool in type I and II fibres of chronically painful trapezius muscle in females

    DEFF Research Database (Denmark)

    Mackey, Abigail; Andersen, Lars L; Frandsen, Ulrik

    2011-01-01

    While strength training has been shown to be effective in mediating hypertrophy and reducing pain in trapezius myalgia, responses at the cellular level have not previously been studied. This study investigated the potential of strength training targeting the affected muscles (SST, n = 18......) and general fitness training (GFT, n = 16) to augment the satellite cell (SC) and macrophage pools in the trapezius muscles of women diagnosed with trapezius myalgia. A group receiving general health information (REF, n = 8) served as a control. Muscle biopsies were collected from the trapezius muscles...... hypertrophy (r = -0.669, P = 0.005). SST also resulted in a 74% enhancement of the trapezius macrophage content (P

  3. Rain Forest Dance Residency.

    Science.gov (United States)

    Watson, Dawn

    1997-01-01

    Outlines the author's experience as a dancer and choreographer artist-in-residence with third graders at a public elementary school, providing a cultural arts experience to tie in with a theme study of the rain forest. Details the residency and the insights she gained working with students, teachers, and theme. (SR)

  4. Residents in difficulty

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh; O'Neill, Lotte; Hansen, Dorthe Høgh;

    2016-01-01

    Background The majority of studies on prevalence and characteristics of residents in difficulty have been conducted in English-speaking countries and the existing literature may not reflect the prevalence and characteristics of residents in difficulty in other parts of the world such as the Scand......Background The majority of studies on prevalence and characteristics of residents in difficulty have been conducted in English-speaking countries and the existing literature may not reflect the prevalence and characteristics of residents in difficulty in other parts of the world...... such as the Scandinavian countries, where healthcare systems are slightly different. The aim of this study was to examine prevalence and characteristics of residents in difficulty in one out of three postgraduate medical training regions in Denmark, and to produce both a quantifiable overview and in-depth understanding...

  5. Interferon-gamma and nitric oxide synthase 2 mediate the aggregation of resident adherent peritoneal exudate cells: implications for the host response to pathogens.

    Directory of Open Access Journals (Sweden)

    Bhagawat S Chandrasekar

    Full Text Available Interferon-gamma (Ifnγ, a key macrophage activating cytokine, plays pleiotropic roles in host immunity. In this study, the ability of Ifnγ to induce the aggregation of resident mouse adherent peritoneal exudate cells (APECs, consisting primarily of macrophages, was investigated. Cell-cell interactions involve adhesion molecules and, upon addition of Ifnγ, CD11b re-localizes preferentially to the sites of interaction on APECs. A functional role of CD11b in enhancing aggregation is demonstrated using Reopro, a blocking reagent, and siRNA to Cd11b. Studies with NG-methyl-L-arginine (LNMA, an inhibitor of Nitric oxide synthase (Nos, NO donors, e.g., S-nitroso-N-acetyl-DL-penicillamine (SNAP or Diethylenetriamine/nitric oxide adduct (DETA/NO, and Nos2-/- mice identified Nitric oxide (NO induced by Ifnγ as a key regulator of aggregation of APECs. Further studies with Nos2-/- APECs revealed that some Ifnγ responses are independent of NO: induction of MHC class II and CD80. On the other hand, Nos2 derived NO is important for other functions: motility, phagocytosis, morphology and aggregation. Studies with cytoskeleton depolymerizing agents revealed that Ifnγ and NO mediate the cortical stabilization of Actin and Tubulin which contribute to aggregation of APECs. The biological relevance of aggregation of APECs was delineated using infection experiments with Salmonella Typhimurium (S. Typhimurium. APECs from orally infected, but not uninfected, mice produce high amounts of NO and aggregate upon ex vivo culture in a Nos2-dependent manner. Importantly, aggregated APECs induced by Ifnγ contain fewer intracellular S. Typhimurium compared to their single counterparts post infection. Further experiments with LNMA or Reopro revealed that both NO and CD11b are important for aggregation; in addition, NO is bactericidal. Overall, this study elucidates novel roles for Ifnγ and Nos2 in regulating Actin, Tubulin, CD11b, motility and morphology during the

  6. Uptake of synthetic naked RNA by skin-resident dendritic cells via macropinocytosis allows antigen expression and induction of T-cell responses in mice.

    Science.gov (United States)

    Selmi, Abderraouf; Vascotto, Fulvia; Kautz-Neu, Kordula; Türeci, Özlem; Sahin, Ugur; von Stebut, Esther; Diken, Mustafa; Kreiter, Sebastian

    2016-09-01

    Intradermal administration of antigen-encoding RNA has entered clinical testing for cancer vaccination. However, insight into the underlying mechanism of RNA uptake, translation and antigen presentation is still limited. Utilizing pharmacologically optimized naked RNA, the dose-response kinetics revealed a rise in reporter signal with increasing RNA amounts and a prolonged RNA translation of reporter protein up to 30 days after intradermal injection. Dendritic cells (DCs) in the dermis were shown to engulf RNA, and the signal arising from the reporter RNA was significantly diminished after DC depletion. Macropinocytosis was relevant for intradermal RNA uptake and translation in vitro and in vivo. By combining intradermal RNA vaccination and inhibition of macropinocytosis, we show that effective priming of antigen-specific CD8(+) T-cells also relies on this uptake mechanism. This report demonstrates that direct antigen translation by dermal DCs after intradermal naked RNA vaccination is relevant for efficient priming of antigen-specific T-cells.

  7. Satellite Sounder Observations of Contrasting Tropospheric Moisture Transport Regimes: Saharan Air Layers, Hadley Cells, and Atmospheric Rivers

    Energy Technology Data Exchange (ETDEWEB)

    Nalli, Nicholas R.; Barnet, Christopher D.; Reale, Tony; Liu, Quanhua; Morris, Vernon R.; Spackman, J. Ryan; Joseph, Everette; Tan, Changyi; Sun, Bomin; Tilley, Frank; Leung, L. Ruby; Wolfe, Daniel

    2016-12-01

    This paper examines the performance of satellite sounder atmospheric vertical moisture proles (AVMP) under tropospheric conditions encompassing moisture contrasts driven by convection and advection transport mechanisms, specifically Atlantic Ocean Saharan air layers (SALs) and Pacific Ocean moisture conveyer belts (MCBs) commonly referred to as atmospheric rivers (ARs), both of these being mesoscale to synoptic meteorological phenomena within the vicinity of subtropical Hadley subsidence zones. Operational AVMP environmental data records retrieved from the Suomi National Polar-orbiting Partnership (SNPP) NOAA-Unique Combined Atmospheric Processing System (NUCAPS) are collocated with dedicated radiosonde observations (RAOBs) obtained from ocean-based intensive field campaigns; these RAOBs provide uniquely independent correlative truth data not assimilated into numerical weather prediction models for satellite sounder validation over open ocean. Using these marine-based data, we empirically assess the performance of the operational NUCAPS AVMP product for detecting and resolving these tropospheric moisture features over otherwise RAOB-sparse regions.

  8. In Vitro Generation of Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature from Murine Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Jennifer Steens

    2017-04-01

    Full Text Available The vascular wall (VW serves as a niche for mesenchymal stem cells (MSCs. In general, tissue-specific stem cells differentiate mainly to the tissue type from which they derive, indicating that there is a certain code or priming within the cells as determined by the tissue of origin. Here we report the in vitro generation of VW-typical MSCs from induced pluripotent stem cells (iPSCs, based on a VW-MSC-specific gene code. Using a lentiviral vector expressing the so-called Yamanaka factors, we reprogrammed tail dermal fibroblasts from transgenic mice containing the GFP gene integrated into the Nestin-locus (NEST-iPSCs to facilitate lineage tracing after subsequent MSC differentiation. A lentiviral vector expressing a small set of recently identified human VW-MSC-specific HOX genes then induced MSC differentiation. This direct programming approach successfully mediated the generation of VW-typical MSCs with classical MSC characteristics, both in vitro and in vivo.

  9. Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport.

    Science.gov (United States)

    Ghosh, Suman; Shinogle, Heather E; Galeva, Nadezhda A; Dobrowsky, Rick T; Blagg, Brian S J

    2016-04-15

    Heat shock protein 90 (HSP90) is a molecular chaperone that is up-regulated in cancer and is required for the folding of numerous signaling proteins. Consequently, HSP90 represents an ideal target for the development of new anti-cancer agents. The human HSP90 isoform, glucose-regulated protein 94 (GRP94), resides in the endoplasmic reticulum and regulates secretory pathways, integrins, and Toll-like receptors, which contribute to regulating immunity and metastasis. However, the cellular function of GRP94 remains underinvestigated. We report that GRP94 knockdown cells are defective in intracellular transport and, consequently, negatively impact the trafficking of F-actin toward the cellular cortex, integrin α2 and integrin αL toward the cell membrane and filopodia, and secretory vesicles containing the HSP90α-AHA1-survivin complex toward the leading edge. As a result, GRP94 knockdown cells form a multipolar spindle instead of bipolar morphology and consequently manifest a defect in cell migration and adhesion.

  10. Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly.

    Science.gov (United States)

    Brzeszczyńska, Joanna; Johns, Neil; Schilb, Alain; Degen, Simone; Degen, Martin; Langen, Ramon; Schols, Annemie; Glass, David J; Roubenoff, Ronenn; Greig, Carolyn A; Jacobi, Carsten; Fearon, Kenneth Ch; Ross, James A

    2016-08-01

    Muscle wasting in old age or cancer may result from failed myofiber regeneration and/or accelerated atrophy. This study aimed to determine from transcriptomic analysis of human muscle the integrity of the cellular stress response system in relation to satellite cell differentiation or apoptosis in patients with cancer (weight-stable (CWS) or weight-losing (CWL)) or healthy elderly (HE) when compared with healthy middle-aged controls (HMA). 28 patients with cancer (CWS: 18 and CWL: 10), HE: 21 and HMA: 20 underwent biopsy of quadriceps muscle. The expression of transcription factors for muscle regeneration (Pax3, Pax7 and MyoD) was increased in CWS and HE compared with HMA (p≤0.001). In contrast, the expression of the late myogenic differentiation marker MyoG was reduced in CWS and CWL but increased in HE (p≤0.0001). Bax was significantly increased in CWS, CWL and HE (p≤0.0001). Expression of the oxidative defense genes SOD2, GCLM, and Nrf2 was decreased in CWS and CWL but increased in HE (p≤0.0001). There is evidence for blockade of satellite cell maturation, upregulation of apoptosis and reduced oxidative defense in the muscle of cancer patients. In the healthy elderly the potential for differentiation and oxidative defense is maintained.

  11. Estimating animal behaviour and residency from movement data

    DEFF Research Database (Denmark)

    Pedersen, Martin Wæver; Patterson, Toby Alexander; Thygesen, Uffe Høgsbro

    2011-01-01

    probability distribution of location and behavior at each point in time. With this, the behavioral state of the animal can be associated to regions in space, thus revealing migration corridors and residence areas. We demonstrate the inferential potential of the method by analyzing satellite-linked archival...

  12. Role of the mTORC1 complex in satellite cell activation by RNA-induced mitochondrial restoration: dual control of cyclin D1 through microRNAs.

    Science.gov (United States)

    Jash, Sukanta; Dhar, Gunjan; Ghosh, Utpalendu; Adhya, Samit

    2014-10-01

    During myogenesis, satellite stem cells (SCs) are induced to proliferate and differentiate to myogenic precursors. The role of energy sensors such as the AMP-activated protein kinase (AMPK) and the mammalian Target of Rapamycin (mTOR) in SC activation is unclear. We previously observed that upregulation of ATP through RNA-mediated mitochondrial restoration (MR) accelerates SC activation following skeletal muscle injury. We show here that during regeneration, the AMPK-CRTC2-CREB and Raptor-mTORC-4EBP1 pathways were rapidly activated. The phosho-CRTC2-CREB complex was essential for myogenesis and activated transcription of the critical cell cycle regulator cyclin D1 (Ccnd1). Knockdown (KD) of either mTORC or its subunit Raptor delayed SC activation without influencing the differentiation program. KD of 4EBP1 had no effect on SC activation but enhanced myofiber size. mTORC1 positively regulated Ccnd1 translation but destabilized Ccnd1 mRNA. These antithetical effects of mTORC1 were mediated by two microRNAs (miRs) targeted to the 3' untranslated region (UTR) of Ccnd1 mRNA: miR-1 was downregulated in mTORC-KD muscle, and depletion of miR-1 resulted in increased levels of mRNA without any effect on Ccnd1 protein. In contrast, miR-26a was upregulated upon mTORC depletion, while anti-miR-26a oligonucleotide specifically stimulated Ccnd1 protein expression. Thus, mTORC may act as a timer of satellite cell proliferation during myogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Burnout Syndrome During Residency.

    Science.gov (United States)

    Turgut, Namigar; Karacalar, Serap; Polat, Cengiz; Kıran, Özlem; Gültop, Fethi; Kalyon, Seray Türkmen; Sinoğlu, Betül; Zincirci, Mehmet; Kaya, Ender

    2016-10-01

    The aim of this study is identified the degree of Burnout Syndrome (BOS) and find out its correlation with years of recidency and sociodemograpfic chareacteristics, training, sleeping habits, such as smoking and alcohol consumption. After approval from the Hospital Ethics Committee and obtaining informed consent, First, second, third, fourth and fifth year of recidency staff (n=127) working in our hospital were involved in this study. The standardized Maslach Burnout Inventory (MBI) was used in this study. Fifty six male (44.1%) and seventy one female (55.9%) residents were enroled in this study (Coranbach Alfa(α)=0.873). 57% of the first year residents smokes cigaret and 54% of them use alcohol. 2% of them gets one day off after hospital night shift, 61% of them suffers from disturbed sleep. 60% of them had been stated that they willingly selected their profession. 61% of them prefers talking to friends and 32% of them prefers shopping to overcome stress. There were statistical difference acording to years of recidency in MBI, Emotional Burnout (EB) and desensitisation scale (DS) points. EB scale points of the second year of residency group was statisticaly higher than fourth year of residency group. DS points of second year of residency group was also statisticaly higher than the third and fourth year of residency group. There was no statistical difference between any groups in Personal Success. BOS is a frequent problem during residency in anaesthesia. Appropriate definition and awareness are the first important steps to prevent this syndrome. Further administrative approaches should be evaluated with regard to their effects.

  14. Satellite cells in slow and fast rat muscles differ in respect to acetylcholinesterase regulation mechanisms they convey to their descendant myofibers during regeneration.

    Science.gov (United States)

    Dolenc, I; Crne-Finderle, N; Erzen, I; Sketelj, J

    1994-02-01

    The hypothesis of satellite cell diversity in slow and fast mammalian muscles was tested by examining acetylcholinesterase (AChE) regulation in muscles regenerating 1) under conditions of muscle disuse (tenotomy, leg immobilization) in which the pattern of neural stimulation is changed, and 2) after cross-transplantation when the regenerating muscle develops under a foreign neural stimulation pattern. Soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were allowed to regenerate after ischemic-toxic injury either in their own sites or had been cross-transplanted to the site of the other muscle. Molecular forms of AChE in regenerating muscles were analyzed by velocity sedimentation in linear sucrose gradients. Neither tenotomy nor limb immobilization significantly affected the characteristic pattern of AChE molecular forms in regenerating SOL muscles, suggesting that the neural stimulation pattern is probably not decisive for its induction. During an early phase of regeneration, the general pattern of AChE molecular forms in the cross-transplanted regenerating muscle was predominantly determined by the type of its muscle of origin, and much less by the innervating nerve which exerted only a modest modifying effect. However, alkali-resistant myofibrillar ATPase activity on which the separation of muscle fibers into type I and type II is based, was determined predominantly by the motor nerve innervating the regenerating muscle. Mature regenerated EDL muscles (13 weeks after injury) which had been innervated by the SOL nerve became virtually indistinguishable from the SOL muscles in regard to their pattern of AChE molecular forms. However, AChE patterns of mature regenerated SOL muscles that had been innervated by the EDL nerve still displayed some features of the SOL pattern. In regard to AChE regulation, muscle satellite cells from slow or fast rat muscles convey to their descendant myotubes the information shifting their initial development in the

  15. Analysis of Resident Case Logs in an Anesthesiology Residency Program

    DEFF Research Database (Denmark)

    Yamamoto, Satoshi; Tanaka, Pedro; Madsen, Matias Vested;

    2016-01-01

    Our goal in this study was to examine Accreditation Council for Graduate Medical Education case logs for Stanford anesthesia residents graduating in 2013 (25 residents) and 2014 (26 residents). The resident with the fewest recorded patients in 2013 had 43% the number of patients compared with the...

  16. Geostationary Satellite (GOES) Images

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Visible and Infrared satellite imagery taken from radiometer instruments on SMS (ATS) and GOES satellites in geostationary orbit. These satellites produced...

  17. Reduction of exposure to blood donors in preterm infants submitted to red blood cell transfusions using pediatric satellite packs

    Directory of Open Access Journals (Sweden)

    Cristina Lika Uezima

    2013-09-01

    Full Text Available OBJECTIVE: In preterm newborn infants transfused with erythrocytes stored up to 28 days, to compare the reduction of blood donor exposure in two groups of infants classified according to birth weight. METHODS: A prospective study was conducted with preterm infants with birth weight <1000g (Group 1 and 1000-1499g (Group 2, born between April, 2008 and December, 2009. Neonates submitted to exchange transfusions, emergency erythrocyte transfusion, or those who died in the first 24 hours of life were excluded. Transfusions were indicated according to the local guideline using pediatric transfusion satellite bags. Demographic and clinical data, besides number of transfusions and donors were assessed. . Logistic regression analysis was performed to determine factors associated with multiple transfusions. RESULTS: 30 and 48 neonates were included in Groups 1 and 2, respectively. The percentage of newborns with more than one erythrocyte transfusion (90 versus 11%, the median number of transfusions (3 versus 1 and the median of blood donors (2 versus 1 were higher in Group 1 (p<0.001, compared to Group 2. Among those with multiple transfusions, 14 (82% and one (50% presented 50% reduction in the number of blood donors, respectively in Groups 1 and 2. Factors associated with multiple transfusions were: birth weight <1000g (OR 11.91; 95%CI 2.14-66.27 and presence of arterial umbilical catheter (OR 8.59; 95%CI 1.94-38.13, adjusted for confounders. CONCLUSIONS: The efficacy of pediatrics satellites bags on blood donor reduction was higher in preterm infants with birth weight <1000g.

  18. Neptune's small satellites

    Science.gov (United States)

    Thomas, P.

    1992-04-01

    The small satellites of Neptune and other planets discovered during the Voyager 2 mission are discussed in terms of their composition and relationship to the planetary systems. The satellite Proteus is described in terms of its orbit, five other satellites are described, and they are compared to ther small satellites and systems. Neptune's satellites are hypothesized to be related to the ring system, and the satellite Galatea is related to the confinement of the rings.

  19. Teaching professionalism to residents.

    Science.gov (United States)

    Klein, Eileen J; Jackson, J Craig; Kratz, Lyn; Marcuse, Edgar K; McPhillips, Heather A; Shugerman, Richard P; Watkins, Sandra; Stapleton, F Bruder

    2003-01-01

    The need to teach professionalism during residency has been affirmed by the Accreditation Council for Graduate Medical Education, which will require documentation of education and evaluation of professionalism by 2007. Recently the American Academy of Pediatrics has proposed the following components of professionalism be taught and measured: honesty/integrity, reliability/responsibility, respect for others, compassion/empathy, self-improvement, self-awareness/knowledge of limits, communication/collaboration, and altruism/advocacy. The authors describe a curriculum for introducing the above principles of professionalism into a pediatrics residency that could serve as a model for other programs. The curriculum is taught at an annual five-day retreat for interns, with 11 mandatory sessions devoted to addressing key professionalism issues. The authors also explain how the retreat is evaluated and how the retreat's topics are revisited during the residency, and discuss general issues of teaching and evaluating professionalism.

  20. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6

    DEFF Research Database (Denmark)

    Scheele, Camilla; Nielsen, Søren; Broholm, Christa

    2012-01-01

    a resistance to IL-6. By utilizing western blot analysis, we demonstrate that IL-6Rα protein was down regulated in skeletal muscle biopsies from obese persons with and without type 2 diabetes. To further investigate the status of IL-6 signaling in skeletal muscle in obesity-associated type 2 diabetes, we......Obesity and type 2 diabetes are associated with chronically elevated systemic levels of IL-6, a pro-inflammatory cytokine with a role in skeletal muscle metabolism that signals through the IL-6 receptor (IL-6Rα). We hypothesized that skeletal muscle in obesity-associated type 2 diabetes develops...... isolated satellite cells from skeletal muscle of people that were healthy (He), obese (Ob) or were obese and had type 2 diabetes (DM), and differentiated them in vitro into myocytes. Down-regulation of IL-6Rα was conserved in Ob myocytes. In addition, acute IL-6 administration for 30, 60 and 120 minutes...

  1. Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus.

    Science.gov (United States)

    Mangin, Jean-Marie; Kunze, Albrecht; Chittajallu, Ramesh; Gallo, Vittorio

    2008-07-23

    Several studies have provided evidence that NG2-expressing (NG2(+)) progenitor cells are anatomically associated to neurons in gray matter areas. By analyzing the spatial distribution of NG2(+) cells in the hilus of the mouse dentate gyrus, we demonstrate that NG2(+) cells are indeed closely associated to interneurons. To define whether this anatomical proximity reflected a specific physiological interaction, we performed patch-clamp recordings on hilar NG2(+) cells and interneurons between 3 and 21 postnatal days. We first observed that hilar NG2(+) cells exhibit spontaneous glutamatergic EPSCs (sEPSCs) whose frequency and amplitude increase during the first 3 postnatal weeks. At the same time, the rise time and decay time of sEPSCs significantly decreased, suggesting that glutamatergic synapses in NG2(+) cells undergo a maturation process that is reminiscent of what has been reported in neurons during the same time period. We also observed that hilar interneurons and associated NG2(+) cells are similarly integrated into the local network, receiving excitatory inputs from both granule cells and CA3 pyramidal neurons. By performing pair recordings, we found that bursts of activity induced by GABAergic antagonists were strongly synchronized between both cell types and that the amplitude of these bursts was positively correlated. Finally, by applying carbachol to increase EPSC activity, we observed that closely apposed cells were more likely to exhibit synchronized EPSCs than cells separated by >200 microm. The finding that NG2(+) cells are sensing patterns of activity arising in closely associated neurons suggests that NG2(+) cell function is finely regulated by the local network.

  2. Integrated bariatric surgery residency

    Directory of Open Access Journals (Sweden)

    Eltorai AE

    2014-11-01

    Full Text Available Adam EM Eltorai Warren Alpert Medical School of Brown University, RI, USA Abstract: Obesity is a major public health concern. Given its lasting efficacy for improving obesity and obesity-related diseases, bariatric surgery is an increasingly common treatment option. As the implementation of the Affordable Care Act progresses, the impending physician shortage will become more severe. Thus there will be an even greater need for doctors specialized in the management and treatment of obese patients. The development of integrated bariatric surgery residency programs could be considered and is discussed herein. Keywords: obesity, bariatric surgery, integrated residency, surgery education

  3. A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal.

    Science.gov (United States)

    Gilbert, Penney M; Corbel, Stephane; Doyonnas, Regis; Havenstrite, Karen; Magnusson, Klas E G; Blau, Helen M

    2012-04-01

    The goal of regenerative medicine is to restore form and function to damaged and aging tissues. Adult stem cells, present in tissues such as skeletal muscle, comprise a reservoir of cells with a remarkable capacity to proliferate and repair tissue damage. Muscle stem cells, known as satellite cells, reside in a quiescent state in an anatomically distinct compartment, or niche, ensheathed between the membrane of the myofiber and the basal lamina. Recently, procedures for isolating satellite cells were developed and experiments testing their function upon transplantation into muscles revealed an extraordinary potential to contribute to muscle fibers and access and replenish the satellite cell compartment. However, these properties are rapidly lost once satellite cells are plated in culture. Accordingly, elucidating the role of extrinsic factors in controlling muscle stem cell fate, in particular self-renewal, is critical. Through careful design of bioengineered culture platforms, analysis of specific proteins presented to stem cells is possible. Critical to the success of the approach is single cell analysis, as more rapidly proliferating progenitors may mask the behavior of stem cells that proliferate slowly. Bioengineering approaches provide a potent means of gaining insight into the role of extrinsic factors in the stem cell microenvironment on stem cell function and the mechanisms that control their diverse fates. Ultimately, the multidisciplinary approach presented here will lead to novel therapeutic strategies for degenerative diseases.

  4. Financial debt of orthopedic residents.

    Science.gov (United States)

    Hwang, John S; Beebe, Kathleen S; Benevenia, Joseph; Karanfilian, Briette; Berberian, Wayne S

    2012-04-01

    Many orthopedic residents accrue considerable debt by residency graduation. These debts for graduating medical students continue to increase due to the yearly increase of medical school tuition. The purpose of this study was to examine the causes of financial debt, as well the effects of debt on orthopedic residents.Orthopedic residents from postgraduate years 1 to 5 (N=27) completed an anonymous, optional financial survey. The survey asked questions regarding the characteristics of the residents' debt and their concern caused by their debt. All residents from our institute (N=27) voluntarily participated in the survey. The residents consisted of 4 (15%) women and 23 (85%) men, with 14 (56%) single residents and 12 (44%) married residents. No statistically significant difference existed in total debt >$100,000 between single and married residents or men and women. Forty-eight percent (n=13) of the residents had medical educational debt >$100,000, whereas 45% (n=12) had total debt >$200,000. Residents with total debt >$100,000 were concerned about their debt, whereas 1 of 4 residents with orthopedic residents financially and may cause stress and hinder their medical training. Appropriate measures should be taken to help residents properly manage their debt and to provide supplemental assistance with their financial struggles.

  5. Resident fatigue in otolaryngology residents: a Web based survey.

    Science.gov (United States)

    Nida, Andrew M; Googe, Benjamin J; Lewis, Andrea F; May, Warren L

    2016-01-01

    Resident fatigue has become a point of emphasis in medical education and its effects on otolaryngology residents and their patients require further study. The purpose of our study was to evaluate the prevalence and nature of fatigue in otolaryngology residents, evaluate various quality of life measures, and investigate associations of increased fatigue with resident safety. Anonymous survey. Internet based. United States allopathic otolaryngology residents. None. The survey topics included demographics, residency structure, sleep habits and perceived stress. Responses were correlated with a concurrent Epworth Sleep Scale questionnaire to evaluate effects of fatigue on resident training and quality of life. 190 residents responded to the survey with 178 completing the Epworth Sleep Scale questionnaire. Results revealed a mean Epworth Sleep Scale score of 9.9±5.1 with a median of 10.0 indicating a significant number of otolaryngology residents are excessively sleepy. Statistically significant correlations between Epworth Sleep Scale and sex, region, hours of sleep, and work hours were found. Residents taking in-house call had significantly fewer hours of sleep compared to home call (p=0.01). Residents on "head and neck" (typically consisting of a large proportion of head and neck oncologic surgery) rotations tended to have higher Epworth Sleep Scale and had significantly fewer hours of sleep (p=.003) and greater work hours (potolaryngology residents are excessively sleepy. Our data suggest that the effects of fatigue play a role in resident well-being and resident safety. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A Fine Arts Residency.

    Science.gov (United States)

    Riggs, Patricia L.

    1982-01-01

    A four-week writer-in-residence program designed to stimulate the creativity of K-5 students was held in the Briar Glen Library Media Center, Wheaton, Illinois, with poet Joan Colby. This description of the program includes information on planning, funding, and future plans. (CHC)

  7. Selection of Anesthesiology Residents.

    Science.gov (United States)

    Baker, J. David, III; And Others

    1993-01-01

    Selection data for all Medical University of South Carolina anesthesiology residency applicants (about 200 per year) and the 8 selected per year were compared for 4 years. Results showed standardized test scores, grades, and class ranks of those selected were not higher than of others, but interview and recommendation scores were higher.…

  8. Summer lodge residency

    OpenAIRE

    Morrad, Annie

    2015-01-01

    The summer lodge residency was based in Nottingham from June 29th to July 10th Each of the artists was given a studio space and technical facilities. There were discussion points and meals, a seminar day, open presentations and reflection time.

  9. Identification of miR-2400 gene as a novel regulator in skeletal muscle satellite cells proliferation by targeting MYOG gene

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei Wei [The Laboratory of Cell and Development, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China); College of Life Sciences and Agriculture & Forestry, Qiqihar University, Qiqihar, Heilongjiang 161006 (China); Tong, Hui Li; Sun, Xiao Feng; Hu, Qian; Yang, Yu; Li, Shu Feng [The Laboratory of Cell and Development, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China); Yan, Yun Qin, E-mail: yanyunqin@sohu.com [The Laboratory of Cell and Development, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China); Li, Guang Peng [The Key Laboratory of Mammal Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, Hohhot 010021 (China)

    2015-08-07

    MicroRNAs play critical roles in skeletal muscle development as well as in regulation of muscle cell proliferation and differentiation. Previous study in our laboratory showed that the expression level of miR-2400, a novel and unique miRNA from bovine, had significantly changed in skeletal muscle-derived satellite cells (MDSCs) during differentiation, however, the function and expression pattern for miR-2400 in MDSCs has not been fully understood. In this report, we firstly identified that the expression levels of miR-2400 were down-regulated during MDSCs differentiation by stem-loop RT-PCR. Over-expression and inhibition studies demonstrated that miR-2400 promoted MDSCs proliferation by EdU (5-ethynyl-2′ deoxyuridine) incorporation assay and immunofluorescence staining of Proliferating cell nuclear antigen (PCNA). Luciferase reporter assays showed that miR-2400 directly targeted the 3′ untranslated regions (UTRs) of myogenin (MYOG) mRNA. These data suggested that miR-2400 could promote MDSCs proliferation through targeting MYOG. Furthermore, we found that miR-2400, which was located within the eighth intron of the Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) gene, was down-regulated in MDSCs in a direct correlation with the WHSC1L1 transcript by Clustered regularly interspaced palindromic repeats interference (CRISPRi). In addition, these observations not only provided supporting evidence for the codependent expression of intronic miRNAs and their host genes in vitro, but also gave insight into the role of miR-2400 in MDSCs proliferation. - Highlights: • miR-2400 is a novel and unique miRNA from bovine. • miR-2400 could promote skeletal muscle satellite cells proliferation. • miR-2400 directly targeted the 3′ untranslated regions of MYOG mRNA. • miR-2400 could be coexpressed together with its host gene WHSC1L1.

  10. Resident mesenchymal progenitors of articular cartilage.

    Science.gov (United States)

    Candela, Maria Elena; Yasuhara, Rika; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2014-10-01

    Articular cartilage has poor capacity of self-renewal and repair. Insufficient number and activity of resident mesenchymal (connective tissue) progenitors is likely one of the underlying reasons. Chondroprogenitors reside not only in the superficial zone of articular cartilage but also in other zones of articular cartilage and in the neighboring tissues, including perichondrium (groove of Ranvier), synovium and fat pad. These cells may respond to injury and contribute to articular cartilage healing. In addition, marrow stromal cells can migrate through subchondral bone when articular cartilage is damaged. We should develop drugs and methods that correctly stimulate resident progenitors for improvement of repair and inhibition of degenerative changes in articular cartilage. Copyright © 2014. Published by Elsevier B.V.

  11. Global Health Simulation During Residency

    Directory of Open Access Journals (Sweden)

    Jane R. Rosenman MD

    2016-08-01

    Full Text Available Resident participation in international health electives (IHEs has been shown to be beneficial, yet not all residents have the opportunity to participate. We sought to determine whether participating in simulated global health cases, via the standardized Simulation Use for Global Away Rotations (SUGAR curriculum, was useful for all pediatric residents, not merely those planning to go on an IHE. Pediatric residents in our program took part in 2 SUGAR cases and provided feedback via an online survey. Thirty-six of 40 residents participated (90%; 72% responded to the survey. Three of 10 residents not previously planning to work in resource-limited settings indicated participation in SUGAR made them more likely to do so. Nearly all residents (88% felt SUGAR should be part of the residency curriculum. All felt better prepared for working cross-culturally. While designed to prepare trainees for work in resource-limited settings, SUGAR may be beneficial for all residents.

  12. Electric energy supply to isolated residences from the network through low power fuel cells; Fronecimento de energia eletrica a residencias isoladas da rede atraves de celulas a combustivel de baixa potencia

    Energy Technology Data Exchange (ETDEWEB)

    Serra, Eduardo Torres; Furtado, Jose Geraldo de Melo [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil)], e-mail: etserra@cepel.br, e-mail: furtado@cepel.br

    2008-07-01

    This paper discusses the technical and socio economical aspects of the utilization of fuel cells for supplying electric power to isolated residences under an analysis on the global and brazilian energy scenarios, focusing the ascertaining of the high inequality of electric energy consumption among the various regions and countries in the world and the electric power access viability for the population lesser favoured. The paper performs an energetic analysis allowing an estimate of daily average consumption of electric energy of a low income family, and also discusses an attendance alternative of this demand by using small generation unities consisting of polymeric membranes fuel cells and reformers of primary fuel. Also, the paper analyses the possibilities of using various fuels for the hydrogen production to be used in fuel cell and estimates the cost of electric energy generated as function the main parameters which characterizes the enterprise.

  13. Leadership Training in Otolaryngology Residency.

    Science.gov (United States)

    Bent, John P; Fried, Marvin P; Smith, Richard V; Hsueh, Wayne; Choi, Karen

    2017-06-01

    Although residency training offers numerous leadership opportunities, most residents are not exposed to scripted leadership instruction. To explore one program's attitudes about leadership training, a group of otolaryngology faculty (n = 14) and residents (n = 17) was polled about their attitudes. In terms of self-perception, more faculty (10 of 14, 71.4%) than residents (9 of 17, 52.9%; P = .461) considered themselves good leaders. The majority of faculty and residents (27 of 31) thought that adults could be taught leadership ability. Given attitudes about leadership ability and the potential for improvement through instruction, consideration should be given to including such training in otolaryngology residency.

  14. Resident-to-resident violence triggers in nursing homes.

    Science.gov (United States)

    Snellgrove, Susan; Beck, Cornelia; Green, Angela; McSweeney, Jean C

    2013-11-01

    Certified nurses' assistants (CNAs) employed by a rural nursing home in Northeast Arkansas described their perceptions of resident-to-resident violence in order to provide insight on factors, including unmet needs, that may trigger the phenomenon. Semistructured interviews were conducted with 11 CNAs. Data were analyzed using content analysis and constant comparison. Two categories of triggers emerged from the data-active and passive. Active triggers involved the actions of other residents that were intrusive in nature, such as wandering into a residents' personal space, taking a resident's belongings, and so forth. Passive triggers did not involve the actions of residents but related to the internal and external environment of the residents. Examples were factors such as boredom, competition for attention and communication difficulties. Results indicate that there are factors, including unmet needs within the nursing home environment that may be identified and altered to prevent violence between residents.

  15. Satellite data compression

    CERN Document Server

    Huang, Bormin

    2011-01-01

    Satellite Data Compression covers recent progress in compression techniques for multispectral, hyperspectral and ultra spectral data. A survey of recent advances in the fields of satellite communications, remote sensing and geographical information systems is included. Satellite Data Compression, contributed by leaders in this field, is the first book available on satellite data compression. It covers onboard compression methodology and hardware developments in several space agencies. Case studies are presented on recent advances in satellite data compression techniques via various prediction-

  16. Trends in communications satellites

    CERN Document Server

    Curtin, Denis J

    1979-01-01

    Trends in Communications Satellites offers a comprehensive look at trends and advances in satellite communications, including experimental ones such as NASA satellites and those jointly developed by France and Germany. The economic aspects of communications satellites are also examined. This book consists of 16 chapters and begins with a discussion on the fundamentals of electrical communications and their application to space communications, including spacecraft, earth stations, and orbit and wavelength utilization. The next section demonstrates how successful commercial satellite communicati

  17. Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

    Science.gov (United States)

    Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2016-10-01

    Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults.

  18. Ground-based diffusion experiments on liquid Sn-In systems using the shear cell technique of the satellite mission Foton-M1.

    Science.gov (United States)

    Suzuki, Shinsuke; Kraatz, Kurt-Helmut; Frohberg, Günter

    2004-11-01

    This study reported in this paper was aimed at testing the shear cell that was developed for the satellite mission Foton-M1 to measure diffusion coefficients in liquid metals under microgravity (microg)-conditions. Thick Layer diffusion experiments were performed in the system Sn90In10 versus Sn under 1 g-conditions. For this system several microg-diffusion results are available as reference data. This combination provides a low, but sufficiently stable, density layering throughout the entire experiment, which is important to avoid buoyancy-driven convection. The experimental results were corrected for the influences of the shear-induced convection and mixing after the final shearing, both of which are typical for the shear cell technique. As the result, the reproducibility and the reliability of the diffusion coefficients in the ground-based experiments were within the limits of error of microg-data. Based on our results we discuss the necessary conditions to avoid buoyancy-driven convection.

  19. The Fundamentals of Resident Dismissal.

    Science.gov (United States)

    Schenarts, Paul J; Langenfeld, Sean

    2017-02-01

    Residents have the rights and responsibilities of both students and employees. Dismissal of a resident from a training program is traumatic and has lasting repercussions for the program director, the faculty, the dismissed resident, and the residency. A review of English language literature was performed using PUBMED and OVID databases, using the search terms, resident dismissal, resident termination, student dismissal, student and resident evaluation, legal aspects of education, and remediation. The references of each publication were also reviewed to identify additional appropriate citations. If the Just Cause threshold has been met, educators have the absolute discretion to evaluate academic and clinical performance. Legal opinion has stated that it is not necessary to wait until a patient is harmed to dismiss a resident. Evaluations should be standard and robust. Negative evaluations are not defamatory as the resident gave consent to be evaluated. Provided departmental and institutional polices have been followed, a resident can be dismissed without a formal hearing. Residencies are entitled to modify academic requirements and dismissal is not considered a breach of contract. Although there is anxiety regarding resident dismissal, the courts have uniformly supported faculty having this role. When indicated, failure to dismiss a resident also places the program director and the faculty at risk for educational malpractice.

  20. Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells

    NARCIS (Netherlands)

    Arutyunyan, Anna; Stoddart, Sonia; Yi, Sun-ju; Fei, Fei; Lim, Min; Groffen, Paula; Feldhahn, Niklas; Groffen, John; Heisterkamp, Nora

    2012-01-01

    Background: Acute lymphoblastic leukemia (ALL) cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs). Results: We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the

  1. Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia

    DEFF Research Database (Denmark)

    Green, Charlotte J; Henriksen, Tora I; Pedersen, Bente K;

    2012-01-01

    Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent......, the glucose-dependency of its extra-pancreatic effects has not been examined....

  2. Lawful Permanent Residents - Annual Report

    Data.gov (United States)

    Department of Homeland Security — A lawful permanent resident (LPR) or 'green card' recipient is defined by immigration law as a person who has been granted lawful permanent residence in the United...

  3. Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

    Directory of Open Access Journals (Sweden)

    Berta Temugin

    2012-03-01

    Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

  4. Analysis of Resident Case Logs in an Anesthesiology Residency Program.

    Science.gov (United States)

    Yamamoto, Satoshi; Tanaka, Pedro; Madsen, Matias Vested; Macario, Alex

    2016-04-15

    Our goal in this study was to examine Accreditation Council for Graduate Medical Education case logs for Stanford anesthesia residents graduating in 2013 (25 residents) and 2014 (26 residents). The resident with the fewest recorded patients in 2013 had 43% the number of patients compared with the resident with the most patients, and in 2014, this equaled 48%. There were residents who had 75% more than the class average number of cases for several of the 12 case types and 3 procedure types required by the Accreditation Council for Graduate Medical Education. Also, there were residents with fewer than half as many for some of the required cases or procedure types. Some of the variability may have been because of the hazards of self-reporting.

  5. Xichang Satellite Launch Center

    Institute of Scientific and Technical Information of China (English)

    LiuJie

    2004-01-01

    Xichang Satellite Launch Center(XSLC) is mainly for geosynchronous orbit launches. The main purpose of XSLC is to launch spacecraft, such as broadcasting,communications and meteorological satellites, into geo-stationary orbit.Most of the commercial satellite launches of Long March vehicles have been from Xichang Satellite Launch Center. With 20 years' development,XSLC can launch 5 kinds of launch vehicles and send satellites into geostationary orbit and polar orbit. In the future, moon exploration satellites will also be launched from XSLC.

  6. Handbook of satellite applications

    CERN Document Server

    Madry, Scott; Camacho-Lara, Sergio

    2017-01-01

    The first edition of this ground breaking reference work was the most comprehensive reference source available about the key aspects of the satellite applications field. This updated second edition covers the technology, the markets, applications and regulations related to satellite telecommunications, broadcasting and networking—including civilian and military systems; precise satellite navigation and timing networks (i.e. GPS and others); remote sensing and meteorological satellite systems. Created under the auspices of the International Space University based in France, this brand new edition is now expanded to cover new innovative small satellite constellations, new commercial launching systems, innovation in military application satellites and their acquisition, updated appendices, a useful glossary and more.

  7. Quiescence of human muscle stem cells is favored by culture on natural biopolymeric films.

    Science.gov (United States)

    Monge, Claire; DiStasio, Nicholas; Rossi, Thomas; Sébastien, Muriel; Sakai, Hiroshi; Kalman, Benoit; Boudou, Thomas; Tajbakhsh, Shahragim; Marty, Isabelle; Bigot, Anne; Mouly, Vincent; Picart, Catherine

    2017-05-02

    Satellite cells are quiescent resident muscle stem cells that present an important potential to regenerate damaged tissue. However, this potential is diminished once they are removed from their niche environment in vivo, prohibiting the long-term study and genetic investigation of these cells. This study therefore aimed to provide a novel biomaterial platform for the in-vitro culture of human satellite cells that maintains their stem-like quiescent state, an important step for cell therapeutic studies. Human muscle satellite cells were isolated from two donors and cultured on soft biopolymeric films of controlled stiffness. Cell adhesive phenotype, maintenance of satellite cell quiescence and capacity for gene manipulation were investigated using FACS, western blotting, fluorescence microscopy and electron microscopy. About 85% of satellite cells cultured in vitro on soft biopolymer films for 3 days maintained expression of the quiescence marker Pax7, as compared with 60% on stiffer films and 50% on tissue culture plastic. The soft biopolymeric films allowed satellite cell culture for up to 6 days without renewing the media. These cells retained their stem-like properties, as evidenced by the expression of stem cell markers and reduced expression of differentiated markers. In addition, 95% of cells grown on these soft biopolymeric films were in the G0/G1 stage of the cell cycle, as opposed to those grown on plastic that became activated and began to proliferate and differentiate. Our study identifies a new biomaterial made of a biopolymer thin film for the maintenance of the quiescence state of muscle satellite cells. These cells could be activated at any point simply by replating them onto a plastic culture dish. Furthermore, these cells could be genetically manipulated by viral transduction, showing that this biomaterial may be further used for therapeutic strategies.

  8. Parameters of proliferation and apoptosis of epithelial cells in the gastric mucosa in indigenous and non-indigenous residents of Khakassia with Helicobacter pylori positive duodenal ulcer disease.

    Science.gov (United States)

    Tsukanov, V V; Shtygasheva, O V; Vasyutin, A V; Amel'chugova, O S; Butorin, N N; Ageeva, E S

    2015-02-01

    We evaluated parameters of apoptosis in the mucosa of the gastric antrum and body of indigenous and non-indigenous residents of Khakassia with duodenal ulcer disease associated with Helicobacter pylori infection. In the gastric antrum, apoptotic index was significantly increased in patients with ulcer disease in comparison with healthy individuals in both populations. The ratio of proliferation index to apoptotic index was lower in patients with ulcer disease in comparison with healthy individuals in both populations. Similar, but less pronounced processes were recorded in the body of the stomach. Significant changes in the parameters of proliferation and apoptosis were noted in the gastric antrum and body of the stomach in both populations, but they were more pronounced in Caucasians in comparison with Khakasses.

  9. Cycle life evaluation of 3 Ah Li xMn 2O 4-based lithium-ion secondary cells for low-earth-orbit satellites . I. Full cell results

    Science.gov (United States)

    Brown, Shelley; Ogawa, Keita; Kumeuchi, Youichi; Enomoto, Shinsuke; Uno, Masatoshi; Saito, Hirobumi; Sone, Yoshitsugu; Abraham, Daniel; Lindbergh, Göran

    Lithium-ion batteries are a candidate for the energy storage system onboard low-earth-orbit satellites. Cycle life performance under both orbital and terrestrial conditions must be investigated in order to evaluate any inadvertent effects due to the former and the validity of the latter, with a successful comparison allowing for the extension of terrestrial experimental matrices in order to identify the effects of ageing. The orbital performance of Li xMn 2O 4-based pouch cells onboard the microsatellite REIMEI was monitored and compared with terrestrial experiments, with the cells found to be unaffected by orbital conditions. A lifetime matrix of different cycling depths-of-discharge (DODs: 0, 20, 40%) and temperatures (25, 45 ° C) was undertaken with periodic reference performance tests. A decrease in both the cell end-of-discharge cycling voltage and capacity was accelerated by both higher temperatures and larger DODs. Impedance spectra measured for all ageing conditions indicated that the increase was small, manifested in a state-of-charge dependent increase of the high-frequency semi-circle and a noticeable increase in the high-frequency real axis intercept. An evaluation of the change of both the resistance and capacity of 3 Ah cells led to the development of a potential prognostic state-of-health indicator. The use of elevated temperatures to accelerate cell ageing was validated.

  10. Cycle life evaluation of 3 Ah Li{sub x}Mn{sub 2}O{sub 4}-based lithium-ion secondary cells for low-earth-orbit satellites. I. Full cell results

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Shelley; Lindbergh, Goeran [School of Chemical Science and Engineering, Department of Chemical Engineering and Technology, Teknikringen 42, Royal Institute of Technology, Stockholm SE-100 44 (Sweden); Ogawa, Keita [Advanced Engineering Services Co., Ltd., 1-6-1 Takezono, Tsukuba, Ibaraki 305-0032 (Japan); Kumeuchi, Youichi; Enomoto, Shinsuke [NEC-Tokin Corporation, 1120 Shimokuzawa, Sagamihara, Kanagawa 229-1198 (Japan); Uno, Masatoshi; Saito, Hirobumi; Sone, Yoshitsugu [Japan Aerospace Exploration Agency, Institute of Space and Astronautical Science, 3-1-1 Yoshinodai, Sagamihara, Kanagawa 229-8510 (Japan); Abraham, Daniel [Chemical Engineering Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States)

    2008-12-01

    Lithium-ion batteries are a candidate for the energy storage system onboard low-earth-orbit satellites. Cycle life performance under both orbital and terrestrial conditions must be investigated in order to evaluate any inadvertent effects due to the former and the validity of the latter, with a successful comparison allowing for the extension of terrestrial experimental matrices in order to identify the effects of ageing. The orbital performance of Li{sub x}Mn{sub 2}O{sub 4}-based pouch cells onboard the microsatellite REIMEI was monitored and compared with terrestrial experiments, with the cells found to be unaffected by orbital conditions. A lifetime matrix of different cycling depths-of-discharge (DODs: 0, 20, 40%) and temperatures (25, 45 C) was undertaken with periodic reference performance tests. A decrease in both the cell end-of-discharge cycling voltage and capacity was accelerated by both higher temperatures and larger DODs. Impedance spectra measured for all ageing conditions indicated that the increase was small, manifested in a state-of-charge dependent increase of the high-frequency semi-circle and a noticeable increase in the high-frequency real axis intercept. An evaluation of the change of both the resistance and capacity of 3 Ah cells led to the development of a potential prognostic state-of-health indicator. The use of elevated temperatures to accelerate cell ageing was validated. (author)

  11. Galileo satellite antenna modeling

    Science.gov (United States)

    Steigenberger, Peter; Dach, Rolf; Prange, Lars; Montenbruck, Oliver

    2015-04-01

    The space segment of the European satellite navigation system Galileo currently consists of six satellites. Four of them belong to the first generation of In-Orbit Validation (IOV) satellites whereas the other two are Full Operational Capability (FOC) satellites. High-precision geodetic applications require detailed knowledge about the actual phase center of the satellite and receiver antenna. The deviation of this actual phase center from a well-defined reference point is described by phase center offsets (PCOs) and phase center variations (PCVs). Unfortunately, no public information is available about the Galileo satellite antenna PCOs and PCVs, neither for the IOV, nor the FOC satellites. Therefore, conventional values for the IOV satellite antenna PCOs have been adopted for the Multi-GNSS experiment (MGEX) of the International GNSS Service (IGS). The effect of the PCVs is currently neglected and no PCOs for the FOC satellites are available yet. To overcome this deficiency in GNSS observation modeling, satellite antenna PCOs and PCVs are estimated for the Galileo IOV satellites based on global GNSS tracking data of the MGEX network and additional stations of the legacy IGS network. Two completely independent solutions are computed with the Bernese and Napeos software packages. The PCO and PCV values of the individual satellites are analyzed and the availability of two different solutions allows for an accuracy assessment. The FOC satellites are built by a different manufacturer and are also equipped with another type of antenna panel compared to the IOV satellites. Signal transmission of the first FOC satellite has started in December 2014 and activation of the second satellite is expected for early 2015. Based on the available observations PCO estimates and, optionally PCVs of the FOC satellites will be presented as well. Finally, the impact of the new antenna model on the precision and accuracy of the Galileo orbit determination is analyzed.

  12. [Resident foreigners in Spain].

    Science.gov (United States)

    Solana, A M; Pascual De Sans, A

    1994-01-01

    The authors review trends in the size of the resident foreign population in Spain over time since the 1940s. A continuing growth over time, with temporal fluctuations, is noted, with a rapid rise in immigration in the 1980s, leading to new legislation designed to control immigration in 1985-1986 and 1991. The authors note that Europeans, particularly from countries of the European Union, make up a large percentage of the foreign population, but that the number of immigrants from developing countries has increased significantly in the last 10 years.

  13. Artificial intelligence systems for rainy areas detection and convective cells' delineation for the south shore of Mediterranean Sea during day and nighttime using MSG satellite images

    Science.gov (United States)

    Tebbi, Mohsene Abdelfettah; Haddad, Boualem

    2016-09-01

    The aim of this study is to investigate the potential of cloud classification by means of support vector machines using high resolution images from northern Algeria. The images were taken from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) on board of the Meteosat Second Generation (MSG) satellite. An automatic system was developed to operate during both day and nighttime by following two steps of data processing. The first aims to detect rainy areas in cloud systems, whereas the second delineates convective cells from stratiform ones. A set of 12 spectral parameters was selected to extract information about cloud properties, which are different from day to night. The training and validation steps of this study were performed by in-situ rainfall measurement data, collected during the rainy season of years 2011 and 2012 via automatic rain gauge stations distributed in northern Algeria. Artificial neural networks (ANNs) and support vector machine (SVM) were explored, by combining spectral parameters derived from MSG images. Better performances were obtained by the SVM classifier, in terms of Critical Success Index and Probability of Detection for rainy areas detection (CSI = 0.81, POD = 91%), and also for convective/stratiform delineation (CSI = 0.55, POD = 74%).

  14. Satellite-Delivered Learning.

    Science.gov (United States)

    Arnall, Gail C.

    1987-01-01

    Discusses the application of satellite information delivery to training. Describes a new trend, horizontal programming. Also discusses vertical programming and in-house production of training materials. Lists vendors of satellite-based training. (CH)

  15. GPS Satellite Simulation Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The GPS satellite simulation facility consists of a GPS satellite simulator controlled by either a Silicon Graphics Origin 2000 or PC depending upon unit under test...

  16. China's Recoverable Satellites

    Institute of Scientific and Technical Information of China (English)

    Tang Boehang

    2008-01-01

    @@ By the end of 2006, China had launched 24 recoverable satellites (FSW) in total. Among them, 23 were launched successfully, of which all but one were successfully recovered. Recoverable satellites launched by China are listed in Table 1.

  17. Satellite Tags- Hawaii EEZ

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Satellite tagging was implemented in 2013. Satellite tagging is conducted using a Dan Inject air rifle and deployment arrows designed by Wildlife Computers. Two...

  18. Satellite communication engineering

    CERN Document Server

    Kolawole, Michael Olorunfunmi

    2013-01-01

    An undeniably rich and thorough guide to satellite communication engineering, Satellite Communication Engineering, Second Edition presents the fundamentals of information communications systems in a simple and succinct way. This book considers both the engineering aspects of satellite systems as well as the practical issues in the broad field of information transmission. Implementing concepts developed on an intuitive, physical basis and utilizing a combination of applications and performance curves, this book starts off with a progressive foundation in satellite technology, and then moves on

  19. Platelet satellitism in infectious disease?

    Science.gov (United States)

    Laskaj, Renata; Sikiric, Dubravka; Skerk, Visnja

    2015-01-01

    Background Platelet satellitism is a phenomenon of unknown etiology of aggregating platelets around polymorphonuclear neutrophils and other blood cells which causes pseudothrombocytopenia, visible by microscopic examination of blood smears. It has been observed so far in about a hundred cases in the world. Case subject and methods Our case involves a 73-year-old female patient with a urinary infection. Biochemical serum analysis (CRP, glucose, AST, ALT, ALP, GGT, bilirubin, sodium, potassium, chloride, urea, creatinine) and blood cell count were performed with standard methods on autoanalyzers. Serum protein fractions were examined by electrophoresis and urinalysis with standard methods on autoanalyzer together with microscopic examination of urine sediment. Erythrocyte sedimentation rate, blood culture and urine culture tests were performed with standard methods. Results Due to typical pathological values for bacterial urinary infection, the patient was admitted to the hospital. Blood smear examination revealed phenomenon, which has persisted for three weeks after the disease has been cured. Blood smears with EDTA as an anticoagulant had platelet satellitism whereas the phenomenon was not observed in tubes with different anticoagulants (Na, Li-heparin) and capillary blood. Discussion We hypothesize that satellitism was induced by some immunological mechanism through formation of antibodies which have mediated platelets binding to neutrophil membranes and vice versa. Unfortunately we were unable to determine the putative trigger for this phenomenon. To our knowledge this is the second case of platelet satellitism ever described in Croatia. PMID:26110042

  20. Taiyuan Satellite Launch Center

    Institute of Scientific and Technical Information of China (English)

    LiuJie

    2004-01-01

    There are three major space launch bases in China, the Jiuquan Satellite Launch Center,the Taiyuan Satellite Launch Center and the Xichang Satellite Launch Center. All the three launch centers are located in sparsely populated areas where the terrain is even and the field of vision is broad. Security, transport conditions and the influence of the axial rotation