The Skeletal Muscle Satellite Cell

Science.gov (United States)

2011-01-01

The skeletal muscle satellite cell was first described and named based on its anatomic location between the myofiber plasma and basement membranes. In 1961, two independent studies by Alexander Mauro and Bernard Katz provided the first electron microscopic descriptions of satellite cells in frog and rat muscles. These cells were soon detected in other vertebrates and acquired candidacy as the source of myogenic cells needed for myofiber growth and repair throughout life. Cultures of isolated myofibers and, subsequently, transplantation of single myofibers demonstrated that satellite cells were myogenic progenitors. More recently, satellite cells were redefined as myogenic stem cells given their ability to self-renew in addition to producing differentiated progeny. Identification of distinctively expressed molecular markers, in particular Pax7, has facilitated detection of satellite cells using light microscopy. Notwithstanding the remarkable progress made since the discovery of satellite cells, researchers have looked for alternative cells with myogenic capacity that can potentially be used for whole body cell-based therapy of skeletal muscle. Yet, new studies show that inducible ablation of satellite cells in adult muscle impairs myofiber regeneration. Thus, on the 50th anniversary since its discovery, the satellite cell’s indispensable role in muscle repair has been reaffirmed. PMID:22147605

Muscle satellite cell heterogeneity and self-renewal

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Motohashi, Norio; Asakura, Atsushi

2014-01-01

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. PMID:25364710

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.

Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche

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Masahiko Yamaguchi

2015-10-01

Full Text Available Calcitonin receptor (Calcr is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]. To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.

Donor Satellite Cell Engraftment is Significantly Augmented When the Host Niche is Preserved and Endogenous Satellite Cells are Incapacitated

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Boldrin, Luisa; Neal, Alice; Zammit, Peter S; Muntoni, Francesco; Morgan, Jennifer E

2012-01-01

Stem cell transplantation is already in clinical practice for certain genetic diseases and is a promising therapy for dystrophic muscle. We used the mdx mouse model of Duchenne muscular dystrophy to investigate the effect of the host satellite cell niche on the contribution of donor muscle stem cells (satellite cells) to muscle regeneration. We found that incapacitation of the host satellite cells and preservation of the muscle niche promote donor satellite cell contribution to muscle regeneration and functional reconstitution of the satellite cell compartment. But, if the host niche is not promptly refilled, or is filled by competent host satellite cells, it becomes nonfunctional and donor engraftment is negligible. Application of this regimen to aged host muscles also promotes efficient regeneration from aged donor satellite cells. In contrast, if the niche is destroyed, yet host satellite cells remain proliferation-competent, donor-derived engraftment is trivial. Thus preservation of the satellite cell niche, concomitant with functional impairment of the majority of satellite cells within dystrophic human muscles, may improve the efficiency of stem cell therapy. Stem Cells2012;30:1971–1984 PMID:22730231

Satellite Cells and the Muscle Stem Cell Niche

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Yin, Hang; Price, Feodor

2013-01-01

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

SCS3 and YFT2 link transcription of phospholipid biosynthetic genes to ER stress and the UPR.

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Robyn D Moir

2012-08-01

Full Text Available The ability to store nutrients in lipid droplets (LDs is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT proteins are conserved ER-resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the ancient ortholog of the FIT gene family first identified in mammals has two homologs in Saccharomyces cerevisiae (SCS3 and YFT2 and other fungi of the Saccharomycotina lineage. Despite the coevolution of these genes for more than 170 million years and their divergence from higher eukaryotes, SCS3, YFT2, and the human FIT2 gene retain some common functions: expression of the yeast genes in a human embryonic kidney cell line promotes LD formation, and expression of human FIT2 in yeast rescues the inositol auxotrophy and chemical and genetic phenotypes of strains lacking SCS3. To better understand the function of SCS3 and YFT2, we investigated the chemical sensitivities of strains deleted for either or both genes and identified synthetic genetic interactions against the viable yeast gene-deletion collection. We show that SCS3 and YFT2 have shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid metabolism, vesicular trafficking, transcription of phospholipid biosynthetic genes, and protein synthesis. The genetic data indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates these processes. Part of this mechanism involves a role for SCS3 in communicating changes in the ER (e.g. due to low inositol to Opi1-regulated transcription of phospholipid biosynthetic genes. We conclude that SCS3 and YFT2 are required for normal ER membrane biosynthesis in response to perturbations in lipid metabolism and ER

Striking similarity in the gene expression levels of individual Myc module members among ESCs, EpiSCs, and partial iPSCs.

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Masataka Hirasaki

Full Text Available Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs. Epiblast stem cells (EpiSCs are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties.

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.

Satellite cells in human skeletal muscle plasticity

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Tim eSnijders

2015-10-01

Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. 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/remodelling 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/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

Satellite cells in human skeletal muscle plasticity.

Science.gov (United States)

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.

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs: An Achievement of Significant Morphological, Numerical and Functional Recovery.

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Tetsuro Tamaki

Full Text Available Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34 and CD34-/45-/29+ (Sk-DN/29+ cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells were also observed. A significant tetanic tension recovery (over 90% of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon and functional (80% vs. 60% in tetanus recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks of recovery was observed in both groups with the expression of key factors (mRNA and protein levels, suggesting the paracrine effects to angiogenesis. These results suggested that the

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

Science.gov (United States)

Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk-SCs

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.

Regulation of Satellite Cell Function in Sarcopenia

Science.gov (United States)

Alway, Stephen E.; Myers, Matthew J.; Mohamed, Junaith S.

2014-01-01

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. PMID:25295003

Spinal Cord Stimulation (SCS) with Anatomically Guided (3D) Neural Targeting Shows Superior Chronic Axial Low Back Pain Relief Compared to Traditional SCS-LUMINA Study.

Science.gov (United States)

Veizi, Elias; Hayek, Salim M; North, James; Brent Chafin, T; Yearwood, Thomas L; Raso, Louis; Frey, Robert; Cairns, Kevin; Berg, Anthony; Brendel, John; Haider, Nameer; McCarty, Matthew; Vucetic, Henry; Sherman, Alden; Chen, Lilly; Mekel-Bobrov, Nitzan

2017-08-01

The aim of this study was to determine whether spinal cord stimulation (SCS) using 3D neural targeting provided sustained overall and low back pain relief in a broad routine clinical practice population. This was a multicenter, open-label observational study with an observational arm and retrospective analysis of a matched cohort. After IPG implantation, programming was done using a patient-specific, model-based algorithm to adjust for lead position (3D neural targeting) or previous generation software (traditional). Demographics, medical histories, SCS parameters, pain locations, pain intensities, disabilities, and safety data were collected for all patients. A total of 213 patients using 3D neural targeting were included, with a trial-to-implant ratio of 86%. Patients used seven different lead configurations, with 62% receiving 24 to 32 contacts, and a broad range of stimulation parameters utilizing a mean of 14.3 (±6.1) contacts. At 24 months postimplant, pain intensity decreased significantly from baseline (ΔNRS = 4.2, N = 169, P  pain subgroup (ΔNRS = 5.3, N = 91, P  low back pain also decreased significantly from baseline to 24 months (ΔNRS = 4.1, N = 70, P  pain responder rates of 51% (traditional SCS) and 74% (neural targeting SCS) and axial low back pain responder rates of 41% and 71% in the traditional SCS and neural targeting SCS cohorts, respectively. Lastly, complications occurred in a total of 33 of the 213 patients, with a 1.6% lead replacement rate and a 1.6% explant rate. Our results suggest that 3D neural targeting SCS and its associated hardware flexibility provide effective treatment for both chronic leg and chronic axial low back pain that is significantly superior to traditional SCS. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Localization of Cortical Oscillations Induced by SCS Using Coherence

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P. Sovka

2007-12-01

Full Text Available This paper suggests a method based on coherence analysis and scalp mapping of coherence suitable for more accurate localization of cortical oscillations induced by electric stimulation of the dorsal spinal cord (SCS, which were previously detected using spectral analysis. While power spectral density shows the increase of power during SCS only at small number of electrodes, coherence extends this area and sharpens its boundary simultaneously. Parameters of the method were experimentally optimized to maximize its reliability. SCS is applied to suppress chronic, intractable pain by patients, whom pharmacotherapy does not relieve. In our study, the pain developed in lower back and lower extremity as the result of unsuccessful vertebral discotomy, which is called failed-back surgery syndrome (FBSS. Our method replicated the results of previous analysis using PSD and extended them with more accurate localization of the area influenced by SCS.

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.

Pervasive satellite cell contribution to uninjured adult muscle fibers.

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Pawlikowski, Bradley; Pulliam, Crystal; Betta, Nicole Dalla; Kardon, Gabrielle; Olwin, Bradley B

2015-01-01

Adult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem cells. Although resident muscle stem cells or satellite cells are required for muscle growth and repair, in uninjured muscle, these cells appear quiescent and metabolically inactive. To investigate the satellite cell contribution to myofibers in adult uninjured skeletal muscle, we labeled satellite cells by inducing a recombination of LSL-tdTomato in Pax7(CreER) mice and scoring tdTomato+ myofibers as an indicator of satellite cell fusion. Satellite cell fusion into myofibers plateaus postnatally between 8 and 12 weeks of age, reaching a steady state in hindlimb muscles, but in extra ocular or diaphragm muscles, satellite cell fusion is maintained at postnatal levels irrespective of the age assayed. Upon recombination and following a 2-week chase in 6-month-old mice, tdTomato-labeled satellite cells fused into myofibers as 20, 50, and 80 % of hindlimb, extra ocular, and diaphragm myofibers, respectively, were tdTomato+. Satellite cells contribute to uninjured myofibers either following a cell division or directly without an intervening cell division. The frequency of satellite cell fusion into the skeletal muscle fibers is greater than previously estimated, suggesting an important functional role for satellite cell fusion into adult myofibers and a requirement for active maintenance of satellite cell numbers in uninjured skeletal muscle.

Plasticity of the Muscle Stem Cell Microenvironment.

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Dinulovic, Ivana; Furrer, Regula; Handschin, Christoph

2017-01-01

Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes.

Beyond the SCS curve number: A new stochastic spatial runoff approach

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Bartlett, M. S., Jr.; Parolari, A.; McDonnell, J.; Porporato, A. M.

2015-12-01

The Soil Conservation Service curve number (SCS-CN) method is the standard approach in practice for predicting a storm event runoff response. It is popular because its low parametric complexity and ease of use. However, the SCS-CN method does not describe the spatial variability of runoff and is restricted to certain geographic regions and land use types. Here we present a general theory for extending the SCS-CN method. Our new theory accommodates different event based models derived from alternative rainfall-runoff mechanisms or distributions of watershed variables, which are the basis of different semi-distributed models such as VIC, PDM, and TOPMODEL. We introduce a parsimonious but flexible description where runoff is initiated by a pure threshold, i.e., saturation excess, that is complemented by fill and spill runoff behavior from areas of partial saturation. To facilitate event based runoff prediction, we derive simple equations for the fraction of the runoff source areas, the probability density function (PDF) describing runoff variability, and the corresponding average runoff value (a runoff curve analogous to the SCS-CN). The benefit of the theory is that it unites the SCS-CN method, VIC, PDM, and TOPMODEL as the same model type but with different assumptions for the spatial distribution of variables and the runoff mechanism. The new multiple runoff mechanism description for the SCS-CN enables runoff prediction in geographic regions and site runoff types previously misrepresented by the traditional SCS-CN method. In addition, we show that the VIC, PDM, and TOPMODEL runoff curves may be more suitable than the SCS-CN for different conditions. Lastly, we explore predictions of sediment and nutrient transport by applying the PDF describing runoff variability within our new framework.

Social Conduct Scale (SCS: a psychometric investigation

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Caroline Tozzi Reppold

2016-01-01

Full Text Available Abstract The social conduct of an individual comprises all the interpersonal behaviors that he or she exhibits in the social contexts he or she is exposed to. The Social Conduct Scale (SCS is a self-report instrument developed to provide researchers and clinicians with information on prosocial, antisocial and oppositional-defiant tendencies of Portuguese-speaking children and adolescents. In the present study, we conducted an analysis of the criterion validity of the SCS by comparing the scores obtained from a large population-based sample (N= 1,172 against an offender (N= 129, a scholar (N= 31, and a clinic-referred (N= 24 sample of adolescents with marked previous conduct problems. As expected, antisocial youths had significantly higher means on antisocial behaviors and lower means on prosocial tendencies when compared to the population-based sample. Overall, findings supported the hypothesized criterion validity of the SCS. The instrument might play a role as a helpful resource for researchers, clinicians and practitioners interested in assessing the social conduct of Brazilian children and adolescents.

FOXO3 Promotes Quiescence in Adult Muscle Stem Cells during the Process of Self-Renewal

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Suchitra D. Gopinath

2014-04-01

Full Text Available Skeletal muscle stem cells, or “satellite cells” (SCs, are required for the regeneration of damaged muscle tissue. Although SCs self-renew during regeneration, the mechanisms that govern SC re-entry into quiescence remain elusive. We show that FOXO3, a member of the forkhead family of transcription factors, is expressed in quiescent SCs (QSCs. Conditional deletion of Foxo3 in QSCs impairs self-renewal and increases the propensity of SCs to adopt a differentiated fate. Transcriptional analysis of SCs lacking FOXO3 revealed a downregulation of Notch signaling, a key regulator of SC quiescence. Conversely, overexpression of Notch intracellular domain (NICD rescued the self-renewal deficit of FOXO3-deficient SCs. We show that FOXO3 regulates NOTCH1 and NOTCH3 receptor expression and that decreasing expression of NOTCH1 and NOTCH3 receptors phenocopies the effect of FOXO3 deficiency in SCs. We demonstrate that FOXO3, perhaps by activating Notch signaling, promotes the quiescent state during SC self-renewal in adult muscle regeneration.

Distribution of myogenic progenitor cells and myonuclei is altered in women with vs. those without chronically painful trapezius muscle

DEFF Research Database (Denmark)

Mackey, Abigail; Andersen, Lars L; Frandsen, Ulrik

2010-01-01

It is hypothesized that repeated recruitment of low-threshold motor units is an underlying cause of chronic pain in trapezius myalgia. This study investigated the distribution of satellite cells (SCs), myonuclei, and macrophages in muscle biopsies from the trapezius muscle of 42 women performing...... repetitive manual work, diagnosed with trapezius myalgia (MYA; 44 ± 8 yr; mean ± SD) and 20 matched healthy controls (CON; 45 ± 9 yr). Our hypothesis was that muscle of MYA, in particular type I fibers, would demonstrate higher numbers of SCs, myonuclei, and macrophages compared with CON. SCs were identified...... was not in line with our hypothesis and suggests that the elevated SC content of MYA was not due to heightened inflammatory cell contents, but rather to provide new myonuclei. The findings of greater numbers of SCs in type I fibers of muscle subjected to repeated low-intensity work support our hypothesis...

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.

SCS-CN based time-distributed sediment yield model

Science.gov (United States)

Tyagi, J. V.; Mishra, S. K.; Singh, Ranvir; Singh, V. P.

2008-05-01

SummaryA sediment yield model is developed to estimate the temporal rates of sediment yield from rainfall events on natural watersheds. The model utilizes the SCS-CN based infiltration model for computation of rainfall-excess rate, and the SCS-CN-inspired proportionality concept for computation of sediment-excess. For computation of sedimentographs, the sediment-excess is routed to the watershed outlet using a single linear reservoir technique. Analytical development of the model shows the ratio of the potential maximum erosion (A) to the potential maximum retention (S) of the SCS-CN method is constant for a watershed. The model is calibrated and validated on a number of events using the data of seven watersheds from India and the USA. Representative values of the A/S ratio computed for the watersheds from calibration are used for the validation of the model. The encouraging results of the proposed simple four parameter model exhibit its potential in field application.

"Known Unknowns": Current Questions in Muscle Satellite Cell Biology.

Science.gov (United States)

Cornelison, Ddw

2018-01-01

Our understanding of satellite cells, now known to be the obligate stem cells of skeletal muscle, has increased dramatically in recent years due to the introduction of new molecular, genetic, and technical resources. In addition to their role in acute repair of damaged muscle, satellite cells are of interest in the fields of aging, exercise, neuromuscular disease, and stem cell therapy, and all of these applications have driven a dramatic increase in our understanding of the activity and potential of satellite cells. However, many fundamental questions of satellite cell biology remain to be answered, including their emergence as a specific lineage, the degree and significance of heterogeneity within the satellite cell population, the roles of their interactions with other resident and infiltrating cell types during homeostasis and regeneration, and the relative roles of intrinsic vs extrinsic factors that may contribute to satellite cell dysfunction in the context of aging or disease. This review will address the current state of these open questions in satellite cell biology. © 2018 Elsevier Inc. All rights reserved.

Regional Calibration of SCS-CN L-THIA Model: Application for Ungauged Basins

OpenAIRE

Jeon, Ji-Hong; Lim, Kyoung; Engel, Bernard

2014-01-01

Estimating surface runoff for ungauged watershed is an important issue. The Soil Conservation Service Curve Number (SCS-CN) method developed from long-term experimental data is widely used to estimate surface runoff from gaged or ungauged watersheds. Many modelers have used the documented SCS-CN parameters without calibration, sometimes resulting in significant errors in estimating surface runoff. Several methods for regionalization of SCS-CN parameters were evaluated. The regionalization met...

Leucocytes, cytokines and satellite cells

DEFF Research Database (Denmark)

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

2012-01-01

uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes......-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...... 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...

A numerical analysis on thermal stratification phenomenon in the SCS piping

International Nuclear Information System (INIS)

Kim, Kwang Chu; Park, Man Heung; Youm, Hag Ki; Lee, Sun Ki; Kim, Tae Ryong

2003-01-01

A numerical study is performed to estimate on an unsteady thermal stratification phenomenon in the Shutdown Cooling System(SCS) piping branched off the Reactor Coolant System(RCS) piping of Nuclear Power Plant. In the results, turbulent penetration reaches to the 1 st isolation valve. At 500sec, the maximum temperature difference between top and bottom inner wall in piping is observed at the starting point of horizontal piping passing elbow. The temperature of coolant in the rear side of the 1 st isolation valve disk is very slowly increased and the inflection point in temperature difference curve for time is observed at 2700sec. At the beginning of turbulent penetration from RCS piping, the fast inflow generates the higher temperature for the inner wall than the outer wall in the SCS piping. In the case the hot-leg injection piping and the drain piping are connected to the SCS piping, the effect of thermal stratification in the SCS piping is decreased due to an increase of heat loss compared with no connection case. The hot-leg injection piping affected by turbulent penetration from the SCS piping has a severe temperature difference that exceeds criterion temperature stated in reference. But the drain piping located in the rear compared with the hot-leg injection piping shows a tiny temperature difference. In a viewpoint of designer, for the purpose of decreasing the thermal stratification effect, it is necessary to increase the length of vertical piping in the SCS piping, and to move the position of the hot-leg injection piping backward

TAK1 modulates satellite stem cell homeostasis and skeletal muscle repair

Science.gov (United States)

Ogura, Yuji; Hindi, Sajedah M.; Sato, Shuichi; Xiong, Guangyan; Akira, Shizuo; Kumar, Ashok

2015-01-01

Satellite cells are resident adult stem cells that are required for regeneration of skeletal muscle. However, signalling mechanisms that regulate satellite cell function are less understood. Here we demonstrate that transforming growth factor-β-activated kinase 1 (TAK1) is important in satellite stem cell homeostasis and function. Inactivation of TAK1 in satellite cells inhibits muscle regeneration in adult mice. TAK1 is essential for satellite cell proliferation and its inactivation causes precocious differentiation. Moreover, TAK1-deficient satellite cells exhibit increased oxidative stress and undergo spontaneous cell death, primarily through necroptosis. TAK1 is required for the activation of NF-κB and JNK in satellite cells. Forced activation of NF-κB improves survival and proliferation of TAK1-deficient satellite cells. Furthermore, TAK1-mediated activation of JNK is essential to prevent oxidative stress and precocious differentiation of satellite cells. Collectively, our study suggests that TAK1 is required for maintaining the pool of satellite stem cells and for regenerative myogenesis. PMID:26648529

Application of GIS-based SCS-CN method in West Bank catchments, Palestine

OpenAIRE

Sameer Shadeed; Mohammad Almasri

2010-01-01

Among the most basic challenges of hydrology are the prediction and quantification of catchment surface runoff. The runoff curve number (CN) is a key factor in determining runoff in the SCS (Soil Conservation Service) based hydrologic modeling method. The traditional SCS-CN method for calculating the composite curve number is very tedious and consumes a major portion of the hydrologic modeling time. Therefore, geographic information systems (GIS) are now being used in combination with the SCS...

Isolation, Culture, Functional Assays, and Immunofluorescence of Myofiber-Associated Satellite Cells.

Science.gov (United States)

Vogler, Thomas O; Gadek, Katherine E; Cadwallader, Adam B; Elston, Tiffany L; Olwin, Bradley B

2016-01-01

Adult skeletal muscle stem cells, termed satellite cells, regenerate and repair the functional contractile cells in adult skeletal muscle called myofibers. Satellite cells reside in a niche between the basal lamina and sarcolemma of myofibers. Isolating single myofibers and their associated satellite cells provides a culture system that partially mimics the in vivo environment. We describe methods for isolating and culturing intact individual myofibers and their associated satellite cells from the mouse extensor digitorum longus muscle. Following dissection and isolation of individual myofibers we provide protocols for myofiber transplantation, satellite cell transfection, immune detection of satellite cell antigens, and assays to examine satellite cell self-renewal and proliferation.

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

Tissue-specific stem cells: Lessons from the skeletal muscle satellite cell

Science.gov (United States)

Brack, Andrew S.; Rando, Thomas A.

2012-01-01

In 1961, the satellite cell was first identified when electron microscopic examination of skeletal muscle demonstrated a cell wedged between the plasma membrane of the muscle fiber and the basement membrane. In recent years it has been conclusively demonstrated that the satellite cell is the primary cellular source for muscle regeneration and is equipped with the potential to self renew, thus functioning as a bone fide skeletal muscle stem cell (MuSC). As we move past the 50th anniversary of the satellite cell, we take this opportunity to discuss the current state of the art and dissect the unknowns in the MuSC field. PMID:22560074

Application of GIS-based SCS-CN method in West Bank catchments, Palestine

Directory of Open Access Journals (Sweden)

Sameer Shadeed

2010-03-01

Full Text Available Among the most basic challenges of hydrology are the prediction and quantification of catchment surface runoff. The runoff curve number (CN is a key factor in determining runoff in the SCS (Soil Conservation Service based hydrologic modeling method. The traditional SCS-CN method for calculating the composite curve number is very tedious and consumes a major portion of the hydrologic modeling time. Therefore, geographic information systems (GIS are now being used in combination with the SCS-CN method. This paper assesses the modeling of flow in West Bank catchments using the GIS-based SCS-CN method. The West Bank, Palestine, is characterized as an arid to semi-arid region with annual rainfall depths ranging between 100 mm in the vicinity of the Jordan River to 700 mm in the mountains extending across the central parts of the region. The estimated composite curve number for the entire West Bank is about 50 assuming dry conditions. This paper clearly demonstrates that the integration of GIS with the SCS-CN method provides a powerful tool for estimating runoff volumes in West Bank catchments, representing arid to semi-arid catchments of Palestine.

Protein Availability and Satellite Cell Dynamics in Skeletal Muscle.

Science.gov (United States)

Shamim, Baubak; Hawley, John A; Camera, Donny M

2018-06-01

Human skeletal muscle satellite cells are activated in response to both resistance and endurance exercise. It was initially proposed that satellite cell proliferation and differentiation were only required to support resistance exercise-induced hypertrophy. However, satellite cells may also play a role in muscle fibre remodelling after endurance-based exercise and extracellular matrix regulation. Given the importance of dietary protein, particularly branched chain amino acids, in supporting myofibrillar and mitochondrial adaptations to both resistance and endurance-based training, a greater understanding of how protein intake impacts satellite cell activity would provide further insight into the mechanisms governing skeletal muscle remodelling with exercise. While many studies have investigated the capacity for protein ingestion to increase post-exercise rates of muscle protein synthesis, few investigations have examined the role for protein ingestion to modulate satellite cell activity. Here we review the molecular mechanisms controlling the activation of satellite cells in response to mechanical stress and protein intake in both in vitro and in vivo models. We provide a mechanistic framework that describes how protein ingestion may enhance satellite activity and promote exercise adaptations in human skeletal muscle.

SLUDGE PARTICLE SEPAPATION EFFICIENCIES DURING SETTLER TANK RETRIEVAL INTO SCS-CON-230

Energy Technology Data Exchange (ETDEWEB)

DEARING JI; EPSTEIN M; PLYS MG

2009-07-16

The purpose of this document is to release, into the Hanford Document Control System, FA1/0991, Sludge Particle Separation Efficiencies for the Rectangular SCS-CON-230 Container, by M. Epstein and M. G. Plys, Fauske & Associates, LLC, June 2009. The Sludge Treatment Project (STP) will retrieve sludge from the 105-K West Integrated Water Treatment System (IWTS) Settler Tanks and transfer it to container SCS-CON-230 using the Settler Tank Retrieval System (STRS). The sludge will enter the container through two distributors. The container will have a filtration system that is designed to minimize the overflow of sludge fines from the container to the basin. FAI/09-91 was performed to quantify the effect of the STRS on sludge distribution inside of and overflow out of SCS-CON-230. Selected results of the analysis and a system description are discussed. The principal result of the analysis is that the STRS filtration system reduces the overflow of sludge from SCS-CON-230 to the basin by roughly a factor of 10. Some turbidity can be expected in the center bay where the container is located. The exact amount of overflow and subsequent turbidity is dependent on the density of the sludge (which will vary with location in the Settler Tanks) and the thermal gradient between the SCS-CON-230 and the basin. Attachment A presents the full analytical results. These results are applicable specifically to SCS-CON-230 and the STRS filtration system's expected operating duty cycles.

Muscle Satellite Cell Protein Teneurin‐4 Regulates Differentiation During Muscle Regeneration

Science.gov (United States)

Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So‐ichiro; Okano, Hideyuki; Takeda, Shin'ichi

2015-01-01

Abstract Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin‐4 (Ten‐4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten‐4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten‐4‐deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten‐4‐deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten‐4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten‐4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. Stem Cells 2015;33:3017–3027 PMID:26013034

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.

Mechanical Researches on Young's Modulus of SCS Nanostructures

Directory of Open Access Journals (Sweden)

Qinhua Jin

2009-01-01

Full Text Available Nanostructures of SingleCrystalSilicon (SCS with superior electrical, mechanical, thermal, and optical properties are emerging in the development of novel nanodevices. Mechanical properties especially Young's modulus are essential in developing and utilizing such nanodevices. In this paper, experimental researches including bending tests, resonance tests, and tensile tests on Young' s modulus of nanoscaled SCS are reviewed, and their results are compared. It was found that the values of E measured by different testing methods cannot match to each other. As the differences cannot be explained as experimental errors, it should be understood by taking surface effect into account. With a simplified model, we qualitatively explained the difference in E value measured by tensile test and by resonance test for Si nanobeams.

Sox2 promotes survival of satellite glial cells in vitro

International Nuclear Information System (INIS)

Koike, Taro; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

2015-01-01

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

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.

Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation During Muscle Regeneration.

Science.gov (United States)

Ishii, Kana; Suzuki, Nobuharu; Mabuchi, Yo; Ito, Naoki; Kikura, Naomi; Fukada, So-Ichiro; Okano, Hideyuki; Takeda, Shin'ichi; Akazawa, Chihiro

2015-10-01

Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin-4 (Ten-4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular functions remain unknown. We therefore aimed to elucidate the function of Ten-4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten-4-deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Furthermore, we found an accelerated activation of satellite cells in the regenerated Ten-4-deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten-4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten-4 functions as a crucial player in maintaining the quiescence of muscle satellite cells. © 2015 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Engineered matrices for skeletal muscle satellite cell engraftment and function.

Science.gov (United States)

Han, Woojin M; Jang, Young C; García, Andrés J

2017-07-01

Regeneration of traumatically injured skeletal muscles is severely limited. Moreover, the regenerative capacity of skeletal muscle declines with aging, further exacerbating the problem. Recent evidence supports that delivery of muscle satellite cells to the injured muscles enhances muscle regeneration and reverses features of aging, including reduction in muscle mass and regenerative capacity. However, direct delivery of satellite cells presents a challenge at a translational level due to inflammation and donor cell death, motivating the need to develop engineered matrices for muscle satellite cell delivery. This review will highlight important aspects of satellite cell and their niche biology in the context of muscle regeneration, and examine recent progresses in the development of engineered cell delivery matrices designed for skeletal muscle regeneration. Understanding the interactions of muscle satellite cells and their niche in both native and engineered systems is crucial to developing muscle pathology-specific cell- and biomaterial-based therapies. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Transient HIF2A inhibition promotes satellite cell proliferation and muscle regeneration.

Science.gov (United States)

Xie, Liwei; Yin, Amelia; Nichenko, Anna S; Beedle, Aaron M; Call, Jarrod A; Yin, Hang

2018-03-13

The remarkable regeneration capability of skeletal muscle depends on coordinated proliferation and differentiation of satellite cells. The self-renewal of satellite cells is critical for long-term maintenance of muscle regeneration potential. Hypoxia profoundly affects the proliferation, differentiation, and self-renewal of cultured myoblasts. However, the physiological relevance of hypoxia and hypoxia signaling in satellite cells in vivo remains largely unknown. Here, we report that satellite cells are in an intrinsic hypoxic state in vivo and express hypoxia-inducible factor 2A (HIF2A). HIF2A promotes the stemness and long-term homeostatic maintenance of satellite cells by maintaining the quiescence, increasing the self-renewal and blocking the myogenic differentiation of satellite cells. HIF2A stabilization in satellite cells cultured under normoxia augmented their engraftment potential in regenerative muscle. Reversely, HIF2A ablation led to the depletion of satellite cells and the consequent regenerative failure in the long-term. In contrast, transient pharmacological inhibition of HIF2A accelerated muscle regeneration by increasing satellite cell proliferation and differentiation. Mechanistically, HIF2A induces the quiescence/self-renewal of satellite cells by binding the promoter of Spry1 gene and activating Spry1 expression. These findings suggest that HIF2A is a pivotal mediator of hypoxia signaling in satellite cells and may be therapeutically targeted to improve muscle regeneration.

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

2017-12-01

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.

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

Energy Technology Data Exchange (ETDEWEB)

Takahara, Kiyoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Asahi, Michio [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Azuma, Haruhito [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan)

2014-04-18

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

International Nuclear Information System (INIS)

Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

2014-01-01

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa

Inducible satellite cell depletion attenuates skeletal muscle regrowth following a scald-burn injury.

Science.gov (United States)

Finnerty, Celeste C; McKenna, Colleen F; Cambias, Lauren A; Brightwell, Camille R; Prasai, Anesh; Wang, Ye; El Ayadi, Amina; Herndon, David N; Suman, Oscar E; Fry, Christopher S

2017-11-01

Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors. Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7 CreER -DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2'-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P satellite cells in the aetiology of lean

Mobilisation of satellite cells following ischaemia and reperfusion in ...

African Journals Online (AJOL)

Enrique

inar is not disturbed, and migration to adjacent myofibres using tissue bridges ... or in group 2, the novel observation of the satellite cell breaking away ... satellite cells of group 1 were significantly longer than the group 2 cells .... Statistical analysis was by unpaired t-test with Welch's cor- ... or fully motile, interfibre myoblasts.

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

Science.gov (United States)

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.

Myostatin signals through Pax7 to regulate satellite cell self-renewal

International Nuclear Information System (INIS)

McFarlane, Craig; Hennebry, Alex; Thomas, Mark; Plummer, Erin; Ling, Nicholas; Sharma, Mridula; Kambadur, Ravi

2008-01-01

Myostatin, a Transforming Growth Factor-beta (TGF-β) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells

Recapitulation of Extracellular LAMININ Environment Maintains Stemness of Satellite Cells In Vitro.

Science.gov (United States)

Ishii, Kana; Sakurai, Hidetoshi; Suzuki, Nobuharu; Mabuchi, Yo; Sekiya, Ichiro; Sekiguchi, Kiyotoshi; Akazawa, Chihiro

2018-02-13

Satellite cells function as precursor cells in mature skeletal muscle homeostasis and regeneration. In healthy tissue, these cells are maintained in a state of quiescence by a microenvironment formed by myofibers and basement membrane in which LAMININs (LMs) form a major component. In the present study, we evaluated the satellite cell microenvironment in vivo and found that these cells are encapsulated by LMα2-5. We sought to recapitulate this satellite cell niche in vitro by culturing satellite cells in the presence of recombinant LM-E8 fragments. We show that treatment with LM-E8 promotes proliferation of satellite cells in an undifferentiated state, through reduced phosphorylation of JNK and p38. On transplantation into injured muscle tissue, satellite cells cultured with LM-E8 promoted the regeneration of skeletal muscle. These findings represent an efficient method of culturing satellite cells for use in transplantation through the recapitulation of the satellite cell niche using recombinant LM-E8 fragments. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

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Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

2012-01-01

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. PMID:22662253

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

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...... 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 ... the placebo group (p whey group increased SCs/myonuclei from 4 % [2; 5] to 10 % [4; 16] (p 

RFID - based Staff Control System (SCS) in Kazakhstan

Science.gov (United States)

Saparkhojayev, N.

2015-06-01

RFID - based Staff Control System (SCS) will allow complete hands-free access control, monitoring the whereabouts of employee and record the attendance of the employee as well. Moreover, with a help of this system, it is possible to have a nice report at the end of the month and based on the total number of worked hours, the salary will be allocated to each personnel. The access tag can be read up to 10 centimeters from the RFID reader. The proposed system is based on UHF RFID readers, supported with antennas at gate and transaction sections, and employee identification cards containing RFID-transponders which are able to electronically store information that can be read / written even without the physical contact with the help of radio medium. This system is an innovative system, which describes the benefits of applying RFID- technology in the Education System process of Republic of Kazakhstan. This paper presents the experiments conducted to set up RFID based SCS.

RFID - based Staff Control System (SCS) in Kazakhstan

International Nuclear Information System (INIS)

Saparkhojayev, N

2015-01-01

RFID - based Staff Control System (SCS) will allow complete hands-free access control, monitoring the whereabouts of employee and record the attendance of the employee as well. Moreover, with a help of this system, it is possible to have a nice report at the end of the month and based on the total number of worked hours, the salary will be allocated to each personnel. The access tag can be read up to 10 centimeters from the RFID reader. The proposed system is based on UHF RFID readers, supported with antennas at gate and transaction sections, and employee identification cards containing RFID-transponders which are able to electronically store information that can be read / written even without the physical contact with the help of radio medium. This system is an innovative system, which describes the benefits of applying RFID- technology in the Education System process of Republic of Kazakhstan. This paper presents the experiments conducted to set up RFID based SCS. (paper)

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

Science.gov (United States)

Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J

2017-06-01

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

Seismic, satellite, and site observations of internal solitary waves in the NE South China Sea.

Science.gov (United States)

Tang, Qunshu; Wang, Caixia; Wang, Dongxiao; Pawlowicz, Rich

2014-06-20

Internal solitary waves (ISWs) in the NE South China Sea (SCS) are tidally generated at the Luzon Strait. Their propagation, evolution, and dissipation processes involve numerous issues still poorly understood. Here, a novel method of seismic oceanography capable of capturing oceanic finescale structures is used to study ISWs in the slope region of the NE SCS. Near-simultaneous observations of two ISWs were acquired using seismic and satellite imaging, and water column measurements. The vertical and horizontal length scales of the seismic observed ISWs are around 50 m and 1-2 km, respectively. Wave phase speeds calculated from seismic observations, satellite images, and water column data are consistent with each other. Observed waveforms and vertical velocities also correspond well with those estimated using KdV theory. These results suggest that the seismic method, a new option to oceanographers, can be further applied to resolve other important issues related to ISWs.

Field calibration and modification of scs design equation for predicting length of border under local conditions

International Nuclear Information System (INIS)

Choudhary, M.R.; Mustafa, U.S.

2009-01-01

Field tests were conducted to calibrate the existing SCS design equation in determining field border length using field data of different field lengths during 2nd and 3rd irrigations under local conditions. A single ring infiltrometer was used to estimate the water movement into and through the irrigated soil profile and in estimating the coefficients of Kostiakov infiltration function. Measurements of the unit discharge and time of advance were carried out during different irrigations on wheat irrigated fields having clay loam soil. The collected field data were used to calibrate the existing SCS design equation developed by USDA for testing its validity under local field conditions. SCS equation was modified further to improve its applicability. Results from the study revealed that the Kostiakov model over predicted the coefficients, which in turn overestimated the water advance length for boarder in the selected field using existing SCS design equation. However, the calibrated SCS design equation after parametric modification produced more satisfactory results encouraging the scientists to make its use at larger scale. (author)

The SCS double hydrometer test in dispersive soil identification

CSIR Research Space (South Africa)

Maharaj, A

2013-09-01

Full Text Available The standard testing procedures for the Soil Conservation Service (SCS) Double Hydrometer test, the Pinhole Test, Crumb test and chemical analyses for the identification of potentially dispersive soils have recently been studied and problems...

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.

2014-01-01

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.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

Pluripotent Stem Cells for Schwann Cell Engineering

NARCIS (Netherlands)

Ma, Ming-San; Boddeke, Erik; Copray, Sjef

Tissue engineering of Schwann cells (SCs) can serve a number of purposes, such as in vitro SC-related disease modeling, treatment of peripheral nerve diseases or peripheral nerve injury, and, potentially, treatment of CNS diseases. SCs can be generated from autologous stem cells in vitro by

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.

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.

Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

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Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

2016-01-01

The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

Comparison of Satellite-Derived Phytoplankton Size Classes Using In-Situ Measurements in the South China Sea

Directory of Open Access Journals (Sweden)

Shuibo Hu

2018-03-01

Full Text Available Ocean colour remote sensing is used as a tool to detect phytoplankton size classes (PSCs. In this study, the Medium Resolution Imaging Spectrometer (MERIS, Moderate Resolution Imaging Spectroradiometer (MODIS, and Sea-viewing Wide Field-of-view Sensor (SeaWiFS phytoplankton size classes (PSCs products were compared with in-situ High Performance Liquid Chromatography (HPLC data for the South China Sea (SCS, collected from August 2006 to September 2011. Four algorithms were evaluated to determine their ability to detect three phytoplankton size classes. Chlorophyll-a (Chl-a and absorption spectra of phytoplankton (aph(λ were also measured to help understand PSC’s algorithm performance. Results show that the three abundance-based approaches performed better than the inherent optical property (IOP-based approach in the SCS. The size detection of microplankton and picoplankton was generally better than that of nanoplankton. A three-component model was recommended to produce maps of surface PSCs in the SCS. For the IOP-based approach, satellite retrievals of inherent optical properties and the PSCs algorithm both have impacts on inversion accuracy. However, for abundance-based approaches, the selection of the PSCs algorithm seems to be more critical, owing to low uncertainty in satellite Chl-a input data

Myostatin Suppression of Akirin1 Mediates Glucocorticoid-Induced Satellite Cell Dysfunction

Science.gov (United States)

Dong, Yanjun; Pan, Jenny S.; Zhang, Liping

2013-01-01

Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex) suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production. PMID:23516508

Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.

Directory of Open Access Journals (Sweden)

Yanjun Dong

Full Text Available Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production.

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

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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. © 2013 FEBS.

Does an NSAID a Day Keep Satellite Cells at Bay?

DEFF Research Database (Denmark)

Mackey, Abigail L

2013-01-01

the activity of satellite cells, the muscle stem cell responsible for repair and maintenance of skeletal muscle. The signaling pathways that are potentially modified by NSAID exposure are also considered. Growth factors as well as inflammatory cells and connective tissue appear to be key factors......, although this clearly requires further study. The long-term implications for the muscle of the apparent inhibitory effect of NSAIDs on satellite cells in younger individuals are not clear and it is possible these may first become apparent with chronic use in athletes training at a high level...... or with advancing age. Reports of the potential for NSAIDs to alter prostaglandin and growth factor signalling provide a basis for further study of the mechanism of NSAID action on satellite cells....

Response of Turkey Muscle Satellite Cells to Thermal Challenge. II. Transcriptome Effects in Differentiating Cells

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Kent M. Reed

2017-11-01

Full Text Available Background: Exposure of poultry to extreme temperatures during the critical period of post-hatch growth can seriously affect muscle development and thus compromise subsequent meat quality. This study was designed to characterize transcriptional changes induced in turkey muscle satellite cells by thermal challenge during differentiation. Our goal is to better define how thermal stress alters breast muscle ultrastructure and subsequent development.Results: Skeletal muscle satellite cells previously isolated from the Pectoralis major muscle of 7-wk-old male turkeys (Meleagris gallopavo from two breeding lines: the F-line (16 wk body weight-selected and RBC2 (randombred control line were used in this study. Cultured cells were induced to differentiate at 38°C (control or thermal challenge temperatures of 33 or 43°C. After 48 h of differentiation, cells were harvested and total RNA was isolated for RNAseq analysis. Analysis of 39.9 Gb of sequence found 89% mapped to the turkey genome (UMD5.0, annotation 101 with average expression of 18,917 genes per library. In the cultured satellite cells, slow/cardiac muscle isoforms are generally present in greater abundance than fast skeletal isoforms. Statistically significant differences in gene expression were observed among treatments and between turkey lines, with a greater number of genes affected in the F-line cells following cold treatment whereas more differentially expressed (DE genes were observed in the RBC2 cells following heat treatment. Many of the most significant pathways involved signaling, consistent with ongoing cellular differentiation. Regulation of Ca2+ homeostasis appears to be significantly affected by temperature treatment, particularly cold treatment.Conclusions: Satellite cell differentiation is directly influenced by temperature at the level of gene transcription with greater effects attributed to selection for fast growth. At lower temperature, muscle-associated genes in the

Evaluation of SCS-CN method using a fully distributed physically based coupled surface-subsurface flow model

Science.gov (United States)

Shokri, Ali

2017-04-01

The hydrological cycle contains a wide range of linked surface and subsurface flow processes. In spite of natural connections between surface water and groundwater, historically, these processes have been studied separately. The current trend in hydrological distributed physically based model development is to combine distributed surface water models with distributed subsurface flow models. This combination results in a better estimation of the temporal and spatial variability of the interaction between surface and subsurface flow. On the other hand, simple lumped models such as the Soil Conservation Service Curve Number (SCS-CN) are still quite common because of their simplicity. In spite of the popularity of the SCS-CN method, there have always been concerns about the ambiguity of the SCS-CN method in explaining physical mechanism of rainfall-runoff processes. The aim of this study is to minimize these ambiguity by establishing a method to find an equivalence of the SCS-CN solution to the DrainFlow model, which is a fully distributed physically based coupled surface-subsurface flow model. In this paper, two hypothetical v-catchment tests are designed and the direct runoff from a storm event are calculated by both SCS-CN and DrainFlow models. To find a comparable solution to runoff prediction through the SCS-CN and DrainFlow, the variance between runoff predictions by the two models are minimized by changing Curve Number (CN) and initial abstraction (Ia) values. Results of this study have led to a set of lumped model parameters (CN and Ia) for each catchment that is comparable to a set of physically based parameters including hydraulic conductivity, Manning roughness coefficient, ground surface slope, and specific storage. Considering the lack of physical interpretation in CN and Ia is often argued as a weakness of SCS-CN method, the novel method in this paper gives a physical explanation to CN and Ia.

Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

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Deanna Gigliotti

Full Text Available Rotator-cuff injury (RCI is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known.Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS and control (ipsilateral deltoid muscles biopsied from participants with RCI (N = 27. Biopsies were prepared for explant culture (to study satellite cell activity, immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ subunit of acetylcholine receptor (γ-AchR. Principal component analysis (PCA for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli.Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs

Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

Science.gov (United States)

Gigliotti, Deanna; Leiter, Jeff R S; MacDonald, Peter B; Peeler, Jason; Anderson, Judy E

Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ) subunit of acetylcholine receptor (γ-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli. Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest

Muscle satellite cells are activated after exercise to exhaustion in Thoroughbred horses.

Science.gov (United States)

Kawai, M; Aida, H; Hiraga, A; Miyata, H

2013-07-01

Although satellite cells are well known as muscle stem cells capable of adding myonuclei during muscle repair and hypertrophy, the response of satellite cells in horse muscles to a run to exhaustion is still unknown. To investigate the time course of satellite cell activation in Thoroughbred horse muscle after running to exhaustion. We hypothesised that this type of intense exercise would induce satellite cell activation in skeletal muscle similar to a resistance exercise. Nine de-trained Thoroughbred horses (6 geldings and 3 mares) aged 3-6 years were studied. Biopsy samples were taken from the gluteus medius muscle of the horses before and 1 min, 3 h, 1 day, 3 days, 1 week and 2 weeks after a treadmill run to exhaustion. The numbers of satellite cells for each fibre type were determined by using immunofluorescence staining. Total RNA was extracted from these samples, and the expressions of interleukin (IL)-6, paired box transcriptional factor (Pax) 7, myogenic differentiation 1 (MyoD), myogenin, proliferating cell nuclear antigen (PCNA), insulin-like growth factor (IGF)-I and hepatocyte growth factor (HGF) mRNA were analysed using real-time reverse transcription-PCR. The numbers of satellite cells were significantly increased in type I and IIa fibres at 1 week and in type IIa/x fibre at 2 weeks post exercise. The expression of IL-6 mRNA increased significantly by 3 h post exercise. The expression of PCNA mRNA also increased by 1 day after running, indicating that running can initiate satellite cell proliferation. The expression of Pax7, MyoD, myogenin, IGF-I and HGF mRNA peaked at 1 week post exercise. Satellite cell activation and proliferation could be enhanced after a run to exhaustion without detectable injury as assessed by the histochemical analysis. Understanding the response of satellite cell activation to running exercise provides fundamental information about the skeletal muscle adaptation in Thoroughbred horses. © 2012 EVJ Ltd.

Seismic, satellite, and site observations of internal solitary waves in the NE South China Sea

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Tang, Qunshu; Wang, Caixia; Wang, Dongxiao; Pawlowicz, Rich

2014-01-01

Internal solitary waves (ISWs) in the NE South China Sea (SCS) are tidally generated at the Luzon Strait. Their propagation, evolution, and dissipation processes involve numerous issues still poorly understood. Here, a novel method of seismic oceanography capable of capturing oceanic finescale structures is used to study ISWs in the slope region of the NE SCS. Near-simultaneous observations of two ISWs were acquired using seismic and satellite imaging, and water column measurements. The vertical and horizontal length scales of the seismic observed ISWs are around 50 m and 1–2 km, respectively. Wave phase speeds calculated from seismic observations, satellite images, and water column data are consistent with each other. Observed waveforms and vertical velocities also correspond well with those estimated using KdV theory. These results suggest that the seismic method, a new option to oceanographers, can be further applied to resolve other important issues related to ISWs. PMID:24948180

A quantitative system for discriminating induced pluripotent stem cells, embryonic stem cells and somatic cells.

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Anyou Wang

Full Text Available Induced pluripotent stem cells (iPSCs derived from somatic cells (SCs and embryonic stem cells (ESCs provide promising resources for regenerative medicine and medical research, leading to a daily identification of new cell lines. However, an efficient system to discriminate the different types of cell lines is lacking. Here, we develop a quantitative system to discriminate the three cell types, iPSCs, ESCs, and SCs. The system consists of DNA-methylation biomarkers and mathematical models, including an artificial neural network and support vector machines. All biomarkers were unbiasedly selected by calculating an eigengene score derived from analysis of genome-wide DNA methylations. With 30 biomarkers, or even with as few as 3 top biomarkers, this system can discriminate SCs from pluripotent cells (PCs, including ESCs and iPSCs with almost 100% accuracy. With approximately 100 biomarkers, the system can distinguish ESCs from iPSCs with an accuracy of 95%. This robust system performs precisely with raw data without normalization as well as with converted data in which the continuous methylation levels are accounted. Strikingly, this system can even accurately predict new samples generated from different microarray platforms and the next-generation sequencing. The subtypes of cells, such as female and male iPSCs and fetal and adult SCs, can also be discriminated with this method. Thus, this novel quantitative system works as an accurate framework for discriminating the three cell types, iPSCs, ESCs, and SCs. This strategy also supports the notion that DNA-methylation generally varies among the three cell types.

Beyond the SCS-CN method: A theoretical framework for spatially lumped rainfall-runoff response

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Bartlett, M. S.; Parolari, A. J.; McDonnell, J. J.; Porporato, A.

2016-06-01

Since its introduction in 1954, the Soil Conservation Service curve number (SCS-CN) method has become the standard tool, in practice, for estimating an event-based rainfall-runoff response. However, because of its empirical origins, the SCS-CN method is restricted to certain geographic regions and land use types. Moreover, it does not describe the spatial variability of runoff. To move beyond these limitations, we present a new theoretical framework for spatially lumped, event-based rainfall-runoff modeling. In this framework, we describe the spatially lumped runoff model as a point description of runoff that is upscaled to a watershed area based on probability distributions that are representative of watershed heterogeneities. The framework accommodates different runoff concepts and distributions of heterogeneities, and in doing so, it provides an implicit spatial description of runoff variability. Heterogeneity in storage capacity and soil moisture are the basis for upscaling a point runoff response and linking ecohydrological processes to runoff modeling. For the framework, we consider two different runoff responses for fractions of the watershed area: "prethreshold" and "threshold-excess" runoff. These occur before and after infiltration exceeds a storage capacity threshold. Our application of the framework results in a new model (called SCS-CNx) that extends the SCS-CN method with the prethreshold and threshold-excess runoff mechanisms and an implicit spatial description of runoff. We show proof of concept in four forested watersheds and further that the resulting model may better represent geographic regions and site types that previously have been beyond the scope of the traditional SCS-CN method.

A Novel View of the Adult Stem Cell Compartment From the Perspective of a Quiescent Population of Very Small Embryonic-Like Stem Cells.

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Ratajczak, Mariusz Z; Ratajczak, Janina; Suszynska, Malwina; Miller, Donald M; Kucia, Magda; Shin, Dong-Myung

2017-01-06

Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed SCs (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs, epiblast SCs, and primordial germ cells suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review, we will critically discuss all these questions and the concept that small dormant SCs related to migratory primordial germ cells, described as very small embryonic-like SCs, are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue-committed SCs and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human very small embryonic-like SC in chemically defined media free from feeder-layer cells open up new and exciting possibilities for their application in regenerative medicine. © 2017 American Heart Association, Inc.

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

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

International Nuclear Information System (INIS)

Nagata, Yosuke; Ohashi, Kazuya; Wada, Eiji; Yuasa, Yuki; Shiozuka, Masataka; Nonomura, Yoshiaki; Matsuda, Ryoichi

2014-01-01

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

The muscle stem cell niche : regulation of satellite cells during regeneration

NARCIS (Netherlands)

Boonen, K.J.M.; Post, M.J.

2008-01-01

Satellite cells are considered to be adult skeletal muscle stem cells. Their ability to regenerate large muscle defects is highly dependent on their specific niche. When these cells are cultured in vitro, the loss of this niche leads to a loss of proliferative capacity and defective regeneration

Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

Science.gov (United States)

Yang, Ruifeng; Zheng, Ying; Burrows, Michelle; Liu, Shujing; Wei, Zhi; Nace, Arben; Guo, Wei; Kumar, Suresh; Cotsarelis, George; Xu, Xiaowei

2014-01-01

Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.

Improved Algorithm of SCS-CN Model Parameters in Typical Inland River Basin in Central Asia

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Wang, Jin J.; Ding, Jian L.; Zhang, Zhe; Chen, Wen Q.

2017-02-01

Rainfall-runoff relationship is the most important factor for hydrological structures, social and economic development on the background of global warmer, especially in arid regions. The aim of this paper is find the suitable method to simulate the runoff in arid area. The Soil Conservation Service Curve Number (SCS-CN) is the most popular and widely applied model for direct runoff estimation. In this paper, we will focus on Wen-quan Basin in source regions of Boertala River. It is a typical valley of inland in Central Asia. First time to use the 16m resolution remote sensing image about high-definition earth observation satellite “Gaofen-1” to provide a high degree accuracy data for land use classification determine the curve number. Use surface temperature/vegetation index (TS/VI) construct 2D scatter plot combine with the soil moisture absorption balance principle calculate the moisture-holding capacity of soil. Using original and parameter algorithm improved SCS-CN model respectively to simulation the runoff. The simulation results show that the improved model is better than original model. Both of them in calibration and validation periods Nash-Sutcliffe efficiency were 0.79, 0.71 and 0.66,038. And relative error were3%, 12% and 17%, 27%. It shows that the simulation accuracy should be further improved and using remote sensing information technology to improve the basic geographic data for the hydrological model has the following advantages: 1) Remote sensing data having a planar characteristic, comprehensive and representative. 2) To get around the bottleneck about lack of data, provide reference to simulation the runoff in similar basin conditions and data-lacking regions.

Regional Calibration of SCS-CN L-THIA Model: Application for Ungauged Basins

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Ji-Hong Jeon

2014-05-01

Full Text Available Estimating surface runoff for ungauged watershed is an important issue. The Soil Conservation Service Curve Number (SCS-CN method developed from long-term experimental data is widely used to estimate surface runoff from gaged or ungauged watersheds. Many modelers have used the documented SCS-CN parameters without calibration, sometimes resulting in significant errors in estimating surface runoff. Several methods for regionalization of SCS-CN parameters were evaluated. The regionalization methods include: (1 average; (2 land use area weighted average; (3 hydrologic soil group area weighted average; (4 area combined land use and hydrologic soil group weighted average; (5 spatial nearest neighbor; (6 inverse distance weighted average; and (7 global calibration method, and model performance for each method was evaluated with application to 14 watersheds located in Indiana. Eight watersheds were used for calibration and six watersheds for validation. For the validation results, the spatial nearest neighbor method provided the highest average Nash-Sutcliffe (NS value at 0.58 for six watersheds but it included the lowest NS value and variance of NS values of this method was the highest. The global calibration method provided the second highest average NS value at 0.56 with low variation of NS values. Although the spatial nearest neighbor method provided the highest average NS value, this method was not statistically different than other methods. However, the global calibration method was significantly different than other methods except the spatial nearest neighbor method. Therefore, we conclude that the global calibration method is appropriate to regionalize SCS-CN parameters for ungauged watersheds.

Storage potential of ‘SCS426 Venice’ apples under different storage technologies

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Mariuccia Schlichting de Martin

2018-04-01

Full Text Available Abstract This study aimed to evaluate the storage potential of SCS426 Venice apples under different storage technologies. Fruits were harvested in an experimental orchard located in Fraiburgo, SC and stored for up to eight and ten months in 2013 and 2014, respectively. Apples were treated or not with methylcyclopropene (1-MCP and stored under air atmosphere (AA, 0.5±0.5 °C/RH 85±5% or controlled atmosphere (CA; 1.5 kPa of O2 and 1.5 kPa of CO2 at 0.7±0.5 °C/RH of 93±3%. Fruits were evaluated every two months of storage, after one and seven days of shelf life (23 ± 0.3 °C/RH 93±3%. The storage period of ‘SCS426 Venice’ apples under AA without 1-MCP application should not extend beyond six months. Under this storage condition, fruits had higher incidence of decay, ethylene production and respiratory rates, higher skin degreening, lower flesh firmness, titratable acidity and soluble solids content than fruits stored under CA or AA with 1-MCP. ‘SCS426 Venice’ apples develop flesh browning and superficial scald after long-term storage. ‘SCS426 Venice’ apples under AA treated with 1-MCP or under CA (regardless of 1-MCP application can be stored for more than eight months, keeping flesh firmness above 14 lb and low incidence of physiological disorders even after ten months of storage.

Validity and extension of the SCS-CN method for computing infiltration and rainfall-excess rates

Science.gov (United States)

Mishra, Surendra Kumar; Singh, Vijay P.

2004-12-01

A criterion is developed for determining the validity of the Soil Conservation Service curve number (SCS-CN) method. According to this criterion, the existing SCS-CN method is found to be applicable when the potential maximum retention, S, is less than or equal to twice the total rainfall amount. The criterion is tested using published data of two watersheds. Separating the steady infiltration from capillary infiltration, the method is extended for predicting infiltration and rainfall-excess rates. The extended SCS-CN method is tested using 55 sets of laboratory infiltration data on soils varying from Plainfield sand to Yolo light clay, and the computed and observed infiltration and rainfall-excess rates are found to be in good agreement.

TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis

Science.gov (United States)

Hindi, Sajedah M.; Kumar, Ashok

2015-01-01

Satellite cells are a stem cell population within adult muscle and are responsible for myofiber regeneration upon injury. Satellite cell dysfunction has been shown to underlie the loss of skeletal muscle mass in many acquired and genetic muscle disorders. The transcription factor paired box-protein-7 (PAX7) is indispensable for supplementing the reservoir of satellite cells and driving regeneration in normal and diseased muscle. TNF receptor–associated factor 6 (TRAF6) is an adaptor protein and an E3 ubiquitin ligase that mediates the activation of multiple cell signaling pathways in a context-dependent manner. Here, we demonstrated that TRAF6-mediated signaling is critical for homeostasis of satellite cells and their function during regenerative myogenesis. Selective deletion of Traf6 in satellite cells of adult mice led to profound muscle regeneration defects and dramatically reduced levels of PAX7 and late myogenesis markers. TRAF6 was required for the activation of MAPKs ERK1/2 and JNK1/2, which in turn activated the transcription factor c-JUN, which binds the Pax7 promoter and augments Pax7 expression. Moreover, TRAF6/c-JUN signaling repressed the levels of the microRNAs miR-1 and miR-206, which promote differentiation, to maintain PAX7 levels in satellite cells. We also determined that satellite cell–specific deletion of Traf6 exaggerates the dystrophic phenotype in the mdx (a mouse model of Duchenne muscular dystrophy) mouse by blunting the regeneration of injured myofibers. Collectively, our study reveals an essential role for TRAF6 in satellite stem cell function. PMID:26619121

Response of turkey muscle satellite cells to thermal challenge. I. transcriptome effects in proliferating cells.

Science.gov (United States)

Reed, Kent M; Mendoza, Kristelle M; Abrahante, Juan E; Barnes, Natalie E; Velleman, Sandra G; Strasburg, Gale M

2017-05-06

Climate change poses a multi-dimensional threat to food and agricultural systems as a result of increased risk to animal growth, development, health, and food product quality. This study was designed to characterize transcriptional changes induced in turkey muscle satellite cells cultured under cold or hot thermal challenge to better define molecular mechanisms by which thermal stress alters breast muscle ultrastructure. Satellite cells isolated from the pectoralis major muscle of 7-weeks-old male turkeys from two breeding lines (16 weeks body weight-selected and it's randombred control) were proliferated in culture at 33 °C, 38 °C or 43 °C for 72 h. Total RNA was isolated and 12 libraries subjected to RNAseq analysis. Statistically significant differences in gene expression were observed among treatments and between turkey lines with a greater number of genes altered by cold treatment than by hot and fewer differences observed between lines than between temperatures. Pathway analysis found that cold treatment resulted in an overrepresentation of genes involved in cell signaling/signal transduction and cell communication/cell signaling as compared to control (38 °C). Heat-treated muscle satellite cells showed greater tendency towards expression of genes related to muscle system development and differentiation. This study demonstrates significant transcriptome effects on turkey skeletal muscle satellite cells exposed to thermal challenge. Additional effects on gene expression could be attributed to genetic selection for 16 weeks body weight (muscle mass). New targets are identified for further research on the differential control of satellite cell proliferation in poultry.

Skeletal Muscle Satellite Cells Are Committed to Myogenesis and Do Not Spontaneously Adopt Nonmyogenic Fates

Science.gov (United States)

Starkey, Jessica D.; Yamamoto, Masakazu; Yamamoto, Shoko; Goldhamer, David J.

2011-01-01

The developmental potential of skeletal muscle stem cells (satellite cells) remains controversial. The authors investigated satellite cell developmental potential in single fiber and clonal cultures derived from MyoDiCre/+;R26REYFP/+ muscle, in which essentially all satellite cells are permanently labeled. Approximately 60% of the clones derived from cells that co-purified with muscle fibers spontaneously underwent adipogenic differentiation. These adipocytes stained with Oil-Red-O and expressed the terminal differentiation markers, adipsin and fatty acid binding protein 4, but did not express EYFP and were therefore not of satellite cell origin. Satellite cells mutant for either MyoD or Myf-5 also maintained myogenic programming in culture and did not adopt an adipogenic fate. Incorporation of additional wash steps prior to muscle fiber plating virtually eliminated the non-myogenic cells but did not reduce the number of adherent Pax7+ satellite cells. More than half of the adipocytes observed in cultures from Tie2-Cre mice were recombined, further demonstrating a non-satellite cell origin. Under adipogenesis-inducing conditions, satellite cells accumulated cytoplasmic lipid but maintained myogenic protein expression and did not fully execute the adipogenic differentiation program, distinguishing them from adipocytes observed in muscle fiber cultures. The authors conclude that skeletal muscle satellite cells are committed to myogenesis and do not spontaneously adopt an adipogenic fate. PMID:21339173

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

Biological characteristics of human menstrual blood-derived endometrial stem cells.

Science.gov (United States)

Liu, Yanli; Niu, Rongcheng; Yang, Fen; Yan, Yan; Liang, Shengying; Sun, Yuliang; Shen, Ping; Lin, Juntang

2018-03-01

Successful isolation of human endometrial stem cells from menstrual blood, namely menstrual blood-derived endometrial stem cells (MenSCs), has provided enticing alternative seed cells for stem cell-based therapy. MenSCs are enriched in the self-regenerative tissue, endometrium, which shed along the periodic menstrual blood and thus their acquisition involves no physical invasiveness. However, the impact of the storage duration of menstrual blood prior to stem cell isolation, the age of the donor, the number of passages on the self-renewing of MenSCs, the paracrine production of biological factors in MenSCs and expression of adhesion molecules on MenSCs remain elusive. In this study, we confirmed that MenSCs reside in shedding endometrium, and documented that up to 3 days of storage at 4°C has little impact on MenSCs, while the age of the donor and the number of passages are negatively associated with proliferation capacity of MenSCs. Moreover, we found that MenSCs were actually immune-privileged and projected no risk of tumour formation. Also, we documented a lung- and liver-dominated, spleen- and kidney-involved organic distribution profile of MenSC 3 days after intravenous transfer into mice. At last, we suggested that MenSCs may have potentially therapeutic effects on diseases through paracrine effect and immunomodulation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells.

Science.gov (United States)

Tosic, Milica; Allen, Anita; Willmann, Dominica; Lepper, Christoph; Kim, Johnny; Duteil, Delphine; Schüle, Roland

2018-01-25

Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

Science.gov (United States)

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

EFFECTS OF VOLUNTARY WHEEL RUNNING ON SATELLITE CELLS IN THE RAT PLANTARIS MUSCLE

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Atsushi Kojima

2009-03-01

Full Text Available 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 differences in muscle weight or fiber area between the groups, the numbers of satellite cells and myonuclei per muscle fiber, percentage of satellite cells, and citrate synthase activity were significantly higher in the training group compared with the control group (p < 0.05. The percentage of satellite cells was also positively correlated with distance run in the training group (r = 0.61, p < 0.05. Voluntary running can induce an increase in the number of satellite cells without changing the mean fiber area in the rat plantaris muscle; this increase in satellite cell content is a function of distance run

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

Science.gov (United States)

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

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 differences in muscle weight or fiber area between the groups, the numbers of satellite cells and myonuclei per muscle fiber, percentage of satellite cells, and citrate synthase activity were significantly higher in the training group compared with the control group (p run in the training group (r = 0.61, p running can induce an increase in the number of satellite cells without changing the mean fiber area in the rat plantaris muscle; this increase in satellite cell content is a function of distance run. Key pointsThere is no study about the effect of voluntary running on satellite cells in the rat plantaris muscle.Voluntary running training causes an increase of citrate synthase activity in the rat plantaris muscle but does not affect muscle weight and mean fiber area in the rat plantaris muscle.Voluntary running can induce an increase in the number of satellite cells without hypertrophy of the rat plantaris muscle.

Topography Estimation of the Core Mantle Boundary with ScS Reverberations and Diffraction Waves

Science.gov (United States)

Hein, B. E.; Nakata, N.

2017-12-01

In this study, we use the propagation of global seismic waves to study the Core Mantle Boundary (CMB). We focus on the use of S-wave reflections at the CMB (ScS reverberations) and outer-core diffracted waves. It is difficult imaging the CMB with the ScS wave because the complexity of the structure in the near surface ( 50 km); the complex structure degrades the signal-to-noise ratio of of the ScS. To avoid estimating the structure in the crust, we rely on the concept of seismic interferometry to extract wave propagation through mantle, but not through the crust. Our approach is compute the deconvolution between the ScS (and its reverberation) and direct S waves generated by intermediate to deep earthquakes (>50 km depth). Through this deconvolution, we have the ability to filter out the direct S wave and retrieve the wave field propagating from only the hypocenter to the outer core, but not between the hypocenter to the receiver. After the deconvolution, we can isolate the CMB reflected waves from the complicated wave phenomena because of the near-surface structure. Utilizing intermediate and deep earthquakes is key since we can suppress the near-surface effect from the surface to the hypocenter of the earthquakes. The variation of such waves (e.g., travel-time perturbation and/or wavefield decorrelation) at different receivers and earthquakes provides the information of the topography of the CMB. In order to get a more detailed image of the topography of the CMB we use diffracted seismic waves such as Pdiff , Sdiff, and P'P'. By using two intermediate to deep earthquakes on a great circle path with a station we can extract the wave propagation between the two earthquakes to simplify the waveform, similar to how it is preformed using the ScS wave. We generate more illumination of the CMB by using diffracted waves rather than only using ScS reverberations. The accurate topography of CMB obtained by these deconvolution analyses may provide new insight of the

Analysis of the Runoff for Watershed Using SCS-CN Method and Geographic Information Systems

OpenAIRE

P.Sundar Kumar; Dr.M.J.Ratna Kanth Babu,; Dr. T.V.Praveen; Venkata kumar.vagolu

2010-01-01

The Soil Conservation Service Curve Number (SCS-CN) method is widely used for predicting direct runoff volume for a given rainfall event. The applicability of the SCS-CN method and the runoff generation mechanism were thoroughly analyzed in a Mediterranean experimental watershed in Hyderabad. The region is characterized by a Mediterranean semi-arid climate. A detailed land cover and soil survey using remote sensing and GIS techniques, showed that the watershed is dominated by coarse soils wit...

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

Science.gov (United States)

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.

Hedgehog-mediated paracrine interaction between hepatic stellate cells and marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Lin Nan; Tang Zhaofeng; Deng Meihai; Zhong Yuesi; Lin Jizong; Yang Xuhui; Xiang Peng; Xu Ruiyun

2008-01-01

During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis

Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

Science.gov (United States)

Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

2017-11-01

Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. J. Cell. Physiol. 232: 2964-2967, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Design of a SOFC/GT/SCs hybrid power system to supply a rural isolated microgrid

International Nuclear Information System (INIS)

Camblong, Haritza; Baudoin, Sylvain; Vechiu, Ionel; Etxeberria, Aitor

2016-01-01

Highlights: • A novel SOFC/GT/SCs HPS is connected to a rural microgrid through a 3LNPC inverter. • An operating strategy that maintains the SOFC power at its rated value is defined. • A robust digital controller that damps current oscillations is designed. • The efficiency, power quality, lifetime, and robustness of the HPS are considered. • An experimental test on an original HPS emulator validates the proposed solutions. - Abstract: The aim of this research study has been to design a Hybrid Power System (HPS) which works with biogas and whose main components are a Solid Oxide Fuel Cell (SOFC), a Gas microTurbine (GT), and a module of SuperCapacities (SCs). The HPS is the only power source of a rural isolated microgrid. Its structure, operating strategy, and controller have been designed considering the following criteria: efficiency, power quality, SOFC lifetime and robustness in stability and performance. The HPS structure includes a unique power converter, a 3-Level Neutral Point Clamped (3LNPC) inverter that connects the HPS to the AC microgrid. Regarding the selected operating strategy, it consists in regulating the SOFC power output to its rated value. Thus, the SCs and the GT must respond to the power demand variations. On the other hand, a study of the HPS shows that its dynamic behavior is not linear. Therefore, a special attention is put on designing a robust HPS controller. The control model is identified and the robust digital controller is designed using the “Tracking and Regulation with Independent Objectives” method. Simulation and experimental results show how the proposed structure, operating strategy, and controller allow ensuring a good behavior of the HPS from the point of view of the abovementioned four criteria.

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.

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

International Nuclear Information System (INIS)

Zhang, Pengpeng; Liang, Xinrong; Shan, Tizhong; Jiang, Qinyang; Deng, Changyan; Zheng, Rong; Kuang, Shihuan

2015-01-01

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 CreER and Mtor 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 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

Energetic, exergetic and economic analysis of an innovative Solar CombiSystem (SCS) producing thermal and electric energies: Application in residential and tertiary households

International Nuclear Information System (INIS)

Hazami, Majdi; Mehdaoui, Farah; Naili, Nabiha; Noro, Marco; Lazzarin, Renato; Guizani, AmenAllah

2017-01-01

Highlights: • The present work studies the potential of using innovative SCS in Tunisia. • In cold months the SCS provide about 50–75% of the total exergy provides. • The SCS produces between 70–150% of electric energy needs. • The SCS payback period (Pb) based on electric water heater was 10.2 years. • The SCS payback period (Pb) based on gas/gas town was about and 8.7 years. - Abstract: The endeavor of this paper is to study of the potential offered by the expenditure of an innovative Solar CombiSystem, SCS, used for the space heating load, the domestic hot water supply and the electric energy production. The investigation achieved in this work was based on an experimental and a simulation studies. A TRNSYS simulation program was achieved in order to evaluate the SCS monthly/annual thermal and electric performances. It was found that the proposed SCS covered between 20 and 45% of the SH energy needs by considering only solar energy. The result shows also that the SCS provided from 40 to 70% of the total DHW needs. It was also found that the SCS electric production ranged between 32 and 225 MJ/m 2 with a gain factor varying between 49 and 125%. An economic appraisal was also achieved to appraise the SCS feasibility. The results of the economic analysis show that the annual energy saved (ARE) and the payback period (Pb) based on electric water heater were respectively equal to 7618.3 kW h/year and 10.2 years. It was found that ARE and Pb based on gas/gas town were about 5825 m 3 and 8.7 years, respectively. The results of the economic analysis shows that the adoption of the SCS saves about 48% of electric energy and about 46% of gas/gas town kept back by the conventional system.

Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism

DEFF Research Database (Denmark)

Nehlin, Jan O; Just, Marlene; Rustan, Arild C

2011-01-01

Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the prolif......Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways...... number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating...... that the observed metabolic defects accompany the induction of a senescent state. The main function of SCs is regeneration and skeletal muscle-build up. Thus, the metabolic defects observed during aging of SC-derived myotubes could have a role in sarcopenia, the gradual age-related loss of muscle mass and strength....

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.......15+/-0.06; mean+/-SD) and females (from 0.11+/-0.04 to 0.13+/-0.05). These results suggest that 12 weeks of resistance training is effective in enhancing the satellite cell pool in skeletal muscle in the elderly....

High intensity training may reverse the fiber type specific decline in myogenic stem cells in multiple sclerosis patients

Directory of Open Access Journals (Sweden)

Jean eFarup

2016-05-01

Full Text Available Multiple sclerosis (MS is associated with loss of skeletal muscle mass and function. The myogenic stem cells (satellite cells – SCs are instrumental to accretion of myonuclei, but remain to be investigated in MS. The present study aimed to compare the SC and myonuclei content between MS patients (n=23 and age matched healthy controls (HC, n=18. Furthermore, the effects of 12 weeks of high intensity training on SC and myonuclei content were explored in MS. Muscle biopsies were obtained from m. Vastus Lateralis at baseline (MS+HC and following 12 weeks of training (MS only. Frozen biopsies were sectioned followed by immunohistochemical analysis for fiber type specific SCs (Pax7+, myonuclei (MN and central nuclei content and fiber cross-sectional area (fCSA using ATPase histochemistry. At baseline the SCs per fiber was lower in type II compared to type I fiber in both MS (119%, p<0.01 and HC (69%, p<0.05, whereas the SCs per fCSA was lower in type II fibers compared to type I only in MS (72%, p<0.05. No differences were observed in MN or central nuclei between MS and HC. Following training the type II fiber SCs per fiber and fCSA in MS patients increased by 165% (p<0.05 and 135% (p<0.05, respectively. Furthermore, the type II fiber MN content increased by 35% (p<0.05 following training. In conclusion, the SC content is lower in type II compared to type I fibers in both MS and HC. Furthermore, high intensity training was observed to selectively increase the SC and myonuclei content in type II fibers in MS patients.

Reduced satellite cell numbers and myogenic capacity in aging can be alleviated by endurance exercise.

Directory of Open Access Journals (Sweden)

Gabi Shefer

2010-10-01

Full Text Available Muscle regeneration depends on satellite cells, myogenic stem cells that reside on the myofiber surface. Reduced numbers and/or decreased myogenic aptitude of these cells may impede proper maintenance and contribute to the age-associated decline in muscle mass and repair capacity. Endurance exercise was shown to improve muscle performance; however, the direct impact on satellite cells in aging was not yet thoroughly determined. Here, we focused on characterizing the effect of moderate-intensity endurance exercise on satellite cell, as possible means to attenuate adverse effects of aging. Young and old rats of both genders underwent 13 weeks of treadmill-running or remained sedentary.Gastrocnemius muscles were assessed for the effect of age, gender and exercise on satellite-cell numbers and myogenic capacity. Satellite cells were identified in freshly isolated myofibers based on Pax7 immunostaining (i.e., ex-vivo. The capacity of individual myofiber-associated cells to produce myogenic progeny was determined in clonal assays (in-vitro. We show an age-associated decrease in satellite-cell numbers and in the percent of myogenic clones in old sedentary rats. Upon exercise, there was an increase in myofibers that contain higher numbers of satellite cells in both young and old rats, and an increase in the percent of myogenic clones derived from old rats. Changes at the satellite cell level in old rats were accompanied with positive effects on the lean-to-fat Gast muscle composition and on spontaneous locomotion levels. The significance of these data is that they suggest that the endurance exercise-mediated boost in both satellite numbers and myogenic properties may improve myofiber maintenance in aging.

HDAC4 regulates satellite cell proliferation and differentiation by targeting P21 and Sharp1 genes.

Science.gov (United States)

Marroncelli, Nicoletta; Bianchi, Marzia; Bertin, Marco; Consalvi, Silvia; Saccone, Valentina; De Bardi, Marco; Puri, Pier Lorenzo; Palacios, Daniela; Adamo, Sergio; Moresi, Viviana

2018-02-22

Skeletal muscle exhibits a high regenerative capacity, mainly due to the ability of satellite cells to replicate and differentiate in response to appropriate stimuli. Epigenetic control is effective at different stages of this process. It has been shown that the chromatin-remodeling factor HDAC4 is able to regulate satellite cell proliferation and commitment. However, its molecular targets are still uncovered. To explain the signaling pathways regulated by HDAC4 in satellite cells, we generated tamoxifen-inducible mice with conditional inactivation of HDAC4 in Pax7 + cells (HDAC4 KO mice). We found that the proliferation and differentiation of HDAC4 KO satellite cells were compromised, although similar amounts of satellite cells were found in mice. Moreover, we found that the inhibition of HDAC4 in satellite cells was sufficient to block the differentiation process. By RNA-sequencing analysis we identified P21 and Sharp1 as HDAC4 target genes. Reducing the expression of these target genes in HDAC4 KO satellite cells, we also defined the molecular pathways regulated by HDAC4 in the epigenetic control of satellite cell expansion and fusion.

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

Science.gov (United States)

Cheng, Cheng; Guo, Luo; Lu, Ling; Xu, Xiaochen; Zhang, ShaSha; Gao, Junyan; Waqas, Muhammad; Zhu, Chengwen; Chen, Yan; Zhang, Xiaoli; Xuan, Chuanying; Gao, Xia; Tang, Mingliang; Chen, Fangyi; Shi, Haibo; Li, Huawei; Chai, Renjie

2017-01-01

Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein-protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

Directory of Open Access Journals (Sweden)

Haibo Shi

2017-04-01

Full Text Available Cochlear supporting cells (SCs have been shown to be a promising resource for hair cell (HC regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

Science.gov (United States)

Cheng, Cheng; Guo, Luo; Lu, Ling; Xu, Xiaochen; Zhang, ShaSha; Gao, Junyan; Waqas, Muhammad; Zhu, Chengwen; Chen, Yan; Zhang, Xiaoli; Xuan, Chuanying; Gao, Xia; Tang, Mingliang; Chen, Fangyi; Shi, Haibo; Li, Huawei; Chai, Renjie

2017-01-01

Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration. PMID:28491023

A new probability density function for spatial distribution of soil water storage capacity leads to SCS curve number method

OpenAIRE

Wang, Dingbao

2018-01-01

Following the Budyko framework, soil wetting ratio (the ratio between soil wetting and precipitation) as a function of soil storage index (the ratio between soil wetting capacity and precipitation) is derived from the SCS-CN method and the VIC type of model. For the SCS-CN method, soil wetting ratio approaches one when soil storage index approaches infinity, due to the limitation of the SCS-CN method in which the initial soil moisture condition is not explicitly represented. However, for the ...

General calibration methodology for a combined Horton-SCS infiltration scheme in flash flood modeling

Science.gov (United States)

Gabellani, S.; Silvestro, F.; Rudari, R.; Boni, G.

2008-12-01

Flood forecasting undergoes a constant evolution, becoming more and more demanding about the models used for hydrologic simulations. The advantages of developing distributed or semi-distributed models have currently been made clear. Now the importance of using continuous distributed modeling emerges. A proper schematization of the infiltration process is vital to these types of models. Many popular infiltration schemes, reliable and easy to implement, are too simplistic for the development of continuous hydrologic models. On the other hand, the unavailability of detailed and descriptive information on soil properties often limits the implementation of complete infiltration schemes. In this work, a combination between the Soil Conservation Service Curve Number method (SCS-CN) and a method derived from Horton equation is proposed in order to overcome the inherent limits of the two schemes. The SCS-CN method is easily applicable on large areas, but has structural limitations. The Horton-like methods present parameters that, though measurable to a point, are difficult to achieve a reliable estimate at catchment scale. The objective of this work is to overcome these limits by proposing a calibration procedure which maintains the large applicability of the SCS-CN method as well as the continuous description of the infiltration process given by the Horton's equation suitably modified. The estimation of the parameters of the modified Horton method is carried out using a formal analogy with the SCS-CN method under specific conditions. Some applications, at catchment scale within a distributed model, are presented.

Paraquat initially damages cochlear support cells leading to anoikis-like hair cell death.

Science.gov (United States)

Zhang, Jianhui; Sun, Hong; Salvi, Richard; Ding, Dalian

2018-07-01

Paraquat (PQ), one of the most widely used herbicides, is extremely dangerous because it generates the highly toxic superoxide radical. When paraquat was applied to cochlear organotypic cultures, it not only damaged the outer hair cells (OHCs) and inner hair cells (IHCs), but also caused dislocation of the hair cell rows. We hypothesized that the dislocation arose from damage to the support cells (SCs) that anchors hair cells within the epithelium. To test this hypothesis, rat postnatal cochlear cultures were treated with PQ. Shortly after PQ treatment, the rows of OHCs separated from one another and migrated radially away from IHCs suggesting loss of cell-cell adhesion that hold the hair cells in proper alignment. Hair cells dislocation was associated with extensive loss of SCs in the organ of Corti, loss of tympanic border cells (TBCs) beneath the basilar membrane, the early appearance of superoxide staining and caspase-8 labeling in SCs below the OHCs and disintegration of E-cadherin and β-catenin in the organ of Corti. Damage to the TBCs and SCs occurred prior to loss of OHC or IHC loss suggesting a form of detachment-induced apoptosis referred to as anoikis. Copyright © 2018 Elsevier B.V. All rights reserved.

Observed travel times for Multiply-reflected ScS waves from a deep-focus earthquake

Directory of Open Access Journals (Sweden)

A. F. ESPISOSA

1966-06-01

Full Text Available Tlie deep-focus Argentinean earthquake of December 8
1962, generated multiply reflected ScS phases which were recorded very
clearly at stations of the IGY and the TJSC&GS standardized worldwide
networks and at Canadian stations. The data gathered from this earthquake
for the multiply-reflected ScS and sScS were used to construct the
travel times and to extend them to shorter epicentral distances. These
new data brought to light an error in published travel times for the 2(ScS
phase.

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

Science.gov (United States)

Murach, Kevin A; White, Sarah H; Wen, Yuan; Ho, Angel; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

2017-07-10

Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Pax7 CreER -R26R DTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p overload (p overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

Science.gov (United States)

Moriya, Nobuki; Miyazaki, Mitsunori

2018-02-14

Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo.

Science.gov (United States)

Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki; Mazda, Osam

2017-04-01

Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207-1216. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Model-based stimulation optimization for chronic pain suppression using percutaneous and surgical leads in spinal cord stimulation (SCS)

NARCIS (Netherlands)

Sankarasubramanian, V.

2013-01-01

The primary indication of SCS is chronic pain, in particular neuropathic pain. It is a highly debilitating condition, and in particular, is estimated to affect about one-fifth of the population in Europe (18% in the Netherlands). SCS, which uses electrical stimulation, is a valuable treatment for

HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration

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Hong, Peng; Chen, Kang; Huang, Bihui; Liu, Min; Cui, Miao; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Barton, Elisabeth R.; Jiang, Xian-Cheng; Siddiqui, M.A.Q.

2012-01-01

The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases. PMID:23023707

Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

Science.gov (United States)

Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

2015-11-01

Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women. Copyright © 2013 John Wiley & Sons, Ltd.

Differential properties of human ACL and MCL stem cells may be responsible for their differential healing capacity

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Fu Freddie H

2011-06-01

Full Text Available Abstract Background The human anterior cruciate ligament (hACL and medial collateral ligament (hMCL of the knee joint are frequently injured, especially in athletic settings. It has been known that, while injuries to the MCL typically heal with conservative treatment, ACL injuries usually do not heal. As adult stem cells repair injured tissues through proliferation and differentiation, we hypothesized that the hACL and hMCL contain stem cells exhibiting unique properties that could be responsible for the differential healing capacity of the two ligaments. Methods To test the above hypothesis, we derived ligament stem cells from normal hACL and hMCL samples from the same adult donors using tissue culture techniques and characterized their properties using immunocytochemistry, RT-PCR, and flow cytometry. Results We found that both hACL stem cells (hACL-SCs and hMCL stem cells (hMCL-SCs formed colonies in culture and expressed stem cell markers nucleostemin and stage-specific embryonic antigen-4 (SSEA-4. Moreover, both hACL-SCs and hMCL-SCs expressed CD surface markers for mesenchymal stem cells, including CD44 and CD90, but not those markers for vascular cells, CD31, CD34, CD45, and CD146. However, hACL-SCs differed from hMCL-SCs in that the size and number of hACL-SC colonies in culture were much smaller and grew more slowly than hMCL-SC colonies. Moreover, fewer hACL-SCs in cell colonies expressed stem cell markers STRO-1 and octamer-binding transcription factor-4 (Oct-4 than hMCL-SCs. Finally, hACL-SCs had less multi-differentiation potential than hMCL-SCs, evidenced by differing extents of adipogenesis, chondrogenesis, and osteogenesis in the respective induction media. Conclusions This study shows for the first time that hACL-SCs are intrinsically different from hMCL-SCs. We suggest that the differences in their properties contribute to the known disparity in healing capabilities between the two ligaments.

General calibration methodology for a combined Horton-SCS infiltration scheme in flash flood modeling

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S. Gabellani

2008-12-01

Full Text Available Flood forecasting undergoes a constant evolution, becoming more and more demanding about the models used for hydrologic simulations. The advantages of developing distributed or semi-distributed models have currently been made clear. Now the importance of using continuous distributed modeling emerges. A proper schematization of the infiltration process is vital to these types of models. Many popular infiltration schemes, reliable and easy to implement, are too simplistic for the development of continuous hydrologic models. On the other hand, the unavailability of detailed and descriptive information on soil properties often limits the implementation of complete infiltration schemes. In this work, a combination between the Soil Conservation Service Curve Number method (SCS-CN and a method derived from Horton equation is proposed in order to overcome the inherent limits of the two schemes. The SCS-CN method is easily applicable on large areas, but has structural limitations. The Horton-like methods present parameters that, though measurable to a point, are difficult to achieve a reliable estimate at catchment scale. The objective of this work is to overcome these limits by proposing a calibration procedure which maintains the large applicability of the SCS-CN method as well as the continuous description of the infiltration process given by the Horton's equation suitably modified. The estimation of the parameters of the modified Horton method is carried out using a formal analogy with the SCS-CN method under specific conditions. Some applications, at catchment scale within a distributed model, are presented.

E-cadherin promotes incorporation of mouse epiblast stem cells into normal development.

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Satoshi Ohtsuka

Full Text Available Mouse epiblast stem cells (mEpiSCs are pluripotent stem cells derived from epiblasts of postimplantation mouse embryos. Their pluripotency is distinct from that of mouse embryonic stem cells (mESCs in several cell biological criteria. One of the distinctions is that mEpiSCs contribute either not at all or at much lower efficiency to chimeric embryos after blastocyst injection compared to mESCs. However, here we showed that mEpiSCs can be incorporated into normal development after blastocyst injection by forced expression of the E-cadherin transgene for 2 days in culture. Using this strategy, mEpiSCs gave rise to live-born chimeras from 5% of the manipulated blastocysts. There were no obvious signs of reprogramming of mEpiSCs toward the mESC-like state during the 2 days after induction of the E-cadherin transgene, suggesting that mEpiSCs possess latent ability to integrate into the normal developmental process as its origin, epiblasts.

Surface Runoff Estimation Using SMOS Observations, Rain-gauge Measurements and Satellite Precipitation Estimations. Comparison with Model Predictions

Science.gov (United States)

Garcia Leal, Julio A.; Lopez-Baeza, Ernesto; Khodayar, Samiro; Estrela, Teodoro; Fidalgo, Arancha; Gabaldo, Onofre; Kuligowski, Robert; Herrera, Eddy

Surface runoff is defined as the amount of water that originates from precipitation, does not infiltrates due to soil saturation and therefore circulates over the surface. A good estimation of runoff is useful for the design of draining systems, structures for flood control and soil utilisation. For runoff estimation there exist different methods such as (i) rational method, (ii) isochrone method, (iii) triangular hydrograph, (iv) non-dimensional SCS hydrograph, (v) Temez hydrograph, (vi) kinematic wave model, represented by the dynamics and kinematics equations for a uniforme precipitation regime, and (vii) SCS-CN (Soil Conservation Service Curve Number) model. This work presents a way of estimating precipitation runoff through the SCS-CN model, using SMOS (Soil Moisture and Ocean Salinity) mission soil moisture observations and rain-gauge measurements, as well as satellite precipitation estimations. The area of application is the Jucar River Basin Authority area where one of the objectives is to develop the SCS-CN model in a spatial way. The results were compared to simulations performed with the 7-km COSMO-CLM (COnsortium for Small-scale MOdelling, COSMO model in CLimate Mode) model. The use of SMOS soil moisture as input to the COSMO-CLM model will certainly improve model simulations.

Validation and Variation of Upper Layer Thickness in South China Sea from Satellite Altimeter Data

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Nan-Jung Kuo

2008-06-01

Full Text Available Satellite altimeter data from 1993 to 2005 has been used to analyze the seasonal variation and the interannual variability of upper layer thickness (ULT in the South China Sea (SCS. Base on in-situ measurements, the ULT is defined as the thickness from the sea surface to the depth of 16°C isotherm which is used to validate the result derived from satellite altimeter data. In comparison with altimeter and in-situ derived ULTs yields a correlation coefficient of 0.92 with a slope of 0.95 and an intercept of 6 m. The basin averaged ULT derived from altimeter is 160 m in winter and 171 m in summer which is similar to the in-situ measurements of 159 m in winter and 175 m in summer. Both results also show similar spatial patterns. It suggests that the sea surface height data derived from satellite sensors are usable for study the variation of ULT in the semi-closed SCS. Furthermore, we also use satellite derived ULT to detect the development of eddy. Interannual variability of two meso-scale cyclonic eddies and one anticyclonic eddy are strongly influenced by El Niño events. In most cases, there are highly positive correlations between ULT and sea surface temperature except the periods of El Niño. During the onset of El Niño event, ULT is deeper when sea surface temperature is lower.

Catchment area-based evaluation of the AMC-dependent SCS-CN-based rainfall-runoff models

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Mishra, S. K.; Jain, M. K.; Pandey, R. P.; Singh, V. P.

2005-09-01

Using a large set of rainfall-runoff data from 234 watersheds in the USA, a catchment area-based evaluation of the modified version of the Mishra and Singh (2002a) model was performed. The model is based on the Soil Conservation Service Curve Number (SCS-CN) methodology and incorporates the antecedent moisture in computation of direct surface runoff. Comparison with the existing SCS-CN method showed that the modified version performed better than did the existing one on the data of all seven area-based groups of watersheds ranging from 0.01 to 310.3 km2.

Depletion of Pax7+ satellite cells does not affect diaphragm adaptations to running in young or aged mice.

Science.gov (United States)

Murach, Kevin A; Confides, Amy L; Ho, Angel; Jackson, Janna R; Ghazala, Lina S; Peterson, Charlotte A; Dupont-Versteegden, Esther E

2017-10-01

Satellite cell depletion does not affect diaphragm adaptations to voluntary wheel running in young or aged mice. Satellite cell depletion early in life (4 months of age) has minimal effect on diaphragm phenotype by old age (24 months). Prolonged satellite cell depletion in the diaphragm does not result in excessive extracellular matrix accumulation, in contrast to what has been reported in hind limb muscles. Up-regulation of Pax3 mRNA+ cells after satellite cell depletion in young and aged mice suggests that Pax3+ cells may compensate for a loss of Pax7+ satellite cells in the diaphragm. Future investigations should focus on the role of Pax3+ cells in the diaphragm during adaptation to exercise and ageing. Satellite cell contribution to unstressed diaphragm is higher compared to hind limb muscles, which is probably attributable to constant activation of this muscle to drive ventilation. Whether satellite cell depletion negatively impacts diaphragm quantitative and qualitative characteristics under stressed conditions in young and aged mice is unknown. We therefore challenged the diaphragm with prolonged running activity in the presence and absence of Pax7+ satellite cells in young and aged mice using an inducible Pax7 CreER -R26R DTA model. Mice were vehicle (Veh, satellite cell-replete) or tamoxifen (Tam, satellite cell-depleted) treated at 4 months of age and were then allowed to run voluntarily at 6 months (young) and 22 months (aged). Age-matched, cage-dwelling, Veh- and Tam-treated mice without wheel access served as activity controls. Diaphragm muscles were analysed from young (8 months) and aged (24 months) mice. Satellite cell depletion did not alter diaphragm mean fibre cross-sectional area, fibre type distribution or extracellular matrix content in young or aged mice, regardless of running activity. Resting in vivo diaphragm function was also unaffected by satellite cell depletion. Myonuclear density was maintained in young satellite cell

Validation of the Spanish versions of the long (26 items) and short (12 items) forms of the Self-Compassion Scale (SCS).

Science.gov (United States)

Garcia-Campayo, Javier; Navarro-Gil, Mayte; Andrés, Eva; Montero-Marin, Jesús; López-Artal, Lorena; Demarzo, Marcelo Marcos Piva

2014-01-10

Self-compassion is a key psychological construct for assessing clinical outcomes in mindfulness-based interventions. The aim of this study was to validate the Spanish versions of the long (26 item) and short (12 item) forms of the Self-Compassion Scale (SCS). The translated Spanish versions of both subscales were administered to two independent samples: Sample 1 was comprised of university students (n = 268) who were recruited to validate the long form, and Sample 2 was comprised of Aragon Health Service workers (n = 271) who were recruited to validate the short form. In addition to SCS, the Mindful Attention Awareness Scale (MAAS), the State-Trait Anxiety Inventory-Trait (STAI-T), the Beck Depression Inventory (BDI) and the Perceived Stress Questionnaire (PSQ) were administered. Construct validity, internal consistency, test-retest reliability and convergent validity were tested. The Confirmatory Factor Analysis (CFA) of the long and short forms of the SCS confirmed the original six-factor model in both scales, showing goodness of fit. Cronbach's α for the 26 item SCS was 0.87 (95% CI = 0.85-0.90) and ranged between 0.72 and 0.79 for the 6 subscales. Cronbach's α for the 12-item SCS was 0.85 (95% CI = 0.81-0.88) and ranged between 0.71 and 0.77 for the 6 subscales. The long (26-item) form of the SCS showed a test-retest coefficient of 0.92 (95% CI = 0.89-0.94). The Intraclass Correlation (ICC) for the 6 subscales ranged from 0.84 to 0.93. The short (12-item) form of the SCS showed a test-retest coefficient of 0.89 (95% CI: 0.87-0.93). The ICC for the 6 subscales ranged from 0.79 to 0.91. The long and short forms of the SCS exhibited a significant negative correlation with the BDI, the STAI and the PSQ, and a significant positive correlation with the MAAS. The correlation between the total score of the long and short SCS form was r = 0.92. The Spanish versions of the long (26-item) and short (12-item) forms of the SCS are valid and

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part I: Single crowns (SCs).

Science.gov (United States)

Sailer, Irena; Makarov, Nikolay Alexandrovich; Thoma, Daniel Stefan; Zwahlen, Marcel; Pjetursson, Bjarni Elvar

2015-06-01

To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported single crowns (SCs) and to describe the incidence of biological, technical and esthetic complications. Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported fixed dental prostheses (FDPs) with a mean follow-up of at least 3 years. This was complimented by an additional hand search and the inclusion of 34 studies from a previous systematic review [1,2]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. Sixty-seven studies reporting on 4663 metal-ceramic and 9434 all-ceramic SCs fulfilled the inclusion criteria. Seventeen studies reported on metal-ceramic crowns, and 54 studies reported on all-ceramic crowns. Meta-analysis of the included studies indicated an estimated survival rate of metal-ceramic SCs of 94.7% (95% CI: 94.1-96.9%) after 5 years. This was similar to the estimated 5-year survival rate of leucit or lithium-disilicate reinforced glass ceramic SCs (96.6%; 95% CI: 94.9-96.7%), of glass infiltrated alumina SCs (94.6%; 95% CI: 92.7-96%) and densely sintered alumina and zirconia SCs (96%; 95% CI: 93.8-97.5%; 92.1%; 95% CI: 82.8-95.6%). In contrast, the 5-year survival rates of feldspathic/silica-based ceramic crowns were lower (pceramic and zirconia crowns exhibited significantly lower survival rates in the posterior region (pceramic fractures than metal-ceramic SCs (pceramic SCs than for metal-ceramic SCs. Survival rates of most types of all-ceramic SCs were similar to those reported for metal-ceramic SCs, both in anterior and posterior regions. Weaker feldspathic/silica-based ceramics should be limited to applications in the anterior region. Zirconia-based SCs should not be considered as primary option due to their high incidence of technical problems. Copyright © 2015 Academy

Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

Science.gov (United States)

Ali, Niwa; Zirak, Bahar; Rodriguez, Robert Sanchez; Pauli, Mariela L; Truong, Hong-An; Lai, Kevin; Ahn, Richard; Corbin, Kaitlin; Lowe, Margaret M; Scharschmidt, Tiffany C; Taravati, Keyon; Tan, Madeleine R; Ricardo-Gonzalez, Roberto R; Nosbaum, Audrey; Bertolini, Marta; Liao, Wilson; Nestle, Frank O; Paus, Ralf; Cotsarelis, George; Abbas, Abul K; Rosenblum, Michael D

2017-06-01

The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of T regs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Using a topographic index to distribute variable source area runoff predicted with the SCS curve-number equation

Science.gov (United States)

Lyon, Steve W.; Walter, M. Todd; Gérard-Marchant, Pierre; Steenhuis, Tammo S.

2004-10-01

Because the traditional Soil Conservation Service curve-number (SCS-CN) approach continues to be used ubiquitously in water quality models, new application methods are needed that are consistent with variable source area (VSA) hydrological processes in the landscape. We developed and tested a distributed approach for applying the traditional SCS-CN equation to watersheds where VSA hydrology is a dominant process. Predicting the location of source areas is important for watershed planning because restricting potentially polluting activities from runoff source areas is fundamental to controlling non-point-source pollution. The method presented here used the traditional SCS-CN approach to predict runoff volume and spatial extent of saturated areas and a topographic index, like that used in TOPMODEL, to distribute runoff source areas through watersheds. The resulting distributed CN-VSA method was applied to two subwatersheds of the Delaware basin in the Catskill Mountains region of New York State and one watershed in south-eastern Australia to produce runoff-probability maps. Observed saturated area locations in the watersheds agreed with the distributed CN-VSA method. Results showed good agreement with those obtained from the previously validated soil moisture routing (SMR) model. When compared with the traditional SCS-CN method, the distributed CN-VSA method predicted a similar total volume of runoff, but vastly different locations of runoff generation. Thus, the distributed CN-VSA approach provides a physically based method that is simple enough to be incorporated into water quality models, and other tools that currently use the traditional SCS-CN method, while still adhering to the principles of VSA hydrology.

MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

Science.gov (United States)

Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

2012-01-01

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process. PMID:22279050

RUNOFF HYDROGRAPHS USING SNYDER AND SCS SYNTHETIC UNIT HYDROGRAPH METHODS: A CASE STUDY OF SELECTED RIVERS IN SOUTH WEST NIGERIA

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Wahab Adebayo Salami

2017-01-01

Full Text Available This paper presents the development of runoff hydrographs for selected rivers in Ogun-Osun river catchment, south west, Nigeria using Snyder and Soil Conservation Service (SCS methods of synthetic unit hydrograph to determine the ordinates. The Soil Conservation Service (SCS curve Number method was used to estimate the excess rainfall from storm of different return periods. The peak runoff hydrographs were determined by convoluting the unit hydrographs ordinates with the excess rainfall and the value of peak flows obtained by both Snyder and SCS methods observed to vary from one river watershed to the other. The peak runoff hydrograph flows obtained based on the unit hydrograph ordinate determined with Snyder method for 20-yr, 50-yr, 100-yr, 200-yr and 500-yr, return period varied from 112.63m3/s and 13364.30m3/s, while those based on the SCS method varied from 304.43m3/s and 6466.84m3/s for the eight watersheds. However, the percentage difference shows that for values of peak flows obtained with Snyder and SCS methods varies from 13.14% to 63.30%. However, SCS method is recommended to estimate the ordinate required for the development of peak runoff hydrograph in the river watersheds because it utilized additional morphometric parameters such as watershed slope and the curve number (CN which is a function of the properties of the soil and vegetation cover of the watershed.

Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

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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.

MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

OpenAIRE

Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

2012-01-01

Muscle repair is regulated by satellite cells, adult skeletal muscle stem cells that control muscle regeneration by proliferating and fusing with injured myofibers. MyoD is required for muscle regeneration; however, the mechanisms regulating MyoD expression in satellite cells are unclear. In this study, Olson and colleagues have demonstrated that deletion of MASTR and MRTF-A, two members of the Myocardin family of transcription factors, leads to skeletal muscle regeneration defects and down-r...

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...

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.

GIS Based Distributed Runoff Predictions in Variable Source Area Watersheds Employing the SCS-Curve Number

Science.gov (United States)

Steenhuis, T. S.; Mendoza, G.; Lyon, S. W.; Gerard Marchant, P.; Walter, M. T.; Schneiderman, E.

2003-04-01

Because the traditional Soil Conservation Service Curve Number (SCS-CN) approach continues to be ubiquitously used in GIS-BASED water quality models, new application methods are needed that are consistent with variable source area (VSA) hydrological processes in the landscape. We developed within an integrated GIS modeling environment a distributed approach for applying the traditional SCS-CN equation to watersheds where VSA hydrology is a dominant process. Spatial representation of hydrologic processes is important for watershed planning because restricting potentially polluting activities from runoff source areas is fundamental to controlling non-point source pollution. The methodology presented here uses the traditional SCS-CN method to predict runoff volume and spatial extent of saturated areas and uses a topographic index to distribute runoff source areas through watersheds. The resulting distributed CN-VSA method was incorporated in an existing GWLF water quality model and applied to sub-watersheds of the Delaware basin in the Catskill Mountains region of New York State. We found that the distributed CN-VSA approach provided a physically-based method that gives realistic results for watersheds with VSA hydrology.

Estimating Composite Curve Number Using an Improved SCS-CN Method with Remotely Sensed Variables in Guangzhou, China

OpenAIRE

Fan, Fenglei; Deng, Yingbin; Hu, Xuefei; Weng, Qihao

2013-01-01

The rainfall and runoff relationship becomes an intriguing issue as urbanization continues to evolve worldwide. In this paper, we developed a simulation model based on the soil conservation service curve number (SCS-CN) method to analyze the rainfall-runoff relationship in Guangzhou, a rapid growing metropolitan area in southern China. The SCS-CN method was initially developed by the Natural Resources Conservation Service (NRCS) of the United States Department of Agriculture (USDA), and is on...

Sea-level trend in the South China Sea observed from 20 years of along-track satellite altimetric data

DEFF Research Database (Denmark)

Cheng, Yongcun; Xu, Qing; Andersen, Ole Baltazar

2014-01-01

The sea-level trend in the South China Sea (SCS) is investigated based on 20 years of along-track data from TOPEX and Jason-1/2 satellite altimetry. The average sea-level rise over all the regions in the study area is observed to have a rate of 5.1 ± 0.8 mm year-1 for the period from 1993 to 2012....... The steric sea level contributes 45% to the observed sea-level trend. These results are consistent with previous studies. In addition, the results demonstrate that the maximum sea-level rise rate of 8.4 mm year-1 is occurring off the east coast of Vietnam and eastern part of SCS. During 2010-2011, the La...... Niña event was highly correlated with the dramatic sea-level rise in the SCS; La Niña events were also associated with the maximum rate of sea rise off the east coast of Vietnam, which occurred during 1993 and 2012. We also evaluated the trends in the geophysical (e.g. dynamical atmospheric correction...

Development of Space Qualified Microlens Arrays for Solar Cells Used on Satellite Power Systems

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Ömer Faruk Keser

2017-08-01

Full Text Available The power system, one of the main systems of satellite, provides energy required for the satellite. Solar cells are also the most used energy source in the power system. The third generation multi-junction solar cells are known as the ones with highest performance. One of the methods to increase the performance of the solar cells is anti-reflective surface coatings with the Micro Lens Array-MLA. It's expected that satellite technologies has high power efficiency and low mass. The space environment has many effects like atomic oxygen, radiation and thermal cycles. Researches for increasing the solar cells performance shows that MLA coated solar cell has increased light absorption performance and less cell heating with very low additional mass. However, it is established that few studies on MLA coatings of solar cells are not applicable on space platforms. In this study, the process of development of MLA which is convenient to space power systems is investigated in a methodological way. In this context, a method which is developed based on MLA coatings of multi-junction solar cells for satellite power systems is presented.

The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53.

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Flamini, Valentina; Ghadiali, Rachel S; Antczak, Philipp; Rothwell, Amy; Turnbull, Jeremy E; Pisconti, Addolorata

2018-03-13

Satellite cells are adult muscle stem cells residing in a specialized niche that regulates their homeostasis. How niche-generated signals integrate to regulate gene expression in satellite cell-derived myoblasts is poorly understood. We undertook an unbiased approach to study the effect of the satellite cell niche on satellite cell-derived myoblast transcriptional regulation and identified the tumor suppressor p53 as a key player in the regulation of myoblast quiescence. After activation and proliferation, a subpopulation of myoblasts cultured in the presence of the niche upregulates p53 and fails to differentiate. When satellite cell self-renewal is modeled ex vivo in a reserve cell assay, myoblasts treated with Nutlin-3, which increases p53 levels in the cell, fail to differentiate and instead become quiescent. Since both these Nutlin-3 effects are rescued by small interfering RNA-mediated p53 knockdown, we conclude that a tight control of p53 levels in myoblasts regulates the balance between differentiation and return to quiescence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

U.S.-Vietnamese Security Cooperation for Access to the SCS

Science.gov (United States)

2015-06-16

of the claimants to islands in the SCS, China has more Coast Guard/MLE vessels than Japan, Indonesia, Malaysia , and the Philippines combined.7...45 In 2011, the U.S. looked at Vietnam, along with other Southeast Asian countries, for its Naval Medical ...human rights; culture, tourism , and sports; as well as continued annual defense dialogue meetings.47 Both Vietnam and the U.S. are concerned about

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...

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

Science.gov (United States)

Velleman, S G; Harding, R L

2017-06-01

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. © 2016 Poultry Science Association Inc.

Ex vivo gene editing of the dystrophin gene in muscle stem cells mediated by peptide nucleic acid single stranded oligodeoxynucleotides induces stable expression of dystrophin in a mouse model for Duchenne muscular dystrophy.

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Nik-Ahd, Farnoosh; Bertoni, Carmen

2014-07-01

Duchenne muscular dystrophy (DMD) is a fatal disease caused by mutations in the dystrophin gene, which result in the complete absence of dystrophin protein throughout the body. Gene correction strategies hold promise to treating DMD. Our laboratory has previously demonstrated the ability of peptide nucleic acid single-stranded oligodeoxynucleotides (PNA-ssODNs) to permanently correct single-point mutations at the genomic level. In this study, we show that PNA-ssODNs can target and correct muscle satellite cells (SCs), a population of stem cells capable of self-renewing and differentiating into muscle fibers. When transplanted into skeletal muscles, SCs transfected with correcting PNA-ssODNs were able to engraft and to restore dystrophin expression. The number of dystrophin-positive fibers was shown to significantly increase over time. Expression was confirmed to be the result of the activation of a subpopulation of SCs that had undergone repair as demonstrated by immunofluorescence analyses of engrafted muscles using antibodies specific to full-length dystrophin transcripts and by genomic DNA analysis of dystrophin-positive fibers. Furthermore, the increase in dystrophin expression detected over time resulted in a significant improvement in muscle morphology. The ability of transplanted cells to return into quiescence and to activate upon demand was confirmed in all engrafted muscles following injury. These results demonstrate the feasibility of using gene editing strategies to target and correct SCs and further establish the therapeutic potential of this approach to permanently restore dystrophin expression into muscle of DMD patients. © 2014 AlphaMed Press.

The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension

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Zhang Hong-Yu

2010-11-01

Full Text Available Abstract Background The ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. It has been shown that chronic hindlimb unloading downregulates the satellite cell activity. This study investigated the role of low-frequency electrical stimulation on satellite cell activity during a 28 d hindlimb suspension in rats. Results Mechanical unloading resulted in a 44% reduction in the myofiber cross-sectional area as well as a 29% and 34% reduction in the number of myonuclei and myonuclear domains, respectively, in the soleus muscles (P vs the weight-bearing control. The number of quiescent (M-cadherin+, proliferating (BrdU+ and myoD+, and differentiated (myogenin+ satellite cells was also reduced by 48-57% compared to the weight-bearing animals (P P Conclusion This study shows that electrical stimulation partially attenuated the decrease in muscle size and satellite cells during hindlimb unloading. The causal relationship between satellite cell activation and electrical stimulation remain to be established.

Improving runoff risk estimates: Formulating runoff as a bivariate process using the SCS curve number method

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Shaw, Stephen B.; Walter, M. Todd

2009-03-01

The Soil Conservation Service curve number (SCS-CN) method is widely used to predict storm runoff for hydraulic design purposes, such as sizing culverts and detention basins. As traditionally used, the probability of calculated runoff is equated to the probability of the causative rainfall event, an assumption that fails to account for the influence of variations in soil moisture on runoff generation. We propose a modification to the SCS-CN method that explicitly incorporates rainfall return periods and the frequency of different soil moisture states to quantify storm runoff risks. Soil moisture status is assumed to be correlated to stream base flow. Fundamentally, this approach treats runoff as the outcome of a bivariate process instead of dictating a 1:1 relationship between causative rainfall and resulting runoff volumes. Using data from the Fall Creek watershed in western New York and the headwaters of the French Broad River in the mountains of North Carolina, we show that our modified SCS-CN method improves frequency discharge predictions in medium-sized watersheds in the eastern United States in comparison to the traditional application of the method.

Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells

DEFF Research Database (Denmark)

Ding, Li; Paszkowski-Rogacz, Maciej; Winzi, Maria

2015-01-01

We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression...... of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell...... identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide...

Advances of Single-Cell Sequencing Technique in Tumors

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Ji-feng FENG

2017-03-01

Full Text Available With the completion of human genome project (HGP and the international HapMap project as well as rapid development of high-throughput biochip technology, whole genomic sequencing-targeted analysis of genomic structures has been primarily finished. Application of single cell for the analysis of the whole genomics is not only economical in material collection, but more importantly, the cell will be more purified, and the laboratory results will be more accurate and reliable. Therefore, exploration and analysis of hereditary information of single tumor cells has become the dream of all researchers in the field of basic research of tumors. At present, single-cell sequencing (SCS on malignancies has been widely used in the studies of pathogeneses of multiple malignancies, such as glioma, renal cancer and hematologic neoplasms, and in the studies of the metastatic mechanism of breast cancer by some researchers. This study mainly reviewed the SCS, the mechanisms and the methods of SCS in isolating tumor cells, and application of SCS technique in tumor-related basic research and clinical treatment.

Pre-mRNA Processing Is Partially Impaired in Satellite Cell Nuclei from Aged Muscles

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Manuela Malatesta

2010-01-01

Full Text Available Satellite cells are responsible for the capacity of mature mammalian skeletal muscles to repair and maintain mass. During aging, skeletal muscle mass as well as the muscle strength and endurance progressively decrease, leading to a condition termed sarcopenia. The causes of sarcopenia are manifold and remain to be completely elucidated. One of them could be the remarkable decline in the efficiency of muscle regeneration; this has been associated with decreasing amounts of satellite cells, but also to alterations in their activation, proliferation, and/or differentiation. In this study, we investigated the satellite cell nuclei of biceps and quadriceps muscles from adult and old rats; morphometry and immunocytochemistry at light and electron microscopy have been combined to assess the organization of the nuclear RNP structural constituents involved in different steps of mRNA formation. We demonstrated that in satellite cells the RNA pathways undergo alterations during aging, possibly hampering their responsiveness to muscle damage.

Characterization of Rat Hair Follicle Stem Cells Selected by Vario Magnetic Activated Cell Sorting System

International Nuclear Information System (INIS)

Huang, Enyi; Lian, Xiaohua; Chen, Wei; Yang, Tian; Yang, Li

2009-01-01

Hair follicle stem cells (HfSCs) play crucial roles in hair follicle morphogenesis and hair cycling. These stem cells are self-renewable and have the multi-lineage potential to generate epidermis, sebaceous glands, and hair follicle. The separation and identification of hair follicle stem cells are important for further research in stem cell biology. In this study, we report on the successful enrichment of rat hair follicle stem cells through vario magnetic activated cell sorting (Vario MACS) and the biological characteristics of the stem cells. We chose the HfSCs positive surface markers CD34, α6-integrin and the negative marker CD71 to design four isolation strategies: positive selection with single marker of CD34, positive selection with single marker of α6-integrin, CD71 depletion followed by CD34 positive selection, and CD71 depletion followed by α6-integrin positive selection. The results of flow cytometry analysis showed that all four strategies had ideal effects. Specifically, we conducted a series of researches on HfSCs characterized by their high level of CD34, termed CD34 bri cells, and low to undetectable expression of CD34, termed CD34 dim cells. CD34 bri cells had greater proliferative potential and higher colony-forming ability than CD34 dim cells. Furthermore, CD34 bri cells had some typical characteristics as progenitor cells, such as large nucleus, obvious nucleolus, large nuclear:cytoplasmic ratio and few cytoplasmic organelles. Our findings clearly demonstrated that HfSCs with high purity and viability could be successfully enriched with Vario MACS

Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women.

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Shoae-Hassani, Alireza; Sharif, Shiva; Seifalian, Alexander M; Mortazavi-Tabatabaei, Seyed Abdolreza; Rezaie, Sassan; Verdi, Javad

2013-10-01

To investigate manufacturing smooth muscle cells (SMCs) for regenerative bladder reconstruction from differentiation of endometrial stem cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri, opens up the possibility of using these cells for tissue engineering applications, such as building up natural tissue to repair prolapsed pelvic floors as well as building urinary bladder wall. Human EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium supplemented with myogenic growth factors. The myogenic factors included: transforming growth factor β, platelet-derived growth factor, hepatocyte growth factor and vascular endothelial growth factor. Differentiated SMCs on bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), western blot (WB) and immunocytochemistry (ICC) analyses. Histology confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth factors decreased the proliferation rate of EnSCs, but they differentiated the human EnSCs into SMCs more efficiently on hydrogel matrices and expressed specific SMC markers including α-smooth muscle actin, desmin, vinculin and calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the hydrogel-coated matrices was significantly higher than uncoated cultures. Human EnSCs were successfully differentiated into SMCs, using hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration without any immunological complications in women. Currently work is in progress using bioabsorbable nanocomposite materials as EnSC scaffolds for developing urinary bladder wall tissue. © 2013 The Authors. BJU International © 2013 BJU International.

Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles

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Elisia D. Tichy

2017-10-01

Full Text Available Muscle stem cells (MuSCs contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres. In corroboration, we demonstrated that telomere attrition is present in human dystrophic MuSCs, which underscores its importance in diseased regenerative failure. The robust technique described herein provides analysis at a single-cell resolution and may be utilized for other cell types, especially rare populations of cells.

E-selectin mediates stem cell adhesion and formation of blood vessels in a murine model of infantile hemangioma.

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Smadja, David M; Mulliken, John B; Bischoff, Joyce

2012-12-01

Hemangioma stem cells (HemSCs) are multipotent cells isolated from infantile hemangioma (IH), which form hemangioma-like lesions when injected subcutaneously into immune-deficient mice. In this murine model, HemSCs are the primary target of corticosteroid, a mainstay therapy for problematic IH. The relationship between HemSCs and endothelial cells that reside in IH is not clearly understood. Adhesive interactions might be critical for the preferential accumulation of HemSCs and/or endothelial cells in the tumor. Therefore, we studied the interactions between HemSCs and endothelial cells (HemECs) isolated from IH surgical specimens. We found that HemECs isolated from proliferating phase IH, but not involuting phase, constitutively express E-selectin, a cell adhesion molecule not present in quiescent endothelial cells. E-selectin was further increased when HemECs were exposed to vascular endothelial growth factor-A or tumor necrosis factor-α. In vitro, HemSC migration and adhesion was enhanced by recombinant E-selectin but not P-selectin; both processes were neutralized by E-selectin-blocking antibodies. E-selectin-positive HemECs also stimulated migration and adhesion of HemSCs. In vivo, neutralizing antibodies to E-selectin strongly inhibited formation of blood vessels when HemSCs and HemECs were co-implanted in Matrigel. These data suggest that endothelial E-selectin could be a major ligand for HemSCs and thereby promote cellular interactions and vasculogenesis in IH. We propose that constitutively expressed E-selectin on endothelial cells in the proliferating phase is one mediator of the stem cell tropism in IH. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

New photo-curable resin compositions for stereolithography with a new photo-fabricator: SCS-300P

International Nuclear Information System (INIS)

Yamamura Tetsuya; Tanabe Takayoshi; Ukachi Takashi

1999-01-01

Stereolithography is the technology which can create a three-dimensional free-forin in short time according to the slice data of an object. A thin layer of the solidified resin is formed at the surface of the liquid UV curable resin by irradiation of UV laser which is driven by the slice data of the object. Ever since the invention of the stereolithography, there has been a considerable interest to realize the CAD date into a practical three dimensional model. Conventional stereolithographic machines equip gas lasers which are operated at high voltage and requires water cooling system. These disadvantages prevent a wide spread of application of stereolithographic technology. A new sterolithographic machine, SCS-300P has been developed and introduced by SONY Corporation last year. This brand new machine is featuring a high power solid-state UV laser, low machine price, small in size and equips easy-resin-exchange system for maintenance. The biggest difference of SCS-300P from the conventional machines is the laser system. SCS-300P equips pulse laser with the wave length of 355 run which is a third harmonic of YAG laser. The energy of each pulse with a duration time of 20 nsec is more than five thousand times higher than that of continuous emission such as Argon ion laser employed in the conventional machines. With using conventional LTV curable resins, high photo-energy tends to give a gelation even in a dark region or give an undesirable excess-cure underneath of the cured layer. It is thus needed to develop the resin suitable for high power pulse lasers. In this paper, we report a newly developed UV curable resin compositions suitable for SCS-300P which equips high power solid-state pulse laser

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...

Application and comparison of the SCS-CN-based rainfall-runoff model in meso-scale watershed and field scale

Science.gov (United States)

Luo, L.; Wang, Z.

2010-12-01

Soil Conservation Service Curve Number (SCS-CN) based hydrologic model, has widely been used for agricultural watersheds in recent years. However, there will be relative error when applying it due to differentiation of geographical and climatological conditions. This paper introduces a more adaptable and propagable model based on the modified SCS-CN method, which specializes into two different scale cases of research regions. Combining the typical conditions of the Zhanghe irrigation district in southern part of China, such as hydrometeorologic conditions and surface conditions, SCS-CN based models were established. The Xinbu-Qiao River basin (area =1207 km2) and the Tuanlin runoff test area (area =2.87 km2)were taken as the study areas of basin scale and field scale in Zhanghe irrigation district. Applications were extended from ordinary meso-scale watershed to field scale in Zhanghe paddy field-dominated irrigated . Based on actual measurement data of land use, soil classification, hydrology and meteorology, quantitative evaluation and modifications for two coefficients, i.e. preceding loss and runoff curve, were proposed with corresponding models, table of CN values for different landuse and AMC(antecedent moisture condition) grading standard fitting for research cases were proposed. The simulation precision was increased by putting forward a 12h unit hydrograph of the field area, and 12h unit hydrograph were simplified. Comparison between different scales show that it’s more effectively to use SCS-CN model on field scale after parameters calibrated in basin scale These results can help discovering the rainfall-runoff rule in the district. Differences of established SCS-CN model's parameters between the two study regions are also considered. Varied forms of landuse and impacts of human activities were the important factors which can impact the rainfall-runoff relations in Zhanghe irrigation district.

Early regenerative effects of NGF-transduced Schwann cells in peripheral nerve repair.

Science.gov (United States)

Shakhbazau, Antos; Kawasoe, Jean; Hoyng, Stefan A; Kumar, Ranjan; van Minnen, Jan; Verhaagen, Joost; Midha, Rajiv

2012-05-01

Peripheral nerve injury leads to a rapid and robust increase in the synthesis of neurotrophins which guide and support regenerating axons. To further optimize neurotrophin supply at the earliest stages of regeneration, we over-expressed NGF in Schwann cells (SCs) by transducing these cells with a lentiviral vector encoding NGF (NGF-SCs). Transplantation of NGF-SCs in a rat sciatic nerve transection/repair model led to significant increase of NGF levels 2weeks after injury and correspondingly to substantial improvement in axonal regeneration. Numbers of NF200, ChAT and CGRP-positive axon profiles, as well as the gastrocnemius muscle weights, were significantly higher in the NGF-Schwann cell group compared to the animals that received control SCs transduced with a lentiviral vector encoding GFP (GFP-SCs). Comparison with other models of NGF application signifies the important role of this neurotrophin during the early stages of regeneration, and supports the importance of developing combined gene and cell therapy for peripheral nerve repair. Copyright © 2012 Elsevier Inc. All rights reserved.

Reviewing and Updating the Major Molecular Markers for Stem Cells

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Calloni, Raquel; Cordero, Elvira Alicia Aparicio; Henriques, João Antonio Pêgas

2013-01-01

Stem cells (SC) are able to self-renew and to differentiate into many types of committed cells, making SCs interesting for cellular therapy. However, the pool of SCs in vivo and in vitro consists of a mix of cells at several stages of differentiation, making it difficult to obtain a homogeneous population of SCs for research. Therefore, it is important to isolate and characterize unambiguous molecular markers that can be applied to SCs. Here, we review classical and new candidate molecular markers that have been established to show a molecular profile for human embryonic stem cells (hESCs), mesenchymal stem cells (MSCs), and hematopoietic stem cells (HSCs). The commonly cited markers for embryonic ESCs are Nanog, Oct-4, Sox-2, Rex-1, Dnmt3b, Lin-28, Tdgf1, FoxD3, Tert, Utf-1, Gal, Cx43, Gdf3, Gtcm1, Terf1, Terf2, Lefty A, and Lefty B. MSCs are primarily identified by the expression of CD13, CD29, CD44, CD49e, CD54, CD71, CD73, CD90, CD105, CD106, CD166, and HLA-ABC and lack CD14, CD31, CD34, CD45, CD62E, CD62L, CD62P, and HLA-DR expression. HSCs are mainly isolated based on the expression of CD34, but the combination of this marker with CD133 and CD90, together with a lack of CD38 and other lineage markers, provides the most homogeneous pool of SCs. Here, we present new and alternative markers for SCs, along with microRNA profiles, for these cells. PMID:23336433

Uterine-derived progenitor cells are immunoprivileged and effectively improve cardiac regeneration when used for cell therapy.

Science.gov (United States)

Ludke, Ana; Wu, Jun; Nazari, Mansoreh; Hatta, Kota; Shao, Zhengbo; Li, Shu-Hong; Song, Huifang; Ni, Nathan C; Weisel, Richard D; Li, Ren-Ke

2015-07-01

Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uterus has distinct immune characteristics, and we showed that reparative uterine SCs home to the myocardium post-MI. Here, we identify immunoprivileged uterine SCs and assess their effects on cardiac regeneration after allogeneic transplantation. We found more than 20% of cells in the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine MHC I((neg)) and MHC I((pos)) cells were separated by magnetic cell sorting. The MHC I((neg)) population expressed the SC markers CD34, Sca-1 and CD90, but did not express MHC II or c-kit. In vitro, MHC I((neg)) and ((pos)) SCs show colony formation and endothelial differentiation capacity. In mixed leukocyte co-culture, MHC I((neg)) cells showed reduced cell death and leukocyte proliferation compared to MHC I((pos)) cells. MHC I((neg)) and ((pos)) cells had significantly greater angiogenic capacity than mesenchymal stem cells. The benefits of intramyocardial injection of allogeneic MHC I((neg)) cells after MI were comparable to syngeneic bone marrow cell transplantation, with engraftment in cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post-MI. MHC I((neg)) cells preserved cardiac function, decreased infarct size and improved regeneration post-MI. This new source of immunoprivileged cells can induce neovascularization and could be used as allogeneic cell therapy for regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Retained Myogenic Potency of Human Satellite Cells from Torn Rotator Cuff Muscles Despite Fatty Infiltration.

Science.gov (United States)

Koide, Masashi; Hagiwara, Yoshihiro; Tsuchiya, Masahiro; Kanzaki, Makoto; Hatakeyama, Hiroyasu; Tanaka, Yukinori; Minowa, Takashi; Takemura, Taro; Ando, Akira; Sekiguchi, Takuya; Yabe, Yutaka; Itoi, Eiji

2018-01-01

Rotator cuff tears (RCTs) are a common shoulder problem in the elderly that can lead to both muscle atrophy and fatty infiltration due to less physical load. Satellite cells, quiescent cells under the basal lamina of skeletal muscle fibers, play a major role in muscle regeneration. However, the myogenic potency of human satellite cells in muscles with fatty infiltration is unclear due to the difficulty in isolating from small samples, and the mechanism of the progression of fatty infiltration has not been elucidated. The purpose of this study was to analyze the population of myogenic and adipogenic cells in disused supraspinatus (SSP) and intact subscapularis (SSC) muscles of the RCTs from the same patients using fluorescence-activated cell sorting. The microstructure of the muscle with fatty infiltration was observed as a whole mount condition under multi-photon microscopy. Myogenic differentiation potential and gene expression were evaluated in satellite cells. The results showed that the SSP muscle with greater fatty infiltration surrounded by collagen fibers compared with the SSC muscle under multi-photon microscopy. A positive correlation was observed between the ratio of muscle volume to fat volume and the ratio of myogenic precursor to adipogenic precursor. Although no difference was observed in the myogenic potential between the two groups in cell culture, satellite cells in the disused SSP muscle showed higher intrinsic myogenic gene expression than those in the intact SSC muscle. Our results indicate that satellite cells from the disused SSP retain sufficient potential of muscle growth despite the fatty infiltration.

Fetal skeletal muscle progenitors have regenerative capacity after intramuscular engraftment in dystrophin deficient mice.

Directory of Open Access Journals (Sweden)

Hiroshi Sakai

Full Text Available Muscle satellite cells (SCs are stem cells that reside in skeletal muscles and contribute to regeneration upon muscle injury. SCs arise from skeletal muscle progenitors expressing transcription factors Pax3 and/or Pax7 during embryogenesis in mice. However, it is unclear whether these fetal progenitors possess regenerative ability when transplanted in adult muscle. Here we address this question by investigating whether fetal skeletal muscle progenitors (FMPs isolated from Pax3(GFP/+ embryos have the capacity to regenerate muscle after engraftment into Dystrophin-deficient mice, a model of Duchenne muscular dystrophy. The capacity of FMPs to engraft and enter the myogenic program in regenerating muscle was compared with that of SCs derived from adult Pax3(GFP/+ mice. Transplanted FMPs contributed to the reconstitution of damaged myofibers in Dystrophin-deficient mice. However, despite FMPs and SCs having similar myogenic ability in culture, the regenerative ability of FMPs was less than that of SCs in vivo. FMPs that had activated MyoD engrafted more efficiently to regenerate myofibers than MyoD-negative FMPs. Transcriptome and surface marker analyses of these cells suggest the importance of myogenic priming for the efficient myogenic engraftment. Our findings suggest the regenerative capability of FMPs in the context of muscle repair and cell therapy for degenerative muscle disease.

Appointing silver and bronze standards for noncovalent interactions: A comparison of spin-component-scaled (SCS), explicitly correlated (F12), and specialized wavefunction approaches

International Nuclear Information System (INIS)

Burns, Lori A.; Marshall, Michael S.; Sherrill, C. David

2014-01-01

A systematic examination of noncovalent interactions as modeled by wavefunction theory is presented in comparison to gold-standard quality benchmarks available for 345 interaction energies of 49 bimolecular complexes. Quantum chemical techniques examined include spin-component-scaling (SCS) variations on second-order perturbation theory (MP2) [SCS, SCS(N), SCS(MI)] and coupled cluster singles and doubles (CCSD) [SCS, SCS(MI)]; also, method combinations designed to improve dispersion contacts [DW-MP2, MP2C, MP2.5, DW-CCSD(T)-F12]; where available, explicitly correlated (F12) counterparts are also considered. Dunning basis sets augmented by diffuse functions are employed for all accessible ζ-levels; truncations of the diffuse space are also considered. After examination of both accuracy and performance for 394 model chemistries, SCS(MI)-MP2/cc-pVQZ can be recommended for general use, having good accuracy at low cost and no ill-effects such as imbalance between hydrogen-bonding and dispersion-dominated systems or non-parallelity across dissociation curves. Moreover, when benchmarking accuracy is desirable but gold-standard computations are unaffordable, this work recommends silver-standard [DW-CCSD(T**)-F12/aug-cc-pVDZ] and bronze-standard [MP2C-F12/aug-cc-pVDZ] model chemistries, which support accuracies of 0.05 and 0.16 kcal/mol and efficiencies of 97.3 and 5.5 h for adenine·thymine, respectively. Choice comparisons of wavefunction results with the best symmetry-adapted perturbation theory [T. M. Parker, L. A. Burns, R. M. Parrish, A. G. Ryno, and C. D. Sherrill, J. Chem. Phys. 140, 094106 (2014)] and density functional theory [L. A. Burns, Á. Vázquez-Mayagoitia, B. G. Sumpter, and C. D. Sherrill, J. Chem. Phys. 134, 084107 (2011)] methods previously studied for these databases are provided for readers' guidance

Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells.

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Zheng, Sheng-Xia; Wang, Jian; Wang, Xue-Li; Ali, Asim; Wu, Li-Min; Liu, Yu-Sheng

2018-04-01

Intrauterine adhesions (IUA) are associated with the loss of stem cells in the endometrium. Menstrual blood‑derived stem cells (MenSCs) can be isolated from the menstrual blood and differentiated into endometrial cells. To check the transplantation feasibility of MenSCs for the treatment of severe IUA, MenSCs were isolated from menstrual blood, cultured in Dulbecco's modified Eagle's medium (DMEM), identified by immunocytochemistry and flow cytometry, differentiated into endometrial cells in vitro, and finally transplanted into the axillary subcutaneous tissue of non‑obese diabetic/severe combined immunodeficiency (NOD‑SCID) mice to create endometrial tissue. Additionally, the cloning efficiency and POU domain class 5 transcription factor 1 (OCT‑4) positivity of MenSCs from patients with severe IUA were compared with those from healthy women. Immunocytochemistry and flow cytometry results showed that 95.1±0.8% cells were OCT‑4‑positive, 0.9±0.4% were cluster of differentiation (CD)45‑positive, 1.8±0.9% were STRO‑1‑positive and 1.0±0.4% were human leukocyte antigen‑antigen D related‑positive. Following differentiation in vitro, the results of immunocytochemistry, reverse transcription‑polymerase chain reaction and western blot analysis showed that the expression of cytokeratin (CK) and vimentin (VIM) was increased in MenSCs compared with that in control subjects. Subsequent to transplantation in mice administered with sequential 17β‑estradiol and progesterone, CK, VIM, estrogen receptor and progesterone receptor were expressed in the transplantation regions, suggesting that MenSCs could differentiate into endometrial tissues in vivo. The cloning efficiency and OCT‑4 positivity of MenSCs from patients with severe IUA was significantly decreased. In conclusion, to the best of our knowledge, this is the first study in which MenSCs could differentiate into endometrial cells in vitro and create endometrial tissue in NOD‑SCID mice

Methods to isolate a large amount of generative cells, sperm cells and vegetative nuclei from tomato pollen for "omics" analysis.

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Lu, Yunlong; Wei, Liqin; Wang, Tai

2015-01-01

The development of sperm cells (SCs) from microspores involves a set of finely regulated molecular and cellular events and the coordination of these events. The mechanisms underlying these events and their interconnections remain a major challenge. Systems analysis of genome-wide molecular networks and functional modules with high-throughput "omics" approaches is crucial for understanding the mechanisms; however, this study is hindered because of the difficulty in isolating a large amount of cells of different types, especially generative cells (GCs), from the pollen. Here, we optimized the conditions of tomato pollen germination and pollen tube growth to allow for long-term growth of pollen tubes in vitro with SCs generated in the tube. Using this culture system, we developed methods for isolating GCs, SCs and vegetative cell nuclei (VN) from just-germinated tomato pollen grains and growing pollen tubes and their purification by Percoll density gradient centrifugation. The purity and viability of isolated GCs and SCs were confirmed by microscopy examination and fluorescein diacetate staining, respectively, and the integrity of VN was confirmed by propidium iodide staining. We could obtain about 1.5 million GCs and 2.0 million SCs each from 180 mg initiated pollen grains, and 10 million VN from 270 mg initiated pollen grains germinated in vitro in each experiment. These methods provide the necessary preconditions for systematic biology studies of SC development and differentiation in higher plants.

Novel Strategies for the Improvement of Stem Cells' Transplantation in Degenerative Retinal Diseases

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Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga

2016-01-01

Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation. PMID:27293444

Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction

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Zhong-Cheng Xin

2016-01-01

Full Text Available Transplanted stem cells (SCs, owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED. However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1 SC niche and SC biological features in vitro; (2 localization and mobilization of endogenous SCs; (3 existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.

Stochastic cellular automata model of cell migration, proliferation and differentiation: validation with in vitro cultures of muscle satellite cells.

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Garijo, N; Manzano, R; Osta, R; Perez, M A

2012-12-07

Cell migration and proliferation has been modelled in the literature as a process similar to diffusion. However, using diffusion models to simulate the proliferation and migration of cells tends to create a homogeneous distribution in the cell density that does not correlate to empirical observations. In fact, the mechanism of cell dispersal is not diffusion. Cells disperse by crawling or proliferation, or are transported in a moving fluid. The use of cellular automata, particle models or cell-based models can overcome this limitation. This paper presents a stochastic cellular automata model to simulate the proliferation, migration and differentiation of cells. These processes are considered as completely stochastic as well as discrete. The model developed was applied to predict the behaviour of in vitro cell cultures performed with adult muscle satellite cells. Moreover, non homogeneous distribution of cells has been observed inside the culture well and, using the above mentioned stochastic cellular automata model, we have been able to predict this heterogeneous cell distribution and compute accurate quantitative results. Differentiation was also incorporated into the computational simulation. The results predicted the myotube formation that typically occurs with adult muscle satellite cells. In conclusion, we have shown how a stochastic cellular automata model can be implemented and is capable of reproducing the in vitro behaviour of adult muscle satellite cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effects of the obesogen tributyltin on the metabolism of Sertoli cells cultured ex vivo.

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Cardoso, Ana M; Alves, Marco G; Sousa, Ana C; Jarak, Ivana; Carvalho, Rui A; Oliveira, Pedro F; Cavaco, José E; Rato, Luís

2018-02-01

Human exposure to environmental contaminants is widespread. Some of these contaminants have the ability to interfere with adipogenesis, being thus considered as obesogens. Recently, obesogens have been singled out as a cause of male infertility. Sertoli cells (SCs) are essential for male fertility and their metabolic performance, especially glucose metabolism, is under a tight endocrine control, being essential for the success of spermatogenesis. Herein, we studied the impact of the model obesogen tributyltin in the metabolic profile of SCs. For that, ex vivo-cultured rat SCs were exposed to increasing doses of tributyltin. SCs proliferation was evaluated by the sulforhodamine B assay and the maturation state of the cells was assessed by the expression of specific markers (inhibin B and the androgen receptor) by quantitative polymerase chain reaction. The metabolic profile of SCs was established by studying metabolites consumption/production by nuclear magnetic resonance spectroscopy and by analyzing the expression of key transporters and enzymes involved in glycolysis by Western blot. The proliferation of SCs was only affected in the cells exposed to the highest dose (1000 nM) of tributyltin. Notably, SCs exposed to 10 nM tributyltin decreased the consumption of glucose and pyruvate, as well as the production of lactate. The decreased lactate production hampers the development of germ cells. Intriguingly, the lowest levels of tributyltin were more prone to modulate the expression of key players of the glycolytic pathway. This is the first study showing that tributyltin reprograms glucose metabolism of SCs under ex vivo conditions, suggesting new targets and mechanisms through which obesogens modulate the metabolism of SCs and thus male (in)fertility.

Geometrical versus Random β-TCP Scaffolds: Exploring the Effects on Schwann Cell Growth and Behavior.

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Lauren Sweet

Full Text Available Numerous studies have demonstrated that Schwann cells (SCs play a role in nerve regeneration; however, their role in innervating a bioceramic scaffold for potential application in bone regeneration is still unknown. Here we report the cell growth and functional behavior of SCs on β-tricalcium phosphate (β-TCP scaffolds arranged in 3D printed-lattice (P-β-TCP and randomly-porous, template-casted (N-β-TCP structures. Our results indicate that SCs proliferated well and expressed the phenotypic markers p75LNGFR and the S100-β subunit of SCs as well as displayed growth morphology on both scaffolds, but SCs showed spindle-shaped morphology with a significant degree of SCs alignment on the P-β-TCP scaffolds, seen to a lesser degree in the N-β-TCP scaffold. The gene expressions of nerve growth factor (β-ngf, neutrophin-3 (nt-3, platelet-derived growth factor (pdgf-bb, and vascular endothelial growth factor (vegf-a were higher at day 7 than at day 14. While no significant differences in protein secretion were measured between these last two time points, the scaffolds promoted the protein secretion at day 3 compared to that on the cell culture plates. These results together imply that the β-TCP scaffolds can support SC cell growth and that the 3D-printed scaffold appeared to significantly promote the alignment of SCs along the struts. Further studies are needed to investigate the early and late stage relationship between gene expression and protein secretion of SCs on the scaffolds with refined characteristics, thus better exploring the potential of SCs to support vascularization and innervation in synthetic bone grafts.

Efficient degradation of sulfamethazine in simulated and real wastewater at slightly basic pH values using Co-SAM-SCS /H2O2 Fenton-like system.

Science.gov (United States)

Cheng, Min; Zeng, Guangming; Huang, Danlian; Lai, Cui; Liu, Yang; Zhang, Chen; Wan, Jia; Hu, Liang; Zhou, Chengyun; Xiong, Weiping

2018-07-01

The presence of antibiotics in aquatic environments has attracted global concern. Fenton process is an attractive yet challenging method for antibiotics degradation, especially when such a reaction can be conducted at neutral pH values. In this study, a novel composite Fe/Co catalyst was synthesized via the modification of steel converter slag (SCS) by salicylic acid-methanol (SAM) and cobalt nitrate (Co(NO 3 ) 2 ). The catalysts were characterized by N 2 -Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results indicated that the Co-SAM-SCS/H 2 O 2 Fenton-like system was very effective for sulfamethazine (SMZ) degradation at a wide pH range. At initial pH of 7.0, the degradation rate of SMZ in Co-SAM-SCS/H 2 O 2 system was 2.48, 3.20, 6.18, and 16.21 times of that in Fe-SAM-SCS/H 2 O 2 , SAM-SCS/H 2 O 2 , Co(NO 3 ) 2 /H 2 O 2 and SCS/H 2 O 2 system, respectively. The preliminary analysis suggested that high surface area of Co-SAM-SCS sample and synergistic effect between introduced Co and SAM-SCS are responsible for the efficient catalytic activity. During the degradation, three main intermediates were identified by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. Based on this, a possible degradation pathway was proposed. The SEM images, XRD patterns and XPS spectra before and after the reactions demonstrate that the crystal and chemical structure of Co-SAM-SCS after five cycles are almost unchanged. Besides, the Co-SAM-SCS presented low iron and cobalt leaching (0.17 mg/L and 2.36 mg/L, respectively). The studied Fenton-like process also showed high degradation of SMZ in river water and municipal wastewater. The progress will bring valuable insights to develop high-performance heterogeneous Fenton-like catalysts for environmental remediation. Copyright © 2018

Reply to comment by Fred L. Ogden et al. on "Beyond the SCS-CN method: A theoretical framework for spatially lumped rainfall-runoff response"

Science.gov (United States)

Bartlett, M. S.; Parolari, A. J.; McDonnell, J. J.; Porporato, A.

2017-07-01

Though Ogden et al. list several shortcomings of the original SCS-CN method, fit for purpose is a key consideration in hydrological modelling, as shown by the adoption of SCS-CN method in many design standards. The theoretical framework of Bartlett et al. [2016a] reveals a family of semidistributed models, of which the SCS-CN method is just one member. Other members include event-based versions of the Variable Infiltration Capacity (VIC) model and TOPMODEL. This general model allows us to move beyond the limitations of the original SCS-CN method under different rainfall-runoff mechanisms and distributions for soil and rainfall variability. Future research should link this general model approach to different hydrogeographic settings, in line with the call for action proposed by Ogden et al.

Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice.

Science.gov (United States)

Lombardo, Ylenia; Scopelliti, Alessandro; Cammareri, Patrizia; Todaro, Matilde; Iovino, Flora; Ricci-Vitiani, Lucia; Gulotta, Gaspare; Dieli, Francesco; de Maria, Ruggero; Stassi, Giorgio

2011-01-01

The limited clinical response observed in many patients with colorectal cancer may be related to the presence of chemoresistant colorectal cancer stem cells (CRC-SCs). Bone morphogenetic protein 4 (BMP4) promotes the differentiation of normal colonic stem cells. We investigated whether BMP4 might be used to induce differentiation of CRC-SCs and for therapeutic purposes. CRC-SCs were isolated from 25 tumor samples based on expression of CD133 or using a selection culture medium. BMP4 expression and activity on CRC-SCs were evaluated in vitro; progeny of the stem cells were evaluated by immunofluorescence, immunoblot, and flow cytometry analyses. The potential therapeutic effect of BMP4 was assessed in immunocompromised mice after injection of CRC-SCs that responded to chemotherapy (n = 4) or that did not (n = 2). CRC-SCs did not express BMP4 whereas differentiated cells did. Recombinant BMP4 promoted differentiation and apoptosis of CRC-SCs in 12 of 15 independent experiments; this effect did not depend on Small Mothers against decapentaplegic (Smad)4 expression level or microsatellite stability. BMP4 activated the canonical and noncanonical BMP signaling pathways, including phosphoInositide 3-kinase (PI3K) and PKB (protein kinase B)/AKT. Mutations in PI3K or loss of Phosphatase and Tensin homolog (PTEN) in Smad4-defective tumors made CRC-SCs unresponsive to BMP4. Administration of BMP4 to immunocompromised mice with tumors that arose from CRC-SCs increased the antitumor effects of 5-fluorouracil and oxaliplatin. BMP4 promotes terminal differentiation, apoptosis, and chemosensitization of CRC-SCs in tumors that do not have simultaneous mutations in Smad4 and constitutive activation of PI3K. BMP4 might be developed as a therapeutic agent against cancer stem cells in advanced colorectal tumors. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

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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

Characterization of Wnt and Notch-Responsive Lgr5+ Hair Cell Progenitors in the Striolar Region of the Neonatal Mouse Utricle

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You, Dan; Guo, Luo; Li, Wenyan; Sun, Shan; Chen, Yan; Chai, Renjie; Li, Huawei

2018-01-01

Dysfunctions in hearing and balance are largely connected with hair cell (HC) loss. Although regeneration of HCs in the adult cochlea does not occur, there is still limited capacity for HC regeneration in the mammalian utricle from a distinct population of supporting cells (SCs). In response to HC damage, these Lgr5+ SCs, especially those in the striolar region, can regenerate HCs. In this study, we isolated Lgr5+ SCs and Plp1+ SCs (which originate from the striolar and extrastriolar regions, respectively) from transgenic mice by flow cytometry so as to compare the properties of these two subsets of SCs. We found that the Lgr5+ progenitors had greater proliferation and HC regeneration ability than the Plp1+ SCs and that the Lgr5+ progenitors responded more strongly to Wnt and Notch signaling than Plp1+ SCs. We then compared the gene expression profiles of the two populations by RNA-Seq and identified several genes that were significantly differentially expressed between the two populations, including genes involved in the cell cycle, transcription and cell signaling pathways. Targeting these genes and pathways might be a potential way to activate HC regeneration. PMID:29760650

N-Cadherin Upregulation Promotes the Neurogenic Differentiation of Menstrual Blood-Derived Endometrial Stem Cells.

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Liu, Yanli; Yang, Fen; Liang, Shengying; Liu, Qing; Fu, Sulei; Wang, Zhenyu; Yang, Ciqing; Lin, Juntang

2018-01-01

Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.

Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

Science.gov (United States)

Hatazawa, Yukino; Ono, Yusuke; Hirose, Yuma; Kanai, Sayaka; Fujii, Nobuharu L; Machida, Shuichi; Nishino, Ichizo; Shimizu, Takahiko; Okano, Masaki; Kamei, Yasutomi; Ogawa, Yoshihiro

2018-03-01

DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5) mRNA was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5) mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.-Hatazawa, Y., Ono, Y., Hirose, Y., Kanai, S., Fujii, N. L., Machida, S., Nishino, I., Shimizu, T., Okano, M., Kamei, Y., Ogawa, Y. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

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.

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

International Nuclear Information System (INIS)

Chatterjee, Somik; Yin, Hongshan; Nam, Deokhwa; Li, Yong; Ma, Ke

2015-01-01

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 −/− 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

Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair

Energy Technology Data Exchange (ETDEWEB)

Zhan, Chuan, E-mail: zhchuansy@163.com; Ma, Cheng-bin; Yuan, Hong-mou; Cao, Bao-yuan; Zhu, Jia-jun

2015-12-04

Background: Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo. Methods: Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated. Results: M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs. Conclusion: M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration. - Highlights: • M2 macrophages-derived MVs elevated migration and proliferation of SCs. • M2 macrophages-derived MVs up-regulated NFG and Laminin expression of SCs. • MiR-223 expression was increased in M2 macrophages-derived MVs. • MiR-223 inhibitor reduced migration and proliferation of SCs co-incubated with MVs. • MiR-223 inhibitor down-regulated NFG and Laminin levels of SCs co-incubated with MVs.

Mobilisation of satellite cells following ischaemia and reperfusion in ...

African Journals Online (AJOL)

Objective. To describe the morphological and morphometric features of activated skeletal muscle satellite cells in primates, using an ischaemic reperfusion model. Setting. The study was undertaken at the Biomedical Resource Centre and the Electron Microscopy Unit of the University of KwaZulu-Natal. Interventions.

The analysis of SCS return momentum effects on the RCS water level during mid-loop operations

Energy Technology Data Exchange (ETDEWEB)

swang Seo, J.; Young Yang, J.; Tack Hwang, S. [Seoul National Univ. (Korea, Republic of)

1995-09-01

An accurate prediction of Reactor Coolant System (RCS) water levels is of importance in the determination of allowable operating range to ensure the safety during the mid-loop operations. However, complex hydraulic phenomena induced by Shutdown Cooling System (SCS) return momentum cause different water levels from those in the loop where the water level indicators are located. This was apparantly observed at the pre-core cold hydro test of the Younggwang Nuclear Unit 3 (YGN 3) in Korea. In this study, in order to analytically understand the effect of the SCS return momentum on the RCS water level and its general trend, a model using one-dimensional momentum equation, hydraulic jump, Bernoulli equation, flow resistance coefficient, and total water volume conservation has been developed to predict the RCS water levels at various RCS locations during the mid-loop conditions and the simulation results were compared with the test data. The analysis shows that the hydraulic jump in the operating cold legs in conjunction with the momentum loss throughout the RCS is the main cause creating the water level differences at various RCS locations. The prediction results provide good explanations for the test data and show the significant effect of the SCS return momentum on the RCS water levels.

The analysis of SCS return momentum effects on the RCS water level during mid-loop operations

International Nuclear Information System (INIS)

swang Seo, J.; Young Yang, J.; Tack Hwang, S.

1995-01-01

An accurate prediction of Reactor Coolant System (RCS) water levels is of importance in the determination of allowable operating range to ensure the safety during the mid-loop operations. However, complex hydraulic phenomena induced by Shutdown Cooling System (SCS) return momentum cause different water levels from those in the loop where the water level indicators are located. This was apparantly observed at the pre-core cold hydro test of the Younggwang Nuclear Unit 3 (YGN 3) in Korea. In this study, in order to analytically understand the effect of the SCS return momentum on the RCS water level and its general trend, a model using one-dimensional momentum equation, hydraulic jump, Bernoulli equation, flow resistance coefficient, and total water volume conservation has been developed to predict the RCS water levels at various RCS locations during the mid-loop conditions and the simulation results were compared with the test data. The analysis shows that the hydraulic jump in the operating cold legs in conjunction with the momentum loss throughout the RCS is the main cause creating the water level differences at various RCS locations. The prediction results provide good explanations for the test data and show the significant effect of the SCS return momentum on the RCS water levels

The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells.

Science.gov (United States)

Fan, F; Bellister, S; Lu, J; Ye, X; Boulbes, D R; Tozzi, F; Sceusi, E; Kopetz, S; Tian, F; Xia, L; Zhou, Y; Bhattacharya, R; Ellis, L M

2015-02-03

Isolation of colorectal cancer (CRC) cell populations enriched for cancer stem cells (CSCs) may facilitate target identification. There is no consensus regarding the best methods for isolating CRC stem cells (CRC-SCs). We determined the suitability of various cellular models and various stem cell markers for the isolation of CRC-SCs. Established human CRC cell lines, established CRC cell lines passaged through mice, patient-derived xenograft (PDX)-derived cells, early passage/newly established cell lines, and cells directly from clinical specimens were studied. Cells were FAC-sorted for the CRC-SC markers CD44, CD133, and aldehyde dehydrogenase (ALDH). Sphere formation and in vivo tumorigenicity studies were used to validate CRC-SC enrichment. None of the markers studied in established cell lines, grown either in vitro or in vivo, consistently enriched for CRC-SCs. In the three other cellular models, CD44 and CD133 did not reliably enrich for stemness. In contrast, freshly isolated PDX-derived cells or early passage/newly established CRC cell lines with high ALDH activity formed spheres in vitro and enhanced tumorigenicity in vivo, whereas cells with low ALDH activity did not. PDX-derived cells, early passages/newly established CRC cell lines and cells from clinical specimen with high ALDH activity can be used to identify CRC-SC-enriched populations. Established CRC cell lines should not be used to isolate CSCs.

Chrodrimanins O-S from the fungus Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus.

Science.gov (United States)

Kong, Fan-Dong; Zhang, Ren-Shuai; Ma, Qing-Yun; Xie, Qing-Yi; Wang, Pei; Chen, Peng-Wei; Zhou, Li-Man; Dai, Hao-Fu; Luo, Du-Qiang; Zhao, You-Xing

2017-10-01

Five new meroterpenoids, chrodrimanins O-S (1-5), as well as a known one (6), were isolated from the fermentation broth of Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus, from Haikou Bay, China. The structures including the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and ECD spectra analysis along with quantum ECD calculations. Among them, compound 1 represents the first example of an unusual trichlorinated meroterpenoid with an unique dichlorine functionality. Compounds 1 and 4-6 displayed inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) with IC 50 values of 71.6, 62.5, 63.1, and 39.6μM, respectively, and showed no apparent activity against three tumor cell lines (A549, HepG2, and Hela) and human umbilical vein endothelial cells (HUVEC) at 10μM. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-Compassion Scale (SCS): Psychometric Properties of The French Translation and Its Relations with Psychological Well-Being, Affect and Depression.

Science.gov (United States)

Kotsou, Ilios; Leys, Christophe

2016-01-01

Over the past few years, the topic of self-compassion has attracted increasing attention from both scientific and clinical fields. The Self-Compassion Scale (SCS) was created to specifically capture this way of being kind and understanding towards oneself in moments of turmoil. In this article, we present a French adaptation of the SCS. We first explore the psychometric properties of this adaptation and then investigate its relation to psychological well-being. As in the original version of the SCS, the French adaptation has a strong 6-factor structure but a weaker hierarchical second order structure. However the bi-factor model yields a good omega index suggesting the relevance of a single score accounting for self-compassion. Moreover, there was a relation between the SCS and classical outcomes such as a positive relation with psychological well-being and negative relation with depressive symptoms. We then hypothesized that self-compassion would have a moderating role on the relation between affect and depression. This hypothesis was confirmed: expressing negative affect is correlated with depressive symptoms; however, being kind with oneself lowers depressive symptoms even when expressing negative affect. In conclusion, this research presents a valid self-compassion measure for French-speaking researchers and clinicians and outlines the need for further research on the concept of self-compassion.

Effect of incubation temperature on neuropeptide Y and neuropeptide Y receptors in turkey and chicken satellite cells.

Science.gov (United States)

Clark, Daniel L; McCormick, Janet L; Velleman, Sandra G

2018-05-01

Neuropeptide Y (NPY) is an appetite stimulating peptide released from the central nervous system and impacts the function of many different cell types. A recent transcriptome study showed that NPY expression was altered when turkey breast muscle satellite cells were incubated at low or high temperatures, suggesting NPY may mediate temperature effects on satellite cells. However, to date minimal information exists describing the expression and function of NPY in satellite cells. The objective of this study was to determine how temperature impacts NPY and NPY receptor gene expression in satellite cells isolated from turkeys and chickens with differing genetic lineages. Two broiler and two turkey breast muscle satellite cell lines were incubated at 35, 38 or 41 °C during proliferation and differentiation. In both turkey lines, NPY, and receptors NPY2R and NPY5R expression increased at elevated temperatures after 72 h of proliferation. During differentiation NPY and NPY5R expression increased in both turkey lines with higher temperatures, whereas NPY2R was minimally affected by temperature. In contrast, in both chicken cell lines there were few significant differences for NPY and NPY receptor expression across temperature during proliferation. During differentiation, the temperature effect was different in the two chicken cell lines. In the BPM8 chicken line, there were few differences in NPY and NPY receptors across temperature; whereas elevated temperatures increased NPY, NPY2R, and NPY5R expression in the 708 line. The differences between turkey and chicken lines suggest NPY has species specific satellite cell functions in response to heat stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

Science.gov (United States)

Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

2016-05-01

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contribution of Nanostructures in High Performance Solar Cells

Science.gov (United States)

Aly, Abouelmaaty M.; Ebrahim, Essamudin A.; Sweelem, Emad

2017-11-01

Nanotechnology has great contributions in various fields, especially in solar energy conversion through solar cells (SCs). Nanostructured SCs can provide high performance with lower fabrication costs. The transition from fossil fuel energy to renewable sustainable energy represents a major technological challenge for the world. In the last years, the industry of SCs has grown rapidly due to strong attention in renewable energy in order to handle the problem of global climate change that is now believed to occur due to use of the fossil fuels. Cost is an influential factor in the eventual success of any solar technology, since inexpensive SCs are needed to produce electricity, especially for rural areas and for third world countries. Therefore, new developments in nanotechnology may open the door for the production of inexpensive and more efficient SCs by reducing the manufacturing costs of SCs. Utilizing nanotechnology in cheaper SCs will help maintain the environment. This article covers a review of the progress that has been made to-date to enhance efficiencies of various nanostructures used in SCs, including utilizations of all the wavelengths present in of the solar spectrum.

Endogenous WNT Signals Mediate BMP-Induced and Spontaneous Differentiation of Epiblast Stem Cells and Human Embryonic Stem Cells

Directory of Open Access Journals (Sweden)

Dorota Kurek

2015-01-01

Full Text Available Therapeutic application of human embryonic stem cells (hESCs requires precise control over their differentiation. However, spontaneous differentiation is prevalent, and growth factors induce multiple cell types; e.g., the mesoderm inducer BMP4 generates both mesoderm and trophoblast. Here we identify endogenous WNT signals as BMP targets that are required and sufficient for mesoderm induction, while trophoblast induction is WNT independent, enabling the exclusive differentiation toward either lineage. Furthermore, endogenous WNT signals induce loss of pluripotency in hESCs and their murine counterparts, epiblast stem cells (EpiSCs. WNT inhibition obviates the need to manually remove differentiated cells to maintain cultures and improves the efficiency of directed differentiation. In EpiSCs, WNT inhibition stabilizes a pregastrula epiblast state with novel characteristics, including the ability to contribute to blastocyst chimeras. Our findings show that endogenous WNT signals function as hidden mediators of growth factor-induced differentiation and play critical roles in the self-renewal of hESCs and EpiSCs.

Membrane organization determines barrier properties of endothelial cells and short-chain sphingolipid-facilitated doxorubicin influx.

Science.gov (United States)

van Hell, A J; Klymchenko, A; Gueth, D M; van Blitterswijk, W J; Koning, G A; Verheij, M

2014-09-01

The endothelial lining and its outer lipid membrane are the first major barriers drug molecules encounter upon intravenous administration. Our previous work identified lipid analogs that counteract plasma membrane barrier function for a series of amphiphilic drugs. For example, short-chain sphingolipids (SCS), like N-octanoyl-glucosylceramide, effectively elevated doxorubicin accumulation in tumor cells, both in vitro and in vivo, and in endothelial cells, whereas other (normal) cells remained unaffected. We hypothesize here that local membrane lipid composition and the degree of lipid ordering define SCS efficacy in individual cells. To this end, we study the differential effect of SCS on bovine aortic endothelial cells (BAEC) in its confluent versus proliferative state, as a model system. While their (plasma membrane) lipidome stays remarkably unaltered when BAECs reach confluency, their lipids segregate to form apical and basolateral domains. Using probe NR12S, we reveal that lipids in the apical membrane are more condensed/liquid-ordered. SCS preferentially attenuate the barrier posed by these condensed membranes and facilitate doxorubicin influx in these particular membrane regions. We confirm these findings in MDCK cells and artificial membranes. In conclusion, SCS-facilitated drug traversal acts on condensed membrane domains, elicited by confluency in resting endothelium. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamic Quantification of Host Schwann Cell Migration into Peripheral Nerve Allografts

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Whitlock, Elizabeth L.; Myckatyn, Terence M.; Tong, Alice Y.; Yee, Andrew; Yan, Ying; Magill, Christina K.; Johnson, Philip J.; Mackinnon, Susan E.

2010-01-01

Host Schwann cell (SC) migration into nerve allografts is the limiting factor in the duration of immunosuppression following peripheral nerve allotransplantation, and may be affected by different immunosuppressive regimens. Our objective was to compare SC migration patterns between clinical and experimental immunosuppression regimens both over time and at the harvest endpoint. Eighty mice that express GFP under the control of the Schwann cell specific S100 promoter were engrafted with allogeneic, nonfluorescent sciatic nerve grafts. Mice received immunosuppression with either tacrolimus (FK506), or experimental T-cell triple costimulation blockade (CSB), consisting of CTLA4-immunoglobulin fusion protein, anti-CD40 monoclonal antibody, and anti-inducible costimulator monoclonal antibody. Migration of GFP-expressing host SCs into wild-type allografts was assessed in vivo every 3 weeks until 15 weeks postoperatively, and explanted allografts were evaluated for immunohistochemical staining patterns to differentiate graft from host SCs. Immunosuppression with tacrolimus exhibited a plateau of SC migration, characterized by significant early migration (< 3 weeks) followed by a constant level of host SCs in the graft (15 weeks). At the endpoint, graft fluorescence was decreased relative to surrounding host nerve, and donor SCs persisted within the graft. CSB-treated mice displayed gradually increasing migration of host SCs into the graft, without the plateau noted in tacrolimus-treated mice, and also maintained a population of donor SCs at the 15-week endpoint. SC migration patterns are affected by immunosuppressant choice, particularly in the immediate postoperative period, and the use of a single treatment of CSB may allow for gradual population of nerve allografts with host SCs. PMID:20633557

Satellite cell frequency in cross-age transplanted rat extensor digitorum longus muscles

Czech Academy of Sciences Publication Activity Database

Rudež, M.; Carlson, B. M.; Sajko, Š.; Kubínová, Lucie; Wernig, A.; Eržen, I.

2004-01-01

Roč. 14, č. 3 (2004), s. 155-159 ISSN 1120-9992 Grant - others:European programme(XE) QLKG-1999-02034 Institutional research plan: CEZ:AV0Z5011922 Keywords : aging * confocal microscopy * satellite cell s Subject RIV: EA - Cell Biology

Advanced Solar Cells for Satellite Power Systems

Science.gov (United States)

Flood, Dennis J.; Weinberg, Irving

1994-01-01

The multiple natures of today's space missions with regard to operational lifetime, orbital environment, cost and size of spacecraft, to name just a few, present such a broad range of performance requirements to be met by the solar array that no single design can suffice to meet them all. The result is a demand for development of specialized solar cell types that help to optimize overall satellite performance within a specified cost range for any given space mission. Historically, space solar array performance has been optimized for a given mission by tailoring the features of silicon solar cells to account for the orbital environment and average operating conditions expected during the mission. It has become necessary to turn to entirely new photovoltaic materials and device designs to meet the requirements of future missions, both in the near and far term. This paper will outline some of the mission drivers and resulting performance requirements that must be met by advanced solar cells, and provide an overview of some of the advanced cell technologies under development to meet them. The discussion will include high efficiency, radiation hard single junction cells; monolithic and mechanically stacked multiple bandgap cells; and thin film cells.

In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice

Directory of Open Access Journals (Sweden)

Bradley J. Walters

2017-04-01

Full Text Available Summary: Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs declines abruptly after postnatal maturation. We find that combining p27Kip1 deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27Kip1 deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates auditory HC regeneration and suggest p27Kip1, GATA3, and POU4F3 as additional therapeutic targets for ATOH1-mediated HC regeneration. : Auditory hair cells are nonregenerative, resulting in persistent hearing loss upon damage. Walters et al. find that manipulating two genes, p27Kip1 and Atoh1, induces the conversion of nonsensory cells to hair cells in adult mice. This effect is mediated by GATA3 and POU4F3, where POU4F3 alone was found to convert nonsensory cells. Keywords: regeneration, aging, differentiation, proliferation, development, cancer, sensory, cochlea, hearing

Schwann Cells in Neuromuscular Junction Formation and Maintenance.

Science.gov (United States)

Barik, Arnab; Li, Lei; Sathyamurthy, Anupama; Xiong, Wen-Cheng; Mei, Lin

2016-09-21

The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation. Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences

The stem cell secretome and its role in brain repair.

Science.gov (United States)

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2013-12-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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

Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

Science.gov (United States)

Celià-Terrassa, Toni

2018-05-04

Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

NARCIS (Netherlands)

Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

2012-01-01

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family

Heterogeneity of limbal basal epithelial progenitor cells.

Science.gov (United States)

Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

2010-11-01

Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

Tracking stem cells in tissue-engineered organs using magnetic nanoparticles

OpenAIRE

Hachani, R.; Lowdell, M.; Birchall, M.; Thanh, N. T.

2013-01-01

The use of human stem cells (SCs) in tissue engineering holds promise in revolutionising the treatment of numerous diseases. There is a pressing need to comprehend the distribution, movement and role of SCs once implanted onto scaffolds. Nanotechnology has provided a platform to investigate this through the development of inorganic magnetic nanoparticles (MNPs). MNPs can be used to label and track SCs by magnetic resonance imaging (MRI) since this clinically available imaging modality has hig...

Essential role of miR-200c in regulating self-renewal of breast cancer stem cells and their counterparts of mammary epithelium

International Nuclear Information System (INIS)

Feng, Zhong-Ming; Qiu, Jun; Chen, Xie-Wan; Liao, Rong-Xia; Liao, Xing-Yun; Zhang, Lu-Ping; Chen, Xu; Li, Yan; Chen, Zheng-Tang; Sun, Jian-Guo

2015-01-01

Breast cancer stem cells (BCSCs) have been reported as the origin of breast cancer and the radical cause of drug resistance, relapse and metastasis in breast cancer. BCSCs could be derived from mutated mammary epithelial stem cells (MaSCs). Therefore, comparing the molecular differences between BCSCs and MaSCs may clarify the mechanism underlying breast carcinogenesis and the targets for gene therapy. Specifically, the distinct miRNome data of BCSCs and MaSCs need to be analyzed to find out the key miRNAs and reveal their roles in regulating the stemness of BCSCs. MUC1 − ESA + cells were isolated from normal mammary epithelial cell line MCF-10A by fluorescence-activated cell sorting (FACS) and tested for stemness by clonogenic assay and multi-potential differentiation experiments. The miRNA profiles of MaSCs, BCSCs and breast cancer MCF-7 cells were compared to obtain the candidate miRNAs that may regulate breast tumorigenesis. An miRNA consecutively upregulated from MaSCs to BCSCs to MCF-7 cells, miR-200c, was chosen to determine its role in regulating the stemness of BCSCs and MaSCs in vitro and in vivo. Based on bioinformatics, the targets of miR-200c were validated by dual-luciferase report system, western blot and rescue experiments. In a 2-D clonogenic assay, MUC1 − ESA + cells gave rise to multiple morphological colonies, including luminal colonies, myoepithelial colonies and mixed colonies. The clonogenic potential of MUC1 − ESA + (61.5 ± 3.87 %) was significantly higher than that of non-stem MCF-10A cells (53.5 ± 3.42 %) (P < 0.05). In a 3-D matrigel culture, MUC1 − ESA + cells grew into mammospheres with duct-like structures. A total of 12 miRNAs of interest were identified, 8 of which were upregulated and 4 downregulated in BCSCs compared with MaSCs. In gain- and lost-of-function assays, miR-200c was sufficient to inhibit the self-renewal of BCSCs and MaSCs in vitro and the growth of BCSCs in vivo. Furthermore, miR-200c negatively regulated

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)

A sediment graph model based on SCS-CN method

Science.gov (United States)

Singh, P. K.; Bhunya, P. K.; Mishra, S. K.; Chaube, U. C.

2008-01-01

SummaryThis paper proposes new conceptual sediment graph models based on coupling of popular and extensively used methods, viz., Nash model based instantaneous unit sediment graph (IUSG), soil conservation service curve number (SCS-CN) method, and Power law. These models vary in their complexity and this paper tests their performance using data of the Nagwan watershed (area = 92.46 km 2) (India). The sensitivity of total sediment yield and peak sediment flow rate computations to model parameterisation is analysed. The exponent of the Power law, β, is more sensitive than other model parameters. The models are found to have substantial potential for computing sediment graphs (temporal sediment flow rate distribution) as well as total sediment yield.

Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells

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Gerard Ruiz-Babot

2018-01-01

Full Text Available Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies.

Culturing muscle fibres in hanging drop: a novel approach to solve an old problem.

Science.gov (United States)

Archacka, Karolina; Pozzobon, Michela; Repele, Andrea; Rossi, Carlo Alberto; Campanella, Michelangelo; De Coppi, Paolo

2014-02-01

The satellite cells (SCs) associated with muscle fibres play a key role in postnatal growth and regeneration of skeletal muscle. Commonly used methods of isolation and in vitro culture of SCs lead to the mixture of their subpopulations that exist within muscle. To solve this problem, we used the well established technique, the hanging drop system, to culture SCs in a three-dimensional environment and thus, to monitor them in their original niche. Using hanging drop technique, we were able to culture SCs associated with the fibre at least for 9 days with one transfer of fibres to the fresh drops. In comparison, in the classical method of myofibres culture, that is, on the dishes coated with Matrigel, SCs leave the fibres within 3 days after the isolation. Cells cultured in both systems differed in expression of Pax7 and MyoD. While almost all cells cultured in adhesion system expressed MyoD before the fifth day of the culture, the majority of SCs cultured in hanging drop still maintained expression of Pax7 and were not characterised by the presence of MyoD. Among the cells cultured with single myofibre for up to 9 days, we identified two different subclones of SCs: low proliferative clone and high proliferative clone, which differed in proliferation rate and membrane potential. The hanging drop enables the myofibres to be kept in suspension for at least 9 days, and thus, allows SCs and their niche to interact each other for prolonged time. In a consequence, SCs cultured in hanging drop maintain expression of Pax7 while those cultured in a traditional adhesion culture, that is, devoid of signals from the original niche, activate and preferentially undergo differentiation as manifested by expression of MyoD. Thus, the innovative method of SCs culturing in the hanging drop system may serve as a useful tool to study the fate of different subpopulations of these cells in their anatomical location and to determine reciprocal interactions between them and their niche. �

Electrically induced brain-derived neurotrophic factor release from Schwann cells.

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Luo, Beier; Huang, Jinghui; Lu, Lei; Hu, Xueyu; Luo, Zhuojing; Li, Ming

2014-07-01

Regulating the production of brain-derived neurotrophic factor (BDNF) in Schwann cells (SCs) is critical for their application in traumatic nerve injury, neurodegenerative disorders, and demyelination disease in both central and peripheral nervous systems. The present study investigated the possibility of using electrical stimulation (ES) to activate SCs to release BDNF. We found that short-term ES was capable of promoting BDNF production from SCs, and the maximal BDNF release was achieved by ES at 6 V (3 Hz, 30 min). We further examined the involvement of intracellular calcium ions ([Ca2+]i) in the ES-induced BDNF production in SCs by pharmacological studies. We found that the ES-induced BDNF release required calcium influx through T-type voltage-gated calcium channel (VGCC) and calcium mobilization from internal calcium stores, including inositol triphosphate-sensitive stores and caffeine/ryanodine-sensitive stores. In addition, calcium-calmodulin dependent protein kinase IV (CaMK IV), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) were found to play important roles in the ES-induced BDNF release from SCs. In conclusion, ES is capable of activating SCs to secrete BDNF, which requires the involvement of calcium influx through T-type VGCC and calcium mobilization from internal calcium stores. In addition, activation of CaMK IV, MAPK, and CREB were also involved in the ES-induced BDNF release. The findings indicate that ES can improve the neurotrophic ability in SCs and raise the possibility of developing electrically stimulated SCs as a source of cell therapy for nerve injury in both peripheral and central nervous systems. Copyright © 2014 Wiley Periodicals, Inc.

Somatic stem cell differentiation is regulated by PI3K/Tor signaling in response to local cues.

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Amoyel, Marc; Hillion, Kenzo-Hugo; Margolis, Shally R; Bach, Erika A

2016-11-01

Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation. These results indicate that there is a local 'differentiation' niche that upregulates PI3K/Tor signaling in the early daughters of CySCs. Finally, we demonstrate that CySCs secrete the Dilp-binding protein ImpL2, the Drosophila homolog of IGFBP7, into the stem cell niche, which blocks InR activation in CySCs. Thus, we show that somatic cell differentiation is controlled by PI3K/Tor signaling downstream of InR and that the local production of positive and negative InR signals regulates the differentiation niche. These results support a model in which leaving the stem cell niche and initiating differentiation are actively induced by signaling. © 2016. Published by The Company of Biologists Ltd.

Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

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Yang Li

Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

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Scimeca, Manuel; Bonanno, Elena; Piccirilli, Eleonora; Baldi, Jacopo; Mauriello, Alessandro; Orlandi, Augusto; Tancredi, Virginia; Gasbarra, Elena; Tarantino, Umberto

2015-01-01

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. PMID:26101529

Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

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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.

[Spinal cord stimulation (SCS) as a treatment for the spread phenomenon related to complex regional pain syndrome type- I (CRPS-I )].

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Goto, Shinichi; Taira, Takaomi; Hori, Tomokatsu

2009-09-01

The authors describe an experience of spinal cord stimulation (SCS) in a 30-year-old woman who developed complex regional pain syndrome type-I (CRPS-I) with spread phenomenon. She had received lumbar SCS under a diagnosis of CRPS-I in her left leg for 8 years. She had refractory pain in her right arm for the recent two years. There was no new lesion explaining her refractory pain on physical or radiological examination. Thus, the pain in her right upper arm was considered as spread phenomenon of CRPS-I. Test stimulation with cervical epidural spinal electrode showed good results and the pulse generator was implanted. It is suggested that the symptom of CRPS-I involving spread phenomenon was possibly due to a cortical reorganization. But a certain effect of SCS may be contributing to the favorable results of test stimulation for the treatment of CRPS-I with spread phenomenon in this case.

Performance Evaluation of Moving Small-Cell Network with Proactive Cache

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Young Min Kwon

2016-01-01

Full Text Available Due to rapid growth in mobile traffic, mobile network operators (MNOs are considering the deployment of moving small-cells (mSCs. mSC is a user-centric network which provides voice and data services during mobility. mSC can receive and forward data traffic via wireless backhaul and sidehaul links. In addition, due to the predictive nature of users demand, mSCs can proactively cache the predicted contents in off-peak-traffic periods. Due to these characteristics, MNOs consider mSCs as a cost-efficient solution to not only enhance the system capacity but also provide guaranteed quality of service (QoS requirements to moving user equipment (UE in peak-traffic periods. In this paper, we conduct extensive system level simulations to analyze the performance of mSCs with varying cache size and content popularity and their effect on wireless backhaul load. The performance evaluation confirms that the QoS of moving small-cell UE (mSUE notably improves by using mSCs together with proactive caching. We also show that the effective use of proactive cache significantly reduces the wireless backhaul load and increases the overall network capacity.

Methods to isolate a large amount of generative cells, sperm cells and vegetative nuclei from tomato pollen for omics analysis

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Yunlong eLu

2015-06-01

Full Text Available The development of sperm cells from microspores involves a set of finely regulated molecular and cellular events and the coordination of these events. The mechanisms underlying these events and their interconnections remain a major challenge. Systems analysis of genome-wide molecular networks and functional modules with high-throughput omics approaches is crucial for understanding the mechanisms; however, this study is hindered because of the difficulty in isolating a large amount of cells of different types, especially generative cells (GCs, from the pollen. Here, we optimized the conditions of tomato pollen germination and pollen tube growth to allow for long-term growth of pollen tubes in vitro with sperm cells (SCs generated in the tube. Using this culture system, we developed methods for isolating GCs, SCs and vegetative-cell nuclei (VN from just-germinated tomato pollen grains and growing pollen tubes and their purification by Percoll density gradient centrifugation. The purity and viability of isolated GCs and SCs were confirmed by microscopy examination and fluorescein diacetate staining, respectively, and the integrity of VN was confirmed by propidium iodide staining. We could obtain about 1.5 million GCs and 2.0 million SCs each from 180 mg initiated pollen grains, and 10 million VN from 270 mg initiated pollen grains germinated in vitro in each experiment. These methods provide the necessary preconditions for systematic biology studies of SC development and differentiation in higher plants.

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.

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Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

2017-04-01

Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.

Aging of mice is associated with p16(Ink4a)- and β-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells.

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Hall, Brandon M; Balan, Vitaly; Gleiberman, Anatoli S; Strom, Evguenia; Krasnov, Peter; Virtuoso, Lauren P; Rydkina, Elena; Vujcic, Slavoljub; Balan, Karina; Gitlin, Ilya; Leonova, Katerina; Polinsky, Alexander; Chernova, Olga B; Gudkov, Andrei V

2016-07-01

Senescent cells (SCs) have been considered a source of age-related chronic sterile systemic inflammation and a target for anti-aging therapies. To understand mechanisms controlling the amount of SCs, we analyzed the phenomenon of rapid clearance of human senescent fibroblasts implanted into SCID mice, which can be overcome when SCs were embedded into alginate beads preventing them from immunocyte attack. To identify putative SC killers, we analyzed the content of cell populations in lavage and capsules formed around the SC-containing beads. One of the major cell types attracted by secretory factors of SCs was a subpopulation of macrophages characterized by p16(Ink4a) gene expression and β-galactosidase activity at pH6.0 (β-gal(pH6)), thus resembling SCs. Consistently, mice with p16(Ink4a) promoter-driven luciferase, developed bright luminescence of their peritoneal cavity within two weeks following implantation of SCs embedded in alginate beads. p16(Ink4a)/β-gal(pH6)-expressing cells had surface biomarkers of macrophages F4/80 and were sensitive to liposomal clodronate used for the selective killing of cells capable of phagocytosis. At the same time, clodronate failed to kill bona fide SCs generated in vitro by genotoxic stress. Old mice with elevated proportion of p16(Ink4a)/β-gal(pH6)-positive cells in their tissues demonstrated reduction of both following systemic clodronate treatment, indicating that a significant proportion of cells previously considered to be SCs are actually a subclass of macrophages. These observations point at a significant role of p16(Ink4a)/β-gal(pH6)-positive macrophages in aging, which previously was attributed solely to SCs. They require re-interpretation of the mechanisms underlying rejuvenating effects following eradication of p16(Ink4a)/β-gal(pH6)-positive cells and reconsideration of potential cellular target for anti-aging treatment.

Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

International Nuclear Information System (INIS)

Zhang, Fenxi; Hong, Yan; Liang, Wenmei; Ren, Tongming; Jing, Suhua; Lin, Juntang

2012-01-01

Highlights: ► Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). ► Presence of SCs dramatically increased proliferation and migration of UCMSCs. ► Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of “nurse” cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

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Zhang, Fenxi, E-mail: fxzhang0824@gmail.com [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Hong, Yan; Liang, Wenmei [Department of Histology and Embryology, Guiyang Medical University, Guizhou 550004, People' s Republic of China (China); Ren, Tongming [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Jing, Suhua [ICU Center, The Third Hospital of Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Lin, Juntang [Stem Cell Center, Xinxiang Medical University, Henan 453003, People' s Republic of China (China)

2012-10-12

Highlights: Black-Right-Pointing-Pointer Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). Black-Right-Pointing-Pointer Presence of SCs dramatically increased proliferation and migration of UCMSCs. Black-Right-Pointing-Pointer Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of 'nurse' cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

Evidence of heterogeneity within bovine satellite cells isolated from young and adult animals.

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Li, J; Gonzalez, J M; Walker, D K; Hersom, M J; Ealy, A D; Johnson, S E

2011-06-01

Satellite cells are a heterogeneous population of myogenic precursors responsible for muscle growth and repair in mammals. The objectives of the experiment were to examine the growth rates and degree of heterogeneity within bovine satellite cells (BSC) isolated from young and adult animals. The BSC were harvested from the semimembranosus of young (4.3 ± 0.5 d) and adult (estimated 24 to 27 mo) cattle and cultured en masse. Young animal BSC re-enter the cell cycle sooner and reach maximal 5-ethynyl-2'-deoxyuridine (EdU) incorporation earlier (P animals after 3, 4, and 5 d in culture. These results indicate that BSC from young animals activate, proliferate, and differentiate sooner than isolates from adult animals. Lineage heterogeneity within BSC was examined using antibodies specific for Pax7 and Myf5, lineage markers of satellite cells, and myoblasts. Immunocytochemistry revealed the majority of Pax7-expressing BSC also express Myf5; a minor population (~5%) fails to exhibit Myf5 immunoreactivity. The percentage of Pax7:Myf5 BSC from young animals decreases sooner (P cell clones were established and analyzed after 10 d. Colonies segregated into 2 groups based upon population doubling time. Immunostaining of the slow-growing colonies (population doubling time ≥ 3 d) revealed that a portion exhibited asymmetric distribution of the lineage markers Pax7 and Myf5, similar to self-renewable mouse muscle stem cells. In summary, these results offer insight into the heterogeneity of BSC and provide evidence for subtle differences between rodent and bovine myogenic precursors.

Investigation of the direct runoff generation mechanism for the analysis of the SCS-CN method applicability to a partial area experimental watershed

OpenAIRE

Soulis, K. X.; Valiantzas, J. D.; Dercas, N.; Londra, P. A.

2009-01-01

The Soil Conservation Service Curve Number (SCS-CN) method is widely used for predicting direct runoff volume for a given rainfall event. The applicability of the SCS-CN method and the direct runoff generation mechanism were thoroughly analysed in a Mediterranean experimental watershed in Greece. The region is characterized by a Mediterranean semi-arid climate. A detailed land cover and soil survey using remote sensing and GIS techniques, showed that the watershed is dominated by coarse soils...

Manipulation of Schwann cell migration across the astrocyte boundary by polysialyltransferase-loaded superparamagnetic nanoparticles under magnetic field

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Xia B

2016-12-01

Full Text Available Bing Xia,* Liangliang Huang,* Lei Zhu, Zhongyang Liu, Teng Ma, Shu Zhu, Jinghui Huang, Zhuojing Luo Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Abstract: Schwann cell (SC transplantation is an attractive strategy for spinal cord injury (SCI. However, the efficacy of SC transplantation has been limited by the poor migratory ability of SCs in the astrocyte-rich central nervous system (CNS environment and the inability to intermingle with the host astrocyte. In this study, we first magnetofected SCs by polysialyltransferase-functionalized superparamagnetic iron oxide nanoparticles (PST/SPIONs to induce overexpression of polysialylation of neural cell adhesion molecule (PSA-NCAM to enhance SC migration ability, before manipulating the direction of SC migration with the assistance of an applied magnetic field (MF. It was found that magnetofection with PST/SPIONs significantly upregulated the expression of PSA-NCAM in SCs, which significantly enhanced the migration ability of SCs, but without preferential direction in the absence of MF. The number and averaged maximum distance of SCs with PST/SPIONs migrating into the astrocyte domain were significantly enhanced by an applied MF. In a 300 µm row along the astrocyte boundary, the number of SCs with PST/SPIONs migrating into the astrocyte domain under an MF was 2.95 and 6.71 times higher than that in the absence of MF and the intact control SCs, respectively. More interestingly, a confrontation assay demonstrated that SCs with PST/SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. In conclusion, SCs with PST/SPIONs showed enhanced preferential migration along the axis of a magnetic force, which might be beneficial for the formation of Büngner bands in the CNS. These findings raise the possibilities of enhancing the

Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating Wnt/β-catenin signaling.

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Bresson, Laura; Faraldo, Marisa M; Di-Cicco, Amandine; Quintanilla, Miguel; Glukhova, Marina A; Deugnier, Marie-Ange

2018-02-21

Stem cells (SCs) drive mammary development, giving rise postnatally to an epithelial bilayer composed of luminal and basal myoepithelial cells. Dysregulation of SCs is thought to be at the origin of certain breast cancers; however, the molecular identity of SCs and the factors regulating their function remain poorly defined. We identified the transmembrane protein podoplanin (Pdpn) as a specific marker of the basal compartment, including multipotent SCs, and found Pdpn localized at the basal-luminal interface. Embryonic deletion of Pdpn targeted to basal cells diminished basal and luminal SC activity and affected the expression of several Wnt/β-catenin signaling components in basal cells. Moreover, Pdpn loss attenuated mammary tumor formation in a mouse model of β-catenin-induced breast cancer, limiting tumor-initiating cell expansion and promoting molecular features associated with mesenchymal-to-epithelial cell transition. In line with the loss-of-function data, we demonstrated that mechanistically Pdpn enhances Wnt/β-catenin signaling in mammary basal cells. Overall, this study uncovers a role for Pdpn in mammary SC function and, importantly, identifies Pdpn as a new regulator of Wnt/β-catenin signaling, a key pathway in mammary development and tumorigenesis. © 2018. Published by The Company of Biologists Ltd.

Frequency of M-cadherin-stained satellite cells declines in human muscles during aging

Czech Academy of Sciences Publication Activity Database

Sajko, Š.; Kubínová, Lucie; Cvetko, E.; Kreft, M.; Wernig, A.; Eržen, I.

2004-01-01

Roč. 52, č. 2 (2004), s. 179-185 ISSN 0022-1554 Grant - others:European programme(XE) QLKG-1999-02034 Institutional research plan: CEZ:AV0Z5011922 Keywords : satellite cells * skeletal muscle * stereology Subject RIV: EA - Cell Biology Impact factor: 2.513, year: 2004

Growth Kinetics, Characterization, and Plasticity of Human Menstrual Blood Stem Cells

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Davood Mehrabani

2016-03-01

Full Text Available One of the readily available sources of mesenchymal stem cells (MSCs is menstrual blood-derived stem cells (Men-SCs, which exhibit characteristics similar to other types of MSCs. This study was performed to determine the growth kinetics, plasticity, and characterization of Men-SCs in women. During spring 2014 in the southern Iranian city of Shiraz, menstrual blood (5 mL was obtained from 10 women on their third day of menstruation in 2 age groups of 30 to 40 and 40 to 50 years old. Ficoll was used to separate the mononuclear cell fraction. After the Men-SCs were cultured, they were subcultured up to passage 4. Growth behavior and population doubling time were evaluated by seeding 5×104 cells into 12- and 24-well culture plates, and the colonies were enumerated. The expression of CD44, CD90, and CD34 was evaluated. The osteogenic potential was assessed by alizarin red staining. The Men-SCs were shown to be plastic adherent and spindle-shaped. Regarding the growth curves in the 12- and 24-well culture plates, it was demonstrated that in the women aged between 30 and 40 years, population doubling time was 55.5 and 62 hours, respectively, while these values in the women aged between 40 and 50 years were 70.4 and 72.4 hours, correspondingly. Positive expression of CD44 and CD90 and negative expression of CD34 were noted. In the osteogenic differentiation medium, the cells differentiated toward osteoblasts. As human Men-SCs are easily collectable without any invasive procedure and are a safe and rapid source of MSCs, they can be a good candidate for stem cell banking and cell transplantation in women.

Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial.

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Zhao, Yong; Jiang, Zhaoshun; Zhao, Tingbao; Ye, Mingliang; Hu, Chengjin; Zhou, Huimin; Yin, Zhaohui; Chen, Yana; Zhang, Ye; Wang, Shanfeng; Shen, Jie; Thaker, Hatim; Jain, Summit; Li, Yunxiang; Diao, Yalin; Chen, Yingjian; Sun, Xiaoming; Fisk, Mary Beth; Li, Heng

2013-07-09

The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease. In an open-label, phase 1/phase 2 study, patients (N=36) with long-standing T2D were divided into three groups (Group A, oral medications, n=18; Group B, oral medications+insulin injections, n=11; Group C having impaired β-cell function with oral medications+insulin injections, n=7). All patients received one treatment with the Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient's circulation. Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61%±1.12 at baseline to 7.25%±0.58 at 12 weeks (P=2.62E-06), and 7.33%±1.02 at one year post-treatment (P=0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production. Clinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in

Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells.

Science.gov (United States)

Ruiz-Babot, Gerard; Balyura, Mariya; Hadjidemetriou, Irene; Ajodha, Sharon J; Taylor, David R; Ghataore, Lea; Taylor, Norman F; Schubert, Undine; Ziegler, Christian G; Storr, Helen L; Druce, Maralyn R; Gevers, Evelien F; Drake, William M; Srirangalingam, Umasuthan; Conway, Gerard S; King, Peter J; Metherell, Louise A; Bornstein, Stefan R; Guasti, Leonardo

2018-01-30

Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs) from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

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Ribeiro-Resende Victor

2012-07-01

Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

Isolation of Human Colon Stem Cells Using Surface Expression of PTK7.

Science.gov (United States)

Jung, Peter; Sommer, Christian; Barriga, Francisco M; Buczacki, Simon J; Hernando-Momblona, Xavier; Sevillano, Marta; Duran-Frigola, Miquel; Aloy, Patrick; Selbach, Matthias; Winton, Douglas J; Batlle, Eduard

2015-12-08

Insertion of reporter cassettes into the Lgr5 locus has enabled the characterization of mouse intestinal stem cells (ISCs). However, low cell surface abundance of LGR5 protein and lack of high-affinity anti-LGR5 antibodies represent a roadblock to efficiently isolate human colonic stem cells (hCoSCs). We set out to identify stem cell markers that would allow for purification of hCoSCs. In an unbiased approach, membrane-enriched protein fractions derived from in vitro human colonic organoids were analyzed by quantitative mass spectrometry. Protein tyrosine pseudokinase PTK7 specified a cell population within human colonic organoids characterized by highest self-renewal and re-seeding capacity. Antibodies recognizing the extracellular domain of PTK7 allowed us to isolate and expand hCoSCs directly from patient-derived mucosa samples. Human PTK7+ cells display features of canonical Lgr5+ ISCs and include a fraction of cells that undergo differentiation toward enteroendocrine lineage that resemble crypt label retaining cells (LRCs). Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Offshore Wind Resources Assessment from Multiple Satellite Data and WRF Modeling over South China Sea

DEFF Research Database (Denmark)

Chang, Rui; Rong, Zhu; Badger, Merete

2015-01-01

offshore winds which can be used for offshore wind resource assessment. First, wind speeds retrieved from Synthetic Aperture Radar (SAR) and Scatterometer ASCAT images were validated against in situ measurements from seven coastal meteorological stations in South China Sea (SCS). The wind roses from...... (SD) of 2.09 m/s (1.83 m/s) and correlation coefficient of R 0.75 (0.80). When the offshore winds (i.e., winds directed from land to sea) are excluded, the comparison results for wind speeds show an improvement of SD and R, indicating that the satellite data are more credible over the open ocean...

Proteome of human stem cells from periodontal ligament and dental pulp.

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Enrica Eleuterio

Full Text Available BACKGROUND: Many adult tissues contain a population of stem cells with the ability to regenerate structures similar to the microenvironments from which they are derived in vivo and represent a promising therapy for the regeneration of complex tissues in the clinical disorder. Human adult stem cells (SCs including bone marrow stem cells (BMSCs, dental pulp stem cells (DPSCs and periodontal ligament stem cells (PDLSCs have been characterized for their high proliferative potential, expression of characteristic SC-associated markers and for the plasticity to differentiate in different lineage in vitro. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study is to define the molecular features of stem cells from oral tissue by comparing the proteomic profiles obtained with 2-DE followed by MALDI-TOF/TOF of ex-vivo cultured human PDLSCs, DPSCs and BMSCs. Our results showed qualitative similarities in the proteome profiles among the SCs examined including some significant quantitative differences. To enrich the knowledge of oral SCs proteome we performed an analysis in narrow range pH 4-7 and 6-9, and we found that DPSCs vs PDLSCs express differentially regulated proteins that are potentially related to growth, regulation and genesis of neuronal cells, suggesting that SCs derived from oral tissue source populations may possess the potential ability of neuronal differentiation which is very consistent with their neural crest origin. CONCLUSION/SIGNIFICANCE: This study identifies some differentially expressed proteins by using comparative analysis between DPSCs and PDLSCs and BMSCs and suggests that stem cells from oral tissue could have a different cell lineage potency compared to BMSCs.

Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro.

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Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping; Zhou, Xiang; Zhu, Zhaowei

2016-05-01

Platelet-rich plasma (PRP) contains various growth factors and appears to have the potential to promote peripheral nerve regeneration, but evidence is lacking regarding its biological effect on Schwann cells (SCs). The present study was designed to investigate the effect of PRP concentration on SCs in order to determine the plausibility of using this plasma-derived therapy for peripheral nerve injury. PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and growth factor concentrations. Primary cultures of rat SCs were exposed to various concentrations of PRP (40%, 20%, 10%, 5% and 2.5%). Cell proliferation assays and flow cytometry were performed to study to assess SC proliferation. Quantitative real-time PCR and ELISA analysis were performed to determine the ability of PRP to induce SCs to produce nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). Microchemotaxis assay was used to analyse the cell migration capacity. The results obtained indicated that the platelet concentration and growth factors in our PRP preparations were significantly higher than in whole blood. Cell culture experiments showed that 2.5-20% PRP significantly stimulated SC proliferation and migration compared to untreated controls in a dose-dependent manner. In addition, the expression and secretion of NGF and GDNF were significantly increased. However, the above effects of SCs were suppressed by high PRP concentrations (40%). In conclusion, the appropriate concentration of PRP had the potency to stimulate cell proliferation, induced the synthesis of neurotrophic factors and significantly increased migration of SCs dose-dependently. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

High intensity low temperature (HILT) performance of space concentrator GaInP/GaInAs/Ge MJ SCs

Energy Technology Data Exchange (ETDEWEB)

Shvarts, Maxim Z., E-mail: shvarts@scell.ioffe.ru; Kalyuzhnyy, Nikolay A.; Mintairov, Sergey A.; Soluyanov, Andrei A.; Timoshina, Nailya Kh. [Ioffe Physical-Technical Institute, 26 Polytekhnicheskaya str., St.-Petersburg, 194021 (Russian Federation); Gudovskikh, Alexander S. [Saint-Petersburg Academic University - Nanotechnology Research and Education Centre RAS, St. Petersburg, 194021 (Russian Federation); Luque, Antonio [Ioffe Physical-Technical Institute, 26 Polytekhnicheskaya str., St.-Petersburg, 194021, Russia and Instituto de Energia Solar, Universidad Politecnica de Madrid, Madrid (Spain)

2014-09-26

In the work, the results of an investigation of GaInP/GaInAs/Ge MJ SCs intended for converting concentrated solar radiation, when operating at low temperatures (down to −190 °C) are presented. A kink of the cell I-V characteristic has been observed in the region close to V{sub oc} starting from −20°C at operation under concentrated sunlight. The causes for its occurrence have been analyzed and the reasons for formation of a built-in potential barrier for majority charge carriers at the n-GaInP/n-Ge isotype hetero-interface are discussed. The effect of charge carrier transport in n-GaInP/n-pGe heterostructures on MJ SC output characteristics at low temperatures has been studied including EL technique.

TIME COURSE ALTERATIONS OF SATELLITE CELL EVENTS IN RESPONSE TO LIGHT MODERATE ENDURANCE TRAINING IN WHITE GASTROCNEMIUS MUSCLE OF THE RAT

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Zong-Yan Cai

2012-01-01

Full Text Available This study investigated satellite cells and their related molecular events adapted to light moderate endurance training in the white gastrocnemius muscle of the rat. The white gastrocnemius muscle of male Sprague-Dawley rats that had been trained for 4 weeks and 8 weeks, with control rats being analysed alongside them, was selected for analysis (n=3 per group. The training protocol consisted of treadmill running at 20 m · min-1 for 30 min on a 0% grade, for 3 days · week-1. Immunohistochemical staining coupled with image analysis was used for quantification. To provide deeper insight into the cell layer, 40 sections per rat, corresponding to 120 values per group, were obtained as a mean value for statistical comparison. The results indicated that at week 4, training effects increased the vascular endothelial growth factor (VEGF content and c-met positive satellite cell numbers. At week 8, the training effect was attenuated for VEGF and c-met satellite cell numbers, but it increased in the muscle fibre area. Additionally, c-met positive satellite cell numbers correlated with VEGF content (r = 0.79, p<0.05. In conclusion, this study suggests that light moderate endurance training could stimulate satellite cell activation that might be related to VEGF signalling. Additionally, the satellite cells activated by moderate endurance training might contribute to slight growth in myocytes.

Speeding up spin-component-scaled third-order pertubation theory with the chain of spheres approximation: the COSX-SCS-MP3 method

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Izsák, Róbert; Neese, Frank

2013-07-01

The 'chain of spheres' approximation, developed earlier for the efficient evaluation of the self-consistent field exchange term, is introduced here into the evaluation of the external exchange term of higher order correlation methods. Its performance is studied in the specific case of the spin-component-scaled third-order Møller--Plesset perturbation (SCS-MP3) theory. The results indicate that the approximation performs excellently in terms of both computer time and achievable accuracy. Significant speedups over a conventional method are obtained for larger systems and basis sets. Owing to this development, SCS-MP3 calculations on molecules of the size of penicillin (42 atoms) with a polarised triple-zeta basis set can be performed in ∼3 hours using 16 cores of an Intel Xeon E7-8837 processor with a 2.67 GHz clock speed, which represents a speedup by a factor of 8-9 compared to the previously most efficient algorithm. Thus, the increased accuracy offered by SCS-MP3 can now be explored for at least medium-sized molecules.

Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells

NARCIS (Netherlands)

D. ten Berge (Derk); D. Kurek (Dorota); T. Blauwkamp (Tim); W. Koole (Wouter); A. Maas (Alex); E. Eroglu (Elif); R.K. Siu (Ronald); R. Nusse (Roel)

2011-01-01

textabstractPluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref.). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive

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

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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. © 2016 Anatomical Society.

Role of Schwann cells in the regeneration of penile and peripheral nerves

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Lin Wang

2015-01-01

Full Text Available Schwann cells (SCs are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED. Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1 the origin and development of SCs in the peripheral and penile nerve system; (2 Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3 how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4 and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED.

SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment

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Genevieve V. Dall

2017-02-01

Full Text Available Estrogen stimulates breast development during puberty and mammary tumors in adulthood through estrogen receptor-α (ERα. These effects are proposed to occur via ERα+ luminal cells and not the mammary stem cells (MaSCs that are ERαneg. Since ERα+ luminal cells express stem cell antigen-1 (SCA-1, we sought to determine if SCA-1 could define an ERα+ subset of EpCAM+/CD24+/CD49fhi MaSCs. We show that the MaSC population has a distinct SCA-1+ population that is abundant in pre-pubertal mammary glands. The SCA-1+ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1neg counterparts. However, they express ERα and specifically enter the cell cycle at puberty. Using estrogen-deficient aromatase knockouts (ArKO, we showed that the SCA-1+ MaSC could be directly modulated by estrogen supplementation. Thus, SCA-1 enriches for an ERα+, estrogen-sensitive subpopulation within the CD24+/CD49fhi MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.

Transplantation of Human Menstrual Blood-Derived Mesenchymal Stem Cells Alleviates Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice

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Yongjia Zhao

2018-04-01

Full Text Available Extracellular β-amyloid (Aβ plaques and neurofibrillary tangles (NFTs are the pathological hallmarks of Alzheimer’s disease (AD. Mesenchymal stem cells (MSCs have shown therapeutic efficacy in many neurodegenerative diseases, including AD. Human menstrual blood-derived stem cells (MenSCs are a novel source of MSCs advantageous for their higher proliferation rate and because they are easy to obtain without ethical concerns. Although MenSCs have exhibited therapeutic efficacy in some diseases, their effects on AD remain elusive. In the present study, we showed that intracerebral transplantation of MenSCs dramatically improved the spatial learning and memory of APP/PS1 mice. In addition, MenSCs significantly ameliorated amyloid plaques and reduced tau hyperphosphorylation in APP/PS1 mice. Remarkably, we also found that intracerebral transplantation of MenSCs markedly increased several Aβ degrading enzymes and modulated a panel of proinflammatory cytokines associated with an altered microglial phenotype, suggesting an Aβ degrading and anti-inflammatory impact of MenSCs in the brains of APP/PS1 mice. In conclusion, these findings suggest that MenSCs are a promising therapeutic candidate for AD.

Framework for event-based semidistributed modeling that unifies the SCS-CN method, VIC, PDM, and TOPMODEL

Science.gov (United States)

Bartlett, M. S.; Parolari, A. J.; McDonnell, J. J.; Porporato, A.

2016-09-01

Hydrologists and engineers may choose from a range of semidistributed rainfall-runoff models such as VIC, PDM, and TOPMODEL, all of which predict runoff from a distribution of watershed properties. However, these models are not easily compared to event-based data and are missing ready-to-use analytical expressions that are analogous to the SCS-CN method. The SCS-CN method is an event-based model that describes the runoff response with a rainfall-runoff curve that is a function of the cumulative storm rainfall and antecedent wetness condition. Here we develop an event-based probabilistic storage framework and distill semidistributed models into analytical, event-based expressions for describing the rainfall-runoff response. The event-based versions called VICx, PDMx, and TOPMODELx also are extended with a spatial description of the runoff concept of "prethreshold" and "threshold-excess" runoff, which occur, respectively, before and after infiltration exceeds a storage capacity threshold. For total storm rainfall and antecedent wetness conditions, the resulting ready-to-use analytical expressions define the source areas (fraction of the watershed) that produce runoff by each mechanism. They also define the probability density function (PDF) representing the spatial variability of runoff depths that are cumulative values for the storm duration, and the average unit area runoff, which describes the so-called runoff curve. These new event-based semidistributed models and the traditional SCS-CN method are unified by the same general expression for the runoff curve. Since the general runoff curve may incorporate different model distributions, it may ease the way for relating such distributions to land use, climate, topography, ecology, geology, and other characteristics.

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

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...... 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...... cells (CD68(+) or CD16(+) cells) was not significantly increased in either of the legs 8 days after exercise and was unaffected by the NSAID. The main finding in the present study was that the NSAID infusion for 7.5 h during the exercise day suppressed the exercise-induced increase in the number...

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

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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.

Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy.

Science.gov (United States)

Popescu, Laurentiu M; Gherghiceanu, Mihaela; Suciu, Laura C; Manole, Catalin G; Hinescu, Mihail E

2011-09-01

This study describes a novel type of interstitial (stromal) cell - telocytes (TCs) - in the human and mouse respiratory tree (terminal and respiratory bronchioles, as well as alveolar ducts). TCs have recently been described in pleura, epicardium, myocardium, endocardium, intestine, uterus, pancreas, mammary gland, etc. (see www.telocytes.com ). TCs are cells with specific prolongations called telopodes (Tp), frequently two to three per cell. Tp are very long prolongations (tens up to hundreds of μm) built of alternating thin segments known as podomers (≤ 200 nm, below the resolving power of light microscope) and dilated segments called podoms, which accommodate mitochondria, rough endoplasmic reticulum and caveolae. Tp ramify dichotomously, making a 3-dimensional network with complex homo- and heterocellular junctions. Confocal microscopy reveals that TCs are c-kit- and CD34-positive. Tp release shed vesicles or exosomes, sending macromolecular signals to neighboring cells and eventually modifying their transcriptional activity. At bronchoalveolar junctions, TCs have been observed in close association with putative stem cells (SCs) in the subepithelial stroma. SCs are recognized by their ultrastructure and Sca-1 positivity. Tp surround SCs, forming complex TC-SC niches (TC-SCNs). Electron tomography allows the identification of bridging nanostructures, which connect Tp with SCs. In conclusion, this study shows the presence of TCs in lungs and identifies a TC-SC tandem in subepithelial niches of the bronchiolar tree. In TC-SCNs, the synergy of TCs and SCs may be based on nanocontacts and shed vesicles.

The Antiaging Properties of Andrographis paniculata by Activation Epidermal Cell Stemness

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Jiyoung You

2015-09-01

Full Text Available Andrographis paniculata (A. paniculata, Chuanxinlian, a medicinal herb with an extremely bitter taste that is native to China and other parts of Southeast Asia, possesses immense therapeutic value; however, its therapeutic properties have rarely been applied in the field of skin care. In this study, we investigated the effect of an A. paniculata extract (APE on human epidermal stem cells (EpSCs, and confirmed its anti-aging effect through in vitro, ex vivo, and in vivo study. An MTT assay was used to determine cell proliferation. A flow cytometric analysis, with propidium iodide, was used to evaluate the cell cycle. The expression of integrin β1 (CD29, the stem cell marker, was detected with antibodies, using flow cytometry in vitro, and immunohistochemical assays in ex vivo. Type 1 collagen and VEGF (vascular endothelial growth factor were measured using an enzyme-linked immunosorbent assay (ELISA. During the clinical study, skin hydration, elasticity, wrinkling, sagging, and dermal density were evaluated before treatment and at four and eight weeks after the treatment with the test product (containing the APE on the face. The proliferation of the EpSCs, treated with the APE, increased significantly. In the cell cycle analysis, the APE increased the G2/M and S stages in a dose-dependent manner. The expression of integrin β1, which is related to epidermal progenitor cell expansion, was up-regulated in the APE-treated EpSCs and skin explants. In addition, the production of VEGF in the EpSCs increased significantly in response to the APE treatment. Consistent with these results, the VEGF and APE-treated EpSCs conditioned medium enhanced the Type 1 collagen production in normal human fibroblasts (NHFs. In the clinical study, the APE improved skin hydration, dermal density, wrinkling, and sagging significantly. Our findings revealed that the APE promotes a proliferation of EpSCs, through the up-regulation of the integrin β1 and VEGF expression

The Antiaging Properties of Andrographis paniculata by Activation Epidermal Cell Stemness.

Science.gov (United States)

You, Jiyoung; Roh, Kyung-Baeg; Li, Zidan; Liu, Guangrong; Tang, Jian; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

2015-09-22

Andrographis paniculata (A. paniculata, Chuanxinlian), a medicinal herb with an extremely bitter taste that is native to China and other parts of Southeast Asia, possesses immense therapeutic value; however, its therapeutic properties have rarely been applied in the field of skin care. In this study, we investigated the effect of an A. paniculata extract (APE) on human epidermal stem cells (EpSCs), and confirmed its anti-aging effect through in vitro, ex vivo, and in vivo study. An MTT assay was used to determine cell proliferation. A flow cytometric analysis, with propidium iodide, was used to evaluate the cell cycle. The expression of integrin β1 (CD29), the stem cell marker, was detected with antibodies, using flow cytometry in vitro, and immunohistochemical assays in ex vivo. Type 1 collagen and VEGF (vascular endothelial growth factor) were measured using an enzyme-linked immunosorbent assay (ELISA). During the clinical study, skin hydration, elasticity, wrinkling, sagging, and dermal density were evaluated before treatment and at four and eight weeks after the treatment with the test product (containing the APE) on the face. The proliferation of the EpSCs, treated with the APE, increased significantly. In the cell cycle analysis, the APE increased the G2/M and S stages in a dose-dependent manner. The expression of integrin β1, which is related to epidermal progenitor cell expansion, was up-regulated in the APE-treated EpSCs and skin explants. In addition, the production of VEGF in the EpSCs increased significantly in response to the APE treatment. Consistent with these results, the VEGF and APE-treated EpSCs conditioned medium enhanced the Type 1 collagen production in normal human fibroblasts (NHFs). In the clinical study, the APE improved skin hydration, dermal density, wrinkling, and sagging significantly. Our findings revealed that the APE promotes a proliferation of EpSCs, through the up-regulation of the integrin β1 and VEGF expression. The VEGF

Concanavalin A-induced and spontaneous suppressor cell activities in peripheral blood lymphocytes and spleen cells from gastric cancer patients.

Science.gov (United States)

Toge, T; Hamamoto, S; Itagaki, E; Yajima, K; Tanada, M; Nakane, H; Kohno, H; Nakanishi, K; Hattori, T

1983-11-01

In 173 gastric cancer patients, activities of Concanavalin-A-induced suppressor cells (Con-AS) and spontaneous suppressor cells (SpS) in peripheral blood lymphocytes (PBL), splenic vein lymphocytes (SVL), and spleen cells (SCs) were investigated. Suppressions by Con-AS in PBL were significantly effective in patients of Stages III and IV, while suppressions by SpS were effective in patients with recurrent tumors. Thus, in PBLs of cancer patients, suppressor precursors, which are considered to be activated in vitro by Concanavalin-A, seemed to appear with the advances of the disease, and SpS activities, which could be already activated in vivo, seemed to increase in the terminal stage. In SCs, increased activities of Con-AS, but normal activities of SpS, were observed, and these suppressor-cell populations consisted of glass nonadherent cells. Suppressor activities of SCs would be due to suppressor T-cells, not to other types of cells. Furthermore, Con-AS existed in the medium-sized lymphocytes, which were fractionated on the basis of cell size, while SpS in the large-sized lymphocytes. A higher proportion of T-cells, bearing Fc receptors for IgG, was observed in the larger-sized lymphocyte fractions. Cell numbers in the large-sized lymphocyte fraction tended to increase with the advances of tumors. From these results, it is suggested that higher presence of suppressor precursors and the increase of SpS activities may occur in cancer patients, depending on the tumor advancing.

Estimating Composite Curve Number Using an Improved SCS-CN Method with Remotely Sensed Variables in Guangzhou, China

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Qihao Weng

2013-03-01

Full Text Available The rainfall and runoff relationship becomes an intriguing issue as urbanization continues to evolve worldwide. In this paper, we developed a simulation model based on the soil conservation service curve number (SCS-CN method to analyze the rainfall-runoff relationship in Guangzhou, a rapid growing metropolitan area in southern China. The SCS-CN method was initially developed by the Natural Resources Conservation Service (NRCS of the United States Department of Agriculture (USDA, and is one of the most enduring methods for estimating direct runoff volume in ungauged catchments. In this model, the curve number (CN is a key variable which is usually obtained by the look-up table of TR-55. Due to the limitations of TR-55 in characterizing complex urban environments and in classifying land use/cover types, the SCS-CN model cannot provide more detailed runoff information. Thus, this paper develops a method to calculate CN by using remote sensing variables, including vegetation, impervious surface, and soil (V-I-S. The specific objectives of this paper are: (1 To extract the V-I-S fraction images using Linear Spectral Mixture Analysis; (2 To obtain composite CN by incorporating vegetation types, soil types, and V-I-S fraction images; and (3 To simulate direct runoff under the scenarios with precipitation of 57mm (occurred once every five years by average and 81mm (occurred once every ten years. Our experiment shows that the proposed method is easy to use and can derive composite CN effectively.

Effect of high temperature annealing on the microstructure of SCS-6 SiC fibers

Science.gov (United States)

Ning, X. J.; Pirouz, P.; Bhatt, R. T.

1992-01-01

The effect of annealing the SCS-6 SiC fiber for one hour at 2000 C in an argon atmosphere is reported. The SiC grains in the fiber coarsen appreciably and the intergranular carbon films segregate to the grain junctions. It would appear that grain growth in the outer part of the fiber is primarily responsible for the loss in fiber strength and improvement in fiber creep resistance.

Histopathological and ultrastructural changes experimentally induced by bee venom in seminiferous epithelium via structural-functional alteration of Sertoli cells.

Science.gov (United States)

Florea, Adrian; Puică, Constantin; Hamed, Sami; Tilinca, Mariana; Matei, Horea

2017-11-01

We tested here the ability of bee venom (BV) to interfere with spermatogenesis in rats in two experimental conditions. The histopathological changes were assessed with brightfield microscopy using a novel staining technique, based on methylene blue, orange G and ponceau xylidine. Transmission electron microscopy was also used to identify fine subcellular changes. BV injection for 30days in daily doses of 700μg BV/kg resulted in reducing testicular weight, along with significant larger diameters of seminiferous tubules and reduced number of Sertoli cells (SCs). SCs were vacuolated, detached from the basement membrane, many necrosed, leading to the basement membrane denudation. Germ cells layers were separated by empty spaces conferring a rarefied aspect to the tissue, and spermatids were detached into lumen. Thus, the seminiferous epithelium was significantly thinned. Many Leydig cells (LCs) were in a necrotic state, with disrupted plasma membrane and without smooth endoplasmic reticulum. The acute treatment with a single LD50 of 62mgBV/kg, was followed by focal disruptions of the basement membrane and localized areas of necrosis, mainly affecting the SCs. Most of the observed SCs as well as some spermatogonia were highly vacuoled, empty spaces being observed within the epithelium. The SCs count was significantly decreased. Spermatids had also the tendency of separation from the SCs, and the significant larger diameter of the tubules found was associated with a thicker epithelium. Many LCs were necrosed, with disrupted plasma membrane, swollen mitochondria, no endoplasmic reticulum and implicitly showing rarefied cytoplasm. We concluded that BV was a testicular toxicant affecting both the LCs and the seminiferous tubules. The SCs cells represented the primary target site of BV whose effects were next extended upon the germ cells. In all cells, BV triggered unspecific degenerative changes that could impaire spermatogenesis. The present study also proposes an

Smad2/3 Upregulates the Expression of Vimentin and Affects Its Distribution in DBP-Exposed Sertoli Cells

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Xi Zhang

2015-01-01

Full Text Available Sertoli cells (SCs in the testes provide physical and nutritional support to germ cells. The vimentin cytoskeleton in SCs is disrupted by dibutyl phthalate (DBP, which leads to SCs dysfunction. In a previous study, we found that peroxisome proliferator-activated receptor alpha (PPARα influenced the distribution of vimentin by affecting its phosphorylation in DBP-exposed SCs. In the present study, we investigated the role of Smad2/3 in regulating the expression of vimentin in DBP-exposed SCs. We hypothesized that Smad2/3 affects the distribution of vimentin by regulating its expression and that there is cross talk between Smad2/3 and PPARα. The real-time PCR and ChIP-qPCR results showed that SB431542 (an inhibitor of Smad2/3 could significantly attenuate the expression of vimentin induced by DBP in SCs. Phosphorylated and soluble vimentin were both downregulated by SB431542 pretreatment. WY14643 (an agonist of PPARα pretreatment stimulated, while GW6471 (an antagonist of PPARα inhibited, the activity of Smad2/3; SB431542 pretreatment also inhibited the activity of PPARα, but it did not rescue the DBP-induced collapse in vimentin. Our results suggest that, in addition to promoting the phosphorylation of vimentin, DBP also stimulates the expression of vimentin by activating Smad2/3 in SCs and thereby induces irregular vimentin distribution.

Effect of colorectal cancer on the number of normal stem cells circulating in peripheral blood.

Science.gov (United States)

Marlicz, Wojciech; Sielatycka, Katarzyna; Serwin, Karol; Kubis, Ewa; Tkacz, Marta; Głuszko, Rafał; Białek, Andrzej; Starzyńska, Teresa; Ratajczak, Mariusz Z

2016-12-01

Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblast‑like stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma. We wondered if a similar correlation occurs in patients with colorectal cancer (CRC). A total of 46 patients were enrolled in this study: 17 with CRC, 18 with benign colonic adenomas (BCA) and 11 healthy individuals. By employing fluorescence-activated cell sorting (FACS) we evaluated the number of BM-derived SCs circulating in PB: i) CD34+/Lin-/CD45- and CD133-/Lin-/CD45- VSELs; ii) CD45-/CD105+/CD90+/CD29+ MSCs; iii) CD45-/CD34+/CD133+/KDR+ endothelial progenitor cells (EPCs); and iv) CD133+/Lin-/CD45+ or CD34+/Lin-/CD45+ cells enriched for hematopoietic stem/progenitor cells (HSPCs). In parallel, we measured in the PB parameters regulating the egress of SCs from BM into PB. In contrast to pancreatic and gastric cancer patients, CRC subjects presented neither an increase in the number of circulating SCs nor the activation of pro-mobilizing factors such as complement, coagulation and fibrinolytic cascade, circulating stromal derived factor 1 (SDF‑1), vascular endothelial growth factor (VEGF) and intestinal permeability marker (zonulin). In conclusion, mobilization of SCs in cancer patients depends on the type of malignancy and its ability to activate pro-mobilization cascades.

Neural differentiation of adipose-derived stem cells by indirect co-culture with Schwann cells

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Li Xiaojie

2009-01-01

Full Text Available To investigate whether adipose-derived stem cells (ADSCs could be subject to neural differentiation induced only by Schwann cell (SC factors, we co-cultured ADSCs and SCs in transwell culture dishes. Immunoassaying, Western blot analysis, and RT-PCR were performed (1, 3, 7, 14 d and the co-cultured ADSCs showed gene and protein expression of S-100, Nestin, and GFAP. Further, qRT-PCR disclosed relative quantitative differences in the above three gene expressions. We think ADSCs can undergo induced neural differentiation by being co-cultured with SCs, and such differentia­tions begin 1 day after co-culture, become apparent after 7 days, and thereafter remain stable till the 14th day.

A frequency-based linguistic approach to protein decoding and design: Simple concepts, diverse applications, and the SCS Package

Science.gov (United States)

Motomura, Kenta; Nakamura, Morikazu; Otaki, Joji M.

2013-01-01

Protein structure and function information is coded in amino acid sequences. However, the relationship between primary sequences and three-dimensional structures and functions remains enigmatic. Our approach to this fundamental biochemistry problem is based on the frequencies of short constituent sequences (SCSs) or words. A protein amino acid sequence is considered analogous to an English sentence, where SCSs are equivalent to words. Availability scores, which are defined as real SCS frequencies in the non-redundant amino acid database relative to their probabilistically expected frequencies, demonstrate the biological usage bias of SCSs. As a result, this frequency-based linguistic approach is expected to have diverse applications, such as secondary structure specifications by structure-specific SCSs and immunological adjuvants with rare or non-existent SCSs. Linguistic similarities (e.g., wide ranges of scale-free distributions) and dissimilarities (e.g., behaviors of low-rank samples) between proteins and the natural English language have been revealed in the rank-frequency relationships of SCSs or words. We have developed a web server, the SCS Package, which contains five applications for analyzing protein sequences based on the linguistic concept. These tools have the potential to assist researchers in deciphering structurally and functionally important protein sites, species-specific sequences, and functional relationships between SCSs. The SCS Package also provides researchers with a tool to construct amino acid sequences de novo based on the idiomatic usage of SCSs. PMID:24688703

A FREQUENCY-BASED LINGUISTIC APPROACH TO PROTEIN DECODING AND DESIGN: SIMPLE CONCEPTS, DIVERSE APPLICATIONS, AND THE SCS PACKAGE

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Kenta Motomura

2013-02-01

Full Text Available Protein structure and function information is coded in amino acid sequences. However, the relationship between primary sequences and three-dimensional structures and functions remains enigmatic. Our approach to this fundamental biochemistry problem is based on the frequencies of short constituent sequences (SCSs or words. A protein amino acid sequence is considered analogous to an English sentence, where SCSs are equivalent to words. Availability scores, which are defined as real SCS frequencies in the non-redundant amino acid database relative to their probabilistically expected frequencies, demonstrate the biological usage bias of SCSs. As a result, this frequency-based linguistic approach is expected to have diverse applications, such as secondary structure specifications by structure-specific SCSs and immunological adjuvants with rare or non-existent SCSs. Linguistic similarities (e.g., wide ranges of scale-free distributions and dissimilarities (e.g., behaviors of low-rank samples between proteins and the natural English language have been revealed in the rank-frequency relationships of SCSs or words. We have developed a web server, the SCS Package, which contains five applications for analyzing protein sequences based on the linguistic concept. These tools have the potential to assist researchers in deciphering structurally and functionally important protein sites, species-specific sequences, and functional relationships between SCSs. The SCS Package also provides researchers with a tool to construct amino acid sequences de novo based on the idiomatic usage of SCSs.

Proinflammatory cytokine tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) suppresses satellite cell self-renewal through inversely modulating Notch and NF-κB signaling pathways.

Science.gov (United States)

Ogura, Yuji; Mishra, Vivek; Hindi, Sajedah M; Kuang, Shihuan; Kumar, Ashok

2013-12-06

Satellite cell self-renewal is an essential process to maintaining the robustness of skeletal muscle regenerative capacity. However, extrinsic factors that regulate self-renewal of satellite cells are not well understood. Here, we demonstrate that TWEAK cytokine reduces the proportion of Pax7(+)/MyoD(-) cells (an index of self-renewal) on myofiber explants and represses multiple components of Notch signaling in satellite cell cultures. The number of Pax7(+) cells is significantly increased in skeletal muscle of TWEAK knock-out (KO) mice compared with wild-type in response to injury. Furthermore, Notch signaling is significantly elevated in cultured satellite cells and in regenerating myofibers of TWEAK-KO mice. Forced activation of Notch signaling through overexpression of the Notch1 intracellular domain (N1ICD) rescued the TWEAK-mediated inhibition of satellite cell self-renewal. TWEAK also activates the NF-κB transcription factor in satellite cells and inhibition of NF-κB significantly improved the number of Pax7(+) cells in TWEAK-treated cultures. Furthermore, our results demonstrate that a reciprocal interaction between NF-κB and Notch signaling governs the inhibitory effect of TWEAK on satellite cell self-renewal. Collectively, our study demonstrates that TWEAK suppresses satellite cell self-renewal through activating NF-κB and repressing Notch signaling.

Reduced satellite cell density and myogenesis in Wagyu compared with Angus cattle as a possible explanation of its high marbling.

Science.gov (United States)

Fu, X; Yang, Q; Wang, B; Zhao, J; Zhu, M; Parish, S M; Du, M

2018-05-01

Mechanisms responsible for excellent marbling in Japanese black cattle, Wagyu, remain to be established. Because both muscle cells and intramuscular adipocytes are developed from mesenchymal progenitor cells during early muscle development, we hypothesized that intramuscular progenitor cells in Wagyu cattle have attenuated myogenic capacity in favor of adipogenesis, leading to high marbling but reduced muscle growth. Biceps femoris muscle biopsy samples were obtained from both Angus (n=3) and Wagyu (n=3) cattle at 12 months of age. Compared with Angus, the density of satellite cells was much lower in Wagyu muscle (by 45.8±10%, PAngus cattle. Because satellite cells are derived from fetal myogenic cells, the reduction in satellite cell density together with lower muscle fiber formation suggests that myogenesis was attenuated during early muscle development in Wagyu cattle. Given the shared pool of mesenchymal progenitor cells, the attenuated myogenesis likely shifts progenitor cells to adipogenesis during early development, which may contribute to high intramuscular adipocyte formation in Wagyu cattle.

Analysis of the runoff generation mechanism for the investigation of the SCS-CN method applicability to a partial area experimental watershed

Science.gov (United States)

Soulis, K. X.; Valiantzas, J. D.; Dercas, N.; Londra, P. A.

2009-01-01

The Soil Conservation Service Curve Number (SCS-CN) method is widely used for predicting direct runoff volume for a given rainfall event. The applicability of the SCS-CN method and the runoff generation mechanism were thoroughly analysed in a Mediterranean experimental watershed in Greece. The region is characterized by a Mediterranean semi-arid climate. A detailed land cover and soil survey using remote sensing and GIS techniques, showed that the watershed is dominated by coarse soils with high hydraulic conductivities, whereas a smaller part is covered with medium textured soils and impervious surfaces. The analysis indicated that the SCS-CN method fails to predict runoff for the storm events studied, and that there is a strong correlation between the CN values obtained from measured runoff and the rainfall depth. The hypothesis that this correlation could be attributed to the existence of an impermeable part in a very permeable watershed was examined in depth, by developing a numerical simulation water flow model for predicting surface runoff generated from each of the three soil types of the watershed. Numerical runs were performed using the HYDRUS-1D code. The results support the validity of this hypothesis for most of the events examined where the linear runoff formula provides better results than the SCS-CN method. The runoff coefficient of this formula can be taken equal to the percentage of the impervious area. However, the linear formula should be applied with caution in case of extreme events with very high rainfall intensities. In this case, the medium textured soils may significantly contribute to the total runoff and the linear formula may significantly underestimate the runoff produced.

Association of pKi-67 with satellite DNA of the human genome in early G1 cells.

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Bridger, J M; Kill, I R; Lichter, P

1998-01-01

pKi-67 is a nucleolar antigen that provides a specific marker for proliferating cells. It has been shown previously that pKi-67's distribution varies in a cell cycle-dependent manner: it coats all chromosomes during mitosis, accumulates in nuclear foci during G1 phase (type I distribution) and localizes within nucleoli in late G1 S and G2 phase (type II distribution). Although no function has as yet been ascribed to pKi-67, it has been found associated with centromeres in G1. In the present study the distribution pattern of pKi-67 during G1 in human dermal fibroblasts (HDFs) was analysed in more detail. Synchronization experiments show that in very early G1 cells pKi-67 coincides with virtually all satellite regions analysed, i.e. with centromeric (alpha-satellite), telomeric (minisatellite) and heterochromatic blocks (satellite III) on chromosomes 1 and Y (type Ia distribution). In contrast, later in the G1 phase, a smaller fraction of satellite DNA regions are found collocalized with pKi-67 foci (type Ib distribution). When all pKi-67 becomes localized within nucleoli, even fewer satellite regions remain associated with the pKi-67 staining. However, all centromeric and short arm regions of the acrocentric chromosomes, which are in very close proximity to or even contain the rRNA genes, are collocalized with anti-pKi-67 staining throughout the remaining interphase of the cell cycle. Thus, our data demonstrate that during post-mitotic reformation and nucleogenesis there is a progressive decline in the fraction of specific satellite regions of DNA that remain associated with pKi-67. This may be relevant to nucleolar reformation following mitosis.

IGF-1 colocalizes with muscle satellite cells following acute exercise in humans.

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Grubb, Amanda; Joanisse, Sophie; Moore, Daniel R; Bellamy, Leeann M; Mitchell, Cameron J; Phillips, Stuart M; Parise, Gianni

2014-04-01

Insulin-like growth factor-1 (IGF-1) regulates stem cell proliferation and differentiation in vitro. The aim of this study was to quantify the change in satellite cell (SC) specific IGF-1 colocalization following exercise. We observed a significant increase (p IGF-1 colocalization from baseline to 72 h after a bout of resistance exercise. This strongly supports a role for IGF-1 in human SC function following exercise.

Solar array experiments on the SPHINX satellite. [Space Plasma High voltage INteraction eXperiment satellite

Science.gov (United States)

Stevens, N. J.

1974-01-01

The Space Plasma, High Voltage Interaction Experiment (SPHINX) is the name given to an auxiliary payload satellite scheduled to be launched in January 1974. The principal experiments carried on this satellite are specifically designed to obtain the engineering data on the interaction of high voltage systems with the space plasma. The classes of experiments are solar array segments, insulators, insulators with pin holes and conductors. The satellite is also carrying experiments to obtain flight data on three new solar array configurations: the edge illuminated-multijunction cells, the teflon encased cells, and the violet cells.

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

OpenAIRE

Zainud-Deen, S. H.; El-Shalaby, N. A.; Gaber, S. M.; Malhat, H. A.

2016-01-01

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 compensatio...

The 1-dinar and ½-dinar banknotes from 1919: The first banknotes of the Kingdom of SCS

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Pantelić Svetlana

2017-01-01

Full Text Available Since the National Bank of the Kingdom of SCS was not constituted until 26 February 1920, the Privileged National Bank of the Kingdom of Serbia released into circulation the banknotes of the Kingdom of SCS to replace its own 10- and 100-dinar banknotes payable in silver, according to the bylaw of the Ministry of Finance as of 17 November 1919. The 1-dinar banknote was released into circulation on 20 November and the 1/2-dinar banknote on 26 November 1919. The 1/2-dinar banknote was prepared in a private printing house in Zagreb, and the 1-dinar banknote in the Banque de France printing house in Paris. The withdrawal of the 1- and 1/2-dinar banknotes from circulation was never officially announced, but they were most probably withdrawn at the same time as the dinar-crown banknotes worth 1 dinar (4 crowns and 1/2 dinars (2 crowns.

Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

Energy Technology Data Exchange (ETDEWEB)

Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

2013-11-01

Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

International Nuclear Information System (INIS)

Chen, Shiwei; Dong, Yushu; Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng; Hou, Wugang; Li, Wei

2013-01-01

Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury

Increase in the Accuracy of Calculating Length of Horizontal Cable SCS in Civil Engineering

Science.gov (United States)

Semenov, A.

2017-11-01

A modification of the method for calculating the horizontal cable consumption of SCS established at civil engineering facilities is proposed. The proposed procedure preserves the prototype simplicity and provides a 5 percent accuracy increase. The values of the achieved accuracy are justified, their compliance with the practice of real projects is proved. The method is brought to the level of the engineering algorithm and formalized in the form of 12/70 rule.

Providing the physical basis of SCS curve number method and its proportionality relationship from Richards' equation

Science.gov (United States)

Hooshyar, M.; Wang, D.

2016-12-01

The empirical proportionality relationship, which indicates that the ratio of cumulative surface runoff and infiltration to their corresponding potentials are equal, is the basis of the extensively used Soil Conservation Service Curve Number (SCS-CN) method. The objective of this paper is to provide the physical basis of the SCS-CN method and its proportionality hypothesis from the infiltration excess runoff generation perspective. To achieve this purpose, an analytical solution of Richards' equation is derived for ponded infiltration in shallow water table environment under the following boundary conditions: 1) the soil is saturated at the land surface; and 2) there is a no-flux boundary which moves downward. The solution is established based on the assumptions of negligible gravitational effect, constant soil water diffusivity, and hydrostatic soil moisture profile between the no-flux boundary and water table. Based on the derived analytical solution, the proportionality hypothesis is a reasonable approximation for rainfall partitioning at the early stage of ponded infiltration in areas with a shallow water table for coarse textured soils.

Tyrosine kinase receptor c-ros-oncogene 1 inhibition alleviates aberrant bone formation of TWIST-1 haploinsufficient calvarial cells from Saethre-Chotzen syndrome patients.

Science.gov (United States)

Camp, Esther; Anderson, Peter J; Zannettino, Andrew C W; Glackin, Carlotta A; Gronthos, Stan

2018-09-01

Saethre-Chotzen syndrome (SCS), associated with TWIST-1 mutations, is characterized by premature fusion of cranial sutures. TWIST-1 haploinsufficiency, leads to alterations in suture mesenchyme cellular gene expression patterns, resulting in aberrant osteogenesis and craniosynostosis. We analyzed the expression of the TWIST-1 target, Tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1) in TWIST-1 haploinsufficient calvarial cells derived from SCS patients and calvaria of Twist-1 del/+ mutant mice and found it to be highly expressed when compared to TWIST-1 wild-type controls. Knock-down of C-ROS-1 expression in TWIST-1 haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro. Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C-ROS-1 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation. Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro. Furthermore, Crizotinib treatment resulted in reduced BMP-2 mediated bone formation potential of whole Twist-1 del/+ mutant mouse calvaria organotypic cultures. Collectively, these results suggest that C-ROS-1 promotes osteogenic differentiation of TWIST-1 haploinsufficient calvarial osteogenic progenitor cells. Furthermore, the aberrant osteogenic potential of these cells is inhibited by the reduction of C-ROS-1. Therefore, targeting C-ROS-1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST-1 function. © 2018 Wiley Periodicals, Inc.

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

AIM: To investigate the influence of lifelong endurance running on the satellite cell pool of type I and type II fibres in healthy human skeletal muscle. METHODS: Muscle biopsies were collected from 15 healthy old trained men (O-Tr) who had been running 43 ± 16 (mean ± SD) kilometres a week for 28...... ± 9 years. Twelve age-matched untrained men (O-Un) and a group of young trained and young untrained men were recruited for comparison. Frozen sections were immunohistochemically stained for Pax7, type I myosin and laminin, from which fibre area, the number of satellite cells, and the relationship......-Un. A strong positive relationship between fibre size and satellite cell content was detected in trained individuals. In line with a history of myofibre repair, a greater number of fibres with centrally located myonuclei were detected in O-Tr. CONCLUSION: Lifelong endurance training (i) does not deplete...

Genetic Analysis of Somatic Cell Score in Danish Holsteins Using a Liability-Normal Mixture Model

DEFF Research Database (Denmark)

Madsen, P; Shariati, M M; Ødegård, J

2008-01-01

Mixture models are appealing for identifying hidden structures affecting somatic cell score (SCS) data, such as unrecorded cases of subclinical mastitis. Thus, liability-normal mixture (LNM) models were used for genetic analysis of SCS data, with the aim of predicting breeding values for such cas...

Label retaining cells (LRCs with myoepithelial characteristic from the proximal acinar region define stem cells in the sweat gland.

Directory of Open Access Journals (Sweden)

Yvonne Leung

Full Text Available Slow cycling is a common feature shared among several stem cells (SCs identified in adult tissues including hair follicle and cornea. Recently, existence of unipotent SCs in basal and lumenal layers of sweat gland (SG has been described and label retaining cells (LRCs have also been localized in SGs; however, whether these LRCs possess SCs characteristic has not been investigated further. Here, we used a H2BGFP LRCs system for in vivo detection of infrequently dividing cells. This system allowed us to specifically localize and isolate SCs with label-retention and myoepithelial characteristics restricted to the SG proximal acinar region. Using an alternative genetic approach, we demonstrated that SG LRCs expressed keratin 15 (K15 in the acinar region and lineage tracing determined that K15 labeled cells contributed long term to the SG structure but not to epidermal homeostasis. Surprisingly, wound healing experiments did not activate proximal acinar SG cells to participate in epidermal healing. Instead, predominantly non-LRCs in the SG duct actively divided, whereas the majority of SG LRCs remained quiescent. However, when we further challenged the system under more favorable isolated wound healing conditions, we were able to trigger normally quiescent acinar LRCs to trans-differentiate into the epidermis and adopt its long term fate. In addition, dissociated SG cells were able to regenerate SGs and, surprisingly, hair follicles demonstrating their in vivo plasticity. By determining the gene expression profile of isolated SG LRCs and non-LRCs in vivo, we identified several Bone Morphogenetic Protein (BMP pathway genes to be up-regulated and confirmed a functional requirement for BMP receptor 1A (BMPR1A-mediated signaling in SG formation. Our data highlight the existence of SG stem cells (SGSCs and their primary importance in SG homeostasis. It also emphasizes SGSCs as an alternative source of cells in wound healing and their plasticity for

Solar satellites

Energy Technology Data Exchange (ETDEWEB)

Poher, C.

1982-01-01

A reference system design, projected costs, and the functional concepts of a satellite solar power system (SSPS) for converting sunlight falling on solar panels of a satellite in GEO to a multi-GW beam which could be received by a rectenna on earth are outlined. Electricity transmission by microwaves has been demonstrated, and a reference design system for supplying 5 GW dc to earth was devised. The system will use either monocrystalline Si or concentrator GaAs solar cells for energy collection in GEO. Development is still needed to improve the lifespan of the cells. Currently, the cell performance degrades 50 percent in efficiency after 7-8 yr in space. Each SSPS satellite would weigh either 34,000 tons (Si) or 51,000 tons (GaAs), thereby requiring the fabrication of a heavy lift launch vehicle or a single-stage-to-orbit transport in order to minimize launch costs. Costs for the solar panels have been estimated at $500/kW using the GaAs technology, with transport costs for materials to GEO being $40/kg.

Solar satellites

Science.gov (United States)

Poher, C.

A reference system design, projected costs, and the functional concepts of a satellite solar power system (SSPS) for converting sunlight falling on solar panels of a satellite in GEO to a multi-GW beam which could be received by a rectenna on earth are outlined. Electricity transmission by microwaves has been demonstrated, and a reference design system for supplying 5 GW dc to earth was devised. The system will use either monocrystalline Si or concentrator GaAs solar cells for energy collection in GEO. Development is still needed to improve the lifespan of the cells. Currently, the cell performance degrades 50 percent in efficiency after 7-8 yr in space. Each SSPS satellite would weigh either 34,000 tons (Si) or 51,000 tons (GaAs), thereby requiring the fabrication of a heavy lift launch vehicle or a single-stage-to-orbit transport in order to minimize launch costs. Costs for the solar panels have been estimated at $500/kW using the GaAs technology, with transport costs for materials to GEO being $40/kg.

Stage-specific damage to synaptonemal complexes and metaphase chromosomes induced by X rays in male mouse germ cells

International Nuclear Information System (INIS)

Backer, L.C.; Sontag, M.R.; Allen, J.W.

1991-01-01

Synaptonemal complexes (SCs) reveal mutagen-induced effects in germ cell meiotic chromosomes. The study was aimed at characterizing relationships between SC and metaphase I chromosome damage following radiation exposure at various stages of spermatogenesis. Male mice were irradiated with doses of 0, 2, or 4 Gy, and spermatocytes were harvested at times consistent with earlier exposures as spermatogonial stem cells, preleptotene cells (premeiotic DNA synthesis), or meiotic prophase cells. After stem-cell exposure, twice as many rearrangements were observed in SCs as in metaphase I chromosomes. Irradiation during premeiotic DNA synthesis resulted in dose-related increases in SC breakage and rearrangements (including novel forms) and in metaphase chromosomal aberrations. Following prophase exposure, various types and levels of SC and metaphase damage were observed. Irradiation of zygotene cells led to high frequencies of chromosome multivalents in metaphase I without a correspondingly high level of damage in preceding prophase SCs. Thus, irradiation of premeiotic and meiotic cells results in variable relationships between SC and metaphase chromosome damage

Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

Science.gov (United States)

Chaillou, Thomas; Lanner, Johanna T

2016-12-01

Reduced oxygen (O 2 ) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O 2 level could affect their activity during muscle regeneration. In this review, we present the idea that O 2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O 2 levels to promote muscle regeneration. Severe hypoxia (≤1% O 2 ) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O 2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity. © FASEB.

The hair follicle bulge: a niche for adult stem cells.

Science.gov (United States)

Pasolli, Hilda Amalia

2011-08-01

Adult stem cells (SCs) are essential for tissue homeostasis and wound repair. They have the ability to both self-renew and differentiate into multiple cell types. They often reside in specialized microenvironments or niches that preserve their proliferative and tissue regenerative capacity. The murine hair follicle (HF) has a specialized and permanent compartment--the bulge, which safely lodges SCs and provides the necessary molecular cues to regulate their function. The HF undergoes cyclic periods of destruction, regeneration, and rest, making it an excellent system to study SC biology.

Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.

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Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

2011-04-01

Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Hyperglycemia Alters the Schwann Cell Mitochondrial Proteome and Decreases Coupled Respiration in the Absence of Superoxide Production

OpenAIRE

Zhang, Liang; Yu, Cuijuan; Vasquez, Francisco E.; Galeva, Nadya; Onyango, Isaac; Swerdlow, Russell H.; Dobrowsky, Rick T.

2010-01-01

Hyperglycemia-induced mitochondrial dysfunction contributes to sensory neuron pathology in diabetic neuropathy. Although Schwann cells (SCs) also undergo substantial degeneration in diabetic neuropathy, the effect of hyperglycemia on SC mitochondrial proteome and mitochondrial function has not been examined. Stable isotope labeling with amino acids in cell culture (SILAC) was used to quantify the temporal effect of hyperglycemia on the mitochondrial proteome of primary SCs isolated from neona...

Investigation of the direct runoff generation mechanism for the analysis of the SCS-CN method applicability to a partial area experimental watershed

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Soulis, K. X.; Valiantzas, J. D.; Dercas, N.; Londra, P. A.

2009-05-01

The Soil Conservation Service Curve Number (SCS-CN) method is widely used for predicting direct runoff volume for a given rainfall event. The applicability of the SCS-CN method and the direct runoff generation mechanism were thoroughly analysed in a Mediterranean experimental watershed in Greece. The region is characterized by a Mediterranean semi-arid climate. A detailed land cover and soil survey using remote sensing and GIS techniques, showed that the watershed is dominated by coarse soils with high hydraulic conductivities, whereas a smaller part is covered with medium textured soils and impervious surfaces. The analysis indicated that the SCS-CN method fails to predict runoff for the storm events studied, and that there is a strong correlation between the CN values obtained from measured runoff and the rainfall depth. The hypothesis that this correlation could be attributed to the existence of an impermeable part in a very permeable watershed was examined in depth, by developing a numerical simulation water flow model for predicting surface runoff generated from each of the three soil types of the watershed. Numerical runs were performed using the HYDRUS-1D code. The results support the validity of this hypothesis for most of the events examined where the linear runoff formula provides better results than the SCS-CN method. The runoff coefficient of this formula can be taken equal to the percentage of the impervious area. However, the linear formula should be applied with caution in case of extreme events with very high rainfall intensities. In this case, the medium textured soils may significantly contribute to the total runoff and the linear formula may significantly underestimate the runoff produced.

Investigation of the direct runoff generation mechanism for the analysis of the SCS-CN method applicability to a partial area experimental watershed

Directory of Open Access Journals (Sweden)

K. X. Soulis

2009-05-01

Full Text Available The Soil Conservation Service Curve Number (SCS-CN method is widely used for predicting direct runoff volume for a given rainfall event. The applicability of the SCS-CN method and the direct runoff generation mechanism were thoroughly analysed in a Mediterranean experimental watershed in Greece. The region is characterized by a Mediterranean semi-arid climate. A detailed land cover and soil survey using remote sensing and GIS techniques, showed that the watershed is dominated by coarse soils with high hydraulic conductivities, whereas a smaller part is covered with medium textured soils and impervious surfaces. The analysis indicated that the SCS-CN method fails to predict runoff for the storm events studied, and that there is a strong correlation between the CN values obtained from measured runoff and the rainfall depth. The hypothesis that this correlation could be attributed to the existence of an impermeable part in a very permeable watershed was examined in depth, by developing a numerical simulation water flow model for predicting surface runoff generated from each of the three soil types of the watershed. Numerical runs were performed using the HYDRUS-1D code. The results support the validity of this hypothesis for most of the events examined where the linear runoff formula provides better results than the SCS-CN method. The runoff coefficient of this formula can be taken equal to the percentage of the impervious area. However, the linear formula should be applied with caution in case of extreme events with very high rainfall intensities. In this case, the medium textured soils may significantly contribute to the total runoff and the linear formula may significantly underestimate the runoff produced.

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; 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

Differential expression of FGF receptors and of myogenic regulatory factors in primary cultures of satellite cells originating from fast (EDL) and slow (Soleus) twitch rat muscles.

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Martelly, I; Soulet, L; Bonnavaud, S; Cebrian, J; Gautron, J; Barritault, D

2000-11-01

In the rat, the fast and slow twitch muscles respectively Extensor digitorum longus (EDL) and Soleus present differential characteristics during regeneration. This suggests that their satellite cells responsible for muscle growth and repair represent distinct cellular populations. We have previously shown that satellite cells dissociated from Soleus and grown in vitro proliferate more readily than those isolated from EDL muscle. Fibroblast growth factors (FGFs) are known as regulators of myoblast proliferation and several studies have revealed a relationship between the response of myoblasts to FGF and the expression of myogenic regulatory factors (MRF) of the MyoD family by myoblasts. Therefore, we presently examined the possibility that the satellite cells isolated from EDL and Soleus muscles differ in the expression of FGF receptors (FGF-R) and of MRF expression. FGF-R1 and -R4 were strongly expressed in proliferating cultures whereas FGF-R2 and R3 were not detected in these cultures. In differentiating cultures, only -R1 was present in EDL satellite cells while FGF-R4 was also still expressed in Soleus cells. Interestingly, the unconventional receptor for FGF called cystein rich FGF receptor (CFR), of yet unknown function, was mainly detected in EDL satellite cell cultures. Soleus and EDL satellite cell cultures also differed in the expression MRFs. These results are consistent with the notion that satellite cells from fast and slow twitch muscles belong to different types of myogenic cells and suggest that satellite cells might play distinct roles in the formation and diversification of fast and slow fibres.

Characterisation of equine satellite cell transcriptomic profile response to ?-hydroxy-?-methylbutyrate (HMB)

OpenAIRE

Szcze?niak, Katarzyna A.; Ciecierska, Anna; Ostaszewski, Piotr; Sadkowski, Tomasz

2016-01-01

?-Hydroxy-?-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 spe...

Species-specific control of cellular proliferation and the impact of large animal models for the use of olfactory ensheathing cells and Schwann cells in spinal cord repair.

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Wewetzer, Konstantin; Radtke, Christine; Kocsis, Jeffery; Baumgärtner, Wolfgang

2011-05-01

Autologous transplantation of olfactory ensheathing cells (OECs) and Schwann cells (SCs) is considered a promising option to promote axonal regrowth and remyelination after spinal cord injury in humans. However, if the experimental data from the rodent model can be directly extrapolated to humans, as widely believed, remains to be established. While limitations of the rodent system have recently been discussed with regard to the distinct organization of the motor systems, the question whether OECs and SCs may display species-specific properties has not been fully addressed. Prompted by recent studies on canine and porcine glia, we performed a detailed analysis of the in vitro and in vivo properties of OECs and SCs and show that rodent but not human, monkey, porcine, and canine glia require mitogens for in vitro expansion, display a complex response to elevated intracellular cAMP, and undergo spontaneous immortalization upon prolonged mitogen stimulation. These data indicate fundamental inter-species differences of the control of cellular proliferation. Whether OECs and SCs from large animals and humans share growth-promoting in vivo properties with their rodent counterpart is not yet clear. Autologous implantation studies in humans did not reveal adverse effects of cell transplantation so far. However, in vivo studies of large animal or human glia and rodent recipients mainly focused on the remyelinating potential of the transplanted cells. Thus, further experimental in vivo studies in large animals are essential to fully define the axonal growth-promoting potential of OECs and SCs. Based on the homology of the in vitro growth control between porcine, canine and human glia, it is concluded that these species may serve as valuable translational models for scaling up human procedures. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. Copyright © 2010 Elsevier Inc. All rights

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

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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.

Spermidine-Activated Satellite Cells Are Associated with Hypoacetylation in ACVR2B and Smad3 Binding to Myogenic Genes in Mice.

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Zhang, Luchu; Gong, Huiying; Sun, Qinwei; Zhao, Ruqian; Jia, Yimin

2018-01-17

Spermidine is an acetyltransferase inhibitor and a specific inducer of autophagy. Recently, spermidine is identified as a potential therapeutic agent for age-related muscle atrophy and inherited myopathies. However, the effect of spermidine on nonpathological skeletal muscle remains unclear. In this study, long-term spermidine administration in mice lowered the mean cross-sectional area of the gastrocnemius muscle and reduced the expression of myosin heavy chain isoforms in the muscle, which was associated with ubiquitination. Moreover, spermidine supplementation induced autophagy in satellite cells and enhanced satellite cell proliferation. ChIP assay revealed that spermidine repressed H3K56ac in the promoter of ACVR2B and lowered the binding affinity of Smad3 to the promoters of Myf5 and MyoD. Altogether, our results indicate that long-term administration of spermidine can activate satellite cells, as well as enhance autophagy, eventually resulting in muscle atrophy. In addition, H3K56ac and Smad3 emerged as key determinants of satellite cell activation.

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.

Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

Directory of Open Access Journals (Sweden)

Kazuko Ino

Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

Telocytes and stem cells in limbus and uvea of mouse eye.

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Luesma, María José; Gherghiceanu, Mihaela; Popescu, Laurenţiu M

2013-08-01

The potential of stem cell (SC) therapies for eye diseases is well-recognized. However, the results remain only encouraging as little is known about the mechanisms responsible for eye renewal, regeneration and/or repair. Therefore, it is critical to gain knowledge about the specific tissue environment (niches) where the stem/progenitor cells reside in eye. A new type of interstitial cell-telocyte (TC) (www.telocytes.com) was recently identified by electron microscopy (EM). TCs have very long (tens of micrometres) and thin (below 200 nm) prolongations named telopodes (Tp) that form heterocellular networks in which SCs are embedded. We found TCs by EM and electron tomography in sclera, limbus and uvea of the mouse eye. Furthermore, EM showed that SCs were present in the anterior layer of the iris and limbus. Adhaerens and gap junctions were found to connect TCs within a network in uvea and sclera. Nanocontacts (electron-dense structures) were observed between TCs and other cells: SCs, melanocytes, nerve endings and macrophages. These intercellular 'feet' bridged the intercellular clefts (about 10 nm wide). Moreover, exosomes (extracellular vesicles with a diameter up to 100 nm) were delivered by TCs to other cells of the iris stroma. The ultrastructural nanocontacts of TCs with SCs and the TCs paracrine influence via exosomes in the epithelial and stromal SC niches suggest an important participation of TCs in eye regeneration. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.

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Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E; Cao, Mengjun; Wu, Yaojiong

2016-12-01

: Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. ©AlphaMed Press.

Monocrystalline solar cells performance coated by silver nanoparticles: Effect of NPs sizes from point of view Mie theory

Science.gov (United States)

Elnoby, Rasha M.; Mourad, M. Hussein; Elnaby, Salah L. Hassab; Abou Kana, Maram T. H.

2018-05-01

Solar based cells coated by nanoparticles (NPs) acknowledge potential utilizing as a part of photovoltaic innovation. The acquired silicon solar cells (Si-SCs) coated with different sizes of silver nanoparticles (Ag NPs) as well as uncoated were fabricated in our lab. The sizes and optical properties of prepared NPs were characterized by spectroscopic techniques and Mie theory respectively. The reflectivity of Si-SCs showed reduction of this property as the size of NPs increased. Electrical properties as open circuit current, fill factor and output power density were assessed and discussed depending on point of view of Mie theory for the optical properties of NPs. Also, photostabilities of SCs were assessed using diode laser of wavelength 450 nm and power 300 mW. Coated SCs with the largest Ag NPs size showed the highest Photostability due to its highest scattering efficiency according to Mie theory concept.

Satellite data lift the veil on offshore platforms in the South China Sea

Science.gov (United States)

Liu, Yongxue; Sun, Chao; Sun, Jiaqi; Li, Hongyi; Zhan, Wenfeng; Yang, Yuhao; Zhang, Siyu

2016-01-01

Oil and gas exploration in the South China Sea (SCS) has garnered global attention recently; however, uncertainty regarding the accurate number of offshore platforms in the SCS, let alone their detailed spatial distribution and dynamic change, may lead to significant misjudgment of the true status of offshore hydrocarbon production in the region. Using both fresh and archived space-borne images with multiple resolutions, we enumerated the number, distribution, and annual rate of increase of offshore platforms across the SCS. Our results show that: (1) a total of 1082 platforms are present in the SCS, mainly located in shallow-water; and (2) offshore oil/gas exploitation in the SCS is increasing in intensity and advancing from shallow to deep water, and even to ultra-deep-water. Nevertheless, our findings suggest that oil and gas exploration in the SCS may have been over-estimated by one-third in previous reports. However, this overestimation does not imply any amelioration of the potential for future maritime disputes, since the rate of increase of platforms in disputed waters is twice that in undisputed waters. PMID:27641542

Satellite data lift the veil on offshore platforms in the South China Sea

Science.gov (United States)

Liu, Yongxue; Sun, Chao; Sun, Jiaqi; Li, Hongyi; Zhan, Wenfeng; Yang, Yuhao; Zhang, Siyu

2016-09-01

Oil and gas exploration in the South China Sea (SCS) has garnered global attention recently; however, uncertainty regarding the accurate number of offshore platforms in the SCS, let alone their detailed spatial distribution and dynamic change, may lead to significant misjudgment of the true status of offshore hydrocarbon production in the region. Using both fresh and archived space-borne images with multiple resolutions, we enumerated the number, distribution, and annual rate of increase of offshore platforms across the SCS. Our results show that: (1) a total of 1082 platforms are present in the SCS, mainly located in shallow-water; and (2) offshore oil/gas exploitation in the SCS is increasing in intensity and advancing from shallow to deep water, and even to ultra-deep-water. Nevertheless, our findings suggest that oil and gas exploration in the SCS may have been over-estimated by one-third in previous reports. However, this overestimation does not imply any amelioration of the potential for future maritime disputes, since the rate of increase of platforms in disputed waters is twice that in undisputed waters.

Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice.

Science.gov (United States)

Brooks, Matthew J; Hajira, Ameena; Mohamed, Junaith S; Alway, Stephen E

2018-02-22

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a non-damaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice (n=6/group) were randomly placed into 5 groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: non-suspended mice-cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation, was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force and decreased the in vivo fatigability and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type type I and IIa MHC abundance, increased fiber cross sectional area (CSA), and an increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7 positive nuclei inside muscle fibers and a greater MyoD to Pax 7 protein ratio when compared to HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR had lower levels of the inactive phosphorylated YAP serine127 which may have contributed to increased satellite cell activation creased with reloading after HSU. These results indicate that voluntary wheel running increased YAP

Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective.

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Takagi, Toshinori; Yoshimura, Shinichi; Sakuma, Rika; Nakano-Doi, Akiko; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-12-01

Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.

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...... of testosterone. The data indicate that low testosterone levels could reduce the differentiation of satellite cells to myonuclei via the bone morphogenetic proteins signalling pathway, resulting in reduced increases in lean leg mass....

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

Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells...... (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...... 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...

Transplantation of olfactory ensheathing cells as adjunct cell therapy for peripheral nerve injury.

Science.gov (United States)

Radtke, Christine; Wewetzer, Konstantin; Reimers, Kerstin; Vogt, Peter M

2011-01-01

Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies. © 2011 Cognizant Comm. Corp.

Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

Science.gov (United States)

Li, Jian; Ouyang, Qing; Chen, Cheng-Wen; Chen, Qian-Bo; Li, Xiang-Nan; Xiang, Zheng-Hua; Yuan, Hong-Bin

2017-09-01

Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. β-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of β-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells. © 2017 American Academy of Pain Medicine

Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage.

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Van Keymeulen, Alexandra; Fioramonti, Marco; Centonze, Alessia; Bouvencourt, Gaëlle; Achouri, Younes; Blanpain, Cédric

2017-08-15

The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER) + and ER - cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER + lineage is maintained by multipotent SCs or by lineage-restricted SCs. To this end, we generated doxycycline-inducible ER-rtTA mice that allowed us to perform genetic lineage tracing of ER + LCs and study their fate and long-term maintenance. Our results show that ER + cells are maintained by lineage-restricted SCs that exclusively contribute to the expansion of the ER + lineage during puberty and their maintenance during adult life. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Exotic open-flavor bcq¯q¯, bcs¯s¯ and qcq¯b¯, scs¯b¯ tetraquark states

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Chen, Wei; Steele, T. G.; Zhu, Shi-Lin

2014-03-01

We study the exotic bcq¯q¯, bcs¯s¯ and qcq¯b¯, scs¯b¯ systems by constructing the corresponding tetraquark currents with JP=0+ and 1+. After investigating the two-point correlation functions and the spectral densities, we perform QCD sum rule analysis and extract the masses of these open-flavor tetraquark states. Our results indicate that the masses of both the scalar and axial vector tetraquark states are about 7.1-7.2 GeV for the bcq¯q¯ system and 7.2-7.3 GeV for the bcs¯s¯ system. For the qcq¯b¯ tetraquark states with JP=0+ and 1+, their masses are extracted to be around 7.1 GeV. The masses for the scalar and axial vector scs¯b¯ states are 7.1 and 6.9-7.1 GeV, respectively. The tetraquark states qcq¯b¯ and scs¯b¯ lie below the thresholds of D(*)B(*) and Ds(*)Bs(*) respectively, but they can decay into Bc plus a light meson. However, the tetraquark states bcq¯q¯ and bcs¯s¯ lie below the D(*)B¯(*) and Ds(*)B¯s(*) thresholds, suggesting dominantly weak decay mechanisms.

Combined effects of rat Schwann cells and 17β-estradiol in a spinal cord injury model.

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Namjoo, Zeinab; Moradi, Fateme; Aryanpour, Roya; Piryaei, Abbas; Joghataei, Mohammad Taghi; Abbasi, Yusef; Hosseini, Amir; Hassanzadeh, Sajad; Taklimie, Fatemeh Ranjbar; Beyer, Cordian; Zendedel, Adib

2018-04-15

Spinal cord injury (SCI) is a devastating traumatic event which burdens the affected individuals and the health system. Schwann cell (SC) transplantation is a promising repair strategy after SCI. However, a large number of SCs do not survive following transplantation. Previous studies demonstrated that 17β-estradiol (E2) protects different cell types and reduces tissue damage in SCI experimental animal model. In the current study, we evaluated the protective potential of E2 on SCs in vitro and investigated whether the combination of hormonal and SC therapeutic strategy has a better effect on the outcome after SCI. Primary SC cultures were incubated with E2 for 72 h. In a subsequent experiment, thoracic contusion SCI was induced in male rats followed by sustained administration of E2 or vehicle. Eight days after SCI, DiI-labeled SCs were transplanted into the injury epicenter in vehicle and E2-treated animals. The combinatory regimen decreased neurological and behavioral deficits and protected neurons and oligodendrocytes in comparison to vehicle rats. Moreover, E2 and SC significantly decreased the number of Iba-1+ (microglia) and GFAP + cells (astrocyte) in the SCI group. In addition, we found a significant reduction of mitochondrial fission-markers (Fis1) and an increase of fusion-markers (Mfn1 and Mfn2) in the injured spinal cord after E2 and SC treatment. These data demonstrated that E2 protects SCs against hypoxia-induced SCI and improves the survival of transplanted SCs.

Transfer of vesicles from Schwann cell to axon: a novel mechanism of communication in the peripheral nervous system

Directory of Open Access Journals (Sweden)

María Alejandra eLopez-Verrilli

2012-06-01

Full Text Available Schwann cells (SCs are the glial component of the peripheral nervous system, with essential roles during development and maintenance of axons, as well as during regenerative processes after nerve injury. SCs increase conduction velocities by myelinating axons, regulate synaptic activity at presynaptic nerve terminals and are a source of trophic factors to neurons. Thus, development and maintenance of peripheral nerves are crucially dependent on local signalling between SCs and axons. In addition to the classic mechanisms of intercellular signalling, the possibility of communication through secreted vesicles has been poorly explored to date. Interesting recent findings suggest the occurrence of lateral transfer mediated by vesicles from glial cells to axons that could have important roles in axonal growth and axonal regeneration. Here, we review the role of vesicular transfer from SCs to axons and propose the benefits of this means in supporting neuronal and axonal maintenance and regeneration after nerve damage.

Effect of β-hydroxy-β-methylbutyrate on miRNA expression in differentiating equine satellite cells exposed to hydrogen peroxide.

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Chodkowska, Karolina A; Ciecierska, Anna; Majchrzak, Kinga; Ostaszewski, Piotr; Sadkowski, Tomasz

2018-01-01

Skeletal muscle injury activates satellite cells to initiate processes of proliferation, differentiation, and hypertrophy in order to regenerate muscle fibers. The number of microRNAs and their target genes are engaged in satellite cell activation. β-Hydroxy-β-methylbutyrate (HMB) is known to prevent exercise-induced muscle damage. The purpose of this study was to evaluate the effect of HMB on miRNA and relevant target gene expression in differentiating equine satellite cells exposed to H 2 O 2 . We hypothesized that HMB may regulate satellite cell activity, proliferation, and differentiation, hence attenuate the pathological processes induced during an in vitro model of H 2 O 2 -related injury by changing the expression of miRNAs. Equine satellite cells (ESC) were isolated from the samples of skeletal muscle collected from young horses. ESC were treated with HMB (24 h) and then exposed to H 2 O 2 (1 h). For the microRNA and gene expression assessment microarrays, technique was used. Identified miRNAs and genes were validated using real-time qPCR. Cell viability, oxidative stress, and cell damage were measured using colorimetric method and flow cytometry. Analysis of miRNA and gene profile in differentiating ESC pre-incubated with HMB and then exposed to H 2 O 2 revealed difference in the expression of 27 miRNAs and 4740 genes, of which 344 were potential target genes for identified miRNAs. Special attention was focused on differentially expressed miRNAs and their target genes involved in processes related to skeletal muscle injury. Western blot analysis showed protein protection in HMB-pre-treated group compared to control. The viability test confirmed that HMB enhanced cell survival after the hydrogen peroxide exposition. Our results suggest that ESC pre-incubated with HMB and exposed to H 2 O 2 could affect expression on miRNA levels responsible for skeletal muscle development, cell proliferation and differentiation, and activation of tissue repair after

3D Printing of Scaffold for Cells Delivery: Advances in Skin Tissue Engineering

Directory of Open Access Journals (Sweden)

Deepti Singh

2016-01-01

Full Text Available Injury or damage to tissue and organs is a major health problem, resulting in about half of the world’s annual healthcare expenditure every year. Advances in the fields of stem cells (SCs and biomaterials processing have provided a tremendous leap for researchers to manipulate the dynamics between these two, and obtain a skin substitute that can completely heal the wounded areas. Although wound healing needs a coordinated interplay between cells, extracellular proteins and growth factors, the most important players in this process are the endogenous SCs, which activate the repair cascade by recruiting cells from different sites. Extra cellular matrix (ECM proteins are activated by these SCs, which in turn aid in cellular migrations and finally secretion of growth factors that can seal and heal the wounds. The interaction between ECM proteins and SCs helps the skin to sustain the rigors of everyday activity, and in an attempt to attain this level of functionality in artificial three-dimensional (3D constructs, tissue engineered biomaterials are fabricated using more advanced techniques such as bioprinting and laser assisted printing of the organs. This review provides a concise summary of the most recent advances that have been made in the area of polymer bio-fabrication using 3D bio printing used for encapsulating stem cells for skin regeneration. The focus of this review is to describe, in detail, the role of 3D architecture and arrangement of cells within this system that can heal wounds and aid in skin regeneration.

Satellite cell proliferation in adult skeletal muscle

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Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

1995-01-01

Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

Stem cells as a novel tool for drug screening and treatment of degenerative diseases.

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Zuba-Surma, Ewa K; Wojakowski, Wojciech; Madeja, Zbigniew; Ratajczak, Mariusz Z

2012-01-01

Degenerative diseases similarly as acute tissue injuries lead to massive cell loss and may cause organ failure of vital organs (e.g., heart, central nervous system). Therefore, they belong to a group of disorders that may significantly benefit from stem cells (SCs)-based therapies. Several stem and progenitor cell populations have already been described as valuable tools for developing therapeutic strategies in regenerative medicine. In particular, pluripotent stem cells (PSCs), including adult-tissue-derived PSCs, neonatal-tissue-derived SCs, embryonic stem cells (ESCs), and recently described induced pluripotent stem cells (iPSCs), are the focus of particular attention because of their capacity to differentiate into all the cell lineages. Although PSCs are predominantly envisioned to be applied for organ regeneration, they may be also successfully employed in drug screening and disease modeling. In particular, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease. In this review, we will focus on the potential applications of SCs, especially PSCs i) in regenerative medicine therapies, ii) in studying mechanisms of disease, as well as iii) in drug screening and toxicology tests that are crucial in new drug development. In particular, we will discuss the application of SCs in developing new therapeutic approaches to treat degenerative diseases of the neural system and heart. The advantage of adult PSCs in all the above-mentioned settings is that they can be directly harvested from patient tissues and used not only as a safe non-immunogenic source of cells for therapy but also as tools for personalized drug screening and pharmacological therapies.

Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model.

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Gil-Sanchis, Claudia; Cervelló, Irene; Khurana, Satish; Faus, Amparo; Verfaillie, Catherine; Simón, Carlos

2015-06-01

To study the involvement of seven types of bone marrow-derived cells (BMDCs) in the endometrial regeneration in mice after total body irradiation. Prospective experimental animal study. University research laboratories. β-Actin-green fluorescent protein (GFP) transgenic C57BL/6-Tg (CAG-EGFP) and C57BL/6J female mice. The BMDCs were isolated from CAG-EGFP mice: unfractionated bone marrow cells, hematopoietic progenitor cells, endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). In addition three murine GFP(+) cell lines were used: mouse Oct4 negative BMDC multipotent adult progenitor cells (mOct4(-)BM-MAPCs), BMDC hypoblast-like stem cells (mOct4(+) BM-HypoSCs), and MSCs. All cell types were injected through the tail vein of 9 Gy-irradiated C57BL/6J female mice. Flow cytometry, cell culture, bone marrow transplantation assays, histologic evaluation, immunohistochemistry, proliferation, apoptosis, and statistical analysis. After 12 weeks, histologic analysis revealed that uteri of mice with mOct4(-)BM-MAPCs and MSC line were significantly smaller than uteri of mice with uncultured BMDCs or mOct4(+) BM-HypoSCs. The percentage of engrafted GFP(+) cells ranged from 0.13%-4.78%. Expression of Ki-67 was lower in all uteri from BMDCs treated mice than in the control, whereas TUNEL(+) cells were increased in the EPCs and mOct4(+)BM-HypoSCs groups. Low number of some BMDCs can be found in regenerating endometrium, including stromal, endotelial, and epithelial compartments. Freshly isolated MSCs and EPCs together with mOct4(+) BM-HypoSCs induced the greatest degree of regeneration, whereas culture isolated MSCs and mOct4(-)BM-MAPCs transplantation may have an inhibitory effect on endometrial regeneration. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

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

2014-01-01

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 CDK inhibitors (CDKI) 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 FGF-2 is found in association with p21 and p16 promoters, and moreover, only in the old cells. Importantly, in the old satellite cells FGF-2/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 asp15INK4B and p27KIP1, 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. PMID:25447026

Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial.

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Delgado, Elias; Perez-Basterrechea, Marcos; Suarez-Alvarez, Beatriz; Zhou, Huimin; Revuelta, Eva Martinez; Garcia-Gala, Jose Maria; Perez, Silvia; Alvarez-Viejo, Maria; Menendez, Edelmiro; Lopez-Larrea, Carlos; Tang, Ruifeng; Zhu, Zhenlong; Hu, Wei; Moss, Thomas; Guindi, Edward; Otero, Jesus; Zhao, Yong

2015-12-01

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet β cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles. In this open-label, phase 1/phase 2 study, Caucasian T1D patients (N = 15) received two treatments with the Stem Cell Educator (SCE) therapy, an approach that uses human multipotent cord blood-derived multipotent stem cells (CB-SCs). SCE therapy involves a closed-loop system that briefly treats the patient's lymphocytes with CB-SCs in vitro and returns the "educated" lymphocytes (but not the CB-SCs) into the patient's blood circulation. This study is registered with ClinicalTrials.gov, NCT01350219. Clinical data demonstrated that SCE therapy was well tolerated in all subjects. The percentage of naïve CD4(+) T cells was significantly increased at 26 weeks and maintained through the final follow-up at 56 weeks. The percentage of CD4(+) central memory T cells (TCM) was markedly and constantly increased at 18 weeks. Both CD4(+) effector memory T cells (TEM) and CD8(+) TEM cells were considerably decreased at 18 weeks and 26 weeks respectively. Additional clinical data demonstrated the modulation of C-C chemokine receptor 7 (CCR7) expressions on naïve T, TCM, and TEM cells. Following two treatments with SCE therapy, islet β-cell function was improved and maintained in individuals with residual β-cell function, but not in those without residual β-cell function. Current clinical data demonstrated the safety and efficacy of SCE therapy in immune modulation. SCE therapy provides lasting reversal of autoimmune memory that could improve islet β-cell function in Caucasian subjects. Obra Social "La Caixa", Instituto de Salud Carlos III, Red de Investigación Renal, European Union FEDER Funds, Principado de

Insights into cell-free therapeutic approach: Role of stem cell "soup-ernatant".

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Raik, Shalini; Kumar, Ajay; Bhattacharyya, Shalmoli

2018-03-01

Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Transplantation of an alginate-matrigel matrix containing isolated ovarian stromal cells: first step in developing an artificial ovary

OpenAIRE

Vanacker, Julie; Dolmans, Marie-Madeleine; des Rieux, Anne; Jaeger, Jonathan; Luyckx, Valérie; Van Langendonckt, Anne; Donnez, Jacques; Andrade Amorim, Christiani; 3rd International Conference “Strategies in Tissue Engineering”

2012-01-01

Introduction: For women diagnosed with leukemia, transplantation of cryopreserved ovarian tissue after disease remission is not advisable due to the risk of reintroduction of malignant cells. To restore fertility in these patients, a biodegradable artificial ovary that offers an environment allowing isolated follicles and stromal cells (SCs) to survive and grow needs to be developed. The aim of this study is therefore to test the survival and proliferation of isolated SCs encapsulated in an a...

Mammary stem cells: angels or demons in mammary gland?

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Chen, Xueman; Liu, Qiang; Song, Erwei

2017-01-01

A highly dynamic development process exits within the epithelia of mammary gland, featuring morphogenetic variation during puberty, pregnancy, lactation, and regression. The identification of mammary stem cells (MaSCs) via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia. A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation. Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes, it still lacks experimental proofs whether MaSCs, the most primitive cells, are the 'seeds' of malignant transformation during most, if not all, tumorigenesis in the breast. Here, we review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells (BCSCs) along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer (BrCa).

Solar array experiments on the Sphinx satellite

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Stevens, N. J.

1973-01-01

The Space Plasma, High Voltage Interaction Experiment (SPHINX) is the name given to an auxiliary payload satellite scheduled to be launched in January 1974. The principal experiments carried on this satellite are specifically designed to obtain the engineering data on the interaction of high voltage systems with the space plasma. The classes of experiments are solar array segments, insulators, insulators with pin holes and conductors. The satellite is also carrying experiments to obtain flight data on three new solar array configurations; the edge illuminated-multijunction cells, the Teflon encased cells and the violet cells.

Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells.

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Huang, Jinghui; Ye, Zhengxu; Hu, Xueyu; Lu, Lei; Luo, Zhuojing

2010-04-01

Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1-fold increase in NGF release from cultured SCs. The ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering.

Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

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Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

2015-12-01

Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

Overexpression of HOXA4 and HOXA9 genes promotes self-renewal and contributes to colon cancer stem cell overpopulation.

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Bhatlekar, Seema; Viswanathan, Vignesh; Fields, Jeremy Z; Boman, Bruce M

2018-02-01

Because HOX genes encode master regulatory transcription factors that regulate stem cells (SCs) during development and aberrant expression of HOX genes occurs in various cancers, our goal was to determine if dysregulation of HOX genes is involved in the SC origin of colorectal cancer (CRC). We previously reported that HOXA4 and HOXD10 are expressed in the colonic SC niche and are overexpressed in CRC. HOX gene expression was studied in SCs from human colon tissue and CRC cells (CSCs) using qPCR and immunostaining. siRNA-mediated knockdown of HOX expression was used to evaluate the role of HOX genes in modulating cancer SC (CSC) phenotype at the level of proliferation, SC marker expression, and sphere formation. All-trans-retinoic-acid (ATRA), a differentiation-inducing agent was evaluated for its effects on HOX expression and CSC growth. We found that HOXA4 and HOXA9 are up-regulated in CRC SCs. siRNA knockdown of HOXA4 and HOXA9 reduced: (i) proliferation and sphere-formation and (ii) gene expression of known SC markers (ALDH1, CD166, LGR5). These results indicate that proliferation and self-renewal ability of CRC SCs are reduced in HOXA4 and HOXA9 knockdown cells. ATRA decreased HOXA4, HOXA9, and HOXD10 expression in parallel with reduction in ALDH1 expression, self-renewal, and proliferation. Overall, our findings indicate that overexpression of HOXA4 and HOXA9 contributes to self-renewal and overpopulation of SCs in CRC. Strategies designed to modulate HOX expression may provide ways to target malignant SCs and to develop more effective therapies for CRC. © 2017 Wiley Periodicals, Inc.

Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline.

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Gaspar, Maria L; Chang, Yu-Fang; Jesch, Stephen A; Aregullin, Manuel; Henry, Susan A

2017-11-10

In the yeast Saccharomyces cerevisiae , the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1 A strain devoid of Scs2p ( scs2 Δ) and a mutant, OPI1FFAT , lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1 These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells.

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Ferrari, Luiz Fernando; Lotufo, Celina Monteiro; Araldi, Dionéia; Rodrigues, Marcos A; Macedo, Larissa P; Ferreira, Sérgio H; Parada, Carlos Amilcar

2014-12-23

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.

Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

OpenAIRE

Daisuke Ino; Hiroshi Sagara; Junji Suzuki; Kazunori Kanemaru; Yohei Okubo; Masamitsu Iino

2015-01-01

Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulati...

Rainfall-runoff modeling of the Chapel Branch Creek Watershed using GIS-based rational and SCS-CN methods

Science.gov (United States)

Elizabeth N. Mihalik; Norm S. Levine; Devendra M. Amatya

2008-01-01

Chapel Branch Creek (CBC), located within the Town of Santee adjacent to Lake Marion in Orangeburg County, SC, is listed on the SC 2004 303(d) list of impaired waterbodies due to elevated levels of nitrogen (N), phosphorus (P), chlorophyll-a, and pH. In this study, using a GIS-based approach, two runoff modeling methods, the Rational and SCS-CN methods, have been...

Genetic parameters for somatic cell score according to udder infection status in Valle del Belice dairy sheep and impact of imperfect diagnosis of infection.

NARCIS (Netherlands)

Riggio, V.; Portolano, B.; Bovenhuis, H.; Scatassa, S.; Bishop, S.C.

2010-01-01

Background Somatic cell score (SCS) has been promoted as a selection criterion to improve mastitis resistance. However, SCS from healthy and infected animals may be considered as separate traits. Moreover, imperfect sensitivity and specificity could influence animals' classification and impact on

Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.

Science.gov (United States)

Ino, Daisuke; Sagara, Hiroshi; Suzuki, Junji; Kanemaru, Kazunori; Okubo, Yohei; Iino, Masamitsu

2015-09-29

Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca(2+) increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination