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Sample records for gps cell niche

  1. A GRFa2/Prop1/stem (GPS cell niche in the pituitary.

    Directory of Open Access Journals (Sweden)

    Montse Garcia-Lavandeira

    Full Text Available BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the

  2. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  3. Periarteriolar Glioblastoma Stem Cell Niches Express Bone Marrow Hematopoietic Stem Cell Niche Proteins

    NARCIS (Netherlands)

    Hira, Vashendriya V. V.; Wormer, Jill R.; Kakar, Hala; Breznik, Barbara; van der Swaan, Britt; Hulsbos, Renske; Tigchelaar, Wikky; Tonar, Zbynek; Khurshed, Mohammed; Molenaar, Remco J.; van Noorden, Cornelis J. F.

    2018-01-01

    In glioblastoma, a fraction of malignant cells consists of therapy-resistant glioblastoma stem cells (GSCs) residing in protective niches that recapitulate hematopoietic stem cell (HSC) niches in bone marrow. We have previously shown that HSC niche proteins stromal cell-derived factor-1α (SDF-1α),

  4. Niche construction game cancer cells play.

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  5. Niche construction game cancer cells play

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  6. An Automatic K-Means Clustering Algorithm of GPS Data Combining a Novel Niche Genetic Algorithm with Noise and Density

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    Xiangbing Zhou

    2017-12-01

    Full Text Available Rapidly growing Global Positioning System (GPS data plays an important role in trajectory and their applications (e.g., GPS-enabled smart devices. In order to employ K-means to mine the better origins and destinations (OD behind the GPS data and overcome its shortcomings including slowness of convergence, sensitivity to initial seeds selection, and getting stuck in a local optimum, this paper proposes and focuses on a novel niche genetic algorithm (NGA with density and noise for K-means clustering (NoiseClust. In NoiseClust, an improved noise method and K-means++ are proposed to produce the initial population and capture higher quality seeds that can automatically determine the proper number of clusters, and also handle the different sizes and shapes of genes. A density-based method is presented to divide the number of niches, with its aim to maintain population diversity. Adaptive probabilities of crossover and mutation are also employed to prevent the convergence to a local optimum. Finally, the centers (the best chromosome are obtained and then fed into the K-means as initial seeds to generate even higher quality clustering results by allowing the initial seeds to readjust as needed. Experimental results based on taxi GPS data sets demonstrate that NoiseClust has high performance and effectiveness, and easily mine the city’s situations in four taxi GPS data sets.

  7. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

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    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  8. Primer and interviews: The dynamic stem cell niche.

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    Kiefer, Julie C

    2011-03-01

    A stem cell niche is a microenvironment that supports self-renewal of a population of stem cells, and their production of differentiated cells. While the definition evokes images of a stem cell Shangri-La-where a serene stem cell pool nestles within a niche that shelters and sustains it-the reality is much more tumultuous. Niches are subject to an ever-changing maelstrom of environmental factors, the ravages of old age, and the sly tactics of disease. Presented here is a basic overview of the different ways in which stem cell niches respond to local and systemic environments, and their impact on stem cell behavior. The primer culminates with a discussion of the topic with stem cell and niche biologists D. Leanne Jones, Ph.D., and Tudorita Tumbar, Ph.D. Copyright © 2011 Wiley-Liss, Inc.

  9. Formation and regulation of the cancer stem cell niche.

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    Takakura, Nobuyuki

    2012-07-01

    It is widely accepted that tumors contain cancer stem cells (CSC) possessing self-renewal potential as well as the ability to generate numerous cancer cells. Cancer stem cells are resistant to conventional cancer therapy and have greater invasive and metastatic behavior. It has been suggested that blood vessels provide a niche that maintains stemness in normal organs. This role also extends to the field of cancer biology. Cancer stem cells have been isolated from leukemias and solid cancers. Identification of these cells and their niche is critical for identifying molecular targets in order to inhibit their growth and to destroy their niche. For this purpose, sorting of living CSC is required to monitor their presence in the presumptive niche to establish whether a CSC candidate actually shows malignant features. Based on and referring to analyses in normal tissues, molecules including nitric oxide, Wnt, neuropilin-1, hepatocyte growth factor and others involved in the maintenance of CSC have been isolated. Stem cells might affect niche cells and niche cells produce stemness factors on such stimulation. Therefore, the niche might be flexible to support self-renewal or differentiation of stem cells even in the same niche cells. © 2012 Japanese Cancer Association.

  10. Live Imaging of the Drosophila Testis Stem Cell Niche.

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    Greenspan, Leah J; Matunis, Erika L

    2017-01-01

    Live imaging of adult tissue stem cell niches provides key insights into the dynamic behavior of stem cells, their differentiating progeny, and their neighboring support cells, but few niches are amenable to this approach. Here we discuss a technique for long-term live imaging of the Drosophila testis stem cell niche. Culturing whole testes ex vivo for up to 12.5 h allows for tracking of cell-type specific behaviors under normal and various chemically or genetically modified conditions. Fixing and staining tissues after live imaging allows for the molecular confirmation of cell identity and behavior. Utilization of live imaging in intact niches will facilitate further understanding of the cellular and molecular mechanisms that regulate stem cell function in vivo.

  11. Stem cell autotomy and niche interaction in different systems.

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    Dorn, David C; Dorn, August

    2015-07-26

    The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells (homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche (hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion (E-cadherin) and the direction of asymmetrical GSC division - as they were found in Drosophila - can hardly be translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon

  12. Stem cell autotomy and niche interaction in different systems

    Science.gov (United States)

    Dorn, David C; Dorn, August

    2015-01-01

    The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells (homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche (hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion (E-cadherin) and the direction of asymmetrical GSC division - as they were found in Drosophila - can hardly be translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon

  13. Modulating the stem cell niche for tissue regeneration

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    Lane, Steven W; Williams, David A; Watt, Fiona M

    2015-01-01

    The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell–extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions. PMID:25093887

  14. Intestinal Stem Cell Niche: The Extracellular Matrix and Cellular Components

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    Laween Meran

    2017-01-01

    Full Text Available The intestinal epithelium comprises a monolayer of polarised columnar cells organised along the crypt-villus axis. Intestinal stem cells reside at the base of crypts and are constantly nourished by their surrounding niche for maintenance, self-renewal, and differentiation. The cellular microenvironment including the adjacent Paneth cells, stromal cells, smooth muscle cells, and neural cells as well as the extracellular matrix together constitute the intestinal stem cell niche. A dynamic regulatory network exists among the epithelium, stromal cells, and the matrix via complex signal transduction to maintain tissue homeostasis. Dysregulation of these biological or mechanical signals could potentially lead to intestinal injury and disease. In this review, we discuss the role of different intestinal stem cell niche components and dissect the interaction between dynamic matrix factors and regulatory signalling during intestinal stem cell homeostasis.

  15. Stem cell dynamics in the hair follicle niche

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    Rompolas, Panteleimon; Greco, Valentina

    2014-01-01

    Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

  16. 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

  17. Haematopoietic stem cell niches: new insights inspire new questions

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    Ugarte, Fernando; Forsberg, E Camilla

    2013-01-01

    Haematopoietic stem cell (HSC) niches provide an environment essential for life-long HSC function. Intense investigation of HSC niches both feed off and drive technology development to increase our capability to assay functionally defined cells with high resolution. A major driving force behind the desire to understand the basic biology of HSC niches is the clear implications for clinical therapies. Here, with particular emphasis on cell type-specific deletion of SCL and CXCL12, we focus on unresolved issues on HSC niches, framed around some very recent advances and novel discoveries on the extrinsic regulation of HSC maintenance. We also provide ideas for possible paths forward, some of which are clearly within reach while others will require both novel tools and vision. PMID:24022369

  18. Aging in hair follicle stem cells and niche microenvironment.

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    Ji, Jiang; Ho, Bryan Siu-Yin; Qian, Ge; Xie, Xiao-Ming; Bigliardi, Paul Lorenz; Bigliardi-Qi, Mei

    2017-10-01

    Hair graying and hair loss are prominent and common characteristics of the elderly population. In some individuals these processes can significantly impact their quality of life, leading to depression, anxiety and other serious mental health problems. Accordingly, there has been much interest in understanding the complex physiological changes within the hair follicle in the aging individual. It is now known that hair follicles represent a prototypical stem cell niche, where both micro- and macroenvironmental influences are integrated alongside stem cell-stem cell and stem cell-stem niche interactions to determine hair growth or hair follicle senescence. Recent studies have identified imbalanced stem cell differentiation and altered stem cell activity as important factors during hair loss, indicating new avenues for the development of therapeutic agents to stimulate hair growth. Here, we pull together the latest findings on the hair follicle stem cell niche and the multifactorial interactions underlying the various forms of hair loss. © 2017 Japanese Dermatological Association.

  19. Complexity of bone marrow hematopoietic stem cell niche.

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    Asada, Noboru; Takeishi, Shoichiro; Frenette, Paul S

    2017-07-01

    Hematopoietic stem cells (HSCs) that produce a variety of hematopoietic lineage cells throughout the life reside in specialized microenvironment called "niche" in the bone marrow (BM) where they are tightly regulated. With the recent advances in experimental technologies enabling the selective deletion of molecules, various types of cells in the BM have been proposed to contribute to HSC niche activity. Among these are stromal cells closely associated with the vasculature. In this review, we provide an overview of recent advances in HSC niche research, and focus on the studies describing the functional roles of perivascular cells for HSC maintenance and mobilization. Not only for physiologic state, we also discuss the recent evidences suggesting the importance of microenvironment for emergence of malignant hematopoietic diseases.

  20. Role for Adhesion Molecules in the Spermatogonial Stem Cell Niche

    NARCIS (Netherlands)

    de Rooij, Dirk G.; Repping, S.; van Pelt, Ans M. M.

    2008-01-01

    In this issue of Cell Stem Cell, Kanatsu-Shinohara et al. (2008) show that beta 1-integrin participates in normal spermatogenesis and is required for spermatogonial stem cell (SSC) homing to the basal membrane niche. The methodology used provides a powerful tool to study the role of other factors in

  1. Mouse Incisor Stem Cell Niche and Myb Transcription Factors

    Czech Academy of Sciences Publication Activity Database

    Švandová, Eva; Veselá, Barbora; Šmarda, J.; Hampl, A.; Radlanski, R.J.; Matalová, Eva

    2015-01-01

    Roč. 44, č. 5 (2015), s. 338-344 ISSN 0340-2096 R&D Projects: GA ČR GAP304/11/1418; GA ČR GCP302/12/J059 Institutional support: RVO:67985904 Keywords : c-Myb * stem cell niches Subject RIV: EA - Cell Biology Impact factor: 0.615, year: 2015

  2. Ovarian Stem Cell Niche and Follicular Renewal in Mammals

    Czech Academy of Sciences Publication Activity Database

    Bukovský, Antonín

    2011-01-01

    Roč. 294, č. 8 (2011), s. 1284-1306 ISSN 1932-8486 Institutional research plan: CEZ:AV0Z50520701 Keywords : ovary * stem cell niche * neo-oogenesis Subject RIV: EA - Cell Biology Impact factor: 1.473, year: 2011

  3. Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse Mammary Epithelium

    National Research Council Canada - National Science Library

    Chepko, Gloria; Hilakivi-Clarke, Leena

    2006-01-01

    Develop an immunohistochemical method for identifying stem cells and stem cell niches, and to use this to determine if in utero estrogenic overstimulation causes changes in the number of stem cells or their niches...

  4. Multifaceted Roles of Connexin 43 in Stem Cell Niches.

    Science.gov (United States)

    Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

    2018-01-01

    Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

  5. Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches.

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    Hira, Vashendriya V V; Van Noorden, Cornelis J F; Carraway, Hetty E; Maciejewski, Jaroslaw P; Molenaar, Remco J

    2017-08-01

    Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes. Thus far, three types of HSC niches are recognized: endosteal, reticular and perivascular niches. However, we argue here that there is only one type of HSC niche, which consists of a periarteriolar compartment and a perisinusoidal compartment. In the periarteriolar compartment, hypoxia and low levels of reactive oxygen species preserve the HSC pool. In the perisinusoidal compartment, hypoxia in combination with higher levels of reactive oxygen species enables proliferation of progenitor cells and their mobilization into the circulation. Because HSC niches offer protection to LSCs against chemotherapy, we review novel therapeutic strategies to inhibit homing of LSCs in niches for the prevention of dedifferentiation of leukemic cells into LSCs and to stimulate migration of leukemic cells out of niches. These strategies enhance differentiation and proliferation and thus sensitize leukemic cells to chemotherapy. Finally, we list clinical trials of therapies that tackle LSCs in HSC niches to circumvent their protection against chemotherapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Osteoblastic activation in the hematopoietic stem cell niche.

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    Calvi, Laura M

    2006-04-01

    Hematopoietic stem cells (HSC) are rare primitive cells capable of reconstituting all blood cell lineages throughout the life of an individual. The microenvironment in which stem cells reside is essential for their survival, self-renewal, and differentiation. This microenvironment, or HSC niche, has been difficult to define in bone and bone marrow, but recent studies from our laboratory and others have shown that osteoblasts, the bone-forming cells, are an essential regulatory component of this complex cellular network. We established that parathyroid hormone (PTH), through activation of the PTH/PTHrP receptor (PTH1R) in osteoblastic cells, could alter the HSC niche resulting in HSC expansion in vivo and in vitro and improving dramatically the survival of mice receiving bone marrow transplants. These findings are of great clinical appeal, because they suggest that a strategy aimed at modifying supportive cells in a stem cell niche can expand HSC. While a number of molecules have been found to be important for hematopoietic/osteoblastic interactions, we have focused on the Jagged1/Notch signaling pathway, which was necessary for the PTH-dependent HSC expansion. Since the Jagged1/Notch signaling pathway has been implicated in the microenvironmental control of stem cell self-renewal in several organ systems, definition of Jagged1 modulation, which is currently poorly understood, should provide additional molecular targets for stem cell regulation and advance the understanding of stem cell-microenvironmental interactions.

  7. Differential cytokine contributions of perivascular haematopoietic stem cell niches.

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    Asada, Noboru; Kunisaki, Yuya; Pierce, Halley; Wang, Zichen; Fernandez, Nicolas F; Birbrair, Alexander; Ma'ayan, Avi; Frenette, Paul S

    2017-03-01

    Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2 + cells, but not from sinusoidal LepR + cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR + cells, but not NG2 + cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

  8. Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches

    NARCIS (Netherlands)

    Hira, Vashendriya V. V.; van Noorden, Cornelis J. F.; Carraway, Hetty E.; Maciejewski, Jaroslaw P.; Molenaar, Remco J.

    2017-01-01

    Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are

  9. Stem-cell niches: nursery rhymes across kingdoms.

    Science.gov (United States)

    Scheres, Ben

    2007-05-01

    Despite the large evolutionary distance between the plant and animal kingdoms, stem cells in both reside in specialized cellular contexts called stem-cell niches. Although stem-cell-specification factors have been recruited from plant-specific gene families, maintenance factors that repress stem-cell differentiation are conserved between plants and animals. Recent evidence indicates that stem cells in multicellular organisms can be specified by kingdom-specific patterning mechanisms that connect to a related core of epigenetic stem-cell factors.

  10. Wnt signaling in the stem cell niche

    NARCIS (Netherlands)

    Rattis, Frédérique Marie; Voermans, Carlijn; Reya, Tannishtha

    2004-01-01

    All the cells present in the blood are derived from the hematopoietic stem cell (HSC). Because mature blood cells have a limited life span, HSCs must perpetuate themselves through self-renewal to maintain a functional hematopoietic compartment for the lifetime of an organism. This review focuses on

  11. Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete for the HSC niche?

    Science.gov (United States)

    Noll, J E; Williams, S A; Purton, L E; Zannettino, A C W

    2012-09-14

    In the adult mammal, normal haematopoiesis occurs predominantly in the bone marrow, where primitive haematopoietic stem cells (HSC) and their progeny reside in specialised microenvironments. The bone marrow microenvironment contains specific anatomical areas (termed niches) that are highly specialised for the development of certain blood cell types, for example HSCs. The HSC niche provides important cell-cell interactions and signalling molecules that regulate HSC self-renewal and differentiation processes. These same signals and interactions are also important in the progression of haematological malignancies, such as multiple myeloma (MM). This review provides an overview of the bone marrow microenvironment and its involvement in normal, physiological HSC maintenance and plasma cell growth throughout MM disease progression.

  12. The Role of Lymphatic Niches in T Cell Differentiation

    Science.gov (United States)

    Capece, Tara; Kim, Minsoo

    2016-01-01

    Long-term immunity to many viral and bacterial pathogens requires CD8+ memory T cell development, and the induction of long-lasting CD8+ memory T cells from a naïve, undifferentiated state is a major goal of vaccine design. Formation of the memory CD8+ T cell compartment is highly dependent on the early activation cues received by naïve CD8+ T cells during primary infection. This review aims to highlight the cellularity of various niches within the lymph node and emphasize recent evidence suggesting that distinct types of T cell activation and differentiation occur within different immune contexts in lymphoid organs. PMID:27306645

  13. Cellular population dynamics control the robustness of the stem cell niche

    Directory of Open Access Journals (Sweden)

    Adam L. MacLean

    2015-11-01

    Full Text Available Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain ‘stemness’ through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell–niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell–cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche – and hence of the stem cell pool in the niche – depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.

  14. Vascular niches for disseminated tumour cells in bone

    Directory of Open Access Journals (Sweden)

    Anjali P. Kusumbe

    2016-09-01

    Full Text Available The vasculature of the skeletal system regulates osteogenesis and hematopoiesis, in addition to its primary function as a transportation network. Recent studies suggest that the vasculature in bone regulates multiple steps involved in the metastatic cascade. Matrix and growth factor abundant vascular microenvironments in bone not only provide a fertile soil for the metastatic growth but also support the dormancy of Disseminated Tumour Cells (DTCs. Interestingly, vasculature also seems to direct the reactivation of dormant DTCs. Targeting such early steps of bone metastasis by directing therapies against vascular niches can lead to the development of effective therapeutic strategies that delay or even prevent the metastatic relapse. However, this would require a detailed understanding of the regulatory mechanisms that govern the interaction between endothelial cells and DTCs in the early stages of bone metastasis. This review aims to highlight the importance of vascular niches and outline their newly identified roles during bone metastasis.

  15. GPS

    African Journals Online (AJOL)

    spamer

    Directorate: Antarctica and Islands and Branch: Marine & Coastal Management of the Department of. Environmental Affairs and Tourism. Prof. C. L. Merry,. Department of Geodetics, University of Cape Town, provided helpful information about GPS accuracy, and commented on a draft. LITERATURE CITED. BUCKLEY, P. A. ...

  16. Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

    Science.gov (United States)

    Ravichandran, Srikanth; Del Sol, Antonio

    2017-02-01

    Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  17. Hedgehog signaling establishes precursors for germline stem cell niches by regulating cell adhesion.

    Science.gov (United States)

    Lai, Chun-Ming; Lin, Kun-Yang; Kao, Shih-Han; Chen, Yi-Ning; Huang, Fu; Hsu, Hwei-Jan

    2017-05-01

    Stem cells require different types of supporting cells, or niches, to control stem cell maintenance and differentiation. However, little is known about how those niches are formed. We report that in the development of the Drosophila melanogaster ovary, the Hedgehog (Hh) gradient sets differential cell affinity for somatic gonadal precursors to specify stromal intermingled cells, which contributes to both germline stem cell maintenance and differentiation niches in the adult. We also report that Traffic Jam (an orthologue of a large Maf transcription factor in mammals) is a novel transcriptional target of Hh signaling to control cell-cell adhesion by negative regulation of E-cadherin expression. Our results demonstrate the role of Hh signaling in niche establishment by segregating somatic cell lineages for differentiation. © 2017 Lai et al.

  18. The vasculature as a neural stem cell niche.

    Science.gov (United States)

    Otsuki, Leo; Brand, Andrea H

    2017-11-01

    Neural stem cells (NSCs) are multipotent, self-renewing progenitors that generate progeny that differentiate into neurons and glia. NSCs in the adult mammalian brain are generally quiescent. Environmental stimuli such as learning or exercise can activate quiescent NSCs, inducing them to proliferate and produce new neurons and glia. How are these behaviours coordinated? The neurovasculature, the circulatory system of the brain, is a key component of the NSC microenvironment, or 'niche'. Instructive signals from the neurovasculature direct NSC quiescence, proliferation, self-renewal and differentiation. During ageing, a breakdown in the niche accompanies NSC dysfunction and cognitive decline. There is much interest in reversing these changes and enhancing NSC activity by targeting the neurovasculature therapeutically. Here we discuss principles of neurovasculature-NSC crosstalk, and the implications for the design of NSC-based therapies. We also consider the emerging contributions to this field of the model organism Drosophila melanogaster. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche.

    Science.gov (United States)

    Wang, Su; Gao, Yuan; Song, Xiaoqing; Ma, Xing; Zhu, Xiujuan; Mao, Ying; Yang, Zhihao; Ni, Jianquan; Li, Hua; Malanowski, Kathryn E; Anoja, Perera; Park, Jungeun; Haug, Jeff; Xie, Ting

    2015-10-09

    Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche.

  20. Stem Cell Niches in Glioblastoma: A Neuropathological View

    Directory of Open Access Journals (Sweden)

    Davide Schiffer

    2014-01-01

    Full Text Available Glioblastoma (GBM stem cells (GSCs, responsible for tumor growth, recurrence, and resistance to therapies, are considered the real therapeutic target, if they had no molecular mechanisms of resistance, in comparison with the mass of more differentiated cells which are insensitive to therapies just because of being differentiated and nonproliferating. GSCs occur in tumor niches where both stemness status and angiogenesis are conditioned by the microenvironment. In both perivascular and perinecrotic niches, hypoxia plays a fundamental role. Fifteen glioblastomas have been studied by immunohistochemistry and immunofluorescence for stemness and differentiation antigens. It has been found that circumscribed necroses develop inside hyperproliferating areas that are characterized by high expression of stemness antigens. Necrosis developed inside them because of the imbalance between the proliferation of tumor cells and endothelial cells; it reduces the number of GSCs to a thin ring around the former hyperproliferating area. The perinecrotic GSCs are nothing else that the survivors remnants of those populating hyperproliferating areas. In the tumor, GSCs coincide with malignant areas so that the need to detect where they are located is not so urgent.

  1. Cigarette Smoke Alters the Hematopoietic Stem Cell Niche

    Directory of Open Access Journals (Sweden)

    Robert W. Siggins

    2014-02-01

    Full Text Available Effects of tobacco smoke on hematologic derangements have received little attention. This study employed a mouse model of cigarette smoke exposure to explore the effects on bone marrow niche function. While lung cancer is the most widely studied consequence of tobacco smoke exposure, other malignancies, including leukemia, are associated with tobacco smoke exposure. Animals received cigarette smoke exposure for 6 h/day, 5 days/week for 9 months. Results reveal that the hematopoietic stem and progenitor cell (HSPC pool size is reduced by cigarette smoke exposure. We next examined the effect of cigarette smoke exposure on one supporting cell type of the niche, the mesenchymal stromal cells (MSCs. Smoke exposure decreased the number of MSCs. Transplantation of naïve HSPCs into irradiated mice with cigarette smoke exposure yielded fewer numbers of engrafted HSPCs. This result suggests that smoke-exposed mice possess dysfunctional niches, resulting in abnormal hematopoiesis. Co-culture experiments using MSCs isolated from control or cigarette smoke-exposed mice with naïve HSPCs in vitro showed that MSCs from cigarette smoke-exposed mice generated marked expansion of naïve HSPCs. These data show that cigarette smoke exposure decreases in vivo MSC and HSC number and also increases pro-proliferative gene expression by cigarette smoke-exposed MSCs, which may stimulate HSPC expansion. These results of this investigation are clinically relevant to both bone marrow donors with a history of smoking and bone marrow transplant (BMT recipients with a history of smoking.

  2. Engineering the hematopoietic stem cell niche: Frontiers in biomaterial science

    Science.gov (United States)

    Choi, Ji Sun; Mahadik, Bhushan P.; Harley, Brendan A. C.

    2016-01-01

    Hematopoietic stem cells (HSCs) play a crucial role in the generation of the body’s blood and immune cells. This process takes place primarily in the bone marrow in specialized ‘niche’ microenvironments, which provide signals responsible for maintaining a balance between HSC quiescence, self-renewal, and lineage specification required for life-long hematopoiesis. While our understanding of these signaling mechanisms continues to improve, our ability to engineer them in vitro for the expansion of clinically relevant HSC populations is still lacking. In this review, we focus on development of biomaterials-based culture platforms for in vitro study of interactions between HSCs and their local microenvironment. The tools and techniques used for both examining HSC-niche interactions as well as applying these findings towards controlled HSC expansion or directed differentiation in 2D and 3D platforms are discussed. These novel techniques hold the potential to push the existing boundaries of HSC cultures towards high-throughput, real-time, and single-cell level biomimetic approaches that enable a more nuanced understanding of HSC regulation and function. Their application in conjunction with innovative biomaterial platforms can pave the way for engineering artificial bone marrow niches for clinical applications as well as elucidating the pathology of blood-related cancers and disorders. PMID:26356030

  3. Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche.

    Science.gov (United States)

    Wang, Xiaoxi; Page-McCaw, Andrea

    2018-02-07

    Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In Drosophila ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or hid expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal. © 2018. Published by The Company of Biologists Ltd.

  4. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  5. [The emerging technology of tissue engineering : Focus on stem cell niche].

    Science.gov (United States)

    Schlötzer-Schrehardt, U; Freudenberg, U; Kruse, F E

    2017-04-01

    Limbal stem cells reside in a highly specialized complex microenvironment that is known as the stem cell niche, an anatomically protected region at the bottom of the Palisades of Vogt, where the stem cells are located and where their quiescence, proliferation and differentiation are maintained in balance. Besides the epithelial stem and progenitor cell clusters, the limbal niche comprises several types of supporting niche cells and a specific extracellular matrix mediating biochemical and biophysical signals. Stem cell-based tissue engineering aims to mimic the native stem cell niche and to present appropriate microenvironmental cues in a controlled and reproducible fashion in order to maintain stem cell function within the graft. Current therapeutic approaches for ex vivo expansion of limbal stem cells only take advantage of surrogate niches. However, new insights into the molecular composition of the limbal niche and innovative biosynthetic scaffolds have stimulated novel strategies for niche-driven stem cell cultivation. Promising experimental approaches include collagen-based organotypic coculture systems of limbal epithelial stem cells with their niche cells and biomimetic hydrogel platforms prefunctionalized with appropriate biomolecular and biophysical signals. Future translation of these novel regenerative strategies into clinical application is expected to improve long-term outcomes of limbal stem cell transplantation for ocular surface reconstruction.

  6. A Global Stem Cell Niche – Need of the Hour

    Directory of Open Access Journals (Sweden)

    Editorial

    2014-11-01

    Full Text Available A Global Stem Cell Niche – Need of the Hour The time, this issue is online, most of us would be aware of the world’s first induced pluripotent stem (iPS cell based clinical trial for age-related macular degeneration which is underway in Japan. The first patient in the trial has been transplanted with the cell sheets of retinal pigment epithelium derived from the patient's own iPS cells in September 2014 [1] and is under follow-up. As we are overwhelmed with this scientific feat, an analysis of the trends of stem cell based clinical trials globally [2] makes us realize that there is a wide variation in the clinical trials between the nations, with differences being observed in diseases that are given priority, cell sources that are being chosen, principles of ethics, regulatory frameworks etc,. A realization dawns that the scientific communities in each group or country have their own niche of cell based research leading to the above mentioned variations. While in Japan, a hi-tech iPS trial has started, Mazini et al from Morocco, describe the hurdles in creating a public cord blood bank in their country with a background of the regulatory guidelines existing there while Lee et al's work from the United States of America (USA focuses on microencapsulation of adipose derived stem cells. While each of the above subject are equally important, a global consortium is the need of the hour, where interactions among all the stake holders of cell based therapies can be established for enabling exchange of information, technology, solutions and products, thereby avoiding repetition of the same work, while gaining the insight of different viewpoints into solving an issue which could be of significance either to a local community or the entire global society. References: Reardon S, Cyranoski D. Japan stem-cell trial stirs envy. Nature. 2014 ;513(7518:287-8. Li MD, Atkins H, Bubela T. The global landscape of stem cell clinical trials. Regen Med. 2014;9(1:27-39.

  7. Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells.

    Science.gov (United States)

    Roch, Aline; Giger, Sonja; Girotra, Mukul; Campos, Vasco; Vannini, Nicola; Naveiras, Olaia; Gobaa, Samy; Lutolf, Matthias P

    2017-08-09

    The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell-cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

  8. Regenerative Endodontic Procedures: A Perspective from Stem Cell Niche Biology.

    Science.gov (United States)

    Marí-Beffa, Manuel; Segura-Egea, Juan José; Díaz-Cuenca, Aránzazu

    2017-01-01

    Endodontics uses cell therapy strategies to treat pulpal and periapical diseases. During these therapies, surgeons aim to reconstruct the natural microenvironments that regulate the activity of dental stem cells. We searched for more than 400 articles in PubMed using key words from regenerative endodontics and dental stem cell biology. In 268 articles, we reviewed what factors may influence histologic results after preclinical dental treatments that use regenerative endodontic procedures after pulpectomy. Several factors, such as the origin of stem cells, the biomimicry of scaffolds used, and the size of lesions, are considered to influence the histologic appearance of the regenerated pulp-dentin complex after treatments. Information is accumulating on transcription factors that generate the pulp-dentin complex and survival/trophic factors that would benefit niche recovery and histologic results. In this article, we discuss the noninterchangeability of stem cells, the influence of dentin-entrapped molecule release on pulp regeneration and survival of stem cells, and the need of positional markers to assess treatments histologically. The ex vivo amplification of appropriate dental stem cells, the search for scaffolds storing the molecular diversity entrapped in the dentin, and the use of positional transcription factors as histologic markers are necessary to improve future preclinical experiments. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. The Haematopoietic Stem Cell Niche: New Insights into the Mechanisms Regulating Haematopoietic Stem Cell Behaviour

    Directory of Open Access Journals (Sweden)

    Andrew J. Lilly

    2011-01-01

    Full Text Available The concept of the haematopoietic stem cell (HSC niche was formulated by Schofield in the 1970s, as a region within the bone marrow containing functional cell types that can maintain HSC potency throughout life. Since then, ongoing research has identified numerous cell types and a plethora of signals that not only maintain HSCs, but also dictate their behaviour with respect to homeostatic requirements and exogenous stresses. It has been proposed that there are endosteal and vascular niches within the bone marrow, which are thought to regulate different HSC populations. However, recent data depicts a more complicated picture, with functional crosstalk between cells in these two regions. In this review, recent research into the endosteal/vascular cell types and signals regulating HSC behaviour are considered, together with the possibility of a single subcompartmentalised niche.

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

    NARCIS (Netherlands)

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

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

  11. Cell jammers, GPS jammers, and other jamming devices.

    Science.gov (United States)

    2012-10-15

    We caution consumers that it is against the law to use a cell or GPS jammer or any other type of device that blocks, : jams or interferes with authorized communications, as well as to import, advertise, sell, or ship such a device. The : FCC Enforcem...

  12. Traffic jam functions in a branched pathway from Notch activation to niche cell fate.

    Science.gov (United States)

    Wingert, Lindsey; DiNardo, Stephen

    2015-07-01

    The niche directs key behaviors of its resident stem cells, and is thus crucial for tissue maintenance, repair and longevity. However, little is known about the genetic pathways that guide niche specification and development. The male germline stem cell niche in Drosophila houses two stem cell populations and is specified within the embryonic gonad, thus making it an excellent model for studying niche development. The hub cells that form the niche are specified early by Notch activation. Over the next few hours, these individual cells then cluster together and take up a defined position before expressing markers of hub cell differentiation. This timing suggests that there are other factors for niche development yet to be defined. Here, we have identified a role for the large Maf transcription factor Traffic jam (Tj) in hub cell specification downstream of Notch. Tj downregulation is the first detectable effect of Notch activation in hub cells. Furthermore, Tj depletion is sufficient to generate ectopic hub cells that can recruit stem cells. Surprisingly, ectopic niche cells in tj mutants remain dispersed in the absence of Notch activation. This led us to uncover a branched pathway downstream of Notch in which Bowl functions to direct hub cell assembly in parallel to Tj downregulation. © 2015. Published by The Company of Biologists Ltd.

  13. Not all renal stem cell niches are the same: anatomy of an evolution

    Directory of Open Access Journals (Sweden)

    Clara Gerosa

    2016-08-01

    Full Text Available The renal stem cell niche represents the most important structure of the developing kidney, responsible for nephrogenesis. Recently, some Authors have reported, at ultrastructural level, a previously unknown complexity of the architecture of renal stem cell niche in experimental models. This study was aimed at studying, at histological level, the anatomy of renal stem cell niches in the human fetal kidney. To this end, ten fetal kidneys, whose gestational ages ranged from 11 up to 24 weeks, were studied. H&E-stained sections were observed at high power. The study of the anatomy of renal stem cell niches in the human kidney revealed a previously unreported complexity: some niches appeared as a roundish arrangement of mesenchymal cells; others showed the initial phases of induction by ureteric buds; in other niches the process of mesenchymal epithelial transition was more evident; finally, in other stem cell niches the first signs of nephron origin were detectable. These findings suggest the existence of niches with different anatomy in the same kidney, indicating different stages of evolution even in adjacent niches. All stem cell niches were in strict contact with the capsular cells, suggesting a major role of the renal capsule in nephrogenesis. Finally, our study confirms the existence of a strict contact between the bud tip cells and the surrounding mesenchyme in the human developing kidney, giving a morphological support to the theory of intercellular channels allowing the passage of transcription factors from the epithelial to the mesenchymal stem/progenitors cells.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  14. Optimization of Femtosecond Laser Polymerized Structural Niches to Control Mesenchymal Stromal Cell Fate in Culture

    Directory of Open Access Journals (Sweden)

    Manuela T. Raimondi

    2014-06-01

    Full Text Available We applied two-photon polymerization to fabricate 3D synthetic niches arranged in complex patterns to study the effect of mechano-topological parameters on morphology, renewal and differentiation of rat mesenchymal stromal cells. Niches were formed in a photoresist with low auto-fluorescence, which enabled the clear visualization of the fluorescence emission of the markers used for biological diagnostics within the internal niche structure. The niches were structurally stable in culture up to three weeks. At three weeks of expansion in the niches, cell density increased by almost 10-fold and was 67% greater than in monolayer culture. Evidence of lineage commitment was observed in monolayer culture surrounding the structural niches, and within cell aggregates, but not inside the niches. Thus, structural niches were able not only to direct stem cell homing and colony formation, but also to guide aggregate formation, providing increased surface-to-volume ratios and space for stem cells to adhere and renew, respectively.

  15. Systemic and local cues drive neural stem cell niche remodelling during neurogenesis in Drosophila.

    Science.gov (United States)

    Spéder, Pauline; Brand, Andrea H

    2018-01-04

    Successful neurogenesis requires adequate proliferation of neural stem cells (NSCs) and their progeny, followed by neuronal differentiation, maturation and survival. NSCs inhabit a complex cellular microenvironment, the niche, which influences their behaviour. To ensure sustained neurogenesis, niche cells must respond to extrinsic, environmental changes whilst fulfilling the intrinsic requirements of the neurogenic program and adapting their roles accordingly. However, very little is known about how different niche cells adjust their properties to such inputs. Here, we show that nutritional and NSC-derived signals induce the remodelling of Drosophila cortex glia, adapting this glial niche to the evolving needs of NSCs. First, nutrition-induced activation of PI3K/Akt drives the cortex glia to expand their membrane processes. Second, when NSCs emerge from quiescence to resume proliferation, they signal to glia to promote membrane remodelling and the formation of a bespoke structure around each NSC lineage. The remodelled glial niche is essential for newborn neuron survival.

  16. Escargot Restricts Niche Cell to Stem Cell Conversion in the Drosophila Testis

    Directory of Open Access Journals (Sweden)

    Justin Voog

    2014-05-01

    Full Text Available Stem cells reside within specialized microenvironments, or niches, that control many aspects of stem cell behavior. Somatic hub cells in the Drosophila testis regulate the behavior of cyst stem cells (CySCs and germline stem cells (GSCs and are a primary component of the testis stem cell niche. The shutoff (shof mutation, characterized by premature loss of GSCs and CySCs, was mapped to a locus encoding the evolutionarily conserved transcription factor Escargot (Esg. Hub cells depleted of Esg acquire CySC characteristics and differentiate as cyst cells, resulting in complete loss of hub cells and eventually CySCs and GSCs, similar to the shof mutant phenotype. We identified Esg-interacting proteins and demonstrate an interaction between Esg and the corepressor C-terminal binding protein (CtBP, which was also required for maintenance of hub cell fate. Our results indicate that niche cells can acquire stem cell properties upon removal of a single transcription factor in vivo.

  17. Interactions between structural and chemical biomimetism in synthetic stem cell niches.

    Science.gov (United States)

    Nava, Michele M; Raimondi, Manuela T; Credi, Caterina; De Marco, Carmela; Turri, Stefano; Cerullo, Giulio; Osellame, Roberto

    2015-01-16

    Advancements in understanding stem cell functions and differentiation are of key importance for the clinical success of stem-cell-based therapies. 3D structural niches fabricated by two-photon polymerization are a powerful platform for controlling stem cell growth and differentiation. In this paper, we investigate the possibility of further controlling stem cell fate by tuning the mechanical properties of such niches through coating with thin layers of biomimetic hyaluronan-based and gelatin-based hydrogels. We first assess the biocompatibility of chemical coatings and then study the interactions between structural and chemical biomimetism on the response of MSCs in terms of proliferation and differentiation. We observed a clear effect of the hydrogel coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated niches we observed a stronger metabolic activity and commitment toward the osteo-chondral lineage with respect to hyaluronan-coated niches. Conversely, a reduction in the homing effect was observed in all the coated niches, especially in gelatin-coated niches. This study demonstrates the feasibility of controlling independently different mechanical cues, in bioengineered stem cell niches, i.e. the 3D scaffold geometry and the surface stiffness. This will allow, on the one hand, understanding their specific role in stem cell proliferation and differentiation and, on the other hand, finely tuning their synergistic effect.

  18. Stem cell niche-specific Ebf3 maintains the bone marrow cavity.

    Science.gov (United States)

    Seike, Masanari; Omatsu, Yoshiki; Watanabe, Hitomi; Kondoh, Gen; Nagasawa, Takashi

    2018-03-01

    Bone marrow is the tissue filling the space between bone surfaces. Hematopoietic stem cells (HSCs) are maintained by special microenvironments known as niches within bone marrow cavities. Mesenchymal cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-positive (LepR + ) cells, are a major cellular component of HSC niches that gives rise to osteoblasts in bone marrow. However, it remains unclear how osteogenesis is prevented in most CAR/LepR + cells to maintain HSC niches and marrow cavities. Here, using lineage tracing, we found that the transcription factor early B-cell factor 3 (Ebf3) is preferentially expressed in CAR/LepR + cells and that Ebf3-expressing cells are self-renewing mesenchymal stem cells in adult marrow. When Ebf3 is deleted in CAR/LepR + cells, HSC niche function is severely impaired, and bone marrow is osteosclerotic with increased bone in aged mice. In mice lacking Ebf1 and Ebf3 , CAR/LepR + cells exhibiting a normal morphology are abundantly present, but their niche function is markedly impaired with depleted HSCs in infant marrow. Subsequently, the mutants become progressively more osteosclerotic, leading to the complete occlusion of marrow cavities in early adulthood. CAR/LepR + cells differentiate into bone-producing cells with reduced HSC niche factor expression in the absence of Ebf1/Ebf3 Thus, HSC cellular niches express Ebf3 that is required to create HSC niches, to inhibit their osteoblast differentiation, and to maintain spaces for HSCs. © 2018 Seike et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence

    DEFF Research Database (Denmark)

    Lataillade, J.J.; Pierre-Louis, O.; Uzan, G.

    2008-01-01

    Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model...... in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation. Mechanisms by which bone marrow niches...

  20. Coordinated regulation of niche and stem cell precursors by hormonal signaling.

    Directory of Open Access Journals (Sweden)

    Dana Gancz

    2011-11-01

    Full Text Available Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs, the precursors of germ line stem cells (GSCs, and somatic niche precursors develop within the larval ovary. Together they form the 16-20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis.

  1. Extreme divergence of Wolbachia tropism for the stem-cell-niche in the Drosophila testis.

    Science.gov (United States)

    Toomey, Michelle E; Frydman, Horacio M

    2014-12-01

    Microbial tropism, the infection of specific cells and tissues by a microorganism, is a fundamental aspect of host-microbe interactions. The intracellular bacteria Wolbachia have a peculiar tropism for the stem cell niches in the Drosophila ovary, the microenvironments that support the cells producing the eggs. The molecular underpinnings of Wolbachia stem cell niche tropism are unknown. We have previously shown that the patterns of tropism in the ovary show a high degree of conservation across the Wolbachia lineage, with closely related Wolbachia strains usually displaying the same pattern of stem cell niche tropism. It has also been shown that tropism to these structures in the ovary facilitates both vertical and horizontal transmission, providing a strong selective pressure towards evolutionary conservation of tropism. Here we show great disparity in the evolutionary conservation and underlying mechanisms of stem cell niche tropism between male and female gonads. In contrast to females, niche tropism in the male testis is not pervasive, present in only 45% of niches analyzed. The patterns of niche tropism in the testis are not evolutionarily maintained across the Wolbachia lineage, unlike what was shown in the females. Furthermore, hub tropism does not correlate with cytoplasmic incompatibility, a Wolbachia-driven phenotype imprinted during spermatogenesis. Towards identifying the molecular mechanism of hub tropism, we performed hybrid analyses of Wolbachia strains in non-native hosts. These results indicate that both Wolbachia and host derived factors play a role in the targeting of the stem cell niche in the testis. Surprisingly, even closely related Wolbachia strains in Drosophila melanogaster, derived from a single ancestor only 8,000 years ago, have significantly different tropisms to the hub, highlighting that stem cell niche tropism is rapidly diverging in males. These findings provide a powerful system to investigate the mechanisms and evolution of

  2. Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning

    OpenAIRE

    Olson, Timothy S.; Caselli, Anna; Otsuru, Satoru; Hofmann, Ted J.; Williams, Richard; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M.

    2013-01-01

    After radioablative conditioning, host megakaryocytes promote endosteal HSC niche expansion and donor stem cell engraftment.Thrombopoietin administration before radiation and bone marrow transplant enhances megakaryocyte promotion of HSC engraftment.

  3. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Cécile eCoste

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  4. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  5. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

    Directory of Open Access Journals (Sweden)

    Roy Blum

    2010-09-01

    Full Text Available Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system.We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2, lipid metabolism (e.g., Srebp1 and cell migration (e.g., Areb6 and Rreb1. Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche.We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may be common to mammalian niches in general. This study provides a

  6. Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model.

    Science.gov (United States)

    Nakagaki, Suguru; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hiroyuki; Nasuno, Masanao; Watanabe, Shuhei; Idogawa, Masashi; Yamashita, Kentaro; Naishiro, Yasuyoshi; Adachi, Yasushi; Suzuki, Hiromu; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

    2015-09-01

    The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This study aimed to determine whether heterotypic interactions between MSCs and colon cancer cells can supply contextual signals towards tumor progression. Xenografts consisting of co-implanted human colorectal cancer cells with rat MSCs in immunodeficient mice were evaluated by tumor progression, angiogenic profiles, and MSC fate. Furthermore, we investigated how MSCs function as a cancer cell niche by co-culture experiments in vitro. Tumor growth progressed in two ways, either independent of or dependent on MSCs. Such cell line-specific dependency could not be explained by host immune competency. COLO 320 xenograft angiogenesis was MSC-dependent, but less dependent on vascular endothelial growth factor (VEGF), whereas HT-29 angiogenesis was not MSC-dependent, but was VEGF-dependent. MSCs and COLO 320 cells established a functional positive feedback loop that triggered formation of a cancer cell niche, leading to AKT activation. Subsequently, MSCs differentiated into pericytes that enhanced angiogenesis as a perivascular niche. In contrast, the MSC niche conferred an anti-proliferative property to HT-29 cells, through mesenchymal-epithelial transition resulting in p38 activation. In conclusion, MSCs demonstrate pleiotropic capabilities as a cancer cell or perivascular niche to modulate colorectal cancer cell fate in a cell line-dependent manner in a xenogeneic context.

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

    Science.gov (United States)

    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.

  8. Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

    Directory of Open Access Journals (Sweden)

    Nikolce Gjorevski

    2017-01-01

    Full Text Available Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

  9. CD133(+) niches and single cells in glioblastoma have different phenotypes

    DEFF Research Database (Denmark)

    Christensen, Karina; Schrøder, Henrik Daa; Kristensen, Bjarne Winther

    2011-01-01

    with CD133 and the candidate stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting showed that the CD133(+) cells in the niches had a significantly higher expression of Sox2, EGFR and nestin compared...

  10. The extraocular muscle stem cell niche is resistant to ageing and disease

    Science.gov (United States)

    Formicola, Luigi; Marazzi, Giovanna; Sassoon, David A.

    2014-01-01

    Specific muscles are spared in many degenerative myopathies. Most notably, the extraocular muscles (EOMs) do not show clinical signs of late stage myopathies including the accumulation of fibrosis and fat. It has been proposed that an altered stem cell niche underlies the resistance of EOMs in these pathologies, however, to date, no reports have provided a detailed characterization of the EOM stem cell niche. PW1/Peg3 is expressed in progenitor cells in all adult tissues including satellite cells and a subset of interstitial non-satellite cell progenitors in muscle. These PW1-positive interstitial cells (PICs) include a fibroadipogenic progenitor population (FAP) that give rise to fat and fibrosis in late stage myopathies. PICs/FAPs are mobilized following injury and FAPs exert a promyogenic role upon myoblasts in vitro but require the presence of a minimal population of satellite cells in vivo. We and others recently described that FAPs express promyogenic factors while satellite cells express antimyogenic factors suggesting that PICs/FAPs act as support niche cells in skeletal muscle through paracrine interactions. We analyzed the EOM stem cell niche in young adult and aged wild-type mice and found that the balance between PICs and satellite cells within the EOM stem cell niche is maintained throughout life. Moreover, in the adult mdx mouse model for Duchenne muscular dystrophy (DMD), the EOM stem cell niche is unperturbed compared to normal mice, in contrast to Tibialis Anterior (TA) muscle, which displays signs of ongoing degeneration/regeneration. Regenerating mdx TA shows increased levels of both PICs and satellite cells, comparable to normal unaffected EOMs. We propose that the increase in PICs that we observe in normal EOMs contributes to preserving the integrity of the myofibers and satellite cells. Our data suggest that molecular cues regulating muscle regeneration are intrinsic properties of EOMs. PMID:25520657

  11. The extraocular muscle stem cell niche is resistant to ageing and disease

    Directory of Open Access Journals (Sweden)

    Luigi eFormicola

    2014-12-01

    Full Text Available Specific muscles are spared in many degenerative myopathies. Most notably, the extraocular muscles (EOMs do not show clinical signs of late stage myopathies including the accumulation of fibrosis and fat. It has been proposed that an altered stem cell niche underlies the resistance of EOMs in these pathologies, however, to date, no reports have provided a detailed characterization of the EOM stem cell niche. PW1/Peg3 is expressed in progenitor cells in all adult tissues including satellite cells and a subset of interstitial non-satellite cell progenitors in muscle. These PW1-positive interstitial cells (PICs include a fibroadipogenic progenitor population (FAPs that give rise to fat and fibrosis in late stage myopathies. PICs/FAPs are mobilized following injury and FAPs exert a promyogenic role upon myoblasts in vitro but require the presence of a minimal population of satellite cells in vivo. We and others recently described that FAPs express promyogenic factors while satellite cells express antimyogenic factors suggesting that PICs/FAPs act as support niche cells in skeletal muscle through paracrine interactions. We analyzed the EOM stem cell niche in young adult and aged wild-type mice and found that the balance between PICs and satellite cells within the EOM stem cell niche is maintained throughout life. Moreover, in the adult mdx mouse model for Duchenne muscular dystrophy, the EOM stem cell niche is unperturbed compared to normal mice, in contrast to Tibialis Anterior (TA muscle, which displays signs of ongoing degeneration/regeneration. Regenerating mdx TA shows increased levels of both PICs and satellite cells, comparable to normal unaffected EOMs. We propose that the increase in PICs that we observe in normal EOMs contributes to preserving the integrity of the myofibers and satellite cells. Our data suggest that molecular cues regulating muscle regeneration are intrinsic properties of EOMs.

  12. The human and murine hematopoietic stem cell niches: are they comparable?

    Science.gov (United States)

    van Pel, Melissa; Fibbe, Willem E; Schepers, Koen

    2016-04-01

    Hematopoietic stem cells (HSCs) reside in specific niches that provide various instructive cues that regulate HSC self-renewal and their development into all mature cells of the peripheral blood. Progress in this research field has largely been guided by mouse studies. However, parallel studies with human subjects, tissues, and cells, in combination with xenotransplantation experiments in immunodeficient mice, have contributed to our increased understanding of the human HSC niche. Here, we summarize our current knowledge of the various specialized subsets of both stromal and hematopoietic cells that support HSCs through cell-cell interactions and secreted factors, and the many parallels between the murine and human HSC niches. Furthermore, we discuss recent technological advances that are likely to improve our understanding of the human HSC niche, a better understanding of which may allow further identification of unique molecular and cellular pathways in the HSC niche. This information may help to further improve the outcome of HSC transplantation and refine the treatment of hematopoietic diseases. © 2015 New York Academy of Sciences.

  13. Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche.

    Science.gov (United States)

    Mitroulis, Ioannis; Chen, Lan-Sun; Singh, Rashim Pal; Kourtzelis, Ioannis; Economopoulou, Matina; Kajikawa, Tetsuhiro; Troullinaki, Maria; Ziogas, Athanasios; Ruppova, Klara; Hosur, Kavita; Maekawa, Tomoki; Wang, Baomei; Subramanian, Pallavi; Tonn, Torsten; Verginis, Panayotis; von Bonin, Malte; Wobus, Manja; Bornhäuser, Martin; Grinenko, Tatyana; Di Scala, Marianna; Hidalgo, Andres; Wielockx, Ben; Hajishengallis, George; Chavakis, Triantafyllos

    2017-10-02

    Hematopoietic stem cells (HSCs) remain mostly quiescent under steady-state conditions but switch to a proliferative state following hematopoietic stress, e.g., bone marrow (BM) injury, transplantation, or systemic infection and inflammation. The homeostatic balance between quiescence, self-renewal, and differentiation of HSCs is strongly dependent on their interactions with cells that constitute a specialized microanatomical environment in the BM known as the HSC niche. Here, we identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, we found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular (CAR) cells, and cells of the osteoblastic lineage. Del-1 promoted critical functions of the HSC niche, as it regulated long-term HSC (LT-HSC) proliferation and differentiation toward the myeloid lineage. Del-1 deficiency in mice resulted in reduced LT-HSC proliferation and infringed preferentially upon myelopoiesis under both steady-state and stressful conditions, such as hematopoietic cell transplantation and G-CSF- or inflammation-induced stress myelopoiesis. Del-1-induced HSC proliferation and myeloid lineage commitment were mediated by β3 integrin on hematopoietic progenitors. This hitherto unknown Del-1 function in the HSC niche represents a juxtacrine homeostatic adaptation of the hematopoietic system in stress myelopoiesis.

  14. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

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    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  15. Different Motile Behaviors of Human Hematopoietic Stem versus Progenitor Cells at the Osteoblastic Niche

    Directory of Open Access Journals (Sweden)

    Katie Foster

    2015-11-01

    Full Text Available Despite advances in our understanding of interactions between mouse hematopoietic stem cells (HSCs and their niche, little is known about communication between human HSCs and the microenvironment. Using a xenotransplantation model and intravital imaging, we demonstrate that human HSCs display distinct motile behaviors to their hematopoietic progenitor cell (HPC counterparts, and the same pattern can be found between mouse HSCs and HPCs. HSCs become significantly less motile after transplantation, while progenitor cells remain motile. We show that human HSCs take longer to find their niche than previously expected and suggest that the niche be defined as the position where HSCs stop moving. Intravital imaging is the only technique to determine where in the bone marrow stem cells stop moving, and future analyses should focus on the environment surrounding the HSC at this point.

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

    Science.gov (United States)

    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

  17. Monitoring Notch Signaling-Associated Activation of Stem Cell Niches within Injured Dental Pulp

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    Thimios A. Mitsiadis

    2017-05-01

    Full Text Available Dental pulp stem/progenitor cells guarantee tooth homeostasis, repair and regeneration throughout life. The decision between renewal and differentiation of these cells is influenced by physical and molecular interactions with stromal cells and extracellular matrix molecules forming the specialized microenvironment of dental pulp stem cell niches. Here we study the activation of putative pulp niches after tooth injury through the upregulation of Notch signaling pathway. Notch1, Notch2, and Notch3 molecules were used as markers of dental pulp stem/progenitor cells. Upon dental injury, Notch1 and Notch3 are detected in cells related to vascular structures suggesting a role of these proteins in the activation of specific pulpal perivascular niches. In contrast, a population of Notch2-positive cells that are actively proliferative is observed in the apical part of the pulp. Kinetics of these cells is followed up with a lipophilic DiI labeling, showing that apical pulp cells migrate toward the injury site where dynamic regenerative/repair events occur. The knowledge of the activation and regulation of dental pulp stem/progenitor cells within their niches in pathologic conditions may be helpful for the realization of innovative dental treatments in the near future.

  18. Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1

    Science.gov (United States)

    Zhou, Bo O; Ding, Lei; Morrison, Sean J

    2015-01-01

    Hematopoietic stem cells (HSCs) are maintained by a perivascular niche in bone marrow but it is unclear whether the niche is reciprocally regulated by HSCs. Here, we systematically assessed the expression and function of Angiopoietin-1 (Angpt1) in bone marrow. Angpt1 was not expressed by osteoblasts. Angpt1 was most highly expressed by HSCs, and at lower levels by c-kit+ hematopoietic progenitors, megakaryocytes, and Leptin Receptor+ (LepR+) stromal cells. Global conditional deletion of Angpt1, or deletion from osteoblasts, LepR+ cells, Nes-cre-expressing cells, megakaryocytes, endothelial cells or hematopoietic cells in normal mice did not affect hematopoiesis, HSC maintenance, or HSC quiescence. Deletion of Angpt1 from hematopoietic cells and LepR+ cells had little effect on vasculature or HSC frequency under steady-state conditions but accelerated vascular and hematopoietic recovery after irradiation while increasing vascular leakiness. Hematopoietic stem/progenitor cells and LepR+ stromal cells regulate niche regeneration by secreting Angpt1, reducing vascular leakiness but slowing niche recovery. DOI: http://dx.doi.org/10.7554/eLife.05521.001 PMID:25821987

  19. Manipulation of signaling thresholds in "engineered stem cell niches" identifies design criteria for pluripotent stem cell screens.

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    Raheem Peerani

    Full Text Available In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC and micro-contact printing (microCP to investigate how niche size controls endogenous signaling thresholds. microCP is used to restrict colony diameter, separation, and degree of clustering. We show, for the first time, spatial control over the activation of the Janus kinase/signal transducer and activator of transcription pathway (Jak-Stat. The functional consequences of this niche-size-dependent signaling control are confirmed by demonstrating that direct and indirect transcriptional targets of Stat3, including members of the Jak-Stat pathway and pluripotency-associated genes, are regulated by colony size. Modeling results and empirical observations demonstrate that colonies less than 100 microm in diameter are too small to maximize endogenous Stat3 activation and that colonies separated by more than 400 microm can be considered independent from each other. These results define parameter boundaries for the use of ESCs in screening studies, demonstrate the importance of context in stem cell responsiveness to exogenous cues, and suggest that niche size is an important parameter in stem cell fate control.

  20. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche.

    Science.gov (United States)

    Nishimura, Emi K; Granter, Scott R; Fisher, David E

    2005-02-04

    Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator Mitf.

  1. Female germline stem cell niches of earwigs are structurally simple and different from those of Drosophila melanogaster.

    Science.gov (United States)

    Tworzydlo, Waclaw; Kloc, Malgorzata; Bilinski, Szczepan M

    2010-05-01

    Stem cells function in niches, which consist of somatic cells that control the stem cells' self-renewal, proliferation, and differentiation. Drosophila ovary germline niche consists of the terminal filament (TF) cells, cap cells, and escort stem cells; signaling from the TF cells and the cap cells is essential for maintenance of germline stem cells (GSCs). Here, we show that in the earwig Opisthocosmia silvestris, the female GSC niche is morphologically simple and consist of the TF cells and several structurally uniform escort cells. The most posterior cell of the TF (the basal cell of the TF) differs from remaining TF cells and is separated from the anterior region of the germarium by the processes of the escort cells, and consequently, does not contact the GSCs directly. We also show that between somatic cells of earwig niche argosome-like vesicles and cytoneme-like extensions are present. (c) 2009 Wiley-Liss, Inc.

  2. Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning.

    Science.gov (United States)

    Olson, Timothy S; Caselli, Anna; Otsuru, Satoru; Hofmann, Ted J; Williams, Richard; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M

    2013-06-27

    Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC. We show that TBI-induced migration of megakaryocytes to the endosteal niche depends on thrombopoietin signaling through the c-MPL receptor on megakaryocytes, as well as CD41 integrin-mediated adhesion. Moreover, niche osteoblast proliferation post-TBI required megakaryocyte-secreted platelet-derived growth factor-BB. Furthermore, blockade of c-MPL-dependent megakaryocyte migration and function after TBI resulted in a significant decrease in donor HSC engraftment in primary and competitive secondary transplantation assays. Finally, we administered thrombopoietin to mice beginning 5 days before marrow radioablation and ending 24 hours before transplant to enhance megakaryocyte function post-TBI, and found that this strategy significantly enhanced donor HSC engraftment, providing a rationale for improving hematopoietic recovery and perhaps overall outcome after clinical HSC transplantation.

  3. Wnt ligand presentation and reception: from the stem cell niche to tissue engineering.

    Science.gov (United States)

    Mills, Kate M; Szczerkowski, James L A; Habib, Shukry J

    2017-08-01

    Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells. We also highlight recent progress in molecular visualization that has allowed for the monitoring of Wnt signalling within the stem cell compartment and new approaches to recapitulate this niche signalling in vitro Indeed, new technologies that present Wnt in a localized manner and mimic the three-dimensional microenvironment of stem cells will advance our understanding of Wnt signalling in the stem cell niche. These advances will expand current horizons to exploit Wnt ligands in the rapidly evolving fields of tissue engineering and regenerative medicine. © 2017 The Authors.

  4. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.

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    Chen-Yuan Tseng

    2014-12-01

    Full Text Available Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs, and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.

  5. Hair follicle stem cells provide a functional niche for melanocyte stem cells.

    Science.gov (United States)

    Tanimura, Shintaro; Tadokoro, Yuko; Inomata, Ken; Binh, Nguyen Thanh; Nishie, Wataru; Yamazaki, Satoshi; Nakauchi, Hiromitsu; Tanaka, Yoshio; McMillan, James R; Sawamura, Daisuke; Yancey, Kim; Shimizu, Hiroshi; Nishimura, Emi K

    2011-02-04

    In most stem cell systems, the organization of the stem cell niche and the anchoring matrix required for stem cell maintenance are largely unknown. We report here that collagen XVII (COL17A1/BP180/BPAG2), a hemidesmosomal transmembrane collagen, is highly expressed in hair follicle stem cells (HFSCs) and is required for the maintenance not only of HFSCs but also of melanocyte stem cells (MSCs), which do not express Col17a1 but directly adhere to HFSCs. Mice lacking Col17a1 show premature hair graying and hair loss. Analysis of Col17a1-null mice revealed that COL17A1 is critical for the self-renewal of HFSCs through maintaining their quiescence and immaturity, potentially explaining the mechanism underlying hair loss in human COL17A1 deficiency. Moreover, forced expression of COL17A1 in basal keratinocytes, including HFSCs, in Col17a1-null mice rescues MSCs from premature differentiation and restores TGF-β signaling, demonstrating that HFSCs function as a critical regulatory component of the MSC niche. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.

    Science.gov (United States)

    Isern, Joan; García-García, Andrés; Martín, Ana M; Arranz, Lorena; Martín-Pérez, Daniel; Torroja, Carlos; Sánchez-Cabo, Fátima; Méndez-Ferrer, Simón

    2014-09-25

    Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

  7. CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice.

    Science.gov (United States)

    Xie, Weiliang; Fisher, John T; Lynch, Thomas J; Luo, Meihui; Evans, Turan I A; Neff, Traci L; Zhou, Weihong; Zhang, Yulong; Ou, Yi; Bunnett, Nigel W; Russo, Andrew F; Goodheart, Michael J; Parekh, Kalpaj R; Liu, Xiaoming; Engelhardt, John F

    2011-08-01

    In cystic fibrosis (CF), a lack of functional CF transmembrane conductance regulator (CFTR) chloride channels causes defective secretion by submucosal glands (SMGs), leading to persistent bacterial infection that damages airways and necessitates tissue repair. SMGs are also important niches for slow-cycling progenitor cells (SCPCs) in the proximal airways, which may be involved in disease-related airway repair. Here, we report that calcitonin gene-related peptide (CGRP) activates CFTR-dependent SMG secretions and that this signaling pathway is hyperactivated in CF human, pig, ferret, and mouse SMGs. Since CGRP-expressing neuroendocrine cells reside in bronchiolar SCPC niches, we hypothesized that the glandular SCPC niche may be dysfunctional in CF. Consistent with this hypothesis, CFTR-deficient mice failed to maintain glandular SCPCs following airway injury. In wild-type mice, CGRP levels increased following airway injury and functioned as an injury-induced mitogen that stimulated SMG progenitor cell proliferation in vivo and altered the proliferative potential of airway progenitors in vitro. Components of the receptor for CGRP (RAMP1 and CLR) were expressed in a very small subset of SCPCs, suggesting that CGRP indirectly stimulates SCPC proliferation in a non-cell-autonomous manner. These findings demonstrate that CGRP-dependent pathways for CFTR activation are abnormally upregulated in CF SMGs and that this sustained mitogenic signal alters properties of the SMG progenitor cell niche in CF airways. This discovery may have important implications for injury/repair mechanisms in the CF airway.

  8. Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators.

    Science.gov (United States)

    Silberstein, Lev; Goncalves, Kevin A; Kharchenko, Peter V; Turcotte, Raphael; Kfoury, Youmna; Mercier, Francois; Baryawno, Ninib; Severe, Nicolas; Bachand, Jacqueline; Spencer, Joel A; Papazian, Ani; Lee, Dongjun; Chitteti, Brahmananda Reddy; Srour, Edward F; Hoggatt, Jonathan; Tate, Tiffany; Lo Celso, Cristina; Ono, Noriaki; Nutt, Stephen; Heino, Jyrki; Sipilä, Kalle; Shioda, Toshihiro; Osawa, Masatake; Lin, Charles P; Hu, Guo-Fu; Scadden, David T

    2016-10-06

    Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Proximity-based differential single cell analysis of the niche to identify stem/progenitor cell regulators

    Science.gov (United States)

    Silberstein, Lev; Goncalves, Kevin A; Kharchenko, Peter V; Turcotte, Raphael; Kfoury, Youmna; Mercier, Francois; Baryawno, Ninib; Severe, Nicolas; Bachand, Jacqueline; Spencer, Joel; Papazian, Ani; Lee, Dongjun; Chitteti, Brahmananda Reddy; Srour, Edward F; Hoggatt, Jonathan; Tate, Tiffany; Celso, Cristina Lo; Ono, Noriaki; Nutt, Stephen; Heino, Jyrki; Sipilä, Kalle; Shioda, Toshihiro; Osawa, Masatake; Lin, Charles P; Hu, Guo-fu; Scadden, David T

    2016-01-01

    SUMMARY Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on differential single-cell gene expression analysis of mesenchymal osteolineage cells close to and further removed from hematopoietic stem/progenitor cells to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. Amongst the genes which were preferentially expressed in proximal cells, we functionally examined three secreted or cell surface molecules not previously connected to HSPC biology: the secreted RNase Angiogenin, the cytokine IL18 and the adhesion molecule Embigin and discovered that all of these factors are HSPC quiescence regulators. Our proximity-based differential single cell approach therefore reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance understanding of microenvironmental regulation of stem cell function. PMID:27524439

  10. Biomimetic brain tumor niche regulates glioblastoma cells towards a cancer stem cell phenotype.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Chen, Pin-Yuan

    2018-05-01

    Glioblastoma (GBM) is the most malignant primary brain tumor and contains tumorigenic cancer stem cells (CSCs), which support the progression of tumor growth. The selection of CSCs and facilitation of the brain tumor niches may assist the development of novel therapeutics for GBM. Herein, hydrogel materials composed of agarose and hydroxypropyl methyl cellulose (HMC) in different concentrations were established and compared to emulate brain tumor niches and CSC microenvironments within a label-free system. Human GBM cell line, U-87 MG, was cultured on a series of HMC-agarose based culture system. Cell aggregation and spheroids formation were investigated after 4 days of culture, and 2.5% HMC-agarose based culture system demonstrated the largest spheroids number and size. Moreover, CD133 marker expression of GBM cells after 6 days of culture in 2.5% HMC-agarose based culture system was 60%, relatively higher than the control group at only 15%. Additionally, cells on 2.5% HMC-agarose based culture system show the highest chemoresistance, even at the high dose of 500 µM temozolomide for 72 h, the live cell ratio was still > 80%. Furthermore, the results also indicate that the expression of ABCG2 gene was up-regulated after culture in 2.5% HMC-agarose based culture system. Therefore, our results demonstrated that biomimetic brain tumor microenvironment may regulate GBM cells towards the CSC phenotype and expression of CSC characteristics. The microenvironment selection and spheroids formation in HMC-agarose based culture system may provide a label-free CSC selection strategy and drug testing model for future biomedical applications.

  11. Cellular players of hematopoietic stem cell mobilization in the bone marrow niche.

    Science.gov (United States)

    Tay, Joshua; Levesque, Jean-Pierre; Winkler, Ingrid G

    2017-02-01

    Hematopoietic stem cells (HSC) reside in perivascular regions of the bone marrow (BM) embedded within a complex regulatory unit called the niche. Cellular components of HSC niches include vascular endothelial cells, mesenchymal stromal progenitor cells and a variety of mature hematopoietic cells such as macrophages, neutrophils, and megakaryocytes-further regulated by sympathetic nerves and complement components as described in this review. Three decades ago the discovery that cytokines induce a large number of HSC to mobilize from the BM into the blood where they are easily harvested, revolutionised the field of HSC transplantation-curative for immune-deficiencies and some malignancies. However, despite now routine use of granulocyte-colony stimulating factor (G-CSF) to mobilise HSC for transplant, only in last 15 years has research on the mechanisms behind why and how HSC can be induced to move into the blood began. These studies have revealed the complexity of the niche that retains HSC in the BM. This review describes how BM niches and HSC themselves change during administration of G-CSF-or in the recovery phase of chemotherapy-to facilitate movement of HSC into the blood, and research now leading to development of novel therapeutics to further boost HSC mobilization and transplant success.

  12. Concise Review: Chronic Myeloid Leukemia: Stem Cell Niche and Response to Pharmacologic Treatment

    Science.gov (United States)

    Arrigoni, Elena; Del Re, Marzia; Galimberti, Sara; Restante, Giuliana; Rofi, Eleonora; Crucitta, Stefania; Baratè, Claudia; Petrini, Mario; Di Paolo, Antonello

    2018-01-01

    Abstract Nowadays, more than 90% of patients affected by chronic myeloid leukemia (CML) survive with a good quality of life, thanks to the clinical efficacy of tyrosine kinase inhibitors (TKIs). Nevertheless, point mutations of the ABL1 pocket occurring during treatment may reduce binding of TKIs, being responsible of about 20% of cases of resistance among CML patients. In addition, the presence of leukemic stem cells (LSCs) represents the most important event in leukemia progression related to TKI resistance. LSCs express stem cell markers, including active efflux pumps and genetic and epigenetic alterations together with deregulated cell signaling pathways involved in self‐renewal, such as Wnt/β‐catenin, Notch, and Hedgehog. Moreover, the interaction with the bone marrow microenvironment, also known as hematopoietic niche, may influence the phenotype of surrounding cells, which evade mechanisms controlling cell proliferation and are less sensitive or frankly resistant to TKIs. This Review focuses on the role of LSCs and stem cell niche in relation to response to pharmacological treatments. A literature search from PubMed database was performed until April 30, 2017, and it has been analyzed according to keywords such as chronic myeloid leukemia, stem cell, leukemic stem cells, hematopoietic niche, tyrosine kinase inhibitors, and drug resistance. Stem Cells Translational Medicine 2018;7:305–314 PMID:29418079

  13. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche

    Science.gov (United States)

    Pastor, Patricia; Cisternas, Pedro; Salazar, Katterine; Silva-Alvarez, Carmen; Oyarce, Karina; Jara, Nery; Espinoza, Francisca; Martínez, Agustín D.; Nualart, Francisco

    2013-01-01

    Known as a critical antioxidant, recent studies suggest that vitamin C plays an important role in stem cell generation, proliferation and differentiation. Vitamin C also enhances neural differentiation during cerebral development, a function that has not been studied in brain precursor cells. We observed that the rat neurogenic niche is structurally organized at day 15 of postnatal development, and proliferation and neural differentiation increase at day 21. In the human brain, a similar subventricular niche was observed at 1-month of postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter 2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral migratory stream (RMS). Low co-distribution of SVCT2 and βIII-tubulin in neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2 and GFAP in type-B or precursor cells was observed. Similar results were obtained in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2, suggesting a role of vitamin C in neural progenitor proliferation. Primary neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which forms neurospheres in vitro, were used to analyze the effect of vitamin C in neural stem cells. Both cell types expressed functional SVCT2 in vitro, and ascorbic acid (AA) induced their neural differentiation, increased βIII-tubulin and SVCT2 expression, and amplified vitamin C uptake. PMID:23964197

  14. Hematopoietic Niche - Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells.

    Science.gov (United States)

    Costa, Marta H G; de Soure, António M; Cabral, Joaquim M S; Ferreira, Frederico Castelo; da Silva, Cláudia L

    2018-02-01

    The adult bone marrow (BM) niche is a complex entity where a homeostatic hematopoietic system is maintained through a dynamic crosstalk between different cellular and non-cellular players. Signaling mechanisms triggered by cell-cell, cell-extracellular matrix (ECM), cell-cytokine interactions, and local microenvironment parameters are involved in controlling quiescence, self-renewal, differentiation, and migration of hematopoietic stem/progenitor cells (HSPC). A promising strategy to more efficiently expand HSPC numbers and tune their properties ex vivo is to mimic the hematopoietic niche through integration of adjuvant stromal cells, soluble cues, and/or biomaterial-based approaches in HSPC culture systems. Particularly, mesenchymal stem/stromal cells (MSC), through their paracrine activity or direct contact with HSPC, are thought to be a relevant niche player, positioning HSPC-MSC co-culture as a valuable platform to support the ex vivo expansion of hematopoietic progenitors. To improve the clinical outcome of hematopoietic cell transplantation (HCT), namely when the available HSPC are present in a limited number such is the case of HSPC collected from umbilical cord blood (UCB), ex vivo expansion of HSPC is required without eliminating the long-term repopulating capacity of more primitive HSC. Here, we will focus on depicting the characteristics of co-culture systems, as well as other bioengineering approaches to improve the functionality of HSPC ex vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Classic and novel stem cell niches in brain homeostasis and repair.

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

    Science.gov (United States)

    Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Zhao, Hong; Zhao, Zhen; Du, Shiyu; Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.; Wong, Stephen T. C.; Jin, Xin; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H.-F.

    2014-01-01

    Summary Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We further elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human datasets analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases. Significance In advanced stages, breast cancer bone metastases are driven by paracrine crosstalk among cancer cells, osteoblasts, and osteoclasts, which constitute a vicious osteolytic cycle. Current therapies targeting this process limit tumor progression, but do not improve patient survival. On the other hand, bone micrometastases may remain indolent for years before activating the vicious cycle, providing a therapeutic opportunity to prevent macrometastases. Here, we show that bone colonization is initiated in a microenvironment niche exhibiting active osteogenesis. Cancer and osteogenic cells form heterotypic adherens junctions, which enhance mTOR activity and drive early-stage bone colonization prior to osteolysis. These results reveal a strong connection between osteogenesis and micrometastasis and suggest potential therapeutic targets to prevent bone macrometastases. PMID:25600338

  17. The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

    Directory of Open Access Journals (Sweden)

    Cosette M. Rivera-Cruz

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

  18. Stem Cell Spheroids and Ex Vivo Niche Modeling: Rationalization and Scaling-Up.

    Science.gov (United States)

    Chimenti, Isotta; Massai, Diana; Morbiducci, Umberto; Beltrami, Antonio Paolo; Pesce, Maurizio; Messina, Elisa

    2017-04-01

    Improved protocols/devices for in vitro culture of 3D cell spheroids may provide essential cues for proper growth and differentiation of stem/progenitor cells (S/PCs) in their niche, allowing preservation of specific features, such as multi-lineage potential and paracrine activity. Several platforms have been employed to replicate these conditions and to generate S/PC spheroids for therapeutic applications. However, they incompletely reproduce the niche environment, with partial loss of its highly regulated network, with additional hurdles in the field of cardiac biology, due to debated resident S/PCs therapeutic potential and clinical translation. In this contribution, the essential niche conditions (metabolic, geometric, mechanical) that allow S/PCs maintenance/commitment will be discussed. In particular, we will focus on both existing bioreactor-based platforms for the culture of S/PC as spheroids, and on possible criteria for the scaling-up of niche-like spheroids, which could be envisaged as promising tools for personalized cardiac regenerative medicine, as well as for high-throughput drug screening.

  19. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs.

    Science.gov (United States)

    Winkler, Ingrid G; Sims, Natalie A; Pettit, Allison R; Barbier, Valérie; Nowlan, Bianca; Helwani, Falak; Poulton, Ingrid J; van Rooijen, Nico; Alexander, Kylie A; Raggatt, Liza J; Lévesque, Jean-Pierre

    2010-12-02

    In the bone marrow, hematopoietic stem cells (HSCs) reside in specific niches near osteoblast-lineage cells at the endosteum. To investigate the regulation of these endosteal niches, we studied the mobilization of HSCs into the bloodstream in response to granulocyte colony-stimulating factor (G-CSF). We report that G-CSF mobilization rapidly depletes endosteal osteoblasts, leading to suppressed endosteal bone formation and decreased expression of factors required for HSC retention and self-renewal. Importantly, G-CSF administration also depleted a population of trophic endosteal macrophages (osteomacs) that support osteoblast function. Osteomac loss, osteoblast suppression, and HSC mobilization occurred concomitantly, suggesting that osteomac loss could disrupt endosteal niches. Indeed, in vivo depletion of macrophages, in either macrophage Fas-induced apoptosis (Mafia) transgenic mice or by administration of clodronate-loaded liposomes to wild-type mice, recapitulated the: (1) loss of endosteal osteoblasts and (2) marked reduction of HSC-trophic cytokines at the endosteum, with (3) HSC mobilization into the blood, as observed during G-CSF administration. Together, these results establish that bone marrow macrophages are pivotal to maintain the endosteal HSC niche and that the loss of such macrophages leads to the egress of HSCs into the blood.

  20. Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles

    Science.gov (United States)

    Sayed, Zafar A.; Stephanopoulos, Nicholas; Berns, Eric J.; Wadhwani, Anil R.; Morrissey, Zachery D.; Chadly, Duncan M.; Kobayashi, Shun; Edelbrock, Alexandra N.; Mashimo, Tomoji; Miller, Charles A.; McGuire, Tammy L.; Stupp, Samuel I.; Kessler, John A.

    2017-01-01

    The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration. PMID:29284013

  1. Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Akihiro J Matsuoka

    Full Text Available The use of human embryonic stem cells (hESCs for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA molecules that display an IKVAV epitope (IKVAV-PA to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration.

  2. Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

    Directory of Open Access Journals (Sweden)

    Heather A. Himburg

    2012-10-01

    Full Text Available The mechanisms through which the bone marrow (BM microenvironment regulates hematopoietic stem cell (HSC fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN in regulating HSC function in the niche. PTN−/− mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.

  3. The dendritic cell niche in chronic obstructive pulmonary disease

    OpenAIRE

    Haczku, Angela

    2012-01-01

    Abstract The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD). The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathog...

  4. Radiation effects on haematopoietic stem cells in vitro: possible role of stromal niches in the stem cell hierarchy

    International Nuclear Information System (INIS)

    Sharp, J.G.; Crouse, D.A.; Jackson, J.D.; Schmidt, C.M.; Ritter, E.K.; Udeaja, G.C.; Mann, S.L.

    1986-01-01

    The authors describe experiments which attempt to elucidate the nature of haemopoietic stem cell and microenvironmental stromal cell interactions which might explain anomalies in explanations of the differential effects of radiation on HSC versus MSC. In particular, there is an attempt to demonstrate the existence of stromal niches. (UK)

  5. Reversible neural stem cell niche dysfunction in a model of multiple sclerosis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Imitola, Jaime; Ayuso-Sacido, Angel

    2011-01-01

    OBJECTIVE: The subventricular zone (SVZ) of the brain constitutes a niche for neural stem and progenitor cells that can initiate repair after central nervous system (CNS) injury. In a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE), the neural stem cells (NSCs) become...... with minocycline, an inhibitor of microglia activation, increases stem cell proliferation in both naive and EAE animals. Minocycline treatment decreases cortical and periventricular pathology in the chronic phase of EAE, improving the proliferation of Sox2 stem cells and NG2 oligodendrocyte precursors cells...

  6. Hematopoietic Stem Cell Niche in Health and Disease.

    Science.gov (United States)

    Hoggatt, Jonathan; Kfoury, Youmna; Scadden, David T

    2016-05-23

    Regulation of stem cells in adult tissues is a key determinant of how well an organism can respond to the stresses of physiological challenge and disease. This is particularly true of the hematopoietic system, where demands on host defenses can call for an acute increase in cell production. Hematopoietic stem cells receive the regulatory signals for cell production in adult mammals in the bone marrow, a tissue with higher-order architectural and functional organization than previously appreciated. Here, we review the data defining particular structural components and heterologous cells in the bone marrow that participate in hematopoietic stem cell function. Further, we explore the case for stromal-hematopoietic cell interactions contributing to neoplastic myeloid disease. As the hematopoietic regulatory networks in the bone marrow are revealed, it is anticipated that strategies will emerge for how to enhance or inhibit production of specific blood cells. In that way, the control of hematopoiesis will enter the domain of therapies to modulate broad aspects of hematopoiesis, both normal and malignant.

  7. Neovascular niche for human myeloma cells in immunodeficient mouse bone.

    Directory of Open Access Journals (Sweden)

    Hirono Iriuchishima

    Full Text Available The interaction with bone marrow (BM plays a crucial role in pathophysiological features of multiple myeloma (MM, including cell proliferation, chemoresistance, and bone lesion progression. To characterize the MM-BM interactions, we utilized an in vivo experimental model for human MM in which a GFP-expressing human MM cell line is transplanted into NOG mice (the NOG-hMM model. Transplanted MM cells preferentially engrafted at the metaphyseal region of the BM endosteum and formed a complex with osteoblasts and osteoclasts. A subpopulation of MM cells expressed VE-cadherin after transplantation and formed endothelial-like structures in the BM. CD138(+ myeloma cells in the BM were reduced by p53-dependent apoptosis following administration of the nitrogen mustard derivative bendamustine to mice in the NOG-hMM model. Bendamustine maintained the osteoblast lining on the bone surface and protected extracellular matrix structures. Furthermore, bendamustine suppressed the growth of osteoclasts and mesenchymal cells in the NOG-hMM model. Since VE-cadherin(+ MM cells were chemoresistant, hypoxic, and HIF-2α-positive compared to the VE-cadherin(- population, VE-cadherin induction might depend on the oxygenation status. The NOG-hMM model described here is a useful system to analyze the dynamics of MM pathophysiology, interactions of MM cells with other cellular compartments, and the utility of novel anti-MM therapies.

  8. The dendritic cell niche in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Haczku Angela

    2012-09-01

    Full Text Available Abstract The pulmonary innate immune system is heavily implicated in the perpetual airway inflammation and impaired host defense characterizing Chronic Obstructive Pulmonary Disease (COPD. The airways of patients suffering from COPD are infiltrated by various immune and inflammatory cells including macrophages, neutrophils, T lymphocytes, and dendritic cells. While the role of macrophages, neutrophils and T lymphocytes is well characterized, the contribution of dendritic cells to COPD pathogenesis is still the subject of emerging research. A paper by Botelho and colleagues in the current issue of Respiratory Research investigates the importance of dendritic cell recruitment in cigarette-smoke induced acute and chronic inflammation in mice. Dendritic cells of the healthy lung parenchyma and airways perform an important sentinel function and regulate immune homeostasis. During inflammatory responses the function and migration pattern of these cells is dramatically altered but the underlying mechanisms are incompletely understood. Botelho and colleagues demonstrate here the importance of IL-1R1/IL-1α related mechanisms including CCL20 production in cigarette-smoke induced recruitment of dendritic cells and T cell activation in the mouse lung.

  9. Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties.

    Science.gov (United States)

    Tong, Xinming; Yang, Fan

    2014-02-01

    Hydrogels have been widely used as artificial cell niche to mimic extracellular matrix with tunable properties. However, changing biochemical cues in hydrogels developed-to-date would often induce simultaneous changes in mechanical properties, which do not support mechanistic studies on stem cell-niche interactions. Here we report the development of a PEG-based interpenetrating network (IPN), which is composed of two polymer networks that can independently and simultaneously crosslink to form hydrogels in a cell-friendly manner. The resulting IPN hydrogel allows independently tunable biochemical and mechanical properties, as well as stable and more homogeneous presentation of biochemical ligands in 3D than currently available methods. We demonstrate the potential of our IPN platform for elucidating stem cell-niche interactions by modulating osteogenic differentiation of human adipose-derived stem cells. The versatility of such IPN hydrogels is further demonstrated using three distinct and widely used polymers to form the mechanical network while keeping the biochemical network constant. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Neutral Competition forDrosophilaFollicle and Cyst Stem Cell Niches Requires Vesicle Trafficking Genes.

    Science.gov (United States)

    Cook, Matthew S; Cazin, Coralie; Amoyel, Marc; Yamamoto, Shinya; Bach, Erika; Nystul, Todd

    2017-07-01

    The process of selecting for cellular fitness through competition plays a critical role in both development and disease. The germarium, a structure at the tip of the ovariole of a Drosophila ovary, contains two follicle stem cells (FSCs) that undergo neutral competition for the stem cell niche. Using the FSCs as a model, we performed a genetic screen through a collection of 126 mutants in essential genes on the X chromosome to identify candidates that increase or decrease competition for the FSC niche. We identified ∼55 and 6% of the mutations screened as putative FSC hypo- or hyper-competitors, respectively. We found that a large majority of mutations in vesicle trafficking genes (11 out of the 13 in the collection of mutants) are candidate hypo-competition alleles, and we confirmed the hypo-competition phenotype for four of these alleles. We also show that Sec16 and another COPII vesicle trafficking component, Sar1, are required for follicle cell differentiation. Lastly, we demonstrate that, although some components of vesicle trafficking are also required for neutral competition in the cyst stem cells of the testis, there are important tissue-specific differences. Our results demonstrate a critical role for vesicle trafficking in stem cell niche competition and differentiation, and we identify a number of putative candidates for further exploration. Copyright © 2017 Cook et al.

  11. Mesenchymal Stem Cells Secretome as a Modulator of the Neurogenic Niche: Basic Insights and Therapeutic Opportunities

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    Antonio eSalgado

    2015-07-01

    Full Text Available Neural stem cells (NSCs and mesenchymal stem cells (MSCs share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g bone and central nervous system that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF, glial derived neurotrophic factor (GDNF, and brain derived neurotrophic factor (BDNF, among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.

  12. The Organoid Reconstitution Assay (ORA) for the Functional Analysis of Intestinal Stem and Niche Cells.

    Science.gov (United States)

    Schewe, Matthias; Sacchetti, Andrea; Schmitt, Mark; Fodde, Riccardo

    2017-11-20

    The intestinal epithelium is characterized by an extremely rapid turnover rate. In mammals, the entire epithelial lining is renewed within 4 - 5 days. Adult intestinal stem cells reside at the bottom of the crypts of Lieberkühn, are earmarked by expression of the Lgr5 gene, and preserve homeostasis through their characteristic high proliferative rate 1 . Throughout the small intestine, Lgr5 + stem cells are intermingled with specialized secretory cells called Paneth cells. Paneth cells secrete antibacterial compounds (i.e., lysozyme and cryptdins/defensins) and exert a controlling role on the intestinal flora. More recently, a novel function has been discovered for Paneth cells, namely their capacity to provide niche support to Lgr5 + stem cells through several key ligands as Wnt3, EGF, and Dll1 2 . When isolated ex vivo and cultured in the presence of specific growth factors and extracellular matrix components, whole intestinal crypts give rise to long-lived and self-renewing 3D structures called organoids that highly resemble the crypt-villus epithelial architecture of the adult small intestine 3 . Organoid cultures, when established from whole crypts, allow the study of self-renewal and differentiation of the intestinal stem cell niche, though without addressing the contribution of its individual components, namely the Lgr5 + and Paneth cells. Here, we describe a novel approach to the organoid assay that takes advantage of the ability of Paneth and Lgr5 + cells to associate and form organoids when co-cultured. This approach, here referred to as "organoid reconstitution assay" (ORA), allows the genetic and biochemical modification of Paneth or Lgr5 + stem cells, followed by reconstitution into organoids. As such, it allows the functional analysis of the two main components of the intestinal stem cell niche.

  13. Stem cell decisions: a twist of fate or a niche market?

    Science.gov (United States)

    Januschke, Jens; Näthke, Inke

    2014-10-01

    Establishing and maintaining cell fate in the right place at the right time is a key requirement for normal tissue maintenance. Stem cells are at the core of this process. Understanding how stem cells balance self-renewal and production of differentiating cells is key for understanding the defects that underpin many diseases. Both, external cues from the environment and cell intrinsic mechanisms can control the outcome of stem cell division. The role of the orientation of stem cell division has emerged as an important mechanism for specifying cell fate decisions. Although, the alignment of cell divisions can dependent on spatial cues from the environment, maintaining stemness is not always linked to positioning of stem cells in a particular microenvironment or `niche'. Alternate mechanisms that could contribute to cellular memory include differential segregation of centrosomes in asymmetrically dividing cells. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self-renewal.

    Science.gov (United States)

    Chen, Kai-Yuan; Srinivasan, Tara; Tung, Kuei-Ling; Belmonte, Julio M; Wang, Lihua; Murthy, Preetish Kadur Lakshminarasimha; Choi, Jiahn; Rakhilin, Nikolai; King, Sarah; Varanko, Anastasia Kristine; Witherspoon, Mavee; Nishimura, Nozomi; Glazier, James A; Lipkin, Steven M; Bu, Pengcheng; Shen, Xiling

    2017-04-28

    The intestinal epithelium is the fastest regenerative tissue in the body, fueled by fast-cycling stem cells. The number and identity of these dividing and migrating stem cells are maintained by a mosaic pattern at the base of the crypt. How the underlying regulatory scheme manages this dynamic stem cell niche is not entirely clear. We stimulated intestinal organoids with Notch ligands and inhibitors and discovered that intestinal stem cells employ a positive feedback mechanism via direct Notch binding to the second intron of the Notch1 gene. Inactivation of the positive feedback by CRISPR/Cas9 mutation of the binding sequence alters the mosaic stem cell niche pattern and hinders regeneration in organoids. Dynamical system analysis and agent-based multiscale stochastic modeling suggest that the positive feedback enhances the robustness of Notch-mediated niche patterning. This study highlights the importance of feedback mechanisms in spatiotemporal control of the stem cell niche. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  15. Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices.

    Science.gov (United States)

    Yang, Hanseul; Adam, Rene C; Ge, Yejing; Hua, Zhong L; Fuchs, Elaine

    2017-04-20

    Adult tissue stem cells (SCs) reside in niches, which, through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single-cell RNA-seq, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions. Using lineage tracing, temporal single-cell analyses, and chromatin landscaping, we show that SC plasticity becomes restricted in a sequentially and spatially choreographed program, culminating in seven spatially arranged unilineage progenitors within TACs of mature follicles. By compartmentalizing SCs into micro-niches, tissues gain precise control over morphogenesis and regeneration: some progenitors specify lineages immediately, whereas others retain potency, preserving self-renewing features established early while progressively restricting lineages as they experience dynamic changes in microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

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    Jiangang Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

  17. Evolutionarily conserved Wolbachia-encoded factors control pattern of stem-cell niche tropism in Drosophila ovaries and favor infection

    Science.gov (United States)

    Toomey, Michelle E.; Panaram, Kanchana; Fast, Eva M.; Beatty, Catherine; Frydman, Horacio M.

    2013-01-01

    Wolbachia are intracellular bacteria that infect invertebrates at pandemic levels, including insect vectors of devastating infectious diseases. Although Wolbachia are providing novel strategies for the control of several human pathogens, the processes underlying Wolbachia’s successful propagation within and across species remain elusive. Wolbachia are mainly vertically transmitted; however, there is also evidence of extensive horizontal transmission. Here, we provide several lines of evidence supporting Wolbachia’s targeting of ovarian stem cell niches—referred to as “niche tropism”—as a previously overlooked strategy for Wolbachia thriving in nature. Niche tropism is pervasive in Wolbachia infecting the Drosophila genus, and different patterns of niche tropism are evolutionarily conserved. Phylogenetic analysis, confirmed by hybrid introgression and transinfection experiments, demonstrates that bacterial factors are the major determinants of differential patterns of niche tropism. Furthermore, bacterial load is increased in germ-line cells passing through infected niches, supporting previous suggestions of a contribution of Wolbachia from stem-cell niches toward vertical transmission. These results support the role of stem-cell niches as a key component for the spreading of Wolbachia in the Drosophila genus and provide mechanistic insights into this unique tissue tropism. PMID:23744038

  18. Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Carsten, A.L.; Brecher, G.

    1979-01-01

    The long term hematologic effects of single whole body sublethal X-ray exposure, 525 rad, and the low level chronic exposure from 137 Cs gamma ray and ingested HTO were investigated in mice. The single X-ray exposure had early severe effect on bone marrows both in terms of total cellularity and the number of pluripotent stem cells. How do animals maintain normal cellularity in the absence of a normal number of the pluripotent stem cells[ The following 3 different mechanisms may be involved: additional division in the cytologically identifiable divisible pool of bone marrows; shortening of cycle time allowing more divisions in the same time with great amplification of a small number of colony-forming unit spleens; and the recruitment of G 0 stem cells into proliferation. The reduction in the number of bone marrow stem cells might be attributed to stromal injury in the marrows such that they cannot support as many stem cells as those before the radiation exposure. As an alternate to the ''niche'' hypothesis, the injury to the stem cell pool such that self-replication was not sufficient to restore normal cell concentration is a possibility. The time sequence of the transfusion of marrows may be important to the ultimate effect. Attempts to fill empty niches 10 and 12 weeks after a single and severe radiation injury may be impossible due to stromal changes which in effect have eliminated the niches. The bone marrows of animals rescued by the transfusion of 4 x 10 6 bone marrow cells will accept 0 to 25% of the second transfusion of 4 x 10 7 cells. (Yamashita, S.)

  19. Cancer Microenvironment: What Can We Learn from the Stem Cell Niche

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    Lukas Lacina

    2015-10-01

    Full Text Available Epidermal stem cells (ESCs are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle—also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs. This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.

  20. Osteoblastic and Vascular Endothelial Niches, Their Control on Normal Hematopoietic Stem Cells, and Their Consequences on the Development of Leukemia

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    Bella S. Guerrouahen

    2011-01-01

    Full Text Available Stem cell self-renewal is regulated by intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments called “niches.” The best-characterized stem cell is the hematopoietic stem cell (HSC. Self-renewal and differentiation ability of HSC are regulated by two major elements: endosteal and vascular regulatory elements. The osteoblastic niche localized at the inner surface of the bone cavity might serve as a reservoir for long-term HSC storage in a quiescent state. Whereas the vascular niche, which consists of sinusoidal endothelial cell lining blood vessel, provides an environment for short-term HSC proliferation and differentiation. Both niches act together to maintain hematopoietic homeostasis. In this paper, we provide some principles applying to the hematopoietic niches, which will be useful in the study and understanding of other stem cell niches. We will discuss altered microenvironment signaling leading to myeloid lineage disease. And finally, we will review some data on the development of acute myeloid leukemia from a subpopulation called leukemia-initiating cells (LIC, and we will discuss on the emerging evidences supporting the influence of the microenvironment on chemotherapy resistance.

  1. Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival.

    Science.gov (United States)

    Müller-Greven, Gaëlle; Carlin, Cathleen R; Burgett, Monica E; Ahluwalia, Manmeet S; Lauko, Adam; Nowacki, Amy S; Herting, Cameron J; Qadan, Maha A; Bredel, Markus; Toms, Steven A; Lathia, Justin D; Hambardzumyan, Dolores; Sarkaria, Jann N; Hamerlik, Petra; Gladson, Candece L

    2017-11-15

    Purpose: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors. Experimental Design: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133 + cells derived from GBM tumors in vitro Bevacizumab internalization, trafficking, and effects on cell survival were analyzed using multilabel confocal microscopy, immunoblotting, and cytotoxicity assays in the presence/absence of inhibitors. Results: In the GBM mouse models, administered anti-mouse-VEGF-A entered the perivascular tumor niche and was internalized by Sox2 + /CD44 + tumor cells. In the perivascular tumor cells, bevacizumab was detected in the recycling compartment or the lysosomes, and increased autophagy was found. Bevacizumab was internalized rapidly by CD133 + /Sox2 + -GBM cells in vitro through macropinocytosis with a fraction being trafficked to a recycling compartment, independent of FcRn, and a fraction to lysosomes. Bevacizumab treatment of CD133 + GBM cells depleted VEGF-A and induced autophagy thereby improving cell survival. An inhibitor of lysosomal acidification decreased bevacizumab-induced autophagy and increased cell death. Inhibition of macropinocytosis increased cell death, suggesting macropinocytosis of bevacizumab promotes CD133 + cell survival. Conclusions: We demonstrate that bevacizumab is internalized by Sox2 + /CD44 + -GBM tumor cells residing in the perivascular tumor niche. Macropinocytosis of bevacizumab and trafficking to the lysosomes promotes CD133 + cell survival, as does the autophagy induced by bevacizumab depletion of VEGF-A. Clin Cancer Res; 23(22); 7059-71. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. The chronically inflamed central nervous system provides niches for long-lived plasma cells.

    Science.gov (United States)

    Pollok, Karolin; Mothes, Ronja; Ulbricht, Carolin; Liebheit, Alina; Gerken, Jan David; Uhlmann, Sylvia; Paul, Friedemann; Niesner, Raluca; Radbruch, Helena; Hauser, Anja Erika

    2017-11-25

    Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma cells also contribute, through secretion of autoantibodies. Long-lived plasma cells are known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, to what extent they are present in autoimmune central nervous system inflammation has not yet been investigated. In brain biopsies from multiple sclerosis patients and other neurological diseases, we could detect non-proliferating plasma cells (CD138 + Ki67 - ) in the parenchyma. Based on this finding, we hypothesized that long-lived plasma cells can persist in the central nervous system (CNS). In order to test this hypothesis, we adapted the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to generate a B cell memory response. Plasma cells were found in the meninges and the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling survival niches for these cells, characterized by an up-regulation of chemokines (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In order to determine the lifetime of plasma cells in the chronically inflamed CNS, we labeled the DNA of proliferating cells with 5-ethynyl-2'-deoxyuridine (EdU). Up to five weeks later, we could detect EdU + long-lived plasma cells in the murine CNS. To our knowledge, this is the first study describing non-proliferating plasma cells directly in the target tissue of a chronic inflammation in humans, as well as the first evidence demonstrating the ability of plasma cells to persist in the CNS, and the ability of the chronically inflamed CNS tissue to promote this persistence. Hence, our results suggest that the CNS provides survival niches for

  3. Stem Cell Interaction with Somatic Niche May Hold the Key to Fertility Restoration in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Deepa Bhartiya

    2012-01-01

    Full Text Available The spontaneous return of fertility after bone marrow transplantation or heterotopic grafting of cryopreserved ovarian cortical tissue has surprised many, and a possible link with stem cells has been proposed. We have reviewed the available literature on ovarian stem cells in adult mammalian ovaries and presented a model that proposes that the ovary harbors two distinct populations of stem cells, namely, pluripotent, quiescent, very small embryonic-like stem cells (VSELs, and slightly larger “progenitor” ovarian germ stem cells (OGSCs. Besides compromising the somatic niche, oncotherapy destroys OGSCs since, like tumor cells, they are actively dividing; however VSELs persist since they are relatively quiescent. BMT or transplanted ovarian cortical tissue may help rejuvenate the ovarian niche, which possibly supports differentiation of persisting VSELs resulting in neo-oogenesis and follicular development responsible for successful pregnancies. Postnatal oogenesis in mammalian ovary from VSELs may be exploited for fertility restoration in cancer survivors including those who were earlier deprived of gametes and/or gonadal tissue cryopreservation options.

  4. Osteogenic and neurogenic stem cells in their own place: unraveling differences and similarities between niches

    Directory of Open Access Journals (Sweden)

    Wanda eLattanzi

    2015-11-01

    Full Text Available Although therapeutic use of stem cells is already available in some tissues (cornea, blood, skin, in most organs we are far from reaching the translational goal of regenerative medicine. In the nervous system, due to intrinsic features which make it refractory to regeneration/repair,it is very hard to obtainfunctionally-integrated regenerative outcomes, evenstarting from its own stem cells(the neural stem cells; NSCs. Besides NSCs, mesenchymal stem cells (MSCs have also been proposed for therapeutic purposes in neurological diseases. Yet, direct (regenerative and indirect (bystander effects are often confused, as are MSCs and bone marrow-derived (stromal, osteogenic stem cells (BMSCs, whoseplasticity isactually overestimated (i.e. trans-differentiation along non-mesodermal lineages, including neural fates.In order to better understand failure in the regenerative use of stem cells for neurological disorders,it could be helpful to understand how NSCs and BMSCs have adapted to their respective organ niches. In this perspective, here the adult osteogenic and neurogenic niches are considered and compared within their in vivo environment.

  5. PHB3 Maintains Root Stem Cell Niche Identity through ROS-Responsive AP2/ERF Transcription Factors in Arabidopsis

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    Xiangpei Kong

    2018-01-01

    Full Text Available The root stem cell niche, which is composed of four mitotically inactive quiescent center (QC cells and the surrounding actively divided stem cells in Arabidopsis, is critical for growth and root development. Here, we demonstrate that the Arabidopsis prohibitin protein PHB3 is required for the maintenance of root stem cell niche identity by both inhibiting proliferative processes in the QC and stimulating cell division in the proximal meristem (PM. PHB3 coordinates cell division and differentiation in the root apical meristem by restricting the spatial expression of ethylene response factor (ERF transcription factors 115, 114, and 109. ERF115, ERF114, and ERF109 mediate ROS signaling, in a PLT-independent manner, to control root stem cell niche maintenance and root growth through phytosulfokine (PSK peptide hormones in Arabidopsis.

  6. WOX5 Suppresses CYCLIN D Activity to Establish Quiescence at the Center of the Root Stem Cell Niche

    NARCIS (Netherlands)

    Forzani, C.; Aichinger, E.; Willemsen, V.; Murray, J.A.

    2014-01-01

    In Arabidopsis, stem cells maintain the provision of new cells for root growth. They surround a group of slowly dividing cells named the quiescent center (QC), and, together, they form the stem cell niche (SCN). The QC acts as the signaling center of the SCN, repressing differentiation of the

  7. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

    Science.gov (United States)

    Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

    2017-02-17

    Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

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    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  9. Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam.

    Science.gov (United States)

    Panchal, Trupti; Chen, Xi; Alchits, Ekaterina; Oh, Youjin; Poon, James; Kouptsova, Jane; Laski, Frank A; Godt, Dorothea

    2017-05-01

    Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2-3 germline stem cells. In particular, we focused on the question of how cap cells form. Cap cells express Tj and are considered the key component of a mature germline stem cell niche. We conclude that Tj controls the specification of cap cells, as the complete loss of Tj function caused the development of additional terminal filament cells at the expense of cap cells, and terminal filament cells developed cap cell characteristics when induced to express Tj. Further, we propose that Tj controls the morphogenetic behavior of cap cells as they adopted the shape and spatial organization of terminal filament cells but otherwise appeared to retain their fate when Tj expression was only partially reduced. Our data indicate that Tj contributes to the establishment of germline stem cells by promoting the cap cell fate, and controls the stem cell-carrying capacity of the niche by regulating niche architecture. Analysis of the interactions between Tj and the Notch (N) pathway indicates that Tj and N have distinct functions in the cap cell specification program. We propose that formation of cap cells depends on the combined activities of Tj and the N pathway, with Tj promoting the cap cell fate by blocking the terminal filament cell fate, and N supporting cap cells by preventing the escort cell fate and/or controlling the number of cap cell precursors.

  10. Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam.

    Directory of Open Access Journals (Sweden)

    Trupti Panchal

    2017-05-01

    Full Text Available Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2-3 germline stem cells. In particular, we focused on the question of how cap cells form. Cap cells express Tj and are considered the key component of a mature germline stem cell niche. We conclude that Tj controls the specification of cap cells, as the complete loss of Tj function caused the development of additional terminal filament cells at the expense of cap cells, and terminal filament cells developed cap cell characteristics when induced to express Tj. Further, we propose that Tj controls the morphogenetic behavior of cap cells as they adopted the shape and spatial organization of terminal filament cells but otherwise appeared to retain their fate when Tj expression was only partially reduced. Our data indicate that Tj contributes to the establishment of germline stem cells by promoting the cap cell fate, and controls the stem cell-carrying capacity of the niche by regulating niche architecture. Analysis of the interactions between Tj and the Notch (N pathway indicates that Tj and N have distinct functions in the cap cell specification program. We propose that formation of cap cells depends on the combined activities of Tj and the N pathway, with Tj promoting the cap cell fate by blocking the terminal filament cell fate, and N supporting cap cells by preventing the escort cell fate and/or controlling the number of cap cell precursors.

  11. Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.

    Directory of Open Access Journals (Sweden)

    Richard C van der Wath

    Full Text Available The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2-3 days in mice (3-5 days in humans and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the 'pedigree' and the 'niche' models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.

  12. Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

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    Ingrid R. Cordeiro

    2015-09-01

    Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

  13. Genetic Basis for Developmental Homeostasis of Germline Stem Cell Niche Number: A Network of Tramtrack-Group Nuclear BTB Factors

    Science.gov (United States)

    Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

    2012-01-01

    The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8–10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches. PMID:23185495

  14. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

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    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  15. β-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

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    Deschene, Elizabeth R; Myung, Peggy; Rompolas, Panteleimon; Zito, Giovanni; Sun, Thomas Yang; Taketo, Makoto M; Saotome, Ichiko; Greco, Valentina

    2014-03-21

    Wnt/β-catenin signaling is critical for tissue regeneration. However, it is unclear how β-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of β-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. β-Catenin activation is sufficient to induce hair growth independently of mesenchymal dermal papilla niche signals normally required for hair regeneration. Wild-type cells are co-opted into new hair growths by β-catenin mutant cells, which non-cell autonomously activate Wnt signaling within the neighboring wild-type cells via Wnt ligands. This study demonstrates a mechanism by which Wnt/β-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration.

  16. Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Carsten, A.L.; Brecher, G.; Feinendegen, L.

    1979-01-01

    Studies were conducted on the appearance of cells in recipient bone marrow with chromosome markers after bone marrow transfusion to recipients that had different treatments. Investigators tried to replete the bone marrow CFV spleen at various times after recovery from maximal sublethal doses of x radiation or during continuous exposure to tritiated water. Studies were made on the effect of diverse treatments on the acceptance of bone marrow transfusions as shown by chromosomal markers. Results showed that the bone marrow of animals rescued by transfusion of 4 x 10 6 bone marrow cells will accept from 0 to 25% of the second transfusion of bone marrow cells given one to 4 months after the first transfusion and examined 2 to 3 weeks after the second transfusion. This may be due to the second transfusion filling up empty niches

  17. Niche Inheritance: A Cooperative Pathway to Enhance Cancer Cell Fitness Through Ecosystem Engineering

    Science.gov (United States)

    Yang, Kimberline R; Mooney, Steven M; Zarif, Jelani C; Coffey, Donald S; Taichman, Russell S; Pienta, Kenneth J

    2014-01-01

    Cancer cells can be described as an invasive species that is able to establish itself in a new environment. The concept of niche construction can be utilized to describe the process by which cancer cells terraform their environment, thereby engineering an ecosystem that promotes the genetic fitness of the species. Ecological dispersion theory can then be utilized to describe and model the steps and barriers involved in a successful diaspora as the cancer cells leave the original host organ and migrate to new host organs to successfully establish a new metastatic community. These ecological concepts can be further utilized to define new diagnostic and therapeutic areas for lethal cancers. 115: 1478–1485, 2014. © 2014 Wiley Periodicals, Inc. PMID:24700698

  18. Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche.

    Science.gov (United States)

    Vanegas, Natalia-Del Pilar; Vernot, Jean-Paul

    2017-01-01

    Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line. After 3 days, the REH-conditioned medium was removed and freshly isolated CD34+ at a density of up to 100,000 cells/ml were added to the leukemic niche. CD34+ cell evaluations (cell cycle, self-renewal gene expression and migration capacity) were performed after 3 further days of co-culture. Additionally, we preliminary investigated the soluble factors present in the leukemic niche and their effect on the mesenchymal stem cells. Statistical significance was assessed by Student's t test or the nonparametric test Kolmogorov-Smirnov. By co-culturing normal mesenchymal stem cells with the REH-conditioned medium we showed that hematopoietic stem cells, normally in a quiescent state, enter cell cycle and proliferate. This loss of quiescence was accompanied by an increased expression of Ki-67 and c-Myc, two well-known cell proliferation-associated markers. Two central regulators of quiescence GATA2 and p53 were also down regulated. Importantly, two genes involved in HSC self-renewal, Klf4 and the histone-lysine N -methyltransferase enzyme Ezh2, were severely affected. On the contrary, c-Kit expression, the stem cell factor receptor, was upregulated in hematopoietic stem cells when compared to the normal niche. Interestingly, mesenchymal stem cells incubated with the REH-conditioned medium stopped growing, showed a flattened morphology with the appearance of small vacuoles, and importantly, became positive for the senescence-associated beta-galactosidase activity. Evaluation of the leukemic

  19. A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells

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    Yulin Xu

    2016-09-01

    Full Text Available Abstract Background The efficient generation of hematopoietic stem cells (HSCs from human-induced pluripotent stem cells (iPSCs holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far. Methods We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro. Results Approximately 70 % of human CD34+ hematopoietic cells accompanied with CD43+ progenitor cells could be derived from this 3D induction system. Colony-forming-unit (CFU assay showed that iPSC-derived CD34+ cells formed all types of hematopoietic colonies including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated with hematopoietic development, were expressed during the differentiation process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid and myeloid lineages in the recipient NOD/SCID mice after transplantation. Conclusions Our study underscores the importance of a synthetic 3D niche system for the derivation of transplantable hematopoietic cells from human iPSCs in vitro thereby establishing a foundation towards utilization of human iPSC-derived HSCs for transplantation therapies in the clinic.

  20. Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance

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    Alessia Fidoamore

    2016-01-01

    Full Text Available Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.

  1. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

    Science.gov (United States)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

    2017-04-01

    Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  2. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche.

    Science.gov (United States)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R; Gumucio, Deborah L; Fu, Jianping

    2017-04-01

    Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  3. Regulation of the hematopoietic stem cell lifecycle by the endothelial niche.

    Science.gov (United States)

    Ramalingam, Pradeep; Poulos, Michael G; Butler, Jason M

    2017-07-01

    Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions. Studies employing genetic vascular models have unequivocally confirmed that ECs provide the essential instructive cues for HSC emergence during embryonic development as well as adult HSC maintenance during homeostasis and regeneration. Aging of ECs may impair their ability to maintain HSC function contributing to the development of aging-associated hematopoietic deficiencies. These findings have opened up new avenues to explore the therapeutic application of ECs. ECs can be adapted to serve as an instructive platform to expand bona fide HSCs and also utilized as a cellular therapy to promote regeneration of the hematopoietic system following myelosuppressive and myeloablative injuries. ECs provide a fertile niche for maintenance of functional HSCs throughout their lifecycle. An improved understanding of the EC-HSC cross-talk will pave the way for development of EC-directed strategies for improving HSC function during aging.

  4. The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression

    Science.gov (United States)

    Machado, CV; Passos, ST; Campos, TMC; Bernardi, L; Vilas-Bôas, DS; Nör, JE; Telles, PDS; Nascimento, IL

    2015-01-01

    Aim To detect cells expressing the stem cell marker ALDH1 (aldehyde dehydrogenase1) in the pulp of human permanent teeth and to investigate the expression of ALDH1 in isolated dental pulp cells. Methodology Pulp tissue was collected and processed for immunohistochemistry to detect ALDH1, STRO-1 and CD90 positive cells. In addition, cells were isolated and analyzed by flow cytometry for ALDH1 activity, and for the cell surface markers CD44, CD73, CD90, STRO-1 and CD45. Cells were also examined for multi-differentiation capacity. Within these cells, an ALDH1+ cell subpopulation was selected and evaluated for multi-differentiation capacity. Results The immunohistochemistry analyses showed that ALDH1, CD90 and STRO-1 positive cells were located mainly in the perivascular areas and nerve fibres of dental pulps. Cells on the fifth passage had high expression for CD44, CD73 and CD90, whereas moderate labeling was observed for STRO-1 and ALDH1 in flow cytometry analysis. On the same passages, cells were able to differentiate into osteogenic, adipogenic and chondrogenic lineages. The ALDH1+ cell subpopulation also demonstrated multi-lineage differentiation ability. Conclusions Dental pulp stem cells reside in the vicinity of blood vessels and nerve fibres, indicating the possible existence of more than one stem cell niche in dental pulps. Furthermore, ALDH1 was expressed by isolated dental pulp cells, which had mesenchymal stem cell characteristics. Thus, it can be suggested that ALDH1 may be used as a DPSC marker. PMID:26198909

  5. Synthetic niches for differentiation of human embryonic stem cells bypassing embryoid body formation.

    Science.gov (United States)

    Liu, Yarong; Fox, Victoria; Lei, Yuning; Hu, Biliang; Joo, Kye-Il; Wang, Pin

    2014-07-01

    The unique self-renewal and pluripotency features of human embryonic stem cells (hESCs) offer the potential for unlimited development of novel cell therapies. Currently, hESCs are cultured and differentiated using methods, such as monolayer culture and embryoid body (EB) formation. As such, achieving efficient differentiation into higher order structures remains a challenge, as well as maintaining cell viability during differentiation into homogeneous cell populations. Here, we describe the application of highly porous polymer scaffolds as synthetic stem cell niches. Bypassing the EB formation step, these scaffolds are capable of three-dimensional culture of undifferentiated hESCs and subsequent directed differentiation into three primary germ layers. H9 hESCs were successfully maintained and proliferated in biodegradable polymer scaffolds based on poly (lactic-co-glycolic acid) (PLGA). The results showed that cells within PLGA scaffolds retained characteristics of undifferentiated pluripotent stem cells. Moreover, the scaffolds allowed differentiation towards the lineage of interest by the addition of growth factors to the culture system. The in vivo transplantation study revealed that the scaffolds could provide a microenvironment that enabled hESCs to interact with their surroundings, thereby promoting cell differentiation. Therefore, this approach, which provides a unique culture/differentiation system for hESCs, will find its utility in various stem cell-based tissue-engineering applications. © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  7. Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

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    Alejandro Luarte

    2016-01-01

    Full Text Available Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

  8. Fractones: extracellular matrix niche controlling stem cell fate and growth factor activity in the brain in health and disease.

    Science.gov (United States)

    Mercier, Frederic

    2016-12-01

    The stem cell niche refers to a specific microenvironment where stem cells proliferate and differentiate to produce new specialized cells throughout an organism's adulthood. Growth factors are crucial signaling molecules that diffuse through the extracellular space, reach the stem cell niche, and ultimately promote stem cell proliferation and differentiation. However, it is not well known how multiple growth factors, often with antagonistic activities, work together in the stem cell niche to select target stem cell populations and determine stem cell fate. There is accumulating evidence suggesting that extracellular matrix (ECM) molecules play an important role in promoting growth factor access and activity in the stem cell niche. In the adult brain neurogenic zone, where neural stem cells (NSCs) reside, there exist specialized ECM structures, which we have named fractones. The processes of NSC allow them to come into contact with fractones and interact with its individual components, which include heparan sulfate proteoglycans (HSPGs) and laminins. We have demonstrated that fractone-associated HSPGs bind growth factors and regulate NSC proliferation in the neurogenic zone. Moreover, emerging results show that fractones are structurally altered in animal models with autism and adult hydrocephalus, as demonstrated by changes in fractone size, quantity, or HSPG content. Interestingly, ECM structures similar to fractones have been found throughout β-amyloid plaques in the brain of patients with Alzheimer's disease. Pathological fractones may cause imbalances in growth factor activity and impair neurogenesis, leading to inflammation and disorder. Generally speaking, these stem cell niche structures play a potentially vital role in controlling growth factor activity during both health and disease.

  9. Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates

    Directory of Open Access Journals (Sweden)

    Mohammad Moad

    2017-08-01

    Full Text Available Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1 enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.

  10. Characterization of lung stem cell niches in a mouse model of bleomycin-induced fibrosis

    Science.gov (United States)

    2012-01-01

    Introduction In lung fibrosis, alveolar epithelium degenerates progressively. The goal of regenerative medicine is to aid repair and regeneration of the lost tissues in parenchyma and airways for which mobilization of tissue-resident endogenous or bone marrow-derived exogenous stem cells niches is a critical step. We used a lung injury model in mice to identify and characterize functional lung stem cells to clarify how stem cell niches counteract this degenerative process. Methods Short term assay (STA) - Bleomycin-induced lung inflammation and fibrosis were assessed in a model of idiopathic pulmonary fibrosis in wild-type (WT), gp91phox-/- (NOX-/-), and gp91phoxMMP-12 double knockout (DKO) mice on C57Bl/6 background and Hoechst 33322 dye effluxing side population (SP) cells characterized. Long term assay (LTA) - In a bleomycin induced lung fibrosis model in C57Bl6 mice, the number of mature cells were quantified over 7, 14, and 21 days in bone marrow (BM), peripheral blood (PB), lung parenchyma (LP) and brochoalveolar lavage (BAL) fluid by FACS. BrdU pulse chase experiment (10 weeks) was used to identify label retaining cells (LRC). BrdU+ and BrdU- cells were characterized by hematopoietic (CD45+), pluripotency (TTF1+, Oct3/4+, SSEA-3+, SSEA-4+, Sca1+, Lin-, CD34+, CD31+), and lung lineage-specific (SPC+, AQP-5+, CC-10+) markers. Clonogenic potential of LRCs were measured by CFU-c assays. Results STA- In lung, cellularity increased by 5-fold in WT and 6-fold in NOX-/- by d7. Lung epithelial markers were very low in expression in all SP flow sorted from lung of all three genotypes cultured ex vivo. (p bleomycin, the SP in NOX-/- lung increased by 3.6-fold over WT where it increased by 20-fold over controls. Type I and II alveolar epithelial cells progressively diminished in all three genotypes by d21 post-bleomycin. D7 post-bleomycin, CD45+ cells in BALf in NOX-/- was 1.7-fold > WT, 57% of which were Mf that decreased by 67% in WT and 83% in NOX-/- by d21.LTA

  11. Wnt Ligands as a Part of the Stem Cell Niche in the Intestine and the Liver.

    Science.gov (United States)

    Degirmenci, Bahar; Hausmann, George; Valenta, Tomas; Basler, Konrad

    2018-01-01

    The term "Wnt signaling" does not refer to one uniform signal transduction cascade. Instead, it describes the multiple discrete signals elicited by Wnt ligands following their interaction with distinct receptor complexes. The interaction of stem cells with niche cells is coordinated by the involvement of different signaling pathways, including Wnt signaling. The stem cell populations are highly sensitive to modulation of Wnt pathway activity. Wnt signaling is of paramount importance for stem cell self-renewal, survival, proliferation, differentiation, movement, and cell polarity. Aberrant activation of Wnt/β-catenin signaling is associated with the pathology of many types of cancer, such as colorectal cancer and hepatocellular carcinoma. Importantly, although often initiated by mutation(s) downstream of the Wnt-receptor complex, the progression of colorectal cancer still seems to be augmented by Wnt ligand-mediated signaling. This chapter focuses on the role of Wnt ligands in the intestine and the liver during homeostasis and cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Extramedullary hematopoiesis: Elucidating the function of the hematopoietic stem cell niche (Review).

    Science.gov (United States)

    Yamamoto, Kouhei; Miwa, Yukako; Abe-Suzuki, Shiho; Abe, Shinya; Kirimura, Susumu; Onishi, Iichiroh; Kitagawa, Masanobu; Kurata, Morito

    2016-01-01

    Extramedullary hematopoiesis (EMH) occurs under various circumstances, including during embryonic/developmental periods, pathological status secondary to insufficient bone marrow function or ineffective hematopoiesis, in hematological disorders, for example malignancies, as well as stromal disorders of the bone. EMH is characterized by hematopoietic cell accumulations in multiple body locations. Common EMH locations observed in clinical and pathological practice include the spleen, liver, lymph nodes and para‑vertebral regions. Among the various organs associated with EMH, the spleen offers a unique site for evaluation of hematopoietic stem cell (HSC)/niche interactions, as this organ is one of the most common sites of EMH. However, the spleen does not have a major role in embryonic/developmental hematopoiesis. A recent study by our group revealed that circulating HSCs may be trapped by chemokine (C‑X‑C motif) ligand 12 (CXCL12)‑positive cells at the margin of sinuses near CXCL12‑positive endothelial cells, resulting in the initiation of the first step of EMH, which is a similar mechanism to bone marrow hematopoiesis. The present review briefly discusses the environment of EMH in extramedullary spaces in order to investigate the mechanisms underlying HSC maintenance, and aid the elucidation of the niche‑stem cell interactions that occur in the bone marrow.

  13. Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling

    NARCIS (Netherlands)

    Spee, B.; Carpino, G.; Schotanus, B.A.; Katoonizadeh, A.; Vander Borght, S.; Gaudio, E.; Roskams, T.

    2010-01-01

    Hepatology Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling Bart Spee1, Guido Carpino2, Baukje A Schotanus3, Azeam Katoonizadeh1, Sara Vander Borght1, Eugenio Gaudio4, Tania Roskams1 + Author Affiliations 1Department of

  14. Direct conversion of root primordium into shoot meristem relies on timing of stem cell niche development.

    Science.gov (United States)

    Rosspopoff, Olga; Chelysheva, Liudmila; Saffar, Julie; Lecorgne, Lena; Gey, Delphine; Caillieux, Erwann; Colot, Vincent; Roudier, François; Hilson, Pierre; Berthomé, Richard; Da Costa, Marco; Rech, Philippe

    2017-04-01

    To understand how the identity of an organ can be switched, we studied the transformation of lateral root primordia (LRP) into shoot meristems in Arabidopsis root segments. In this system, the cytokinin-induced conversion does not involve the formation of callus-like structures. Detailed analysis showed that the conversion sequence starts with a mitotic pause and is concomitant with the differential expression of regulators of root and shoot development. The conversion requires the presence of apical stem cells, and only LRP at stages VI or VII can be switched. It is engaged as soon as cell divisions resume because their position and orientation differ in the converting organ compared with the undisturbed emerging LRP. By alternating auxin and cytokinin treatments, we showed that the root and shoot organogenetic programs are remarkably plastic, as the status of the same plant stem cell niche can be reversed repeatedly within a set developmental window. Thus, the networks at play in the meristem of a root can morph in the span of a couple of cell division cycles into those of a shoot, and back, through transdifferentiation. © 2017. Published by The Company of Biologists Ltd.

  15. The aging hematopoietic stem cell niche: Phenotypic and functional changes and mechanisms that contribute to hematopoietic aging.

    Science.gov (United States)

    Latchney, Sarah E; Calvi, Laura M

    2017-01-01

    The hematopoietic system has the remarkable ability to provide a lifelong supply of mature cells that make up the entire blood and immune system. However, similar to other adult stem cell niches, the hematopoietic system is vulnerable to the detrimental effects of aging. This is a substantial health concern as the trend for population aging continues to increase. Identifying mechanisms that underlie hematopoietic aging is vital for understanding hematopoietic-related diseases. In this review, we first discuss the cellular hierarchy of the hematopoietic system and the components that make up the surrounding hematopoietic niche. We then provide an overview of the major phenotypes associated with hematopoietic aging and discuss recent research investigating cell-intrinsic and cell-extrinsic mechanisms of hematopoietic stem cell (HSCs) aging. We end by discussing the exciting new concept of possibly reversing the HSC aging process along with outstanding questions that remain to be answered. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Ruri; Minami, Kaori; Tanaka, Satowa [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Nagai, Mami [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Matsui, Keiji; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Asano, Shigetaka [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan)

    2013-10-11

    Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.

  17. Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering.

    Directory of Open Access Journals (Sweden)

    M Sean Peach

    Full Text Available Rotator cuff (RC tears represent a large proportion of musculoskeletal injuries attended to at the clinic and thereby make RC repair surgeries one of the most widely performed musculoskeletal procedures. Despite the high incidence rate of RC tears, operative treatments have provided minimal functional gains and suffer from high re-tear rates. The hypocellular nature of tendon tissue poses a limited capacity for regeneration. In recent years, great strides have been made in the area of tendonogenesis and differentiation towards tendon cells due to a greater understanding of the tendon stem cell niche, development of advanced materials, improved scaffold fabrication techniques, and delineation of the phenotype development process. Though in vitro models for tendonogenesis have shown promising results, in vivo models have been less successful. The present work investigates structured matrices mimicking the tendon microenvironment as cell delivery vehicles in a rat RC tear model. RC injuries augmented with a matrix delivering rat mesenchymal stem cells (rMSCs showed enhanced regeneration over suture repair alone or repair with augmentation, at 6 and 12-weeks post-surgery. The local delivery of rMSCs led to increased mechanical properties and improved tissue morphology. We hypothesize that the mesenchymal stem cells function to modulate the local immune and bioactivity environment through autocrine/paracrine and/or cell homing mechanisms. This study provides evidence for improved tendon healing with biomimetic matrices and delivered MSCs with the potential for translation to larger, clinical animal models. The enhanced regenerative healing response with stem cell delivering biomimetic matrices may represent a new treatment paradigm for massive RC tendon tears.

  18. A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells

    Directory of Open Access Journals (Sweden)

    Fanny Ehret

    2015-11-01

    Full Text Available The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell–cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membrane for both adherent monolayers and neurospheres to address the potential influence of different niche cell types in the neurogenic zone of the adult hippocampus of mice. Astrocytes and endothelial cells enhanced precursor cell proliferation and neurosphere formation. Endothelial factors also led to a prolonged increase in proliferation after growth factor withdrawal, which otherwise induces differentiation. All niche cell types enhanced cell survival in monolayer cultures, endothelial cells also stimulated neuronal differentiation. A parallel trend elicited by astrocytes did not reach conventional statistical significance. Pericytes had variable effects here. We did not observe changes in differentiation in neurosphere co-cultures. In summary, our data indicate that in precursor cell culture protocols survival could be improved by adding as yet unknown factors physiologically contributed by astrocytes and endothelial cells. Our findings also underscore the complexity of the niche and the differential impact of factors from the different sources on distinct aspects of neuronal development. With the help of the models presented here, identification of these factors and their specific biological activity can now be initiated.

  19. Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.

    Science.gov (United States)

    Cantú, Andrea V; Altshuler-Keylin, Svetlana; Laird, Diana J

    2016-07-18

    Inheritance depends on the expansion of a small number of primordial germ cells (PGCs) in the early embryo. Proliferation of mammalian PGCs is concurrent with their movement through changing microenvironments; however, mechanisms coordinating these conflicting processes remain unclear. Here, we find that PGC proliferation varies by location rather than embryonic age. Ror2 and Wnt5a mutants with mislocalized PGCs corroborate the microenvironmental regulation of the cell cycle, except in the hindgut, where Wnt5a is highly expressed. Molecular and genetic evidence suggests that Wnt5a acts via Ror2 to suppress β-catenin-dependent Wnt signaling in PGCs and limit their proliferation in specific locations, which we validate by overactivating β-catenin in PGCs. Our results suggest that the balance between expansion and movement of migratory PGCs is fine-tuned in different niches by the opposing β-catenin-dependent and Ror2-mediated pathways through Wnt5a This could serve as a selective mechanism to favor early and efficient migrators with clonal dominance in the ensuing germ cell pool while penalizing stragglers. © 2016 Cantú et al.

  20. FCC press release and consumer/retailer enforcement advisories regarding cell jammers, GPS jammers, and other jamming devices

    Science.gov (United States)

    2011-02-09

    FCC ENFORCEMENT BUREAU STEPS UP EDUCATION AND ENFORCEMENT EFFORTS AGAINST CELLPHONE AND GPS JAMMING. CONSUMERS BEWARE: It is Unlawful to Use Cell Jammers and Other Equipment : that Blocks, Jams, or Interferes with Authorized Radio Communication...

  1. The extracellular matrix niche microenvironment of neural and cancer stem cells in the brain.

    Science.gov (United States)

    Reinhard, Jacqueline; Brösicke, Nicole; Theocharidis, Ursula; Faissner, Andreas

    2016-12-01

    Numerous studies demonstrated that neural stem cells and cancer stem cells (NSCs/CSCs) share several overlapping characteristics such as self-renewal, multipotency and a comparable molecular repertoire. In addition to the intrinsic cellular properties, NSCs/CSCs favor a similar environment to acquire and maintain their characteristics. In the present review, we highlight the shared properties of NSCs and CSCs in regard to their extracellular microenvironment called the NSC/CSC niche. Moreover, we point out that extracellular matrix (ECM) molecules and their complementary receptors influence the behavior of NSCs/CSCs as well as brain tumor progression. Here, we focus on the expression profile and functional importance of the ECM glycoprotein tenascin-C, the chondroitin sulfate proteoglycan DSD-1-PG/phosphacan but also on other important glycoprotein/proteoglycan constituents. Within this review, we specifically concentrate on glioblastoma multiforme (GBM). GBM is the most common malignant brain tumor in adults and is associated with poor prognosis despite intense and aggressive surgical and therapeutic treatment. Recent studies indicate that GBM onset is driven by a subpopulation of CSCs that display self-renewal and recapitulate tumor heterogeneity. Based on the CSC hypothesis the cancer arises just from a small subpopulation of self-sustaining cancer cells with the exclusive ability to self-renew and maintain the tumor. Besides the fundamental stem cell properties of self-renewal and multipotency, GBM stem cells share further molecular characteristics with NSCs, which we would like to review in this article. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Synthetic Light-Curable Polymeric Materials Provide a Supportive Niche for Dental Pulp Stem Cells.

    Science.gov (United States)

    Vining, Kyle H; Scherba, Jacob C; Bever, Alaina M; Alexander, Morgan R; Celiz, Adam D; Mooney, David J

    2018-01-01

    Dental disease annually affects billions of patients, and while regenerative dentistry aims to heal dental tissue after injury, existing polymeric restorative materials, or fillings, do not directly participate in the healing process in a bioinstructive manner. There is a need for restorative materials that can support native functions of dental pulp stem cells (DPSCs), which are capable of regenerating dentin. A polymer microarray formed from commercially available monomers to rapidly identify materials that support DPSC adhesion is used. Based on these findings, thiol-ene chemistry is employed to achieve rapid light-curing and minimize residual monomer of the lead materials. Several triacrylate bulk polymers support DPSC adhesion, proliferation, and differentiation in vitro, and exhibit stiffness and tensile strength similar to existing dental materials. Conversely, materials composed of a trimethacrylate monomer or bisphenol A glycidyl methacrylate, which is a monomer standard in dental materials, do not support stem cell adhesion and negatively impact matrix and signaling pathways. Furthermore, thiol-ene polymerized triacrylates are used as permanent filling materials at the dentin-pulp interface in direct contact with irreversibly injured pulp tissue. These novel triacrylate-based biomaterials have potential to enable novel regenerative dental therapies in the clinic by both restoring teeth and providing a supportive niche for DPSCs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche.

    Science.gov (United States)

    Issigonis, Melanie; Matunis, Erika

    2012-08-15

    Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAK-STAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche.

    Science.gov (United States)

    Aguado, Brian A; Caffe, Jordan R; Nanavati, Dhaval; Rao, Shreyas S; Bushnell, Grace G; Azarin, Samira M; Shea, Lonnie D

    2016-03-01

    Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM-coated poly(ε-caprolactone) (PCL) scaffolds as mimics of the pre-metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM-coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. The pre-metastatic niche consists partially of ECM proteins that promote metastatic cell colonization to a target organ. We present a biomaterials-based approach to mimic this niche and identify ECM mediators of colonization. Using murine breast cancer models, we implanted microporous PCL scaffolds to recruit colonizing tumor cells in vivo. As a strategy to modulate colonization, we coated scaffolds with various ECM proteins, including decellularized lung and liver matrix from

  5. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts

    NARCIS (Netherlands)

    Sato, T.; van Es, J.H.; Snippert, H.J.G.; Stange, D.E.; Vries, R.G.J.; van den Born, M.M.W.; Barker, N.; Shroyer, N.F.; van de Wetering, M.L.; Clevers, H.

    2010-01-01

    Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such

  6. Synthetic niche substrates engineered via two‐photon laser polymerization for the expansion of human mesenchymal stromal cells

    Science.gov (United States)

    Di Maggio, Nunzia; Zandrini, Tommaso; Cerullo, Giulio; Osellame, Roberto; Martin, Ivan; Raimondi, Manuela T.

    2016-01-01

    Abstract The present study reports on the development of an innovative culture substrate, micro‐fabricated by two‐photon laser polymerization (2PP) in a hybrid organic–inorganic photoresin. It was previously demonstrated that this substrate is able to guide spontaneous homing and colonization of mesenchymal stromal cells by the presence of synthetic microniches. Here, the number of niches covering the culture substrate was increased up to 10% of the total surface. Human bone marrow‐derived mesenchymal stromal cells were expanded for 3 weeks and then their proliferation, clonogenic capacity and bilineage differentiation potential towards the osteogenic and adipogenic lineage were evaluated, both by colorimetric assays and by real‐time polymerase chain reaction. Compared with cells cultured on glass substrates, cells expanded on 2PP substrates showed a greater colony diameter, which is an index of clonogenic potential. Following medium conditioning on 2PP‐cultured cells, the expression of RUNX2 and BSP genes, as well as PPAR‐gamma, was significantly greater than that measured on glass controls. Thus, human cells expanded on the synthetic niche substrate maintained their proliferative potential, clonogenic capacity and bilineage differentiation potential more effectively than cells expanded on glass substrates and in some aspects were comparable to non‐expanded cells. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. PMID:27296669

  7. Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

    Science.gov (United States)

    Willis, Lisa; Refahi, Yassin; Wightman, Raymond; Landrein, Benoit; Teles, José; Huang, Kerwyn Casey; Meyerowitz, Elliot M.

    2016-01-01

    Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3–4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell–cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control. PMID:27930326

  8. Molecular Targets of Chromatin Repressive Mark H3K9me3 in Primate Progenitor Cells within Adult Neurogenic Niches

    Directory of Open Access Journals (Sweden)

    Michael R Foret

    2014-07-01

    Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

  9. Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche.

    Science.gov (United States)

    Pekar, Olga; Ow, Maria C; Hui, Kailyn Y; Noyes, Marcus B; Hall, Sarah E; Hubbard, E Jane Albert

    2017-08-15

    The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of lag-2 in the DTC in a daf-3- dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  10. Endothelial cells create a stem cell niche in glioblastoma by providing Notch ligands that nurture self-renewal of cancer stem-like cells

    Science.gov (United States)

    Zhu, Thant S.; Costello, Mark A.; Talsma, Caroline E.; Flack, Callie G.; Crowley, Jessica G.; Hamm, Lisa L.; He, Xiaobing; Hervey-J umper, Shawn L.; Heth, Jason A.; Muraszko, Karin M.; DiMeco, Francesco; Vescovi, Angelo L.; Fan, Xing

    2012-01-01

    One important function of endothelial cells in glioblastoma (GBM) is to create a niche that helps promote self-renewal of cancer stem-like cells (CSLCs). However, the underlying molecular mechanism for this endothelial function is not known. Since activation of Notch signaling has been found to be required for propagation of GBM CSLCs, we hypothesized that the GBM endothelium may provide the source of Notch ligands. Here we report a corroboration of this concept with a demonstration that Notch ligands are expressed in endothelial cells adjacent to Nestin and Notch receptor-positive cancer cells in primary GBMs. Co-culturing human brain microvascular endothelial cells (hBMECs) or Notch ligand with GBM neurospheres promoted GBM cell growth and increased CSLC self-renewal. Notably, RNAi-mediated knockdown of Notch ligands in hBMECs abrogated their ability to induce CSLC self-renewal and GBM tumor growth, both in vitro and in vivo. Thus, our findings establish that Notch activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells and their surrounding endothelial cells in the tumor microenvironment, suggesting that targeting both CSLCs and their niche may provide a novel strategy to deplete CSLCs and improve GBM treatment. PMID:21788346

  11. Transition from non-renewable to renewable energy sources: fuel cells in Antarctica as an economically attractive niche

    International Nuclear Information System (INIS)

    Marschoff, C.M.

    1998-01-01

    There is a growing amount of evidence that indicates that fuel cells might be commercially attractive in several market niches in Latin America; however, political approval of demonstration projects has been elusive. In this paper, the results of an economic study carried out on the assumption of introducing an environmentally friendly fuel, such as methanol, for feeding fuel cell systems for electricity generation and heat production in the six bases that Argentina has in Antarctica are reported. It is seen that, in this particular case, there is a net cost benefit, even if the assets resulting from diminishing pollution in Antarctica are not taken into account. (Author)

  12. Interstitial interfaces show marked differences in regenerating tubules, matured tubules, and the renal stem/progenitor cell niche.

    Science.gov (United States)

    Minuth, Will W; Denk, Lucia

    2012-05-01

    Stem/progenitor cells are promising candidates for the regeneration of parenchyma in acute and chronic renal failure. After an implantation stem/progenitor cells must migrate through the interstitial space to concentrate at the site of damage. However, information is lacking to what extent the interstitial interface is influencing the development of stem/progenitor cells into nephron structures. In consequence, tubule regeneration within an artificial polyester interstitium was analyzed by electron microscopy in comparison with the interstitial interface of matured tubules and the interstitium within the renal stem/progenitor cell niche. The experiments demonstrate that fixation of specimens with glutaraldehyde (GA) is leading in all cases to inconspicuously looking interstitial interfaces. In contrast, fixation of regenerating tubules in GA containing ruthenium red and tannic acid shows a dense network of fibers lining along the basal lamina. In contrast, matured tubules reveal after ruthenium red label an extremely thickened basal lamina, while only a punctate pattern is obtained after tannic acid treatment. Finally, within the renal stem/progenitor cell niche ruthenium red and tannic acid label reveals large amounts of extracellular matrix spanning through the interstitium. Thus, fixation of tissue in GA containing ruthenium red and tannic acid exhibits an unexpectedly regional heterogeneity of the renal interstitial interface. This fact has to be considered for an optimal therapeutic repair of parenchyma, since contacts between stem/progenitor cells with the interstitial interface influence further development. Copyright © 2012 Wiley Periodicals, Inc.

  13. Cholangiocarcinomas: New Insights from the Discovery of Stem Cell Niches in Peribiliary Glands of the Biliary Tree

    Directory of Open Access Journals (Sweden)

    Vincenzo Cardinale

    2014-01-01

    Full Text Available Peribiliary glands (PBGs are located in the large intrahepatic and extrahepatic bile ducts. Although they were described many years ago, their functions have been elucidated only in the last couple of years when our group demonstrated that PBGs are niches of multipotent stem/progenitor cells of endodermal origin. These cells express genes of multipotency and can be rapidly differentiated in vitro into hepatocytes, cholangiocytes, and endocrine pancreatic cells. PBGs share common features, in terms of stem/progenitor cell niches, with pancreatic duct glands and colon crypts, glandular structures representing in the adult life the endodermal remnants of fetal life. PBG stem/progenitor cells participate in the renewal of surface biliary epithelium and are active players in chronic pathologies of the biliary tree as well as in cholangiocarcinomas (CCA. Specifically, a large amount of recent evidence indicates that the pure mucin-CCA originates from PBGs; this could explain the similarities with pancreatic ductal adenocarcinoma and colorectal cancer, which also originate from transformed gland cells. In this paper, we summarized our recent findings concerning structure and functions of PBGs with the implications for liver pathophysiology and, specifically, for cancers of the biliary tree.

  14. Adult neurogenesis in the crayfish brain: the hematopoietic anterior proliferation center has direct access to the brain and stem cell niche.

    Science.gov (United States)

    Chaves da Silva, Paula Grazielle; Benton, Jeanne L; Sandeman, David C; Beltz, Barbara S

    2013-04-01

    Neuronal stem cells residing in a niche on the surface of the adult crayfish (Procambarus clarkii) brain are not self-renewing. However, the neuronal precursors in the niche are not depleted despite continued neurogenesis and the exit of precursor cells from the niche throughout the organism's life. The neurogenic niche is therefore not a closed system, and we have previously proposed that the stem cell pool is replenished from the hematopoietic system. Noonin et al. (2012) demonstrated that the hematopoietic system in the crayfish Pacifastacus leniusculus includes an anterior proliferation center (APC) lying near the brain; they suggest that multipotent stem cells are concentrated in this region, and that the APC may provide neuronal stem cells for adult neurogenesis. The present study extends this work by describing the location and cellular organization of hematopoietic tissues in P. clarkii. We find that the APC lies within the cor frontale, or auxiliary heart, which pumps hemolymph to the brain and eyes through the cerebral and ophthalmic arteries, respectively. Vascular extensions of the cerebral artery converge on the neurogenic niche. APC cells lie in layered sheets within the cor frontale and form rosette-like structures reminiscent of stem cells in other developing tissues. We confirm here that APC cells in P. clarkii have characteristics of multipotent stem cells, and that their location within the cor frontale allows direct access to regions in the central nervous system in which adult neurogenesis occurs.

  15. Pre-procambial cells are niches for pluripotent and totipotent stem-like cells for organogenesis and somatic embryogenesis in the peach palm: a histological study.

    Science.gov (United States)

    de Almeida, Marcilio; de Almeida, Cristina Vieira; Mendes Graner, Erika; Ebling Brondani, Gilvano; Fiori de Abreu-Tarazi, Monita

    2012-08-01

    The direct induction of adventitious buds and somatic embryos from explants is a morphogenetic process that is under the influence of exogenous plant growth regulators and its interactions with endogenous phytohormones. We performed an in vitro histological analysis in peach palm (Bactris gasipaes Kunth) shoot apexes and determined that the positioning of competent cells and their interaction with neighboring cells, under the influence of combinations of exogenously applied growth regulators (NAA/BAP and NAA/TDZ), allows the pre-procambial cells (PPCs) to act in different morphogenic pathways to establish niche competent cells. It is likely that there has been a habituation phenomenon during the regeneration and development of the microplants. This includes promoting the tillering of primary or secondary buds due to culturing in the absence of NAA/BAP or NAA/TDZ after a period in the presence of these growth regulators. Histological analyses determined that the adventitious roots were derived from the dedifferentiation of the parenchymal cells located in the basal region of the adventitious buds, with the establishment of rooting pole, due to an auxin gradient. Furthermore, histological and histochemical analyses allowed us to characterize how the PPCs provide niches for multipotent, pluripotent and totipotent stem-like cells for vascular differentiation, organogenesis and somatic embryogenesis in the peach palm. The histological and histochemical analyses also allowed us to detect the unicellular or multicellular origin of somatic embryogenesis. Therefore, our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells. Our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to

  16. Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Abbuehl, Jean-Paul; Tatarova, Zuzana; Held, Werner; Huelsken, Joerg

    2017-08-03

    Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E + (CD73) + ENG - (CD105) - LY6A + (SCA1) + BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Lack of galectin-3 disturbs mesenteric lymph node homeostasis and B cell niches in the course of Schistosoma mansoni infection.

    Science.gov (United States)

    Oliveira, Felipe L; Brand, Camila; Paula, Adelzon A; Arcanjo, Kátia D; Hsu, Daniel K; Liu, Fu-Tong; Takiya, Christina M; Borojevic, Radovan; Chammas, Roger; El-Cheikh, Márcia C

    2011-05-06

    Galectin-3 is a β-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAcβ1-4(Fucα1-3)GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine β1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in non-lymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S.mansoni.

  18. Lack of galectin-3 disturbs mesenteric lymph node homeostasis and B cell niches in the course of Schistosoma mansoni infection.

    Directory of Open Access Journals (Sweden)

    Felipe L Oliveira

    Full Text Available Galectin-3 is a β-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs during chronic schistosomiasis, using WT and galectin-3(-/- mice. Schistosoma mansoni synthesizes GalNAcβ1-4(Fucα1-3GlcNAc(Lac-DiNAc structures (N-acetylgalactosamine β1-4 N-acetylglucosamine, which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/- mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+/PI(- cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in non-lymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S.mansoni.

  19. Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells

    Science.gov (United States)

    Coşkun, Süleyman; Chao, Hsu; Vasavada, Hema; Heydari, Kartoosh; Gonzales, Naomi; Zhou, Xin; de Crombrugghe, Benoit; Hirschi, Karen K.

    2014-01-01

    SUMMARY Hematopoietic stem cells (HSC) reside within a specialized niche where interactions with vasculature, osteoblasts and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSC emerged at E16.5, coincident with marrow vascularization, and were contained within the c-Kit+Sca-1+Lin− (KSL) population. We used Osterix-null (Osx−/−) mice that form vascularized marrow, but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx−/− fetal bone marrow cells formed multi-lineage colonies in vitro, but were hyper-proliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multi-lineage progenitors, but interactions with osteolineage cells are needed to regulate LT-HSC proliferation and potential. PMID:25310984

  20. Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells

    Directory of Open Access Journals (Sweden)

    Süleyman Coşkun

    2014-10-01

    Full Text Available Hematopoietic stem cells (HSCs reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5, coincident with marrow vascularization, and were contained within the c-Kit+Sca-1+Lin− (KSL population. We used Osterix-null (Osx−/− mice that form vascularized marrow but lack osteolineage cells to dissect the role(s of these cellular components in HSC development. Osx−/− fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential.

  1. Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells.

    Science.gov (United States)

    Coşkun, Süleyman; Chao, Hsu; Vasavada, Hema; Heydari, Kartoosh; Gonzales, Naomi; Zhou, Xin; de Crombrugghe, Benoit; Hirschi, Karen K

    2014-10-23

    Hematopoietic stem cells (HSCs) reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5), coincident with marrow vascularization, and were contained within the c-Kit(+)Sca-1(+)Lin(-) (KSL) population. We used Osterix-null (Osx(-/-)) mice that form vascularized marrow but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx(-/-) fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance

    Science.gov (United States)

    Hakata, Yoshiyuki; Motozono, Chihiro; McMaster, Sean R.; Masumoto, Tomoko; Fujisawa, Makoto; Chikaishi, Tomomi; Komeda, Junko; Itoh, Jun; Umemura, Miki; Kyusai, Ami; Woodland, David L.; Kohlmeier, Jacob E.; Miyazawa, Masaaki

    2016-01-01

    CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site–specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens. PMID:27815325

  3. Pre-metastatic niches

    DEFF Research Database (Denmark)

    Peinado, Héctor; Zhang, Haiying; Matei, Irina R.

    2017-01-01

    -secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche....

  4. A Comparative Pan-Genome Perspective of Niche-Adaptable Cell-Surface Protein Phenotypes in Lactobacillus rhamnosus

    Science.gov (United States)

    Kant, Ravi; Sigvart-Mattila, Pia; Paulin, Lars; Mecklin, Jukka-Pekka; Saarela, Maria; Palva, Airi; von Ossowski, Ingemar

    2014-01-01

    Lactobacillus rhamnosus is a ubiquitously adaptable Gram-positive bacterium and as a typical commensal can be recovered from various microbe-accessible bodily orifices and cavities. Then again, other isolates are food-borne, with some of these having been long associated with naturally fermented cheeses and yogurts. Additionally, because of perceived health benefits to humans and animals, numerous L. rhamnosus strains have been selected for use as so-called probiotics and are often taken in the form of dietary supplements and functional foods. At the genome level, it is anticipated that certain genetic variances will have provided the niche-related phenotypes that augment the flexible adaptiveness of this species, thus enabling its strains to grow and survive in their respective host environments. For this present study, we considered it functionally informative to examine and catalogue the genotype-phenotype variation existing at the cell surface between different L. rhamnosus strains, with the presumption that this might be relatable to habitat preferences and ecological adaptability. Here, we conducted a pan-genomic study involving 13 genomes from L. rhamnosus isolates with various origins. In using a benchmark strain (gut-adapted L. rhamnosus GG) for our pan-genome comparison, we had focused our efforts on a detailed examination and description of gene products for certain functionally relevant surface-exposed proteins, each of which in effect might also play a part in niche adaptability among the other strains. Perhaps most significantly of the surface protein loci we had analyzed, it would appear that the spaCBA operon (known to encode SpaCBA-called pili having a mucoadhesive phenotype) is a genomic rarity and an uncommon occurrence in L. rhamnosus. However, for any of the so-piliated L. rhamnosus strains, they will likely possess an increased niche-specific fitness, which functionally might presumably be manifested by a protracted transient colonization of

  5. A comparative pan-genome perspective of niche-adaptable cell-surface protein phenotypes in Lactobacillus rhamnosus.

    Directory of Open Access Journals (Sweden)

    Ravi Kant

    Full Text Available Lactobacillus rhamnosus is a ubiquitously adaptable Gram-positive bacterium and as a typical commensal can be recovered from various microbe-accessible bodily orifices and cavities. Then again, other isolates are food-borne, with some of these having been long associated with naturally fermented cheeses and yogurts. Additionally, because of perceived health benefits to humans and animals, numerous L. rhamnosus strains have been selected for use as so-called probiotics and are often taken in the form of dietary supplements and functional foods. At the genome level, it is anticipated that certain genetic variances will have provided the niche-related phenotypes that augment the flexible adaptiveness of this species, thus enabling its strains to grow and survive in their respective host environments. For this present study, we considered it functionally informative to examine and catalogue the genotype-phenotype variation existing at the cell surface between different L. rhamnosus strains, with the presumption that this might be relatable to habitat preferences and ecological adaptability. Here, we conducted a pan-genomic study involving 13 genomes from L. rhamnosus isolates with various origins. In using a benchmark strain (gut-adapted L. rhamnosus GG for our pan-genome comparison, we had focused our efforts on a detailed examination and description of gene products for certain functionally relevant surface-exposed proteins, each of which in effect might also play a part in niche adaptability among the other strains. Perhaps most significantly of the surface protein loci we had analyzed, it would appear that the spaCBA operon (known to encode SpaCBA-called pili having a mucoadhesive phenotype is a genomic rarity and an uncommon occurrence in L. rhamnosus. However, for any of the so-piliated L. rhamnosus strains, they will likely possess an increased niche-specific fitness, which functionally might presumably be manifested by a protracted transient

  6. Bioengineered fibrin-based niche to direct outgrowth of circulating progenitors into neuron-like cells for potential use in cellular therapy

    Science.gov (United States)

    Tara, S.; Krishnan, Lissy K.

    2015-06-01

    Objective. Autologous cells are considered to be the best choice for use in transplantation therapy. However, the challenges and risks associated with the harvest of transplantable autologous cells limit their successful therapeutic application. The current study explores the possibility of isolating neural progenitor cells from circulating multipotent adult progenitor cells for potential use in cell-based and patient-specific therapy for neurological diseases. Approach. To enable the selection of neural progenitor cells from human peripheral blood mononuclear cells, and to support their lineage maintenance, the composition of a fibrin-based niche was optimized. Morphological examination and specific marker analysis were carried out, employing a qualitative/quantitative polymerase chain reaction followed by immunocytochemistry to: (i) characterize neural progenitor cells in culture; (ii) monitor proliferation/survival; and (iii) track their differentiation status. Main results. The presence of neural progenitors in circulation was confirmed by the presence of nestin+ cells at the commencement of the culture. The isolation, proliferation and differentiation of circulating neural progenitors to neuron-like cells were directed by the engineered niche. Neural cell isolation to near homogeneity was confirmed by the expression of β-III tubulin in ∼95% of cells, whereas microtubule associated protein-2 expression confirmed their ability to differentiate. The concentration of potassium chloride in the niche was found to favour neuron-like cell lengthening, cell-cell contact, and expressions of synaptophysin and tyrosine hydroxylase. Significance. The purpose of this research was to find out if peripheral blood could serve as a potential source of neural progenitors for cell based therapy. The study established that neural progenitors could be selectively isolated from peripheral blood mononuclear cells using a biomimetic niche. The selected cells could multiply and

  7. Illustration of extensive extracellular matrix at the epithelial-mesenchymal interface within the renal stem/progenitor cell niche

    Directory of Open Access Journals (Sweden)

    Minuth Will W

    2012-09-01

    Full Text Available Abstract Background Stem/progenitor cells are promising candidates to treat diseased renal parenchyma. However, implanted stem/progenitor cells are exposed to a harmful atmosphere of degenerating parenchyma. To minimize hampering effects after an implantation investigations are in progress to administer these cells within an artificial polyester interstitum supporting survival. Learning from nature the renal stem/progenitor cell niche appears as a valuable model. At this site epithelial stem/progenitor cells within the collecting duct ampulla face mesenchymal stem/progenitor cells. Both cell types do not have close contact but are separated by a wide interstitium. Methods To analyze extracellular matrix in this particular interstitium, special contrasting for transmission electron microscopy was performed. Kidneys of neonatal rabbits were fixed in solutions containing glutaraldehyde (GA or in combination with cupromeronic blue, ruthenium red and tannic acid. Results GA revealed a basal lamina at the ampulla and a bright but inconspicuously looking interstitial space. In contrast, GA containing cupromeronic blue exhibits numerous proteoglycan braces lining from the ampulla towards the interstitial space. GA containing ruthenium red or tannic acid demonstrates clouds of extracellular matrix protruding from the basal lamina of the ampulla to the surface of mesenchymal stem/progenitor cells. Conclusions The actual data show that the interstitium between epithelial and mesenchymal stem/progenitor cells contains much more and up to date unknown extracellular matrix than earlier observed by classical GA fixation.

  8. Hacking GPS

    CERN Document Server

    Kingsley-Hughes, Kathie

    2005-01-01

    * This is the "user manual" that didn't come with any of the 30 million GPS receivers currently in use, showing readers how to modify, tweak, and hack their GPS to take it to new levels!* Crazy-cool modifications include exploiting secret keycodes, revealing hidden features, building power cords and cables, hacking the battery and antenna, protecting a GPS from impact and falls, making a screen protector, and solar-powering a GPS* Potential power users will take the function and performance of their GPS to a whole new level by hacking into the firmware and hacking into a PC connection with a GPS* Fear not! Any potentially dangerous mod (to the device) is clearly labeled, with precautions listed that should be taken* Game time! Readers can check out GPS games, check into hacking geocaching, and even use a GPS as a metal detector

  9. Design approach for solar cell and battery of a persistent solar powered GPS tracker

    Science.gov (United States)

    Sahraei, Nasim; Watson, Sterling M.; Pennes, Anthony; Marius Peters, Ian; Buonassisi, Tonio

    2017-08-01

    Sensors with wireless communication can be powered by photovoltaic (PV) devices. However, using solar power requires thoughtful design of the power system, as well as a careful management of the power consumption, especially for devices with cellular communication (because of their higher power consumption). A design approach can minimize system size, weight, and/or cost, while maximizing device performance (data transmission rate and persistence). In this contribution, we describe our design approach for a small form-factor, solar-powered GPS tracker with cellular communication. We evaluate the power consumption of the device in different stages of operation. Combining measured power consumption and the calculated energy-yield of a solar cell, we estimate the battery capacity and solar cell area required for 5 years of continuous operation. We evaluate trade-offs between PV and battery size by simulating the battery state of charge. The data show a trade-off between battery capacity and solar-cell area for given target data transmission rate and persistence. We use this analysis to determine the combination of solar panel area and battery capacity for a given application and the data transmission rate that results in minimum cost or total weight of the system.

  10. Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization.

    Science.gov (United States)

    Theodore, Lindsay N; Hagedorn, Elliott J; Cortes, Mauricio; Natsuhara, Kelsey; Liu, Sarah Y; Perlin, Julie R; Yang, Song; Daily, Madeleine L; Zon, Leonard I; North, Trista E

    2017-05-09

    Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb + HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling. In contrast, Mmp9 was dispensable for HSPC budding, being instead required for proper colonization of secondary niches. Significantly, these migration defects were mimicked by overexpression and blocked by knockdown of C-X-C motif chemokine-12 (cxcl12), suggesting that Mmp9 controls CHT homeostasis through chemokine regulation. Our findings indicate Mmp2 and Mmp9 play distinct but complementary roles in developmental HSPC production and migration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Rac1 GTPase Promotes Interaction of Hematopoietic Stem/Progenitor Cell with Niche and Participates in Leukemia Initiation and Maintenance in Mouse.

    Science.gov (United States)

    Chen, Shuying; Li, Huan; Li, Shouyun; Yu, Jing; Wang, Min; Xing, Haiyan; Tang, Kejing; Tian, Zheng; Rao, Qing; Wang, Jianxiang

    2016-07-01

    Interaction between hematopoietic stem/progenitor cells (HSPCs) with their niche is critical for HSPC function. The interaction also plays an important role in the multistep process of leukemogenesis. Rac1 GTPase has been found to be highly expressed and activated in leukemia patients. Here, by forced expression of constitutively active form of Rac1 (Rac1-V12) in HSPCs, we demonstrate that active Rac1 promotes interaction of HSPC with niche. We then established an active Rac1 associated acute myeloid leukemia (AML) model by expression of Rac1-V12 cooperated with AML1-ETO9a (AE9a) in mouse HSPCs. Compared with AE9a alone, Rac1-V12 cooperated with AE9a (AER) drives an AML with a short latency, demonstrating that activation of Rac1 GTPase in mice promotes AML development. The mechanism of this AML promotion is by a better homing and lodging of leukemia cells in niche, which further enhancing their colony formation, quiescence and preventing leukemia cells from apoptosis. Further study showed that an inhibitor targeting activated Rac1 can increase the efficacy of chemotherapeutic agents to leukemia cells. This study provides evidence that activation of Rac1 promotes leukemia development through enhancing leukemia cells' homing and retention in niche, and suggests that inhibition of Rac1 GTPase could be an effective way of eliminating AML cells. Stem Cells 2016;34:1730-1741. © 2016 AlphaMed Press.

  12. Microcavity arrays as an in vitro model system of the bone marrow niche for hematopoietic stem cells.

    Science.gov (United States)

    Wuchter, Patrick; Saffrich, Rainer; Giselbrecht, Stefan; Nies, Cordula; Lorig, Hanna; Kolb, Stephanie; Ho, Anthony D; Gottwald, Eric

    2016-06-01

    In previous studies human mesenchymal stromal cells (MSCs) maintained the "stemness" of human hematopoietic progenitor cells (HPCs) through direct cell-cell contact in two-dimensional co-culture systems. We establish a three-dimensional (3D) co-culture system based on a custom-made chip, the 3(D)-KITChip, as an in vitro model system of the human hematopoietic stem cell niche. This array of up to 625 microcavities, with 300 μm size in each orientation, was inserted into a microfluidic bioreactor. The microcavities of the 3(D)-KITChip were inoculated with human bone marrow MSCs together with umbilical cord blood HPCs. MSCs used the microcavities as a scaffold to build a complex 3D mesh. HPCs were distributed three-dimensionally inside this MSC network and formed ß-catenin- and N-cadherin-based intercellular junctions to the surrounding MSCs. Using RT(2)-PCR and western blots, we demonstrate that a proportion of HPCs maintained the expression of CD34 throughout a culture period of 14 days. In colony-forming unit assays, the hematopoietic stem cell plasticity remained similar after 14 days of bioreactor co-culture, whereas monolayer co-cultures showed increasing signs of HPC differentiation and loss of stemness. These data support the notion that the 3D microenvironment created within the microcavity array preserves vital stem cell functions of HPCs more efficiently than conventional co-culture systems.

  13. Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8+ T Cells

    Science.gov (United States)

    2017-01-01

    Abstract Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority. CD8+ Tissue-resident memory T (TRM) cells are a newly defined population that resides permanently in the nonlymphoid tissues including the lung. These cells are capable of providing local protection immediately after infection, thereby promoting rapid host recovery. Recent studies have offered new insights into the anatomical niches that harbor lung CD8+ TRM cells, and also identified the requirement and limitations of TRM maintenance. However, it remains controversial whether lung CD8+ TRM cells are continuously replenished by new cells from the circulation or permanently lodged in this site. A better understanding of how lung CD8+ TRM cells are generated and maintained and the tissue-specific factors that drive local TRM formation is required for optimal vaccine development. This review focuses on recent advance in our understanding of CD8+ TRM cell establishment and maintenance in the lung, and describes how those processes are uniquely regulated in this tissue. PMID:28418771

  14. Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD–induced myeloproliferation

    Science.gov (United States)

    Matsuoka, Sahoko; Thongjuea, Supat; Jamieson, Lauren; Atkinson, Deborah; Kharazi, Shabnam; Suda, Toshio

    2017-01-01

    Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation found Flt3 mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment. Competitive transplantation experiments established that Flt3-ITD compromises HSCs through an extrinsically mediated mechanism of disrupting HSC-supporting bone marrow stromal cells, with reduced numbers of endothelial and mesenchymal stromal cells showing increased inflammation-associated gene expression. Tumor necrosis factor (TNF), a cell-extrinsic potent negative regulator of HSCs, was overexpressed in bone marrow niche cells from FLT3-ITD mice, and anti-TNF treatment partially rescued the HSC phenotype. These findings, which establish that Flt3-ITD–driven myeloproliferation results in cell-extrinsic suppression of the normal HSC reservoir, are of relevance for several aspects of acute myeloid leukemia biology. PMID:28637883

  15. bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Victoria; Tokusumi, Tsuyoshi; Tokusumi, Yumiko; Schulz, Robert A., E-mail: rschulz@nd.edu

    2014-10-24

    Highlights: • bantam miRNA is endogenously expressed in the hematopoietic progenitor niche. • bantam is necessary and sufficient to induce cellular proliferation in the PSC. • bantam is upstream of the Insulin Receptor signaling pathway. • A model for positive regulation of hematopoietic niche growth is proposed. - Abstract: The Drosophila hematopoietic system is utilized in this study to gain novel insights into the process of growth control of the hematopoietic progenitor niche in blood development. The niche microenvironment is an essential component controlling the balance between progenitor populations and differentiated, mature blood cells and has been shown to lead to hematopoietic malignancies in humans when misregulated. MicroRNAs are one class of regulators associated with blood malignancies; however, there remains a relative paucity of information about the role of miRNAs in the niche. Here we demonstrate that bantam miRNA is endogenously active in the Drosophila hematopoietic progenitor niche, the posterior signaling center (PSC), and functions in the primary hematopoietic organ, the lymph gland, as a positive regulator of growth. Loss of bantam leads to a significant reduction in the PSC and overall lymph gland size, as well as a loss of the progenitor population and correlative premature differentiation of mature hemocytes. Interestingly, in addition to being essential for proper lymph gland development, we have determined bantam to be a novel upstream component of the insulin signaling cascade in the PSC and have unveiled dMyc as one factor central to bantam activity. These important findings identify bantam as a new hematopoietic regulator, place it in an evolutionarily conserved signaling pathway, present one way in which it is regulated, and provide a mechanism through which it facilitates cellular proliferation in the hematopoietic niche.

  16. bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche

    International Nuclear Information System (INIS)

    Lam, Victoria; Tokusumi, Tsuyoshi; Tokusumi, Yumiko; Schulz, Robert A.

    2014-01-01

    Highlights: • bantam miRNA is endogenously expressed in the hematopoietic progenitor niche. • bantam is necessary and sufficient to induce cellular proliferation in the PSC. • bantam is upstream of the Insulin Receptor signaling pathway. • A model for positive regulation of hematopoietic niche growth is proposed. - Abstract: The Drosophila hematopoietic system is utilized in this study to gain novel insights into the process of growth control of the hematopoietic progenitor niche in blood development. The niche microenvironment is an essential component controlling the balance between progenitor populations and differentiated, mature blood cells and has been shown to lead to hematopoietic malignancies in humans when misregulated. MicroRNAs are one class of regulators associated with blood malignancies; however, there remains a relative paucity of information about the role of miRNAs in the niche. Here we demonstrate that bantam miRNA is endogenously active in the Drosophila hematopoietic progenitor niche, the posterior signaling center (PSC), and functions in the primary hematopoietic organ, the lymph gland, as a positive regulator of growth. Loss of bantam leads to a significant reduction in the PSC and overall lymph gland size, as well as a loss of the progenitor population and correlative premature differentiation of mature hemocytes. Interestingly, in addition to being essential for proper lymph gland development, we have determined bantam to be a novel upstream component of the insulin signaling cascade in the PSC and have unveiled dMyc as one factor central to bantam activity. These important findings identify bantam as a new hematopoietic regulator, place it in an evolutionarily conserved signaling pathway, present one way in which it is regulated, and provide a mechanism through which it facilitates cellular proliferation in the hematopoietic niche

  17. MicroRNA 16 enhances differentiation of human bone marrow mesenchymal stem cells in a cardiac niche toward myogenic phenotypes in vitro.

    Science.gov (United States)

    Liu, Ju-Li; Jiang, Li; Lin, Qiu-Xiong; Deng, Chun-Yu; Mai, Li-Ping; Zhu, Jie-Ning; Li, Xiao-Hong; Yu, Xi-Yong; Lin, Shu-Guang; Shan, Zhi-Xin

    2012-06-27

    Upregulation of microRNA 16 (miR-16) contributed to the differentiation of human bone marrow mesenchymal stem cells (hMSCs) toward myogenic phenotypes in a cardiac niche, the present study aimed to determine the role of miR-16 in this process. hMSCs and neonatal rat ventricular myocytes were co-cultured indirectly in two chambers to set up a cardiac microenvironment (niche). miRNA expression profile in cardiac-niche-induced hMSCs was detected by miRNA microarray. Cardiac marker expression and cell cycle analysis were determined in different treatment hMSCs. Quantitative real-time PCR and Western blot were used to identify the expression of mRNA, mature miRNA and protein of interest. miRNA dysregulation was shown in hMSCs after cardiac niche induction. miR-16 was upregulated in cardiac-niche-induced hMSCs. Overexpression of miR-16 significantly increased G1-phase arrest of the cell cycle in hMSCs and enhanced the expression of cardiac marker genes, including GATA4, NK2-5, MEF2C and TNNI3. Differentiation-inducing factor 3 (DIF-3), a G0/G1 cell cycle arrest compound, was used to induce G1 phase arrest in cardiac-niche-induced hMSCs, and the expression of cardiac marker genes was up-regulated in DIF-3-treated hMSCs. The expression of CCND1, CCND2 and CDK6 was suppressed by miR-16 in hMSCs. CDK6, CCND1 or CCND2 knockdown resulted in G1 phase arrest in hMSCs and upregulation of cardiac marker gene expression in hMSCs in a cardiac niche. miR-16 enhances G1 phase arrest in hMSCs, contributing to the differentiation of hMSCs toward myogenic phenotypes when in a cardiac niche. This mechanism provides a novel strategy for pre-modification of hMSCs before hMSC-based transplantation therapy for severe heart diseases. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  18. Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation.

    Science.gov (United States)

    Winkler, I G; Pettit, A R; Raggatt, L J; Jacobsen, R N; Forristal, C E; Barbier, V; Nowlan, B; Cisterne, A; Bendall, L J; Sims, N A; Lévesque, J-P

    2012-07-01

    The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.

  19. Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cell–collagen constructs: A three-dimensional in vitro model to study hematopoietic stem cell niche

    Directory of Open Access Journals (Sweden)

    WY Lai

    2013-10-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and osteoblasts are important niche cells for hematopoietic stem cells (HSCs in bone marrow osteoblastic niche. Here, we aim to partially reconstitute the bone marrow HSC niche in vitro using collagen microencapsulation for investigation of the interactions between HSCs and MSCs. Mouse MSCs (mMSCs microencapsulated in collagen were osteogenically differentiated to derive a bone-like matrix consisting of osteocalcin, osteopontin, and calcium deposits and secreted bone morphogenic protein 2 (BMP2. Decellularized bone-like matrix was seeded with fluorescence-labeled human MSCs and HSCs. Comparing with pure collagen scaffold, significantly more HSCs and HSC–MSC pairs per unit area were found in the decellularized bone-like matrix. Moreover, incubation with excess neutralizing antibody of BMP2 resulted in a significantly higher number of HSC per unit area than that without in the decellularized matrix. This work suggests that the osteogenic differentiated MSC–collagen microsphere is a valuable three-dimensional in vitro model to elucidate cell–cell and cell–matrix interactions in HSC niche.

  20. Interplay of the serine/threonine-kinase StkP and the paralogs DivIVA and GpsB in pneumococcal cell elongation and division.

    Directory of Open Access Journals (Sweden)

    Aurore Fleurie

    2014-04-01

    Full Text Available Despite years of intensive research, much remains to be discovered to understand the regulatory networks coordinating bacterial cell growth and division. The mechanisms by which Streptococcus pneumoniae achieves its characteristic ellipsoid-cell shape remain largely unknown. In this study, we analyzed the interplay of the cell division paralogs DivIVA and GpsB with the ser/thr kinase StkP. We observed that the deletion of divIVA hindered cell elongation and resulted in cell shortening and rounding. By contrast, the absence of GpsB resulted in hampered cell division and triggered cell elongation. Remarkably, ΔgpsB elongated cells exhibited a helical FtsZ pattern instead of a Z-ring, accompanied by helical patterns for DivIVA and peptidoglycan synthesis. Strikingly, divIVA deletion suppressed the elongated phenotype of ΔgpsB cells. These data suggest that DivIVA promotes cell elongation and that GpsB counteracts it. Analysis of protein-protein interactions revealed that GpsB and DivIVA do not interact with FtsZ but with the cell division protein EzrA, which itself interacts with FtsZ. In addition, GpsB interacts directly with DivIVA. These results are consistent with DivIVA and GpsB acting as a molecular switch to orchestrate peripheral and septal PG synthesis and connecting them with the Z-ring via EzrA. The cellular co-localization of the transpeptidases PBP2x and PBP2b as well as the lipid-flippases FtsW and RodA in ΔgpsB cells further suggest the existence of a single large PG assembly complex. Finally, we show that GpsB is required for septal localization and kinase activity of StkP, and therefore for StkP-dependent phosphorylation of DivIVA. Altogether, we propose that the StkP/DivIVA/GpsB triad finely tunes the two modes of peptidoglycan (peripheral and septal synthesis responsible for the pneumococcal ellipsoid cell shape.

  1. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell.

    Directory of Open Access Journals (Sweden)

    Luciano Conti

    2005-09-01

    Full Text Available Pluripotent mouse embryonic stem (ES cells multiply in simple monoculture by symmetrical divisions. In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells has proven elusive. Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres. The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated. Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2 and epidermal growth factor (EGF is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS cells. NS cells were derived first from mouse ES cells. Neural lineage induction was followed by growth factor addition in basal culture media. In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic. After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain. Colonies generated from single NS cells all produce neurons upon growth factor withdrawal. NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia. Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain. Similar NS cells can be generated from human ES cells and human foetal brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells. The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying

  2. Bong-Han Corpuscles as Possible Stem Cell Niches on the Organ-Surfaces

    Directory of Open Access Journals (Sweden)

    Min Su Kim

    2008-03-01

    Full Text Available Objectives : Showing that Bong-Han corpuscles(BHC are suppliers of the stem cells in adulthood, and the Bong-Han ducts(BHD are transportation routes of stem cells. Methods : BHC and BHD were obtained from the internal organ-surfaces of rats. The sliced BHC and BHD were immunostained with various stem cell markers. Extracellular matrices were also analyzed by immunohistochemistry. Result : The presence of mesenchymal stem cells was confirmed by the expression of Integrin beta 1, Collagen type 1 and Fibronectin. But CD54 was not expressed. The hematopoietic stem cell marker, Thy 1 was strongly expressed. BHDs showed Collagen type 1, Fibronectin, and vWF expression. Conclusion : Both hematopoietic and mesenchymal stem cell markers were expressed strongly in BHC similarly as in bone marrow. An endothelial cell marker(vWF demonstrated the possibility of the stem cell transportation routes of BHD.

  3. Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics.

    Science.gov (United States)

    Dhaliwal, Anandika; Brenner, Matthew; Wolujewicz, Paul; Zhang, Zheng; Mao, Yong; Batish, Mona; Kohn, Joachim; Moghe, Prabhas V

    2016-11-01

    A predictive framework for the evolution of stem cell biology in 3-D is currently lacking. In this study we propose deep image informatics of the nuclear biology of stem cells to elucidate how 3-D biomaterials steer stem cell lineage phenotypes. The approach is based on high content imaging informatics to capture minute variations in the 3-D spatial organization of splicing factor SC-35 in the nucleoplasm as a marker to classify emergent cell phenotypes of human mesenchymal stem cells (hMSCs). The cells were cultured in varied 3-D culture systems including hydrogels, electrospun mats and salt leached scaffolds. The approach encompasses high resolution 3-D imaging of SC-35 domains and high content image analysis (HCIA) to compute quantitative 3-D nuclear metrics for SC-35 organization in single cells in concert with machine learning approaches to construct a predictive cell-state classification model. Our findings indicate that hMSCs cultured in collagen hydrogels and induced to differentiate into osteogenic or adipogenic lineages could be classified into the three lineages (stem, adipogenic, osteogenic) with ⩾80% precision and sensitivity, within 72h. Using this framework, the augmentation of osteogenesis by scaffold design exerted by porogen leached scaffolds was also profiled within 72h with ∼80% high sensitivity. Furthermore, by employing 3-D SC-35 organizational metrics, differential osteogenesis induced by novel electrospun fibrous polymer mats incorporating decellularized matrix could also be elucidated and predictably modeled at just 3days with high precision. We demonstrate that 3-D SC-35 organizational metrics can be applied to model the stem cell state in 3-D scaffolds. We propose that this methodology can robustly discern minute changes in stem cell states within complex 3-D architectures and map single cell biological readouts that are critical to assessing population level cell heterogeneity. The sustained development and validation of bioactive

  4. Identification of the homing molecules that escort pluripotent stem cells-derived hematopoietic stem cells to their niches and human activated T-cells to inflammatory sites.

    KAUST Repository

    Ali, Amal

    2017-12-01

    Hematopoietic cells exploit the multistep paradigm of cell migration to ultimately enable them to perform their function. This process is dictated by the ability of adhesion molecules on the circulating hematopoietic cells to find their counter-receptors on endothelial cells. Of those molecules, the selectin family and their respective ligands induce the initial transient interactions between circulating cells and the opposing endothelium. In this thesis, I focused on studying E-selectin mediated cellular migration in two hematopoietic cell types, namely human hematopoietic stem and progenitor cells (HSPCs) and human T-lymphocytes. HSPCs derived from pluripotent sources theoretically offers a novel, unlimited source for hematopoietic stem cell transplantation therapy. In vitro pluripotent stem cell derived- hematopoietic stem/progenitor cells (ES/iPS-HSPCs) behave much like somatic HSPCs in that they exhibit clonal expansion and multilineage hematopoietic capacity. However, unlike somatic sources, ES/iPS-HSPCs do not give rise to effective hematopoietic repopulation, which may be due to insufficient HSPCs homing to the bone marrow. HSPCs exploit E- and P-selectin to home and engraft into bone marrow niches. Thus, one of my objectives in this thesis was to study the expression of E-selectin ligands associated with ES/iPS-HSPCs. I showed that ES/iPS-HSPCs lack functional E-selectin ligand(s). In an effort to enhance the interaction between Eselectin and ES/iPS-HSPCs, we decorated the cell surface with sialyl-Lewis x (sLex) using the ex-vivo glycan engineering technology. However, this decoration did not improve the engraftment capacity of ES/iPS-HSPCs, in vivo. Induction of E-selectin expression during inflammation is key to recruitment of immune cells and therefore I also focused on analyzing the expression of E-selectin ligands on activated human T-cells. I identified several novel glycoproteins that may function as E-selectin ligands. Specifically, I compared the

  5. Elucidating the Tumor-Suppressive Role of SLITs in Maintaining the Basal Cell Niche

    Science.gov (United States)

    2011-10-01

    metastasis by inhibiting detachment of tumor cells. Overexpression of SLIT2 in MCF7 cells has been shown to reduce the amount of beta- catenin in the... detachment from the tissue culture plate [59, 60]. These findings suggest that SEMA3F may play a pro-metastatic role by promoting tumor cell detachment ...for SLIT/ROBO4 function based on studies of pathologic angiogenesis in the retina (13). Both in this context and in the mammary gland, there are two

  6. Toxoplasma gondii Development of Its Replicative Niche: in Its Host Cell and Beyond

    Science.gov (United States)

    2014-01-01

    Intracellular pathogens can replicate efficiently only after they manipulate and modify their host cells to create an environment conducive to replication. While diverse cellular pathways are targeted by different pathogens, metabolism, membrane and cytoskeletal architecture formation, and cell death are the three primary cellular processes that are modified by infections. Toxoplasma gondii is an obligate intracellular protozoan that infects ∼30% of the world's population and causes severe and life-threatening disease in developing fetuses, in immune-comprised patients, and in certain otherwise healthy individuals who are primarily found in South America. The high prevalence of Toxoplasma in humans is in large part a result of its ability to modulate these three host cell processes. Here, we highlight recent work defining the mechanisms by which Toxoplasma interacts with these processes. In addition, we hypothesize why some processes are modified not only in the infected host cell but also in neighboring uninfected cells. PMID:24951442

  7. Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche

    Energy Technology Data Exchange (ETDEWEB)

    Katano, Takahito [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Ootani, Akifumi [Department of Gastroenterology and GI Endoscopy Center, Shin-Kokura Hospital, Federation of National Public Service Personnel Mutual Aid Associations, 1-3-1 Kanada, Kokurakita-ku, Kitakyushu 803-0816 (Japan); Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501 (Japan); Mizoshita, Tsutomu, E-mail: tmizoshi@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Tanida, Satoshi; Tsukamoto, Hironobu; Ozeki, Keiji; Ebi, Masahide; Mori, Yoshinori; Kataoka, Hiromi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Toda, Shuji [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501 (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-03-22

    Highlights: ► We established a 3D culture system to allow long-term culture of stomach cells. ► In this culture system, gastric epithelial cells grew for about 3 months. ► The cultured cells differentiated into multi-units of the stomach. ► This culture method should be useful for elucidating the cause of gastric diseases. -- Abstract: Compared to the small intestine and colon, little is known about stem cells in the stomach because of a lack of specific stem cell markers and an in vitro system that allows long-term culture. Here we describe a long-term three-dimensional (3D) primary gastric culture system within the stem cell niche. Glandular stomach cells from neonatal mice cultured in collagen gel yielded expanding sphere-like structures for 3 months. The wall of the gastrospheres consisted of a highly polarized epithelial monolayer with an outer lining of myofibroblasts. The epithelial cells showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm as well as expression of MUC5AC, indicating differentiation into gastric surface mucous cells. These cells demonstrated the features of fully differentiated gastric surface mucous cells such as microvilli, junctional complexes, and glycogen and secretory granules. Fewer than 1% of cultured epithelial cells differentiated into enteroendocrine cells. Active proliferation of the epithelial cells and many apoptotic cells in the inner lumen revealed the rapid cell turnover in gastrospheres in vitro. This method enables us to investigate the role of signaling between cell–cell and epithelial–mesenchymal interactions in an environment that is extremely similar to the in vivo environment.

  8. Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche

    International Nuclear Information System (INIS)

    Katano, Takahito; Ootani, Akifumi; Mizoshita, Tsutomu; Tanida, Satoshi; Tsukamoto, Hironobu; Ozeki, Keiji; Ebi, Masahide; Mori, Yoshinori; Kataoka, Hiromi; Kamiya, Takeshi; Toda, Shuji; Joh, Takashi

    2013-01-01

    Highlights: ► We established a 3D culture system to allow long-term culture of stomach cells. ► In this culture system, gastric epithelial cells grew for about 3 months. ► The cultured cells differentiated into multi-units of the stomach. ► This culture method should be useful for elucidating the cause of gastric diseases. -- Abstract: Compared to the small intestine and colon, little is known about stem cells in the stomach because of a lack of specific stem cell markers and an in vitro system that allows long-term culture. Here we describe a long-term three-dimensional (3D) primary gastric culture system within the stem cell niche. Glandular stomach cells from neonatal mice cultured in collagen gel yielded expanding sphere-like structures for 3 months. The wall of the gastrospheres consisted of a highly polarized epithelial monolayer with an outer lining of myofibroblasts. The epithelial cells showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm as well as expression of MUC5AC, indicating differentiation into gastric surface mucous cells. These cells demonstrated the features of fully differentiated gastric surface mucous cells such as microvilli, junctional complexes, and glycogen and secretory granules. Fewer than 1% of cultured epithelial cells differentiated into enteroendocrine cells. Active proliferation of the epithelial cells and many apoptotic cells in the inner lumen revealed the rapid cell turnover in gastrospheres in vitro. This method enables us to investigate the role of signaling between cell–cell and epithelial–mesenchymal interactions in an environment that is extremely similar to the in vivo environment

  9. Stem cells and tissue niche: two faces of the same coin of muscle regeneration

    Directory of Open Access Journals (Sweden)

    Bianca Maria Scicchitano

    2016-11-01

    Full Text Available Capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program. However, muscle regeneration is severely compromised in several pathological conditions. It is likely that the restricted tissue repair program under pathological conditions is due to either progressive loss of stem cell populations or to missing signals that limit the damaged tissues to efficiently activate a regenerative program. It is therefore plausible that loss of control over these cell fates might lead to a pathological cell transdifferentiation, limiting the ability of a pathological muscle to sustain an efficient regenerative process. The critical role of microenvironment on stem cells activity and muscle regeneration is discussed.

  10. Market survey of fuel cells in Mexico: Niche for low power portable systems

    Science.gov (United States)

    Ramírez-Salgado, Joel; Domínguez-Aguilar, Marco A.

    This work provides an overview of the potential market in Mexico for portable electronic devices to be potentially powered by direct methanol fuel cells. An extrapolation method based on data published in Mexico and abroad served to complete this market survey. A review of electronics consumption set the basis for the future forecast and technology assimilation. The potential market for fuel cells for mobile phones in Mexico will be around 5.5 billion USD by 2013, considering a cost of 41 USD per cell in a market of 135 million mobile phones. Likewise, the market for notebook computers, PDAs and other electronic devices will likely grow in the future, with a combined consumption of fuel cell technology equivalent to 1.6 billion USD by 2014.

  11. GPS & Roadpricing

    DEFF Research Database (Denmark)

    Zabic, Martina

    2005-01-01

    I denne artikel præsenteres analysemetoderne og resultaterne fra et eksamensprojekt omhandlende en analyse af GPS kvaliteten i forhold til roadpricing i København. Denne undersøgelse af GPS kvaliteten i forbindelse med roadpricing, er foretaget i tilknytning til det danske AKTA forsøg (www.......akta-kbh.dk), hvor GPS data er indsamlet for 500 biler over en 2-årig periode (2001-2003). Artiklen præsenterer således en analyse af GPS nøjagtigheden med henblik på at undersøge om kvalitet og pålidelighed er tilstrækkelig, til et GPS-baseret roadpricingssystem i København. Ved GPS-baseret roadpricing, udstyres...... med henblik på enhedsomkostningerne skulle være økonomisk realisable til brug i et så omfattende roadpricingssystem. Endvidere vanskeliggøres positionerings forholdene, idet bilen der ønskes positionsbestemt er i bevægelse. Når både satellitterne og GPS modtageren er i bevægelse, reduceres...

  12. The niche-derived glial cell line-derived neurotrophic factor (GDNF induces migration of mouse spermatogonial stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Lisa Dovere

    Full Text Available In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF, a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.

  13. Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

    Directory of Open Access Journals (Sweden)

    Felipe de Almeida Sassi

    2012-01-01

    Full Text Available Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.

  14. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells

    Science.gov (United States)

    Lehtinen, Maria K.; Zappaterra, Mauro W.; Chen, Xi; Yang, Yawei J.; Hill, Anthony; Lun, Melody; Maynard, Thomas; Gonzalez, Dilenny; Kim, Seonhee; Ye, Ping; D’Ercole, A. Joseph; Wong, Eric T.; LaMantia, Anthony S.; Walsh, Christopher A.

    2011-01-01

    Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions. PMID:21382550

  15. DIABETES IMPAIRS HEMATOPOIETIC STEM CELL MOBILIZATION THROUGH ALTERATION OF NICHE FUNCTION

    Science.gov (United States)

    Ferraro, Francesca; Lymperi, Stefania; Méndez-Ferrer, Simón; Saez, Borja; Spencer, Joel A; Yeap, Beow Y; Masselli, Elena; Graiani, Gallia; Prezioso, Lucia; Rizzini, Elisa Lodi; Mangoni, Marcellina; Rizzoli, Vittorio; Sykes, Stephen M; Lin, Charles P.; Frenette, Paul S.; Quaini, Federico; Scadden, David T.

    2013-01-01

    Autologous hematopoietic stem/progenitor cells (HSPC) transplantation success depends upon adequate cell collection after G-CSF-administration that a substantial fraction of patients fails to achieve. Retrospective analysis of patient records demonstrated that diabetes correlated with lower CD34+ cell mobilization. Using mouse models, we found impaired HSPC egress from the bone marrow in either streptozotocin-induced or db/db diabetic animals. HSPC aberrantly localized within the marrow microenvironment of diabetic animals in association with abnormalities in sympathetic neuron number and function. Markedly increased sympathetic neuron density was accompanied by abnormal response to β-adrenergic stimulation and a failure to generate the G-CSF-induced CXCL12 gradient in nestin-expressing mesenchymal cells associated with HSPC mobilization. Alternative mobilization by direct pharmacologic inhibition of CXCL12-CXCR4 interaction rescued the defect. These data reveal diabetes-induced changes in bone marrow physiology and microanatomy and point to a pathophysiologically based approach to overcome HSPC mobilization defects in diabetic patients. PMID:21998408

  16. Evidence for an intracellular niche for Bordetella pertussis in broncho-alveolar lavage cells of mice

    NARCIS (Netherlands)

    Hellwig, SMM; Hazenbos, WLW; van de Winkel, JGJ; Mooi, FR

    1999-01-01

    Bordetella pertussis can attach, invade and survive intracellularly in human macrophages in vitro. To study the significance of this bacterial feature in vivo, we analyzed the presence of viable bacteria in broncho-alveolar lavage (BAL) cells of mice infected with B, pertussis. We found B. pertussis

  17. Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence

    DEFF Research Database (Denmark)

    Lataillade, J.J.; Pierre-Louis, O.; Uzan, G.

    2008-01-01

    Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable mod...

  18. An epidermal stem cells niche microenvironment created by engineered human amniotic membrane.

    Science.gov (United States)

    Ji, Shi-zhao; Xiao, Shi-chu; Luo, Peng-fei; Huang, Guo-feng; Wang, Guang-yi; Zhu, Shi-hui; Wu, Min-juan; Xia, Zhao-fan

    2011-11-01

    How to amplify epidermal stem cells (ESCs) rapidly is a challenging crux in skin tissue engineering research. The present study describes the preparation of 3D micronized (300-600 μm) amniotic membrane (mAM) by means of repeated freeze-thawing cycles to deplete cell components and homogenized with a macrohomogenizer in liquid nitrogen. This newly prepared mAM not only possessed the characteristics of a microcarrier but completely retained the basement membrane structure and abundant active substances such as NGF, HGF, KGF, bFGF, TGF-β1 and EGF in the AM matrix. The result showed that mAM combined with rotary cell culture system (RCCS) was able to amplify ESCs quickly. The relative cell viability at day 7 and 14 was significantly higher than that of the conventional 2D plate culture (326 ± 28% and 535 ± 47% versus 232 ± 21% and 307 ± 32%, P human body favorable for ex vivo culture and amplification of ESCs but can be used as the dermal scaffold in constructing a skin substitute containing ESCs for the repair of full-thickness skin defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Global Remodeling of the Vascular Stem Cell Niche in Bone Marrow of Diabetic Patients

    Science.gov (United States)

    Spinetti, Gaia; Cordella, Daniela; Fortunato, Orazio; Sangalli, Elena; Losa, Sergio; Gotti, Ambra; Carnelli, Franco; Rosa, Francesco; Riboldi, Stefano; Sessa, Fausto; Avolio, Elisa; Beltrami, Antonio Paolo; Emanueli, Constanza; Madeddu, Paolo

    2013-01-01

    Rationale The impact of diabetes mellitus on bone marrow (BM) structure is incompletely understood. Objective Investigate the effect of type-2 diabetes mellitus (T2DM) on BM microvascular and hematopoietic cell composition in patients without vascular complications. Methods and Results Bone samples were obtained from T2DM patients and nondiabetic controls (C) during hip replacement surgery and from T2DM patients undergoing amputation for critical limb ischemia. BM composition was assessed by histomorphometry, immunostaining, and flow cytometry. Expressional studies were performed on CD34pos immunosorted BM progenitor cells (PCs). Diabetes mellitus causes a reduction of hematopoietic tissue, fat deposition, and microvascular rarefaction, especially when associated with critical limb ischemia. Immunohistochemistry documented increased apoptosis and reduced abundance of CD34pos-PCs in diabetic groups. Likewise, flow cytometry showed scarcity of BM PCs in T2DM and T2DM+critical limb ischemia compared with C, but similar levels of mature hematopoietic cells. Activation of apoptosis in CD34pos-PCs was associated with upregulation and nuclear localization of the proapoptotic factor FOXO3a and induction of FOXO3a targets, p21 and p27kip1. Moreover, microRNA-155, which regulates cell survival through inhibition of FOXO3a, was downregulated in diabetic CD34pos-PCs and inversely correlated with FOXO3a levels. The effect of diabetes mellitus on anatomic and molecular end points was confirmed when considering background covariates. Furthermore, exposure of healthy CD34pos-PCs to high glucose reproduced the transcriptional changes induced by diabetes mellitus, with this effect being reversed by forced expression of microRNA-155. Conclusions We provide new anatomic and molecular evidence for the damaging effect of diabetes mellitus on human BM, comprising microvascular rarefaction and shortage of PCs attributable to activation of proapoptotic pathway. PMID:23250986

  20. Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells

    Directory of Open Access Journals (Sweden)

    Giacomo Palazzolo

    2016-01-01

    Full Text Available The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs. We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C, known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis.

  1. Metabolic diversity and ecological niches of Achromatium populations revealed with single-cell genomic sequencing

    Directory of Open Access Journals (Sweden)

    Muammar eMansor

    2015-08-01

    Full Text Available Large, sulfur-cycling, calcite-precipitating bacteria in the genus Achromatium represent a significant proportion of bacterial communities near sediment-water interfaces throughout the world. Our understanding of their potentially crucial roles in calcium, carbon, sulfur, nitrogen, and iron cycling is limited because they have not been cultured or sequenced using environmental genomics approaches to date. We utilized single-cell genomic sequencing to obtain one incomplete and two nearly complete draft genomes for Achromatium collected at Warm Mineral Springs, FL. Based on 16S rRNA gene sequences, the three cells represent distinct and relatively distant Achromatium populations (91-92% identity. The draft genomes encode key genes involved in sulfur and hydrogen oxidation; oxygen, nitrogen and polysulfide respiration; carbon and nitrogen fixation; organic carbon assimilation and storage; chemotaxis; twitching motility; antibiotic resistance; and membrane transport. Known genes for iron and manganese energy metabolism were not detected. The presence of pyrophosphatase and vacuolar (V-type ATPases, which are generally rare in bacterial genomes, suggests a role for these enzymes in calcium transport, proton pumping, and/or energy generation in the membranes of calcite-containing inclusions.

  2. The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.

    Directory of Open Access Journals (Sweden)

    Berna C Özdemir

    Full Text Available The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism, where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction. The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse from the cancer cell (human transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B. As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST. Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1 seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction

  3. GPS Composite Clock Analysis

    OpenAIRE

    Wright, James R.

    2008-01-01

    The GPS composite clock defines GPS time, the timescale used today in GPS operations. GPS time is illuminated by examination of its role in the complete estimation and control problem relative to UTC/TAI. The phase of each GPS clock is unobservable from GPS pseudorange measurements, and the mean phase of the GPS clock ensemble (GPS time) is unobservable. A new and useful observability definition is presented, together with new observability theorems, to demonstrate explicitly that GPS time is...

  4. Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.

    Science.gov (United States)

    Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa

    2017-10-01

    Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

  5. 3D Printed Structures Filled with Carbon Fibers and Functionalized with Mesenchymal Stem Cell Conditioned Media as In Vitro Cell Niches for Promoting Chondrogenesis

    Directory of Open Access Journals (Sweden)

    Josefa Predestinación García-Ruíz

    2017-12-01

    Full Text Available In this study, we present a novel approach towards the straightforward, rapid, and low-cost development of biomimetic composite scaffolds for tissue engineering strategies. The system is based on the additive manufacture of a computer-designed lattice structure or framework, into which carbon fibers are subsequently knitted or incorporated. The 3D-printed lattice structure acts as support and the knitted carbon fibers perform as driving elements for promoting cell colonization of the three-dimensional construct. A human mesenchymal stem cell (h-MSC conditioned medium (CM is also used for improving the scaffold’s response and promoting cell adhesion, proliferation, and viability. Cell culture results—in which scaffolds become buried in collagen type II—provide relevant information regarding the viability of the composite scaffolds used and the prospective applications of the proposed approach. In fact, the advanced composite scaffold developed, together with the conditioned medium functionalization, constitutes a biomimetic stem cell niche with clear potential, not just for tendon and ligament repair, but also for cartilage and endochondral bone formation and regeneration strategies.

  6. Microprinted Stem Cell Niches Reveal Compounding Effect of Colony Size on Stromal Cells-Mediated Neural Differentiation.

    Science.gov (United States)

    Joshi, Ramila; Thakuri, Pradip Shahi; Buchanan, James C; Li, Jun; Tavana, Hossein

    2018-03-01

    Microenvironmental factors have a major impact on differentiation of embryonic stem cells (ESCs). Here, a novel phenomenon that size of ESC colonies has a significant regulatory role on stromal cells induced differentiation of ESCs to neural cells is reported. Using a robotic cell microprinting technology, defined densities of ESCs are confined within aqueous nanodrops over a layer of supporting stromal cells immersed in a second, immiscible aqueous phase to generate ESC colonies of defined sizes. Temporal protein and gene expression studies demonstrate that larger ESC colonies generate disproportionally more neural cells and longer neurite processes. Unlike previous studies that attribute neural differentiation of ESCs solely to interactions with stromal cells, it is found that increased intercellular signaling of ESCs significantly enhances neural differentiation. This study offers an approach to generate neural cells with improved efficiency for potential use in translational research. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Temporally and spatially dynamic germ cell niches in Botryllus schlosseri revealed by expression of a TGF-beta family ligand and vasa

    Directory of Open Access Journals (Sweden)

    Adam D. Langenbacher

    2016-04-01

    Full Text Available Abstract Background Germ cells are specified during early development and are responsible for generating gametes in the adult. After germ cells are specified, they typically migrate to a particular niche in the organism where they reside for the remainder of its lifetime. For some model organisms, the specification and migration of germ cells have been extensively studied, but how these events occur in animals that reproduce both sexually and asexually is not well understood. Results We have identified a novel TGF-β family member in Botryllus schlosseri, tgfβ-f, and found that it is expressed by follicle cell progenitors and the differentiated follicle and support cells surrounding the maturing gametes. Using the expression of tgfβ-f and the germ cell marker vasa, we have found that nearly all germ cells in Botryllus are associated with tgfβ-f-expressing follicle progenitors in clusters consisting solely of those two cell types. These clusters were mostly small, consisting of ten or fewer cells, and generally contained between a 2:1 and 1:1 ratio of follicle progenitors to germ cells. Clusters of germ and follicle progenitor cells were primarily localized to niches in the primary and secondary buds, but could also be found in other locations including the vasculature. We analyzed the location of germ cell clusters throughout the asexual life cycle of Botryllus and found that at the stage when germ cells are first detected in the secondary bud niche, a dramatic change in the size and location of germ/follicle cell clusters also occurred. Conclusions Our findings suggest that germ/follicle cell clusters have predictable migratory patterns during the weekly asexual developmental cycle in Botryllus. An increased number of small clusters and the presence of clusters in the vasculature coinciding with the appearance of clusters in the secondary bud suggest that fragmentation of clusters and the migration of smaller clusters through the vasculature

  8. Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor-Initiating Cells

    Science.gov (United States)

    2011-04-01

    been suggested that bTICs are the cells within tumors with metastatic potential and the ability to “ seed ” in distant organs [16-18]. Therefore, the...breast cancer stem cells in metastasis, given their innate dormant state and ability to proliferate and differentiate upon activation [11,16...implications in recurrence and metastatic latency , the mechanisms contributing to breast cancer dormancy remain poorly understood [34-36]. Current

  9. Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor Initiating Cells

    Science.gov (United States)

    2013-06-01

    Department of Ecology and Evolution Temporary Laboratory Technician Responsibilities: - Preparation of plasmids - Sequencing various bacterial genes...compen- sate for a high proliferation of the tumor cells. Alterna- tively, this disruption in homeostasis may occur as a later event during tumor...Robinson AE, Kale S, Long MW, Chen J (2003) Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 102: 1249

  10. Niche matters: The comparison between bone marrow stem cells and endometrial stem cells and stromal fibroblasts reveal distinct migration and cytokine profiles in response to inflammatory stimulus.

    Directory of Open Access Journals (Sweden)

    Masuma Khatun

    Full Text Available Intrinsic inflammatory characteristics play a pivotal role in stem cell recruitment and homing through migration where the subsequent change in niche has been shown to alter these characteristics. The bone marrow mesenchymal stem cells (bmMSCs have been demonstrated to migrate to the endometrium contributing to the stem cell reservoir and regeneration of endometrial tissue. Thus, the aim of the present study was to compare the inflammation-driven migration and cytokine secretion profile of human bmMSCs to endometrial mesenchymal stem cells (eMSCs and endometrial fibroblasts (eSFs.The bmMSCs were isolated from bone marrow aspirates through culturing, whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their surface marker, proliferation profiles and migration properties towards serum and inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets was analysed in each cell type at basal level along with lipopolysaccharide (LPS-induced state.Both stem cell types, bmMSCs and eMSCs, presented with similar stem cell surface marker profiles as well as possessed high proliferation and migration potential compared to eSFs. In multiplex assays, the secretion of 16 cytokine targets was detected and LPS stimulation expanded the cytokine secretion pattern by triggering the secretion of several targets. The bmMSCs exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF-A, stromal cell-derived factor-1 alpha (SDF-1α, interleukin-1 receptor antagonist (IL-1RA, IL-6, interferon-gamma inducible protein (IP-10, monocyte chemoattractant protein (MCP-1, macrophage inflammatory protein (MIP1α and RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8 secretion was higher in both endometrial cell types compared to bmMSCs.Our results highlight that similar to bmMSCs, the eMSCs possess high migration activity while the differentiation process towards stromal fibroblasts seemed

  11. Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice.

    Science.gov (United States)

    Mihalj, Martina; Kellermayer, Zoltán; Balogh, Peter

    2013-07-01

    Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular Th cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-β receptor antagonist treatment slightly reduced TFH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of TFH cells of the memory phenotype, thus allowing their escape during T-cell depletion.

  12. GPS for land surveyors

    CERN Document Server

    Van Sickle, Jan

    2008-01-01

    The GPS SignalGlobal Positioning System (GPS) Signal StructureTwo ObservablesPseudorangingCarrier Phase RangingBiases and SolutionsThe Error BudgetDifferencingThe FrameworkTechnological ForerunnersVery Long Baseline InterferometryTransitNavstar GPSGPS Segment OrganizationGPS ConstellationThe Control SegmentReceivers and MethodsCommon Features of GPS ReceiversChoosing a GPS ReceiverSome GPS Surveying MethodsCoordinatesA Few Pertinent Ideas About Geodetic Datums for GPSState Plane CoordinatesHeightsGPS Surveying TechniquesStatic GPS SurveyingReal-Time Kinematic (RTK) and Differential GPS (DGPS)T

  13. The zebrafish flotte lotte mutant reveals that the local retinal environment promotes the differentiation of proliferating precursors emerging from their stem cell niche.

    Science.gov (United States)

    Cerveny, Kara L; Cavodeassi, Florencia; Turner, Katherine J; de Jong-Curtain, Tanya A; Heath, Joan K; Wilson, Stephen W

    2010-07-01

    It is currently unclear how intrinsic and extrinsic mechanisms cooperate to control the progression from self-renewing to neurogenic divisions in retinal precursor cells. Here, we use the zebrafish flotte lotte (flo) mutant, which carries a mutation in the elys (ahctf1) gene, to study the relationship between cell cycle progression and neuronal differentiation by investigating how proliferating progenitor cells transition towards differentiation in a retinal stem cell niche termed the ciliary marginal zone (CMZ). In zebrafish embryos without Elys, CMZ cells retain the capacity to proliferate but lose the ability to enter their final neurogenic divisions to differentiate as neurons. However, mosaic retinae composed of wild-type and flo cells show that despite inherent cell cycle defects, flo mutant cells progress from proliferation to differentiation when in the vicinity of wild-type retinal neurons. We propose that the differentiated retinal environment limits the proliferation of precursors emerging from the CMZ in a manner that explains the spatial organisation of cells in the CMZ and ensures that proliferative retinal progenitors are driven towards differentiation.

  14. Peritoneal milky spots serve as a hypoxic niche and favor gastric cancer stem/progenitor cell peritoneal dissemination through hypoxia-inducible factor 1α.

    Science.gov (United States)

    Miao, Zhi-Feng; Wang, Zhen-Ning; Zhao, Ting-Ting; Xu, Ying-Ying; Gao, Jian; Miao, Feng; Xu, Hui-Mian

    2014-12-01

    Peritoneal dissemination is the most common cause of death in gastric cancer patients. The hypoxic microenvironment plays a major role in controlling the tumor stem cell phenotype and is associated with patients' prognosis through hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor that responds to hypoxic stimuli. During the peritoneal dissemination process, gastric cancer stem/progenitor cells (GCSPCs) are thought to enter into and maintained in peritoneal milky spots (PMSs), which have hypoxic microenvironments. However, the mechanism through which the hypoxic environment of PMSs regulated GCSPC maintenance is still poorly understood. Here, we investigated whether hypoxic PMSs were an ideal cancer stem cell niche suitable for GCSPC engraftment. We also evaluated the mechanisms through which the HIF-1α-mediated hypoxic microenvironment regulated GCSPC fate. We observed a positive correlation between HIF-1α expression and gastric cancer peritoneal dissemination (GCPD) in gastric cancer patients. Furthermore, the GCSPC population expanded in primary gastric cancer cells under hypoxic condition in vitro, and hypoxic GCSPCs showed enhanced self-renewal ability, but reduced differentiation capacity, mediated by HIF-1α. In an animal model, GCSPCs preferentially resided in the hypoxic zone of PMSs; moreover, when the hypoxic microenvironment in PMSs was destroyed, GCPD was significantly alleviated. In conclusion, our results demonstrated that PMSs served as a hypoxic niche and favored GCSPCs peritoneal dissemination through HIF-1α both in vitro and in vivo. These results provided new insights into the GCPD process and may lead to advancements in the clinical treatment of gastric cancer. © 2014 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  15. [Ecological niches of ectoparasites].

    Science.gov (United States)

    Balashov, Iu S

    2005-01-01

    On mammals and birds communities of ectoparasites are present, which can include scores of ticks, mites and insects species. The parasitizing of arthropods terrestrial vertebrates appeared as far back a the Cretaceous period, and after 70-100 mil. years of the coevolution ectoparasites have assimilated all food resources and localities of the hosts' bodies. To the present only spatial and (to the less extent) trophic niches of parasitic insects, ticks and mites are studied completely enough. The main results these investigations are discussed in the present paper. A high abundance of the communities is reached because of their partition into the number of ecological niches. Host is complex of ecological niches for many ectoparasites species. These niches reiterate in the populations of a species closely related species of hosts and repeat from generation to generation. The each part of host (niche) being assimilated be certain parasite species is available potentially for other species. The partition of host into ecological niches is clearer than the structure of ecosystems including free-living organisms. A real extent of the ecological niches occupation by different species of ticks, mites and insects is considerably lower than a potential maximum. The degree of ecological niches saturation depends on the history of the coevolution of parasites community components, previous colonization be new ectoparasite species and many other ecological factors affecting host-parasite system. The use of the ecological niche conception in parasitology is proved to be rather promising. Ectoparasites communities because of their species diversity, different types of feeding and a number of habitats on host represent convenient models and study of them can contribute significantly to the developmeht of the general conception of ecological niche.

  16. Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche.

    Science.gov (United States)

    Kobolak, Julianna; Dinnyes, Andras; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Ali

    2016-04-15

    Mesenchymal stem cells (MSCs) are multipotent stem cells. Although they were originally identified in bone marrow and described as 'marrow stromal cells', they have since been identified in many other anatomical locations in the body. MSCs can be isolated from bone marrow, adipose tissue, umbilical cord and other tissues but the richest tissue source of MSCs is fat. Since they are adherent to plastic, they may be expanded in vitro. MSCs have a distinct morphology and express a specific set of CD (cluster of differentiation) molecules. The phenotypic pattern for the identification of MSCs cells requires expression of CD73, CD90, and CD105 and lack of CD34, CD45, and HLA-DR antigens. Under appropriate micro-environmental conditions MSCs can proliferate and give rise to other cell types. Therefore, they are ideally suited for the treatment of systemic inflammatory and autoimmune conditions. They have also been implicated as key players in regenerating injured tissue following injury and trauma. MSC populations isolated from adipose tissue may also contain regulatory T (Treg) cells, which have the capacity for modulating the immune system. The immunoregulatory and regenerative properties of MSCs make them ideal for use as therapeutic agents in vivo. In this paper we review the literature on the identification, phenotypic characterization and biological properties of MSCs and discuss their potential for applications in cell therapy and regenerative medicine. We also discuss strategies for biomaterial micro-engineering of the stem cell niche. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. CXCR4+ CD45- Cells are Niche Forming for Osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 Signaling Pathways in Bone Marrow.

    Science.gov (United States)

    Goto, Yoh; Aoyama, Mineyoshi; Sekiya, Takeo; Kakita, Hiroki; Waguri-Nagaya, Yuko; Miyazawa, Ken; Asai, Kiyofumi; Goto, Shigemi

    2016-11-01

    Bone homeostasis comprises the balance between bone-forming osteoblasts and bone-resorbing osteoclasts (OCs), with an acceleration of osteoclastic bone resorption leading to osteoporosis. OCs can be generated from bone marrow cells (BMCs) under the tightly regulated local bone environment. However, it remained difficult to identify the critical cells responsible for providing an osteoclastogenesis niche. In this study, we used a fluorescence-activated cell sorting technique to determine the cell populations important for forming an appropriate microenvironment for osteoclastogenesis and to verify the associated interactions between osteoclast precursor cells and non-OCs. We isolated and removed a small cell population specific for osteoclastogenesis (CXCR4 + CD45 - ) from mouse BMCs and cultured the remaining cells with receptor activator of nuclear factor-kappa B ligand (RANKL) and macrophage-colony stimulating factor. The resulting cultures showed significantly less large osteoclast formation. Quantitative RT-PCR analysis revealed that these CXCR4 + CD45 - cells expressed low levels of RANK and RANKL, but high levels of critical chemokines including stromal cell derived factor 1 (SDF-1), chemokine (C-X-C motif) ligand 7 (CXCL7), and chemokine (C-X3-C motif) ligand 1 (CX3CL1). Furthermore, an SDF-1-specific antibody strongly suppressed OC formation in RAW264.7 cells and antibodies against SDF-1, CXCL7, and CX3CL1 suppressed OC formation in BMCs. These results suggest that isolated CXCR4 + CD45 - cells support an appropriate microenvironment for osteoclastogenesis with a direct effect on the cells expressing SDF-1, CXCL7, and CX3CL1 receptors. The regulation of CXCR4 + CD45 - cell function might therefore inform therapeutic strategies for diseases involving loss of bone homeostasis. Stem Cells 2016;34:2733-2743. © 2016 AlphaMed Press.

  18. Differentiation and Protective Capacity of Virus-Specific CD8+T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche.

    Science.gov (United States)

    Tomov, Vesselin T; Palko, Olesya; Lau, Chi Wai; Pattekar, Ajinkya; Sun, Yuhang; Tacheva, Ralitza; Bengsch, Bertram; Manne, Sasikanth; Cosma, Gabriela L; Eisenlohr, Laurence C; Nice, Timothy J; Virgin, Herbert W; Wherry, E John

    2017-10-17

    Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8 + T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8 + T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased to detect virus within 72 hours of challenge, demonstrating rapid sequestration of viral replication away from T cells. Our studies revealed a strategy of immune evasion by MNV via the induction of a CD8 + T cell program normally reserved for latent pathogens and persistence in an immune-privileged enteric niche. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Extracellular Vesicles within the Bone Marrow Niche : A novel way of communication between osteoblasts and hematopoietic progenitor cells

    NARCIS (Netherlands)

    J. Morhayim (Jess)

    2016-01-01

    markdownabstractCell-to-cell communication plays an essential role in regulating homeostasis in multicellular organisms. Recent evidence indicates that cells effectively communicate via extracellular vesicles (EVs), which carry bioactive cargo, such as proteins, lipids and RNA, between cells.

  20. Loss of Sfrp2 in the Niche Amplifies Stress-Induced Cellular Responses, and Impairs the In Vivo Regeneration of the Hematopoietic Stem Cell Pool.

    Science.gov (United States)

    Ruf, Franziska; Schreck, Christina; Wagner, Alina; Grziwok, Sandra; Pagel, Charlotta; Romero, Sandra; Kieslinger, Matthias; Shimono, Akihiko; Peschel, Christian; Götze, Katharina S; Istvanffy, Rouzanna; Oostendorp, Robert A J

    2016-09-01

    Sfrp2 is overexpressed in stromal cells which maintain hematopoietic stem cells (HSCs) during in vitro culture. We here showed, that coculture of hematopoetic cells with stromal cells with reduced expression of Sfrp2 increases the number lineage-negative Kit(+) Sca-1(+) (LSK) and progenitor cells in vitro. The LSK cells from these cocultures showed activation of canonical Wnt signaling, higher levels of Ki-67, BrdU incorporation, and the number of γH2A.X positive foci. Total repopulating activity of these cultures was, however, diminished, indicating loss of HSC. To extend these in vitro data, we modelled stress in vivo, i.e., by aging, or 5-FU treatment in Sfrp2(-) (/) (-) mice, or replicative stress in regeneration of HSCs in Sfrp2(-) (/) (-) recipients. In all three in vivo stress situations, we noted an increase of LSK cells, characterized by increased levels of β-catenin and cyclin D1. In the transplantation experiments, the increase in LSK cells in primary recipients was subsequently associated with a progressive loss of HSCs in serial transplantations. Similar to the in vitro coculture stress, in vivo genotoxic stress in 5-FU-treated Sfrp2(-) (/) (-) mice increased cell cycle activity of LSK cells with higher levels of BrdU incorporation, increased expression of Ki-67, and canonical Wnt signaling. Importantly, as noted in vitro, increased cycling of LSKs in vivo was accompanied by a defective γH2A.X-dependent DNA damage response and depolarized localization of acetylated H4K16. Our experiments support the view that Sfrp2 expression in the niche is required to maintain the HSC pool by limiting stress-induced DNA damage and attenuating canonical Wnt-mediated HSC activation. Stem Cells 2016;34:2381-2392. © 2016 AlphaMed Press.

  1. Niche similarities among introduced and native mountain ungulates.

    Science.gov (United States)

    Lowrey, B; Garrott, R A; McWhirter, D E; White, P J; DeCesare, N J; Stewart, S T

    2018-03-24

    The niche concept provides a strong foundation for theoretical and applied research among a broad range of disciplines. When two ecologically similar species are sympatric, theory predicts they will occupy distinct ecological niches to reduce competition. Capitalizing on the increasing availability of spatial data, we built from single species habitat suitability models to a multispecies evaluation of the niche partitioning hypothesis with sympatric mountain ungulates - native bighorn sheep (BHS; Ovis canadensis) and introduced mountain goats (MTG; Oreamnos americanus) in the northeast Greater Yellowstone Area. We characterized seasonal niches using two-stage resource selection functions with a used-available design and descriptive summaries of the niche attributes associated with used GPS locations. We evaluated seasonal similarity in niche space according to confidence interval overlap of model coefficients and similarity in geographic space by comparing model predicted values with Schoener's D metric. Our sample contained 37,962 summer locations from 53 individuals (BHS = 31, MTG = 22), and 79,984 winter locations from 57 individuals (BHS = 35, MTG = 22). Slope was the most influential niche component for both species and seasons, and showed the strongest evidence of niche partitioning. Bighorn sheep occurred on steeper slopes than mountain goats in summer and mountain goats occurred on steeper slopes in winter. The pattern of differential selection among species was less prevalent for the remaining covariates, indicating similarity in niche space. Model predictions in geographic space showed broad seasonal similarity (summer D = 0.88, winter D = 0.87), as did niche characterizations from used GPS locations. The striking similarities in seasonal niches suggest that introduced mountain goats will continue to increase their spatial overlap with native bighorn. Our results suggest that reducing densities of mountain goats in hunted areas where they are sympatric

  2. Runaway cultural niche construction

    Science.gov (United States)

    Rendell, Luke; Fogarty, Laurel; Laland, Kevin N.

    2011-01-01

    Cultural niche construction is a uniquely potent source of selection on human populations, and a major cause of recent human evolution. Previous theoretical analyses have not, however, explored the local effects of cultural niche construction. Here, we use spatially explicit coevolutionary models to investigate how cultural processes could drive selection on human genes by modifying local resources. We show that cultural learning, expressed in local niche construction, can trigger a process with dynamics that resemble runaway sexual selection. Under a broad range of conditions, cultural niche-constructing practices generate selection for gene-based traits and hitchhike to fixation through the build up of statistical associations between practice and trait. This process can occur even when the cultural practice is costly, or is subject to counteracting transmission biases, or the genetic trait is selected against. Under some conditions a secondary hitchhiking occurs, through which genetic variants that enhance the capability for cultural learning are also favoured by similar dynamics. We suggest that runaway cultural niche construction could have played an important role in human evolution, helping to explain why humans are simultaneously the species with the largest relative brain size, the most potent capacity for niche construction and the greatest reliance on culture. PMID:21320897

  3. Dual-label flow cytometry-based host cell adhesion assay to ascertain the prospect of probiotic Lactobacillus plantarum in niche-specific antibacterial therapy.

    Science.gov (United States)

    Mukherjee, Sandipan; Ramesh, Aiyagari

    2017-12-01

    Host cell adhesion assays that provide quantitative insight on the potential of lactic acid bacteria (LAB) to inhibit adhesion of intestinal pathogens can be leveraged for the development of niche-specific anti-adhesion therapy. Herein, we report a dual-colour flow cytometry (FCM) analysis to assess the ability of probiotic Lactobacillus plantarum strains to impede adhesion of Enterococcus faecalis, Listeria monocytogenes and Staphylococcus aureus onto HT-29 cells. FCM in conjunction with a hierarchical cluster analysis could discern the anti-adhesion potential of L. plantarum strains, wherein the efficacy of L. plantarum DF9 was on a par with the probiotic L. rhamnosus GG. Combination of FCM with principal component analysis illustrated the relative influence of LAB strains on adhesion parameters kd and em of the pathogen and identified probiotic LAB suitable for anti-adhesion intervention. The analytical merit of the FCM analysis was captured in host cell adhesion assays that measured relative elimination of adhered LAB vis-à-vis pathogens, on exposure to either LAB bacteriocins or therapeutic antibiotics. It is envisaged that the dual-colour FCM-based adhesion assay described herein would enable a fundamental understanding of the host cell adhesion process and stimulate interest in probiotic LAB as safe anti-adhesion therapeutic agents against gastrointestinal pathogens.

  4. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Beck, Mette

    2015-01-01

    , decreased vessel density and inhibition of metastases. CONCLUSION: The S100A4 blocking antibody (6B12) reduces tumor growth and metastasis in a model of spontaneous breast cancer. The 6B12 antibody treatment inhibits T cell accumulation at the primary and pre-metastatic tumor sites. The 6B12 antibody acts......BACKGROUND: The tumor microenvironment plays a determinative role in stimulating tumor progression and metastasis. Notably, tumor-stroma signals affect the pattern of infiltrated immune cells and the profile of tumor-released cytokines. Among the known molecules that are engaged in stimulating...... the metastatic spread of tumor cells is the S100A4 protein. S100A4 is known as an inducer of inflammatory processes and has been shown to attract T-cells to the primary tumor and to the pre-metastatic niche. The present study aims to examine the immunomodulatory role of S100A4 in vivo and in vitro and assess...

  5. Association of TGFβ signaling with the maintenance of a quiescent stem cell niche in human oral mucosa.

    Science.gov (United States)

    Andl, Claudia D; Le Bras, Grégoire F; Loomans, Holli; Kim, Annette S; Zhou, Linli; Zhang, Yuhang; Andl, Thomas

    2016-11-01

    A dogma in squamous epithelial biology is that proliferation occurs in the basal cell layer. Notable exceptions are squamous epithelia of the human oral cavity, esophagus, ectocervix, and vagina. In these human epithelia, proliferation is rare in the basal cell layer, and the vast majority of cells positive for Ki67 and other proliferation markers are found in para- and suprabasal cell layers. This unique human feature of a generally quiescent basal cell layer overlaid by highly proliferative cells offers the rare opportunity to study the molecular features of undifferentiated, quiescent, putative stem cells in their natural context. Here, we show that the quiescent human oral mucosa basal cell layer expresses putative markers of stemness, while para- and suprabasal cells are characterized by cell cycle genes. We identified a TGFβ signature in this quiescent basal cell layer. In in vitro organotypic cultures, human keratinocytes could be induced to express markers of these quiescent basal cells when TGFβ signaling is activated. The study suggests that the separation of basal cell layer and proliferation in human oral mucosa may function to accommodate high proliferation rates and the protection of a quiescent reserve stem cell pool. Psoriasis, an epidermal inflammatory hyperproliferative disease, exhibits features of a quiescent basal cell layer mimicking normal oral mucosa. Our data indicate that structural changes in the organization of epithelial proliferation could contribute to longevity and carcinogenesis.

  6. Reduced Latency in the Metastatic Niche Contributes to the More Aggressive Phenotype of LM8 Compared to Dunn Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Matthias J. E. Arlt

    2013-01-01

    Full Text Available Metastasis is the major cause of death of osteosarcoma patients and its diagnosis remains difficult. In preclinical studies, however, forced expression of reporter genes in osteosarcoma cells has remarkably improved the detection of micrometastases and, consequently, the quality of the studies. We recently showed that Dunn cells equipped with a lacZ reporter gene disseminated from subcutaneous primary tumors as frequently as their highly metastatic subline LM8, but only LM8 cells grew to macrometastases. In the present time-course study, tail-vein-injected Dunn and LM8 cells settled within 24 h at the same frequency in the lung, liver, and kidney of mice. Furthermore, Dunn cells also grew to macrometastases, but, compared to LM8, with a delay of two weeks in lung and one week in liver and kidney tissue, consistent with prolonged survival of the mice. Dunn- and LM8-cell-derived ovary and spine metastases occurred less frequently. In vitro, Dunn cells showed less invasiveness and stronger contact inhibition and intercellular adhesion than LM8 cells and several cancer- and dormancy-related genes were differentially expressed. In conclusion, Dunn cells, compared to LM8, have a similar capability but a longer latency to form macrometastases and provide an interesting new experimental system to study tumor cell dormancy.

  7. Studying Niche Colonization and the Dynamics of Imprint Erasure During In Vitro Acquisition of Pluripotency in Germ Cells

    OpenAIRE

    Oliveros, Marisabel

    2014-01-01

    Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. Scalable in vitro differentiation of PGCs from pluripotent cell types has emerged as a model to study PGC biology. The in vitro PGCs (iPGCs) obtained from ESCs through the embryoid body (EB) differentiation method correspond to a pregonadal stage of PGC development. Thus, extending the applications of this model to the study of more developmentally advanced germ cells requires maturation of iPGCs to different develop...

  8. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

    Directory of Open Access Journals (Sweden)

    Maria Akhmanova

    2015-01-01

    Full Text Available Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity, viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement, and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems.

  9. LNG niche market development

    NARCIS (Netherlands)

    Beata Kviatek

    2011-01-01

    Project focusing on developing a public affairs advice for the corporate business case aiming at development of LNG niche market. The advice is based on research in five areas: (1) an overview of existent regulatory framework with regard to the use of LNG in a small scale market in the EU and

  10. GPS Satellite Simulation Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The GPS satellite simulation facility consists of a GPS satellite simulator controlled by either a Silicon Graphics Origin 2000 or PC depending upon unit under test...

  11. Effect of extracellular matrix on bovine spermatogonial stem cells and gene expression of niche factors regulating their development in vitro.

    Science.gov (United States)

    Akbarinejad, V; Tajik, P; Movahedin, M; Youssefi, R; Shafiei, S; Mazaheri, Z

    2015-06-01

    Extracellular matrix (ECM) could influence cells function through providing structural and functional networks facilitating the cellular interactions. The present study was conducted to evaluate the effect of culture on ECM versus plastic on bovine spermatogonial stem cells (SSCs) and growth factors regulating their development. Following isolation, bovine testicular cells were cultured on ECM-coated or uncoated (control) plates for 12 days. The colonization of SSCs was assessed by inverted microscope and the gene expression was evaluated using quantitative real-time PCR. The colonization rate was greater in ECM than the control group (P<0.05). The expression of markers of undifferentiated spermatogonia increased in response to conventional culture (P<0.05). Conversely, the expression of ckit as a marker for differentiated spermatogonia was reduced following culture in the control and ECM groups (P<0.05), but this decrease was less in ECM group (P<0.05). Accordingly, while cells cultured on uncoated plates had greater expression of markers of undifferentiated spermatogonia (P<0.05), cells cultured on ECM-coated plates showed higher expression of ckit (P<0.05). Moreover, culture on ECM resulted in higher expression of kit ligand (Kitlg; P<0.05), whereas culture on plastic led to greater expression of glial cell line-derived neurotrophic factor (Gdnf; P<0.05). In conclusion, the present study revealed that the permissive effect of ECM on bovine SSCs differentiation in vitro, which was probably mediated through upregulation of KITLG expression. Moreover, the results imply that GDNF might contribute to germ cells self-renewal during conventional culture. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Therapeutic strategy for hair regeneration: Hair cycle activation, niche environment modulation, wound-induced follicle neogenesis and stem cell engineering

    Science.gov (United States)

    Chueh, Shan-Chang; Lin, Sung-Jan; Chen, Chih-Chiang; Lei, Mingxing; Wang, Ling Mei; Widelitz, Randall B.; Hughes, Michael W.; Jiang, Ting-Xing; Chuong, Cheng Ming

    2013-01-01

    Introduction There are major new advancements in the fields of stem cell biology, developmental biology, regenerative hair cycling, and tissue engineering. The time is ripe to integrate, translate and apply these findings to tissue engineering and regenerative medicine. Readers will learn about new progress in cellular and molecular aspects of hair follicle development, regeneration and potential therapeutic opportunities these advances may offer. Areas covered Here we use hair follicle formation to illustrate this progress and to identify targets for potential strategies in therapeutics. Hair regeneration is discussed in four different categories. (1) Intra-follicle regeneration (or renewal) is the basic production of hair fibers from hair stem cells and dermal papillae in existing follicles. (2) Chimeric follicles via epithelial-mesenchymal recombination to identify stem cells and signaling centers. (3) Extra-follicular factors including local dermal and systemic factors can modulate the regenerative behavior of hair follicles, and may be relatively easy therapeutic targets. (4) Follicular neogenesis means the de novo formation of new follicles. In addition, scientists are working to engineer hair follicles, which require hair forming competent epidermal cells and hair inducing dermal cells. Expert opinion Ideally self-organizing processes similar to those occurring during embryonic development should be elicited with some help from biomaterials. PMID:23289545

  13. The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches

    Directory of Open Access Journals (Sweden)

    Marco Mineo

    2016-06-01

    Full Text Available Long non-coding RNAs (lncRNAs have an undefined role in the pathobiology of glioblastoma multiforme (GBM. These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2 as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal, and hypoxia-dependent molecular reprogramming. Among the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Downregulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome and targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context.

  14. Making Blood: The Haematopoietic Niche throughout Ontogeny

    Directory of Open Access Journals (Sweden)

    Mohammad A. Al-Drees

    2015-01-01

    Full Text Available Approximately one-quarter of all cells in the adult human body are blood cells. The haematopoietic system is therefore massive in scale and requires exquisite regulation to be maintained under homeostatic conditions. It must also be able to respond when needed, such as during infection or following blood loss, to produce more blood cells. Supporting cells serve to maintain haematopoietic stem and progenitor cells during homeostatic and pathological conditions. This coalition of supportive cell types, organised in specific tissues, is termed the haematopoietic niche. Haematopoietic stem and progenitor cells are generated in a number of distinct locations during mammalian embryogenesis. These stem and progenitor cells migrate to a variety of anatomical locations through the conceptus until finally homing to the bone marrow shortly before birth. Under stress, extramedullary haematopoiesis can take place in regions that are typically lacking in blood-producing activity. Our aim in this review is to examine blood production throughout the embryo and adult, under normal and pathological conditions, to identify commonalities and distinctions between each niche. A clearer understanding of the mechanism underlying each haematopoietic niche can be applied to improving ex vivo cultures of haematopoietic stem cells and potentially lead to new directions for transplantation medicine.

  15. Niching as a Macrostructural Procedure*

    Directory of Open Access Journals (Sweden)

    Rufus H. Gouws

    2011-10-01

    Full Text Available

    Abstract: Niching is a macrostructural procedure of textual condensation which results in different dictionary articles being clustered into one textblock as subarticles headed by sublemmata. This article offers an identification and critical discussion of different types of niching. Examples from dictionaries are used to examine problems which dictionary users experience as a result of the application of niching. The emphasis is on problems regarding the search route of users via the outer access structure of dictionaries. A distinction is made between single niching and multiple niching. Different aspects of multiple niching receive attention, e.g. the use of remote and exclusively remote multiple niching. The focus is also on an increased degree of textual condensation resulting from these procedures as well as problems in the domain of the access structure. Attention is drawn to the influence of the inclusion of homonym pairs on the application of multiple niching. Problems arising from an inconsistent application of multiple niching are identified and solutions are suggested for these problems in order to enhance the quality of the lexicographic practice. It is shown that a user-driven dictionary would rather opt for the application of procedures of single niching and first level nesting instead of multiple niching.

    Keywords: EXCLUSIVELY REMOTE MULTIPLE NICHING, FIRST LEVEL NESTING, HETEROGENEOUS NICHING, HOMOGENEOUS NICHING, HYBRID NICHING, MULTIPLE NICHING, NESTING, NICHING, PARTIAL ARTICLE STRETCH, REMOTE NICHING, SINGLE NICHING, TEXTUAL CONDENSATION

    Opsomming: Nisting as 'n makrostrukturele prosedure. Nisting is 'n makrostrukturele teksverdigtingsprosedure waardeur woordeboekartikels in een teksblok as subartikels met sublemmata gegroepeer word. Hierdie artikel bevat 'n beskrywing en kritiese bespreking van verskillende tipes nisting. Aan die hand van woordeboekvoorbeelde word probleme wat gebruikers met die toepassing

  16. GAS6/Mer axis regulates the homing and survival of the E2A/PBX1 positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche

    OpenAIRE

    Shiozawa, Yusuke; Pedersen, Elisabeth A.; Taichman, Russell S.

    2009-01-01

    Despite improvements in current combinational chemotherapy regimens, the prognosis of the (1;19)(q23;p13) translocation (E2A/PBX1) positive B-cell precursor acute lymphoblastic leukemia (ALL) is poor in pediatric leukemia patients. In this study, we examined the roles of GAS6/Mer axis in the interactions between E2A/PBX1 positive B-cell precursor ALL cells and the osteoblastic niche in the bone marrow. The data show that primary human osteoblasts secrete GAS6 in response to the Mer-over-expre...

  17. The Fluctuation Niche in Plants

    International Nuclear Information System (INIS)

    Terradas, J.; Penuelas, J.; Lloret, F.; Penuelas, J.

    2009-01-01

    Classical approaches to niche in coexisting plants have undervalued temporal fluctuations. We propose that fluctuation niche is an important dimension of the total niche and interacts with habitat and life-history niches to provide a better understanding of the multidimensional niche space where ecological interactions occur. To scale a fluctuation niche, it is necessary to relate environmental constrictions or species performance not only to the absolute values of the usual environmental and eco physiological variables but also to their variances or other measures of variability. We use Mediterranean plant communities as examples, because they present characteristic large seasonal and inter annual fluctuations in water and nutrient availabilities, along an episodic-constant gradient, and because the plant responses include a number of syndromes coupled to this gradient.

  18. The Fluctuation Niche in Plants

    Directory of Open Access Journals (Sweden)

    Jaume Terradas

    2009-01-01

    Full Text Available Classical approaches to niche in coexisting plants have undervalued temporal fluctuations. We propose that fluctuation niche is an important dimension of the total niche and interacts with habitat and life-history niches to provide a better understanding of the multidimensional niche space where ecological interactions occur. To scale a fluctuation niche, it is necessary to relate environmental constrictions or species performance not only to the absolute values of the usual environmental and ecophysiological variables but also to their variances or other measures of variability. We use Mediterranean plant communities as examples, because they present characteristic large seasonal and interannual fluctuations in water and nutrient availabilities, along an episodic-constant gradient, and because the plant responses include a number of syndromes coupled to this gradient.

  19. GPS Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Global Positioning System (GPS) Test Facility Instrumentation Suite (GPSIS) provides great flexibility in testing receivers by providing operational control of...

  20. Exosomes as novel regulators of adult neurogenic niches

    Directory of Open Access Journals (Sweden)

    Luis Federico Batiz

    2016-01-01

    Full Text Available Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ of the dentate gyrus (DG in the hippocampus, and the sub-ventricular zone (SVZ of the lateral ventricles. SGZ newborn neurons are destined to the granular cell layer of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb. The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs, which reside in a unique and specialized microenvironment known as neurogenic niche. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs. EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs, proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult

  1. Amniotic fluid stem cells restore the muscle cell niche in a HSA-Cre, Smn(F7/F7) mouse model.

    Science.gov (United States)

    Piccoli, Martina; Franzin, Chiara; Bertin, Enrica; Urbani, Luca; Blaauw, Bert; Repele, Andrea; Taschin, Elisa; Cenedese, Angelo; Zanon, Giovanni Franco; André-Schmutz, Isabelle; Rosato, Antonio; Melki, Judith; Cavazzana-Calvo, Marina; Pozzobon, Michela; De Coppi, Paolo

    2012-08-01

    Mutations in the survival of motor neuron gene (SMN1) are responsible for spinal muscular atrophy, a fatal neuromuscular disorder. Mice carrying a homozygous deletion of Smn exon 7 directed to skeletal muscle (HSA-Cre, Smn(F7/F7) mice) present clinical features of human muscular dystrophies for which new therapeutic approaches are highly warranted. Herein we demonstrate that tail vein transplantation of mouse amniotic fluid stem (AFS) cells enhances the muscle strength and improves the survival rate of the affected animals. Second, after cardiotoxin injury of the Tibialis Anterior, only AFS-transplanted mice efficiently regenerate. Most importantly, secondary transplants of satellite cells (SCs) derived from treated mice show that AFS cells integrate into the muscle stem cell compartment and have long-term muscle regeneration capacity indistinguishable from that of wild-type-derived SC. This is the first study demonstrating the functional and stable integration of AFS cells into the skeletal muscle, highlighting their value as cell source for the treatment of muscular dystrophies. Copyright © 2012 AlphaMed Press.

  2. GPS system simulation methodology

    Science.gov (United States)

    Ewing, Thomas F.

    1993-01-01

    The following topics are presented: background; Global Positioning System (GPS) methodology overview; the graphical user interface (GUI); current models; application to space nuclear power/propulsion; and interfacing requirements. The discussion is presented in vugraph form.

  3. The Statistics of GPS

    National Research Council Canada - National Science Library

    Matsakis, Demetrios

    2007-01-01

    The Global Positioning System (GPS) is an extremely effective satellite-based system that broadcasts sufficient information for a user to determine time and position from any location on or near the Earth...

  4. Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche

    Czech Academy of Sciences Publication Activity Database

    Hayakawa, Y.; Ariyama, H.; Stančíková, Jitka; Sakitani, S.; Asfaha, S.; Renz, B.W.; Dubeykovskaya, Z.A.; Shibata, W.; Wang, H.S.; Westphalen, C.B.; Chen, X.W.; Takemoto, Y.; Kim, W.; Khurana, S.S.; Tailor, Y.; Nagar, K.; Tomita, H.; Hara, A.; Sepulveda, A.R.; Setlik, W.; Gershon, M.D.; Saha, S.; Ding, L.; Shen, Z.L.; Fox, J.G.; Friedman, R.A.; Konieczny, S.F.; Worthley, D.; Kořínek, Vladimír; Wang, T.C.

    2015-01-01

    Roč. 28, č. 6 (2015), s. 800-814 ISSN 1535-6108 R&D Projects: GA ČR GAP305/11/1780; GA ČR(CZ) GA14-33952S Institutional support: RVO:68378050 Keywords : Innate lymphoid- cell s * Intraepithelial neoplasia * Maintenance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 23.214, year: 2015

  5. Fibrocytes and the tissue niche in lung repair

    Directory of Open Access Journals (Sweden)

    Bjermer Leif

    2011-06-01

    Full Text Available Abstract Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.

  6. GPS satellite surveying

    CERN Document Server

    Leick, Alfred; Tatarnikov, Dmitry

    2015-01-01

    THE MOST COMPREHENSIVE, UP-TO-DATE GUIDE ON GPS TECHNOLOGY FOR SURVEYING Three previous editions have established GPS Satellite Surveying as the definitive industry reference. Now fully updated and expanded to reflect the newest developments in the field, this Fourth Edition features cutting-edge information on GNSS antennas, precise point positioning, real-time relative positioning, lattice reduction, and much more. Expert authors examine additional tools and applications, offering complete coverage of geodetic surveying using satellite technologies. The past decade has seen a major evolut

  7. Structural ECM components in the premetastatic and metastatic niche

    DEFF Research Database (Denmark)

    Høye, Anette M; Erler, Janine T

    2016-01-01

    The aim of this review is to give an overview of the extracellular matrix (ECM) components that are important for creating structural changes in the premetastatic and metastatic niche. The successful arrival and survival of cancer cells that have left the primary tumor and colonized distant sites...... depends on the new microenvironment they encounter. The primary tumor itself releases factors into the circulation that travel to distant organs and then initiate structural changes, both non-enzymatic and enzymatic, to create a favorable niche for the disseminating tumor cells. Therapeutic strategies...

  8. Ecological niche of plant pathogens

    Directory of Open Access Journals (Sweden)

    Ecaterina Fodor

    2011-02-01

    Full Text Available Disease ecology is a new approach to the understanding of the spread and dynamics of pathogens in natural and man-made environments. Defining and describing the ecological niche of the pathogens is one of the major tasks for ecological theory, as well as for practitioners preoccupied with the control and forecasting of established and emerging diseases. Niche theory has been periodically revised, not including in an explicit way the pathogens. However, many progresses have been achieved in niche modeling of disease spread, but few attempts were made to construct a theoretical frame for the ecological niche of pathogens. The paper is a review of the knowledge accumulated during last decades in the niche theory of pathogens and proposes an ecological approach in research. It quest for new control methods in what concerns forest plant pathogens, with a special emphasis on fungi like organisms of the genus Phytophthora. Species of Phytophthora are the most successful plant pathogens of the moment, affecting forest and agricultural systems worldwide, many of them being invasive alien organisms in many ecosystems. The hyperspace of their ecological niche is defined by hosts, environment and human interference, as main axes. To select most important variables within the hyperspace, is important for the understanding of the complex role of pathogens in the ecosystems as well as for control programs. Biotic relationships within ecosystem of host-pathogen couple are depicted by ecological network and specific metrics attached to this. The star shaped network is characterized by few high degree nodes, by short path lengths and relatively low connectivity, premises for a rapid disturbance spread.

  9. Ecological niche of plant pathogens

    Directory of Open Access Journals (Sweden)

    Ecaterina Fodor

    2011-06-01

    Full Text Available Disease ecology is a new approach to the understanding of the spread and dynamics of pathogens in natural and man-made environments. Defining and describing the ecological niche of the pathogens is one of the major tasks for ecological theory, as well as for practitioners preoccupied with the control and forecasting of established and emerging diseases. Niche theory has been periodically revised, not including in an explicit way the pathogens. However, many progresses have been achieved in niche modeling of disease spread, but few attempts were made to construct a theoretical frame for the ecological niche of pathogens. The paper is a review of the knowledge accumulated during last decades in the niche theory of pathogens and proposes an ecological approach in research. It quest for new control methods in what concerns forest plant pathogens, with a special emphasis on fungi like organisms of the genus Phytophthora. Species of Phytophthora are the most successful plant pathogens of the moment, affecting forest and agricultural systems worldwide, many of them being invasive alien organisms in many ecosystems. The hyperspace of their ecological niche is defined by hosts, environment and human interference, as main axes. To select most important variables within the hyperspace, is important the understanding of the complex role of pathogens in the ecosystems as well as for control programs. Biotic relationships within ecosystem of host-pathogen couple are depicted by ecological network and specific metrics attached to this. The star shaped network is characterized by few high degree nodes, by short path lengths and relatively low connectivity, premises for a rapid disturbance spread. 

  10. GPS Ephemeris Message Broadcast Simulation

    National Research Council Canada - National Science Library

    Browne, Nathan J; Light, James J

    2005-01-01

    The warfighter constantly needs increased accuracy from GPS and a means to increasing this accuracy to the decimeter level is a broadcast ephemeris message containing GPS satellite orbit and clock corrections...

  11. Variability in GPS sources

    NARCIS (Netherlands)

    Jauncey, DL; King, EA; Bignall, HE; Lovell, JEJ; Kedziora-Chudczer, L; Tzioumis, AK; Tingay, SJ; Macquart, JP; McCulloch, PM

    2003-01-01

    Flux density monitoring data at 2.3 and 8.4 GHz is presented for a sample of 33 southern hemisphere GPS sources, drawn from the 2.7 GHz Parkes survey. This monitoring data, together with VLBI monitoring data, shows that a small fraction of these sources, similar to10%, vary. Their variability falls

  12. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    Directory of Open Access Journals (Sweden)

    Tony DeFalco

    2015-08-01

    Full Text Available The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs. Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1 and enzymes involved in retinoic acid (RA biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  13. Efficient GPS Position Determination Algorithms

    National Research Council Canada - National Science Library

    Nguyen, Thao Q

    2007-01-01

    ... differential GPS algorithm for a network of users. The stand-alone user GPS algorithm is a direct, closed-form, and efficient new position determination algorithm that exploits the closed-form solution of the GPS trilateration equations and works...

  14. Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma

    NARCIS (Netherlands)

    Groen, R.W.J.; van Noort, W.A.; Raymakers, R.A.; Prins, H.J.; Aalders, L.; Hofhuis, F.M.; Moerer, P.; van Velzen, J.F.; Bloem, A.C.; van Kessel, B.; Rozemuller, H.; van Binsbergen, E.; Buijs, A.; Yuan, Huipin; de Bruijn, Joost Dick; de Weers, M.; Parren, P.W.H.I.; Schuringa, J.J.; Lokhorst, H.M.; Mutis, T.; Martens, ACM

    2012-01-01

    Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM

  15. Indoor Positioning Using GPS Revisited

    DEFF Research Database (Denmark)

    Kjærgaard, Mikkel Baun; Blunck, Henrik; Godsk, Torben

    2010-01-01

    It has been considered a fact that GPS performs too poorly inside buildings to provide usable indoor positioning. We analyze results of a measurement campaign to improve on the understanding of indoor GPS reception characteristics. The results show that using state-of-the-art receivers GPS...... low signal-to-noise ratios, multipath phenomena or bad satellite constellation geometry. We have also measured the indoor performance of embedded GPS receivers in mobile phones which provided lower availability and accuracy than state-of-the-art ones. Finally, we consider how the GPS performance...

  16. Niching as a macrostructural procedure | Gouws | Lexikos

    African Journals Online (AJOL)

    Examples from dictionaries are used to examine problems which dictionary users experience as a result of the application of niching. The emphasis is on problems regarding the search route of users via the outer access structure of dictionaries. A distinction is made between single niching and multiple niching. Different ...

  17. GPS antenna designs

    Science.gov (United States)

    Laube, Samuel J. P.

    1987-05-01

    Application of the current GPS NAVSTAR system to civilian service requires that a right hand, circularly polarized, -160 dBW spread spectrum signal be received from an orbiting satellite, where the antenna environment is also moving. This presents a design challenge when inexpensive antennas are desired. The intent of this survey is to provide information on the antennas mentioned and to construct and test prototypes to determine whether the choice made by the industry, the quadrifilar helix, is the best. The helix antenna is currently the low cost standard for GPS. Prototype versions were constructed using 12 gauge wire and subminiature coaxial hardline. The constructed antennas were tested using a signal generator and a reference turnstile. A spectrum analyzer was used to measure the level of the received signal.

  18. Programmable Off-The-Shelf cell-enabled GPS loggers optimized for retrieving after being used as a float in large river experiments.

    Science.gov (United States)

    Hut, Rolf; Bogaard, Thom

    2017-04-01

    Throwing something in a river and seeing how fast it floats downstream is the first thing that every hydrologists does when encountering a new river. Using a collection of floats allows estimation of gauge surface water velocity and dispersion characteristics. To use floats over long (hundreds of kilometers) stretches of river requires either a crew that keeps an eye on the floats (labor intensive) or having high-tech floats that upload their location on regular intervals, such that they can be retrieved at the end of the experiment. GPS floats with communication units have been custom build by scientists before. Connecting GPS units to GSM modems used to require deep knowledge on micro-electronics and network protocols. In this work we present a version that is build using only off-the-shelf electronics that require no deep knowledge of either micro electronics nor network protocols. The new cellular enabled Particle Electron development board made it possible to connect a Sparkfun OpenLog (SD-card based logger) to a GPS tracker with no soldering and little programming. Because scientist can program the device themselves, settings like sample time can be adapted to the needs of specific experiments and additional sensors can be easily added. When writing GPS location every minute to SD and reporting every fifteen minutes online, our logger can run for three days on a single 2200 mAh LiPo battery (provided with the Particle Electron). Cost of components for our logger is less than 150. The durability of our GPS loggers will be tested during a field campaign at the end of January 2017 where 15 floats will float down the Irrawaddy river over a length of more than 200 km, during two days.

  19. Niche energy markets in rural areas

    International Nuclear Information System (INIS)

    Walsh, M.; McCarthy, S.

    1996-01-01

    The objective of this project is the development of a standard methodology for integrating non-food crops in rural areas with niche energy markets. This has involved a number of steps including (i) identification of 3 niche markets for energy crops which are of common interest to the partners, (ii) application of the standard costing methodology to investigate these three niche markets and (iii) comparison of the results from this work in three workshops (one for each market). Three tightly defined niche markets were identified; these were chosen following an examination of the national energy marekts in each of the partners countries (Ireland, Germany, Netherlands, UK, Greece and Portugal). This paper gives an overview of the national energy markets which were examined. The three niche markets are introduced and the reasons for their selection given. The application of the methodology to each of the niche markets is presented along with the conclusions of the partners regarding the niche markets. (Author)

  20. Niche-specific cognitive strategies

    DEFF Research Database (Denmark)

    Hulgard, K.; Ratcliffe, J. M.

    2014-01-01

    Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should ...... the niche-specific cognitive strategies hypothesis and suggest that for gleaning and clutter-resistant aerial hawking bats, learning to associate shape with food interferes with subsequent spatial memory learning.......Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should...... rely more on object memory than on spatial memory for finding food and that the opposite is true of frugivorous and nectivorous species. Specifically, we predicted that: (1) predatory bats would readily learn to associate shapes with palatable prey and (2) once bats had made such associations...

  1. Standardization of GPS data processing

    International Nuclear Information System (INIS)

    Park, Pil Ho

    2001-06-01

    A nationwide GPS network has been constructed with about 60 permanent GPS stations after late 1990s in Korea. For using the GPS in variety of application area like crustal deformation, positioning, or monitoring upper atmosphere, it is necessary to have ability to process the data precisely. Now Korea Astronomy Observatory has the precise GPS data processing technique in Korea because it is difficult to understand characteristics of the parameters we want to estimate, resolve the integer ambiguity, and analyze many errors. There are three reliable GPS data processing software in the world ; Bernese(University of Berne), GIPSY-OASIS(JPL), GAMIT(MIT). These software allow us to achieve millimeter accuracy in the horizontal position and about 1 cm accuracy vertically even for regional networks with a diameter of several thousand kilometers. But we established the standard of GPS data processing using Bernese as main tool and GIPSY O ASIS as side

  2. How is the rate of climatic-niche evolution related to climatic-niche breadth?

    Science.gov (United States)

    Fisher-Reid, M Caitlin; Kozak, Kenneth H; Wiens, John J

    2012-12-01

    The rate of climatic-niche evolution is important to many research areas in ecology, evolution, and conservation biology, including responses of species to global climate change, spread of invasive species, speciation, biogeography, and patterns of species richness. Previous studies have implied that clades with higher rates of climatic-niche evolution among species should have species with narrower niche breadths, but there is also evidence suggesting the opposite pattern. However, the relationships between rate and breadth have not been explicitly analyzed. Here, we examine the relationships between the rate of climatic-niche evolution and climatic-niche breadth using phylogenetic and climatic data for 250 species in the salamander family Plethodontidae, a group showing considerable variation in both rates of climatic-niche evolution and climatic-niche breadths. Contrary to some expectations, we find no general relationship between climatic-niche breadth and the rate of climatic-niche evolution. Climatic-niche breadths for some ecologically important climatic variables considered separately (temperature seasonality and annual precipitation) do show significant relationships with the rate of climatic-niche evolution, but rates are faster in clades in which species have broader (not narrower) niche breadths. In summary, our results show that narrower niche breadths are not necessarily associated with faster rates of niche evolution. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  3. Phylogenetic conservatism of environmental niches in mammals.

    Science.gov (United States)

    Cooper, Natalie; Freckleton, Rob P; Jetz, Walter

    2011-08-07

    Phylogenetic niche conservatism is the pattern where close relatives occupy similar niches, whereas distant relatives are more dissimilar. We suggest that niche conservatism will vary across clades in relation to their characteristics. Specifically, we investigate how conservatism of environmental niches varies among mammals according to their latitude, range size, body size and specialization. We use the Brownian rate parameter, σ(2), to measure the rate of evolution in key variables related to the ecological niche and define the more conserved group as the one with the slower rate of evolution. We find that tropical, small-ranged and specialized mammals have more conserved thermal niches than temperate, large-ranged or generalized mammals. Partitioning niche conservatism into its spatial and phylogenetic components, we find that spatial effects on niche variables are generally greater than phylogenetic effects. This suggests that recent evolution and dispersal have more influence on species' niches than more distant evolutionary events. These results have implications for our understanding of the role of niche conservatism in species richness patterns and for gauging the potential for species to adapt to global change.

  4. Human bone perivascular niche-on-a-chip for studying metastatic colonization.

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Nava, Michele Maria; Yeager, Keith; Chramiec, Alan; Hao, Luke; Robinson, Samuel; Guo, Edward; Raimondi, Manuela Teresa; Vunjak-Novakovic, Gordana

    2018-02-06

    Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.

  5. Spatial distributions of niche-constructing populations

    Directory of Open Access Journals (Sweden)

    Xiaozhuo Han

    2015-12-01

    Full Text Available Niche construction theory regards organisms not only as the object of natural selection but also an active subject that can change their own selective pressure through eco-evolutionary feedbacks. Through reviewing the existing works on the theoretical models of niche construction, here we present the progress made on how niche construction influences genetic structure of spatially structured populations and the spatial-temporal dynamics of metapopulations, with special focuses on mathematical models and simulation methods. The majority of results confirmed that niche construction can significantly alter the evolutionary trajectories of structured populations. Organism-environmental interactions induced by niche construction can have profound influence on the dynamics, competition and diversity of metapopulations. It can affect fine-scale spatially distribution of species and spatial heterogeneity of the environment. We further propose a few research directions with potentials, such as applying adaptive dynamics or spatial game theory to explore the effect of niche construction on phenotypic evolution and diversification.

  6. Human niche construction in interdisciplinary focus

    OpenAIRE

    Kendal, Jeremy; Tehrani, Jamshid J.; Odling-Smee, John

    2011-01-01

    Niche construction is an endogenous causal process in evolution, reciprocal to the causal process of natural selection. It works by adding ecological inheritance, comprising the inheritance of natural selection pressures previously modified by niche construction, to genetic inheritance in evolution. Human niche construction modifies selection pressures in environments in ways that affect both human evolution, and the evolution of other species. Human ecological inheritance is exceptionally po...

  7. Same size--same niche? Foraging niche separation between sympatric juvenile Galapagos sea lions and adult Galapagos fur seals.

    Science.gov (United States)

    Jeglinski, Jana W E; Goetz, Kimberley T; Werner, Christiane; Costa, Daniel P; Trillmich, Fritz

    2013-05-01

    1. In vertebrates, patterns of resource utilization change throughout development according to age- and or size-specific abilities and requirements. Thus, interspecific competition affects different age classes differently. 2. Adults of sympatric species often show distinct foraging niche segregation, but juvenile resource use might overlap with adult competitors of similar body size. Resultant negative effects on juveniles can have important consequences for population dynamics, yet such interactions have received little attention in studies of mammalian communities. 3. Using GPS tracking devices, time-depth recorders and stable isotope data, we compared diving depth, activity time, trophic position and foraging habitat characteristics to investigate foraging niche overlap between similar-sized sympatric juvenile Galapagos sea lions (Zalophus wollebaeki) and adult Galapagos fur seals (Arctocephalus galapagoensis) and compared each group with much larger-bodied adult Galapagos sea lions. 4. We found little indication for direct competition but a complex pattern of foraging niche segregation: juvenile sea lions and adult fur seals dived to shallow depths at night, but foraged in different habitats with limited spatial overlap. Conversely, juvenile and adult sea lions employed different foraging patterns, but their foraging areas overlapped almost completely. 5. Consistency of foraging habitat characteristics between juvenile and adult sea lions suggests that avoidance of competition may be important in shaping foraging habitat utilization. Resultant specialization on a limited habitat could contribute to low sea lion numbers that contrast with high fur seal abundance. Our data suggest that exploitation by multiple predators within spatially restricted foraging ranges of juveniles might negatively impact juvenile foraging success and ultimately influence population dynamics. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

  8. The GPS odograph user's guide

    Science.gov (United States)

    The GPS-based Odograph Prototype (GOP or GPS Odograph) was developed in an effort sponsored by The Federal Highway Administration (FHWA). The purpose of this effort was to develop a means of using inexpensive commercial off-the-self laptop (or notebo...

  9. High Gain Advanced GPS Receiver

    National Research Council Canada - National Science Library

    Brown, Alison; Zhang, Gengsheng

    2006-01-01

    NAVSYS High Gain Advanced GPS Receiver (HAGR) uses a digital beam-steering antenna array to enable up to eight GPS satellites to be tracked, each with up to 10 dBi of additional antenna gain over a conventional receiver solution...

  10. GENERALIZED PROCESSOR SHARING (GPS) TECHNIQUES

    African Journals Online (AJOL)

    Olumide

    popular technique, Generalized Processor Sharing (GPS), provided an effective and efficient utilization of the available resources at the face of stringent and varied QoS requirements. This paper, therefore, presents the comparison of two GPS techniques –. PGPS and CDGPS – based on performance with limited resources ...

  11. Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae).

    Science.gov (United States)

    Gómez, Camila; Tenorio, Elkin A; Montoya, Paola; Cadena, Carlos Daniel

    2016-02-10

    Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour. © 2016 The Author(s).

  12. Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae)

    Science.gov (United States)

    Gómez, Camila; Tenorio, Elkin A.; Montoya, Paola; Cadena, Carlos Daniel

    2016-01-01

    Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour. PMID:26865303

  13. GPS Position Time Series @ JPL

    Science.gov (United States)

    Owen, Susan; Moore, Angelyn; Kedar, Sharon; Liu, Zhen; Webb, Frank; Heflin, Mike; Desai, Shailen

    2013-01-01

    Different flavors of GPS time series analysis at JPL - Use same GPS Precise Point Positioning Analysis raw time series - Variations in time series analysis/post-processing driven by different users. center dot JPL Global Time Series/Velocities - researchers studying reference frame, combining with VLBI/SLR/DORIS center dot JPL/SOPAC Combined Time Series/Velocities - crustal deformation for tectonic, volcanic, ground water studies center dot ARIA Time Series/Coseismic Data Products - Hazard monitoring and response focused center dot ARIA data system designed to integrate GPS and InSAR - GPS tropospheric delay used for correcting InSAR - Caltech's GIANT time series analysis uses GPS to correct orbital errors in InSAR - Zhen Liu's talking tomorrow on InSAR Time Series analysis

  14. Evidential recovery from GPS devices

    Directory of Open Access Journals (Sweden)

    Brian Cusack

    Full Text Available Global Positioning Systems (GPS have become more affordable, are now widely used in motor vehicles and in other frequently used applications. As a consequence GPS are increasingly becoming an important source of evidential data for digital forensic investigations. This paper acknowledges there are only disparate documents for the guidance of an investigator when extracting evidence form such systems. The focus of this paper is to provide the technical details of recovering artifacts from four GPS currently available to the New Zealand market. Navman brand GPS are used, following a forensically robust process. The steps of the process are described, results analysed and the associated risks are discussed. In addition, the paper discusses techniques related to the visual presentation of evidence suitable for Google Maps. Automation attempts to speed up the analysis to visualization steps are also included. The outcome is a road map that may assist digital forensic investigators develop GPS examination strategies for implementation in their own organizations.

  15. Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation

    NARCIS (Netherlands)

    Dominguez-Brauer, Carmen; Hao, Zhenyue; Elia, Andrew J.; Fortin, Jérôme M.; Nechanitzky, Robert; Brauer, Patrick M.; Sheng, Yi; Mana, Miyeko D.; Chio, Iok In Christine; Haight, Jillian; Pollett, Aaron; Cairns, Robert; Tworzyanski, Leanne; Inoue, Satoshi; Reardon, Colin; Marques, Ana; Silvester, Jennifer; Cox, Maureen A.; Wakeham, Andrew; Yilmaz, Omer H.; Sabatini, David M.; van Es, Johan H.; Clevers, Hans; Sato, Toshiro; Mak, Tak W.

    2016-01-01

    The E3 ubiquitin ligase Mule is often overexpressed in human colorectal cancers, but its role in gut tumorigenesis is unknown. Here, we show in vivo that Mule controls murine intestinal stem and progenitor cell proliferation by modulating Wnt signaling via c-Myc. Mule also regulates protein levels

  16. Driving without a GPS

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    in the best way possible; and that the differences in their knowledge systems is acknowledged and used as an asset in these international programmes. With these factors in place, on the other hand, programmes with international faculty and diverse student audiences in which this diversity is exploited...... as students as well as the lecturers themselves represent a diverse range of first languages, cultures and knowledge systems; at the same time, the teaching and learning must reach at least the same high quality standards as in more traditional mono-lingual and mono-cultural settings. For a lecturer...... in an appropriate way, may have a considerable added value that positively impacts on the knowledge, skills and competences developed by their graduates. However, lecturers often feel at a loss because they are not sure how to do this and teaching becomes like driving in unknown territory without a GPS. Based...

  17. Stitch the niche - a practical philosophy and visual schematic for the niche concept

    NARCIS (Netherlands)

    McInerny, Greg J.; Etienne, Rampal S.

    2012-01-01

    By over-focusing on precise definitions, ecology has produced a confused idea of the niche concept. This, our second paper, develops a practical philosophy for the niche that approaches the concept at the correct level of abstraction. We deconstruct the niche into effect and response components and

  18. Trophic niche shifts driven by phytoplankton in sandy beach ecosystems

    Science.gov (United States)

    Bergamino, Leandro; Martínez, Ana; Han, Eunah; Lercari, Diego; Defeo, Omar

    2016-10-01

    Stable isotopes (δ13C and δ15N) together with chlorophyll a and densities of surf diatoms were used to analyze changes in trophic niches of species in two sandy beaches of Uruguay with contrasting morphodynamics (i.e. dissipative vs. reflective). Consumers and food sources were collected over four seasons, including sediment organic matter (SOM), suspended particulate organic matter (POM) and the surf zone diatom Asterionellopsis guyunusae. Circular statistics and a Bayesian isotope mixing model were used to quantify food web differences between beaches. Consumers changed their trophic niche between beaches in the same direction of the food web space towards higher reliance on surf diatoms in the dissipative beach. Mixing models indicated that A. guyunusae was the primary nutrition source for suspension feeders in the dissipative beach, explaining their change in dietary niche compared to the reflective beach where the proportional contribution of surf diatoms was low. The high C/N ratios in A. guyunusae indicated its high nutritional value and N content, and may help to explain the high assimilation by suspension feeders at the dissipative beach. Furthermore, density of A. guyunusae was higher in the dissipative than in the reflective beach, and cell density was positively correlated with chlorophyll a only in the dissipative beach. Therefore, surf diatoms are important drivers in the dynamics of sandy beach food webs, determining the trophic niche space and productivity. Our study provides valuable insights on shifting foraging behavior by beach fauna in response to changes in resource availability.

  19. Mapping of potential neurogenic niche in the human temporal lobe

    Directory of Open Access Journals (Sweden)

    Adriano Barreto Nogueira

    2014-10-01

    Full Text Available The subgranular zone (SGZ of the dentate gyrus and the subventricular zone (SVZ are known neurogenic niches in adult mammals. Nonetheless, the existence of neurogenic niches in adult humans is controversial. We hypothesized that mapping neurogenic niches in the human temporal lobe could clarify this issue. Neurogenic niches and neurogenesis were investigated in 28 temporal lobes via immunostaining for nestin and doublecortin (DCX, respectively. Nestin was observed in a continuous layer formed by the SVZ, the subpial zone of the medial temporal lobe and the SGZ, terminating in the subiculum. In the subiculum, remarkable DCX expression was observed through the principal efferent pathway of the hippocampus to the fimbria. A possible explanation for the results is that the SVZ, the subpial zone of the medial temporal lobe and the SGZ form a unit containing neural stem cells that differentiate into neurons in the subiculum. Curiously, the area previously identified as the human rostral migratory stream may in truth be the fornix, which contains axons that originate in the subiculum. This study suggests that neurogenesis may occur in an orchestrated manner in a broad area of the human temporal lobe.

  20. Brief report: Using global positioning system (GPS) enabled cell phones to examine adolescent travel patterns and time in proximity to alcohol outlets.

    Science.gov (United States)

    Byrnes, Hilary F; Miller, Brenda A; Morrison, Christopher N; Wiebe, Douglas J; Remer, Lillian G; Wiehe, Sarah E

    2016-07-01

    As adolescents gain freedom to explore new environments unsupervised, more time in proximity to alcohol outlets may increase risks for alcohol and marijuana use. This pilot study: 1) Describes variations in adolescents' proximity to outlets by time of day and day of the week, 2) Examines variations in outlet proximity by drinking and marijuana use status, and 3) Tests feasibility of obtaining real-time data to study adolescent proximity to outlets. U.S. adolescents (N = 18) aged 16-17 (50% female) carried GPS-enabled smartphones for one week with their locations tracked. The geographic areas where adolescents spend time, activity spaces, were created by connecting GPS points sequentially and adding spatial buffers around routes. Proximity to outlets was greater during after school and evening hours. Drinkers and marijuana users were in proximity to outlets 1½ to 2 times more than non-users. Findings provide information about where adolescents spend time and times of greatest risk, informing prevention efforts. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  1. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A niche width model of optimal specialization

    NARCIS (Netherlands)

    Bruggeman, J.P.; Ó Nualláin, Breanndán

    2000-01-01

    Niche width theory, a part of organizational ecology, predicts whether “specialist” or “generalist” forms of organizations have higher “fitness,” in a continually changing environment. To this end, niche width theory uses a mathematical model borrowed from biology. In this paper, we first loosen the

  3. Target Article with Commentaries: Developmental Niche Construction

    Science.gov (United States)

    Flynn, Emma G.; Laland, Kevin N.; Kendal, Rachel L.; Kendal, Jeremy R.

    2013-01-01

    Niche construction is the modification of components of the environment through an organism's activities. Humans modify their environments mainly through ontogenetic and cultural processes, and it is this reliance on learning, plasticity and culture that lends human niche construction a special potency. In this paper we aim to facilitate…

  4. Autophagy and the hematopoietic niche: a regulatory role for the Forkhead-box transcription factors

    NARCIS (Netherlands)

    Gomez Puerto, MC

    2016-01-01

    Two main components of the hematopoietic niche are hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). FOXO transcription factors play a fundamental role in the maintenance of these cells through the regulation of cell cycle and oxidative stress. Other gene expression programs

  5. Hastighedskort for Danmark vha. GPS

    DEFF Research Database (Denmark)

    Andersen, Ove; Lahrmann, Harry; Torp, Kristian

    2011-01-01

    Hastighed på vejnettet er en central metrik indenfor trafikplanlægning og trafikoptimering. I denne artikel beskrives, hvorledes et hastighedskort for hele Danmark er skabt udelukkende vha. GPS data. To tilgangsvinkler til at beregne hastigheder vha. GPS data er præsenteret. Dette er hhv. en....... Opsummeret anses den turbaseret for at beregne det mest akkurate estimat, men metoden er meget datakrævende. Det er derfor nødvendigt at have den punktbaserede at falde tilbage på. Generelt mangler metoder til beregning af hastigheder vha. GPS data at blive valideret. Hvordan en sådan validering kan...

  6. GPS Navigation and Tracking Device

    OpenAIRE

    Yahya Salameh Khraisat; Mohammad Al-Khateeb; Yahya Abu-Alreesh; Anas Ayyash; Osama Lahlouh

    2011-01-01

    Since the introduction of GPS Navigation systems in the marketplace, consumers and businesses have been coming up with innovative ways to use the technology in their everyday life. GPS Navigation and Tracking systems keep us from getting lost when we are in strange locations, they monitor children when they are away from home, keep track of business vehicles and can even let us know where a philandering partner is at all times. Because of this we attend to build a GPS tracking device to solve...

  7. A variational approach to niche construction.

    Science.gov (United States)

    Constant, Axel; Ramstead, Maxwell J D; Veissière, Samuel P L; Campbell, John O; Friston, Karl J

    2018-04-01

    In evolutionary biology, niche construction is sometimes described as a genuine evolutionary process whereby organisms, through their activities and regulatory mechanisms, modify their environment such as to steer their own evolutionary trajectory, and that of other species. There is ongoing debate, however, on the extent to which niche construction ought to be considered a bona fide evolutionary force, on a par with natural selection. Recent formulations of the variational free-energy principle as applied to the life sciences describe the properties of living systems, and their selection in evolution, in terms of variational inference. We argue that niche construction can be described using a variational approach. We propose new arguments to support the niche construction perspective, and to extend the variational approach to niche construction to current perspectives in various scientific fields. © 2018 The Authors.

  8. Market positioning: the shifting effects of niche overlap

    NARCIS (Netherlands)

    Bruggeman, J.; Grunow, D.; Leenders, M.A.A.M.; Vermeulen, I.; Kuilman, J.G.

    2012-01-01

    Organizational ecology models of market dynamics emphasize the competition-inducing role of inter-organizational niche overlap—targeting similar market niches increases competitive pressure and thus reduces organizations’ fitness. Recent studies, however, have suggested that moderate niche overlap

  9. Market positioning : The shifting effects of niche overlap

    NARCIS (Netherlands)

    Bruggeman, J.; Grunow, D.; Leenders, M.A.A.M.; Vermeulen, I.; Kuilman, J.G.

    2012-01-01

    Organizational ecology models of market dynamics emphasize the competition-inducing role of inter-organizational niche overlap—targeting similar market niches increases competitive pressure and thus reduces organizations’ fitness. Recent studies, however, have suggested that moderate niche overlap

  10. 75 FR 8928 - Announcement of IS-GPS-200, IS-GPS-705, IS-GPS-800 Interface Control Working Group (ICWG...

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF DEFENSE Department of the Air Force Announcement of IS-GPS-200, IS-GPS-705, IS-GPS... document/s IS-GPS-200E (NAVSTAR GPS Space Segment/Navigation User Interfaces), IS-GPS-705A (NAVSTAR GPS Space Segment/User Segment L5 Interfaces), and IS-GPS-800A (NAVSTAR GPS Space Segment/User Segment L1C...

  11. Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review)

    Science.gov (United States)

    Katoh, Masaru

    2017-01-01

    Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49). Aberrant canonical and non-canonical WNT signaling in human malignancies, including breast, colorectal, gastric, lung, ovary, pancreatic, prostate and uterine cancers, leukemia and melanoma, are involved in CSC survival, bulk-tumor expansion and invasion/metastasis. WNT signaling-targeted therapeutics, such as anti-FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb (cirmtuzumab), anti-RSPO3 mAb (rosmantuzumab), small-molecule porcupine inhibitors (ETC-159, WNT-C59 and WNT974), tankyrase inhibitors (AZ1366, G007-LK, NVP-TNKS656 and XAV939) and β-catenin inhibitors (BC2059, CWP232228, ICG-001 and PRI-724), are in clinical trials or preclinical studies for the treatment of patients with WNT-driven cancers. WNT signaling-targeted therapeutics are applicable for combination therapy with BCR-ABL, EGFR, FLT3, KIT or RET inhibitors to treat a subset of tyrosine kinase-driven cancers because WNT and tyrosine kinase signaling cascades converge to β-catenin for the maintenance and expansion of CSCs. WNT signaling-targeted therapeutics might also be applicable for combination therapy with immune checkpoint blockers, such as atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab, to treat cancers

  12. Niche Extracellular Matrix Components and Their Influence on HSC.

    Science.gov (United States)

    Domingues, Mélanie J; Cao, Huimin; Heazlewood, Shen Y; Cao, Benjamin; Nilsson, Susan K

    2017-08-01

    Maintenance of hematopoietic stem cells (HSC) takes place in a highly specialized microenvironment within the bone marrow. Technological improvements, especially in the field of in vivo imaging, have helped unravel the complexity of the niche microenvironment and have completely changed the classical concept from what was previously believed to be a static supportive platform, to a dynamic microenvironment tightly regulating HSC homeostasis through the complex interplay between diverse cell types, secreted factors, extracellular matrix molecules, and the expression of different transmembrane receptors. To add to the complexity, non-protein based metabolites have also been recognized as a component of the bone marrow niche. The objective of this review is to discuss the current understanding on how the different extracellular matrix components of the niche regulate HSC fate, both during embryonic development and in adulthood. Special attention will be provided to the description of non-protein metabolites, such as lipids and metal ions, which contribute to the regulation of HSC behavior. J. Cell. Biochem. 118: 1984-1993, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Evaluating elk habitat interactions with GPS collars

    Science.gov (United States)

    Mark A. Rumble; Lakhdar Benkobi; Fredrick Lindzey; R. Scott Gamo

    2001-01-01

    Global positioning systems (GPS) are likely to revolutionize animal telemetry studies. GPS collars allow biologists to collect systematically scheduled data when VHF telemetry data is difficult or impossible to collect. Past studies have shown that the success of GPS telemetry is greater when animals are standing, or in open habitats. To make effective use of GPS...

  14. GPS Navigation and Tracking Device

    Directory of Open Access Journals (Sweden)

    Yahya Salameh Khraisat

    2011-10-01

    Full Text Available Since the introduction of GPS Navigation systems in the marketplace, consumers and businesses have been coming up with innovative ways to use the technology in their everyday life. GPS Navigation and Tracking systems keep us from getting lost when we are in strange locations, they monitor children when they are away from home, keep track of business vehicles and can even let us know where a philandering partner is at all times. Because of this we attend to build a GPS tracking device to solve the mentioned problems. Our work consists of the GPS module that collects data from satellites and calculates the position information before transmitting them to the user’s PC (of Navigation system or observers (of Tracking System using wireless technology (GSM.

  15. Scintillation-Hardened GPS Receiver

    Science.gov (United States)

    Stephens, Donald R.

    2015-01-01

    CommLargo, Inc., has developed a scintillation-hardened Global Positioning System (GPS) receiver that improves reliability for low-orbit missions and complies with NASA's Space Telecommunications Radio System (STRS) architecture standards. A software-defined radio (SDR) implementation allows a single hardware element to function as either a conventional radio or as a GPS receiver, providing backup and redundancy for platforms such as the International Space Station (ISS) and high-value remote sensing platforms. The innovation's flexible SDR implementation reduces cost, weight, and power requirements. Scintillation hardening improves mission reliability and variability. In Phase I, CommLargo refactored an open-source GPS software package with Kalman filter-based tracking loops to improve performance during scintillation and also demonstrated improved navigation during a geomagnetic storm. In Phase II, the company generated a new field-programmable gate array (FPGA)-based GPS waveform to demonstrate on NASA's Space Communication and Navigation (SCaN) test bed.

  16. LADOTD GPS technology management plan.

    Science.gov (United States)

    2012-02-01

    Over many years, Global Positioning System (GPS) technology has been adopted by different sections within the Louisiana : Department of Transportation and Development (DOTD), with no uniform standards for accuracy, operation, hardware, or : software....

  17. Continuous professional development for GPs

    DEFF Research Database (Denmark)

    Kjaer, N K; Steenstrup, A P; Pedersen, L B

    2014-01-01

    randomly chosen Danish GPs. RESULTS: Focus groups: CPD activities are chosen based on personal needs analysis, and in order to be professionally updated, to meet engaged colleagues and to prevent burnout. GPs also attend CPD to assess their own pre-existing level of competence. CPD activities need...... by topics strengthening their professional capacity and preventing burnout. There would seem to be no need for a mandatory system....

  18. The niche construction perspective: a critical appraisal.

    Science.gov (United States)

    Scott-Phillips, Thomas C; Laland, Kevin N; Shuker, David M; Dickins, Thomas E; West, Stuart A

    2014-05-01

    Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g., evolutionary process). © 2013 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  19. Toward a Periodic Table of Niches, or Exploring the Lizard Niche Hypervolume.

    Science.gov (United States)

    Pianka, Eric R; Vitt, Laurie J; Pelegrin, Nicolás; Fitzgerald, Daniel B; Winemiller, Kirk O

    2017-11-01

    Widespread niche convergence suggests that species can be organized according to functional trait combinations to create a framework analogous to a periodic table. We compiled ecological data for lizards to examine patterns of global and regional niche diversification, and we used multivariate statistical approaches to develop the beginnings for a periodic table of niches. Data (50+ variables) for five major niche dimensions (habitat, diet, life history, metabolism, defense) were compiled for 134 species of lizards representing 24 of the 38 extant families. Principal coordinates analyses were performed on niche dimensional data sets, and species scores for the first three axes were used as input for a principal components analysis to ordinate species in continuous niche space and for a regression tree analysis to separate species into discrete niche categories. Three-dimensional models facilitate exploration of species positions in relation to major gradients within the niche hypervolume. The first gradient loads on body size, foraging mode, and clutch size. The second was influenced by metabolism and terrestrial versus arboreal microhabitat. The third was influenced by activity time, life history, and diet. Natural dichotomies are activity time, foraging mode, parity mode, and habitat. Regression tree analysis identified 103 cases of extreme niche conservatism within clades and 100 convergences between clades. Extending this approach to other taxa should lead to a wider understanding of niche evolution.

  20. The United States pork niche market phenomenon.

    Science.gov (United States)

    Honeyman, M S; Pirog, R S; Huber, G H; Lammers, P J; Hermann, J R

    2006-08-01

    After the broad industrialization of the US pork industry, there has been a development of niche markets for export and domestic pork; that is, there is a pork niche market phenomenon. The US pork niche market phenomenon is characterized, and 2 of the major markets are explained in detail. With the Midwest's tradition of a diversified family-based agriculture and record low hog prices of the late 1990s, the conditions were conducive for this phenomenon to develop. Pork niche markets utilize various sales methods including Internet sales, local abattoir sales, direct marketing, farmer networks, and targeting to organized groups. In 2003, there were approximately 35 to 40 active pork niche marketing efforts in Iowa. The Berkshire breed is an example of a swine breed that has had a recent resurgence because of niche markets. Berkshire pork is known for tenderness and excellent quality. Berkshire registrations have increased 4-fold in the last 10 yr. One of the larger niche marketers of "natural pork" is Niman Ranch Pork, which has more than 400 farmer-producers and processes about 2,500 pigs weekly. Many US consumers of pork are interested in issues concerning the environment, food safety, pig welfare, and pig farm ownership and structure. These consumers may be willing to pay more for pork from farmers who are also concerned about these issues. Small- and medium-sized swine farmers are active in pork niche markets. Niche markets claim product differentiation by superior or unique product quality and social attributes. Quality attributes include certain swine breeds, and meat quality, freshness, taste or flavor, and tenderness. Social or credence attributes often are claimed and include freedom from antibiotics and growth promotants; local family farm production; natural, organic, outdoor, or bedded rearing; humane rearing; known origin; environmentally friendly production; and the absence of animal by-products in the feed. Niche pork markets and alternative swine

  1. GPS measurements in Satakunta area

    International Nuclear Information System (INIS)

    Poutanen, M.; Nyberg, S.; Ahola, J.

    2010-10-01

    The Finnish Geodetic Institute, the Geological Survey of Finland, Posiva Ltd and municipalities in the district of Satakunta launched the GeoSatakunta research program in 2002 to carry out interdisciplinary studies on regional bedrock stress field and to apply the results e.g. in land use planning in the Satakunta area. The area was chosen for many reasons. Its geological diversity, extensive multi-disciplinary data coverage, and various interests of participants made the area suitable for the project. The purpose of the GPS observations is to get detailed information on recent crustal deformations in the area. The Finnish Geodetic Institute maintains e.g. national GPS network, FinnRef, and since 1995 a local research network in the Olkiluoto area. The Satakunta network differs from these, and this is the first time to obtain such detailed information of a regional network in Finland. The Satakunta GPS network consists of 13 concrete pillars for episodic GPS campaigns and the Olkiluoto permanent GPS station in the FinnRef network. The distances between the concrete pillars are 10-15 km, and the sites were chosen in a co-operation with the Geological Survey of Finland taking into account the geological structures in the area. The City of Pori made the final reconnaissance in the field and constructed eight pillars in 2003. The original network was expanded in 2005-2006 in Eurajoki and Rauma, and at the City of Rauma joined the co-operation. The five new pillars join the previous Olkiluoto network into the Satakunta network. There have been three annual GPS campaigns in 2003-2008. Time series of the Satakunta network are shorter than in the Olkiluoto network, and also the distances are longer. Therefore, the same accuracy than in Olkiluoto has not yet achieved. However, mm-sized movements can be excluded. Estimated velocities were small (0.2 mm/a) and mostly statistically insignificant because of relatively short time series. In this publication we describe the

  2. GPS/INS Sensor Fusion Using GPS Wind up Model

    Science.gov (United States)

    Williamson, Walton R. (Inventor)

    2013-01-01

    A method of stabilizing an inertial navigation system (INS), includes the steps of: receiving data from an inertial navigation system; and receiving a finite number of carrier phase observables using at least one GPS receiver from a plurality of GPS satellites; calculating a phase wind up correction; correcting at least one of the finite number of carrier phase observables using the phase wind up correction; and calculating a corrected IMU attitude or velocity or position using the corrected at least one of the finite number of carrier phase observables; and performing a step selected from the steps consisting of recording, reporting, or providing the corrected IMU attitude or velocity or position to another process that uses the corrected IMU attitude or velocity or position. A GPS stabilized inertial navigation system apparatus is also described.

  3. CROSS DRIFT ALCOVE/NICHE UTILITIES ANALYSIS

    International Nuclear Information System (INIS)

    S. Goodin

    1999-01-01

    The purpose of this analysis is to provide the design basis and general arrangement requirements of the non-potable water, waste water, compressed air and ventilation (post excavation) utilities required in support of the Cross Drift alcoves and niches

  4. Assisted living captures profitable market niche.

    Science.gov (United States)

    Pallarito, K

    1995-05-08

    The $15 billion assisted-living industry has captured a profitable market niche and created a star on Wall Street. Sunrise Retirement Home of Falls Church (Va.), right, is a facility of the nation's largest assisted-living provider.

  5. Ecological niches of open ocean phytoplankton taxa

    DEFF Research Database (Denmark)

    Brun, Philipp Georg; Vogt, Meike; Payne, Mark

    2015-01-01

    We characterize the realized ecological niches of 133 phytoplankton taxa in the open ocean based on observations from the MAREDAT initiative and a statistical species distribution model (MaxEnt). The models find that the physical conditions (mixed layer depth, temperature, light) govern large......-scale patterns in phytoplankton biogeography over nutrient availability. Strongest differences in the realized niche centers were found between diatoms and coccolithophores. Diatoms (87 species) occur in habitats with significantly lower temperatures, light intensity and salinity, with deeper mixed layers...... conditions in the open ocean. Our estimates of the realized niches roughly match the predictions of Reynolds' C-S-R model for the global ocean, namely that taxa classified as nutrient stress tolerant have niches at lower nutrient and higher irradiance conditions than light stress tolerant taxa. Yet...

  6. NICHE MARKET STRATEGY PADA INDUSTRI KERAMIK KASONGAN, YOGYAKARTA

    OpenAIRE

    Hadiprojo, Angelia Cindy

    2014-01-01

    Penelitian ini bertujuan untuk meneliti bagaimana cara perusahaan mengidentifikasi niche market, menentukan faktor yang penting untuk kesuksesan niche market, dan menjelaskan manfaat penerapan niche market strategy bagi perusahaan, serta menemukan peran niche market dalam industri keramik di masa depan. Pengumpulan data dalam penelitian ini menggunakan metode wawancara dan observasi. Penelitian dilakukan terhadap perusahaan keramik di Kasongan, Bantul, Yogyakarta yang termasuk di dalam ind...

  7. Inversion of GPS meteorology data

    Directory of Open Access Journals (Sweden)

    K. Hocke

    Full Text Available The GPS meteorology (GPS/MET experiment, led by the Universities Corporation for Atmospheric Research (UCAR, consists of a GPS receiver aboard a low earth orbit (LEO satellite which was launched on 3 April 1995. During a radio occultation the LEO satellite rises or sets relative to one of the 24 GPS satellites at the Earth's horizon. Thereby the atmospheric layers are successively sounded by radio waves which propagate from the GPS satellite to the LEO satellite. From the observed phase path increases, which are due to refraction of the radio waves by the ionosphere and the neutral atmosphere, the atmospheric parameter refractivity, density, pressure and temperature are calculated with high accuracy and resolution (0.5–1.5 km. In the present study, practical aspects of the GPS/MET data analysis are discussed. The retrieval is based on the Abelian integral inversion of the atmospheric bending angle profile into the refractivity index profile. The problem of the upper boundary condition of the Abelian integral is described by examples. The statistical optimization approach which is applied to the data above 40 km and the use of topside bending angle profiles from model atmospheres stabilize the inversion. The retrieved temperature profiles are compared with corresponding profiles which have already been calculated by scientists of UCAR and Jet Propulsion Laboratory (JPL, using Abelian integral inversion too. The comparison shows that in some cases large differences occur (5 K and more. This is probably due to different treatment of the upper boundary condition, data runaways and noise. Several temperature profiles with wavelike structures at tropospheric and stratospheric heights are shown. While the periodic structures at upper stratospheric heights could be caused by residual errors of the ionospheric correction method, the periodic temperature fluctuations at heights below 30 km are most likely caused by atmospheric waves (vertically

  8. GPS test range mission planning

    Science.gov (United States)

    Roberts, Iris P.; Hancock, Thomas P.

    The principal features of the Test Range User Mission Planner (TRUMP), a PC-resident tool designed to aid in deploying and utilizing GPS-based test range assets, are reviewed. TRUMP features time history plots of time-space-position information (TSPI); performance based on a dynamic GPS/inertial system simulation; time history plots of TSPI data link connectivity; digital terrain elevation data maps with user-defined cultural features; and two-dimensional coverage plots of ground-based test range assets. Some functions to be added during the next development phase are discussed.

  9. TAGGING, TRACKING AND LOCATING WITHOUT GPS

    Energy Technology Data Exchange (ETDEWEB)

    Cordaro, J.; Coleman, T.; Shull, D.

    2012-07-08

    The Savannah River National Laboratory (SRNL) was requested to lead a Law Enforcement Working Group that was formed to collaborate on common operational needs. All agencies represented on the working group ranked their need to tag, track, and locate a witting or unwitting target as their highest priority. Specifically, they were looking for technologies more robust than Global Positioning Satellite (GPS), could communicate back to the owner, and worked where normal cell phone communications did not work or were unreliable. SRNL brought together multiple technologies in a demonstration that was held in in various Alaska venues, including metropolitan, wilderness, and at-sea that met the working group's requirements. Using prototypical technologies from Boeing, On Ramp, and Fortress, SRNL was able to demonstrate the ability to track personnel and material in all scenarios including indoors, in heavily wooden areas, canyons, and in parking garages. In all cases GPS signals were too weak to measure. Bi-directional communication was achieved in areas that Wi-Fi, cell towers, or traditional radios would not perform. The results of the exercise will be presented. These technologies are considered ideal for tracking high value material such has nuclear material with a platform that allows seamless tracking anywhere in the world, indoors or outdoors.

  10. Why developmental niche construction is not selective niche construction: and why it matters.

    Science.gov (United States)

    Stotz, Karola

    2017-10-06

    In the last decade, niche construction has been heralded as the neglected process in evolution. But niche construction is just one way in which the organism's interaction with and construction of the environment can have potential evolutionary significance. The constructed environment does not just select for , it also produces new variation. Nearly 3 decades ago, and in parallel with Odling-Smee's article 'Niche-constructing phenotypes', West and King introduced the 'ontogenetic niche' to give the phenomena of exo genetic inheritance a formal name. Since then, a range of fields in the life sciences and medicine has amassed evidence that parents influence their offspring by means other than DNA (parental effects), and proposed mechanisms for how heritable variation can be environmentally induced and developmentally regulated. The concept of 'developmental niche construction' (DNC) elucidates how a diverse range of mechanisms contributes to the transgenerational transfer of developmental resources. My most central of claims is that whereas the selective niche of niche construction theory is primarily used to explain the active role of the organism in its selective environment, DNC is meant to indicate the active role of the organism in its developmental environment. The paper highlights the differences between the construction of the selective and the developmental niche, and explores the overall significance of DNC for evolutionary theory.

  11. GPS operations at Olkiluoto in 2011

    International Nuclear Information System (INIS)

    Koivula, H.; Kallio, U.; Nyberg, S.; Jokela, J.; Poutanen, M.

    2012-06-01

    The Finnish Geodetic Institute has studied crustal deformations at Olkiluoto, Kivetty and Romuvaara in co-operation with Posiva Oy since 1995. At Olkiluoto a total of 32 GPS campaigns have been carried out at inner network since 1995 and 17 campaigns at outer network since 2003. Kivetty and Romuvaara were not measured in 2011. In the Olkiluoto inner network 80 percent of the estimated change rates are smaller than 0.10 mm/a. One third of the change rates are statistically significant. They are mainly related to the Olkiluoto permanent station (GPS1) and to the pillars GPS6 and GPS13. The change rates related to GPS6 are not realistic due to the site-specific changes affecting the time series. The maximum change rate (-0.20 mm/a ± 0.05 mm/a) is related to GPS13. The time series of GPS13 is half the length of other pillars and therefore, the change rates are more uncertain. In the Olkiluoto outer network the maximum and statistically significant change rate is between GPS1-GPS11 (0.39 mm/a ± 0.06 mm/a). Pillar GPS12 was not observed this year. The change rates of baselines GPS1-GPS14 and GPS1-GPS15 are first time statistically significant. The change rates indicate a small movement of the GPS1 pillar. The baseline GPS1-GPS11 crosses an old fracture zone locating in the direction of the Eurajoensalmi, which might be a reason for the deformation. On the other hand, the Onkalo excavations in the vicinity of the Olkiluoto permanent station (GPS1) may cause some movement. Electronic distance measurements have been performed at Olkiluoto at the baseline GPS7-GPS8 using the Mekometer since 2002. The measurements have been carried out simultaneously with GPS campaigns. Based on 19 measurements in 10 years, the trends of the two time series seems to be similar. Due to unmodelled or dismodelled geometrical offsets and the scale difference between GPS measurements and EDM there is about 0.3 mm difference between distances GPS7-GPS8 derived from GPS measurements and EDM. It is

  12. Implementing GPS into Pave-IR.

    Science.gov (United States)

    2009-03-01

    To further enhance the capabilities of the Pave-IR thermal segregation detection system developed at the Texas Transportation Institute, researchers incorporated global positioning system (GPS) data collection into the thermal profiles. This GPS capa...

  13. Location - Global Positioning System (GPS) Photos

    Data.gov (United States)

    Army Corps of Engineers, Department of the Army, Department of Defense — Digital photos tagged with GPS location information. The St. Paul District maintains a digital library of over 10,000 GPS photos. Photos are often associated with...

  14. CLPX-Airborne: Airborne GPS Bistatic Radar

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set consists of measurements of GPS signals reflected from the Earth's surface and collected on an airborne platform. A modified GPS Delay Mapping Receiver...

  15. GPS operations at Olkiluoto in 2011

    Energy Technology Data Exchange (ETDEWEB)

    Koivula, H.; Kallio, U.; Nyberg, S.; Jokela, J.; Poutanen, M. [Finnish Geodetic Institute, Masala (Finland)

    2012-06-15

    The Finnish Geodetic Institute has studied crustal deformations at Olkiluoto, Kivetty and Romuvaara in co-operation with Posiva Oy since 1995. At Olkiluoto a total of 32 GPS campaigns have been carried out at inner network since 1995 and 17 campaigns at outer network since 2003. Kivetty and Romuvaara were not measured in 2011. In the Olkiluoto inner network 80 percent of the estimated change rates are smaller than 0.10 mm/a. One third of the change rates are statistically significant. They are mainly related to the Olkiluoto permanent station (GPS1) and to the pillars GPS6 and GPS13. The change rates related to GPS6 are not realistic due to the site-specific changes affecting the time series. The maximum change rate (-0.20 mm/a {+-} 0.05 mm/a) is related to GPS13. The time series of GPS13 is half the length of other pillars and therefore, the change rates are more uncertain. In the Olkiluoto outer network the maximum and statistically significant change rate is between GPS1-GPS11 (0.39 mm/a {+-} 0.06 mm/a). Pillar GPS12 was not observed this year. The change rates of baselines GPS1-GPS14 and GPS1-GPS15 are first time statistically significant. The change rates indicate a small movement of the GPS1 pillar. The baseline GPS1-GPS11 crosses an old fracture zone locating in the direction of the Eurajoensalmi, which might be a reason for the deformation. On the other hand, the Onkalo excavations in the vicinity of the Olkiluoto permanent station (GPS1) may cause some movement. Electronic distance measurements have been performed at Olkiluoto at the baseline GPS7-GPS8 using the Mekometer since 2002. The measurements have been carried out simultaneously with GPS campaigns. Based on 19 measurements in 10 years, the trends of the two time series seems to be similar. Due to unmodelled or dismodelled geometrical offsets and the scale difference between GPS measurements and EDM there is about 0.3 mm difference between distances GPS7-GPS8 derived from GPS measurements and EDM

  16. Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture.

    Science.gov (United States)

    Levis, Hannah J; Massie, Isobel; Dziasko, Marc A; Kaasi, Andreas; Daniels, Julie T

    2013-11-01

    Limbal epithelial stem cells are responsible for the maintenance of the human corneal epithelium and these cells reside in a specialised stem cell niche. They are located at the base of limbal crypts, in a physically protected microenvironment in close proximity to a variety of neighbouring niche cells. Design and recreation of elements of various stem cell niches have allowed researchers to simplify aspects of these complex microenvironments for further study in vitro. We have developed a method to rapidly and reproducibly create bioengineered limbal crypts (BLCs) in a collagen construct using a simple one-step method. Liquid is removed from collagen hydrogels using hydrophilic porous absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting topography on the surface of the thin collagen constructs resembles the dimensions of the stromal crypts of the human limbus. Human limbal epithelial cells seeded onto the surface of the constructs populate these BLCs and form numerous layers with a high proportion of the cells lining the crypts expressing putative stem cell marker, p63α. The HPAs are produced using a moulding process that is flexible and can be adapted depending on the requirements of the end user. Creation of defined topographical features using this process could be applicable to numerous tissue-engineering applications where varied 3-dimensional niche architectures are required. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Classification and comparison of niche services for developing strategy of medical tourism in Asian countries.

    Science.gov (United States)

    Chen, Hung-chi; Kuo, Hsin-chih; Chung, Kuo-Piao; Chang, Sophia; Su, Syi; Yang, Ming-chin

    2010-01-01

    , and (3) banned procedures that are not allowed legally in home countries of foreign patients, such as stem cell therapy. In establishing a niche service, a high-quality, nonmedical segment should be integrated as well.

  18. Contents of GPS Data Files

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, John P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Carver, Matthew Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Norman, Benjamin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-12-09

    There are no very detailed descriptions of most of these instruments in the literature – we will attempt to fix that problem in the future. The BDD instruments are described in [1]. One of the dosimeter instruments on CXD boxes is described in [2]. These documents (or web links to them) and a few others are in this directory tree. The cross calibration of the CXD electron data with RBSP is described in [3]. Each row in the data file contains the data from one time bin from a CXD or BDD instrument along with a variety of parameters derived from the data. Time steps are commandable but 4 minutes is a typical setting. These instruments are on many (but not all) GPS satellites which are currently in operation. The data come from either BDD instruments on GPS Block IIR satellites (SVN41 and 48), or else CXD-IIR instruments on GPS Block IIR and IIR-M satellites (SVN53-61) or CXD-IIF instruments on GPS block IIF satellites (SVN62-73). The CXD-IIR instruments on block IIR and IIR(M) satellites use the same design.

  19. The SMS-GPS-Trip-Method

    DEFF Research Database (Denmark)

    Reinau, Kristian Hegner; Harder, Henrik; Weber, Michael

    2015-01-01

    This article presents a new method for collecting travel behavior data, based on a combination of GPS tracking and SMS technology, coined the SMS–GPS-Trip method. The state-of-the-art method for collecting data for activity based traffic models is a combination of travel diaries and GPS tracking...

  20. Case: The Global Positioning System (GPS)

    Science.gov (United States)

    2014-05-01

    supporting four dedicated GPS Ground Antennas at Cape Canaveral Air Force Station in Florida, the Kwajalein Atoll, the Ascension Islands , and Diego Garcia...study earthquakes using GPS receivers placed along fault lines; and ... GPS also plays a major role in military combat, guiding missiles and bombs to

  1. Diagnosing dementia with confidence by GPs.

    NARCIS (Netherlands)

    Hout, H.P.J. van; Vernooij-Dassen, M.J.F.J.; Stalman, W.A.B.

    2007-01-01

    BACKGROUND: Earlier reports suggest limited clinical reasoning and substantial uncertainty of GPs in assessing patients suspected of dementia. OBJECTIVE: To explore the predictors of GPs to decide on the presence and absence of dementia as well as the predictors of diagnostic confidence of GPs.

  2. Niche Formation in the Mashup Ecosystem

    Directory of Open Access Journals (Sweden)

    Michael Weiss

    2013-05-01

    Full Text Available Mashups enable end-users to "mix and match" data and services available on the web to create applications. Their creation is supported by a complex ecosystem of i data providers who offer open APIs to users, ii users who combine APIs into mashups, and iii platforms, such as the ProgrammableWeb or Mashape, that facilitate the construction and publication of mashups. In this article, we argue that the evolution of the mashup ecosystem can be explained in terms of ecosystem niches anchored around hub or keystone APIs. The members of a niche are focused on an area of specialization (e.g., mapping applications and contribute their knowledge to the value proposition of the ecosystem as a whole. To demonstrate the formation of niches in the mashup ecosystem, we model groups of related mashups as species, and we reconstruct the evolution of mashup species through phylogenetic analysis.

  3. GPS in Travel and Activity Surveys

    DEFF Research Database (Denmark)

    Nielsen, Thomas Alexander Sick; Hovgesen, Henrik Harder

    2004-01-01

    The use of GPS-positioning as a monitoring tool in travel and activity surveys opens up a range of possibilities. Using a personal GPS device, the locations and movements of respondents can be followed over a longer period of time. It will then be possible to analyse how the use of urban spaces...... area. The paper presents the possibilities in travel and activity surveys with GPS and electronic questionnaires. Demonstrative mapping of test data from passive GPS registration of Copenhagen respondents is presented. The different survey possibilities given a combination of GPS and PDA based...

  4. A practioner's view on Strategic Niche Management

    International Nuclear Information System (INIS)

    Mourik, R.; Raven, R.P.J.M.

    2006-11-01

    Strategic Niche Management (SNM) is a tool to support the societal introduction of radical sustainable innovations. However, it has been mainly used in retrospective to analyse historical case studies. This report discusses SNM from a practioner's perspective with the main aim to articulate questions that should be addressed for translating SNM from an ex-post to an ex-ante tool. The main conclusion is that an SNM tool should focus on the level of 'niches' rather than single projects, i.e. SNM should aim to support (program) managers who aim at orchestrating the interaction between multiple experiments

  5. Sharing Representations Through Cognitive Niche Construction

    Directory of Open Access Journals (Sweden)

    Emanuele Bardone

    2007-03-01

    Full Text Available As a matter of fact, humans continuously delegate and distribute cognitive functions to the environment to lessen their limits. They build models, representations, and other various mediating structures that are thought to be good constructions. In doing this, humans are engaged in a process of cognitive niche construction. More precisely, we argue that a cognitive niche emerges from a network of continuous interplay between individuals and environment, in which people alter and modify the environment by mimetically externalizing fleeting thoughts, private ideas, etc., into external supports. This can turn out to be useful, especially for all those situations that require information transmission, shared knowledge, and more generally, cognitive resources.

  6. Identificação do nicho de progenitores mesenquimais no fígado de embriões e fetos caninos: uma fonte de células-tronco para terapia celular Identification of mesenchymal progenitor niches from liver of embryo and fetuses of canines: a source of stem cells for cell therapy

    Directory of Open Access Journals (Sweden)

    Daniele S. Martins

    2012-12-01

    potential. This organ during the fetal period in mammals acts as a transient hematopoietic niche, being the main organ responsible for hematopoiesis in the fetus, and contribute to the formation of permanent niche in the adult bone marrow, thus can be considered a niche for mesenchymal stem cells (MSC and parents. However, little is known about the location of these cells in FF, so the present study aims to identify the niche of mesenchymal progenitors in FF and dogs in order to contribute to the techniques of cell isolation and extraction. Together was performed to verify the expression of the transcription factor Oct-3/4 of the protein and DNA polymerase delta (PCNA. For the analysis of five embryos were used and 11 canine fetuses with gestational ages ranging from 25-60 days. The results elucidated from 25 days of gestation showed the FF is bulky and composed of all the typical structures, among them the portal triad, bile ducts and hepatic artery branches. With 30 days of gestation were identified the first requirements of mesenchymal progenitors (MP at 60 days while the niches were completely formed with location similar to adult liver (AL. However, cells immunoreactives for Oct-3/4 were not identified, therefore, point out that the FL is a source of PM, presenting as an alternative for therapeutic purposes as well as for studying the developmental biology of MSC and parents.

  7. Niche versus neutrality: a dynamical analysis

    Science.gov (United States)

    Michael Kalyuzhny; Efrat Seri; Rachel Chocron; Curtis H. Flather; Ronen Kadmon; Nadav M. Shnerb

    2014-01-01

    Understanding the forces shaping ecological communities is of crucial importance for basic science and conservation. After 50 years in which ecological theory has focused on either stable communities driven by niche-based forces or nonstable “neutral” communities driven by demographic stochasticity, contemporary theories suggest that ecological communities are driven...

  8. An emerging niche market opportunity. Part I.

    Science.gov (United States)

    Pulaski, M J

    1997-01-01

    Society is split between a desire for access to quality health care and a reluctance, by some, to pay for it. Looking at this cost/access dichotomy historically enables one to recognize an emerging niche market--discriminating, affluent consumers willing to pay for better health care.

  9. Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment

    NARCIS (Netherlands)

    Eisenblaetter, M.; Flores-Borja, F.; Lee, J.J.; Wefers, C.; Smith, H.; Hueting, R.; Cooper, M.S.; Blower, P.J.; Patel, D.; Rodriguez-Justo, M.; Milewicz, H.; Vogl, T.; Roth, J.; Tutt, A.; Schaeffter, T.; Ng, T.

    2017-01-01

    Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal

  10. Are we overestimating the niche? Removing marginal localities helps ecological niche models detect environmental barriers

    OpenAIRE

    Soley?Guardia, Mariano; Guti?rrez, Eli?cer E.; Thomas, Darla M.; Ochoa?G, Jos?; Aguilera, Marisol; Anderson, Robert P.

    2016-01-01

    Abstract Correlative ecological niche models (ENMs) estimate species niches using occurrence records and environmental data. These tools are valuable to the field of biogeography, where they are commonly used to infer potential connectivity among populations. However, a recent study showed that when locally relevant environmental data are not available, records from patches of suitable habitat protruding into otherwise unsuitable regions (e.g., gallery forests within dry areas) can lead to ov...

  11. Applications of GPS technologies to field sports.

    Science.gov (United States)

    Aughey, Robert J

    2011-09-01

    Global positioning system (GPS) technology was made possible after the invention of the atomic clock. The first suggestion that GPS could be used to assess the physical activity of humans followed some 40 y later. There was a rapid uptake of GPS technology, with the literature concentrating on validation studies and the measurement of steady-state movement. The first attempts were made to validate GPS for field sport applications in 2006. While GPS has been validated for applications for team sports, some doubts continue to exist on the appropriateness of GPS for measuring short high-velocity movements. Thus, GPS has been applied extensively in Australian football, cricket, hockey, rugby union and league, and soccer. There is extensive information on the activity profile of athletes from field sports in the literature stemming from GPS, and this includes total distance covered by players and distance in velocity bands. Global positioning systems have also been applied to detect fatigue in matches, identify periods of most intense play, different activity profiles by position, competition level, and sport. More recent research has integrated GPS data with the physical capacity or fitness test score of athletes, game-specific tasks, or tactical or strategic information. The future of GPS analysis will involve further miniaturization of devices, longer battery life, and integration of other inertial sensor data to more effectively quantify the effort of athletes.

  12. Ten Niche Strategies To Commercialize New High-Tech Products

    NARCIS (Netherlands)

    Ortt, J.R.; Langley, D.J.; Pals, N.

    2013-01-01

    There are serious gaps in the scientific literature relating to niche strategies as a means for commercializing new high-tech products. In particular, there is no clarity about what types of niche strategies can be distinguished, or how a niche strategy can be selected to suit a certain ituation. In

  13. Functional traits, convergent evolution, and periodic tables of niches.

    Science.gov (United States)

    Winemiller, Kirk O; Fitzgerald, Daniel B; Bower, Luke M; Pianka, Eric R

    2015-08-01

    Ecology is often said to lack general theories sufficiently predictive for applications. Here, we examine the concept of a periodic table of niches and feasibility of niche classification schemes from functional trait and performance data. Niche differences and their influence on ecological patterns and processes could be revealed effectively by first performing data reduction/ordination analyses separately on matrices of trait and performance data compiled according to logical associations with five basic niche 'dimensions', or aspects: habitat, life history, trophic, defence and metabolic. Resultant patterns then are integrated to produce interpretable niche gradients, ordinations and classifications. Degree of scheme periodicity would depend on degrees of niche conservatism and convergence causing species clustering across multiple niche dimensions. We analysed a sample data set containing trait and performance data to contrast two approaches for producing niche schemes: species ordination within niche gradient space, and niche categorisation according to trait-value thresholds. Creation of niche schemes useful for advancing ecological knowledge and its applications will depend on research that produces functional trait and performance datasets directly related to niche dimensions along with criteria for data standardisation and quality. As larger databases are compiled, opportunities will emerge to explore new methods for data reduction, ordination and classification. © 2015 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  14. Niching genetic algorithms for optimization in electromagnetics - I. Fundamentals

    OpenAIRE

    Sareni, Bruno; Krähenbühl, Laurent; Nicolas, Alain

    1998-01-01

    Niching methods extend genetic algorithms and permit the investigation of multiple optimal solutions in the search space. In this paper, we review and discuss various strategies of niching for optimization in electromagnetics. Traditional mathematical problems and an electromagnetic benchmark are solved using niching genetic algorithms to show their interest in real world optimization.

  15. Combgap Promotes Ovarian Niche Development and Chromatin Association of EcR-Binding Regions in BR-C.

    Directory of Open Access Journals (Sweden)

    Anna Hitrik

    2016-11-01

    Full Text Available The development of niches for tissue-specific stem cells is an important aspect of stem cell biology. Determination of niche size and niche numbers during organogenesis involves precise control of gene expression. How this is achieved in the context of a complex chromatin landscape is largely unknown. Here we show that the nuclear protein Combgap (Cg supports correct ovarian niche formation in Drosophila by controlling ecdysone-Receptor (EcR- mediated transcription and long-range chromatin contacts in the broad locus (BR-C. Both cg and BR-C promote ovarian growth and the development of niches for germ line stem cells. BR-C levels were lower when Combgap was either reduced or over-expressed, indicating an intricate regulation of the BR-C locus by Combgap. Polytene chromosome stains showed that Cg co-localizes with EcR, the major regulator of BR-C, at the BR-C locus and that EcR binding to chromatin was sensitive to changes in Cg levels. Proximity ligation assay indicated that the two proteins could reside in the same complex. Finally, chromatin conformation analysis revealed that EcR-bound regions within BR-C, which span ~30 KBs, contacted each other. Significantly, these contacts were stabilized in an ecdysone- and Combgap-dependent manner. Together, these results highlight Combgap as a novel regulator of chromatin structure that promotes transcription of ecdysone target genes and ovarian niche formation.

  16. The Impact of Ecological Niche on Adaptive Flexibility of Sensory Circuitry

    Directory of Open Access Journals (Sweden)

    Sarah L. Pallas

    2017-06-01

    Full Text Available Evolution and development are interdependent, particularly with regard to the construction of the nervous system and its position as the machine that produces behavior. On the one hand, the processes directing development and plasticity of the brain provide avenues through which natural selection can sculpt neural cell fate and connectivity, and on the other hand, they are themselves subject to selection pressure. For example, mutations that produce heritable perturbations in neuronal birth and death rates, transcription factor expression, or availability of axon guidance factors within sensory pathways can markedly affect the development of form and thus the function of stimulus decoding circuitry. This evolvability of flexible circuits makes them more adaptable to environmental variation. Although there is general agreement on this point, whether the sensitivity of circuits to environmental influence and the mechanisms underlying development and plasticity of sensory pathways are similar across species from different ecological niches has received almost no attention. Neural circuits are generally more sensitive to environmental influences during an early critical period, but not all niches afford the same access to stimuli in early life. Furthermore, depending on predictability of the habitat and ecological niche, sensory coding circuits might be more susceptible to sensory experience in some species than in others. Despite decades of work on understanding the mechanisms underlying critical period plasticity, the importance of ecological niche in visual pathway development has received little attention. Here, I will explore the relationship between critical period plasticity and ecological niche in mammalian sensory pathways.

  17. GPS User Devices Parameter Control Methods

    OpenAIRE

    Klūga, A; Kuļikovs, M; Beļinska, V; Zeļenkovs, A

    2007-01-01

    In our day’s wide assortment of GPS user devices is manufacture. How to verify that parameters of the real device corresponds to parameters that manufacture shows. How to verify that parameters have not been changed during the operation time. The last one is very important for aviation GPS systems, which must be verified before the flight, but the values of parameter in time of repair works. This work analyses GPS user devices parameters control methods.

  18. Global Positioning System III (GPS III)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-292 Global Positioning System III ( GPS III) As of FY 2017 President’s Budget Defense...Acquisition Management Information Retrieval (DAMIR) March 23, 2016 16:15:29 UNCLASSIFIED GPS III December 2015 SAR March 23, 2016 16:15:29 UNCLASSIFIED 2...Document OSD - Office of the Secretary of Defense O&S - Operating and Support PAUC - Program Acquisition Unit Cost GPS III December 2015 SAR March 23

  19. Miniaturized GPS/MEMS IMU integrated board

    Science.gov (United States)

    Lin, Ching-Fang (Inventor)

    2012-01-01

    This invention documents the efforts on the research and development of a miniaturized GPS/MEMS IMU integrated navigation system. A miniaturized GPS/MEMS IMU integrated navigation system is presented; Laser Dynamic Range Imager (LDRI) based alignment algorithm for space applications is discussed. Two navigation cameras are also included to measure the range and range rate which can be integrated into the GPS/MEMS IMU system to enhance the navigation solution.

  20. Identification of a Developmental Gene Expression Signature, Including HOX Genes, for the Normal Human Colonic Crypt Stem Cell Niche: Overexpression of the Signature Parallels Stem Cell Overpopulation During Colon Tumorigenesis

    OpenAIRE

    Bhatlekar, Seema; Addya, Sankar; Salunek, Moreh; Orr, Christopher R.; Surrey, Saul; McKenzie, Steven; Fields, Jeremy Z.; Boman, Bruce M.

    2013-01-01

    Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region—the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other cryp...

  1. GPS/GNSS Antenna Characterization : GPS-ABC Workshop V RTCA Washington, DC October 14, 2016.

    Science.gov (United States)

    2016-10-14

    One component of the Department of Transportations GPS Adjacent Band : Compatibility Study is the characterization of GPS/GNSS receiver antennas : Such characterization is needed to: : Compare radiated and conducted (wired) test result...

  2. GPS operations at Olkiluoto in 2009

    International Nuclear Information System (INIS)

    Kallio, U.; Nyberg, S.; Koivula, H.; Jokela, J.; Poutanen, M.; Ahola, J.

    2010-06-01

    The GPS based deformation studies have been made at the investigation areas of Posiva since 1995, when the network of ten GPS pillars was established at Olkiluoto. One pillar in the investigation area belongs to the Finnish permanent GPS network, FinnRef. 28 GPS measurement campaigns have been carried out at Olkiluoto since 1995. According to the time series of the GPS results 1/3 of the baselines at Olkiluoto have statistically significant change rates. However, the observed movements are smaller than ±0.20 mm/a. There are five pillars, which have statistically significant horizontal velocities at Olkiluoto. These local velocity components are small but taking into account the standard deviations the largest velocity components seems to be reliably determined. At Olkiluoto a baseline for electronic distance measurements (EDM) was built in 2002. The baseline has been measured using EDM instruments in connection to the GPS observations. Changes in he difference between the GPS and EDM results indicate the systematic change in GPS results. No corrections based on only one baseline were not applied to GPS vectors. The GPS network at Olkiluoto was extended in 2003. The new pillars were built close to Kuivalahti village and on a small island of Iso Pyrekari. According to the geological evidence it is expected that a fracture zone is located between the new stations, thus enabling the determination of possible deformations along the fracture zone. The new pillars have been observed since 2003 and now we have computed the first deformation analysis from the six years data. Four new permanent stations will be established in summer 2010 at Olkiluoto. We have automated the processing of the campaign data by using the Bernese processing engine (BPE) together with our own Perl scripts. The local crustal deformations have been studied in GeoSatakunta project, too. This GPS network is located in Cities of Pori and Rauma and their neighbouring municipalities. Two new pillars

  3. The GPS Laser Retroreflector Array Project

    Science.gov (United States)

    Merkowitz, Stephen M.

    2012-01-01

    Systematic co-location in space through the precision orbit determination of GPS satellites via satellite laser ranging will contribute significantly towards improving the accuracy and stability of the international terrestrial reference frame. NASA recently formed the GPS Laser Retroreflector Array Project to develop and deliver retroreflectors for integration on the next generation of GPS satellites. These retroreflectors will be an important contributor to achieving a global accuracy of 1.0 mm and 0.1 mm/year stability in the international terrestrial reference frame. We report here the current status of the GPS Laser Retroreflector Array Project.

  4. [Niche comparison of dominant entomopathogenic fungi in three forest ecosystems].

    Science.gov (United States)

    Chen, Ming-Jun; Huang, Bo; Li, Zeng-Zhi

    2011-05-01

    An investigation was made on the quantitative composition, niche width, and niche overlap of dominant entomopathogenic fungi in three different forest ecosystems, i.e., natural broad-leaved forest, natural secondary broad-leaved forest, and pure Masson' s pine plantation. In the three forest ecosystems, Beauveria bassiana was the first dominant species in natural secondary broad-leaved forest, the second in pure Masson's pine plantation, and the third in natural broad-leaved forest. B. bassiana had the broadest temporal niche width and nutritional niche width, whereas the dominant species Isaria cateinannulata, L. farinose, and I. tenuipes had much smaller niche widths. Meanwhile, B. bassiana had larger temporal niche overlaps but smaller nutritional niche overlaps with other dominant entomopathogenic fungi. It was suggested that in the three forest ecosystems, B. bassiana had the longest occurrence duration, widest host range, and strongest environmental adaptability.

  5. Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.

    Science.gov (United States)

    Bhatlekar, Seema; Addya, Sankar; Salunek, Moreh; Orr, Christopher R; Surrey, Saul; McKenzie, Steven; Fields, Jeremy Z; Boman, Bruce M

    2014-01-15

    Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis.

  6. Mammalian niche conservation through deep time.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

  7. Human niche, human behaviour, human nature.

    Science.gov (United States)

    Fuentes, Agustin

    2017-10-06

    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  8. Identifying Walking Trips Using GPS Data.

    Science.gov (United States)

    Cho, Gi-Hyoug; Rodríguez, Daniel A; Evenson, Kelly R

    2011-02-01

    this study developed and tested algorithms to identify outdoor walking trips from portable global positioning system (GPS) units in free-living conditions. the study included a calibration and a validation phase. For the calibration phase, we determined the best algorithm from 35 person-days of data. Measures of agreement regarding the daily number and duration of diary-reported and GPS-identified trips were used. In the validation phase, the best algorithm was applied to an additional and separate 136 person-days of diary and GPS data. the preferred algorithm in the calibration phase resulted in 90% of trips identified from the GPS data being found in the diary, whereas 81% of trips reported in the diary being found in the GPS data. The preferred algorithm used 1) a maximum 3-min gap between points to define a trip, 2) at least 5 min or more of continuous GPS points, 3) a speed range between 2 and 8.0 km·h, 4) at least 30 m of displacement between the start and end points of a trip, and 5) merged walking trips when the time gap between trips was less than 3 min. With the validation data, substantial agreement between the GPS and the diary was achieved, with 86% of trips identified from the GPS data found in the diary and 77% of trips reported in the diary found in the GPS data. the algorithm identified free-living walking trips of more than 5 min in duration. The ability to identify outdoor walking trips from GPS data can be improved by reducing recording intervals used in the GPS units and monitoring participant compliance. Further research is desirable to determine whether concurrent wearing of an accelerometer may improve the ability to detect walking more accurately.

  9. Multidimensional tree niches in a tropical dry forest.

    Science.gov (United States)

    Pulla, Sandeep; Suresh, Hebbalalu S; Dattaraja, Handanakere S; Sukumar, Raman

    2017-05-01

    The extent to which interspecific niche differences structure plant communities is highly debated, with extreme viewpoints ranging from fine-scaled niche partitioning, where every species in the community is specialized to a distinct niche, to neutrality, where species have no niche or fitness differences. However, there exists a default position wherein niches of species in a community are determined by their evolutionary and biogeographic histories, irrespective of other species within the community. According to this viewpoint, a broad range of pair-wise niche overlaps-from completely overlapping to completely distinct-are expected in any community without the need to invoke interspecific interactions. We develop a method that can test for both habitat associations and niche differences along an arbitrary number of spatial and temporal niche dimensions and apply it to a 24-yr data set of the eight dominant woody-plant species (representing 84% and 76% of total community abundance and basal area, respectively) from a 50-ha permanent plot in a southern Indian tropical dry forest, using edaphic, topographic, and precipitation variables as niche axes. Species separated into two broad groups in niche space-one consisting of three canopy species and the other of a canopy species and four understory species-along axes that corresponded mainly to variation in soil P, Al and a topographic index of wetness. Species within groups tended to have significantly greater niche overlap than expected by chance. Community-wide niche overlap in spatial and temporal niche axes was never smaller than expected by chance. Species-habitat associations were neither necessary nor sufficient preconditions for niche differences to be present. Our results suggest that this tropical dry-forest community consists of several tree species with broadly overlapping niches, and where significant niche differences do exist, they are not readily interpretable as evidence for niche differentiation. We

  10. Development of GPS survey data management protocols/policy.

    Science.gov (United States)

    2010-08-01

    This project developed a statewide policy and criteria for collecting, analyzing, and managing global position system (GPS) survey data. The research project determined the needs of the Department in adopting the GPS real time kinetic (GPS RTK) stake...

  11. Ideas for Future GPS Timing Improvements

    Science.gov (United States)

    Hutsell, Steven T.

    1996-01-01

    Having recently met stringent criteria for full operational capability (FOC) certification, the Global Positioning System (GPS) now has higher customer expectations than ever before. In order to maintain customer satisfaction, and the meet the even high customer demands of the future, the GPS Master Control Station (MCS) must play a critical role in the process of carefully refining the performance and integrity of the GPS constellation, particularly in the area of timing. This paper will present an operational perspective on several ideas for improving timing in GPS. These ideas include the desire for improving MCS - US Naval Observatory (USNO) data connectivity, an improved GPS-Coordinated Universal Time (UTC) prediction algorithm, a more robust Kalman Filter, and more features in the GPS reference time algorithm (the GPS composite clock), including frequency step resolution, a more explicit use of the basic time scale equation, and dynamic clock weighting. Current MCS software meets the exceptional challenge of managing an extremely complex constellation of 24 navigation satellites. The GPS community will, however, always seek to improve upon this performance and integrity.

  12. External Review of GPS LifePlan

    Science.gov (United States)

    Arendale, David R.

    2008-01-01

    The GPS LifePlan is an interactive resource that helps students succeed in reaching their career, education and personal goals. GPS stands for "GOALS + PLANS = SUCCESS". http://gpslifeplan.org This holistic academic and student development program provides a structure for students to define their goals and helps them establish plans to…

  13. GPS queues with heterogeneous traffic classes

    NARCIS (Netherlands)

    Borst, Sem; Mandjes, M.R.H.; van Uitert, Miranda

    2002-01-01

    We consider a queue fed by a mixture of light-tailed and heavy-tailed traffic. The two traffic classes are served in accordance with the generalized processor sharing (GPS) discipline. GPS-based scheduling algorithms, such as weighted fair queueing (WFQ), have emerged as an important mechanism for

  14. Stigma and GPs' perceptions of dementia

    NARCIS (Netherlands)

    Gove, D.; Downs, M.; Vernooij-Dassen, M.; Small, N.

    2016-01-01

    OBJECTIVES: General practitioners (GPs) are crucial to improving timely diagnosis, but little is reported about how they perceive dementia, and whether their perceptions display any elements of stigma. The aim of this study was to explore how GPs' perceptions of dementia map onto current

  15. Wave Measurements Using GPS Velocity Signals

    Directory of Open Access Journals (Sweden)

    Chia Chuen Kao

    2011-01-01

    Full Text Available This study presents the idea of using GPS-output velocity signals to obtain wave measurement data. The application of the transformation from a velocity spectrum to a displacement spectrum in conjunction with the directional wave spectral theory are the core concepts in this study. Laboratory experiments were conducted to verify the accuracy of the inversed displacement of the surface of the sea. A GPS device was installed on a moored accelerometer buoy to verify the GPS-derived wave parameters. It was determined that loss or drifting of the GPS signal, as well as energy spikes occurring in the low frequency band led to erroneous measurements. Through the application of moving average skill and a process of frequency cut-off to the GPS output velocity, correlations between GPS-derived, and accelerometer buoy-measured significant wave heights and periods were both improved to 0.95. The GPS-derived one-dimensional and directional wave spectra were in agreement with the measurements. Despite the direction verification showing a 10° bias, this exercise still provided useful information with sufficient accuracy for a number of specific purposes. The results presented in this study indicate that using GPS output velocity is a reasonable alternative for the measurement of ocean waves.

  16. Dietary niche variation and its relationship to lizard population density.

    Science.gov (United States)

    Novosolov, Maria; Rodda, Gordon H; Gainsbury, Alison M; Meiri, Shai

    2018-01-01

    Insular species are predicted to broaden their niches, in response to having fewer competitors. They can thus exploit a greater proportion of the resource spectrum. In turn, broader niches are hypothesized to facilitate (or be a consequence of) increased population densities. We tested whether insular lizards have broader dietary niches than mainland species, how it relates to competitor and predator richness, and the nature of the relationship between population density and dietary niche breadth. We collected population density and dietary niche breadth data for 36 insular and 59 mainland lizard species, and estimated competitor and predator richness at the localities where diet data were collected. We estimated dietary niche shift by comparing island species to their mainland relatives. We controlled for phylogenetic relatedness, body mass and the size of the plots over which densities were estimated. We found that island and mainland species had similar niche breadths. Dietary niche breadth was unrelated to competitor and predator richness, on both islands and the mainland. Population density was unrelated to dietary niche breadth across island and mainland populations. Our results indicate that dietary generalism is not an effective way of increasing population density nor is it result of lower competitive pressure. A lower variety of resources on islands may prevent insular animals from increasing their niche breadths even in the face of few competitors. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  17. Evolution of pollination niches in a generalist plant clade.

    Science.gov (United States)

    Gómez, José María; Perfectti, Francisco; Abdelaziz, Mohamed; Lorite, Juan; Muñoz-Pajares, Antonio Jesús; Valverde, Javier

    2015-01-01

    It is widely assumed that floral diversification occurs by adaptive shifts between pollination niches. In contrast to specialized flowers, identifying pollination niches of generalist flowers is a challenge. Consequently, how generalist pollination niches evolve is largely unknown. We apply tools from network theory and comparative methods to investigate the evolution of pollination niches among generalist species belonging to the genus Erysimum. These species have similar flowers. We found that the studied species may be grouped in several multidimensional niches separated not by a shift of pollinators, but instead by quantitative variation in the relative abundance of pollinator functional groups. These pollination niches did not vary in generalization degree; we did not find any evolutionary trend toward specialization within the studied clade. Furthermore, the evolution of pollination niche fitted to a Brownian motion model without phylogenetic signal, and was characterized by frequent events of niche convergences and divergences. We presume that the evolution of Erysimum pollination niches has occurred mostly by recurrent shifts between slightly different generalized pollinator assemblages varying spatially as a mosaic and without any change in specialization degree. Most changes in pollination niches do not prompt floral divergence, a reason why adaptation to pollinators is uncommon in generalist plants. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  18. Niche conservatism and the invasive potential of the wild boar.

    Science.gov (United States)

    Sales, Lilian Patrícia; Ribeiro, Bruno R; Hayward, Matt Warrington; Paglia, Adriano; Passamani, Marcelo; Loyola, Rafael

    2017-09-01

    Niche conservatism, i.e. the retention of a species' fundamental niche through evolutionary time, is cornerstone for biological invasion assessments. The fact that species tend to maintain their original climate niche allows predictive maps of invasion risk to anticipate potential invadable areas. Unravelling the mechanisms driving niche shifts can shed light on the management of invasive species. Here, we assessed niche shifts in one of the world's worst invasive species: the wild boar Sus scrofa. We also predicted potential invadable areas based on an ensemble of three ecological niche modelling methods, and evaluated the performance of models calibrated with native vs. pooled (native plus invaded) species records. By disentangling the drivers of change on the exotic wild boar population's niches, we found strong evidence for niche conservatism during biological invasion. Ecological niche models calibrated with both native and pooled range records predicted convergent areas. Also, observed niche shifts are mostly explained by niche unfilling, i.e. there are unoccupied areas in the exotic range where climate is analogous to the native range. Niche unfilling is expected as result of recent colonization and ongoing dispersal, and was potentially stronger for the Neotropics, where a recent wave of introductions for pig-farming and game-hunting has led to high wild boar population growth rates. The invasive potential of wild boar in the Neotropics is probably higher than in other regions, which has profound management implications if we are to prevent their invasion into species-rich areas, such as Amazonia, coupled with expansion of African swine fever and possibly great economic losses. Although the originally Eurasian-wide distribution suggests a pre-adaptation to a wide array of climates, the wild boar world-wide invasion does not exhibit evidence of niche evolution. The invasive potential of the wild boar therefore probably lies on the reproductive, dietary and

  19. Using GPS for studying pastoral mobility

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine

    2017-01-01

    geographer familiar with satellite remote sensing and GIS, I pondered how these relatively new technologies could be combined with classic ethnographic fieldwork, which we also use in human geography. I decided to use handheld GPS devices for tracking the pastoralists and their herds. My study was, as far...... as I know, the first one to use GPS for studying pastoral mobility. A total of 10 pastoralists were trained in using a GPS and asked to map their movements. This information was combined with satellite imagery on one hand and qualitative interviews on the other. This case study provides an account...... of the practical aspects of using GPS, taking the reader to the heart of some methodological issues that arose in the course of the research. The case sheds light on the particular challenges in using GPS for eliciting information about pastoral mobility. Thinking about such challenges leads to more general...

  20. GPS Precision Timing at CERN

    CERN Document Server

    Beetham, C G

    1999-01-01

    For the past decade, the Global Positioning System (GPS) has been used to provide precise time, frequency and position co-ordinates world-wide. Recently, equipment has become available specialising in providing extremely accurate timing information, referenced to Universal Time Co-ordinates (UTC). This feature has been used at CERN to provide time of day information for systems that have been installed in the Proton Synchrotron (PS), Super Proton Synchrotron (SPS) and the Large Electron Positron (LEP) machines. The different systems are described as well as the planned developments, particularly with respect to optical transmission and the Inter-Range Instrumentation Group IRIG-B standard, for future use in the Large Hadron Collider (LHC).

  1. Citizen-science, Geoethics and Human Niche

    Science.gov (United States)

    Bohle, Martin

    2017-04-01

    The anthropogenic biogeosphere or 'human niche' is the intersection of the biogeosphere and the sphere of human activities of social, economic, cultural and political nature. The application case for geoethics, namely "appropriate behaviours and practices, wherever human activities interact with the Earth system" [1], is about niche building. Geoethics is about the conduct of people and geoscientists, respectively their ordinary lifestyles and professional activities. Geoscience professionals notice the diverse economic, social and cultural living conditions of people, and the application cases of geosciences mirror the diversity of the global social sphere. Subsequently it is argued: A) when considering the ethical dimensions of global niche building then geosciences should feature 'citizen geoscience'; and B) when considering the functioning of a knowledge-based society under conditions of anthropogenic global change then 'citizen geoscience' facilitates applying that knowledge base. (A) Regarding 'niche building': The design of production systems and consumption patterns embeds geoscience know-how and relates it to the everyday life. Any citizen's activities purposefully interconnect to the biogeosphere for well-being, care-taking, and reproduction, although habitually without involving a geoscientist in professional capacity. In that implicit manner the everyday behaviours and practices of people influence Earth system dynamic. This renders their inherent geoscience know-how a public good as it makes their ignorance a public risk. A comfortable human niche for billions of people requires a global biogeosphere that is disrupted little by citizens' activities and exposes them to hazards that can be tamed. Quite the reverse, anthropogenic global change will disturb living conditions for many citizen. Much geoscience know-how will have to be deployed to tame disturbances in a socially sustainable manner. Sustainability in turn needs involvement of citizens in

  2. Erythroblastic Islands: Specialized Mircoenvironmental Niches forErythropoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Chasis, Joel Anne

    2006-01-06

    This review focuses on current understanding of molecular mechanisms operating within erythroblastic islands including cell-cell adhesion, regulatory feedback, and central macrophage function. RECENT FINDINGS: Erythroblasts express a variety of adhesion molecules and recently two interactions have been identified that appear to be critical for island integrity. Erythroblast macrophage protein, expressed on erythroblasts and macrophages, mediates cell-cell attachments via homophilic binding. Erythroblast intercellular adhesion molecule-4 links erythroblasts to macrophages through interaction with macrophage alphav integrin. In intercellular adhesion molecule-4 knockout mice, erythroblastic islands are markedly reduced, whereas the erythroblast macrophage protein null phenotype is severely anemic and embryonic lethal. Retinoblastoma tumor suppressor (Rb) protein stimulates macrophage differentiation by counteracting inhibition of Id2 on PU.1, a transcription factor that is a crucial regulator of macrophage differentiation. Rb-deficient macrophages do not bind Rb null erythroblasts and the Rb null phenotype is anemic and embryonic lethal. Lastly, extruded nuclei rapidly expose phosphatidylserine on their surface, providing a recognition signal similar to apoptotic cells. SUMMARY: Although understanding of molecular mechanisms operating within islands is at an early stage, tantalizing evidence suggests that erythroblastic islands are specialized niches where intercellular interactions in concert with cytokines play critical roles in regulating erythropoiesis.

  3. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

    Directory of Open Access Journals (Sweden)

    Marc Amoyel

    2016-01-01

    Full Text Available The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs, which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs, which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.

  4. Climate niche differentiation between two passerines despite ongoing gene flow.

    Science.gov (United States)

    Shaner, Pei-Jen L; Tsao, Tzu-Hsuan; Lin, Rong-Chien; Liang, Wei; Yeh, Chia-Fen; Yang, Xiao-Jun; Lei, Fu-Min; Zhou, Fang; Yang, Can-Chao; Hung, Le Manh; Hsu, Yu-Cheng; Li, Shou-Hsien

    2015-05-01

    Niche evolution underpins the generation and maintenance of biological diversity, but niche conservatism, in which niches remain little changed over time in closely related taxa, and the role of ecology in niche evolution are continually debated. To test whether climate niches are conserved in two closely related passerines in East Asia - the vinous-throated (Paradoxornis webbianus) and ashy-throated (P. alphonsianus) parrotbills - we established their potential allopatric and sympatric regions using ecological niche models and compared differences in their climate niches using niche overlap indices in background tests and multivariate statistical analyses. We also used polymorphism data on 44 nuclear genes to infer their divergence demography. We found that these two parrotbills occupy different climate niches, in both their allopatric and potential sympatric regions. Because the potential sympatric region is the area predicted to be suitable for both parrotbills based on the ecological niche models, it can serve as a natural common garden. Therefore, their observed niche differences in this potential sympatry were not simply rendered by phenotypic plasticity and probably had a genetic basis. Our genetic analyses revealed that the two parrotbills are not evolutionarily independent for the most recent part of their divergence history. The two parrotbills diverged c. 856,000 years ago and have had substantial gene flow since a presumed secondary contact c. 290,000 years ago. This study provides an empirical case demonstrating that climate niches may not be homogenized in nascent species in spite of substantial, ongoing gene flow, which in turn suggests a role for ecology in promoting and maintaining diversification among incipient species. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

  5. Evidence of climatic niche shift during biological invasion

    OpenAIRE

    Broennimann, Olivier; Treier, Urs A.; Müller-Schärer, Heinz; Thuiller, W.; Peterson, A. T.; Guisan, Antoine

    2007-01-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species’ invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of th...

  6. Niche entrepreneurs in urban systems integration : On the role of individuals in niche formation

    NARCIS (Netherlands)

    Pesch, U.; Vernay, A.L.; van Bueren, E.M.; Pandis Iveroth, S

    2017-01-01

    In many sustainable urban innovation projects, the efforts, endurance and enthusiasm of individuals at key positions are considered a crucial factor for success. This article studies the role of individual agency in sociotechnical niches by using Kingdon’s agenda-setting model. Although strategic

  7. PiVoT GPS Receiver

    Science.gov (United States)

    Wennersten, Miriam Dvorak; Banes, Anthony Vince; Boegner, Gregory J.; Dougherty, Lamar; Edwards, Bernard L.; Roman, Joseph; Bauer, Frank H. (Technical Monitor)

    2001-01-01

    NASA Goddard Space Flight Center has built an open architecture, 24 channel space flight GPS receiver. The CompactPCI PiVoT GPS receiver card is based on the Mitel/GEC Plessey Builder-2 board. PiVoT uses two Plessey 2021 correlators to allow tracking of up to 24 separate GPS SV's on unique channels. Its four front ends can support four independent antennas, making it a useful card for hosting GPS attitude determination algorithms. It has been built using space quality, radiation tolerant parts. The PiVoT card will track a weaker signal than the original Builder 2 board. It also hosts an improved clock oscillator. The PiVoT software is based on the original Plessey Builder 2 software ported to the Linux operating system. The software is POSIX complaint and can easily be converted to other POSIX operating systems. The software is open source to anyone with a licensing agreement with Plessey. Additional tasks can be added to the software to support GPS science experiments or attitude determination algorithms. The next generation PiVoT receiver will be a single radiation hardened CompactPCI card containing the microprocessor and the GPS receiver optimized for use above the GPS constellation. PiVoT was flown successfully on a balloon in July, 2001, for its first non-simulated flight.

  8. Briefing highlights space weather risks to GPS

    Science.gov (United States)

    Tretkoff, Ernie

    2011-07-01

    Solar storms, which are expected to increase as the Sun nears the most active phase of the solar cycle, can disrupt a variety of technologies on which society relies. Speakers at a 22 June briefing on Capitol Hill in Washington, D. C., focused on how space weather can affect the Global Positioning System (GPS), which is used in a wide range of industries, including commercial air travel, agriculture, national security, and emergency response. Rocky Stone, chief technical pilot for United Airlines, noted that GPS allows more aircraft to be in airspace, saves fuel, and helps aircraft move safely on runways. “Improvements in space weather forecasting need to be pursued,” he said. Precision GPS has also “changed the whole nature of farming,” said Ron Hatch, Director of Navigation Systems, NavCom Technology/John Deere. GPS makes it possible for tractors to be driven in the most efficient paths and for fertilizer and water to be applied precisely to the areas that most need them. Space weather-induced degradation of GPS signals can cause significant loss to farms that rely on GPS. Elizabeth Zimmerman, Deputy Associate Administrator for the Office of Response and Recovery at the Federal Emergency Management Agency (FEMA), described how FEMA relies on GPS for disaster recovery. The agency is developing an operations plan for dealing with space weather, she said.

  9. PBO Facility Construction: GPS Network Status

    Science.gov (United States)

    Feaux, K.; Jackson, M.; Anderson, G.; Mencin, D.; Pauk, B.; Hafner, K.; Coyle, B.; Walls, C.; Friesen, B.; Borenstein, S.

    2005-12-01

    The Plate Boundary Observatory (PBO), part of the larger NSF-funded EarthScope project, will study the three-dimensional strain field resulting from active plate boundary deformation across the Western United States. PBO is a large construction project involving the reconnaissance, permitting, installation, documentation, and maintenance of 875 permanent GPS stations in five years. PBO has a demanding 5-year project installation schedule, for both GPS and strainmeter installations. During the second year of the project, the GPS Operations of PBO had accelerated production goals in reconnaissance, permitting, and installation activities. Some of the construction highlights in Year 2 include the Mount Saint Helens emergency response, the Magnitude 6.0 Parkfield earthquake emergency response, and GPS installations on the Akutan Volcano. GPS operations also prioritized permitting activity and installations in response to the Magnitude 5.2 Southern California earthquake and the Magnitude 6.7 Northern California earthquake in June, 2005. In addition to network construction, the GPS operations stepped up its maintenance activities which will continue to accelerate over the course of the project. To date, PBO has installed 270+ of the 482 GPS stations scheduled to be installed by the end of Year 3.

  10. Market niche analysis in the casino gaming industry.

    Science.gov (United States)

    Dandurand, L

    1990-03-01

    This article discusses the nature of market niche analysis in the casino gaming industry. It presents four approaches for conducting market niche analysis. An an example of one approach, the Las Vegas Visitor Profile Study is used to identify a premium niche in the Las Vegas Slot Target Market. A detailed examination of the premium niche profile provides a description of the typical premium slot player. The description of the typical premium player leads to hypotheses regarding needs (the unique preference set) of the premium player. An analysis of the unique preference set suggests an appropriate enhanced marketing program.

  11. Ecological niche transferability using invasive species as a case study.

    Directory of Open Access Journals (Sweden)

    Miguel Fernández

    Full Text Available Species distribution modeling is widely applied to predict invasive species distributions and species range shifts under climate change. Accurate predictions depend upon meeting the assumption that ecological niches are conserved, i.e., spatially or temporally transferable. Here we present a multi-taxon comparative analysis of niche conservatism using biological invasion events well documented in natural history museum collections. Our goal is to assess spatial transferability of the climatic niche of a range of noxious terrestrial invasive species using two complementary approaches. First we compare species' native versus invasive ranges in environmental space using two distinct methods, Principal Components Analysis and Mahalanobis distance. Second we compare species' native versus invaded ranges in geographic space as estimated using the species distribution modeling technique Maxent and the comparative index Hellinger's I. We find that species exhibit a range of responses, from almost complete transferability, in which the invaded niches completely overlap with the native niches, to a complete dissociation between native and invaded ranges. Intermediate responses included expansion of dimension attributable to either temperature or precipitation derived variables, as well as niche expansion in multiple dimensions. We conclude that the ecological niche in the native range is generally a poor predictor of invaded range and, by analogy, the ecological niche may be a poor predictor of range shifts under climate change. We suggest that assessing dimensions of niche transferability prior to standard species distribution modeling may improve the understanding of species' dynamics in the invaded range.

  12. Mining significant semantic locations from GPS data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian S.

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  13. Mining Significant Semantic Locations from GPS Data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian Søndergaard

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  14. Evidence of niche shift and invasion potential of Lithobates catesbeianus in the habitat of Mexican endemic frogs

    OpenAIRE

    Becerra López, Jorge Luis; Esparza Estrada, Citlalli Edith; Romero Méndez, Ulises; Sigala Rodríguez, José Jesús; Mayer Goyenechea, Irene Goyenechea; Castillo Cerón, Jesús Martín

    2017-01-01

    Invasive alien species are one of most severe threats to biodiversity and natural resources. These biological invasions have been studied from the niche conservatism and niche shifts perspective. Niche differentiation may result from changes in fundamental niche or realized niche or both; in biological invasions, niche differences between native and non-native ranges can appear through niche expansion, niche unfilling and niche stability. The American bullfrog Lithobates catesbeianus is an in...

  15. Real-time GPS Signal Simulator

    Data.gov (United States)

    National Aeronautics and Space Administration — With a minimal FTE investment and no additional procurement funds, the development of a low fidelity orbital GPS Signal simulator would is possible.  This IRAD...

  16. Convective towers detection using GPS radio occultations

    DEFF Research Database (Denmark)

    Biondi, Riccardo; Neubert, Torsten; Syndergaard, S.

    an important role since they lead to deep convective activity. With this work we want to investigate if severe storms leave a significant signature in radio occultation profiles in the tropical tropopause layer. The GPS radio occultation (RO) technique is useful for studying severe weather phenomena because...... the GPS signals penetrate through clouds and allow measurements of atmospheric profiles related to temperature, pressure, and water vapour with high vertical resolution. Using tropical cyclone best track database and data from different GPS RO missions (COSMIC, GRACE, CHAMP, SACC and GPSMET), we selected...... 1194 profiles in a time window of 3 hours and a space window of 300 km from the eye of the cyclone. We show that the bending angle anomaly of a GPS RO signal is typically larger than the climatology above the tropopause. Comparisons with co-located radiosondes, climatology of tropopause altitudes...

  17. LADOTD GPS technology management plan : tech summary.

    Science.gov (United States)

    2012-02-01

    Global Positioning System (GPS) technology has been adopted by diff erent sections within the Louisiana : Department of Transportation and Development (LADOTD) over the last decade with no uniform standards : for their use, procurement, training, and...

  18. Overview of GPS Adjacent Band Compatibility Assessment

    Science.gov (United States)

    2014-09-18

    January 13, 2012 National SpaceBased Positioning, Navigation, and Timing (PNT) Executive Committee (EXCOM) cochair letter to National Telecommunications and Information Administration (NTIA) proposed to draft new Global Positioning System (GPS)...

  19. SMEX03 Airborne GPS Bistatic Radar Data

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains measurements of Global Positioning System (GPS) signals reflected from the Earth’s surface and collected on an airborne platform. The...

  20. Global Positioning System (GPS) Energetic Particle Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Energetic particle data from the CXD and BDD instrument on the GPS constellation are available to the space weather research community. The release of these data...

  1. GPS Design Considerations: Displaying Nearest Airport Information

    National Research Council Canada - National Science Library

    Williams, Kevin

    1998-01-01

    Thirty-six participants were tested in a flight simulator on their ability to orient toward the nearest airport, based on the manner in which information was presented on a global positioning system (GPS) display...

  2. Scintillation-Hardened GPS, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A Communications, Navigation, and Networking reConfigurable Testbed (CoNNeCT) experiment is proposed to improve the performance of GPS during geomagnetic storms....

  3. PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.

    Science.gov (United States)

    Zhu, Guo; Rankin, Sherri L; Larson, Jon D; Zhu, Xiaoyan; Chow, Lionel M L; Qu, Chunxu; Zhang, Jinghui; Ellison, David W; Baker, Suzanne J

    2017-01-01

    Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis.

    Science.gov (United States)

    Balandrán, Juan Carlos; Purizaca, Jessica; Enciso, Jennifer; Dozal, David; Sandoval, Antonio; Jiménez-Hernández, Elva; Alemán-Lazarini, Leticia; Perez-Koldenkova, Vadim; Quintela-Núñez Del Prado, Henry; Rios de Los Ríos, Jussara; Mayani, Héctor; Ortiz-Navarrete, Vianney; Guzman, Monica L; Pelayo, Rosana

    2016-01-01

    Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis.

  5. En Billig GPS Data Analyse Platform

    DEFF Research Database (Denmark)

    Andersen, Ove; Christiansen, Nick; Larsen, Niels T.

    2011-01-01

    Denne artikel præsenterer en komplet software platform til analyse af GPS data. Platformen er bygget udelukkende vha. open-source komponenter. De enkelte komponenter i platformen beskrives i detaljer. Fordele og ulemper ved at bruge open-source diskuteres herunder hvilke IT politiske tiltage, der...... organisationer med et digitalt vejkort og GPS data begynde at lave trafikanalyser på disse data. Det er et krav, at der er passende IT kompetencer tilstede i organisationen....

  6. Niche marketing potentials for farm entrepreneurs in Nigeria ...

    African Journals Online (AJOL)

    Niche marketing can be a form of diversification and a means to achieving business success in all economic climates-boom, recession and depression. There are several niche marketing potentials farm entrepreneurs can exploit in start-up and existing small and large farm businesses. Dynamic entrepreneurism, and ...

  7. Distance Education and Niche Markets in Conventional Education.

    Science.gov (United States)

    Hayduk, Allan W.

    1994-01-01

    Examines barriers to conventional education and explains how distance education can fill the niche markets created by these barriers. Curriculum barriers and economic barriers are discussed; core attributes of distance education are described; and planning for niche markets is addressed based on the core attributes. (Contains five references.)…

  8. Competition in a technological niche: the cars of the future

    NARCIS (Netherlands)

    Bakker, S.; Lente, H. van; Engels, R.

    2012-01-01

    The notion of ‘niche’has proved to be useful to account for the emergence of radical innovations. Most studies, however, deal with the development of single emerging technologies. In this paper we address the competition between multiple niche technologies.Within the niche of the ‘car of the future’

  9. A note on structural holes theory and niche overlap

    NARCIS (Netherlands)

    Bruggeman, J.P.; Carnabuci, G.; Carnabuci, Gianluca; Vermeulen, Ivar

    2003-01-01

    Diffuse competition due to niche overlap between actors without (direct) ties with each other, constrains their structural autonomy. This is not dealt with in Burt’s mathematical model of his well-known structural holes theory. We fix his model by introducing a network measure of niche overlap.

  10. The evolution of climatic niches in squamate reptiles.

    Science.gov (United States)

    Pie, Marcio R; Campos, Leonardo L F; Meyer, Andreas L S; Duran, Andressa

    2017-07-12

    Despite the remarkable diversity found in squamate reptiles, most of their species tend to be found in warm/dry environments, suggesting that climatic requirements played a crucial role in their diversification, yet little is known about the evolution of their climatic niches. In this study, we integrate climatic information associated with the geographical distribution of 1882 squamate species and their phylogenetic relationships to investigate the tempo and mode of climatic niche evolution in squamates, both over time and among lineages. We found that changes in climatic niche dynamics were pronounced over their recent squamate evolutionary history, and we identified extensive evidence for rate heterogeneity in squamate climatic niche evolution. Most rate shifts involved accelerations, particularly over the past 50 Myr. Most squamates occupy similar regions of the climatic niche space, with only a few lineages diversifying into colder and humid climatic conditions. The changes from arid to mesic conditions in some regions of the globe may have provided opportunities for climatic niche evolution, although most lineages tended to remain near their ancestral niche. Variation in rates of climatic niche evolution seems common, particularly in response to the availability of new climatic conditions over evolutionary time. © 2017 The Author(s).

  11. Using specialty advertising in a niche marketing plan.

    Science.gov (United States)

    Schwisow, C R

    1992-01-01

    While niche marketing is not a new strategy, an increasing number of competitors are pursuing the same niches, resulting in stiff competition within the health care industry, writes C. Ronald Schwisow. This means marketers need to be resourceful to maximize their communications efforts. One such approach is specialty advertising.

  12. In search of a temporal niche: Environmental factors

    NARCIS (Netherlands)

    Hut, Roelof A.; Kronfeld-Schor, Noga; van der Vinne, Vincent; De la Iglesia, Horacio

    2012-01-01

    Time as an ecological niche variable or "temporal niche" can be defined in the context of the most prominent environmental cycles, including the tidal cycle, the lunar day and month, the solar day, and the earth year. For the current review, we focus on the 24-h domain generated through the earth's

  13. Teachers Unions in Turbulent Times: Maintaining Their Niche

    Science.gov (United States)

    Young, Tamara V.

    2011-01-01

    Drawing on niche theory, I describe the resource dimensions that compose teachers unions' niche and explain how aspects of the current political landscape buttress or undermine teachers unions' realization of those resources. I also discuss teachers unions' strategies to oppose any threats that undermine the realization of the resource arrays that…

  14. Intraspecific genetic variation and competition interact to influence niche expansion.

    Science.gov (United States)

    Agashe, Deepa; Bolnick, Daniel I

    2010-10-07

    Theory and empirical evidence show that intraspecific competition can drive selection favouring the use of novel resources (i.e. niche expansion). The evolutionary response to such selection depends on genetic variation for resource use. However, while genetic variation might facilitate niche expansion, genetically diverse groups may also experience weaker competition, reducing density-dependent selection on resource use. Therefore, genetic variation for fitness on different resources could directly facilitate, or indirectly retard, niche expansion. To test these alternatives, we factorially manipulated both the degree of genetic variation and population density in flour beetles (Tribolium castaneum) exposed to both novel and familiar food resources. Using stable carbon isotope analysis, we measured temporal change and individual variation in beetle diet across eight generations. Intraspecific competition and genetic variation acted on different components of niche evolution: competition facilitated niche expansion, while genetic variation increased individual variation in niche use. In addition, genetic variation and competition together facilitated niche expansion, but all these impacts were temporally variable. Thus, we show that the interaction between genetic variation and competition can also determine niche evolution at different time scales.

  15. Probabilistic and spatially variable niches inferred from demography

    Science.gov (United States)

    Jeffrey M. Diez; Itamar Giladi; Robert Warren; H. Ronald. Pulliam

    2014-01-01

    Summary 1. Mismatches between species distributions and habitat suitability are predicted by niche theory and have important implications for forecasting how species may respond to environmental changes. Quantifying these mismatches is challenging, however, due to the high dimensionality of species niches and the large spatial and temporal variability in population...

  16. Overlap and partitioning of the ecological and isotopic niches

    Science.gov (United States)

    Elizabeth A. Flaherty; Merav Ben-David

    2010-01-01

    Recently, it was proposed that stable isotope patterns can be used to quantify the width of the ecological niche of animals. However, the potential effects of habitat use on isotopic patterns of consumers have not been fully explored and consequently isotopic patterns may yield deceptive estimates of niche width. Here, we simulated four different scenarios of a...

  17. Geomagnetic storm effects on GPS based navigation

    Directory of Open Access Journals (Sweden)

    P. V. S. Rama Rao

    2009-05-01

    Full Text Available The energetic events on the sun, solar wind and subsequent effects on the Earth's geomagnetic field and upper atmosphere (ionosphere comprise space weather. Modern navigation systems that use radio-wave signals, reflecting from or propagating through the ionosphere as a means of determining range or distance, are vulnerable to a variety of effects that can degrade the performance of the navigational systems. In particular, the Global Positioning System (GPS that uses a constellation of earth orbiting satellites are affected due to the space weather phenomena.

    Studies made during two successive geomagnetic storms that occurred during the period from 8 to 12 November 2004, have clearly revealed the adverse affects on the GPS range delay as inferred from the Total Electron Content (TEC measurements made from a chain of seven dual frequency GPS receivers installed in the Indian sector. Significant increases in TEC at the Equatorial Ionization anomaly crest region are observed, resulting in increased range delay during the periods of the storm activity. Further, the storm time rapid changes occurring in TEC resulted in a number of phase slips in the GPS signal compared to those on quiet days. These phase slips often result in the loss of lock of the GPS receivers, similar to those that occur during strong(>10 dB L-band scintillation events, adversely affecting the GPS based navigation.

  18. GPS in Pedestrian and Spatial Behaviour Surveys

    DEFF Research Database (Denmark)

    Nielsen, Thomas Alexander Sick; Hovgesen, Henrik Harder

    The planning of the environment for pedestrians can be improved by using the newest gps tools for monitoring changes in human activity patterns in time and space. Using a personal GPS device, the locations and movements of respondents can be followed over a longer period of time. It will then be ......The planning of the environment for pedestrians can be improved by using the newest gps tools for monitoring changes in human activity patterns in time and space. Using a personal GPS device, the locations and movements of respondents can be followed over a longer period of time....... It will then be possible to analyse how the use of urban spaces are embedded in the wider context of activity patterns (work, school etc.). The general pattern of everyday itineraries, including route choice and time spent at different locations ?on the way? can also be analysed.    If the personal GPS device is combined...... position in the urban area. Thus a new form of integration between research into activity patterns and urban places will be possible.    The paper presents the possibilities in spatial behaviour and pedestrian surveys with GPS and electronic questionnaires. Demonstrative mapping of test data from passive...

  19. Assessing fitness for work: GPs judgment making.

    Science.gov (United States)

    Foley, Michelle; Thorley, Kevan; Van Hout, Marie-Claire

    2013-12-01

    The complexity of a fitness for work consultation is well documented. General practitioners (GPs) find that such consultations often create conflict and they feel ill-prepared for the task. We aimed to examine the consultation process in the fitness for work consultation and to report on the response of GPs to two hypothetical consultations of work related sickness absence, one of a psychological and one of a physical nature. Three areas of the consultation were examined; social/family circumstances, workplace history and information required assessing the severity of the condition. We used a randomized design using an online questionnaire completed by 62 GPs located in the Republic of Ireland. Analysis was conducted in NVivo 8 qualitative software using thematic and content analysis techniques. GPs may be expected to collect and consider information relating to social, domestic, financial, lifestyle and workplace factors, including workload, job satisfaction, job strain, work ethic, inter staff relationships and employee support mechanisms. The mode of presentation may trigger specific information seeking in the consultation. GPs may evaluate fitness for work in a variety of ways depending on medical and non-medical factors. Further research should further examine the factors that may influence the GPs decision to prescribe sickness leave.

  20. Niche divergence accelerates evolution in Asian endemic Procapra gazelles.

    Science.gov (United States)

    Hu, Junhua; Jiang, Zhigang; Chen, Jing; Qiao, Huijie

    2015-05-07

    Ecological niche divergence and adaptation to new environments are thought to play important roles in driving speciation. Whether recently evolved species show evidence for niche divergence or conservation is vital towards understanding the role of ecology in the process of speciation. The genus Procapra is an ancient, monophyletic lineage endemic to Asia that contains three extant species (P. gutturosa, P. przewalskii and P. picticaudata). These species mainly inhabit the Qinghai-Tibetan and Mongolian Plateaus, and today have primarily allopatric distributions. We applied a series of geographic information system-based analyses to test for environmental variation and niche divergence among these three species. We found substantial evidence for niche divergence in species' bioclimatic preferences, which supports the hypothesis that niche divergence accelerates diversification in Procapra. Our results provide important insight into the evolutionary history of ungulates in Asia and help to elucidate how environmental changes accelerate lineage diversification.

  1. Evidence of climatic niche shift during biological invasion.

    Science.gov (United States)

    Broennimann, O; Treier, U A; Müller-Schärer, H; Thuiller, W; Peterson, A T; Guisan, A

    2007-08-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk of introduction and establishment of newly or not-yet-introduced neophytes, but may not predict the full extent of invasions.

  2. Evidence of climatic niche shift during biological invasion

    DEFF Research Database (Denmark)

    Broennimann, O.; Treier, Urs; Müller-Schärer, H.

    2007-01-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche...... in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical...... evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk...

  3. Phylogenetic signals in the climatic niches of the world's amphibians

    DEFF Research Database (Denmark)

    Hof, Christian; Rahbek, Carsten; Araújo, Miguel B.

    2010-01-01

    The question of whether closely related species share similar ecological requirements has attracted increasing attention, because of its importance for understanding global diversity gradients and the impacts of climate change on species distributions. In fact, the assumption that related species...... in the realised climatic niches is explained on higher taxonomic levels, and whether the climatic niches of species within a given taxonomic group are more similar than between taxonomic groups. We found evidence for phylogenetic signals in realised climatic niches although the strength of the signal varied among...... amphibian orders and across biogeographical regions. To our knowledge, this is the first study providing a comprehensive analysis of the phylogenetic signal in species climatic niches for an entire clade across the world. Even though our results do not provide a strong test of the niche conservatism...

  4. Language, embodiment, and the cognitive niche.

    Science.gov (United States)

    Clark, Andy

    2006-08-01

    Embodied agents use bodily actions and environmental interventions to make the world a better place to think in. Where does language fit into this emerging picture of the embodied, ecologically efficient agent? One useful way to approach this question is to consider language itself as a cognition-enhancing animal-built structure. To take this perspective is to view language as a kind of self-constructed cognitive niche: a persisting but never stationary material scaffolding whose crucial role in promoting thought and reason remains surprisingly poorly understood. It is the very materiality of this linguistic scaffolding, I suggest, that gives it some key benefits. By materializing thought in words, we create structures that are themselves proper objects of perception, manipulation, and (further) thought.

  5. Plate Boundary Observatory GPS Network Status in California

    Science.gov (United States)

    Walls, C. P.; Austin, K. E.; Dittman, T.; Mann, D.; Basset, A.; Turner, R.; Lawrence, S.; Woolace, A. C.; Kasmer, D.; Hodgkinson, K. M.; Feaux, K.; Mattioli, G. S.

    2015-12-01

    The EarthScope PBO GPS network, funded by the NSF and operated by UNAVCO, is comprised of 599 permanent GPS stations spanning three principal tectonic regimes and is administered by separate management regions (Subduction - Pacific Northwest [91 sites], Extension - East [41 sites], Transform - Southwest [467 sites]). Since the close of construction in September 2008 various enhancements have been implemented through additional funding by the NSF, NOAA, and NASA and in collaboration with stakeholders such as Caltrans, Scripps, and the USGS. Initially, the majority of stations used first generation IP based cellular modems and radios capable of ~10KB/s data rates. The bandwidth limitation was a challenge for regional high-rate data downloads for GPS-seismology and airborne LiDAR surveys, and real-time data flow. Today, only 13 of the original cell modems remain with 297 upgraded cell modems providing 3G/4G/LTE data communications with transfer rates ranging from 80-400 KB/s. Ongoing radio network expansion and upgrades continue to harden communications. 32 VSAT and one manual download site remain. In CA, the network capabilities for 1Hz and 5Hz downloads or real-time streaming are ~95%, ~80% and ~65%, respectively. During the past year, uptime ranged from 94-99% with data return for 15 s data exceeding 99%. Real-time (1 Hz) data from 204 sites are distributed in BINEX and RTCM 2.3/3.1 formats with an average latency of 0.5 s and completion of 86%. A variety of geophysical sensors are co-located with the GPS stations and include: 21 MEMS accelerometers, 31 strong motion and broadband seismometers, 9 borehole strainmeters and 1 long baseline strainmeter. Vaisala meteorological instruments are located at 60 sites of which 38 stream GPS/Met data. In an effort to modernize the network, Trimble NetRS receivers are gradually being replaced with GNSS-capable/enabled receivers and antennas. Today, 11 stations are GLONASS enabled and 84 are GNSS capable.

  6. Combined GPS/GLONASS Precise Point Positioning with Fixed GPS Ambiguities

    Science.gov (United States)

    Pan, Lin; Cai, Changsheng; Santerre, Rock; Zhu, Jianjun

    2014-01-01

    Precise point positioning (PPP) technology is mostly implemented with an ambiguity-float solution. Its performance may be further improved by performing ambiguity-fixed resolution. Currently, the PPP integer ambiguity resolutions (IARs) are mainly based on GPS-only measurements. The integration of GPS and GLONASS can speed up the convergence and increase the accuracy of float ambiguity estimates, which contributes to enhancing the success rate and reliability of fixing ambiguities. This paper presents an approach of combined GPS/GLONASS PPP with fixed GPS ambiguities (GGPPP-FGA) in which GPS ambiguities are fixed into integers, while all GLONASS ambiguities are kept as float values. An improved minimum constellation method (MCM) is proposed to enhance the efficiency of GPS ambiguity fixing. Datasets from 20 globally distributed stations on two consecutive days are employed to investigate the performance of the GGPPP-FGA, including the positioning accuracy, convergence time and the time to first fix (TTFF). All datasets are processed for a time span of three hours in three scenarios, i.e., the GPS ambiguity-float solution, the GPS ambiguity-fixed resolution and the GGPPP-FGA resolution. The results indicate that the performance of the GPS ambiguity-fixed resolutions is significantly better than that of the GPS ambiguity-float solutions. In addition, the GGPPP-FGA improves the positioning accuracy by 38%, 25% and 44% and reduces the convergence time by 36%, 36% and 29% in the east, north and up coordinate components over the GPS-only ambiguity-fixed resolutions, respectively. Moreover, the TTFF is reduced by 27% after adding GLONASS observations. Wilcoxon rank sum tests and chi-square two-sample tests are made to examine the significance of the improvement on the positioning accuracy, convergence time and TTFF. PMID:25237901

  7. Evaluation of solar radio bursts' effect on GPS receiver signal tracking within International GPS Service network

    Science.gov (United States)

    Chen, Zhiyu; Gao, Yang; Liu, Zhizhao

    2005-06-01

    The direct interference from solar radio bursts (SRB) has not usually been considered as a potential threat to global positioning system (GPS) signal tracking, since the flux densities of most bursts are below 40,000 solar flux units (sfu), a threat threshold to GPS L1 frequency proposed by Klobuchar et al. (1999). Recent analysis indicated that a much lower threshold should be adopted for codeless or semicodeless dual-frequency GPS receivers. In this investigation, severe signal corruptions were found at dayside International GPS Service GPS receiver stations during a large solar radio burst that accompanied the super flare of 28 October 2003. Almost no GPS L2 signals were tracked during the solar flux peak time for areas near the subsolar point. Correlation analysis was performed between the rate of loss of lock on GPS L2 frequency and solar radio flux density at different bands, and a correlation index as high as 0.75 is revealed in the 1415 MHz solar radiation band, which is located between the two GPS operating frequencies L2 (1227.60 MHz) and L1 (1575.42 MHz). The correlation analysis indicates that GPS signal losses of lock were primarily caused by microwave in-band interference and that the threat threshold of SRB effects on the GPS system should be re-evaluated, since the flux density of the burst at 1415 MHz was just 4,000-12,000 sfu, which is far below the previously proposed threat threshold. The signal-tracking performance of different types of GPS receivers during such a super flare event is also presented.

  8. Diet and trophic niche of Lithobates catesbeianus (Amphibia: Anura

    Directory of Open Access Journals (Sweden)

    Peterson T. Leivas

    2012-10-01

    Full Text Available Lithobates catesbeianus (Shaw, 1802 is an invasive anuran introduced in Brazil that is associated with the displacement and the decline of populations of native species worldwide. There is evidence that biological invasions are facilitated by certain attributes of the invading species, for instance niche breath, and that invasive species have a broader ecological niche with respect to native ones. We designed a study to ascertain the temporal, ontogenetic, and sex differences in the niche dynamics of the American bullfrog. We sampled monthly from June 2008 to May 2009 in the state of Paraná, southern Brazil. For each individual, we gathered biometric and stomach content data. We then estimated the niche breath of the juveniles and adults, and compared it between the sexes. A total of 104 females and 77 males were sampled. Lithobates catesbeianus has a generalist diet, preying upon invertebrates and vertebrates. Even though the diet of the studied population varied seasonally, it did not differ between the sexes nor did it respond to biometric variables. Niche breadth was more restricted in the winter than in the autumn. The trophic niche of juveniles and adults did not overlap much when compared with the trophic niche overlap between males and females. Adult males and females had a considerable niche overlap, but females had a broader trophic niche than males in the winter and in the spring. These niche characteristics point to an opportunistic predation strategy that may have facilitated the process of invasion and establishment of this species in the study area.

  9. Identification of hair shaft progenitors that create a niche for hair pigmentation.

    Science.gov (United States)

    Liao, Chung-Ping; Booker, Reid C; Morrison, Sean J; Le, Lu Q

    2017-04-15

    Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20 + cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. © 2017 Liao et al.; Published by Cold Spring Harbor Laboratory Press.

  10. GPS Space Service Volume: Ensuring Consistent Utility Across GPS Design Builds for Space Users

    Science.gov (United States)

    Bauer, Frank H.; Parker, Joel Jefferson Konkl; Valdez, Jennifer Ellen

    2015-01-01

    GPS availability and signal strength originally specified for users on or near surface of Earth with transmitted power levels specified at edge-of-Earth, 14.3 degrees. Prior to the SSV specification, on-orbit performance of GPS varied from block build to block build (IIA, IIRM, IIF) due to antenna gain and beam width variances. Unstable on-orbit performance results in significant risk to space users. Side-lobe signals, although not specified, were expected to significantly boost GPS signal availability for users above the constellation. During GPS III Phase A, NASA noted significant discrepancies in power levels specified in GPS III specification documents, and measured on-orbit performance. To stabilize the signal for high altitude space users, NASA DoD team in 2003-2005 led the creation of new Space Service Volume (SSV) definition and specifications.

  11. Development of automatic techniques for GPS data management

    International Nuclear Information System (INIS)

    Park, Pil Ho

    2001-06-01

    It is necessary for GPS center to establish automatization as effective management of GPS network including data gathering, data transformation, data backup, data sending to IGS (International GPS Service for geodynamics), and precise ephemerides gathering. The operating program of GPS center has been adopted at KCSC (Korea Cadastral Survey Corporation), NGI (National Geography Institute), MOMAF (Ministry of Maritime Affairs and Fisheries) without self-development of core technique. The automatic management of GPS network is consists of GPS data management and data processing. It is also fundamental technique, which should be accomplished by every GPS centers. Therefore, this study carried out analyzing of Japanese GPS center, which has accomplished automatization by module considering applicability for domestic GPS centers

  12. Tempo and mode of climatic niche evolution in Primates.

    Science.gov (United States)

    Duran, Andressa; Pie, Marcio R

    2015-09-01

    Climatic niches have increasingly become a nexus in our understanding of a variety of ecological and evolutionary phenomena, from species distributions to latitudinal diversity gradients. Despite the increasing availability of comprehensive datasets on species ranges, phylogenetic histories, and georeferenced environmental conditions, studies on the evolution of climate niches have only begun to understand how niches evolve over evolutionary timescales. Here, using primates as a model system, we integrate recently developed phylogenetic comparative methods, species distribution patterns, and climatic data to explore primate climatic niche evolution, both among clades and over time. In general, we found that simple, constant-rate models provide a poor representation of how climatic niches evolve. For instance, there have been shifts in the rate of climatic niche evolution in several independent clades, particularly in response to the increasingly cooler climates of the past 10 My. Interestingly, rate accelerations greatly outnumbered rate decelerations. These results highlight the importance of considering more realistic evolutionary models that allow for the detection of heterogeneity in the tempo and mode of climatic niche evolution, as well as to infer possible constraining factors for species distributions in geographical space. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  13. Niches after cesarean section in a population seeking hysteroscopic sterilization.

    Science.gov (United States)

    van der Voet, Lucy Lucet F; Limperg, Tobias; Veersema, Sebastiaan; Timmermans, Anne; Bij de Vaate, A Marjolein J; Brölmann, Hans A M; Huirne, Judith A F

    2017-07-01

    To study the prevalence of hysteroscopically evaluated disruptions of the integrity of the uterine wall ('niches') in women with and without a previous cesarean section. A prospective cohort study was performed in a teaching hospital in the Netherlands. Women seeking hysteroscopic sterilization were included. A hysteroscopic evaluation of the anterior wall of the uterus and cervix to identify the existence of disruptions (niches) was performed in a standard manner. Primary outcome was the presence of a uterine niche, defined as any visible defect, disruption, or concavity (gap) in the anterior wall. Secondary outcome was to develop a registration form of niche features for hysteroscopic evaluation. In total, 713 women were included, 603 without and 110 with a previous cesarean section. In women with a previous cesarean Section 83 (75%) niches were observed using hysteroscopy. Anterior wall disruptions were not observed in women without a cesarean section. The following niche features were identified and incorporated in a registration form: polyps, cysts, myometrium defect, fibrotic tissue, (abnormal) vascular pattern, lateral branches, mucus production inside the defect, and bleeding. In a prospective cohort study among women undergoing hysteroscopic sterilization, a uterine niche could be detected by hysteroscopy in 75% of women with a previous cesarean section. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Intraspecific competition reduces niche width in experimental populations.

    Science.gov (United States)

    Parent, Christine E; Agashe, Deepa; Bolnick, Daniel I

    2014-10-01

    Intraspecific competition is believed to drive niche expansion, because otherwise suboptimal resources can provide a refuge from competition for preferred resources. Competitive niche expansion is well supported by empirical observations, experiments, and theory, and is often invoked to explain phenotypic diversification within populations, some forms of speciation, and adaptive radiation. However, some foraging models predict the opposite outcome, and it therefore remains unclear whether competition will promote or inhibit niche expansion. We conducted experiments to test whether competition changes the fitness landscape to favor niche expansion, and if competition indeed drives niche expansion as expected. Using Tribolium castaneum flour beetles fed either wheat (their ancestral resource), corn (a novel resource) or mixtures of both resources, we show that fitness is maximized on a mixed diet. Next, we show that at higher population density, the optimal diet shifts toward greater use of corn, favoring niche expansion. In stark contrast, when beetles were given a choice of resources, we found that competition caused niche contraction onto the ancestral resource. This presents a puzzling mismatch between how competition alters the fitness landscape, versus competition's effects on resource use. We discuss several explanations for this mismatch, highlighting potential reasons why optimality models might be misleading.

  15. Physical applications of GPS geodesy: a review.

    Science.gov (United States)

    Bock, Yehuda; Melgar, Diego

    2016-10-01

    Geodesy, the oldest science, has become an important discipline in the geosciences, in large part by enhancing Global Positioning System (GPS) capabilities over the last 35 years well beyond the satellite constellation's original design. The ability of GPS geodesy to estimate 3D positions with millimeter-level precision with respect to a global terrestrial reference frame has contributed to significant advances in geophysics, seismology, atmospheric science, hydrology, and natural hazard science. Monitoring the changes in the positions or trajectories of GPS instruments on the Earth's land and water surfaces, in the atmosphere, or in space, is important for both theory and applications, from an improved understanding of tectonic and magmatic processes to developing systems for mitigating the impact of natural hazards on society and the environment. Besides accurate positioning, all disturbances in the propagation of the transmitted GPS radio signals from satellite to receiver are mined for information, from troposphere and ionosphere delays for weather, climate, and natural hazard applications, to disturbances in the signals due to multipath reflections from the solid ground, water, and ice for environmental applications. We review the relevant concepts of geodetic theory, data analysis, and physical modeling for a myriad of processes at multiple spatial and temporal scales, and discuss the extensive global infrastructure that has been built to support GPS geodesy consisting of thousands of continuously operating stations. We also discuss the integration of heterogeneous and complementary data sets from geodesy, seismology, and geology, focusing on crustal deformation applications and early warning systems for natural hazards.

  16. UAV ONBOARD GPS IN POSITIONING DETERMINATION

    Directory of Open Access Journals (Sweden)

    K. N. Tahar

    2016-06-01

    Full Text Available The establishment of ground control points is a critical issue in mapping field, especially for large scale mapping. The fast and rapid technique for ground control point’s establishment is very important for small budget projects. UAV onboard GPS has the ability to determine the point positioning. The objective of this research is to assess the accuracy of unmanned aerial vehicle onboard global positioning system in positioning determination. Therefore, this research used UAV onboard GPS as an alternative to determine the point positioning at the selected area. UAV is one of the powerful tools for data acquisition and it is used in many applications all over the world. This research concentrates on the error contributed from the UAV onboard GPS during observation. There are several points that have been used to study the pattern of positioning error. All errors were analyzed in world geodetic system 84- coordinate system, which is the basic coordinate system used by the global positioning system. Based on this research, the result of UAV onboard GPS positioning could be used in ground control point establishment with the specific error. In conclusion, accurate GCP establishment could be achieved using UAV onboard GPS by applying a specific correction based on this research.

  17. Countering GPS jamming and EW threat

    Science.gov (United States)

    Pereira, Carlos M.; Rastegar, J.; McLain, Clifford E.; Alanson, T.; McMullan, Charles; Nguyen, H.-L.

    2007-09-01

    Efforts at the U.S. Army Research, Development and Engineering Center (ARDEC) at Picatinny, New Jersey are focused on developing methods to counter GPS jamming and electronic warfare (EW) threat by eliminating GPS dependency entirely. In addition, the need for munitions cost reduction requires alternatives to expensive high-grade inertia components. Efforts at ARDEC include investigations of novel methods for onboard measurement of munitions full position and angular orientation independent of GPS signals or high-grade inertia components. Currently, two types of direct angular measurement sensors are being investigated. A first sensor, Radio Frequency Polarized Sensor (RFPS), uses an electromagnetic field as a reference. A second sensor is based on magnetometers, using the Earth magnetic field for orientation measurement. Magnetometers, however, can only provide two independent orientation measurements. The RFPS may also be used to make full object position and angular orientation measurement relative to a reference coordinate system, which may be moving or stationary. The potential applications of novel RFPS sensors is in providing highly effective inexpensive replacement for GPS, which could be used in a "Layered Navigation" scheme employing alternate referencing methods and reduce the current dependency on GPS as a primary reference for guided gun-fired munitions. Other potential applications of RFPSs is in UAVs, UGVs, and robotic platforms.

  18. Evolution of climatic niche specialization: a phylogenetic analysis in amphibians.

    Science.gov (United States)

    Bonetti, Maria Fernanda; Wiens, John J

    2014-11-22

    The evolution of climatic niche specialization has important implications for many topics in ecology, evolution and conservation. The climatic niche reflects the set of temperature and precipitation conditions where a species can occur. Thus, specialization to a limited set of climatic conditions can be important for understanding patterns of biogeography, species richness, community structure, allopatric speciation, spread of invasive species and responses to climate change. Nevertheless, the factors that determine climatic niche width (level of specialization) remain poorly explored. Here, we test whether species that occur in more extreme climates are more highly specialized for those conditions, and whether there are trade-offs between niche widths on different climatic niche axes (e.g. do species that tolerate a broad range of temperatures tolerate only a limited range of precipitation regimes?). We test these hypotheses in amphibians, using phylogenetic comparative methods and global-scale datasets, including 2712 species with both climatic and phylogenetic data. Our results do not support either hypothesis. Rather than finding narrower niches in more extreme environments, niches tend to be narrower on one end of a climatic gradient but wider on the other. We also find that temperature and precipitation niche breadths are positively related, rather than showing trade-offs. Finally, our results suggest that most amphibian species occur in relatively warm and dry environments and have relatively narrow climatic niche widths on both of these axes. Thus, they may be especially imperilled by anthropogenic climate change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  19. Predicting the past distribution of species climatic niches

    DEFF Research Database (Denmark)

    Nogues, David Bravo

    2009-01-01

    Predicting past distributions of species climatic niches, hindcasting, by using climate envelope models (CEMs) is emerging as an exciting research area. CEMs are used to examine veiled evolutionary questions about extinctions, locations of past refugia and migration pathways, or to propose...... the theoretical assumptions behind niche modelling and using inadequate methods for hindcasting CEMs may well entail a cascade of errors and naïve ecological and evolutionary inferences. We should also push integrative research lines linking macroecology, physiology, population biology, palaeontology......, evolutionary biology and CEMs for a better understanding of niche dynamics across space and time....

  20. Strategic Positioning of Goods in a Market with a Niche

    OpenAIRE

    Eleftherios Zacharias

    2013-01-01

    We use the Hotelling's model allowing for a "gap" in the consumers' preferences. As a result, the characteristics space is divided in two separate intervals. The largest one represents the main market, and the smallest represents a niche. We find that in this set up the principle of maximum differentiation may not hold. We also, examine the incentives of a firm to adopt a niche marketing strategy. That is, to relocate and price its product so that to maximize its profits from the niche market...

  1. Integrating GPS with Dead Reckoning Sensors

    DEFF Research Database (Denmark)

    Cederholm, Jens Peter

    2000-01-01

    A vehicle positioning system comprising a GPS receiver, a digital compass, and an odometer was tested on a 2.8-km stretch in Aalborg, Denmark. The system, which merges observations from the three instruments using a Kalman filter, has an update rate of 1 Hz and is intended for use in both urban a...... and rural areas. The filtered positions follow the travelled route closely. A simulation suggests that the system will work even when the GPS coverage is insufficient.......A vehicle positioning system comprising a GPS receiver, a digital compass, and an odometer was tested on a 2.8-km stretch in Aalborg, Denmark. The system, which merges observations from the three instruments using a Kalman filter, has an update rate of 1 Hz and is intended for use in both urban...

  2. PBO Facility Construction: GPS Network Completed

    Science.gov (United States)

    Feaux, F.; Jackson, M.; Blume, F.; Coyle, B.; Walls, C.; Friesen, B.; Austin, K.; Basset, A.; Williams, T.; Jenkins, F.; Kasmer, D.; Lawrence, S.; Enders, M.

    2008-12-01

    The Plate Boundary Observatory (PBO), part of the larger NSF-funded EarthScope project, will study the three-dimensional strain field resulting from active plate boundary deformation across the Western United States. The PBO construction phase is now completed, which involved the reconnaissance, permitting, installation, documentation, and maintenance of 891 permanent GPS stations and the upgrade of 209 existing stations in five years. Some of the GPS construction highlights from the project will be presented. These highlights include the San Simeon earthquake response, Mount Saint Helens volcano emergency response, the Magnitude 6.0 Parkfield earthquake emergency response, and GPS and tiltmeter installations on Augustine, Akutan, and Unimak Island in Alaska.

  3. Single-Receiver GPS Phase Bias Resolution

    Science.gov (United States)

    Bertiger, William I.; Haines, Bruce J.; Weiss, Jan P.; Harvey, Nathaniel E.

    2010-01-01

    Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ftp

  4. Combining GPS measurements and IRI model predictions

    International Nuclear Information System (INIS)

    Hernandez-Pajares, M.; Juan, J.M.; Sanz, J.; Bilitza, D.

    2002-01-01

    The free electrons distributed in the ionosphere (between one hundred and thousands of km in height) produce a frequency-dependent effect on Global Positioning System (GPS) signals: a delay in the pseudo-orange and an advance in the carrier phase. These effects are proportional to the columnar electron density between the satellite and receiver, i.e. the integrated electron density along the ray path. Global ionospheric TEC (total electron content) maps can be obtained with GPS data from a network of ground IGS (international GPS service) reference stations with an accuracy of few TEC units. The comparison with the TOPEX TEC, mainly measured over the oceans far from the IGS stations, shows a mean bias and standard deviation of about 2 and 5 TECUs respectively. The discrepancies between the STEC predictions and the observed values show an RMS typically below 5 TECUs (which also includes the alignment code noise). he existence of a growing database 2-hourly global TEC maps and with resolution of 5x2.5 degrees in longitude and latitude can be used to improve the IRI prediction capability of the TEC. When the IRI predictions and the GPS estimations are compared for a three month period around the Solar Maximum, they are in good agreement for middle latitudes. An over-determination of IRI TEC has been found at the extreme latitudes, the IRI predictions being, typically two times higher than the GPS estimations. Finally, local fits of the IRI model can be done by tuning the SSN from STEC GPS observations

  5. Social intelligence, human intelligence and niche construction.

    Science.gov (United States)

    Sterelny, Kim

    2007-04-29

    This paper is about the evolution of hominin intelligence. I agree with defenders of the social intelligence hypothesis in thinking that externalist models of hominin intelligence are not plausible: such models cannot explain the unique cognition and cooperation explosion in our lineage, for changes in the external environment (e.g. increasing environmental unpredictability) affect many lineages. Both the social intelligence hypothesis and the social intelligence-ecological complexity hybrid I outline here are niche construction models. Hominin evolution is hominin response to selective environments that earlier hominins have made. In contrast to social intelligence models, I argue that hominins have both created and responded to a unique foraging mode; a mode that is both social in itself and which has further effects on hominin social environments. In contrast to some social intelligence models, on this view, hominin encounters with their ecological environments continue to have profound selective effects. However, though the ecological environment selects, it does not select on its own. Accidents and their consequences, differential success and failure, result from the combination of the ecological environment an agent faces and the social features that enhance some opportunities and suppress others and that exacerbate some dangers and lessen others. Individuals do not face the ecological filters on their environment alone, but with others, and with the technology, information and misinformation that their social world provides.

  6. Invasive plants have broader physiological niches.

    Science.gov (United States)

    Higgins, Steven I; Richardson, David M

    2014-07-22

    Invasive species cost the global economy billions of dollars each year, but ecologists have struggled to predict the risk of an introduced species naturalizing and invading. Although carefully designed experiments are needed to fully elucidate what makes some species invasive, much can be learned from unintentional experiments involving the introduction of species beyond their native ranges. Here, we assess invasion risk by linking a physiologically based species distribution model with data on the invasive success of 749 Australian acacia and eucalypt tree species that have, over more than a century, been introduced around the world. The model correctly predicts 92% of occurrences observed outside of Australia from an independent dataset. We found that invasiveness is positively associated with the projection of physiological niche volume in geographic space, thereby illustrating that species tolerant of a broader range of environmental conditions are more likely to be invasive. Species achieve this broader tolerance in different ways, meaning that the traits that define invasive success are context-specific. Hence, our study reconciles studies that have failed to identify the traits that define invasive success with the urgent and pragmatic need to predict invasive success.

  7. Pseudomonas biofilm matrix composition and niche biology

    Science.gov (United States)

    Mann, Ethan E.; Wozniak, Daniel J.

    2014-01-01

    Biofilms are a predominant form of growth for bacteria in the environment and in the clinic. Critical for biofilm development are adherence, proliferation, and dispersion phases. Each of these stages includes reinforcement by, or modulation of, the extracellular matrix. Pseudomonas aeruginosa has been a model organism for the study of biofilm formation. Additionally, other Pseudomonas species utilize biofilm formation during plant colonization and environmental persistence. Pseudomonads produce several biofilm matrix molecules, including polysaccharides, nucleic acids, and proteins. Accessory matrix components shown to aid biofilm formation and adaptability under varying conditions are also produced by pseudomonads. Adaptation facilitated by biofilm formation allows for selection of genetic variants with unique and distinguishable colony morphology. Examples include rugose small-colony variants and wrinkly spreaders (WS), which over produce Psl/Pel or cellulose, respectively, and mucoid bacteria that over produce alginate. The well-documented emergence of these variants suggests that pseudomonads take advantage of matrix-building subpopulations conferring specific benefits for the entire population. This review will focus on various polysaccharides as well as additional Pseudomonas biofilm matrix components. Discussions will center on structure–function relationships, regulation, and the role of individual matrix molecules in niche biology. PMID:22212072

  8. Host specialist clownfishes are environmental niche generalists.

    Science.gov (United States)

    Litsios, Glenn; Kostikova, Anna; Salamin, Nicolas

    2014-11-22

    Why generalist and specialist species coexist in nature is a question that has interested evolutionary biologists for a long time. While the coexistence of specialists and generalists exploiting resources on a single ecological dimension has been theoretically and empirically explored, biological systems with multiple resource dimensions (e.g. trophic, ecological) are less well understood. Yet, such systems may provide an alternative to the classical theory of stable evolutionary coexistence of generalist and specialist species on a single resource dimension. We explore such systems and the potential trade-offs between different resource dimensions in clownfishes. All species of this iconic clade are obligate mutualists with sea anemones yet show interspecific variation in anemone host specificity. Moreover, clownfishes developed variable environmental specialization across their distribution. In this study, we test for the existence of a relationship between host-specificity (number of anemones associated with a clownfish species) and environmental-specificity (expressed as the size of the ecological niche breadth across climatic gradients). We find a negative correlation between host range and environmental specificities in temperature, salinity and pH, probably indicating a trade-off between both types of specialization forcing species to specialize only in a single direction. Trade-offs in a multi-dimensional resource space could be a novel way of explaining the coexistence of generalist and specialists. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  9. Volcano deformation and subdaily GPS products

    Science.gov (United States)

    Grapenthin, Ronni

    Volcanic unrest is often accompanied by hours to months of deformation of the ground that is measurable with high-precision GPS. Although GPS receivers are capable of near continuous operation, positions are generally estimated for daily intervals, which I use to infer characteristics of a volcano’s plumbing system. However, GPS based volcano geodesy will not be useful in early warning scenarios unless positions are estimated at high rates and in real time. Visualization and analysis of dynamic and static deformation during the 2011 Tohokuoki earthquake in Japan motivates the application of high-rate GPS from a GPS seismology perspective. I give examples of dynamic seismic signals and their evolution to the final static offset in 30 s and 1 s intervals, which demonstrates the enhancement of subtle rupture dynamics through increased temporal resolution. This stresses the importance of processing data at recording intervals to minimize signal loss. Deformation during the 2009 eruption of Redoubt Volcano, Alaska, suggested net deflation by 0.05 km³ in three distinct phases. Mid-crustal aseismic precursory inflation began in May 2008 and was detected by a single continuous GPS station about 28 km NE of Redoubt. Deflation during the explosive and effusive phases was sourced from a vertical ellipsoidal reservoir at about 7-11.5 km. From this I infer a model for the temporal evolution of a complex plumbing system of at least 2 sources during the eruption. Using subdaily GPS positioning solutions I demonstrate that plumes can be detected and localized by utilizing information on phase residuals. The GPS network at Bezymianny Volcano, Kamchatka, records network wide subsidence at rapid rates between 8 and 12 mm/yr from 2005-2010. I hypothesize this to be caused by continuous deflation of a ˜30 km deep sill under Kluchevskoy Volcano. Interestingly, 1-2 explosive events per year cause little to no deformation at any site other than the summit site closest to the vent. I

  10. A Bridge Deflection Monitoring with GPS

    Science.gov (United States)

    Figurski, M.; Gałuszkiewicz, M.; Wrona, M.

    2007-01-01

    This paper introduces results of investigation carried on by The Applied Geomatics Section in Military University of Technology. Research includes possibilities of monitoring dynamic behavior of a bridge using high rate GPS data. Whole event was executed with collaboration of The Road and Bridge Management and The Warsaw Geodesy Company. Interdisciplinary approach with this project allows authors to get reliable information about investigating constructions and their respond for true traffic loading detected by GPS receivers. Way of compute data and used software (TRACK) are also shown in this paper.

  11. Effect of GPS errors on Emission model

    DEFF Research Database (Denmark)

    Lehmann, Anders; Gross, Allan

    n this paper we will show how Global Positioning Services (GPS) data obtained from smartphones can be used to model air quality in urban settings. The paper examines the uncertainty of smartphone location utilising GPS, and ties this location uncertainty to air quality models. The results presented...... in this paper indicates that the location error from using smartphones is within the accuracy needed to use the location data in air quality modelling. The nature of smartphone location data enables more accurate and near real time air quality modelling and monitoring. The location data is harvested from user...

  12. Arctic tides from GPS on sea ice

    DEFF Research Database (Denmark)

    Kildegaard Rose, Stine; Skourup, Henriette; Forsberg, René

    The presence of sea-ice in the Arctic Ocean plays a significant role in the Arctic climate. Sea ice dampens the ocean tide amplitude with the result that global tidal models which use only astronomical data perform less accurately in the polar regions. This study presents a kinematic processing...... of Global Positioning System (GPS) buoys placed on sea-ice at five different sites north of Greenland for the study of sea level height and tidal analysis to improve tidal models in the Central Arctic. The GPS measurements are compared with the Arctic tidal model AOTIM-5, which assimilates tide...

  13. Are we overestimating the niche? Removing marginal localities helps ecological niche models detect environmental barriers.

    Science.gov (United States)

    Soley-Guardia, Mariano; Gutiérrez, Eliécer E; Thomas, Darla M; Ochoa-G, José; Aguilera, Marisol; Anderson, Robert P

    2016-03-01

    Correlative ecological niche models (ENMs) estimate species niches using occurrence records and environmental data. These tools are valuable to the field of biogeography, where they are commonly used to infer potential connectivity among populations. However, a recent study showed that when locally relevant environmental data are not available, records from patches of suitable habitat protruding into otherwise unsuitable regions (e.g., gallery forests within dry areas) can lead to overestimations of species niches and their potential distributions. Here, we test whether this issue obfuscates detection of an obvious environmental barrier existing in northern Venezuela - that of the hot and xeric lowlands separating the Península de Paraguaná from mainland South America. These conditions most likely promote isolation between mainland and peninsular populations of three rodent lineages occurring in mesic habitat in this region. For each lineage, we calibrated optimally parameterized ENMs using mainland records only, and leveraged existing habitat descriptions to assess whether those assigned low suitability values corresponded to instances where the species was collected within locally mesic conditions amidst otherwise hot dry areas. When this was the case, we built an additional model excluding these records. We projected both models onto the peninsula and assessed whether they differed in their ability to detect the environmental barrier. For the two lineages in which we detected such problematic records, only the models built excluding them detected the barrier, while providing additional insights regarding peninsular populations. Overall, the study reveals how a simple procedure like the one applied here can deal with records problematic for ENMs, leading to better predictions regarding the potential effects of the environment on lineage divergence.

  14. The Intricate Link among Gut “Immunological Niche,” Microbiota, and Xenobiotics in Intestinal Pathology

    Directory of Open Access Journals (Sweden)

    Danilo Pagliari

    2017-01-01

    Full Text Available Inflammatory bowel diseases (IBDs are diseases characterized by various degrees of inflammation involving the gastrointestinal tract. Ulcerative colitis and Crohn’s disease are characterized by a dysregulated immune response leading to structural gut alterations in genetically predisposed individuals. Diverticular disease is characterized by abnormal immune response to normal gut microbiota. IBDs are linked to a lack of physiological tolerance of the mucosal immune system to resident gut microbiota and pathogens. The disruption of immune tolerance involves inflammatory pathways characterized by an unbalance between the anti-inflammatory regulatory T cells and the proinflammatory Th1/Th17 cells. The interaction among T cell subpopulations and their related cytokines, mediators of inflammation, gut microbiota, and the intestinal mucosa constitute the gut “immunological niche.” Several evidences have shown that xenobiotics, such as rifaximin, can positively modulate the inflammatory pathways at the site of gut immunological niche, acting as anti-inflammatory agents. Xenobiotics may interfere with components of the immunological niche, leading to activation of anti-inflammatory pathways and inhibition of several mediators of inflammation. In summary, xenobiotics may reduce disease-related gut mucosal alterations and clinical symptoms. Studying the complex interplay between gut immunological niche and xenobiotics will certainly open new horizons in the knowledge and therapy of intestinal pathologies.

  15. EvoDevo and niche construction: building bridges.

    Science.gov (United States)

    Laland, Kevin N; Odling-Smee, John; Gilbert, Scott F

    2008-11-15

    Evolutionary developmental biology and niche-construction theory have much in common, despite independent intellectual origins. Both place emphasis on the role of ontogenetic processes in evolution. The same historical events shaped them, and similar philosophical and sociological barriers hindered their respective advances. Both perspectives maintain that neo-Darwinism needs a theory of macroevolutionary variation and that such a theory can now be adduced from developmental biology. Some proponents of both EvoDevo and niche construction propose additional evolutionary mechanisms, and specify a key role for stable extra-genetic forms of inheritance. Similarly, proponents of each lay emphasis on "reciprocal causation" in the relationship between organism and environment. We illustrate here how EvoDevo and niche construction could gain "added value" from each other, and demonstrate how the niche-construction perspective potentially provides a useful conduit to integrate evolutionary and developmental biology. Copyright 2008 Wiley-Liss, Inc.

  16. AN ANALYSIS OF FUNDING DECISIONS FOR NICHE AGRICULTURAL PRODUCTS

    OpenAIRE

    HOWARD VAN AUKEN; SHAWN CARRAHER

    2012-01-01

    This paper examines the flow of funds from providers of capital to niche agricultural users of capital. Various programs through the US government, state/local economic development and private agencies work to improve the flow of capital to the niche agricultural sector. However, despite the expansion of programs aimed at providing financial resources to the agricultural sector, many sectors remain poorly served. Previous studies have suggested that agencies need to facilitate the flow of cap...

  17. GPS Attitude Determination for Launch Vehicles, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Toyon Research Corporation proposes to develop a family of compact, low-cost GPS-based attitude (GPS/A) sensors for launch vehicles. In order to obtain 3-D attitude...

  18. USGS Earthquake Program GPS Use Case : Earthquake Early Warning

    Science.gov (United States)

    2015-03-12

    USGS GPS receiver use case. Item 1 - High Precision User (federal agency with Stafford Act hazard alert responsibilities for earthquakes, volcanoes and landslides nationwide). Item 2 - Description of Associated GPS Application(s): The USGS Eart...

  19. IceBridge GPS L0 Raw Satellite Navigation Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge GPS L0 Raw Satellite Navigation Data (IPUTG0) data set contains GPS readings, including latitude, longitude, track, ground speed, off distance,...

  20. IceBridge L0 Raw Kinematics GPS Time Codes

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge L0 Raw Kinematics GPS Time Codes (ITKTC0) data set contains time codes generated during flights over Antarctica using the TrueTime 705-101 GPS...

  1. Global Positioning Systems Wing : GPS IIR-20 (SVN-49) Information.

    Science.gov (United States)

    2010-01-25

    Purpose for this briefing: : -Discuss SVN-49 signal problem with GPS community : -Provide information on potential mitigations : -Present way forward for SVN-49 : Background: : -SVN-49 unlike other GPS IIR Satellites had L5 R&D Demonstration Payload ...

  2. How does pollen versus seed dispersal affect niche evolution?

    Science.gov (United States)

    Aguilée, Robin; Shaw, Frank H; Rousset, François; Shaw, Ruth G; Ronce, Ophélie

    2013-03-01

    In heterogeneous landscapes, the genetic and demographic consequences of dispersal influence the evolution of niche width. Unless pollen is limiting, pollen dispersal does not contribute directly to population growth. However, by disrupting local adaptation, it indirectly affects population dynamics. We compare the effect of pollen versus seed dispersal on the evolution of niche width in heterogeneous habitats, explicitly considering the feedback between maladaptation and demography. We consider two scenarios: the secondary contact of two subpopulations, in distinct, formerly isolated habitats, and the colonization of an empty habitat with dispersal between the new and ancestral habitat. With an analytical model, we identify critical levels of genetic variance leading to niche contraction (secondary contact scenario), or expansion (new habitat scenario). We confront these predictions with simulations where the genetic variance freely evolves. Niche contraction occurs when habitats are very different. It is faster as total gene flow increases or as pollen predominates in overall gene flow. Niche expansion occurs when habitat heterogeneity is not too high. Seed dispersal accelerates it, whereas pollen dispersal tends to retard it. In both scenarios very high seed dispersal leads to extinction. Overall, our results predict a wider niche for species dispersing seeds more than pollen. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  3. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    Science.gov (United States)

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks.

  4. Vacuoles of Candida yeast as a specialized niche for Helicobacter pylori.

    Science.gov (United States)

    Siavoshi, Farideh; Saniee, Parastoo

    2014-05-14

    Helicobacter pylori (H. pylori) are resistant to hostile gastric environments and antibiotic therapy, reflecting the possibility that they are protected by an ecological niche, such as inside the vacuoles of human epithelial and immune cells. Candida yeast may also provide such an alternative niche, as fluorescently labeled H. pylori were observed as fast-moving and viable bacterium-like bodies inside the vacuoles of gastric, oral, vaginal and foodborne Candida yeasts. In addition, H. pylori-specific genes and proteins were detected in samples extracted from these yeasts. The H. pylori present within these yeasts produce peroxiredoxin and thiol peroxidase, providing the ability to detoxify oxygen metabolites formed in immune cells. Furthermore, these bacteria produce urease and VacA, two virulence determinants of H. pylori that influence phago-lysosome fusion and bacterial survival in macrophages. Microscopic observations of H. pylori cells in new generations of yeasts along with amplification of H. pylori-specific genes from consecutive generations indicate that new yeasts can inherit the intracellular H. pylori as part of their vacuolar content. Accordingly, it is proposed that yeast vacuoles serve as a sophisticated niche that protects H. pylori against the environmental stresses and provides essential nutrients, including ergosterol, for its growth and multiplication. This intracellular establishment inside the yeast vacuole likely occurred long ago, leading to the adaptation of H. pylori to persist in phagocytic cells. The presence of these bacteria within yeasts, including foodborne yeasts, along with the vertical transmission of yeasts from mother to neonate, provide explanations for the persistence and propagation of H. pylori in the human population. This Topic Highlight reviews and discusses recent evidence regarding the evolutionary adaptation of H. pylori to thrive in host cell vacuoles.

  5. Fundamentals of GPS Receivers A Hardware Approach

    CERN Document Server

    Doberstein, Dan

    2012-01-01

    While much of the current literature on GPS receivers is aimed at those intimately familiar with their workings, this volume summarizes the basic principles using as little mathematics as possible, and details the necessary specifications and circuits for constructing a GPS receiver that is accurate to within 300 meters. Dedicated sections deal with the features of the GPS signal and its data stream, the details of the receiver (using a hybrid design as exemplar), and more advanced receivers and topics including time and frequency measurements. Later segments discuss the Zarlink GPS receiver chip set, as well as providing a thorough examination of the TurboRogue receiver, one of the most accurate yet made. Guiding the reader through the concepts and circuitry, from the antenna to the solution of user position, the book’s deployment of a hybrid receiver as a basis for discussion allows for extrapolation of the core ideas to more complex, and more accurate designs. Digital methods are used, but any analogue c...

  6. The covariance of GPS coordinates and frames

    International Nuclear Information System (INIS)

    Lachieze-Rey, Marc

    2006-01-01

    We explore, in the general relativistic context, the properties of the recently introduced global positioning system (GPS) coordinates, as well as those of the associated frames and coframes that they define. We show that they are covariant and completely independent of any observer. We show that standard spectroscopic and astrometric observations allow any observer to measure (i) the values of the GPS coordinates at his position (ii) the components of his 4-velocity and (iii) the components of the metric in the GPS frame. This provides this system with a unique value both for conceptual discussion (no frame dependence) and for practical use (involved quantities are directly measurable): localization, motion monitoring, astrometry, cosmography and tests of gravitation theories. We show explicitly, in the general relativistic context, how an observer may estimate his position and motion, and reconstruct the components of the metric. This arises from two main results: the extension of the velocity fields of the probes to the whole (curved) spacetime, and the identification of the components of the observer's velocity in the GPS frame with the (inversed) observed redshifts of the probes. Specific cases (non-relativistic velocities, Minkowski and Friedmann-Lemaitre spacetimes, geodesic motions) are studied in detail

  7. Extra gps-ontvanger verhoogt nauwkeurigheid

    NARCIS (Netherlands)

    Schans, van der D.A.

    2009-01-01

    Akkerbouwers en loonwerkers stellen hoge eisen aan de nauwkeurigheid van de plaatsbepaling met gps. Betere ontvangers, het plaatsen van meer rtk-referentiepunten en het inrichten van rtk-netwerken moeten daarvoor zorgen. Maar zorgt dat wel voor een nauwkeurige aansturing van het werktuig? PPO zocht

  8. Exploring female GPs' perceptions about medical leadership.

    Science.gov (United States)

    Price, Karen; Clearihan, Lynette

    2015-06-01

    Women are increasingly entering the Australian general practice workforce. This study aims to explore female general practitioners' (GPs') perceptions of possible barriers to leadership and professional roles in the workforce. A purposive, convenience sample of 30 female GPs in active practice was approached in February, 2012. An anonymous, pa-per-based, semi-quantitative survey sought to identify participation and leadership confidence within general practice in a number of professional roles. The top two barriers participants identified for after-hours medical meetings were energy to attend and geographical location. For after-hours care, the top two barriers identified were energy and self-motivation. Few participants aspired to 'leadership' activities. 'Medical mentoring' was most likely to attract them into leadership. It is important female GPs' perspectives are explored in general practice. This small survey suggests further studies are needed in the importance of energy limitations and lack of self-confidence in restricting female GPs' capacity to fully engage in professional roles.

  9. Using Unmanned Aerial Vehicles and GPS Receivers

    Science.gov (United States)

    Gary, B.

    1995-01-01

    It is proposed that a small fleet of unmanned aerial vehicles (UAVs) be used over a period of years to monitor the rise of pressure surfaces caused by the hypothesized rise in average temperature of the troposphere due to global warming. Global Positioning Satellite System (GPS) receivers would be used for the precise tracking required.

  10. International Heliophysical Year: GPS Network in Africa

    Science.gov (United States)

    Amory-Mazaudier, C.; Basu, S.; Bock, O.; Combrink, A.; Groves, K.; Fuller Rowell, T.; Lassudrie-Duchesne, P.; Petitdidier, M.; Yizengaw, E.

    2009-04-01

    The main scientific objectives of the International Heliophysical Year are to discover and study all the physical processes coupling the Earth to the Sun. During the IHY a number of scientific instruments are being deployed all over the world. This brief report presents the scientific objectives, the GPS receiver network over Africa and the long lasting research planned for the next decades in Africa.

  11. Ionospheric irregularities at Antarctic using GPS measurements

    Indian Academy of Sciences (India)

    receiver is modified high performance NOVATEL. OEM4 dual frequency GPS C/A code .... purpose of TEC analysis, ionospheric data is con- sidered above 20. ◦ elevation of ... Contour of occurrence of amplitude scintillation (left panel) and phase scintillation (right panel) at Maitri during. March 2008. Maps are overlapped ...

  12. SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury

    Science.gov (United States)

    Niswander, Lisa M.; Fegan, Katherine H.; Kingsley, Paul D.; McGrath, Kathleen E.

    2014-01-01

    Megakaryocyte (MK) development in the bone marrow progresses spatially from the endosteal niche, which promotes MK progenitor proliferation, to the sinusoidal vascular niche, the site of terminal maturation and thrombopoiesis. The chemokine stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in the maturational chemotaxis of MKs toward sinusoidal vessels. Here, we demonstrate that both IV administration of SDF-1 and stabilization of endogenous SDF-1 acutely increase MK-vasculature association and thrombopoiesis with no change in MK number. In the setting of radiation injury, we find dynamic fluctuations in marrow SDF-1 distribution that spatially and temporally correlate with variations in MK niche occupancy. Stabilization of altered SDF-1 gradients directly affects MK location. Importantly, these SDF-1-mediated changes have functional consequences for platelet production, as the movement of MKs away from the vasculature decreases circulating platelets, while MK association with the vasculature increases circulating platelets. Finally, we demonstrate that manipulation of SDF-1 gradients can improve radiation-induced thrombocytopenia in a manner additive with earlier TPO treatment. Taken together, our data support the concept that SDF-1 regulates the spatial distribution of MKs in the marrow and consequently circulating platelet numbers. This knowledge of the microenvironmental regulation of the MK lineage could lead to improved therapeutic strategies for thrombocytopenia. PMID:24735964

  13. TLALOCNet continuous GPS-Met Array in Mexico supporting the 2017 NAM GPS Hydrometeorological Network.

    Science.gov (United States)

    Cabral-Cano, E.; Salazar-Tlaczani, L.; Adams, D. K.; Vivoni, E. R.; Grutter, M.; Serra, Y. L.; DeMets, C.; Galetzka, J.; Feaux, K.; Mattioli, G. S.; Miller, M. M.

    2017-12-01

    TLALOCNet is a network of continuous GPS and meteorology stations in Mexico to study atmospheric and solid earth processes. This recently completed network spans most of Mexico with a strong coverage emphasis on southern and western Mexico. This network, funded by NSF, CONACyT and UNAM, recently built 40 cGPS-Met sites to EarthScope Plate Boundary Observatory standards and upgraded 25 additional GPS stations. TLALOCNet provides open and freely available raw GPS data, and high frequency surface meteorology measurements, and time series of daily positions. This is accomplished through the development of the TLALOCNet data center (http://tlalocnet.udg.mx) that serves as a collection and distribution point. This data center is based on UNAVCO's Dataworks-GSAC software and also works as part of UNAVCO's seamless archive for discovery, sharing, and access to GPS data. The TLALOCNet data center also contains contributed data from several regional GPS networks in Mexico for a total of 100+ stations. By using the same protocols and structure as the UNAVCO and other COCONet regional data centers, the scientific community has the capability of accessing data from the largest Mexican GPS network. This archive provides a fully queryable and scriptable GPS and Meteorological data retrieval point. In addition, real-time 1Hz streams from selected TLALOCNet stations are available in BINEX, RTCM 2.3 and RTCM 3.1 formats via the Networked Transport of RTCM via Internet Protocol (NTRIP) for real-time seismic and weather forecasting applications. TLALOCNet served as a GPS-Met backbone for the binational Mexico-US North American Monsoon GPS Hydrometeorological Network 2017 campaign experiment. This innovative experiment attempts to address water vapor source regions and land-surface water vapor flux contributions to precipitation (i.e., moisture recycling) during the 2017 North American Monsoon in Baja California, Sonora, Chihuahua, and Arizona. Models suggest that moisture recycling is

  14. 77 FR 70421 - GPS Satellite Simulator Control Working Group Meeting

    Science.gov (United States)

    2012-11-26

    ... DEPARTMENT OF DEFENSE Department of the Air Force GPS Satellite Simulator Control Working Group Meeting AGENCY: Space and Missile Systems Center, Global Positioning Systems (GPS) Directorate, Department of the Air Force, DoD. ACTION: Meeting Notice. SUMMARY: This meeting notice is to inform GPS...

  15. 78 FR 63459 - GPS Satellite Simulator Control Working Group Meeting

    Science.gov (United States)

    2013-10-24

    ... DEPARTMENT OF DEFENSE Air Force GPS Satellite Simulator Control Working Group Meeting AGENCY: Department of the Air Force. ACTION: Meeting Notice. SUMMARY: This meeting notice is to inform GPS simulator manufacturers, who supply products to the Department of Defense (DoD), and GPS simulator users, both government...

  16. 78 FR 67132 - GPS Satellite Simulator Control Working Group Meeting

    Science.gov (United States)

    2013-11-08

    ... DEPARTMENT OF DEFENSE Department of the Air Force GPS Satellite Simulator Control Working Group Meeting AGENCY: Space and Missile Systems Center, Global Positioning Systems (GPS) Directorate, Air Force... the Federal Register on October 24, 2013 Vol. 78 No. 206. This new meeting notice is to inform GPS...

  17. Low-cost implementation of Differential GPS using Arduino

    OpenAIRE

    Svaton, Martin

    2016-01-01

    The thesis proposes the low-cost solution of Differential GPS using Arduino as a Master Control Unit. The thesis provides the methods of GPS position augmentation, which is available for varied applications such as drones or autonomous lawnmowers operated in a private sector. Used methods of GPS positioning accuracy improvements are based on a Satellite-Based Augmentation System (SBAS) and pseudorange residuals.

  18. How does the workload and work activities of procedural GPs compare to non-procedural GPs?

    Science.gov (United States)

    Russell, Deborah J; McGrail, Matthew R

    2017-08-01

    To investigate patterns of Australian GP procedural activity and associations with: geographical remoteness and population size hours worked in hospitals and in total; and availability for on-call DESIGN AND PARTICIPANTS: National annual panel survey (Medicine in Australia: Balancing Employment and Life) of Australian GPs, 2011-2013. Self-reported geographical work location, hours worked in different settings, and on-call availability per usual week, were analysed against GP procedural activity in anaesthetics, obstetrics, surgery or emergency medicine. Analysis of 9301 survey responses from 4638 individual GPs revealed significantly increased odds of GP procedural activity in anaesthetics, obstetrics or emergency medicine as geographical remoteness increased and community population size decreased, albeit with plateauing of the effect-size from medium-sized (population 5000-15 000) rural communities. After adjusting for confounders, procedural GPs work more hospital and more total hours each week than non-procedural GPs. In 2011 this equated to GPs practising anaesthetics, obstetrics, surgery, and emergency medicine providing 8% (95%CI 0, 16), 13% (95%CI 8, 19), 8% (95%CI 2, 15) and 18% (95%CI 13, 23) more total hours each week, respectively. The extra hours are attributable to longer hours worked in hospital settings, with no reduction in private consultation hours. Procedural GPs also carry a significantly higher burden of on-call. The longer working hours and higher on-call demands experienced by rural and remote procedural GPs demand improved solutions, such as changes to service delivery models, so that long-term procedural GP careers are increasingly attractive to current and aspiring rural GPs. © 2016 National Rural Health Alliance Inc.

  19. Intraspecies Competition for Niches in the Distal Gut Dictate Transmission during Persistent Salmonella Infection

    Science.gov (United States)

    Lam, Lilian H.; Monack, Denise M.

    2014-01-01

    In order to be transmitted, a pathogen must first successfully colonize and multiply within a host. Ecological principles can be applied to study host-pathogen interactions to predict transmission dynamics. Little is known about the population biology of Salmonella during persistent infection. To define Salmonella enterica serovar Typhimurium population structure in this context, 129SvJ mice were oral gavaged with a mixture of eight wild-type isogenic tagged Salmonella (WITS) strains. Distinct subpopulations arose within intestinal and systemic tissues after 35 days, and clonal expansion of the cecal and colonic subpopulation was responsible for increases in Salmonella fecal shedding. A co-infection system utilizing differentially marked isogenic strains was developed in which each mouse received one strain orally and the other systemically by intraperitoneal (IP) injection. Co-infections demonstrated that the intestinal subpopulation exerted intraspecies priority effects by excluding systemic S. Typhimurium from colonizing an extracellular niche within the cecum and colon. Importantly, the systemic strain was excluded from these distal gut sites and was not transmitted to naïve hosts. In addition, S. Typhimurium required hydrogenase, an enzyme that mediates acquisition of hydrogen from the gut microbiota, during the first week of infection to exert priority effects in the gut. Thus, early inhibitory priority effects are facilitated by the acquisition of nutrients, which allow S. Typhimurium to successfully compete for a nutritional niche in the distal gut. We also show that intraspecies colonization resistance is maintained by Salmonella Pathogenicity Islands SPI1 and SPI2 during persistent distal gut infection. Thus, important virulence effectors not only modulate interactions with host cells, but are crucial for Salmonella colonization of an extracellular intestinal niche and thereby also shape intraspecies dynamics. We conclude that priority effects and

  20. Coordinating with the "Inner GPS".

    Science.gov (United States)

    Fenton, André A

    2015-06-01

    The 2014 Nobel Prize for Physiology or Medicine was awarded for the discoveries that have elucidated the components of the internal positioning system that is centered on the hippocampus and entorhinal cortex. Here I provide a less than objective discussion of the importance of these accomplishments to systems neuroscience. By identifying positioning components like place, direction, distance, borders and the like, the field is given the opportunity to have a shot at piecing together how these components are integrated into the synthetic positioning sense. We are also given what is in my view, the most experimentally accessible and therefore potentially understandable, cognitive representation. Lest we feel too confident in the completeness of our understanding, and to inspire redoubled curiosity, I briefly describe a preliminary observation from our work with the psychosis-inducing drug phencyclidine (PCP). While PCP does not disturb where individual place cells fire, it dramatically discoordinates how these cells discharge together in time. Trying to understand how the positioning component cells are coordinated to provide useful knowledge is an exciting and tenable problem to be working on. © 2015 Wiley Periodicals, Inc.

  1. The impact of GPS ephemeris on the accuracy of precise orbit determination for LEO using GPS

    Science.gov (United States)

    Peng, D. J.; Wu, B.

    2008-10-01

    Today more and more Low Earth orbiting satellites (LEOs) of new scientific missions are equipped with a GPS receiver for precise orbit determination (POD), on-board GPS has become one of the main POD approaches. However, the on-board GPS POD accuracy obviously relies on the accuracy of GPS orbit and clock products. Based on the zero-difference dynamic POD approach of SHORDE-III program, this paper shows the influence of GPS orbit and clock on the POD accuracy of LEO using real GRACE data and three types of IGS orbit products between 1 Aug. and 7 Aug. The results indicate that IGS final precise orbit product (igs) and rapid orbit product (igr) have the equal POD accuracy which is about 9.5cm, the POD accuracy using ultra-rapid orbit product (igu) is about 10.5cm which is a little worse than igs and igr; High-rate GPS clock products have an impact of about 1--6 cm on the POD accuracy of LEO.

  2. Evaluating methods for estimating home ranges using GPS collars: A comparison using proboscis monkeys (Nasalis larvatus).

    Science.gov (United States)

    Stark, Danica J; Vaughan, Ian P; Ramirez Saldivar, Diana A; Nathan, Senthilvel K S S; Goossens, Benoit

    2017-01-01

    The development of GPS tags for tracking wildlife has revolutionised the study of home ranges, habitat use and behaviour. Concomitantly, there have been rapid developments in methods for estimating habitat use from GPS data. In combination, these changes can cause challenges in choosing the best methods for estimating home ranges. In primatology, this issue has received little attention, as there have been few GPS collar-based studies to date. However, as advancing technology is making collaring studies more feasible, there is a need for the analysis to advance alongside the technology. Here, using a high quality GPS collaring data set from 10 proboscis monkeys (Nasalis larvatus), we aimed to: 1) compare home range estimates from the most commonly used method in primatology, the grid-cell method, with three recent methods designed for large and/or temporally correlated GPS data sets; 2) evaluate how well these methods identify known physical barriers (e.g. rivers); and 3) test the robustness of the different methods to data containing either less frequent or random losses of GPS fixes. Biased random bridges had the best overall performance, combining a high level of agreement between the raw data and estimated utilisation distribution with a relatively low sensitivity to reduced fixed frequency or loss of data. It estimated the home range of proboscis monkeys to be 24-165 ha (mean 80.89 ha). The grid-cell method and approaches based on local convex hulls had some advantages including simplicity and excellent barrier identification, respectively, but lower overall performance. With the most suitable model, or combination of models, it is possible to understand more fully the patterns, causes, and potential consequences that disturbances could have on an animal, and accordingly be used to assist in the management and restoration of degraded landscapes.

  3. Evaluating methods for estimating home ranges using GPS collars: A comparison using proboscis monkeys (Nasalis larvatus.

    Directory of Open Access Journals (Sweden)

    Danica J Stark

    Full Text Available The development of GPS tags for tracking wildlife has revolutionised the study of home ranges, habitat use and behaviour. Concomitantly, there have been rapid developments in methods for estimating habitat use from GPS data. In combination, these changes can cause challenges in choosing the best methods for estimating home ranges. In primatology, this issue has received little attention, as there have been few GPS collar-based studies to date. However, as advancing technology is making collaring studies more feasible, there is a need for the analysis to advance alongside the technology. Here, using a high quality GPS collaring data set from 10 proboscis monkeys (Nasalis larvatus, we aimed to: 1 compare home range estimates from the most commonly used method in primatology, the grid-cell method, with three recent methods designed for large and/or temporally correlated GPS data sets; 2 evaluate how well these methods identify known physical barriers (e.g. rivers; and 3 test the robustness of the different methods to data containing either less frequent or random losses of GPS fixes. Biased random bridges had the best overall performance, combining a high level of agreement between the raw data and estimated utilisation distribution with a relatively low sensitivity to reduced fixed frequency or loss of data. It estimated the home range of proboscis monkeys to be 24-165 ha (mean 80.89 ha. The grid-cell method and approaches based on local convex hulls had some advantages including simplicity and excellent barrier identification, respectively, but lower overall performance. With the most suitable model, or combination of models, it is possible to understand more fully the patterns, causes, and potential consequences that disturbances could have on an animal, and accordingly be used to assist in the management and restoration of degraded landscapes.

  4. SDF-1 Inhibition Targets the Bone Marrow Niche for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Aldo M. Roccaro

    2014-10-01

    Full Text Available Bone marrow (BM metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM. Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12 is highly expressed in active MM, as well as in BM sites of tumor metastasis and report on the discovery of the high-affinity anti-SDF-1 PEGylated mirror-image l-oligonucleotide (olaptesed-pegol. In vivo confocal imaging showed that SDF-1 levels are increased within MM cell-colonized BM areas. Using in vivo murine and xenograft mouse models, we document that in vivo SDF-1 neutralization within BM niches leads to a microenvironment that is less receptive for MM cells and reduces MM cell homing and growth, thereby inhibiting MM disease progression. Targeting of SDF-1 represents a valid strategy for preventing or disrupting colonization of the BM by MM cells.

  5. Systemic translocation of Salmonella enterica serovar Dublin in cattle occurs predominantly via efferent lymphatics in a cell-free niche and requires type III secretion system 1 (T3SS-1) but not T3SS-2.

    Science.gov (United States)

    Pullinger, Gillian D; Paulin, Susan M; Charleston, Bryan; Watson, Patricia R; Bowen, Alison J; Dziva, Francis; Morgan, Eirwen; Villarreal-Ramos, Bernardo; Wallis, Timothy S; Stevens, Mark P

    2007-11-01

    Salmonella enterica is an important diarrheal pathogen, and infections may involve severe systemic sequelae depending on serovar- and host-specific factors. The molecular mechanisms underlying translocation of host-restricted and -specific serovars of S. enterica from the intestines to distal organs are ill defined. By surgical cannulation of lymph and blood vessels draining the distal ileum in cattle, S. enterica serovar Dublin was observed to translocate predominantly via mesenteric lymph nodes to efferent lymphatics in a manner that correlates with systemic virulence, since the fowl typhoid-associated serovar Gallinarum translocated at a significantly lower level. While both S. enterica serovars Dublin and Gallinarum were intracellular while in the intestinal mucosa and associated with major histocompatibility complex class II-positive cells, the bacteria were predominantly extracellular within efferent lymph. Screening of a library of signature-tagged serovar Dublin mutants following oral inoculation of calves defined the role of 36 virulence-associated loci in enteric and systemic phases of infection. The number and proportion of tagged clones reaching the liver and spleen early after oral infection were identical to the values in efferent lymph, implying that this may be a relevant mode of dissemination. Coinfection studies confirmed that lymphatic translocation requires the function of type III secretion system 1 (T3SS-1) but, remarkably, not T3SS-2. This is the first description of the mode and genetics of systemic translocation of serovar Dublin in its natural host.

  6. Preliminary Analysis of the CASES GPS Receiver Performance during Simulated Seismic Displacements

    Science.gov (United States)

    De la Rosa-Perkins, A.; Reynolds, A.; Crowley, G.; Azeem, I.

    2014-12-01

    We explore the ability of a new GPS software receiver, called CASES (Connected Autonomous Space Environment Sensor), to measure seismic displacements in realtime. Improvements in GPS technology over the last 20 years allow for precise measurement of ground motion during seismic events. For example, GPS data has been used to calculate displacement histories at an earthquake's epicenter and fault slip estimations with great accuracy. This is supported by the ability to measure displacements directly using GPS, bypassing the double integration that accelerometers require, and by higher clipping limits than seismometers. The CASES receiver developed by ASTRA in collaboration with Cornell University and the University of Texas, Austin represents a new geodetic-quality software-based GPS receiver that measures ionospheric space weather in addition to the usual navigation solution. To demonstrate, in a controlled environment, the ability of the CASES receiver to measure seismic displacements, we simulated ground motions similar to those generated during earthquakes, using a shake box instrumented with an accelerometer and a GPS antenna. The accelerometer measured the box's actual displacement. The box moved on a manually controlled axis that underwent varied one-dimensional motions (from mm to cm) at different frequencies and amplitudes. The CASES receiver was configured to optimize the accuracy of the position solution. We quantified the CASES GPS receiver performance by comparing the GPS solutions against the accelerometer data using various statistical analysis methods. The results of these tests will be presented. The CASES receiver is designed with multiple methods of accessing the data in realtime, ranging from internet connection, blue-tooth, cell-phone modem and Iridium modem. Because the CASES receiver measures ionospheric space weather in addition to the usual navigation solution, CASES provides not only the seimic signal, but also the ionospheric space weather

  7. The HysNiche trial: Hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial

    NARCIS (Netherlands)

    A.J.M.W. Vervoort; L.F. Van der Voet; M. Witmer; A.L. Thurkow; C.M. Radder; P.J.M. van Kesteren; H.W.P. Quartero; W.K.H. Kuchenbecker (Walter); M.Y. Bongers; P.M.A.J. Geomini; L.H.M. de Vleeschouwer (Marloes); M.H.A. van Hooff (Marcel); H.A. van Vliet; S. Veersema (S.); W.B. Renes; H.S. van Meurs (Hannah); J. Bosmans (Johan); K.O. Rengerink (Katrien Oude); H.A.M. Brölmann (H. A M); B.W.J. Mol (Ben W.J.); J.A.F. Huirne (Judith)

    2015-01-01

    textabstractBackground: A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is

  8. The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial

    NARCIS (Netherlands)

    Vervoort, A. J. M. W.; van der Voet, L. F.; Witmer, M.; Thurkow, A. L.; Radder, C. M.; van Kesteren, P. J. M.; Quartero, H. W. P.; Kuchenbecker, W. K. H.; Bongers, M. Y.; Geomini, P. M. A. J.; de Vleeschouwer, L. H. M.; van Hooff, M. H. A.; van Vliet, H. A. A. M.; Veersema, S.; Renes, W. B.; van Meurs, H. S.; Bosmans, J.; Oude Rengerink, K.; Brölmann, H. A. M.; Mol, B. W. J.; Huirne, J. A. F.

    2015-01-01

    A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce

  9. MEAT GOAT DEMOGRAPHICS AND NICHE MARKETING

    Directory of Open Access Journals (Sweden)

    Jeffrey Fisher

    2009-06-01

    religious concerns, convenience, food safety, and food quality issues. Opportunities exist to develop niche marketing opportunities for fresh goat with local ethnic or faith based populations.

  10. Impact of GPS tracking data of LEO satellites on global GPS solutions

    Science.gov (United States)

    Rothacher, M.; Svehla, D.

    Already at present quite a few Low Earth Orbiting (LEO) satellites (SAC-C, CHAMP, JASON-1, GRACE-1 and GRACE-2) are equipped with one or more GPS receivers for precise orbit determination or other applications (atmospheric sounding, gravity field recovery, . . . ). This trend will continue in the near future (e.g., with the GOCE and COSMIC missions) and we will soon have an entire "constellation" of LEO satellites tracked by GPS at our disposal. In this contribution we want to study the impact of LEO GPS measurements (from a single LEO satellite or from a LEO constellation) on global GPS solutions, where GPS satellite orbits and clocks, Earth rotation parameters (ERPs), station coordinates and troposphere zenith delays are determined simultaneously using the data of the global network of the International GPS Service (IGS). In order to assess the impact of the LEO GPS data on global IGS results, we have to perform a combined analysis of the space-borne and the ground-based GPS data. Such a combination may benefit on one hand from the differences between a ground station and a LEO, e.g., (1) the different tracking geometry (coverage of isolated geographical areas by LEOs, rapidly changing geometry, . . . ), (2) that LEOs connect all ground stations within 1-2 hours, (3) that baselines between LEO and ground stations may be longer than station-station baselines, (4) that no tropospheric delays have to be estimated for LEOs, and (5) that LEOs orbit the Earth within the ionosphere and may therefore contribute to global ionosphere models. On the other hand we have to deal with difficult aspects of precise orbit determination for the LEOs: only if we succeed to obtain very accurate dynamic or reduced-dynamic orbits for the LEOs, we will have a chance at all to improve the global GPS results. We present first results concerning the influence of LEO data on GPS orbits, ERPs, site coordinates, and troposphere zenith delays using both, variance-covariance analyses based on

  11. Using GPS to determine vehicle attitude - USS Yorktown test results

    Science.gov (United States)

    Kruczynski, Leonard R.; Li, Pui C.; Evans, Alan G.; Hermann, Bruce R.

    Prototype GPS orientation equipment was tested aboard the USS Yorktown, a U.S. Navy guided missile cruiser, to demonstrate that GPS could be used to determine orientation on a moving vessel. Initialization, integer maintenance, and accuracy in a real-time dynamic environment were addressed. The tests confirmed GPS-based real-time orientation determination, provided real-world data to exercise enhanced orientation algorithms, and identified equipment improvements that will make GPS a viable source of vehicle attitude in addition to GPS's superior positioning capabilities.

  12. Horses for Courses: Designing a GPS Tracking Data Collection

    DEFF Research Database (Denmark)

    Reinau, Kristian Hegner; Harder, Henrik; Overgård, Christian Hansen

    2014-01-01

    During the last decade, GPS tracking has become a key technology for data collection. In this chapter, the authors develop a practice-ready guideline for how to design and conduct GPS tracking investigations. They do so by first developing a V-model for GPS tracking, which describes the different...... phases of a GPS tracking data collection and the choices that have to be made in each phase. Thereafter, the authors show how this model can be applied in practice in a case study. The V-model is the first model that systematically combines methodological insights from the literature on GPS tracking...... and practical experiences from a number of GPS tracking projects into a practical guideline. Researchers can use this model as a starting point when designing a GPS tracking data collection. The authors hope that the model can constitute a first step towards the development of best practice....

  13. Niche construction, sources of selection and trait coevolution.

    Science.gov (United States)

    Laland, Kevin; Odling-Smee, John; Endler, John

    2017-10-06

    Organisms modify and choose components of their local environments. This 'niche construction' can alter ecological processes, modify natural selection and contribute to inheritance through ecological legacies. Here, we propose that niche construction initiates and modifies the selection directly affecting the constructor, and on other species, in an orderly, directed and sustained manner. By dependably generating specific environmental states, niche construction co-directs adaptive evolution by imposing a consistent statistical bias on selection. We illustrate how niche construction can generate this evolutionary bias by comparing it with artificial selection. We suggest that it occupies the middle ground between artificial and natural selection. We show how the perspective leads to testable predictions related to: (i) reduced variance in measures of responses to natural selection in the wild; (ii) multiple trait coevolution, including the evolution of sequences of traits and patterns of parallel evolution; and (iii) a positive association between niche construction and biodiversity. More generally, we submit that evolutionary biology would benefit from greater attention to the diverse properties of all sources of selection.

  14. The making and transnationalization of an ethnic niche: Vietnamese manicurists.

    Science.gov (United States)

    Eckstein, Susan; Nguyen, Thanh-Nghi

    2011-01-01

    The article addresses how Vietnamese immigrant women developed an urban employment niche in the beauty industry, in manicuring. They are shown to have done so by creating a market for professional nail care, through the transformation of nailwork into what might be called McNails, entailing inexpensive, walk-in, impersonal service, in stand-alone salons, nationwide, and by making manicures and pedicures de riguer across class and racial strata. Vietnamese are shown to have simultaneously gained access to institutional means to surmount professional manicure credentializing barriers, and to have developed formal and informal ethnic networks that fueled their growing monopolization of jobs in the sector, to the exclusion of non-Vietnamese. The article also elucidates conditions contributing to the Vietnamese build-up and transformation of the niche, to the nation-wide formation of the niche and, most recently, to the transnationalization of the niche. It also extrapolates from the Vietnamese manicure experience propositions concerning the development, expansion, maintenance, and transnationalization of immigrant-formed labor market niches.

  15. IDEAL framework in surgical innovation applied on laparoscopic niche repair.

    Science.gov (United States)

    Nikkels, C; Vervoort, Anke J M W; Mol, Ben Willem; Hehenkamp, Wouter J K; Huirne, Judith A F; Brölmann, Hans A M

    2017-08-01

    The research objective of the current systematic literature review is to classify the laparoscopic niche repair according to the IDEAL framework of 'innovation stages' and to recommend the required research setting to facilitate safe and properly timed implementation of the technique. In doing so, we are also able to evaluate the practical applicability of the IDEAL framework. A systematic search of the available literature on laparoscopic niche repair was performed in PubMed, Embase, and the Wiley/Cochrane library. Articles were classified according to the IDEAL framework and recommendations were given on additional required research before the technique can be safely implemented. Practical applicability of the IDEAL framework was also evaluated. Introduction of laparoscopic niche repair matches Idea (1) and Development (2a), according to the stages of IDEAL framework, although most studies are retrospective and complications have not been registered structurally in a considerable number of the articles. As feasibility and safety have been more or less established and surgery has been further developed we enter stage 2b (Exploration) and need prospective trials preferably comparing the effectiveness of laparoscopic niche repair to expectant management, the current standard care. Available studies were classified with the use of the IDEAL framework, achieving an overall IDEAL stage to be 2a Development. As clinical outcomes, though poorly registered, have been substantially improved, laparoscopic niche repair needs to be carried forward by more advanced study designs. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ecological niche modeling of Cryptococcus gattii in British Columbia, Canada.

    Science.gov (United States)

    Mak, Sunny; Klinkenberg, Brian; Bartlett, Karen; Fyfe, Murray

    2010-05-01

    Cryptococcus gattii emerged on Vancouver Island, British Columbia (BC), Canada, in 1999, causing human and animal illness. Environmental sampling for C.gattii in southwestern BC has isolated the fungal organism from native vegetation, soil, air, and water. Our aim was to help public health officials in BC delineate where C.gattii is currently established and forecast areas that could support C.gattii in the future. We also examined the utility of ecological niche modeling (ENM) based on human and animal C.gattii disease surveillance data. We performed ENM using the Genetic Algorithm for Rule-set Prediction (GARP) to predict the optimal and potential ecological niche areas of C.gattii in BC. Human and animal surveillance and environmental sampling data were used to build and test the models based on 15 predictor environmental data layers. ENM provided very accurate predictions (> 98% accuracy, p-value models identified optimal C.gattii ecological niche areas along the central and south eastern coast of Vancouver Island and within the Vancouver Lower Mainland. Elevation, biogeoclimatic zone, and January temperature were good predictors for identifying the ecological niche of C.gattii in BC. The use of human and animal case data for ENM proved useful and effective in identifying the ecological niche of C.gattii in BC. These results are shared with public health to increase public and physician awareness of cryptococcal disease in regions at risk of environmental colonization of C.gattii.

  17. GPS and Injury Prevention in Professional Soccer.

    Science.gov (United States)

    Ehrmann, Fabian E; Duncan, Craig S; Sindhusake, Doungkamol; Franzsen, William N; Greene, David A

    2016-02-01

    This study investigated the relationship between GPS variables measured in training and gameplay and injury occurrences in professional soccer. Nineteen professional soccer players competing in the Australian Hyundai A-League were monitored for 1 entire season using 5 Hz Global Positioning System (GPS) units (SPI-Pro GPSports) in training sessions and preseason games. The measurements obtained were total distance, high-intensity running distance, very-high-intensity running distance, new body load, and meters per minute. Noncontact soft tissue injuries were documented throughout the season. Players' seasons were averaged over 1- and 4-week blocks according to when injuries occurred. These blocks were compared with each other and with players' seasonal averages. Players performed significantly higher meters per minute in the weeks preceding an injury compared with their seasonal averages (+9.6 and +7.4% for 1- and 4-week blocks, respectively) (p sports scientists to consider when planning and monitoring training.

  18. High dynamic GPS receiver validation demonstration

    Science.gov (United States)

    Hurd, W. J.; Statman, J. I.; Vilnrotter, V. A.

    1985-01-01

    The Validation Demonstration establishes that the high dynamic Global Positioning System (GPS) receiver concept developed at JPL meets the dynamic tracking requirements for range instrumentation of missiles and drones. It was demonstrated that the receiver can track the pseudorange and pseudorange rate of vehicles with acceleration in excess of 100 g and jerk in excess of 100 g/s, dynamics ten times more severe than specified for conventional High Dynamic GPS receivers. These results and analytic extensions to a complete system configuration establish that all range instrumentation requirements can be met. The receiver can be implemented in the 100 cu in volume required by all missiles and drones, and is ideally suited for transdigitizer or translator applications.

  19. Mapping forest communities using GPS and GIS

    OpenAIRE

    Ford, Bob

    2002-01-01

    Students in a general education, general ecology class collect vegetation data within a national park and prepare