WorldWideScience

Sample records for regulate tissue organization

  1. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  2. Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis

    OpenAIRE

    Papusheva, Ekaterina; Heisenberg, Carl-Philipp

    2010-01-01

    The Heisenberg laboratory reviews the spatial organization of signalling complexes at cell–matrix and cell–cell contact sites and its impact on cell integrity, cellular polarity and tissue morphogenesis.

  3. Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization.

    Science.gov (United States)

    Dzamba, Bette J; Jakab, Karoly R; Marsden, Mungo; Schwartz, Martin A; DeSimone, Douglas W

    2009-03-01

    In this study we demonstrate that planar cell polarity signaling regulates morphogenesis in Xenopus embryos in part through the assembly of the fibronectin (FN) matrix. We outline a regulatory pathway that includes cadherin adhesion and signaling through Rac and Pak, culminating in actin reorganization, myosin contractility, and tissue tension, which, in turn, directs the correct spatiotemporal localization of FN into a fibrillar matrix. Increased mechanical tension promotes FN fibril assembly in the blastocoel roof (BCR), while reduced BCR tension inhibits matrix assembly. These data support a model for matrix assembly in tissues where cell-cell adhesions play an analogous role to the focal adhesions of cultured cells by transferring to integrins the tension required to direct FN fibril formation at cell surfaces.

  4. Hormonal regulation of epithelial organization in a three-dimensional breast tissue culture model.

    Science.gov (United States)

    Speroni, Lucia; Whitt, Gregory S; Xylas, Joanna; Quinn, Kyle P; Jondeau-Cabaton, Adeline; Barnes, Clifford; Georgakoudi, Irene; Sonnenschein, Carlos; Soto, Ana M

    2014-01-01

    The establishment of hormone target breast cells in the 1970's resulted in suitable models for the study of hormone control of cell proliferation and gene expression using two-dimensional (2D) cultures. However, to study mammogenesis and breast tumor development in vitro, cells must be able to organize in three-dimensional (3D) structures like in the tissue. We now report the development of a hormone-sensitive 3D culture model for the study of mammogenesis and neoplastic development. Hormone-sensitive T47D breast cancer cells respond to estradiol in a dose-dependent manner by forming complex epithelial structures. Treatment with the synthetic progestagen promegestone, in the presence of estradiol, results in flat epithelial structures that display cytoplasmic projections, a phenomenon reported to precede side-branching. Additionally, as in the mammary gland, treatment with prolactin in the presence of estradiol induces budding structures. These changes in epithelial organization are accompanied by collagen remodeling. Collagen is the major acellular component of the breast stroma and an important player in tumor development and progression. Quantitative analysis of second harmonic generation of collagen fibers revealed that collagen density was more variable surrounding budding and irregularly shaped structures when compared to more regular structures; suggesting that fiber organization in the former is more anisotropic than in the latter. In sum, this new 3D model recapitulates morphogenetic events modulated by mammogenic hormones in the breast, and is suitable for the evaluation of therapeutic agents.

  5. Organ and Tissue-specific Sucrose Transporters. Important Hubs in Gene and Metabolite Networks Regulating Carbon Use in Wood-forming Tissues of Populus

    Energy Technology Data Exchange (ETDEWEB)

    Harding, Scott A. [Univ. of Georgia, Athens, GA (United States); Tsai, Chung-Jui [Univ. of Georgia, Athens, GA (United States)

    2016-01-04

    The overall project objective was to probe the relationship between sucrose transporters and plant productivity in the biomass for biofuels woody perennial, Populus. At the time the proposal was written, sucrose transporters had already been investigated in many plant model systems, primarily with respect to the export of photosynthate sucrose from source leaves, and the uptake of sucrose in storage organs and seeds. Preliminary findings by the PI found that in Populus, sucrose transporter genes (SUTs) were well expressed in wood-forming tissues that comprise the feedstock for biofuels production. Because sucrose comprises by far the predominant form in which photosynthate is delivered from source organs to sink organs like roots and wood-forming tissues, SUTs control a gate that nominally at least could impact the allocation or partitioning of sucrose for potentially competing end uses like growth (stem biomass) and storage. In addition, water use might be conditioned by the way in which sucrose is distributed throughout the plant, and/or by the way in which sucrose is partitioned intracellularly. Several dozen transgenic lines were produced in year 1 of the project to perturb the expression ratio of multiple plasma membrane (PM) SUTs (intercellular trafficking), versus the single tonoplast membrane (TM) sucrose transporter that effectively regulates intracellular trafficking of sucrose. It was possible to obtain transgenic lines with dual SUT gene knockdown using the 35S promoter, but not the wood-specific TUA1 promoter. By the end of project year 2, a decision was made to work with the 35S plants while archiving the TUA1 plants. The PhD candidate charged with producing the transgenic lines abandoned the project during its second year, substantially contributing to the decision to operate with just the 35S lines. That student’s interests ranged more toward evolutionary topics, and a report on SUT gene evolution was published (Peng et al 2014).

  6. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    Science.gov (United States)

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

  7. Tissue bioengineering and artificial organs.

    Science.gov (United States)

    Llames, Sara; García, Eva; Otero Hernández, Jesús; Meana, Alvaro

    2012-01-01

    The scarcity of organs and tissues for transplant and the need of immunosuppressive drugs to avoid rejection constitute two reasons that justify organ and tissue production in the laboratory. Tissue engineering based tissues (TE) could allow to regenerate the whole organ from a fragment or even to produce several organs from an organ donor for grafting purposes. TE is based in: (1) the ex vivo expansion of cells, (2) the seeding of these expanded cells in tridimensional structures that mimic physiological conditions and, (3) grafting the prototype. In order to graft big structures it is necessary that the organ or tissue produced "ex vivo" bears a vascular tree to ensure the nutrition of its deep layers. At present, no technology has been developed to provide this vascular tree to TE derived products. Thus, these tissues must be thin enough to acquire nutrients during the first days by diffusion from surrounding tissues. This fact constitutes nowadays the greatest limitation of technologies for organ development in the laboratory.In this chapter, all these problems and their possible solutions are commented. Also, the present status of TE techniques in the regeneration of different organ systems is reviewed.

  8. A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion ligands regulates 3D spatial organization of cells and tissue.

    Science.gov (United States)

    Lee, Min Kyung; Rich, Max H; Lee, Jonghwi; Kong, Hyunjoon

    2015-07-01

    Bioactive hydrogels have been extensively studied as a platform for 3D cell culture and tissue regeneration. One of the key desired design parameters is the ability to control spatial organization of biomolecules and cells and subsequent tissue in a 3D matrix. To this end, this study presents a simple but advanced method to spatially organize microchanneled, cell adherent gel blocks and non-adherent ones in a single construct. This hydrogel system was prepared by first fabricating a bimodal hydrogel in which the microscale, alginate gel blocks modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD peptides), and those free of RGD peptides, were alternatingly presented. Then, anisotropically aligned microchannels were introduced by uniaxial freeze-drying of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal cells to adhere to and differentiate into neuron and glial cells exclusively in microchannels of the alginate gel blocks modified with RGD peptides. Separately, the bimodal gel loaded with microparticles releasing vascular endothelial growth factor stimulated vascular growth solely into microchannels of the RGD-alginate gel blocks in vivo. These results were not attained by the bimodal hydrogel fabricated to present randomly oriented micropores. Overall, the bimodal gel system could regulate spatial organization of nerve-like tissue or blood vessels at sub-micrometer length scale. We believe that the hydrogel assembly demonstrated in this study will be highly useful in developing a better understanding of diverse cellular behaviors in 3D tissue and further improve quality of a wide array of engineered tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. The Maize MID-COMPLEMENTING ACTIVITY homolog CELL NUMBER REGULATOR13/NARROW ODD DWARF, coordinates organ growth and tissue patterning

    Science.gov (United States)

    Organogenesis occurs from cell division, expansion and differentiation. How these cellular processes are coordinated remains elusive. The maize leaf provides an excellent system to study cellular differentiation because it has several different tissues and cell types. The narrow odd dwarf (nod) mut...

  10. Aging changes in organs - tissue - cells

    Science.gov (United States)

    ... and structure to the skin and internal organs. Epithelial tissue provides a covering for deeper body layers. The ... such as the gastrointestinal system, are made of epithelial tissue. Muscle tissue includes three types of tissue: Striated ...

  11. Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

    Science.gov (United States)

    Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

    2016-01-27

    Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non

  12. Mechanical homeostasis regulating adipose tissue volume

    Directory of Open Access Journals (Sweden)

    Svedman Paul

    2007-09-01

    Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

  13. Combinatorial regulation of tissue specification by GATA and FOG factors

    Science.gov (United States)

    Chlon, Timothy M.; Crispino, John D.

    2012-01-01

    The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

  14. Regulation of macrophage development and function in peripheral tissues

    Science.gov (United States)

    Lavin, Yonit; Mortha, Arthur; Rahman, Adeeb; Merad, Miriam

    2015-01-01

    Macrophages are immune cells of haematopoietic origin that provide crucial innate immune defence and have tissue-specific functions in the regulation and maintenance of organ homeostasis. Recent studies of macrophage ontogeny, as well as transcriptional and epigenetic identity, have started to reveal the decisive role of the tissue stroma in the regulation of macrophage function. These findings suggest that most macrophages seed the tissues during embryonic development and functionally specialize in response to cytokines and metabolites that are released by the stroma and drive the expression of unique transcription factors. In this Review, we discuss how recent insights into macrophage ontogeny and macrophage–stroma interactions contribute to our understanding of the crosstalk that shapes macrophage function and the maintenance of organ integrity. PMID:26603899

  15. Arabidopsis thaliana sucrose phosphate synthase (sps) genes are expressed differentially in organs and tissues, and their transcription is regulated by osmotic stress.

    Science.gov (United States)

    Solís-Guzmán, María Gloria; Argüello-Astorga, Gerardo; López-Bucio, José; Ruiz-Herrera, León Francisco; López-Meza, Joel Edmundo; Sánchez-Calderón, Lenin; Carreón-Abud, Yazmín; Martínez-Trujillo, Miguel

    2017-11-01

    Sucrose is synthesized from UDP-Glc and Fru-6-phosphate via the activity of sucrose-phosphate synthase (SPS) enzymes, which produce Suc-6-phosphate. Suc-6-phosphate is rapidly dephosphorylated by phosphatases to produce Suc and inorganic phosphate. Arabidopsis has four sps genes encoding SPS enzymes. Of these enzymes, AtSPS1F and AtSPS2F have been grouped with other dicotyledonous SPS enzymes, while AtSPS3F and AtSPS4F are included in groups with both dicotyledonous and monocotyledonous SPS enzymes. In this work, we generated Arabidopsis thaliana transformants containing the promoter region of each sps gene fused to gfp::uidA reporter genes. A detailed characterization of expression conferred by the sps promoters in organs and tissues was performed. We observed expression of AtSPS1F, AtSPS2F and AtSPS3F in the columella roots of the plants that support sucrose synthesis. Hence, these findings support the idea that sucrose synthesis occurs in the columella cells, and suggests that sucrose has a role in this tissue. In addition, the expression of AtSPS4F was identified in embryos and suggests its participation in this developmental stage. Quantitative transcriptional analysis of A. thaliana plants grown in media with different osmotic potential showed that AtSPS2F and AtSPS4F respond to osmotic stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Tissue and Organ 3D Bioprinting.

    Science.gov (United States)

    Xia, Zengmin; Jin, Sha; Ye, Kaiming

    2018-02-01

    Three-dimensional (3D) bioprinting enables the creation of tissue constructs with heterogeneous compositions and complex architectures. It was initially used for preparing scaffolds for bone tissue engineering. It has recently been adopted to create living tissues, such as cartilage, skin, and heart valve. To facilitate vascularization, hollow channels have been created in the hydrogels by 3D bioprinting. This review discusses the state of the art of the technology, along with a broad range of biomaterials used for 3D bioprinting. It provides an update on recent developments in bioprinting and its applications. 3D bioprinting has profound impacts on biomedical research and industry. It offers a new way to industrialize tissue biofabrication. It has great potential for regenerating tissues and organs to overcome the shortage of organ transplantation.

  17. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Ethical issues in organ and tissue transplantation.

    Science.gov (United States)

    Abouna, George M

    2003-12-01

    Clinical organ transplantation provides a way of giving the gift of life to patients with terminal failure of vital organs, which requires the participation of other fellow human beings and of society by donating organs from deceased or living individuals. The increasing incidence of vital organ failure and the inadequate supply of organs, especially from cadavers, has created a wide gap between organ supply and organ demand, which has resulted in very long waiting times to receive an organ as well as an increasing number of deaths while waiting. These events have raised many ethical, moral and societal issues regarding supply, the methods of organ allocation the use of living donors as volunteers including minors. It has also led to the practice of organ sale by entrepreneurs for financial gains in some parts the world through exploitation of the poor, for the benefit of the wealthy. The current advances in immunology and tissue engineering and the use of animal organs, xenotransplantation, while offering very promising solutions to many of these problems, also raise additional ethical and medical issues, which must be considered by the medical profession as well as society. This review deals with the ethical and moral issues generated by the current advances in organ transplantation, the problem of organ supply versus organ demand and the appropriate allocation of available organs. It deals with the risks and benefits of organ donation from living donors, the appropriate and acceptable methods to increase organ donation from the deceased through the adoption of the principle of 'presumed consent', the right methods of providing acceptable appreciation and compensation for the family of the deceased as well as volunteer and altruistic donors, and the duties and responsibilities of the medical profession and society to help fellow humans. The review also deals with the appropriate and ethically acceptable ways of utilizing the recent advances of stem cell

  19. Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis.

    Science.gov (United States)

    Honarpisheh, Mohsen; Desai, Jyaysi; Marschner, Julian A; Weidenbusch, Marc; Lech, Maciej; Vielhauer, Volker; Anders, Hans-Joachim; Mulay, Shrikant R

    2016-12-01

    The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively. © 2016 The Author(s).

  20. 3D bioprinting of tissues and organs.

    Science.gov (United States)

    Murphy, Sean V; Atala, Anthony

    2014-08-01

    Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

  1. Tissue Engineering Organs for Space Biology Research

    Science.gov (United States)

    Vandenburgh, H. H.; Shansky, J.; DelTatto, M.; Lee, P.; Meir, J.

    1999-01-01

    Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures.

  2. Polyethylene and methyl methacrylate particle-stimulated inflammatory tissue and macrophages up-regulate bone resorption in a murine neonatal calvaria in vitro organ system.

    Science.gov (United States)

    Ren, Weiping; Wu, Bin; Mayton, Lois; Wooley, Paul H

    2002-09-01

    There is considerable evidence that orthopaedic wear debris plays a crucial role in the pathology of aseptic loosening of joint prostheses. This study examined the effect of inflammatory membranes stimulated with methyl methacrylate and polyethylene on bone resorption, using the murine air pouch model. The capacity of RAW 264.7 mouse macrophages exposed to polymer particles to produce factors affecting bone metabolism was also studied. Neonatal calvaria bones were co-cultured with either pouch membranes or conditioned media from activated macrophages. Bone resorption was measured by the release of calcium from cultured bones, and the activity of tartrate-resistant acid phosphatase in both bone sections and culture medium was also assayed. Results showed that inflammatory pouch membrane activated by methyl methacrylate and polyethylene enhanced osteoclastic bone resorption. Conditioned media from particles stimulated mouse macrophages also stimulated bone resorption, although this effect was weaker than resorption induced by inflammatory pouch membranes. The addition of the particles directly into the medium of cultured calvaria bones had little effect on bone resorption. Our observations indicate that both inflammatory tissue and macrophages provoked by particles can stimulate bone resorption in cultured mouse neonatal calvaria bones. This simple in vitro bone resorption system allows us to investigate the fundamental cellular and molecular mechanism of wear debris induced bone resorption and to screen potential therapeutic approaches for aseptic loosening.

  3. Space research on organs and tissues

    Science.gov (United States)

    Tischler, Marc E.; Morey-Holton, Emily

    1993-01-01

    Studies in space on various physiological systems have and will continue to provide valuable information on how they adapt to reduced gravitational conditions, and how living in a 1 g (gravity) environment has guided their development. Muscle and bone are the most notable tissues that respond to unweighting caused by lack of gravity. The function of specific muscles and bones relates directly to mechanical loading, so that removal of 'normal forces' in space, or in bedridden patients, causes dramatic loss of tissue mass. The cardiovascular system is also markedly affected by reduced gravity. Adaptation includes decreased blood flow to the lower extremities, thus decreasing the heart output requirement. Return to 1 g is associated with a period of reconditioning due to the deconditioning that occurs in space. Changes in the cardiovascular system are also related to responses of the kidney and certain endocrine (hormone-producing) organs. Changes in respiratory function may also occur, suggesting an effect on the lungs, though this adaptation is poorly understood. The neurovestibular system, including the brain and organs of the inner ear, must adapt to the disorientation caused by lack of gravity. Preliminary findings have been reported for liver. Additionally, endocrine organs responsible for release of hormones such as insulin, growth hormone, glucocorticoids, and thyroid hormone may respond to spaceflight.

  4. Exercise Regulation of Marrow Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Gabriel M Pagnotti

    2016-07-01

    Full Text Available Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally-supportive tissues, inhibits bone resorption and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot, or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a 5-fold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  5. The Organization of Regulated Production

    DEFF Research Database (Denmark)

    Jansen, Jos; Jeon, Doh-Shin; Menicucci, Domenico

    2008-01-01

    We analyze the choice between vertical separation (VS) and vertical integration (VI) when two regulated firms produce complementary inputs with correlated costs and are protected by ex post break-even constraints. First, in the absence of collusion the regulator prefers VI (VS) for negative...

  6. 3D Bioprinting of Tissue/Organ Models.

    Science.gov (United States)

    Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

    2016-04-04

    In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Expression cartography of human tissues using self organizing maps

    Directory of Open Access Journals (Sweden)

    Löffler Markus

    2011-07-01

    Full Text Available Abstract Background Parallel high-throughput microarray and sequencing experiments produce vast quantities of multidimensional data which must be arranged and analyzed in a concerted way. One approach to addressing this challenge is the machine learning technique known as self organizing maps (SOMs. SOMs enable a parallel sample- and gene-centered view of genomic data combined with strong visualization and second-level analysis capabilities. The paper aims at bridging the gap between the potency of SOM-machine learning to reduce dimension of high-dimensional data on one hand and practical applications with special emphasis on gene expression analysis on the other hand. Results The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues. SOM mapping reduces the dimension of expression data from ten of thousands of genes to a few thousand metagenes, each representing a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of genes related to specific molecular processes in the respective tissue. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering are better represented and provide better signal-to-noise ratios if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues broadly into three clusters containing nervous, immune system and the remaining tissues

  8. Acellular organ scaffolds for tumor tissue engineering

    Science.gov (United States)

    Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

    2015-12-01

    Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

  9. Integrating physiological regulation with stem cell and tissue homeostasis

    Science.gov (United States)

    Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

    2015-01-01

    Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

  10. Additive Manufacturing of Biomaterials, Tissues, and Organs.

    Science.gov (United States)

    Zadpoor, Amir A; Malda, Jos

    2017-01-01

    The introduction of additive manufacturing (AM), often referred to as three-dimensional (3D) printing, has initiated what some believe to be a manufacturing revolution, and has expedited the development of the field of biofabrication. Moreover, recent advances in AM have facilitated further development of patient-specific healthcare solutions. Customization of many healthcare products and services, such as implants, drug delivery devices, medical instruments, prosthetics, and in vitro models, would have been extremely challenging-if not impossible-without AM technologies. The current special issue of the Annals of Biomedical Engineering presents the latest trends in application of AM techniques to healthcare-related areas of research. As a prelude to this special issue, we review here the most important areas of biomedical research and clinical practice that have benefited from recent developments in additive manufacturing techniques. This editorial, therefore, aims to sketch the research landscape within which the other contributions of the special issue can be better understood and positioned. In what follows, we briefly review the application of additive manufacturing techniques in studies addressing biomaterials, (re)generation of tissues and organs, disease models, drug delivery systems, implants, medical instruments, prosthetics, orthotics, and AM objects used for medical visualization and communication.

  11. 3D Bioprinting Technologies for Hard Tissue and Organ Engineering

    OpenAIRE

    Wang, Xiaohong; Ao, Qiang; Tian, Xiaohong; Fan, Jun; Wei, Yujun; Hou, Weijian; Tong, Hao; Bai, Shuling

    2016-01-01

    Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especial...

  12. Intrinsic regulation of blood flow in adipose tissue

    DEFF Research Database (Denmark)

    Henriksen, O; Nielsen, Steen Levin; Paaske, W

    1976-01-01

    Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated...... subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue...... vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (autoregulation), venous...

  13. 3D Bioprinting Technologies for Hard Tissue and Organ Engineering

    Science.gov (United States)

    Wang, Xiaohong; Ao, Qiang; Tian, Xiaohong; Fan, Jun; Wei, Yujun; Hou, Weijian; Tong, Hao; Bai, Shuling

    2016-01-01

    Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering. PMID:28773924

  14. 3D Bioprinting Technologies for Hard Tissue and Organ Engineering

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    2016-09-01

    Full Text Available Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

  15. 3D Bioprinting Technologies for Hard Tissue and Organ Engineering.

    Science.gov (United States)

    Wang, Xiaohong; Ao, Qiang; Tian, Xiaohong; Fan, Jun; Wei, Yujun; Hou, Weijian; Tong, Hao; Bai, Shuling

    2016-09-27

    Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

  16. Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment.

    Science.gov (United States)

    Lyra-Leite, Davi M; Andres, Allen M; Petersen, Andrew P; Ariyasinghe, Nethika R; Cho, Nathan; Lee, Jezell A; Gottlieb, Roberta A; McCain, Megan L

    2017-10-01

    Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O 2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix

  17. Tissue strands as "bioink" for scale-up organ printing.

    Science.gov (United States)

    Yu, Yin; Ozbolat, Ibrahim T

    2014-01-01

    Organ printing, takes tissue spheroids as building blocks together with additive manufacturing technique to engineer tissue or organ replacement parts. Although a wide array of cell aggregation techniques has been investigated, and gained noticeable success, the application of tissue spheroids for scale-up tissue fabrication is still worth investigation. In this paper, we introduce a new micro-fabrication technique to create tissue strands at the scale of 500-700μm as a "bioink" for future robotic tissue printing. Printable alginate micro-conduits are used as semi-permeable capsules for tissue strand fabrication. Mouse insulinoma beta TC3 cell tissue strands were formed upon 4 days post fabrication with reasonable mechanical strength, high cell viability close to 90%, and tissue specific markers expression. Fusion was readily observed between strands when placing them together as early as 24h. Also, tissue strands were deposited with human umbilical vein smooth muscle cells (HUVSMCs) vascular conduits together to fabricated miniature pancreatic tissue analog. Our study provided a novel technique using tissue strands as "bioink" for scale-up bioprinting of tissues or organs.

  18. Tissue architecture: the ultimate regulator of breast epithelial function

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Mian, Saira

    2003-10-20

    A problem in developmental biology that continues to take center stage is how higher organisms generate diverse tissues and organs given the same cellular genotype. In cell and tumor biology, the key question is not the production of form, but its preservation: how do tissues and organs maintain homeostasis, and how do cells within tissues lose or overcome these controls in cancer? Undoubtedly, mechanisms that maintain tissue specificity should share features with those employed to drive formation of the tissues. However, they are unlikely to be identical. At a simplistic level, developmental pathways may be thought of as a series of extremely rapid short-term events. Each new step depends on what came before, and the outcome is the organism itself at birth. All organs, with a few notable exceptions, such as the mammary gland and the brain, 'arrive' together and are complete when the organism is born. In mice and humans, these events occur in a mere 21 days and 9 months respectively. The stability of the differentiated state and the homeostasis of the organism, on the other hand, will last 40-110 times longer. How does the organism achieve this feat? How are tissues maintained? These questions also relate fundamentally to how tissues become malignant and, although not discussed here, to aging. While there is much literature on differentiation - loosely defined as the gain of a single or a series of functions - we know much less about the forces and the pathways that maintain organ morphology and function as a unit. This may be partly because it is difficult to study a tissue as a unit in vivo and there are few techniques that allow maintenance of organs in vitro long enough and in such a way as to make cell and molecular biology experiments possible. Techniques for culturing cells in three-dimensional gels (3D) as a surrogate for tissues, however, have been steadily improving and the method is now used by several laboratories. In this commentary we

  19. Connective tissue fibroblasts and Tcf4 regulate myogenesis

    Science.gov (United States)

    Mathew, Sam J.; Hansen, Jody M.; Merrell, Allyson J.; Murphy, Malea M.; Lawson, Jennifer A.; Hutcheson, David A.; Hansen, Mark S.; Angus-Hill, Melinda; Kardon, Gabrielle

    2011-01-01

    Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis. PMID:21177349

  20. Ethics and regulation in organ procurement research.

    Science.gov (United States)

    Ackerman, Terrence F; Winsett, Rebecca P

    2002-12-01

    This article explores the role of ethics and regulation in human research conducted by organ procurement agencies; basic ethical principles for human research are outlined. Organ procurement agencies are not required to observe federal regulations; however, voluntary adherence will ensure that procurement research is conducted according to current standards of ethical practice. Although most organ procurement research will qualify for exempt status, this determination should be made by an institutional review board. Even if studies qualify for exempt status, there is a moral presumption that informed consent should be sought, unless certain narrow conditions for waiver of consent are satisfied. Finally, when future research utilizing organ procurement records is anticipated, procurement coordinators should provide sufficiently detailed information to families about such plans to permit their advance informed consent to research activities.

  1. Trend Analysis of Organ and Tissue Donation for Transplantation.

    Science.gov (United States)

    Dos Santos, M J; Leal de Moraes, E; Santini Martins, M; Carlos de Almeida, E; Borges de Barros E Silva, L; Urias, V; Silvano Corrêa Pacheco Furtado, M C; Brito Nunes, Á; El Hage, S

    2018-03-01

    The goal of this study was to identify the tendency toward donations of tissue and organs from donors with brain death between 2001 and 2016 as registered by an organ procurement organization in São Paulo City. This quantitative, retrospective, exploratory study encompassed all Tissue and Organ Donation Terms signed between 2001 and 2016. A logistic regression model was applied to verify whether there was an upward or downward trend in donation. After statistical analysis, a significant change trend was identified in skin, bones, valve, vessel, heart, lung, and pancreas donations, indicating an increase in the donation rate through the years. The donation rate did not show changes over the years for donations of liver, kidneys, and corneas. The decision-making process regarding organ and tissue donation is restricted not only to the dilemma of whether to donate but another question then arises as well: which organs and tissues are to be donated? The discrepancy between the authorization for organ donation and the authorization for tissue donation, as well as the option for one or another organ and/or tissue, must be thoroughly examined because these factors directly affect the number of transplants and acquirements effectively accomplished. These factors may be related to explaining to one's relatives aspects of the surgery, body reassembling, and usage of such organs and/or tissues. They may also be related to the lack of knowledge concerning organ donation and the symbolism represented by the organ and/or tissue, among other factors. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. 3D Printing of Personalized Organs and Tissues

    Science.gov (United States)

    Ye, Kaiming

    2015-03-01

    Authors: Kaiming Ye and Sha Jin, Department of Biomedical Engineering, Watson School of Engineering and Applied Science, Binghamton University, State University of New York, Binghamton, NY 13902-6000 Abstract: Creation of highly organized multicellular constructs, including tissues and organs or organoids, will revolutionize tissue engineering and regenerative medicine. The development of these technologies will enable the production of individualized organs or tissues for patient-tailored organ transplantation or cell-based therapy. For instance, a patient with damaged myocardial tissues due to an ischemic event can receive a myocardial transplant generated using the patient's own induced pluripotent stem cells (iPSCs). Likewise, a type-1 diabetic patient can be treated with lab-generated islets to restore his or her physiological insulin secretion capability. These lab-produced, high order tissues or organs can also serve as disease models for pathophysiological study and drug screening. The remarkable advances in stem cell biology, tissue engineering, microfabrication, and materials science in the last decade suggest the feasibility of generating these tissues and organoids in the laboratory. Nevertheless, major challenges still exist. One of the critical challenges that we still face today is the difficulty in constructing or fabricating multicellular assemblies that recapitulate in vivo microenvironments essential for controlling cell proliferation, migration, differentiation, maturation and assembly into a biologically functional tissue or organoid structure. These challenges can be addressed through developing 3D organ and tissue printing which enables organizing and assembling cells into desired tissue and organ structures. We have shown that human pluripotent stem cells differentiated in 3D environments are mature and possess high degree of biological function necessary for them to function in vivo.

  3. Translational research: cells, tissues and organisms

    International Nuclear Information System (INIS)

    Chang, P.Y.

    2003-01-01

    Exposure to the complex space radiation environment poses an important health hazard for astronauts in long-term space missions. The central theme of NASA's space radiation health research effort is to acquire scientific knowledge to understand the mechanisms of particle radiation effects in biological systems and to use this knowledge to set exposure limits and to design countermeasures that will protect the astronauts. During the past few decades, a rich body of data has been developed to characterize HZE-induced biological responses both in vitro and in vivo using ground-based accelerator facilities available in a number of facilities around the world. Although much is known about particle-radiation-induced DNA damage and cell killing in cultured cell lines, recent evidence suggest that numerous other factors, such as membrane effects, altered gene expression, bystander effects and specific cell-type dependent features also play critical roles in cellular responses. Dose- and particle-dependent studies are also available for multicellular tissues and animal model systems where emerging information demonstrates complex interactions between cells including intercellular communications, activation of proteins, alterations in the microenvironment, tissue-specificity, and genetic status and these contribute in determining the consequences of HZE radiation. Due to the lack of human data, risk estimates depend on the extrapolation of experimental results in animals and cultured cell systems to man. In this presentation, selected topics reviewing particle radiation effects in cells, tissues and animal will be used to illustrate the importance of translational research and some of the limitations of such approaches

  4. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala

    2010-04-28

    The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

  5. Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells.

    Science.gov (United States)

    Salmasi, Shima; Kalaskar, Deepak M; Yoon, Wai-Weng; Blunn, Gordon W; Seifalian, Alexander M

    2015-03-26

    Recent regenerative medicine and tissue engineering strategies (using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional (3D) organs, such as bone, skin, liver, kidney and ear, using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nano-surface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.

  6. Tissue specific regulation of lipogenesis by thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Blennemann, B.; Freake, H. (Univ. of Connecticut, Storrs (United States))

    1990-02-26

    Thyroid hormone stimulates long chain fatty acid synthesis in rat liver by increasing the amounts of key lipogenic enzymes. Sparse and conflicting data exist concerning its action on this pathway in other tissues. The authors recently showed that, in contrast to liver, hypothyroidism stimulates lipogenesis in brown adipose tissue and have now systematically examined the effects of thyroid state on fatty acid synthesis in other rat tissues. Lipogenesis was assessed by tritiated water incorporation. Euthyroid hepatic fatty acid synthesis (16.6um H/g/h) was reduced to 30% in hypothyroid rats and increased 3 fold in hyperthyroidism. Lipogenesis was detected in euthyroid kidney and heart and these levels were also stimulated by thyroid hormone treatment. Brown adipose tissue was unique in showing increased lipogenesis in the hypothyroid state. Hyperthyroid levels were not different from euthyroid. Effects in white adipose tissue were small and inconsistent. Brain, skin and lung were all lipogenically active, but did not respond to changes in thyroid state. Low but detectable levels of fatty acid synthesis were measured in muscle, which also were non-responsive. A wide spectrum of responses to thyroid hormone are seen in different rat tissues and thus the pathway of long chain fatty acid synthesis would appear to be an excellent model for examining the tissue specific regulation of gene expression by thyroid hormone.

  7. Tissue specific regulation of lipogenesis by thyroid hormone

    International Nuclear Information System (INIS)

    Blennemann, B.; Freake, H.

    1990-01-01

    Thyroid hormone stimulates long chain fatty acid synthesis in rat liver by increasing the amounts of key lipogenic enzymes. Sparse and conflicting data exist concerning its action on this pathway in other tissues. The authors recently showed that, in contrast to liver, hypothyroidism stimulates lipogenesis in brown adipose tissue and have now systematically examined the effects of thyroid state on fatty acid synthesis in other rat tissues. Lipogenesis was assessed by tritiated water incorporation. Euthyroid hepatic fatty acid synthesis (16.6um H/g/h) was reduced to 30% in hypothyroid rats and increased 3 fold in hyperthyroidism. Lipogenesis was detected in euthyroid kidney and heart and these levels were also stimulated by thyroid hormone treatment. Brown adipose tissue was unique in showing increased lipogenesis in the hypothyroid state. Hyperthyroid levels were not different from euthyroid. Effects in white adipose tissue were small and inconsistent. Brain, skin and lung were all lipogenically active, but did not respond to changes in thyroid state. Low but detectable levels of fatty acid synthesis were measured in muscle, which also were non-responsive. A wide spectrum of responses to thyroid hormone are seen in different rat tissues and thus the pathway of long chain fatty acid synthesis would appear to be an excellent model for examining the tissue specific regulation of gene expression by thyroid hormone

  8. Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues.

    Science.gov (United States)

    Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A

    2015-07-01

    Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Transcriptomics resources of human tissues and organs

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Hallström, Björn M.; Lindskog, Cecilia

    2016-01-01

    a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue-restricted manner. Here, we review publicly available human transcriptome resources and discuss body-wide data from independent genome......Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large-scale transcriptomics studies have analyzed the expression of protein-coding genes across tissues. These datasets provide...

  10. Conveyance of natural gas. Organization and regulation

    International Nuclear Information System (INIS)

    1995-01-01

    This International Energy Agency (IEA) study deals with the conveyance of natural gas. The socio-economic factors are given as well as the different organization and regulations modes of natural gas conveyance and storage in the IEA countries and in central and eastern Europe. The main questions forming the subject of discussions in the IEA countries are analyzed too. (O.L.). 50 refs., 55 figs., 16 tabs

  11. Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

    Science.gov (United States)

    Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

    2014-12-01

    Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. © 2014 Wiley Periodicals, Inc.

  12. Smart-grid investments, regulation and organization

    International Nuclear Information System (INIS)

    Agrell, Per J.; Bogetoft, Peter; Mikkers, Misja

    2013-01-01

    Grid infrastructure managers worldwide are facing demands for reinvestments in new assets with higher on-grid and off-grid functionality in order to meet new environmental targets. The roles of the current actors will change as the vertical interfaces between regulated and unregulated tasks become blurred. In this paper, we characterize some of the effects of new asset investments policy on the network tasks, assets and costs and contrast this with the assumptions of the current economic network regulation. To provide structure, we present a model of investment provision under regulation between a distribution system operator and a potential investor–generator. The results from the model confirm the hypothesis that network regulation should find a focal point, should integrate externalities in the performance assessment and should avoid wide delegation of contracting-billing for smart-grid investments. - Highlights: ► We review regulatory solutions for smart-grid and DER investments. ► What matters more than upfront incentives is organization and delegation. ► We model regulated investment under private information by a generator or a DSO. ► Highest welfare for high-powered incentives and centralized information. ► Market approaches likely to give poor outcomes for this case.

  13. Neutron organ dose and the influence of adipose tissue

    Science.gov (United States)

    Simpkins, Robert Wayne

    Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

  14. Development, regulation, metabolism and function of bone marrow adipose tissues.

    Science.gov (United States)

    Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

    2018-05-01

    Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Bioprinting scale-up tissue and organ constructs for transplantation.

    Science.gov (United States)

    Ozbolat, Ibrahim T

    2015-07-01

    Bioprinting is an emerging field that is having a revolutionary impact on the medical sciences. It offers great precision for the spatial placement of cells, proteins, genes, drugs, and biologically active particles to better guide tissue generation and formation. This emerging biotechnology appears to be promising for advancing tissue engineering toward functional tissue and organ fabrication for transplantation, drug testing, research investigations, and cancer or disease modeling, and has recently attracted growing interest worldwide among researchers and the general public. In this Opinion, I highlight possibilities for the bioprinting scale-up of functional tissue and organ constructs for transplantation and provide the reader with alternative approaches, their limitations, and promising directions for new research prospects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Tissue and organ regeneration in adults extension of the paradigm to several organs

    CERN Document Server

    Yannas, Ioannis V

    2015-01-01

    This textbook describes the basic principles of induced organ regeneration in skin and peripheral nerves and extends the original successful paradigm to other organs. A set of trans-organ rules is established and its use in regeneration of several organs is illustrated from the works of several independent investigators who worked with a variety of organs, such as the lung, the bladder, and the Achilles tendon, using collagen-based scaffolds somewhat similar to the original one. These critical medical treatments fill the clinical need that is not met by organ transplantation. New to this second edition: New information extending the paradigm of tissue regeneration from organ regeneration in skin and peripheral nerves to other organs Guidelines, known as trans-organ rules, are described for the first time for extending this unique medical treatment to organs of several medical specialties The work serves as a comprehensive text and reference for students and practitioners of tissue engineering  

  17. A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity.

    Science.gov (United States)

    Cerchiari, Alec E; Garbe, James C; Jee, Noel Y; Todhunter, Michael E; Broaders, Kyle E; Peehl, Donna M; Desai, Tejal A; LaBarge, Mark A; Thomson, Matthew; Gartner, Zev J

    2015-02-17

    Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo- and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.

  18. 3D Bioprinting for Tissue and Organ Fabrication.

    Science.gov (United States)

    Zhang, Yu Shrike; Yue, Kan; Aleman, Julio; Moghaddam, Kamyar Mollazadeh; Bakht, Syeda Mahwish; Yang, Jingzhou; Jia, Weitao; Dell'Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

    2017-01-01

    The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.

  19. 3D Bioprinting for Tissue and Organ Fabrication

    Science.gov (United States)

    Zhang, Yu Shrike; Yang, Jingzhou; Jia, Weitao; Dell’Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

    2016-01-01

    The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development. PMID:27126775

  20. [Ornithine decarboxylase in mammalian organs and tissues at hibernation and artificial hypobiosis].

    Science.gov (United States)

    Logvinovich, O S; Aksenova, G E

    2013-01-01

    Ornithine decarboxylase (ODC, EC 4.1.1.17.) is a short-lived and dynamically regulated enzyme of polyamines biosynthesis. Regulation of functional, metabolic and proliferative state of organs and tissues involves the modifications of the ODC enzymatic activity. The organ-specific changes in ODC activity were revealed in organs and tissues (liver, spleen, bone marrow, kidney, and intestinal mucosa) of hibernating mammals - squirrels Spermophilus undulates - during the hibernating season. At that, a positive correlation was detected between the decline and recovery of the specialized functions of organs and tissues and the respective modifications of ODC activity during hibernation bouts. Investigation of changes in ODC activity in organs and tissues of non-hibernating mammals under artificial hypobiosis showed that in Wistar rats immediately after exposure to hypothermia-hypoxia-hypercapnia (hypobiosis) the level of ODC activity was low in thymus, spleen, small intestine mucosa, neocortex, and liver. The most marked reduction in enzyme activity was observed in actively proliferating tissues: thymus, spleen, small intestine mucosa. In bone marrow of squirrels, while in a state of torpor, as well as in thymus of rats after exposure to hypothermia-hypoxia-hypercapnia, changes in the ODC activity correlated with changes in the rate of cell proliferation (by the criterion of cells distribution over cell cycle). The results obtained, along with the critical analysis of published data, indicate that the ODC enzyme is involved in biochemical adaptation of mammals to natural and artificial hypobiosis. A decline in the ODC enzymatic activity indicates a decline in proliferative, functional, and metabolic activity of organs and tissues of mammals (bone marrow, mucosa of small intestine, thymus, spleen, neocortex, liver, kidneys) when entering the state of hypobiosis.

  1. Critical Point in Self-Organized Tissue Growth

    Science.gov (United States)

    Aguilar-Hidalgo, Daniel; Werner, Steffen; Wartlick, Ortrud; González-Gaitán, Marcos; Friedrich, Benjamin M.; Jülicher, Frank

    2018-05-01

    We present a theory of pattern formation in growing domains inspired by biological examples of tissue development. Gradients of signaling molecules regulate growth, while growth changes these graded chemical patterns by dilution and advection. We identify a critical point of this feedback dynamics, which is characterized by spatially homogeneous growth and proportional scaling of patterns with tissue length. We apply this theory to the biological model system of the developing wing of the fruit fly Drosophila melanogaster and quantitatively identify signatures of the critical point.

  2. Regulating plant physiology with organic electronics.

    Science.gov (United States)

    Poxson, David J; Karady, Michal; Gabrielsson, Roger; Alkattan, Aziz Y; Gustavsson, Anna; Doyle, Siamsa M; Robert, Stéphanie; Ljung, Karin; Grebe, Markus; Simon, Daniel T; Berggren, Magnus

    2017-05-02

    The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants.

  3. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala, M D

    2012-10-11

    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat

  4. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

    Science.gov (United States)

    Pachori, Alok S; Melo, Luis G; Hart, Melanie L; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D; Stahl, Gregory L; Pratt, Richard E; Dzau, Victor J

    2004-08-17

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  5. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

    Science.gov (United States)

    Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

    2004-08-01

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  6. Tissue expression and developmental regulation of chicken cathelicidin antimicrobial peptides

    Directory of Open Access Journals (Sweden)

    Achanta Mallika

    2012-05-01

    Full Text Available Abstract Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.

  7. Regucalcin expression in bovine tissues and its regulation by sex steroid hormones in accessory sex glands.

    Directory of Open Access Journals (Sweden)

    Laura Starvaggi Cucuzza

    Full Text Available Regucalcin (RGN is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle.

  8. European regulations and their impact on tissue banking.

    Science.gov (United States)

    Tatarenko, Alina

    2006-01-01

    Extensive CoE-EU cooperation ensures coherence and complementarities between the principles of the CoE guides which can be regarded as recommendations on best practice, and the technical requirements of the EU directives which set out legally binding requirements. This means that the same standards now exist throughout European continent. Having a common set of standards facilitates cooperation between different healthcare systems, especially in cases of emergencies, and the export-import issues. Adoption of the same quality management and traceability systems helps to minimise the risks and prevent disease transmissions. It reassures patients who undergo treatments outside of their countries. The tissue establishments need to introduce technical and structural changes to adhere to the new regulations which ultimately results in saving and improving of lives of many patients.

  9. Genetic control of organ shape and tissue polarity.

    Directory of Open Access Journals (Sweden)

    Amelia A Green

    2010-11-01

    Full Text Available The mechanisms by which genes control organ shape are poorly understood. In principle, genes may control shape by modifying local rates and/or orientations of deformation. Distinguishing between these possibilities has been difficult because of interactions between patterns, orientations, and mechanical constraints during growth. Here we show how a combination of growth analysis, molecular genetics, and modelling can be used to dissect the factors contributing to shape. Using the Snapdragon (Antirrhinum flower as an example, we show how shape development reflects local rates and orientations of tissue growth that vary spatially and temporally to form a dynamic growth field. This growth field is under the control of several dorsoventral genes that influence flower shape. The action of these genes can be modelled by assuming they modulate specified growth rates parallel or perpendicular to local orientations, established by a few key organisers of tissue polarity. Models in which dorsoventral genes only influence specified growth rates do not fully account for the observed growth fields and shapes. However, the data can be readily explained by a model in which dorsoventral genes also modify organisers of tissue polarity. In particular, genetic control of tissue polarity organisers at ventral petal junctions and distal boundaries allows both the shape and growth field of the flower to be accounted for in wild type and mutants. The results suggest that genetic control of tissue polarity organisers has played a key role in the development and evolution of shape.

  10. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-08-01

    Full Text Available Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis.

  11. From bioavailability science to regulation of organic chemicals

    NARCIS (Netherlands)

    Ortega-Calvo, J.J.; Harmsen, J.; Parsons, J.R.; Semple, K.T.; Aitkin, M.D.; Ajao, C.; Eadsforth, C.; Galay-Burgos, M.; Naidu, R.; Oliver, R.; Peijnenburg, W.J.G.M.; Römbke, J.; Streck, G.; Versonnen, B.

    2015-01-01

    The bioavailability of organic chemicals in soil and sediment is an important area of scientific investigation for environmental scientists, although this area of study remains only partially recognized by regulators and industries working in the environmental sector. Regulators have recently

  12. Human colon tissue in organ culture: calcium and multi-mineral-induced mucosal differentiation.

    Science.gov (United States)

    Dame, Michael K; Veerapaneni, Indiradevi; Bhagavathula, Narasimharao; Naik, Madhav; Varani, James

    2011-01-01

    We have recently shown that a multi-mineral extract from the marine red algae, Lithothamnion calcareum, suppresses colon polyp formation and inflammation in mice. In the present study, we used intact human colon tissue in organ culture to compare responses initiated by Ca(2+) supplementation versus the multi-mineral extract. Normal human colon tissue was treated for 2 d in culture with various concentrations of calcium or the mineral-rich extract. The tissue was then prepared for histology/immunohistochemistry, and the culture supernatants were assayed for levels of type I procollagen and type I collagen. At higher Ca(2+) concentrations or with the mineral-rich extract, proliferation of epithelial cells at the base and walls of the mucosal crypts was suppressed, as visualized by reduced Ki67 staining. E-cadherin, a marker of differentiation, was more strongly expressed at the upper third of the crypt and at the luminal surface. Treatment with Ca(2+) or with the multi-mineral extract influenced collagen turnover, with decreased procollagen and increased type I collagen. These data suggest that calcium or mineral-rich extract has the capacity to (1) promote differentiation in human colon tissue in organ culture and (2) modulate stromal function as assessed by increased levels of type I collagen. Taken together, these data suggest that human colon tissue in organ culture (supporting in vivo finding in mice) will provide a valuable model for the preclinical assessment of agents that regulate growth and differentiation in the colonic mucosa.

  13. Cell type-specific characterization of nuclear DNA contents within complex tissues and organs

    Directory of Open Access Journals (Sweden)

    Lambert Georgina M

    2005-10-01

    Full Text Available Abstract Background Eukaryotic organisms are defined by the presence of a nucleus, which encloses the chromosomal DNA, and is characterized by its DNA content (C-value. Complex eukaryotic organisms contain organs and tissues that comprise interspersions of different cell types, within which polysomaty, endoreduplication, and cell cycle arrest is frequently observed. Little is known about the distribution of C-values across different cell types within these organs and tissues. Results We have developed, and describe here, a method to precisely define the C-value status within any specific cell type within complex organs and tissues of plants. We illustrate the application of this method to Arabidopsis thaliana, specifically focusing on the different cell types found within the root. Conclusion The method accurately and conveniently charts C-value within specific cell types, and provides novel insight into developmental processes. The method is, in principle, applicable to any transformable organism, including mammals, within which cell type specificity of regulation of endoreduplication, of polysomaty, and of cell cycle arrest is suspected.

  14. Elimination of copper in tissues and organs of rainbow trout

    Directory of Open Access Journals (Sweden)

    Gaye Dogan

    2011-01-01

    Full Text Available Copper (Cu elimination was investigated in the tissue and organs of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792, after Cu-free diets exposure. In the current study, fish were fed to satiation on diets containing 0.022 (Group 1; Control, 0.043 (Group 2, 0.123 (Group 3, 0.424 (Group 4 g Cu*kg-1 diet for 60 days before elimination experiment. A total of 288 fish (mean weight 84.28±1.05 g were randomly transferred to 12 fibreglass tanks. The fish were fed the Cu-free diet twice daily, until apparent satiation, during 60 days. Subsequently, the experiment was established for a period of elimination, during which samples were taken at days 15, 30, 45 and 60. Cu concentration in the muscle, gill tissue, digestive system, liver and whole body of fish were determined after 60 days depuration. Cu concentrations in tissues of rainbow trout decreased during depuration period, and the order of Cu elimination in tissue and organs of rainbow trout was: digestive system (73.1 %, then gill (41.1 %, muscle (31.5 % and liver (17.2 % for group 2; digestive system (74.1%, then muscle (65.8%, gill (60.0% and liver (34.6% for group 3; and digestive system (85.8%, then muscle (80.8%, liver (50.5% and less/equal in gill (50.2% for group 4. In statistical analysis, both groups and time were significant factors (P less than 0.05 on elimination rate. Moreover, significant interaction between groups and time were identified on elimination rate. Digestive system showed the fastest elimination rates of Cu at all groups compared with other tissues.

  15. Leiomyosarcoma: A rare soft tissue cancer arising from multiple organs

    Directory of Open Access Journals (Sweden)

    Zorawar Singh

    2018-03-01

    Full Text Available Leiomyosarcoma (LMS, a smooth muscle connective tissue tumor, is a rare form of cancer which accounts for 5–10% of soft tissue sarcomas. This type of cancer is highly unpredictable. LMS is a resistant type of cancer and can remain in the dormant state for long time. It can recur in the later stages of life. LMS has been reported in different animals including humans. A wide literature search was done. The PubMed database was used to search for journal articles on the occurrence of LMS in different organs from 1950 to 2016. LMS has been reported to be associated with different organs, including esophagus, stomach, intestine, anus and uterus. In this article, an attempt has been made to review the studies based on occurrence of LMS with respect to the organs affected and frequency of publications. Finding the organ-associated occurrence of LMS may be useful in assessing the overall risk and formulating future cancer preventive strategies.

  16. Regulation of organic anion transport in the liver

    NARCIS (Netherlands)

    Roelofsen, H; Jansen, PLM

    1997-01-01

    In several liver diseases the biliary transport is disturbed, resulting in, for example, jaundice and cholestasis. Many of these symptoms can be attributed to altered regulation of hepatic transporters. Organic anion transport, mediated by the canalicular multispecific organic anion transporter

  17. The necessity of strengthening the cooperation between tissue banks and organ transplant organizations at national, regional, and international levels.

    Science.gov (United States)

    Morales Pedraza, Jorge

    2013-12-01

    The donation of tissues and organs increases significantly when tissue banks and organ transplant organizations work together in the procurement of organs and tissues at donor sources (hospitals, coroners system, organ procurement agencies, and funeral homes, among others). To achieve this important goal, national competent health authorities should considered the establishment of a mechanism that promote the widest possible cooperation between tissue banks and organ transplant organizations with hospitals, research medical institutions, universities, and other medical institutions and facilities. One of the issues that can facilitate this cooperation is the establishment of a coding and traceability system that could identify all tissues and organs used in transplant activities carried out in any country. The promotion of national, regional, and international cooperation between tissue banks and organ transplant organizations would enable the sharing of relevant information that could be important for medical practice and scientific studies carried out by many countries, particularly for those countries with a weak health care system.

  18. Profile of effective donors from organ and tissue procurement services

    Science.gov (United States)

    Rodrigues, Simey de Lima Lopes; Ferraz Neto, Jose Ben-Hur de Escobar; Sardinha, Luiz Antonio da Costa; Araujo, Sebastião; Zambelli, Helder Jose Lessa; Boin, Ilka de Fátima Santana Ferreira; Athayde, Maria Valeria de Omena; Montone, Eliete Bombarda Bachega; Panunto, Marcia Raquel

    2014-01-01

    Objective To characterize the profile of effective organ and tissue donors and to understand which organs and tissues were donated for transplantation. Methods This was a quantitative, descriptive, exploratory, retrospective study that analyzed clinical data from 305 donors between January 2006 to December 2010. The data were then analyzed using descriptive analyses, generating frequency tables, measures of position (mean, minimum and maximum) and measures of dispersion (standard deviation) for data that was social and clinical in nature. Results There was an overall predominance of white (72%) and male (55%) individuals between the ages of 41 and 60 years (44%). The primary cause of brain death was cerebrovascular accident (55%). In the patient history, 31% of the patients were classified as overweight, 27% as hypertensive and only 4.3% as having diabetes mellitus. Vasoactive drugs were used in 92.7% of the donors, and the main drug of choice was noradrenaline (81.6%). Hyperglycemia and hypernatremia were diagnosed in 78% and 71% of the donors, respectively. Conclusion Significant hemodynamic changes were found, and the results indicate that the use of vasoactive drugs was the main strategy used to control these changes. Furthermore, most donors presented with hyperglycemia and hypernatremia, which were frequently reported in association with brain death. The persistent nature of these findings suggests that the organ donors were inadequately maintained. PMID:24770685

  19. The promise of organ and tissue preservation to transform medicine

    Science.gov (United States)

    Giwa, Sebastian; Lewis, Jedediah K; Alvarez, Luis; Langer, Robert; Roth, Alvin E; Church, George M; Markmann, James F; Sachs, David H; Chandraker, Anil; Wertheim, Jason A; Rothblatt, Martine; Boyden, Edward S; Eidbo, Elling; Lee, W P Andrew; Pomahac, Bohdan; Brandacher, Gerald; Weinstock, David M; Elliott, Gloria; Nelson, David; Acker, Jason P; Uygun, Korkut; Schmalz, Boris; Weegman, Brad P; Tocchio, Alessandro; Fahy, Greg M; Storey, Kenneth B; Rubinsky, Boris; Bischof, John; Elliott, Janet A W; Woodruff, Teresa K; Morris, G John; Demirci, Utkan; Brockbank, Kelvin G M; Woods, Erik J; Ben, Robert N; Baust, John G; Gao, Dayong; Fuller, Barry; Rabin, Yoed; Kravitz, David C; Taylor, Michael J; Toner, Mehmet

    2017-01-01

    The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science. PMID:28591112

  20. The promise of organ and tissue preservation to transform medicine.

    Science.gov (United States)

    Giwa, Sebastian; Lewis, Jedediah K; Alvarez, Luis; Langer, Robert; Roth, Alvin E; Church, George M; Markmann, James F; Sachs, David H; Chandraker, Anil; Wertheim, Jason A; Rothblatt, Martine; Boyden, Edward S; Eidbo, Elling; Lee, W P Andrew; Pomahac, Bohdan; Brandacher, Gerald; Weinstock, David M; Elliott, Gloria; Nelson, David; Acker, Jason P; Uygun, Korkut; Schmalz, Boris; Weegman, Brad P; Tocchio, Alessandro; Fahy, Greg M; Storey, Kenneth B; Rubinsky, Boris; Bischof, John; Elliott, Janet A W; Woodruff, Teresa K; Morris, G John; Demirci, Utkan; Brockbank, Kelvin G M; Woods, Erik J; Ben, Robert N; Baust, John G; Gao, Dayong; Fuller, Barry; Rabin, Yoed; Kravitz, David C; Taylor, Michael J; Toner, Mehmet

    2017-06-07

    The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

  1. Selective Regulator Decoupling and Organizations' Strategic Responses

    NARCIS (Netherlands)

    Heese, Jonas; Krishnan, Ranjani; Moers, Frank

    2016-01-01

    Organizations often respond to institutional pressures by symbolically adopting policies and procedures but decoupling them from actual practice. Literature has examined why organizations decouple from regulatory pressures. In this study, we argue that decoupling occurs within regulatory agencies

  2. Leading Efforts to Increase Organ Donation Through Professionalization of Organ Procurement Organizations and Establishment of Organ and Tissue Donor Registries.

    Science.gov (United States)

    Vertanous, T; Czer, L S C; de Robertis, M; Kiankhooy, A; Kobashigawa, J; Esmailian, F; Trento, A

    2016-01-01

    The influence of new donor registrations through the California Organ and Tissue Donor Registry on the local OneLegacy Organ Procurement Organization (OPO) was examined during a 6-year period. Publicly available data from Donate Life America for California were examined for the 6 calendar years of 2009-2014. Performance data from OneLegacy for the same 6 years for organ donors and number of transplants were also examined. The donor designation rate (DDR) was defined as the rate at which new individuals joined the state donor registry as a percentage of all driver licenses and ID cards issued within a calendar year. The total donor designation (TDD) was defined as the sum of the new and existing people who were registered organ donors. Donor designation share (DDS) was the total number of designated donors as a percentage of all residents of the state who were ≥18 years old. The business practices and educational efforts of the OneLegacy OPO were examined as well. In California, from 2009 through 2014, the DDR was 25.5%-28%. When added to the existing donor registrations, the TDD and DDS increased each year from 2009 through 2014. With the current level of growth, it is projected that California will be able to reach a DDS of 50% by 2017. For the OneLegacy OPO, designated donors from the California Organ and Tissue Donor Registry made up 15% of the total donations in 2009, and 39% of the total donations in 2014, increasing by ∼5% each year since 2009. By increasing professionalization and transparency, and widening its educational and training efforts, OneLegacy was able to take advantage of an increasing percentage of donors who were designated donors and to increase the overall number of donors and organs transplanted, becoming one of the largest OPOs in the nation. This can be a model for OPOs in other donor service areas, and it may set the stage for the United States to serve as an example to the global community in the practice of organ donation. Copyright

  3. Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

    Science.gov (United States)

    Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

    2016-12-01

    17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

  4. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  5. Smart-grid Investments, Regulation and Organization

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter; Mikkers, Misja

    2013-01-01

    Grid infrastructure managers worldwide are facing demands for reinvestments in new assets with higher on-grid and off-grid functionality in order to meet new environmental targets. The roles of the current actors will change as the vertical interfaces between regulated and unregulated tasks become...... blurred. In this paper, we characterize some of the effects of new asset investments policy on the network tasks, assets and costs and contrast this with the assumptions of the current economic network regulation. To provide structure, we present a model of investment provision under regulation between...

  6. Tissue engineering as a potential alternative or adjunct to surgical reconstruction in treating pelvic organ prolapse

    DEFF Research Database (Denmark)

    Boennelycke, M; Gräs, Søren; Lose, G

    2013-01-01

    Cell-based tissue engineering strategies could potentially provide attractive alternatives to surgical reconstruction of native tissue or the use of surgical implants in treating pelvic organ prolapse (POP).......Cell-based tissue engineering strategies could potentially provide attractive alternatives to surgical reconstruction of native tissue or the use of surgical implants in treating pelvic organ prolapse (POP)....

  7. Wnt and BMP signaling crosstalk in regulating dental stem cells: Implications in dental tissue engineering

    Directory of Open Access Journals (Sweden)

    Fugui Zhang

    2016-12-01

    Full Text Available Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs, and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

  8. Regulation of gene expression in neuronal tissue by RNA interference and editing

    DEFF Research Database (Denmark)

    Venø, Morten Trillingsgaard

    No tissue in the mammalian organism is more complex than the brain. This complexity is in part the result of precise timing and interplay of a large number mechanisms modulating gene expression post-transcriptionally. Fine-tuning mechanisms such as A-to-I editing of RNA transcripts and regulation...... mediated by microRNAs are crucial for the correct function of the mammalian brain. We are addressing A-to-I editing and regulation by microRNAs with spatio-temporal resolution in the embryonic porcine brain by Solexa sequencing of microRNAs and 454 sequencing of edited neuronal messenger RNAs, resulting...... in detailed data of both of these fine-tuning mechanisms in the embryonic development of the pig. Editing levels of transcripts examined are generally seen to increase through development, in agreement with editing of specific microRNA also examined in the Solexa sequencing study. Three studies examining...

  9. TiGER: a database for tissue-specific gene expression and regulation.

    Science.gov (United States)

    Liu, Xiong; Yu, Xueping; Zack, Donald J; Zhu, Heng; Qian, Jiang

    2008-06-09

    Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation. The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation). The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM) detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes. We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.

  10. TiGER: A database for tissue-specific gene expression and regulation

    Directory of Open Access Journals (Sweden)

    Zack Donald J

    2008-06-01

    Full Text Available Abstract Background Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation. Results The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation. The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes. Conclusion We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.

  11. Organ and tissue donation: what do high school students know?

    Directory of Open Access Journals (Sweden)

    Marcela Cristina de Lemos

    2007-09-01

    Full Text Available Objectives: To know the opinion of senior high school students in publicand private schools on the process of donating and transplanting organsand tissues, and their desire to be donors. Methods: A descriptive crosssectionalstudy, conducted from 2004 to 2005, on the opinion/knowledgeof senior high school students in public and private schools in the VilaMariana region of the city of São Paulo, on the process of organ and tissuedonation and transplantation. The convenience sample was made up of140 (81% students from two private schools and 167 (51% studentsfrom a public school. The project was approved by the Research EthicsCommittee of the UNIFESP. Results: Data showed that 163 (53.1%students believe that donation is by presumed consent and 147 (47.9%that consider that it occurs by informed consent. Of the public schoolstudents, 120 (71.9% believe that transplants are public and free ofcharge in Brazil versus 94 (67.1% of the students from private schools.Students know that donations may be made by living or dead donors(121 - 86.4% private schools versus 113 – 67.7% public school. Wehighlight that 22 (15.7% of the private school students and 16 (9.6%of those from the public school believe that the commerce of organs isallowed in Brazil. As to intentions of being a donor, 108 (77.1% of theprivate school students declared themselves organ and tissue donorsversus 106 (63.5% from the public school, and 63 (59.4% from thepublic versus 61 (56.5% from the private schools have already informedtheir families. Conclusion: There was no difference in knowledge andopinion among the students from the public and private schools as toaspects regarding donation and transplantation.

  12. Essays on regulation, institutions, and industrial organization

    Science.gov (United States)

    Bergara, Mario Esteban

    Essay I develops a comparative institutional analysis of network access price regulation and "light-handed" regulation. While the former is a specific-agency-based arrangement with higher political influence, the latter is a court-based system. Consequently, the main trade-off between both frameworks reflects the merits of having efficient political and judicial institutions. Price regulation is superior when distributional concerns are irrelevant and information asymmetries are lower. Poorly functioning political systems and high welfare costs of raising funds make price regulation less attractive. Light regulation is more attractive when potential rents are smaller, the monopolist is more risk averse, the judicial system is more efficient, and the threat of government intervention is more credible. The possibility of private transfers makes price regulation more advantageous. Higher information asymmetries among firms makes light-handed regulation more attractive. The main results are consistent with a plausible interpretation of the drastic deregulatory process in New Zealand. Essay II studies the preliminary effects of the deregulation of direct access in the New Zealand's electricity market. A slight improvement in quality standards and an overall efficiency increase took place after two years of deregulation. Retailers were able to successfully enter in large demand, dense areas, with a large proportion of industrial and commercial users, where incumbents were not distributing electricity efficiently. Pricing policies appears to be influenced by market forces (associated to economic and demographic characteristics) as expected in a light regulatory framework. Essay III focuses on the possibility of endogenous sunk costs and the introduction of new products. Firms that exert some monopoly power in one market and introduce a new good whose demand is determined by a broader set of consumers might be forced to change their competing strategies. If the new product

  13. Exercise and Regulation of Bone and Collagen Tissue Biology.

    Science.gov (United States)

    Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

    2015-01-01

    The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. © 2015 Elsevier Inc. All rights reserved.

  14. Warts signaling controls organ and body growth through regulation of ecdysone

    DEFF Research Database (Denmark)

    Møller, Morten Erik; Nagy, Stanislav; Gerlach, Stephan Uwe

    2017-01-01

    Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms...... under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin....../insulin-like growth factor (IGF) (insulin) signaling [2, 5]. The interplay between insulin and ecdysone signaling regulates systemic growth and controls organismal size. Here, we show that Warts (Wts; LATS1/2) signaling regulates systemic growth in Drosophila by activating basal ecdysone production, which negatively...

  15. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  16. Environmental regulation of valvulogenesis:implications for tissue engineering

    NARCIS (Netherlands)

    Riem Vis, P.W.; Kluin, J.; Sluijter, J.P.G.; Herwerden, van L.A.; Bouten, C.V.C.

    2011-01-01

    Ongoing research efforts aim at improving the creation of tissue-engineered heart valves for in vivo systemic application. Hence, in vitro studies concentrate on optimising culture protocols incorporating biological as well as biophysical stimuli for tissue development. Important lessons can be

  17. Exercise and Regulation of Bone and Collagen Tissue Biology

    DEFF Research Database (Denmark)

    Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja

    2015-01-01

    The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensur...

  18. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  19. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  20. Regulation of annexins following infection like tissue damage – investigated by 2-dimensional gel electrophoresis

    DEFF Research Database (Denmark)

    Wulff, Tune; Nielsen, Michael Engelbrecht

    are regulated after tissue damaged on the protein level. These proteins have been assign to functions like regulation of coagulation, apoptosis, and exocytosis, indicating their importance following infection and subsequent repair in fish. In addition the regulation observed in this study are supported...... an established model. In the model infection is mimicked by a well-defined tissue damage allowing each fish to be equally affected. Samples were taken 7 days after tissue damage and included samples from the damaged tissue, internal control and an external control. Changes in protein expression between the wound...... by previous findings on the mRNA level, where both proteins are regulated following infection. In conclusion this study show regulation on the protein level of two members of the annexin protein family after infection like tissue damage....

  1. Smart-Grid Investments, Regulation and Organization

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    on the network tasks, assets and costs and contrast this with the assumptions implicit or explicit in current economic network regulation. The resulting challenge is identified as the change in the direction of higher asymmetry of information and higher capital intensity, combined with ambiguities in terms......Worldwide, but in particular in North America and Europe, the grid infrastructure managers are facing demands for reinvestments in new assets with higher on-grid and off-grid functionality in order to promote energy efficiency and low-carbon conversion of the energy sector. To meet societal policy...

  2. Organization and regulation of energy markets in the European Union

    International Nuclear Information System (INIS)

    Vasconcelos, J.

    2002-01-01

    The energy regulation policy and the organization of power matters in the European Union as well as the energy markets are discussed in this Keynote Paper. The Council of European Energy Regulators is introduced. The goal of the European Union regarding energy generation and consumption in the future are analyzed. (R.P.)

  3. Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

    Science.gov (United States)

    Lenas, Petros; Luyten, Frank P; Doblare, Manuel; Nicodemou-Lena, Eleni; Lanzara, Andreina Elena

    2011-06-01

    Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Regulation of cytoskeletal organization by syndecan transmembrane proteoglycans

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Couchman, John R

    2003-01-01

    have recently suggested that signaling through core protein of syndecans can regulate cytoskeletal organization through their clustering, association with cytoskeletal structures, binding to cytoplasmic binding proteins, and intracellular phosphorylation. Here we will review current understanding...... of signaling through syndecans in cytoskeletal organization....

  5. Ghrelin receptor regulates adipose tissue inflammation in aging.

    Science.gov (United States)

    Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

  6. Geometry-driven cell organization determines tissue growths in scaffold pores: consequences for fibronectin organization.

    Directory of Open Access Journals (Sweden)

    Pascal Joly

    Full Text Available To heal tissue defects, cells have to bridge gaps and generate new extracellular matrix (ECM. Macroporous scaffolds are frequently used to support the process of defect filling and thus foster tissue regeneration. Such biomaterials contain micro-voids (pores that the cells fill with their own ECM over time. There is only limited knowledge on how pore geometry influences cell organization and matrix production, even though it is highly relevant for scaffold design. This study hypothesized that 1 a simple geometric description predicts cellular organization during pore filling at the cell level and that 2 pore closure results in a reorganization of ECM. Scaffolds with a broad distribution of pore sizes (macroporous starPEG-heparin cryogel were used as a model system and seeded with primary fibroblasts. The strategies of cells to fill pores could be explained by a simple geometrical model considering cells as tensioned chords. The model matched qualitatively as well as quantitatively by means of cell number vs. open cross-sectional area for all pore sizes. The correlation between ECM location and cell position was higher when the pores were not filled with tissue (Pearson's coefficient ρ = 0.45±0.01 and reduced once the pores were closed (ρ = 0.26±0.04 indicating a reorganization of the cell/ECM network. Scaffold pore size directed the time required for pore closure and furthermore impacted the organization of the fibronectin matrix. Understanding how cells fill micro-voids will help to design biomaterial scaffolds that support the endogenous healing process and thus allow a fast filling of tissue defects.

  7. Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

    DEFF Research Database (Denmark)

    Nielsen, Thomas Svava; Jessen, Niels; Jørgensen, Jens Otto Lunde

    2014-01-01

    is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue. This response is crucial in order to provide the organism with a sufficient supply......Lipolysis is the process by which triglycerides are hydrolyzed to free fatty acids (FFA) and glycerol. In adipocytes, this is achieved by the sequential action of Adipose Triglyceride Lipase (ATGL), Hormone Sensitive Lipase (HSL) and Monoglyceride Lipase (MGL). The activity in the lipolytic pathway...... of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. Since the discovery of ATGL in 2004, substantial progress has been...

  8. On the connective tissue regulator Follistatin-like 1

    NARCIS (Netherlands)

    Sylva, M.

    2014-01-01

    Even though for many years the molecular mechanisms underlying cardiac development have been studied, the majority of cardiac defects remain unexplained. Defects in the cardiac connective tissue component result in a large proportion of heart defects such as valve and septal defects. Previous

  9. Tissue-specific regulation of mouse MicroRNA genes in endoderm-derived tissues

    OpenAIRE

    Gao, Yan; Schug, Jonathan; McKenna, Lindsay B.; Le Lay, John; Kaestner, Klaus H.; Greenbaum, Linda E.

    2010-01-01

    MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here, we determine the entire microRNAome of three endoderm-derived tissues, liver, jejunum and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After...

  10. Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration

    DEFF Research Database (Denmark)

    Ohki, Makiko; Ohki, Yuichi; Ishihara, Makoto

    2010-01-01

    tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool......-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b(+) cells and VEGFR-1(+) cells, but not carrier-mobilized cells or CD11b(-) cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb...... and mobilizes CD45(+)CD11b(+) proangiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b(+) cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF...

  11. Impact of Growth Hormone on Regulation of Adipose Tissue.

    Science.gov (United States)

    Troike, Katie M; Henry, Brooke E; Jensen, Elizabeth A; Young, Jonathan A; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2017-06-18

    Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output. We will provide an overview of GH structure and function and define several human conditions and cognate mouse lines with extremes in GH action that have helped shape our understanding of GH and AT. A detailed discussion of the GH/AT relationship will be included that addresses adipokine production, immune cell populations, lipid metabolism, senescence, differentiation, and fibrosis, as well as brown AT and beiging of white AT. A brief overview of how GH levels are altered in an obese state, and the efficacy of GH as a therapeutic option to manage obesity will be given. As we will reveal, the effects of GH on AT are numerous, dynamic and depot-dependent. © 2017 American Physiological Society. Compr Physiol 7:819-840, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  12. Cdkal1, a type 2 diabetes susceptibility gene, regulates mitochondrial function in adipose tissue

    Directory of Open Access Journals (Sweden)

    Colin J. Palmer

    2017-10-01

    Conclusions: Cdkal1 is necessary for normal mitochondrial morphology and function in adipose tissue. These results suggest that the type 2 diabetes susceptibility gene CDKAL1 has novel functions in regulating mitochondrial activity.

  13. Textile Technologies and Tissue Engineering: A Path Towards Organ Weaving

    Science.gov (United States)

    Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein

    2016-01-01

    Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, pore size and mechanical properties of the fabrics play important role in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. PMID:26924450

  14. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  15. The Nanomechanics of Biomineralized Soft-Tissues and Organic Matrices

    Science.gov (United States)

    Bezares-Chavez, Jiddu

    The research reported on in this dissertation is concerned with the macro-molecular constitution and geometrical organization of the soft-tissue comprising the matrix of the nacreous portion of the shell of Haliotis rufescens, the Red abalone. Nacre is one of literally legions of intricate biomineralized structures that exist in nature and has long served as a paradigm for elegant and optimized structural de-sign. Biomineralization involves, inter alia, the uptake and synthesis of elements and compounds from the environment and their incorporation into highly optimized functional structures. Nacre has a structure described as a brick wall like with a matrix of biopolymer layers that are preformed and serve as a template into which nanocrystalline tiles of CaCO3 precipitate. The matrix, or what are known as inter-lamellar layers, are of particular interest as they impart both toughness and strength to the composite ceramic nacre structure. The work first involved a histochemical mapping of the macromolecular structure of the interlamellar layers; this revealed the locations of proteins and functional molecular groups that serve as nucleation sites for the ceramic tiles. Parallel studies on the nacre of Nautilus pompilius, the Chambered Nautilus, revealed the generality of the findings. Of particular interest was determining both the content and layout of chitin within these layers. In fact it was determined that chitin was organized as mostly unidirectional architecture of fibrils, with a certain fraction of fibrils laying at cross directions. Most remarkably, it was found that the fibrils possessed a very long range connectivity that spanned many tiles. This was determined by systematic atomic force (afm) and analytical optical histochemical microscopy. These findings were further verified by a unique form of mechanical testing whereby tensile testing was conducted on groups of interlamellar layers extracted from nacre. Mechanical testing led to a quantitative

  16. Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment

    Directory of Open Access Journals (Sweden)

    Kvido Smitka

    2015-01-01

    Full Text Available Adipose tissue is recognized as an active endocrine organ that produces a number of endocrine substances referred to as “adipokines” including leptin, adiponectin, adipolin, visfatin, omentin, tumour necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, resistin, pigment epithelium-derived factor (PEDF, and progranulin (PGRN which play an important role in the food intake regulation and significantly influence insulin sensitivity and in some cases directly affect insulin resistance in skeletal muscle, liver, and adipose tissue. The review summarizes current knowledge about adipose tissue-derived hormones and their influence on energy homeostasis regulation. The possible therapeutic potential of these adipokines in the treatment of insulin resistance, endothelial dysfunction, a pro-inflammatory response, obesity, eating disorders, progression of atherosclerosis, type 1 diabetes, and type 2 diabetes is discussed.

  17. Dietary intake and burden of lanthanide in main organs and tissues for Chinese man

    International Nuclear Information System (INIS)

    Zhu Hongda; Liu Qingfeng; Ouyang Li; Liu Husheng; Wang Naifen; Liu Yaqiong; Zhang Yongbao; Wang Ke; Chen Rusong

    2004-01-01

    Objective: To determine lanthanide concentrations in dietary foods and main organs or tissues for Chinese adult man and to estimate their daily intakes by ingestion and organ or tissue burdens. Methods: Ten kinds of organ or tissue samples collected in autopsy from 21 supplemental subjects of 4 areas with different dietary types in China who died suddenly, and had been healthy and normal before death. The concentrations of 11 lanthanide in foods and 14 lanthanide in these organ or tissue samples, including those collected from 31 subjects in the past, were analyzed by using ICP-MS or INAA technique as well as necessary QC measures. With uses of the local diet composition and relevant organ or tissue weights for Chinese Reference Man, their daily intakes and organ or tissue burdens were estimated. Results: The concentrations of 14 lanthanide in 12 categories of foods and 10 kinds of organ or tissue samples, their dietary daily intakes and organ or tissue burdens for Chinese adult men were obtained. Conclusion: Besides updating the relevant data of La, Ce and Eu in 5 kinds of organ or tissue and diet, this research obtained data on concentrations of other 11 lanthanide in Chinese foods and 10 kinds of organ or tissue, their daily intakes and burdens for the first time in China. The results provide more systematic bases for developing the parameters of Chinese Reference Man than before. This study provides also comparative data for different kinds of lanthanide, foods, organs or tissues and also the background values of Chinese soil

  18. Tissue oxygen demand in regulation of the behavior of the cells in the vasculature.

    Science.gov (United States)

    Barvitenko, Nadezhda N; Aslam, Muhammad; Filosa, Jessica; Matteucci, Elena; Nikinmaa, Mikko; Pantaleo, Antonella; Saldanha, Carlota; Baskurt, Oguz K

    2013-08-01

    The control of arteriolar diameters in microvasculature has been in the focus of studies on mechanisms matching oxygen demand and supply at the tissue level. Functionally, important vascular elements include EC, VSMC, and RBC. Integration of these different cell types into functional units aimed at matching tissue oxygen supply with tissue oxygen demand is only achieved when all these cells can respond to the signals of tissue oxygen demand. Many vasoactive agents that serve as signals of tissue oxygen demand have their receptors on all these types of cells (VSMC, EC, and RBC) implying that there can be a coordinated regulation of their behavior by the tissue oxygen demand. Such functions of RBC as oxygen carrying by Hb, rheology, and release of vasoactive agents are considered. Several common extra- and intracellular signaling pathways that link tissue oxygen demand with control of VSMC contractility, EC permeability, and RBC functioning are discussed. © 2013 John Wiley & Sons Ltd.

  19. Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

    Science.gov (United States)

    2015-08-01

    Symbol Entrez Gene Name Fold Change GPX5 glutathione peroxidase 5 (epididymal androgen-related protein) 13.6 SPAG11B sperm associated antigen 11B 13.0...family 2, subfamily F, polypeptide 1 4.8 HBD hemoglobin, delta 4.6 Down-regulated  Symbol Entrez Gene Name Fold Change SPAG11B sperm associated antigen...Cxcl5 and Mac-3 IHC staining results, we used the manual function to count the stromal cells that stained posi- tively on 20 images acquired randomly at

  20. Impact of training state on fasting-induced regulation of adipose tissue metabolism in humans

    DEFF Research Database (Denmark)

    Bertholdt, Lærke; Gudiksen, Anders; Stankiewicz, Tomasz

    2018-01-01

    Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study was to investig......Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study...... was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained (VO2max 55ml......RNA content were higher in trained subjects than untrained subjects. In addition, trained subjects had higher adipose tissue hormone sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acids concentration than untrained subjects during...

  1. Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

    Science.gov (United States)

    Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein; Khademhosseini, Ali

    2016-04-06

    Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    Science.gov (United States)

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Textile Technologies and Tissue Engineering: A Path Towards Organ Weaving

    OpenAIRE

    Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein; Khademhosseini, Ali

    2016-01-01

    Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, pore size and mechanical properties of the fabrics play important role in the effective use of textile technol...

  4. [Local impact of antiseptic medical textile on tissues of organism].

    Science.gov (United States)

    Nazarchuk, O A; Vernyhorods'kyĭ, S V; Paliĭ, V H; Nazarchuk, H H; Paliĭ, D V; Honchar, O O; Zadereĭ, N V

    2013-07-01

    Morphological investigation for studying of a local impact on the tissues, localized in the antiseptic textile implantation zone, was conducted. The textile was impregnated by composition of decametoxine with modified polysaccharides. Basing on the investigation result there was established the absence of a toxic impact of antiseptic medical textile on the macroorganism tissues, the regenerative processes course, the wounds epithelization, antioedematous and anti-inflammatory effects.

  5. Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in the Drosophila melanogaster Wing Imaginal Disc.

    Science.gov (United States)

    Brock, Amanda R; Seto, Mabel; Smith-Bolton, Rachel K

    2017-07-01

    Regeneration is a complex process that requires an organism to recognize and repair tissue damage, as well as grow and pattern new tissue. Here, we describe a genetic screen to identify novel regulators of regeneration. We ablated the Drosophila melanogaster larval wing primordium by inducing apoptosis in a spatially and temporally controlled manner and allowed the tissue to regenerate and repattern. To identify genes that regulate regeneration, we carried out a dominant-modifier screen by assessing the amount and quality of regeneration in adult wings heterozygous for isogenic deficiencies. We have identified 31 regions on the right arm of the third chromosome that modify the regenerative response. Interestingly, we observed several distinct phenotypes: mutants that regenerated poorly, mutants that regenerated faster or better than wild-type, and mutants that regenerated imperfectly and had patterning defects. We mapped one deficiency region to cap-n-collar ( cnc ), the Drosophila Nrf2 ortholog, which is required for regeneration. Cnc regulates reactive oxygen species levels in the regenerating epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth, debris localization, and pupariation timing. Here, we present the results of our screen and propose a model wherein Cnc regulates regeneration by maintaining an optimal level of reactive oxygen species to promote JNK signaling. Copyright © 2017 by the Genetics Society of America.

  6. Chapter 8. Ionisation radiation and human organism. Radioactivity of human tissues

    International Nuclear Information System (INIS)

    Toelgyessy, J.; Harangozo, M.

    2000-01-01

    This is a chapter of textbook of radioecology for university students. In this chapter authors deal with ionisation radiation and human organism as well as with radioactivity of human tissues. Chapter consists of next parts: (1) Radiation stress of human organism; (2) Radioactivity of human tissues and the factors influencing radioactive contamination; (3) Possibilities of decreasing of radiation stress

  7. Regulation of Genetically Modified Organisms in the European Union

    NARCIS (Netherlands)

    Grossman, M.R.; Bryan Endres, A.

    2000-01-01

    To be successful, laws that regulate genetically modified organisms (GMOs) must help society decide rationally when to pause and when to proceed in adopting new biotechnological developments. In the context of European Union (EU) institutions and lawmaking procedures, this article examines European

  8. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  9. Present state of nuclear regulation organizations of main countries in the world. Importance of regulation staffs and requirements

    International Nuclear Information System (INIS)

    Nishida, Naoki

    2013-01-01

    After Fukushima accident, NRA (Nuclear Regulation Authority) was established in Japan as an independent organization from promotion. In order to perform effective and reliable nuclear regulation, it was important management organization such as nuclear regulation commission worked efficiently, and also requirements for nuclear regulation staffs engaged in actual regulatory works were of importance so as for appropriate decision making or judgments of management organization. Since regulation staffs needed professional expertise and technical judgment capabilities in wide areas including other than nuclear energy, various efforts had been done to get able regulation staffs in US, France and UK nuclear regulation organizations concerned, which became clarified after overseas investigation for this article. Since knowledge in nuclear industry could be used for effective regulation, mid-career recruitment had been employed in regulation organization of each country so as to take such knowledge and so it was important how to utilize industrial knowledge under appropriate conditions compatible with independence of regulation organization. (T. Tanaka)

  10. MSX-1 gene expression and regulation in embryonic palatal tissue.

    Science.gov (United States)

    Nugent, P; Greene, R M

    1998-01-01

    The palatal cleft seen in Msx-1 knock-out mice suggests a role for this gene in normal palate development. The cleft is presumed secondary to tooth and jaw malformations, since in situ hybridization suggests that Msx-1 mRNA is not highly expressed in developing palatal tissue. In this study we demonstrate, by Northern blot analysis, the expression of Msx-1, but not Msx-2, in the developing palate and in primary cultures of murine embryonic palate mesenchymal cells. Furthermore, we propose a role for Msx-1 in retinoic acid-induced cleft palate, since retinoic acid inhibits Msx-1 mRNA expression in palate mesenchymal cells. We also demonstrate that transforming growth factor beta inhibits Msx-1 mRNA expression in palate mesenchymal cells, with retinoic acid and transforming growth factor beta acting synergistically when added simultaneously to these cells. These data suggest a mechanistic interaction between retinoic acid, transforming growth factor beta, and Msx-1 in the etiology of retinoic acid-induced cleft palate.

  11. [Attitude towards organ and tissue donation in Europe : Prerequisite for osteochondral allograft treatment].

    Science.gov (United States)

    Schmidt, S; Schulte, A; Schwarz, S; Hofmann, N; Tietz, S; Boergel, M; Sixt, S U

    2017-11-01

    The biggest obstacle to overcome for routine treatment of various pathologies with fresh osteochondral allograft is the availability of tissue for transplantation. Large fresh osteochondral allografts are usually harvested from organ donors, but in contrast to organs, tissues can be procured after cardiac arrest. Medical staff as well the general public are much less aware of the possibilities and requirements of tissue donation compared to organ donation. This review aims to highlight the current situation of organ and tissue donation in Europe and to raise this much needed awareness. For this research, PubMed database was scanned using the terms "tissue/organ donation", "bone donation/transplantation", "cartilage transplantation/allografts" and "osteochrondral allografts". Relatives of potential donors are often not approached because physicians and nurses do not feel sufficiently prepared for this task and, thus, are reluctant to address this topic. Different options could alleviate the pressure medical staff is feeling. Furthermore, there are different factors influencing consent that can be addressed to increase donation rates. Currently, a lot of potential concerning musculoskeletal tissue grafts remains unused. Most importantly, families should be encouraged to speak about their potenzial will to donate and educational programs should be established to increase trust in organ and tissue donation and the allocation system and to increase knowledge about the importance of transplantation medicine. But joined efforts of different parts of the medical systems and different organizations involved in tissue transplantation should improve the situation for patients waiting for much needed transplants.

  12. Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

    Science.gov (United States)

    Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

    2011-09-01

    Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

  13. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

    Directory of Open Access Journals (Sweden)

    Mervi Toriseva

    Full Text Available Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13 in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/- and wild type (WT mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42% at day 21 in Mmp13(-/- mice. Granulation tissue in Mmp13(-/- mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/- mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/- mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/- granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/- mice compared to WT mice. Mmp13(-/- mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

  14. Impact of organic hydroperoxides on rat testicular tissue and ...

    African Journals Online (AJOL)

    The effects of hydroperoxides on testicular tissue and epididymal sperm were investigated. Male Wistar rats aged 10 - 12 weeks were randomly placed in groups and received standard rat chow and water ad libitum. Animals were injected intraperitoneally with saline (0.5 ml), t-butyl hydroperoxide (5, 10, 20 and 40 ìM; 0.5 ...

  15. Aspergillus: a rare primary organism in soft-tissue infections.

    Science.gov (United States)

    Johnson, M A; Lyle, G; Hanly, M; Yeh, K A

    1998-02-01

    Nonclostridial necrotizing soft-tissue infections are usually polymicrobial, with greater than 90 per cent involving beta-hemolytic streptococci or coagulase-positive staphylococci. The remaining 10 per cent are usually due to Gram-negative enteric pathogens. We describe the case of a 46-year-old woman with bilateral lower extremity fungal soft tissue infections. She underwent multiple surgical debridements of extensive gangrenous necrosis of the skin and subcutaneous fat associated with severe acute arteritis. Histopathological examination revealed Aspergillus niger as the sole initial pathogen. Despite aggressive surgical debridement, allografts, and intravenous amphotericin B, her condition clinically deteriorated and she ultimately died of overwhelming infection. Treatment for soft-tissue infections include surgical debridement and intravenous antibiotics. More specifically, Aspergillus can be treated with intravenous amphotericin B, 5-fluorocytosine, and rifampin. Despite these treatment modalities, necrotizing fascitis is associated with a 60 per cent mortality rate. Primary fungal pathogens should be included in the differential diagnosis of soft-tissue infections.

  16. Self-Organization and the Self-Assembling Process in Tissue Engineering

    Science.gov (United States)

    Eswaramoorthy, Rajalakshmanan; Hadidi, Pasha; Hu, Jerry C.

    2015-01-01

    In recent years, the tissue engineering paradigm has shifted to include a new and growing subfield of scaffoldless techniques which generate self-organizing and self-assembling tissues. This review aims to provide a cogent description of this relatively new research area, with special emphasis on applications toward clinical use and research models. Particular emphasis is placed on providing clear definitions of self-organization and the self-assembling process, as delineated from other scaffoldless techniques in tissue engineering and regenerative medicine. Significantly, during formation, self-organizing and self-assembling tissues display biological processes similar to those that occur in vivo. These help lead to the recapitulation of native tissue morphological structure and organization. Notably, functional properties of these tissues also approach native tissue values; some of these engineered tissues are already in clinical trials. This review aims to provide a cohesive summary of work in this field, and to highlight the potential of self-organization and the self-assembling process to provide cogent solutions to current intractable problems in tissue engineering. PMID:23701238

  17. The Hippo pathway: key interaction and catalytic domains in organ growth control, stem cell self-renewal and tissue regeneration.

    Science.gov (United States)

    Cherrett, Claire; Furutani-Seiki, Makoto; Bagby, Stefan

    2012-01-01

    The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homoeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), consequently disabling their transcriptional co-activation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins.

  18. Technical support organization of national regulators: Challenges and strategy

    International Nuclear Information System (INIS)

    Mallick, S.A.; Maqbul, N.; Kanwal, S.; Hashmi, J.A.

    2007-01-01

    Design, construction and operation of nuclear power plants has always been a complex activity and so is regulating the nuclear power plants. The rapid innovation in design of nuclear power plants with substantial increase in design life from 40 years to 60 years is now considered a norm. The public acceptability of nuclear as a clean source of energy is also on the increase but with this increase is also the demand for more safety against accidental release of radioactivity. It is therefore essential that high standards of nuclear and radiation safety should be maintained and applied all over the world. However the increase acceptability will also lead to a rapid growth in nuclear energy generation capacity both in terms of construction of new nuclear power plants as well as life extension of older nuclear power plants. This will result in an unprecedented pressure on the national regulators during the licensing process. Nuclear and radiation safety are based on technical, administrative and organizational provisions. There is, therefore, a need to separate the technical review and assessment work from the main licensing process by delegating this responsibility to the technical support organizations so that regulatory decision making is not driven by the time constraints imposed by the licensing process. The paper examines the role technical support organization can play to enhance quality of technical review and thereby the effectiveness of national regulators. For the national regulators that belong to countries that import nuclear power plants and may lack an advanced industrial infrastructure at par with other exporting countries, the establishment of technical support organization within a regulatory body or as a separate organization is gaining increased importance. Pakistan Nuclear Regulatory Authority (PNRA) has realized this importance and proposed the Government of Pakistan for allocation of Rs. 480.00 million ($ 8 million) for the establishment of

  19. Geo-PET: A novel generic organ-pet for small animal organs and tissues

    Science.gov (United States)

    Sensoy, Levent

    Reconstructed tomographic image resolution of small animal PET imaging systems is improving with advances in radiation detector development. However the trend towards higher resolution systems has come with an increase in price and system complexity. Recent developments in the area of solid-state photomultiplication devices like silicon photomultiplier arrays (SPMA) are creating opportunities for new high performance tools for PET scanner design. Imaging of excised small animal organs and tissues has been used as part of post-mortem studies in order to gain detailed, high-resolution anatomical information on sacrificed animals. However, this kind of ex-vivo specimen imaging has largely been limited to ultra-high resolution muCT. The inherent limitations to PET resolution have, to date, excluded PET imaging from these ex-vivo imaging studies. In this work, we leverage the diminishing physical size of current generation SPMA designs to create a very small, simple, and high-resolution prototype detector system targeting ex-vivo tomographic imaging of small animal organs and tissues. We investigate sensitivity, spatial resolution, and the reconstructed image quality of a prototype small animal PET scanner designed specifically for imaging of excised murine tissue and organs. We aim to demonstrate that a cost-effective silicon photomultiplier (SiPM) array based design with thin crystals (2 mm) to minimize depth of interaction errors might be able to achieve sub-millimeter resolution. We hypothesize that the substantial decrease in sensitivity associated with the thin crystals can be compensated for with increased solid angle detection, longer acquisitions, higher activity and wider acceptance energy windows (due to minimal scatter from excised organs). The constructed system has a functional field of view (FoV) of 40 mm diameter, which is adequate for most small animal specimen studies. We perform both analytical (3D-FBP) and iterative (ML-EM) methods in order to

  20. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis.

    Science.gov (United States)

    Klose, Christoph S N; Artis, David

    2016-06-21

    Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.

  1. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    Science.gov (United States)

    Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

    2013-08-08

    Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

  2. An analysis of knowledge and attitudes of hospice staff towards organ and tissue donation.

    Science.gov (United States)

    Wale, J; Arthur, A; Faull, C

    2014-03-01

    Only a minority of hospice patients eligible to donate tissue and organs choose to do so. Hospice care staff play a key role in discussions about donation, but their willingness to engage in these discussions and their understanding of issues around tissue and organ donation is poorly understood. To (i) identify factors associated with the wish of hospice doctors, nurses and healthcare assistants to donate their own organs after death; (ii) survey the experience of discussing the subject with patients; (iii) determine staff members' knowledge of organ and tissue donation and (iv) identify factors associated with knowledge of organ and tissue donation. Cross-sectional questionnaire survey of hospice care staff. 76 of the 94 care staff of one large UK hospice completed and returned the questionnaire. Staff wishing to donate their organs after death (43/76 56.6%) were more likely to be doctors or nurses than healthcare assistants (p=0.011) and more likely to have discussed organ or tissue donation with their family (pdonation with patients had more years' experience (p=0.045) and had similarly discussed donation with their own family (p=0.039). Those with greater knowledge were more likely to have discussed organ or tissue donation with a patient (p=0.042). A reluctance to instigate discussions about organ and tissue donation may prevent palliative patients and their families being allowed the opportunity to donate. Suboptimal knowledge among hospice staff suggests the need for greater liaison between hospice staff, and the organ and tissue donation teams.

  3. From the Cover: Adipose tissue mass can be regulated through the vasculature

    Science.gov (United States)

    Rupnick, Maria A.; Panigrahy, Dipak; Zhang, Chen-Yu; Dallabrida, Susan M.; Lowell, Bradford B.; Langer, Robert; Judah Folkman, M.

    2002-08-01

    Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.

  4. The profile of potential organ and tissue donors.

    Science.gov (United States)

    Moraes, Edvaldo Leal de; Silva, Leonardo Borges de Barros E; Moraes, Tatiana Cristine de; Paixão, Nair Cordeiro dos Santos da; Izumi, Nelly Miyuki Shinohara; Guarino, Aparecida de Jesus

    2009-01-01

    This study aimed to characterize donors according to gender, age group, cause of brain death; quantify donors with hypernatremia, hyperpotassemia and hypopotassemia; and get to know which organs were the most used in transplantations. This quantitative, descriptive, exploratory and retrospective study was performed at the Organ Procurement Organization of the University of São Paulo Medical School Hospital das Clínicas. Data from the medical records of 187 potential donors were analyzed. Cerebrovascular accidents represented 53.48% of all brain death causes, sodium and potassium disorders occurred in 82.36% of cases and 45.46% of the potential donors were between 41 and 60 years old. The results evidenced that natural death causes exceeded traumatic deaths, and that most donors presented sodium and potassium alterations, likely associated to inappropriate maintenance.

  5. Regulation of homocysteine metabolism and methylation in human and mouse tissues

    Science.gov (United States)

    Chen, Natalie C.; Yang, Fan; Capecci, Louis M.; Gu, Ziyu; Schafer, Andrew I.; Durante, William; Yang, Xiao-Feng; Wang, Hong

    2010-01-01

    Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine β-synthase, cystathionine-γ-lyase, paraxonase 1, 5,10-methylenetetrahydrofolate reductase, betaine:homocysteine methyltransferase, methionine adenosyltransferase, phosphatidylethanolamine N-methyltransferases and glycine N-methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl-tRNA synthase, 5-methyltetrahydrofolate:Hcy methyltransferase, S-adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone-lysine N-methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation.—Chen, N. C., Yang, F., Capecci, L. M., Gu, Z., Schafer, A. I., Durante, W., Yang, X.-F., Wang, H. Regulation of homocysteine metabolism and methylation in human and mouse tissues. PMID:20305127

  6. Down-regulate of Djrfc2 causes tissues hypertrophy during planarian regeneration.

    Science.gov (United States)

    Guo, Qi; Zhao, Guixia; Ni, Jiajia; Guo, Yanan; Zhang, Yizhe; Tian, Qingnan; Zhang, Shoutao

    2017-11-25

    Planarians are an ideal model organism for regeneration research due to their amazing ability to regenerate. DNA replication is crucial for genome stability. Replication factor C (RFC), which is a replication factor C-like complex and plays an important role during DNA replication in eukaryotes, has been reported as a wound response factor during planarian regeneration. However, how RFC controls regeneration in planarians by regulating DNA replication remains to be explained. Here, we used a two-dimensional electrophoresis (2-DE) proteomic approach to identify differentially expressed proteins in intact and regenerated planarians. Approximately 132 protein spots showed differences between intact and regenerative tissues. We selected 21 significantly expressed protein spots and processed them using TOF MS analysis. Finally, we cloned three of these candidate genes (Djhsp70, Djrfc2, Djfaim), focusing on the function of Djrfc2 during regeneration. We found that the distribution of Djrfc2 tends toward the wound site. RNA interference (RNAi) of Djrfc2 increases the number of dividing cells and the expression level of planarian neoblast marker genes, which may result in hyper-proliferation. Our studies use an available approach to directly study the regeneration dynamic at the protein level and provide further evidence to support a function of Djrfc2 in planarian regeneration. Copyright © 2017. Published by Elsevier Inc.

  7. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Science.gov (United States)

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  8. RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

    Science.gov (United States)

    Pascali, Chiara; Teichmann, Martin

    2013-01-01

    RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.

  9. Experience of nurses in the process of donation of organs and tissues for transplant.

    Science.gov (United States)

    de Moraes, Edvaldo Leal; dos Santos, Marcelo José; Merighi, Miriam Aparecida Barbosa; Massarollo, Maria Cristina Komatsu Braga

    2014-01-01

    to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation. this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo. the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation process, and interventions performed. The meaning of the action to maintain the viability of organs and tissues for transplantation was described by the categories: to change paradigms, to humanize the donation process, to expand the donation, and to save lives. knowledge of the experience of the nurses in this process is important for healthcare professionals who work in different realities, indicating strategies to optimize the procurement of organs and tissues for transplantation.

  10. Experience of nurses in the process of donation of organs and tissues for transplant

    Directory of Open Access Journals (Sweden)

    Edvaldo Leal de Moraes

    2014-04-01

    Full Text Available OBJECTIVE: to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation.METHOD: this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo.RESULTS: the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation process, and interventions performed. The meaning of the action to maintain the viability of organs and tissues for transplantation was described by the categories: to change paradigms, to humanize the donation process, to expand the donation, and to save lives.FINAL CONSIDERATIONS: knowledge of the experience of the nurses in this process is important for healthcare professionals who work in different realities, indicating strategies to optimize the procurement of organs and tissues for transplantation.

  11. Whole-organ isolation approach as a basis for tissue-specific analyses in Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Steffen Hahnel

    Full Text Available BACKGROUND: Schistosomiasis is one of the most important parasitic diseases worldwide, second only to malaria. Schistosomes exhibit an exceptional reproductive biology since the sexual maturation of the female, which includes the differentiation of the reproductive organs, is controlled by pairing. Pathogenicity originates from eggs, which cause severe inflammation in their hosts. Elucidation of processes contributing to female maturation is not only of interest to basic science but also considering novel concepts combating schistosomiasis. METHODOLOGY/PRINCIPAL FINDINGS: To get direct access to the reproductive organs, we established a novel protocol using a combined detergent/protease-treatment removing the tegument and the musculature of adult Schistosoma mansoni. All steps were monitored by scanning electron microscopy (SEM and bright-field microscopy (BF. We focused on the gonads of adult schistosomes and demonstrated that isolated and purified testes and ovaries can be used for morphological and structural studies as well as sources for RNA and protein of sufficient amounts for subsequent analyses such as RT-PCR and immunoblotting. To this end, first exemplary evidence was obtained for tissue-specific transcription within the gonads (axonemal dynein intermediate chain gene SmAxDynIC; aquaporin gene SmAQP as well as for post-transcriptional regulation (SmAQP. CONCLUSIONS/SIGNIFICANCE: The presented method provides a new way of getting access to tissue-specific material of S. mansoni. With regard to many still unanswered questions of schistosome biology, such as elucidating the molecular processes involved in schistosome reproduction, this protocol provides opportunities for, e.g., sub-transcriptomics and sub-proteomics at the organ level. This will promote the characterisation of gene-expression profiles, or more specifically to complete knowledge of signalling pathways contributing to differentiation processes, so discovering involved

  12. New aspects of fenestrated vasculature and tissue dynamics in the sensory circumventricular organs of adult brains

    Directory of Open Access Journals (Sweden)

    Seiji eMiyata

    2015-10-01

    Full Text Available The blood–brain barrier (BBB generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs, which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT, subfornical organ (SFO, and area postrema (AP, have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF signaling may be involved in angiogenesis and

  13. Experience of nurses in the process of donation of organs and tissues for transplant

    OpenAIRE

    Moraes,Edvaldo Leal de; Santos,Marcelo José dos; Merighi,Miriam Aparecida Barbosa; Massarollo,Maria Cristina Komatsu Braga

    2014-01-01

    OBJECTIVE: to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation.METHOD: this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo.RESULTS: the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation proce...

  14. Regulation of adipokine production in human adipose tissue by propionic acid

    NARCIS (Netherlands)

    Al-Lahham, Sa'ad H.; Roelofsen, Han; Priebe, Marion; Weening, Desiree; Dijkstra, Martijn; Hoek, Annemieke; Rezaee, Farhad; Venema, Koen; Vonk, Roel J.

    P>Background Dietary fibre (DF) has been shown to be protective for the development of obesity, insulin resistance and type 2 diabetes. Short-chain fatty acids, produced by colonic fermentation of DF might mediate this beneficial effect. Adipose tissue plays a key role in the regulation of energy

  15. Regulation of adipokine production in human adipose tissue by propionic acid

    NARCIS (Netherlands)

    Al-Lahham, S.H.; Roelofsen, H.; Priebe, M.; Weening, D.; Dijkstra, M.; Hoek, A.; Rezaee, F.; Venema, K.; Vonk, R.J.

    2010-01-01

    Background Dietary fibre (DF) has been shown to be protective for the development of obesity, insulin resistance and type 2 diabetes. Short-chain fatty acids, produced by colonic fermentation of DF might mediate this beneficial effect. Adipose tissue plays a key role in the regulation of energy

  16. Tissue-specific 5' heterogeneity of PPARα transcripts and their differential regulation by leptin.

    Directory of Open Access Journals (Sweden)

    Emma S Garratt

    Full Text Available The genes encoding nuclear receptors comprise multiple 5'untranslated exons, which give rise to several transcripts encoding the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR α genes have multiple promoters, although their function is unknown. Here we have characterised the rat PPARα promoter region and have identified three alternative PPARα transcripts, which have different transcription start sites owing to the utilisation of distinct first exons. Moreover these alternative PPARα transcripts were differentially expressed between adipose tissue and liver. We show that while the major adipose (P1 and liver (P2 transcripts were both induced by dexamethasone, they were differentially regulated by the PPARα agonist, clofibric acid, and leptin. Leptin had no effect on the adipose-specific P1 transcript, but induced liver-specific P2 promoter activity via a STAT3/Sp1 mechanism. Moreover in Wistar rats, leptin treatment between postnatal day 3-13 led to an increase in P2 but not P1 transcription in adipose tissue which was sustained into adulthood. This suggests that the expression of the alternative PPARα transcripts are in part programmed by early life exposure to leptin leading to persistent change in adipose tissue fatty acid metabolism through specific activation of a quiescent PPARα promoter. Such complexity in the regulation of PPARα may allow the expression of PPARα to be finely regulated in response to environmental factors.

  17. Tissue-Specific 5′ Heterogeneity of PPARα Transcripts and Their Differential Regulation by Leptin

    Science.gov (United States)

    Garratt, Emma S.; Vickers, Mark H.; Gluckman, Peter D.; Hanson, Mark A.

    2013-01-01

    The genes encoding nuclear receptors comprise multiple 5′untranslated exons, which give rise to several transcripts encoding the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR) α genes have multiple promoters, although their function is unknown. Here we have characterised the rat PPARα promoter region and have identified three alternative PPARα transcripts, which have different transcription start sites owing to the utilisation of distinct first exons. Moreover these alternative PPARα transcripts were differentially expressed between adipose tissue and liver. We show that while the major adipose (P1) and liver (P2) transcripts were both induced by dexamethasone, they were differentially regulated by the PPARα agonist, clofibric acid, and leptin. Leptin had no effect on the adipose-specific P1 transcript, but induced liver-specific P2 promoter activity via a STAT3/Sp1 mechanism. Moreover in Wistar rats, leptin treatment between postnatal day 3–13 led to an increase in P2 but not P1 transcription in adipose tissue which was sustained into adulthood. This suggests that the expression of the alternative PPARα transcripts are in part programmed by early life exposure to leptin leading to persistent change in adipose tissue fatty acid metabolism through specific activation of a quiescent PPARα promoter. Such complexity in the regulation of PPARα may allow the expression of PPARα to be finely regulated in response to environmental factors. PMID:23825665

  18. Tissue Specific Roles of Dynein Light Chain 1 in Regulating Germ Cell Apoptosis in Ceanorhabditis elegans

    DEFF Research Database (Denmark)

    Morthorst, Tine Hørning

    2015-01-01

    in the etiology of many diseases, including cancer, neurodegenerative, cardiovascular and autoimmune diseases. Several of the first genes found to regulate apoptosis were discovered in the nematode Caenorhabditis elegans. In this project, two different and tissue specific roles of C. elegans dynein light chain 1...

  19. Formation of modern theoretical regulations about organization concerning management development

    Directory of Open Access Journals (Sweden)

    Zhalinska I.V.

    2017-03-01

    Full Text Available The article deals with the scientific concepts about an organization as the entity of management concerning management development. The author studies the principal theoretical regulations about an organization within the most spread schools of management and context of development of other managerial concepts in particular, strategic management. It is found out that an organization and its development had not considered as the factor of an effective activity before. Researches paid their attention to single aspects of organization activity where the aspects allowed to increase economic efficiency. However, the objective complication of conditions of enterprises’ activities caused the necessity of scientific research of adequate models of functioning and development of organizations, which currently cannot be provided by traditional management concepts. Thus, theoretical and practical prerequisites arise for a separate scientific set of researches within the science of management such as the theory of an organization. The article describes the main classified approaches to the models of an organization. The paper researches the challenges in present management, and those ones, which have caused the crisis in modern management. It is singled out the following actual aspects of modern organizational processes as the all-round use of modern information and computer systems, the development of integration and in cooperation in management, the appearance of new management technologies, the use of new assessment criteria for organization activity, striving for organizational shifts and innovations. Due to the generalization of the study results, the authors single out such key aspects in the development of the science of management, as the crisis of traditional management influences upon practical activity of modern organizations; the achievements of traditional management schools are becoming necessary, but not determinant factors of organization

  20. Soil organic matter regulates molybdenum storage and mobility in forests

    Science.gov (United States)

    Marks, Jade A; Perakis, Steven; King, Elizabeth K.; Pett-Ridge, Julie

    2015-01-01

    The trace element molybdenum (Mo) is essential to a suite of nitrogen (N) cycling processes in ecosystems, but there is limited information on its distribution within soils and relationship to plant and bedrock pools. We examined soil, bedrock, and plant Mo variation across 24 forests spanning wide soil pH gradients on both basaltic and sedimentary lithologies in the Oregon Coast Range. We found that the oxidizable organic fraction of surface mineral soil accounted for an average of 33 %of bulk soil Mo across all sites, followed by 1.4 % associated with reducible Fe, Al, and Mn-oxides, and 1.4 % in exchangeable ion form. Exchangeable Mo was greatest at low pH, and its positive correlation with soil carbon (C) suggests organic matter as the source of readily exchangeable Mo. Molybdenum accumulation integrated over soil profiles to 1 m depth (τMoNb) increased with soil C, indicating that soil organic matter regulates long-term Mo retention and loss from soil. Foliar Mo concentrations displayed no relationship with bulk soil Mo, and were not correlated with organic horizon Mo or soil extractable Mo, suggesting active plant regulation of Mo uptake and/or poor fidelity of extractable pools to bioavailability. We estimate from precipitation sampling that atmospheric deposition supplies, on average, over 10 times more Mo annually than does litterfall to soil. In contrast, bedrock lithology had negligible effects on foliar and soil Mo concentrations and on Mo distribution among soil fractions. We conclude that atmospheric inputs may be a significant source of Mo to forest ecosystems, and that strong Mo retention by soil organic matter limits ecosystem Mo loss via dissolution and leaching pathways.

  1. Matrix production and organization by endothelial colony forming cells in mechanically strained engineered tissue constructs.

    Directory of Open Access Journals (Sweden)

    Nicky de Jonge

    Full Text Available AIMS: Tissue engineering is an innovative method to restore cardiovascular tissue function by implanting either an in vitro cultured tissue or a degradable, mechanically functional scaffold that gradually transforms into a living neo-tissue by recruiting tissue forming cells at the site of implantation. Circulating endothelial colony forming cells (ECFCs are capable of differentiating into endothelial cells as well as a mesenchymal ECM-producing phenotype, undergoing Endothelial-to-Mesenchymal-transition (EndoMT. We investigated the potential of ECFCs to produce and organize ECM under the influence of static and cyclic mechanical strain, as well as stimulation with transforming growth factor β1 (TGFβ1. METHODS AND RESULTS: A fibrin-based 3D tissue model was used to simulate neo-tissue formation. Extracellular matrix organization was monitored using confocal laser-scanning microscopy. ECFCs produced collagen and also elastin, but did not form an organized matrix, except when cultured with TGFβ1 under static strain. Here, collagen was aligned more parallel to the strain direction, similar to Human Vena Saphena Cell-seeded controls. Priming ECFC with TGFβ1 before exposing them to strain led to more homogenous matrix production. CONCLUSIONS: Biochemical and mechanical cues can induce extracellular matrix formation by ECFCs in tissue models that mimic early tissue formation. Our findings suggest that priming with bioactives may be required to optimize neo-tissue development with ECFCs and has important consequences for the timing of stimuli applied to scaffold designs for both in vitro and in situ cardiovascular tissue engineering. The results obtained with ECFCs differ from those obtained with other cell sources, such as vena saphena-derived myofibroblasts, underlining the need for experimental models like ours to test novel cell sources for cardiovascular tissue engineering.

  2. Organ and plantlet regeneration of Menyanthes trifoliata through tissue culture

    Directory of Open Access Journals (Sweden)

    Urszula Adamczyk-Rogozińska

    2014-01-01

    Full Text Available The conditions for the regeneration of plants through organogenesis from callus tissues of Menyanthes trifoliata are described. The shoot multiplication rate was affected by basal culture media, the type and concentration of cytokinin and subculture number. The best response was obtained when caulogenic calli were cultured on the modified Schenk and Hildebrandt medium (SH-M containing indole-3-acetic acid (IAA 0,5 mg/l and 6-benzyladenine (BA 1 mg/l or zeatin (2 mg/l. Under these conditions ca 7 shoots (mostly 1 cm or more in length per culture in the 5th and 6th passages could be developed. In older cultures (after 11-12 passages there was a trend for more numerous but shorter shoot formation. All regenerated shoots could be rooted on the SH-M medium supplemented with 0.5 mg/l IAA within 6 weeks; 80% of in vitro rooted plantlets survived their transfer to soil.

  3. Antibiotic effects against periodontal bacteria in organ cultured tissue.

    Science.gov (United States)

    Takeshita, Masaaki; Haraguchi, Akira; Miura, Mayumi; Hamachi, Takafumi; Fukuda, Takao; Sanui, Terukazu; Takano, Aiko; Nishimura, Fusanori

    2017-02-01

    Mechanical reduction of infectious bacteria by using physical instruments is considered the principal therapeutic strategy for periodontal disease; addition of antibiotics is adjunctive. However, local antibiotic treatment, combined with conventional mechanical debridement, has recently been shown to be more effective in periodontitis subjects with type 2 diabetes. This suggests that some bacteria may invade the inflamed inner gingival epithelium, and mechanical debridement alone will be unable to reduce these bacteria completely. Therefore, we tried to establish infected organ culture models that mimic the inner gingival epithelium and aimed to see the effects of antibiotics in these established models. Mouse dorsal skin epithelia were isolated, and periodontal bacteria were injected into the epithelia. Infected epithelia were incubated with test antibiotics, and colony-forming ability was evaluated. Results indicated that effective antibiotics differed according to injected bacteria and the bacterial combinations tested. Overall, in organ culture model, the combination of amoxicillin or cefdinir and metronidazole compensate for the effects of less effective bacterial combinations on each other. This in vitro study would suggest effective periodontal treatment regimens, especially for severe periodontitis.

  4. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

    Science.gov (United States)

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie; Wang, Xiu-Ping

    2015-04-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. The Hippo-YAP Pathway Regulates 3D Organ Formation and Homeostasis.

    Science.gov (United States)

    Ishihara, Erika; Nishina, Hiroshi

    2018-04-17

    The vertebrate body shape is formed by the specific sizes and shapes of its resident tissues and organs, whose alignments are essential for proper functioning. To maintain tissue and organ shape, and thereby function, it is necessary to remove senescent, transformed, and/or damaged cells, which impair function and can lead to tumorigenesis. However, the molecular mechanisms underlying three-dimensional (3D) organ formation and homeostasis are not fully clear. Yes-associated protein (YAP) is a transcriptional co-activator that is involved in organ size control and tumorigenesis. Recently, we reported that YAP is essential for proper 3D body shape through regulation of cell tension by using a unique medaka fish mutant, hirame ( hir ). In Madin–Darby canine kidney (MDCK) epithelial cells, active YAP-transformed cells are eliminated apically when surrounded by normal cells. Furthermore, in a mosaic mouse model, active YAP-expressing damaged hepatocytes undergo apoptosis and are eliminated from the liver. Thus, YAP functions in quantitative and quality control in organogenesis. In this review, we describe the various roles of YAP in vertebrates, including in the initiation of liver cancer.

  6. Catalase activity prevents exercise-induced up-regulation of vasoprotective proteins in venous tissue.

    Science.gov (United States)

    Dao, Vu Thao-Vi; Floeren, Melanie; Kumpf, Stephanie; Both, Charlotte; Peter, Bärbel; Balz, Vera; Suvorava, Tatsiana; Kojda, Georg

    2011-11-01

    Physical activity induces favourable changes of arterial gene expression and protein activity, although little is known about its effect in venous tissue. Although our understanding of the initiating molecular signals is still incomplete, increased expression of endothelial nitric oxide synthase (eNOS) is considered a key event. This study sought to investigate the effects of two different training protocols on the expression of eNOS and extracellular superoxide dismutase (ecSOD) in venous and lung tissue and to evaluate the underlying molecular mechanisms. C57Bl/6 mice underwent voluntary exercise or forced physical activity. Changes of vascular mRNA and protein levels and activity of eNOS, ecSOD and catalase were determined in aorta, heart, lung and vena cava. Both training protocols similarly increased relative heart weight and resulted in up-regulation of aortic and myocardial eNOS. In striking contrast, eNOS expression in vena cava and lung remained unchanged. Likewise, exercise up-regulated ecSOD in the aorta and in left ventricular tissue but remained unchanged in lung tissue. Catalase expression in lung tissue and vena cava of exercised mice exceeded that in aorta by 6.9- and 10-fold, respectively, suggesting a lack of stimulatory effects of hydrogen peroxide. In accordance, treatment of mice with the catalase inhibitor aminotriazole for 6 weeks resulted in significant up-regulation of eNOS and ecSOD in vena cava. These data suggest that physiological venous catalase activity prevents exercise-induced up-regulation of eNOS and ecSOD. Furthermore, therapeutic inhibition of vascular catalase might improve pulmonary rehabilitation. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  7. Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology.

    Directory of Open Access Journals (Sweden)

    Marcela Montes de Oca

    2016-01-01

    Full Text Available Tumor necrosis factor (TNF is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1 cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.

  8. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    , a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

  9. Functional Organization of Neuronal and Humoral Signals Regulating Feeding Behavior

    Science.gov (United States)

    Schwartz, Gary J.; Zeltser, Lori M.

    2014-01-01

    Energy homeostasis- ensuring that energy availability matches energy requirements- is essential for survival. One way that energy balance is achieved is through coordinated action of neural and neuroendocrine feeding circuits, which promote energy intake when energy supply is limited. Feeding behavior engages multiple somatic and visceral tissues distributed throughout the body – contraction of skeletal and smooth muscles in the head and along the upper digestive tract required to consume and digest food, as well as stimulation of endocrine and exocrine secretions from a wide range of organs. Accordingly, neurons that contribute to feeding behaviors are localized to central, peripheral and enteric nervous systems. To promote energy balance, feeding circuits must be able to identify and respond to energy requirements, as well as the amount of energy available from internal and external sources, and then direct appropriate coordinated responses throughout the body. PMID:23642202

  10. Molecular characterization of Quercus suber MYB1, a transcription factor up-regulated in cork tissues.

    Science.gov (United States)

    Almeida, Tânia; Menéndez, Esther; Capote, Tiago; Ribeiro, Teresa; Santos, Conceição; Gonçalves, Sónia

    2013-01-15

    The molecular processes associated with cork development in Quercus suber L. are poorly understood. A previous molecular approach identified a list of genes potentially important for cork formation and differentiation, providing a new basis for further molecular studies. This report is the first molecular characterization of one of these candidate genes, QsMYB1, coding for an R2R3-MYB transcription factor. The R2R3-MYB gene sub-family has been described as being involved in the phenylpropanoid and lignin pathways, both involved in cork biosynthesis. The results showed that the expression of QsMYB1 is putatively mediated by an alternative splicing (AS) mechanism that originates two different transcripts (QsMYB1.1 and QsMYB1.2), differing only in the 5'-untranslated region, due to retention of the first intron in one of the variants. Moreover, within the retained intron, a simple sequence repeat (SSR) was identified. The upstream regulatory region of QsMYB1 was extended by a genome walking approach, which allowed the identification of the putative gene promoter region. The relative expression pattern of QsMYB1 transcripts determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) revealed that both transcripts were up-regulated in cork tissues; the detected expression was several times higher in newly formed cork harvested from trees producing virgin, second or reproduction cork when compared with wood. Moreover, the expression analysis of QsMYB1 in several Q. suber organs showed very low expression in young branches and roots, whereas in leaves, immature acorns or male flowers, no expression was detected. These preliminary results suggest that QsMYB1 may be related to secondary growth and, in particular, with the cork biosynthesis process with a possible alternative splicing mechanism associated with its regulatory function. Copyright © 2012 Elsevier GmbH. All rights reserved.

  11. Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.

    Science.gov (United States)

    Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J

    2013-05-01

    FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.

  12. Fuz regulates craniofacial development through tissue specific responses to signaling factors.

    Directory of Open Access Journals (Sweden)

    Zichao Zhang

    Full Text Available The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/- mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/- mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/- mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.

  13. Proteomics analysis of apoptosis-regulating proteins in tissues with different radiosensitivity

    International Nuclear Information System (INIS)

    An, Jeung-Hee; Seong, Jin-Sil

    2006-01-01

    The aim of this study was to identify of radiosusceptibility proteins in tissues with different radiosensitivity. C3H/HeJ mice were exposed to 10 Gy. The tissues were processed for proteins extraction and were analyzed by 2-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionizing time-of-flight mass spectrometry and validated by immunohistochemical staining and Western blotting. The peaks of apoptosis levels were 35.3±1.7% and 0.6±0.2% in the spleen and the liver, respectively, after ionizing radiation. Analysis of liver tissue showed that the expression level of reactive oxygen species (ROS) related proteins such as cytochrome c, glutathione S transferase, NADH dehydrogenase and peroxiredoxin VI increased after radiation. The expression level of cytochrome c increased to 3-fold after ionizing radiation in both tissues. However in spleen tissue, the expression level of various kinds of apoptosis regulating proteins increased after radiation. These involved iodothyronine, CD 59A glycoprotein precursor, fas antigen and tumor necrosis factor -inducible protein TSG-6nprecursor after radiation. The difference in the apoptosis index between the liver and spleen tissues is closely associated with the expression of various kinds of apoptosis-related proteins. The result suggests that the expression of apoptosis-related protein and redox proteins play important roles in this radiosusceptibility. (author)

  14. Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

    Science.gov (United States)

    Akiyama, Toru; Tanaka, Sakae

    2011-08-01

    One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

  15. Differential feedback regulation of ethylene biosynthesis in pulp and peel tissues of banana fruit.

    Science.gov (United States)

    Inaba, Akitsugu; Liu, Xuejun; Yokotani, Naoki; Yamane, Miki; Lu, Wang-Jin; Nakano, Ryohei; Kubo, Yasutaka

    2007-01-01

    The feedback regulation of ethylene biosynthesis in banana [Musa sp. (AAA group, Cavendish subgroup) cv. Grand Nain] fruit was investigated in an attempt to clarify the opposite effect of 1-methylcyclopropene (1-MCP), an ethylene action inhibitor, before and after the onset of ripening. 1-MCP pre-treatment completely prevented the ripening-induced effect of propylene in pre-climacteric banana fruit, whereas treatment after the onset of ripening stimulated ethylene production. In pre-climacteric fruit, higher concentrations of propylene suppressed ethylene production more strongly, despite their earlier ethylene-inducing effect. Exposure of the fruit ripened by propylene to 1-MCP increased ethylene production concomitantly with an increase in 1-aminocyclopropane-1-carboxylate (ACC) synthase activity and ACC content, and prevented a transient decrease in MA-ACS1 transcripts in the pulp tissues. In contrast, in the peel of ripening fruit, 1-MCP prevented the increase in ethylene production and subsequently the ripening process by reduction of the increase in MA-ACS1 and MA-ACO1 transcripts and of ACC synthase and ACC oxidase activities. These results suggest that ethylene biosynthesis in ripening banana fruit may be controlled negatively in the pulp tissue and positively in the peel tissue. This differential regulation by ethylene in pulp and peel tissues was also observed for MA-PL, MA-Exp, and MA-MADS genes.

  16. Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics

    DEFF Research Database (Denmark)

    Manohara, S. R.; Hanagodimath, S. M.; Gerward, Leif

    2011-01-01

    Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary......, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor...... of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Zeff. These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues...

  17. Two-photon Microscopy and Polarimetry for Assessment of Myocardial Tissue Organization

    Science.gov (United States)

    Archambault-Wallenburg, Marika

    Optical methods can provide useful tissue characterization tools. For this project, two-photon microscopy and polarized light examinations (polarimetry) were used to assess the organizational state of myocardium in healthy, infarcted, and stem-cell regenerated states. Two-photon microscopy visualizes collagen through second-harmonic generation and myocytes through two-photon excitation autofluorescence, providing information on the composition and structure/organization of the tissue. Polarimetry measurements yield a value of linear retardance that can serve as an indicator of tissue anisotropy, and with a dual-projection method, information about the anisotropy axis orientation can also be extracted. Two-photon microscopy results reveal that stem-cell treated tissue retains more myocytes and structure than infarcted myocardium, while polarimetry findings suggest that the injury caused by temporary ligation of a coronary artery is less severe and more diffuse that than caused by a permanent ligation. Both these methods show potential for tissue characterization.

  18. The organic seed regulations framework in Europe - current status and recommendations for future development

    NARCIS (Netherlands)

    Döring, T.F.; Bocci, R.; Hitchings, R.; Howlett, S.; Lammerts Van Bueren, E.; Pautasso, M.; Raaijmakers, M.; Rey, F.; Stubsgaard, A.; Weinhappel, M.; Wilbois, K.P.; Winkler, L.R.; Wolfe, M.S.

    2012-01-01

    Organic agriculture regulations, in particular European regulation EC 889/2008, prescribe the use of organically produced seed. For many cultivated plants, however, organic seed is often not available. This is mainly because investment in organic plant breeding and seed production has been low in

  19. Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

    Directory of Open Access Journals (Sweden)

    Koch Wolfgang

    2008-07-01

    Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

  20. Characterization of the mechanical properties of resected porcine organ tissue using optical fiber photoelastic polarimetry.

    Science.gov (United States)

    Hudnut, Alexa W; Babaei, Behzad; Liu, Sonya; Larson, Brent K; Mumenthaler, Shannon M; Armani, Andrea M

    2017-10-01

    Characterizing the mechanical behavior of living tissue presents an interesting challenge because the elasticity varies by eight orders of magnitude, from 50Pa to 5GPa. In the present work, a non-destructive optical fiber photoelastic polarimetry system is used to analyze the mechanical properties of resected samples from porcine liver, kidney, and pancreas. Using a quasi-linear viscoelastic fit, the elastic modulus values of the different organ systems are determined. They are in agreement with previous work. In addition, a histological assessment of compressed and uncompressed tissues confirms that the tissue is not damaged during testing.

  1. From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.

    Science.gov (United States)

    Lemay, Danielle G; Pollard, Katherine S; Martin, William F; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J Bruce; Rijnkels, Monique

    2013-01-01

    Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival.

  2. Regulating expressin of cell and tissue-specific genes by modifying transcription

    Energy Technology Data Exchange (ETDEWEB)

    Beachy, Roger N. [Donald Danforth Plant Science Center, St. Louis, MO (United States); Dai, Shunhong [Donald Danforth Plant Science Center, St. Louis, MO (United States)

    2009-12-15

    Transcriptional regulation is the primary step to control gene expression, therefore function. Such regulation is achieved primarily via a combination of the activities of the promoter cis regulatory DNA elements and trans regulatory proteins that function through binding to these DNA elements. Our research supported by this program has led to the identification of rice bZIP transcription factors RF2a, RF2b and RLP1 that play key roles in regulating the activity of a vascular tissue specific promoter isolated from Rice Tungro Bacilliform Virus (RTBV) through their interactions with the Box II essential cis element located in the promoter. RF2a, RF2b and RLP1 possess multiple regulatory domains. Functional characterization reveals that those domains can activate or repress the activity of the RTBV promoter. Studies of transcriptional regulation of the RTBV promoter by this group of bZIP proteins not only provide insights about gene expression in the vascular tissue, but also insights about general mechanisms of transcription activation and repression. The knowledge gained from this research will also enable us to develop a well-described set of tools that can be used to control expression of multiple genes in transgenic plants and to improve biofuel feedstock.

  3. Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury

    Directory of Open Access Journals (Sweden)

    Kristin M. Priebatsch

    2017-03-01

    Full Text Available Divalent metal ions are essential nutrients for all living organisms and are commonly protein-bound where they perform important roles in protein structure and function. This regulatory control from metals is observed in the relatively abundant plasma protein histidine-rich glycoprotein (HRG, which displays preferential binding to the second most abundant transition element in human systems, Zinc (Zn2+. HRG has been proposed to interact with a large number of protein ligands and has been implicated in the regulation of various physiological and pathological processes including the formation of immune complexes, apoptotic/necrotic and pathogen clearance, cell adhesion, antimicrobial activity, angiogenesis, coagulation and fibrinolysis. Interestingly, these processes are often associated with sites of tissue injury or tumour growth, where the concentration and distribution of Zn2+ is known to vary. Changes in Zn2+ levels have been shown to modify HRG function by altering its affinity for certain ligands and/or providing protection against proteolytic disassembly by serine proteases. This review focuses on the molecular interplay between HRG and Zn2+, and how Zn2+ binding modifies HRG-ligand interactions to regulate function in different settings of tissue injury.

  4. Sociocultural perspective on organ and tissue donation among reservation-dwelling American Indian adults.

    Science.gov (United States)

    Fahrenwald, Nancy L; Stabnow, Wendy

    2005-11-01

    To discover the sociocultural patterns that influence decisions about organ and tissue donation among American Indian (AI) adults. This qualitative ethnographic study used a social-ecological framework. A snowball sampling technique was used to recruit 21 Oglala Lakota Sioux participants (age >or= 19 years) living on the Pine Ridge Indian Reservation in South Dakota, USA. Face-to-face interviews were conducted using open-ended questions derived from the social-ecological perspective of Stokols (1992). Interviews were audiotaped and transcribed. Data were categorized into construct codes to identify concepts and to discover emerging themes. Personal and environmental themes regarding organ and tissue donation emerged. There were two personal themes: uncertain knowledge and the diabetes crisis. Participants knew very little about organ and tissue donation but there was a basic understanding of donor/recipient compatibility. The prevalence of diabetes in the community is contributing to a dire need for kidney donors. The diabetes crisis was acknowledged by every participant. There were three environmental themes: cultural transitions, healthcare system competence and outreach efforts. Traditional cultural beliefs such as entering the spirit world with an intact body were acknowledged. However, conversations reflected re-examination of traditional beliefs because of the need for kidney donors. The healthcare environmental context of organ and tissue donation emerged as a theme. Participants were not confident that the local health system was prepared to either address traditional beliefs about organ and tissue donation or implement a donation protocol. The final theme was the environmental context of outreach efforts. Participants desired relevant outreach targeted to the community and disseminated through local communication networks including the family, the media and tribal leaders. Sociocultural factors relevant to the personal and environmental context of the

  5. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    International Nuclear Information System (INIS)

    Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

    2011-01-01

    Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

  6. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  7. Differential HFE gene expression is regulated by alternative splicing in human tissues.

    Science.gov (United States)

    Martins, Rute; Silva, Bruno; Proença, Daniela; Faustino, Paula

    2011-03-03

    The pathophysiology of HFE-derived Hereditary Hemochromatosis and the function of HFE protein in iron homeostasis remain uncertain. Also, the role of alternative splicing in HFE gene expression regulation and the possible function of the corresponding protein isoforms are still unknown. The aim of this study was to gain insights into the physiological significance of these alternative HFE variants. Alternatively spliced HFE transcripts in diverse human tissues were identified by RT-PCR, cloning and sequencing. Total HFE transcripts, as well as two alternative splicing transcripts were quantified using a real-time PCR methodology. Intracellular localization, trafficking and protein association of GFP-tagged HFE protein variants were analysed in transiently transfected HepG2 cells by immunoprecipitation and immunofluorescence assays. Alternatively spliced HFE transcripts present both level- and tissue-specificity. Concerning the exon 2 skipping and intron 4 inclusion transcripts, the liver presents the lowest relative level, while duodenum presents one of the highest amounts. The protein resulting from exon 2 skipping transcript is unable to associate with β2M and TfR1 and reveals an ER retention. Conversely, the intron 4 inclusion transcript gives rise to a truncated, soluble protein (sHFE) that is mostly secreted by cells to the medium in association with β2M. HFE gene post-transcriptional regulation is clearly affected by a tissue-dependent alternative splicing mechanism. Among the corresponding proteins, a sHFE isoform stands out, which upon being secreted into the bloodstream, may act in remote tissues. It could be either an agonist or antagonist of the full length HFE, through hepcidin expression regulation in the liver or by controlling dietary iron absorption in the duodenum.

  8. Differential HFE gene expression is regulated by alternative splicing in human tissues.

    Directory of Open Access Journals (Sweden)

    Rute Martins

    Full Text Available BACKGROUND: The pathophysiology of HFE-derived Hereditary Hemochromatosis and the function of HFE protein in iron homeostasis remain uncertain. Also, the role of alternative splicing in HFE gene expression regulation and the possible function of the corresponding protein isoforms are still unknown. The aim of this study was to gain insights into the physiological significance of these alternative HFE variants. METHODOLOGY/PRINCIPAL FINDINGS: Alternatively spliced HFE transcripts in diverse human tissues were identified by RT-PCR, cloning and sequencing. Total HFE transcripts, as well as two alternative splicing transcripts were quantified using a real-time PCR methodology. Intracellular localization, trafficking and protein association of GFP-tagged HFE protein variants were analysed in transiently transfected HepG2 cells by immunoprecipitation and immunofluorescence assays. Alternatively spliced HFE transcripts present both level- and tissue-specificity. Concerning the exon 2 skipping and intron 4 inclusion transcripts, the liver presents the lowest relative level, while duodenum presents one of the highest amounts. The protein resulting from exon 2 skipping transcript is unable to associate with β2M and TfR1 and reveals an ER retention. Conversely, the intron 4 inclusion transcript gives rise to a truncated, soluble protein (sHFE that is mostly secreted by cells to the medium in association with β2M. CONCLUSIONS/SIGNIFICANCE: HFE gene post-transcriptional regulation is clearly affected by a tissue-dependent alternative splicing mechanism. Among the corresponding proteins, a sHFE isoform stands out, which upon being secreted into the bloodstream, may act in remote tissues. It could be either an agonist or antagonist of the full length HFE, through hepcidin expression regulation in the liver or by controlling dietary iron absorption in the duodenum.

  9. Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

    Science.gov (United States)

    Collier, Mary E. W.; Ettelaie, Camille

    2011-01-01

    The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

  10. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    Science.gov (United States)

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  11. The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Hillary Johnston-Cox

    Full Text Available High fat diet (HFD-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR, an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance. As the A2bAR is expressed in different tissues, here, we provide the first lead to cellular mechanism by demonstrating that the receptor's influence on tissue insulin sensitivity is mediated via its expression in macrophages. This was shown using a newly generated transgenic mouse model expressing the A2bAR gene in the macrophage lineage on an otherwise A2bAR null background. Reinstatement of macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance and tissue insulin signaling to the level of control mice. The molecular mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine monophosphate in macrophages, reducing the expression and release of inflammatory cytokines, which downregulate insulin receptor-2. Thus, our results illustrate that macrophage A2bAR signaling is needed and sufficient for relaying the protective effect of the A2bAR against HFD-induced tissue inflammation and insulin resistance in mice.

  12. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    Science.gov (United States)

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  13. Granulocytes and vascularization regulate uterine bleeding and tissue remodeling in a mouse menstruation model.

    Directory of Open Access Journals (Sweden)

    Astrid Menning

    Full Text Available Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery.

  14. Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells

    Directory of Open Access Journals (Sweden)

    Tessa Bergsbaken

    2017-04-01

    Full Text Available Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8+ T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103−CD69+ Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN-β and interleukin-12 (IL-12, which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103−CD69+ Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2+ IL-12-producing cells reduced the size of the CD103− Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.

  15. Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

    International Nuclear Information System (INIS)

    Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu

    2004-01-01

    Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

  16. Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives.

    Science.gov (United States)

    Ravnic, Dino J; Leberfinger, Ashley N; Koduru, Srinivas V; Hospodiuk, Monika; Moncal, Kazim K; Datta, Pallab; Dey, Madhuri; Rizk, Elias; Ozbolat, Ibrahim T

    2017-07-01

    : Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

  17. 4D printing of polymeric materials for tissue and organ regeneration.

    Science.gov (United States)

    Miao, Shida; Castro, Nathan; Nowicki, Margaret; Xia, Lang; Cui, Haitao; Zhou, Xuan; Zhu, Wei; Lee, Se-Jun; Sarkar, Kausik; Vozzi, Giovanni; Tabata, Yasuhiko; Fisher, John; Zhang, Lijie Grace

    2017-12-01

    Four dimensional (4D) printing is an emerging technology with great capacity for fabricating complex, stimuli-responsive 3D structures, providing great potential for tissue and organ engineering applications. Although the 4D concept was first highlighted in 2013, extensive research has rapidly developed, along with more-in-depth understanding and assertions regarding the definition of 4D. In this review, we begin by establishing the criteria of 4D printing, followed by an extensive summary of state-of-the-art technological advances in the field. Both transformation-preprogrammed 4D printing and 4D printing of shape memory polymers are intensively surveyed. Afterwards we will explore and discuss the applications of 4D printing in tissue and organ regeneration, such as developing synthetic tissues and implantable scaffolds, as well as future perspectives and conclusions.

  18. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering

    NARCIS (Netherlands)

    Stamatialis, Dimitrios; Papenburg, B.J.; Girones nogue, Miriam; Saiful, S.; Bettahalli Narasimha, M.S.; Schmitmeier, Stephanie; Wessling, Matthias

    2008-01-01

    This paper covers the main medical applications of artificial membranes. Specific attention is given to drug delivery systems, artificial organs and tissue engineering which seem to dominate the interest of the membrane community this period. In all cases, the materials, methods and the current

  19. A histological atlas of the tissues and organs of neotenic and metamorphosed axolotl.

    Science.gov (United States)

    Demircan, Turan; İlhan, Ayşe Elif; Aytürk, Nilüfer; Yıldırım, Berna; Öztürk, Gürkan; Keskin, İlknur

    2016-09-01

    Axolotl (Ambystoma Mexicanum) has been emerging as a promising model in stem cell and regeneration researches due to its exceptional regenerative capacity. Although it represents lifelong lasting neoteny, induction to metamorphosis with thyroid hormones (THs) treatment advances the utilization of Axolotl in various studies. It has been reported that amphibians undergo anatomical and histological remodeling during metamorphosis and this transformation is crucial for adaptation to terrestrial conditions. However, there is no comprehensive histological investigation regarding the morphological alterations of Axolotl organs and tissues throughout the metamorphosis. Here, we reveal the histological differences or resemblances between the neotenic and metamorphic axolotl tissues. In order to examine structural features and cellular organization of Axolotl organs, we performed Hematoxylin & Eosin, Luxol-Fast blue, Masson's trichrome, Alcian blue, Orcein and Weigart's staining. Stained samples from brain, gallbladder, heart, intestine, liver, lung, muscle, skin, spleen, stomach, tail, tongue and vessel were analyzed under the light microscope. Our findings contribute to the validation of the link between newly acquired functions and structural changes of tissues and organs as observed in tail, skin, gallbladder and spleen. We believe that this descriptive work provides new insights for a better histological understanding of both neotenic and metamorphic Axolotl tissues. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Balancing hope and despair at the end of life: The contribution of organ and tissue donation.

    Science.gov (United States)

    Walker, Wendy; Sque, Magi

    2016-04-01

    Concern for the grieving family can moderate the intentions of critical care staff to advocate deceased organ and tissue donation. Conversely, benevolent actions may provoke distress through missed opportunities to save or transform lives. This article provides insight into the perceived benefits of organ and tissue donation for grieving families who experienced end-of-life care in the intensive care unit. Data were collected via semistructured, face-to-face or telephone interviews with 43 participants from 31 donor families. Audio recordings were transcribed verbatim and subjected to qualitative content analysis. The study findings affirmed the importance of person-centered end-of-life care. Donor families shared examples of good-quality care and communication that contained the hallmarks of compassion, respect, dignity, and choice. We uncovered a trajectory of hope and despair in which the option of organ and tissue donation appeared to give meaning to the life and death of the deceased person and was comforting to some families in their bereavement. Our study findings underlined the significance of donation decision making for grieving families. Organ and tissue donation has the potential to balance hope and despair at the end of life when the wishes of the dying, deceased, and bereaved are fulfilled. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Concentrations of transuranic elements in critical organs and tissues of goats (CAPRA HIRCUS)

    International Nuclear Information System (INIS)

    Averin, V.S.; Vaskovtsova, V.A.; Kuhtsevich, A.B.; Tagai, S.A.; Tsarenok, A.A.; Buzdalkin, K.N.; Gvozdik, A.F.; Makarovets, I.V.; Nilova, E.K.

    2012-01-01

    Parameters of Am 241 and Pu 238, 239+240 transfer from the dietary soil-based component (mineral soil) to organs and tissues of goats during a grazing period of 80 and 160 days have been determined. The maximum specific activities of transuranic elements have been found in liver of goats. (authors)

  2. West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients

    Centers for Disease Control (CDC) Podcasts

    2013-11-19

    William Hale reads an abridged version of the Emerging Infectious Diseases’ dispatch, West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients.  Created: 11/19/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/21/2013.

  3. "Project ACTS": An Intervention to Increase Organ and Tissue Donation Intentions among African Americans

    Science.gov (United States)

    Arriola, Kimberly; Robinson, Dana H.; Thompson, Nancy J.; Perryman, Jennie P.

    2010-01-01

    This study sought to evaluate the effectiveness of "Project ACTS: About Choices in Transplantation and Sharing," which was developed to increase readiness for organ and tissue donation among African American adults. Nine churches (N = 425 participants) were randomly assigned to receive donation education materials currently available to consumers…

  4. The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue.

    Science.gov (United States)

    Anderson, L A; McTernan, P G; Harte, A L; Barnett, A H; Kumar, S

    2002-05-01

    Clinical observations suggest a role for testosterone in the accumulation of central adiposity and with an associated increased risk of disease. To date, no human study has analysed the role of dihydrotestosterone (DHT) on adipose tissue mass regulation in vitro. This study investigated the role of DHT and androgen receptors (AR) in the regulation of lipolysis and lipogenesis by examining the key enzymes hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) respectively. Isolated abdominal subcutaneous adipocytes (Scad) (n = 15) were treated with either DHT (10(-7)-10(-9) m), an antiandrogen, flutamide (FLT: 10(-7)-10(-9) m) or a combination of DHT (10(-7)-10(-9) m) with FLT (10(-8) m). Relative protein expression of HSL, LPL and AR was determined. In Scad, DHT inhibited HSL expression maximally at 10(-9) m (0.7 +/- 0.4**; p DHT10(-9) m (2.22 +/- 0.48*; p DHT + FLT compared with DHT alone. Androgen receptor expression studies showed an inverse correlation with DHT, whereas DHT + FLT reduced AR expression. These studies indicate that DHT may alter HSL and LPL expression, whereas only LPL expression appears mediated by AR. These findings suggest a physiological role for DHT in the control of adipose tissue mass in women, and indicate that androgens may also play an important role in regulating lipid metabolism.

  5. 4E-BP1 regulates the differentiation of white adipose tissue.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

    2013-07-01

    4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  6. Family perspectives on organ and tissue donation for transplantation: a principlist analysis.

    Science.gov (United States)

    Dos Santos, Marcelo José; Feito, Lydia

    2017-01-01

    The family interview context is permeated by numerous ethical issues which may generate conflicts and impact on organ donation process. This study aims to analyze the family interview process with a focus on principlist bioethics. This exploratory, descriptive study uses a qualitative approach. The speeches were collected using the following prompt: "Talk about the family interview for the donation of organs and tissues for transplantation, from the preparation for the interview to the decision of the family to donate or not." For the treatment of qualitative data, we chose the method of content analysis and categorical thematic analysis. The study involved 18 nurses who worked in three municipal organ procurement organizations in São Paulo, Brazil, and who conducted family interviews for organ donation. Ethical considerations: The data were collected after approval of the study by the Research Ethics Committee of the School of Nursing of the University of São Paulo. The results were classified into four categories and three subcategories. The categories are the principles adopted by principlist bioethics. The principles of autonomy, beneficence, non-maleficence, and justice permeate the family interview and reveal their importance in the organs and tissues donation process for transplantation. The analysis of family interviews for the donation of organs and tissues for transplantation with a focus on principlist bioethics indicates that the process involves many ethical considerations. The elucidation of these aspects contributes to the discussion, training, and improvement of professionals, whether nurses or not, who work in organ procurement organizations and can improve the curriculum of existing training programs for transplant coordinators who pursue ethics in donation and transplantation as their foundation.

  7. The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

    Directory of Open Access Journals (Sweden)

    Brábek Jan

    2010-09-01

    Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

  8. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  9. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  10. Decorin-transforming growth factor- interaction regulates matrix organization and mechanical characteristics of three-dimensional collagen matrices.

    Science.gov (United States)

    Ferdous, Zannatul; Wei, Victoria Mariko; Iozzo, Renato; Höök, Magnus; Grande-Allen, Kathryn Jane

    2007-12-07

    The small leucine-rich proteoglycan decorin has been demonstrated to be a key regulator of collagen fibrillogenesis; decorin deficiencies lead to irregularly shaped collagen fibrils and weakened material behavior in postnatal murine connective tissues. In an in vitro investigation of the contributions of decorin to tissue organization and material behavior, model tissues were engineered by seeding embryonic fibroblasts, harvested from 12.5-13.5 days gestational aged decorin null (Dcn(-/-)) or wild-type mice, within type I collagen gels. The resulting three-dimensional collagen matrices were cultured for 4 weeks under static tension. The collagen matrices seeded with Dcn(-/-) cells exhibited greater contraction, cell density, ultimate tensile strength, and elastic modulus than those seeded with wild-type cells. Ultrastructurally, the matrices seeded with Dcn(-/-) cells contained a greater density of collagen. The decorin-null tissues contained more biglycan than control tissues, suggesting that this related proteoglycan compensated for the absence of decorin. The effect of transforming growth factor-beta (TGF-beta), which is normally sequestered by decorin, was also investigated in this study. The addition of TGF-beta1 to the matrices seeded with wild-type cells improved their contraction and mechanical strength, whereas blocking TGF-beta1 in the Dcn(-/-) cell-seeded matrices significantly reduced the collagen gel contraction. These results indicate that the inhibitory interaction between decorin and TGF-beta1 significantly influenced the matrix organization and material behavior of these in vitro model tissues.

  11. The complementarity of the technical tools of tissue engineering and the concepts of artificial organs for the design of functional bioartificial tissues.

    Science.gov (United States)

    Lenas, Petros; Moreno, Angel; Ikonomou, Laertis; Mayer, Joerg; Honda, Hiroyuki; Novellino, Antonio; Pizarro, Camilo; Nicodemou-Lena, Eleni; Rodergas, Silvia; Pintor, Jesus

    2008-09-01

    Although tissue engineering uses powerful biological tools, it still has a weak conceptual foundation, which is restricted at the cell level. The design criteria at the cell level are not directly related with the tissue functions, and consequently, such functions cannot be implemented in bioartificial tissues with the currently used methods. On the contrary, the field of artificial organs focuses on the function of the artificial organs that are treated in the design as integral entities, instead of the optimization of the artificial organ components. The field of artificial organs has already developed and tested methodologies that are based on system concepts and mathematical-computational methods that connect the component properties with the desired global organ function. Such methodologies are needed in tissue engineering for the design of bioartificial tissues with tissue functions. Under the framework of biomedical engineering, artificial organs and tissue engineering do not present competitive approaches, but are rather complementary and should therefore design a common future for the benefit of patients.

  12. The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Wang, Hong X; Konopka, James B

    2013-11-26

    Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

  13. Distinct mechanisms regulate Lck spatial organization in activated T cells

    Directory of Open Access Journals (Sweden)

    Natasha eKapoor-Kaushik

    2016-03-01

    Full Text Available Phosphorylation of the T cell receptor (TCR by the kinase Lck is the first detectable signaling event upon antigen engagement. The distribution of Lck within the plasma membrane, its conformational state, kinase activity and protein interactions all contribute to determine how efficiently Lck phosphorylates the engaged TCR. Here we used cross-correlation raster image spectroscopy (ccRICS and photoactivated localization microscopy (PALM to identify two mechanisms of Lck clustering: an intrinsic mechanism of Lck clustering induced by locking Lck in its open conformation, and an extrinsic mechanism of clustering controlled by the phosphorylation of tyrosine 192, which regulates the affinity of Lck SH2 domain. Both mechanisms of clustering were differently affected by the absence of the kinase Zap70 or the adaptor Lat. We further observed that the adaptor TSAd bound to and promoted the diffusion of Lck when it is phosphorylated on tyrosine 192. Our data suggest that while Lck open conformation drives aggregation and clustering, the spatial organization of Lck is further controlled by signaling events downstream of TCR phosphorylation.

  14. Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.

    Science.gov (United States)

    Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed

    2017-08-04

    Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.

  15. Intermittent fasting up-regulates Fsp27/Cidec gene expression in white adipose tissue.

    Science.gov (United States)

    Karbowska, Joanna; Kochan, Zdzislaw

    2012-03-01

    Fat-specific protein of 27 kDa (FSP27) is a novel lipid droplet protein that promotes triacylglycerol storage in white adipose tissue (WAT). The regulation of the Fsp27 gene expression in WAT is largely unknown. We investigated the nutritional regulation of FSP27 in WAT. The effects of intermittent fasting (48 d, eight cycles of 3-d fasting and 3-d refeeding), caloric restriction (48 d), fasting-refeeding (3-d fasting and 3-d refeeding), and fasting (3 d) on mRNA expression of FSP27, peroxisome proliferator-activated receptor γ (PPARγ2), CCAAT/enhancer binding protein α (C/EBPα), and M isoform of carnitine palmitoyltransferase 1 (a positive control for PPARγ activation) in epididymal WAT and on serum triacylglycerol, insulin, and leptin levels were determined in Wistar rats. We also determined the effects of PPARγ activation by rosiglitazone or pioglitazone on FSP27 mRNA levels in primary rat adipocytes. Long-term intermittent fasting, in contrast to other dietary manipulations, significantly up-regulated Fsp27 gene expression in WAT. Moreover, in rats subjected to intermittent fasting, serum insulin levels were elevated; PPARγ2 and C/EBPα mRNA expression in WAT was increased, and there was a positive correlation of Fsp27 gene expression with PPARγ2 and C/EBPα mRNA levels. FSP27 mRNA expression was also increased in adipocytes treated with PPARγ agonists. Our study demonstrates that the transcription of the Fsp27 gene in adipose tissue may be induced in response to nutritional stimuli. Furthermore, PPARγ2, C/EBPα, and insulin may be involved in the nutritional regulation of FSP27. Thus intermittent fasting, despite lower caloric intake, may promote triacylglycerol deposition in WAT by increasing the expression of genes involved in lipid storage, such as Fsp27. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Sensing of EGTA Mediated Barrier Tissue Disruption with an Organic Transistor

    Directory of Open Access Journals (Sweden)

    Scherrine Tria

    2013-01-01

    Full Text Available Barrier tissue protects the body against external factors by restricting the passage of molecules. The gastrointestinal epithelium is an example of barrier tissue with the primary purpose of allowing the passage of ions and nutrients, while restricting the passage of pathogens and toxins. It is well known that the loss of barrier function can be instigated by a decrease in extracellular calcium levels, leading to changes in protein conformation and an increase in paracellular transport. In this study, ethylene glycol-bis(beta-aminoethyl ether-N,N,N',N'-tetra acetic acid (EGTA, a calcium chelator, was used to disrupt the gastrointestinal epithelial barrier. The effect of EGTA on barrier tissue was monitored by a novel label-free method based on an organic electrochemical transistor (OECT integrated with living cells and validated against conventional methods for measuring barrier tissue integrity. We demonstrate that the OECT can detect breaches in barrier tissue upon exposure to EGTA with the same sensitivity as existing methods but with increased temporal resolution. Due to the potential of low cost processing techniques and the flexibility in design associated with organic electronics, the OECT has great potential for high-throughput, disposable sensing and diagnostics.

  17. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

    Energy Technology Data Exchange (ETDEWEB)

    Arrebola, J.P., E-mail: jparrebola@ugr.es [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); CIBER en Epidemiología y Salud Pública (CIBERESP) (Spain); Fernández-Rodríguez, M.; Artacho-Cordón, F. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); University of Granada, Radiology and Physical Medicine Department (Spain); Garde, C. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Perez-Carrascosa, F.; Linares, I.; Tovar, I. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); González-Alzaga, B. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Escuela Andaluza de Salud Pública, Granada (Spain); Expósito, J. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); Torne, P. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); and others

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends = 0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends = 0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend = 0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends = 0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend = 0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. - Highlights: • The role of POP exposure on the pathogenesis breast cancer is still controversial. • POPs were analyzed in serum and adipose tissue from breast cancer patients. • POP concentrations were associated with breast cancer prognostic markers. • POPs in serum and adipose tissue of breast cancer patients may provide different clues.

  18. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

    International Nuclear Information System (INIS)

    Arrebola, J.P.; Fernández-Rodríguez, M.; Artacho-Cordón, F.; Garde, C.; Perez-Carrascosa, F.; Linares, I.; Tovar, I.; González-Alzaga, B.; Expósito, J.; Torne, P.

    2016-01-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends = 0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends = 0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend = 0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends = 0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend = 0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. - Highlights: • The role of POP exposure on the pathogenesis breast cancer is still controversial. • POPs were analyzed in serum and adipose tissue from breast cancer patients. • POP concentrations were associated with breast cancer prognostic markers. • POPs in serum and adipose tissue of breast cancer patients may provide different clues.

  19. Levels of Cs-137 and pathological shifts in the organs and tissues of dead humans

    International Nuclear Information System (INIS)

    Lushnikov, E.F.; Koleganov, Yu.F.; Lantsov, S.I.; Mozhaev, V.K.; Solov'eva, L.P.; Fomin, S.D.

    1996-01-01

    Measurements of the levels of Cs-137, alpha- and beta-radionuclides in the organs and tissues of 30 subjects dead 6 years after the accident, assessment of the pathological shifts and relationships between these shifts and exposure was carried out at territories contaminated with radionuclides in the Bryansk and Kaluga districts, in the town of Obninsk, and in region of Russia free of radionuclides. Study of radioautographs did not show alpha- or beta-radionuclides in any of the dead subjects. Cs-137 was detected in small quantities in the organs of all cadavers (3 to 424 Bq/kg) irrespective of their residence. The extent of radioactivity varied for different organs and was unrelated to organ pathology. Moreover, Cs-137 was detected in the organs of dead newborns and two-month-old infants, whose patients lived at territories contaminated with radionuclides [ru

  20. Present dose limits and their relation to radiosensitivity of different organs and tissues

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    Dose equivalent limits in relation to dose thresholds are considered for injury of various tissues and organs to evaluate the protection agains non-stochastic irradiation effects by the existing system of dose limitation for radiotherapeutic personnel. Data on tissue radiosensitivity in relation to non-stochastic effects, obtained from radiotherapeutic experience, are presented. Dose threshold values, derived for patients, with a correction in the direction of increase, may be applied to conditions of occupational exposure except for bone marrow, gonads and eye lens, where threshold doses are lower

  1. Modelling organs, tissues, cells and devices using Matlab and Comsol multiphysics

    CERN Document Server

    Dokos, Socrates

    2017-01-01

    This book presents a theoretical and practical overview of computational modeling in bioengineering, focusing on a range of applications including electrical stimulation of neural and cardiac tissue, implantable drug delivery, cancer therapy, biomechanics, cardiovascular dynamics, as well as fluid-structure interaction for modelling of organs, tissues, cells and devices. It covers the basic principles of modeling and simulation with ordinary and partial differential equations using MATLAB and COMSOL Multiphysics numerical software. The target audience primarily comprises postgraduate students and researchers, but the book may also be beneficial for practitioners in the medical device industry.

  2. Evaluation of Specific Metabolic Rates of Major Organs and Tissues: Comparison Between Nonobese and Obese Women

    OpenAIRE

    Wang, ZiMian; Ying, Zhiliang; Bosy-Westphal, Anja; Zhang, Junyi; Heller, Martin; Later, Wiebke; Heymsfield, Steven B.; Müller, Manfred J.

    2011-01-01

    Elia (1992) identified the specific resting metabolic rates (Ki) of major organs and tissues in young adults with normal weight: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue and 12 for residual mass (all units in kcal/kg per day). The aim of the present study was to assess the applicability of Elia’s Ki values for obese adults. A sample of young women (n = 80) was divided into two groups, nonobese (BMI

  3. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    Science.gov (United States)

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

    Directory of Open Access Journals (Sweden)

    Laura L Gathercole

    Full Text Available Patients with glucocorticoid (GC excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc and omental (om adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

  5. About problematic peculiarities of Fault Tolerance digital regulation organization

    Science.gov (United States)

    Rakov, V. I.; Zakharova, O. V.

    2018-05-01

    The solution of problems concerning estimation of working capacity of regulation chains and possibilities of preventing situations of its violation in three directions are offered. The first direction is working out (creating) the methods of representing the regulation loop (circuit) by means of uniting (combining) diffuse components and forming algorithmic tooling for building predicates of serviceability assessment separately for the components and the for regulation loops (circuits, contours) in general. The second direction is creating methods of Fault Tolerance redundancy in the process of complex assessment of current values of control actions, closure errors and their regulated parameters. The third direction is creating methods of comparing the processes of alteration (change) of control actions, errors of closure and regulating parameters with their standard models or their surroundings. This direction allows one to develop methods and algorithmic tool means, aimed at preventing loss of serviceability and effectiveness of not only a separate digital regulator, but also the whole complex of Fault Tolerance regulation.

  6. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    Science.gov (United States)

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  7. Strain-induced collagen organization at the micro-level in fibrin-based engineered tissue constructs

    NARCIS (Netherlands)

    Jonge, de N.; Kanters, F.M.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    2013-01-01

    Full understanding of strain-induced collagen organization in complex tissue geometries to create tissues with predefined collagen architecture has not been achieved. This is mainly due to our limited knowledge of collagen remodeling in developing tissues. Here we investigate strain-induced collagen

  8. Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man.

    Directory of Open Access Journals (Sweden)

    Evangelia Charmandari

    Full Text Available Circulating cortisol fluctuates diurnally under the control of the "master" circadian CLOCK, while the peripheral "slave" counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans.We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs as non-synchronized controls.GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo.Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night.

  9. Peripheral CLOCK Regulates Target-Tissue Glucocorticoid Receptor Transcriptional Activity in a Circadian Fashion in Man

    Science.gov (United States)

    Charmandari, Evangelia; Chrousos, George P.; Lambrou, George I.; Pavlaki, Aikaterini; Koide, Hisashi; Ng, Sinnie Sin Man; Kino, Tomoshige

    2011-01-01

    Context and Objective Circulating cortisol fluctuates diurnally under the control of the “master” circadian CLOCK, while the peripheral “slave” counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR) at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans. Design and Participants We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs) obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs) as non-synchronized controls. Results GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo. Conclusions Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night. PMID:21980503

  10. BZLF1 Expression of EBV is correlated with PARP1 Regulation on Nasopharyngeal Carcinoma Tissues

    Directory of Open Access Journals (Sweden)

    Wahyu nur laili fajri, Ahmad Rofi'i, Fatchiyah Fatchiyah

    2013-04-01

    Full Text Available Nasopharyngeal carcinomas (NPC is a cancer that arises in the epithelial tissue that covers the inside of the nasopharyngeal mucosa and nasopharynx. Infected Epstein Barr Virus (EBV cell in a latent infection associated with the expression of nine latent proteins. Latent Membrane Protein 1 (LMP1 is one of latent proteins, and mayor EBV oncoprotein, with functions including virus growth, and to activate BamHI-Z Leftward Reading Frame 1 (BZLF1-EBV, which can inhibit p53 to induce apoptotic resistance, metastasis, and immune modulation. The body will respond to the expansion of EBV infection with activation of Poly(ADP-ribosePolymerase-1 (PARP1. The objective of study is to observe the expression of BZLF1 and determine PARP1 regulation in nasopharyngeal tissues. NPC-T2, NPC-T3 and polyp tissues slides are from Ulin Hospital, Banjarmasin. To characterize the necrotic cells such as pyknosis, karyorrhexsis, and karyolysis, histological slides were stained by HE that the necrotic cells measured by using a BX-53 microscope (Olympus with CellSens Standard software. Tissues slides were stained by using immunofluorohistochemistry with EBV-BZLF1 antibody-Mouse anti-EBV monoclonal antibody against Goat anti-mouse IgG-FITC and anti-PARP1 antibody (MC-10 against Goat anti-mouse IgG labeled Rhodamin. The expression intensities were measured by Confocal Laser Scanning Microscope (Olympus. The percentage number of necrotic cells and BZLF1 and PARP1 expression intensity were analyzed using SPSS 16.0 by one-way ANOVA test with α = 0.05, beside that we use correlate and regression analyze. The research showed that the amount of karryorhexis higher than pyknosis and karyolysis in both tissues. BZLF1 expression 1.79 INT/sel (in polyp, 2.76 INT/sel (NPC Type 2 and 4.36 INT/sel (NPC Type 3, PARP1 expression 2.25 INT/sel (in polyp, 3.31 INT/sel (NPC Type 2, dan 5.93 INT/sel (NPC Type 3.The high of intensity of expression BZLF1 induced the increasing of PARP1 expression

  11. A novel radiation responsive cis-acting element regulates gene induction and mediates tissue injury

    International Nuclear Information System (INIS)

    Hallahan, Dennis E.; Virudachalam, Subbulakshmi; Kuchibahtla, Jaya

    1997-01-01

    containing binding domains for the transcription factors AP-1 and Ets. This DNA sequence (TGCCTCAGTTTCCC) is similar to antioxidant responsive element. X-ray- mediated transcriptional activation of the 5' regulatory region of ICAM-1 required the antioxidant responsive element (ARE). Electrophoretic mobility shift analysis of nuclear proteins from irradiated endothelial cells incubated with the ARE binding domain (5'-GCTGCTGCCTCAGTTTCCC-3') showed increased protein-DNA complexes at 60 and 120 minutes after irradiation. Conclusions: 1) ICAM induction in irradiated tissue occurs in the microvascular endothelium. 2) ICAM expression contributes to the pathogenesis of radiation-mediated tissue injury and the ICAM knockout serves as a model for the study of the pathogenesis of tissue injury. 3) ICAM expression is regulated by a novel radiation-inducible cis-acting element that has homology to previously identified antioxidant responsive elements

  12. Quantum dots versus organic fluorophores in fluorescent deep-tissue imaging--merits and demerits.

    Science.gov (United States)

    Bakalova, Rumiana; Zhelev, Zhivko; Gadjeva, Veselina

    2008-12-01

    The use of fluorescence in deep-tissue imaging is rapidly expanding in last several years. The progress in fluorescent molecular probes and fluorescent imaging techniques gives an opportunity to detect single cells and even molecular targets in live organisms. The highly sensitive and high-speed fluorescent molecular sensors and detection devices allow the application of fluorescence in functional imaging. With the development of novel bright fluorophores based on nanotechnologies and 3D fluorescence scanners with high spatial and temporal resolution, the fluorescent imaging has a potential to become an alternative of the other non-invasive imaging techniques as magnetic resonance imaging, positron-emission tomography, X-ray, computing tomography. The fluorescent imaging has also a potential to give a real map of human anatomy and physiology. The current review outlines the advantages of fluorescent nanoparticles over conventional organic dyes in deep-tissue imaging in vivo and defines the major requirements to the "perfect fluorophore". The analysis proceeds from the basic principles of fluorescence and major characteristics of fluorophores, light-tissue interactions, and major limitations of fluorescent deep-tissue imaging. The article is addressed to a broad readership - from specialists in this field to university students.

  13. Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

    Science.gov (United States)

    He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

    2013-01-01

    A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

  14. Estimate of the absorbed dose in the mouse organs and tissues after tritium administration

    International Nuclear Information System (INIS)

    Saito, Masahiro

    2000-01-01

    Chronic and accidental release of tritium from future fusion facilities may cause some extent of hazardous effect to the public health. Various experiments using small animals such as mice have been performed to mimic the dose accumulation due to tritium intake by the human body. An difficulty in such animal experiments using small animals is that it is rather difficult to administer tritium orally and estimate the dose to small organs or tissues. In the course of our study, a simple method to administer THO and T-labeled amino acids orally to the mouse was dictated and dose accumulation in various organs and tissues was determined. The tritium retention in the bone marrow was also determined using the micro-centrifuge method. Throughout our experiment, colony-bred DDY mice were used. The 8-10 week old male mice were orally and intraperitoneally administered THO water or T-amino acids mixture solution. For the purpose of oral administration, a 10 μl aliquot of T-containing saline solution was placed on the tongue of the mice using an automatic micropipette. At various times after tritium administration, the animals were sacrificed and the amount of tritium in various tissues and organs including bone marrow was examined. Dose accumulation pattern after THO intake and T-amino acids was compared between intraperitoneal injection and oral administration. The accumulated dose after oral administration of THO exhibited a tendency to be 10-20% higher than after intraperitoneal injection. The bone marrow dose after oral intake of THO was found to be lower than the doses to urine, blood, liver and testis. In contrast, the blood dose gave a conservative estimate for the dose to the other tissues and organs. (author)

  15. Compined preoperative diagnosis of stomach cancer involvement of the abdominal and retroperitoneal organs and tissues

    International Nuclear Information System (INIS)

    Fisher, M.E.; Gabuniya, R.I.; Kolesnikova, E.K.; Bal'ter, S.A.; Ostrovtsev, I.V.; Dolgushin, B.I.; Mazurov, S.T.; Mironova, G.T.

    1987-01-01

    An analysis of 136 cases of stomach cancer led to the determination of the role and place of gammatopography, echography, computerized X-ray tomography, angiography and laparoscopy in specified preoperative diagnosis of extraorganic spreading of primary tumors. The informative value and shortcomings of certain methods were shown. A high accuracy of the entire set of diagnostic procedures (94.8%) in the preoperative definition of stomach cancer involvement of the abdominal and retroperitoneal organs and tissues was emphasized

  16. Development on traceability based on changes of stable isotopes in animal tissues and organs

    International Nuclear Information System (INIS)

    Cai Xianfeng; Guo Boli; Wei Yimin; Sun Shumin; Wei Shuai

    2011-01-01

    Stable isotope analysis is a new method in food traceability, which can be used to trace animals' geographical origin and life history. This paper reviews the recent progress of researches on characteristics of stable isotopes and turnover time in different animal tissues and organs, as well as their influence caused by feed, drinking water, geographical origin, storing and processing. The aim of this paper is to provide theoretical reference for studies on the traceability of animal derived food and animals' life history. (authors)

  17. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions.

    Science.gov (United States)

    Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

    2017-03-29

    High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

  18. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

    Directory of Open Access Journals (Sweden)

    Dong-Mei Zhang

    2017-03-01

    Full Text Available High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2 and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG, free fatty acid (FFA, uric acid (UA and methylglyoxal (MG. Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

  19. Legal Issues Related to Donation of Organs, Tissues and Cells of Human Origin

    Directory of Open Access Journals (Sweden)

    Gabriela Mironov

    2010-06-01

    Full Text Available Scientific developments, positive changes in attitude of the man and the new legal framework allow the donation of organs, tissues and cells of human origin. In this context it is necessary to clarifywhether the donation covered by the special law is, legally, one and the same as that covered by the Romanian Civil Code in force and qualified the successor’s right to accept or reject late withdrawals for transplantation. The right to life and physical integrity is personal patrimony; it is a subjective civil right that has no economic content and it cannot be measured in money. Consequently, the content of these rights can not be expressed in money, the property does not belong to their owner. Given the above view, "the right of disposal" to donation of organs, tissues and cells of human origin is an attribute of ownership, right to life and physical integrity, as a personal right that is an intimate attribute patrimonial related to the person’s right to dispose of his body as it wishes, within the law. Addressing these issues it is necessary to clarify the legal consequences of donating organs, tissues and cells of human origin, considering that medical activities are becoming more numerous.

  20. Chitinase-like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?

    Science.gov (United States)

    Sutherland, Tara E

    2018-02-19

    Chitinases and chitinase-like proteins (CLPs) belong to the glycoside hydrolase family 18 of proteins. Chitinases are expressed in mammals and lower organisms, facilitate chitin degradation, and hence act as host-defence enzymes. Gene duplication and loss-of-function mutations of enzymatically active chitinases have resulted in the expression of a diverse range of CLPs across different species. CLPs are genes that are increasingly associated with inflammation and tissue remodelling not only in mammals but also across distant species. While the focus has remained on understanding the functions and expression patterns of CLPs during disease in humans, studies in mouse and lower organisms have revealed important and overlapping roles of the CLP family during physiology, host defence and pathology. This review will summarise recent insights into the regulatory functions of CLPs on innate immune pathways and discuss how these effects are not only important for host defence and tissue injury/repair after pathogen invasion, but also how they have extensive implications for pathological processes involved in diseases such as asthma. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Bioprinting of Micro-Organ Tissue Analog for Drug Metabolism Study

    Science.gov (United States)

    Sun, Wei

    An evolving application of tissue engineering is to develop in vitro 3D cell/tissue models for drug screening and pharmacological study. In order to test in space, these in vitro models are mostly manufactured through micro-fabrication techniques and incorporate living cells with MEMS or microfluidic devices. These cell-integrated microfluidic devices, or referred as microorgans, are effective in furnishing reliable and inexpensive drug metabolism and toxicity studies [1-3]. This paper will present an on-going research collaborated between Drexel University and NASA JSC Radiation Physics Laboratory for applying a direct cell printing technique to freeform fabrication of 3D liver tissue analog in drug metabolism study. The paper will discuss modeling, design, and solid freeform fabrication of micro-fluidic flow patterns and bioprinting of 3D micro-liver chamber that biomimics liver physiological microenvironment for enhanced drug metabolization. Technical details to address bioprinting of 3D liver tissue analog, integration with a microfluidic device, and basic drug metabolism study for NASA's interests will presented. 1. Holtorf H. Leslie J. Chang R, Nam J, Culbertson C, Sun W, Gonda S, "Development of a Three-Dimensional Tissue-on-a-Chip Micro-Organ Device for Pharmacokinetic Analysis", the 47th Annual Meeting of the American Society for Cell Biology, Washington, DC, December 1-5, 2007. 2. Chang, R., Nam, J., Culbertson C., Holtorf, H., Jeevarajan, A., Gonda, S. and Sun, W., "Bio-printing and Modeling of Flow Patterns for Cell Encapsulated 3D Liver Chambers For Pharmacokinetic Study", TERMIS North America 2007 Conference and Exposition, Westin Harbour Castle, Toronto, Canada, June 13-16, 2007. 3.Starly, B., Chang, R., Sun, W., Culbertson, C., Holtorf, H. and Gonda, S., "Bioprinted Tissue-on-chip Application for Pharmacokinetic Studies", Proceedings of World Congress on Tissue Engineering and Regenerative Medicine, Pittsburgh, PA, USA, April 24-27, 2006.

  2. Whole body plastination, intra-organ heterogeneity, and tissue based diagnosis – a survey

    Directory of Open Access Journals (Sweden)

    Gunther von Hagens

    2018-04-01

    Full Text Available  Background: The corpse is the final structural relict of life. Its detailed analysis, the autopsy formed the basis and contributed significantly to our understanding of location, function and interaction of organs in man. Today, autopsies are performed rarely. They have been replaced by radiological in vivo visualization techniques and the analysis of organ excisions and biopsies. Which attributes do whole body preservations possess in this context? Techniques of Whole Body Analysis: In vivo imaging transfers the appearance of body organs and cellular structures in virtual images. The patient’s exposure to X-rays, fundamental particles (electrons, positrons, etc., strong magnetic fields (nuclear resonance, or ultra sounds release the corresponding signals. The obtained images are interpreted in search for local abnormalities such as cancer, acute and chronic infections, inborn errors, hypertrophy or atrophy. Autopsies require the removal and visual inspection of organs shortly after the victim’s death. In addition, tissue probes of suspicious lesions are fixed and microscopically analyzed. The search for gene or protein abnormalities are added dependent upon the clinical history and gross findings. The whole body plastination is performed in separated steps which include fixation, anatomical dissection, forced polymer impregnation, positioning and curing. Organs and other tissue structures can be taken out of the body and separately demonstrated, or aligned and fixed within the body. Additional tissue examinations are possible at this stage, which is followed by hardening and fixation of the still flexible body. Fixation is done with heat, light or gas.   Results and Interpretation: Tissue conservation is a prerequisite to analyze and investigate in diagnosis and forecast of disease occurrence and behaviour. In history, autopsies have opened the door to localize the position and to understand the functions of organs. Today, they have been

  3. Effects of chronic exposure to tributyltin on tissue-specific cytochrome P450 1 regulation in juvenile common carp.

    Science.gov (United States)

    Li, Zhi-Hua; Zhong, Li-Qiao; Mu, Wei-Na; Wu, Yan-Hua

    2016-01-01

    1. The purpose of this study was to compare tributyltin (TBT)-induced cytochrome P450 1 (CYP450 1) regulation in liver, gills and muscle of juvenile common carp (Cyprinus carpio). 2. Fish were exposed to sublethal concentrations of TBT (75, 0.75 and 7.5 μg/L) for 60 days. CYP450 1A was measured at the enzyme activity level as 7-ethoxyresorufin-O-deethylase (EROD) activity, as well as the mRNA expression of CYP450 1 family genes (CYP1A, CYP1B, CYP1C1 and CYP1C2) in fish tissues. 3. Based on the results, the liver displayed the highest absolute levels of EROD activity, both under nonexposed and exposed conditions. Additional, EROD activities and CYP1A gene levels showed a good correlation in all three organs. According to the mRNA expression of CYP450 1 family genes, it suggested that CYP1A was to accommodate most EROD activity in fish, but other CYP450 forms also involved in this proceeding. 4. Overall, the study revealed both similarities and differences in the concentration-dependent CYP450 1 responses of the three target organs, which could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

  4. 1 CFR 21.14 - Deviations from standard organization of the Code of Federal Regulations.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Deviations from standard organization of the... CODIFICATION General Numbering § 21.14 Deviations from standard organization of the Code of Federal Regulations. (a) Any deviation from standard Code of Federal Regulations designations must be approved in advance...

  5. Organ and tissue donation in a regional paediatric intensive care unit: evaluation of practice.

    Science.gov (United States)

    Carone, Laura; Alurkar, Shrirang; Kigozi, Phoebe; Vyas, Harish

    2018-05-01

    Approximately 2% of those on the organ transplant list in the UK are children. Early identification of donors and referral to organ donation teams (ODT) has proven to increase both the success rate of gaining consent and the number of organs actually retrieved. To evaluate the practice relating to organ donation for children receiving end-of-life care on a paediatric intensive care unit (PICU) measured against the National Guidelines. All children 0-18 who received their end-of-life care and died on the PICU. A retrospective cohort study of organ donation patterns including referral, approach, consent and donation. This involved a review of case notes on PICU between the years 2009 and 2014. One hundred five deaths were identified and 100 notes were examined and data analysed to ascertain if religion, age and length of stay on PICU impacted on practice. Eighty-six children met the early identification criteria for potential donors, 40 (46.5%) children were referred to the ODT and 33 (38.3%) families were approached regarding donation. Twenty-one (24.4%) families consented to donation. Seventeen donations took place with a total of 41 sets of organs/tissues retrieved. Despite the majority of children meeting early identification for potential donors, many were not being referred. All children on end-of-life care should be referred for potential organ donation. Organ donation needs to be seen as a priority for hospitals as a part of routine end-of-life care to help increase referral rates and give families the opportunity to donate. Many paediatric deaths are not referred for consideration of organ donation, despite guidelines stating that this process should be standard of care. Further optimization of referral rates may aid in increasing the number of organs available for donation. What is Known: • Shortage of organs continues to be a national problem. • NICE guidelines state that all patients who are on end-of-life care should have the option of organ donation

  6. Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures

    International Nuclear Information System (INIS)

    Eigėlienė, Natalija; Härkönen, Pirkko; Erkkola, Risto

    2006-01-01

    Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells. The aim of this study was to investigate the effects of 17β-estradiol and medroxyprogesterone acetate on proliferation, apoptosis, expression of differentiation markers and steroid hormone receptors in breast epithelium using an in vitro model of freshly isolated human breast tissue, in which a proper interaction of breast epithelium and stroma has been maintained. Human breast tissues were obtained from women undergoing surgery for breast tumours. Peritumoral tissues were excised and explants were cultured for 3 weeks in medium supplemented with E 2 or MPA or with E 2 +MPA. Endpoints included histopathological, histomorphometric and immunohistochemical assessment of the breast explants. Culture of breast explants for 14 or 21 days with steroid hormones increased proliferative activity and the thickness of acinar and ductal epithelium. E 2 -treatment led to hyperplastic epithelial morphology, MPA to hypersecretory single-layered epithelium and E 2 +MPA to multilayered but organised epithelium. The proliferative response to E 2 in comparison to control (p < 0.001) was more pronounced than to MPA (p < 0.05) or E 2 +MPA (p < 0.05) at 7 and 14 days for Ki-67 and PCNA. E 2 treatment also decreased the proportion of apoptotic cells after 7 (p < 0.01) and 14 (p < 0.01) days. In addition, the relative number of ERα, ERβ and PR positive epithelial cells was decreased by all

  7. Extracellular Matrix components regulate cellular polarity and tissue structure in the developing and mature Retina

    Directory of Open Access Journals (Sweden)

    Shweta Varshney

    2015-01-01

    Full Text Available While genetic networks and other intrinsic mechanisms regulate much of retinal development, interactions with the extracellular environment shape these networks and modify their output. The present review has focused on the role of one family of extracellular matrix molecules and their signaling pathways in retinal development. In addition to their effects on the developing retina, laminins play a role in maintaining Müller cell polarity and compartmentalization, thereby contributing to retinal homeostasis. This article which is intended for the clinical audience, reviews the fundamentals of retinal development, extracellular matrix organization and the role of laminins in retinal development. The role of laminin in cortical development is also briefly discussed.

  8. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

    DEFF Research Database (Denmark)

    Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene

    2017-01-01

    Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils...... in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability...... of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source...

  9. Results from the organ and tissue transplant program in Nuevo Leon, Mexico, 1996 to 2001.

    Science.gov (United States)

    Carbajal, H; Cabriales, H

    2003-12-01

    Before 1996, solid organs from cadaveric donors (CD) did not account for more than 2% of all transplants. The need for more transplants led the state to undergo several legislative, societal, organizational, and infrastructure changes. A descriptive analysis of the evolution of the transplant program in the State of Nuevo León, Mexico, from 1996 to 2001. Trimester reports have been routinely performed since 1996 from the 14 institutions that are licensed to perform organ and tissue transplants in the State of Nuevo León, Mexico. All reports were concentrated and a descriptive analysis is presented herein. From 1996 until 2001, a total of 1457 organ and tissue (OT) transplants have been performed. At the end of this period, there was a 214% increase in the total number of transplants. By 2001, 73% of the program's total of 1457 OT transplants came from cadaveric donors. The state transplant program of Nuevo León has experienced a dramatic growth since 1996. The percent of organs transplanted from cadaveric donors is one of the highest in Mexico. There is still much work to be done at the state and national levels; better epidemiological studies and dialysis registries are needed as well as investment in transplant research.

  10. Evidence of the Association Between Psychology and Tissue and Organ Transplantation in Brazil.

    Science.gov (United States)

    Silva, J D A; Ariente, L C; Roza, B A; Mucci, S

    2016-09-01

    The addition of psychologists to organ transplant teams is still new in Brazil. In seeking the efficient performance of this professional, the knowledge of the scientific production and the development of research in the area is fundamental. In this sense, this study aims to survey the Brazilian scientific research that has investigated the psychologic aspects involved in tissue and organ transplantation. A literature narrative review was performed with the use of the "Transplante AND Psicologia" descriptors in the Biblioteca Virtual em Saúde and the CAPES Journal Portal. Fifty-three articles were found, of which 22 met the inclusion criteria: publications dating from 2000 to 2014 and the main topic of interest of the studies being quality of life, followed by organ donation. The instruments used most frequently were interviews developed by the researchers and the SF-36 Quality of Life Questionnaire. Recent Brazilian studies on the association between psychology and transplantation are still scarce, possibly because of the recent addition of psychologists to transplantation teams. Therefore, it is suggested that more scientific research is made in the area and that the objects of study are more varied, to ensure adequacy of the psychologist to meet the specific demands of organ and tissue transplantation process. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Cause marketing for tissue and organ donation to increase public awareness

    International Nuclear Information System (INIS)

    Strong, M.; Neely, D.; Warnack, K.; Willits, M.; Yriondo, L.

    1999-01-01

    Today the science of marketing is being applied more and more to increase the rate of tissue and organ donation in the United States. To benefit from the proven tools and techniques of successful marketing in the for-profit world transplantation agencies across the country are turning to integrated marketing communications strategies and strategic partnerships to help achieve their goals.The methods used in cause marketing include: Establishing clear and measurable outcomes and goals; building a marketing plan and timeline to achieve the goals; gathering resources (funding, personnel, organizations, partnerships) to execute the plan, implementation, and measurement of outcomes. This session will review the Tissue and Organ Donation campaign implemented in the Northwest and will touch on the national awareness program developed by United Network for Organ Sharing (UNOS) in the United States. Segments of the Northwest's integrated campaign will include market segmentation strategies and targeted marketing, campaign development, public service advertising and public education campaigns. Media utilized include print, bus signs and billboards, broadcast (radio and TV), video and the internet. Strategies include public service advertising, paid advertising through sponsorships, direct mail, workshops and public speaking. The success of traditional product marketing can be achieved in cause marketing with a long-term, focused public education campaign. The potential benefit to the international community warrants exploration of similar strategies to overcome cultural resistance to life saving transplantation

  12. The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue cryopreservation.

    Science.gov (United States)

    Lewis, Jedediah K; Bischof, John C; Braslavsky, Ido; Brockbank, Kelvin G M; Fahy, Gregory M; Fuller, Barry J; Rabin, Yoed; Tocchio, Alessandro; Woods, Erik J; Wowk, Brian G; Acker, Jason P; Giwa, Sebastian

    2016-04-01

    The first Organ Banking Summit was convened from Feb. 27 - March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery - and even space travel. Key remaining scientific sub-challenges were discussed including ice nucleation and growth, cryoprotectant and osmotic toxicities, chilling injury, thermo-mechanical stress, the need for rapid and uniform rewarming, and ischemia/reperfusion injury. A variety of opportunities to overcome these challenge areas were discussed, i.e. preconditioning for enhanced stress tolerance, nanoparticle rewarming, cyroprotectant screening strategies, and the use of cryoprotectant cocktails including ice binding agents. Copyright © 2015.

  13. PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

    Science.gov (United States)

    Felizola, Saulo J. A.; Nakamura, Yasuhiro; Ono, Yoshikiyo; Kitamura, Kanako; Kikuchi, Kumi; Onodera, Yoshiaki; Ise, Kazue; Takase, Kei; Sugawara, Akira; Hattangady, Namita; Rainey, William E.; Satoh, Fumitoshi; Sasano, Hironobu

    2014-01-01

    Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells. PMID:24403568

  14. RHEB: a potential regulator of chondrocyte phenotype for cartilage tissue regeneration.

    Science.gov (United States)

    Ashraf, S; Ahn, J; Cha, B-H; Kim, J-S; Han, I; Park, H; Lee, S-H

    2017-09-01

    As articular cartilage has a limited ability to self-repair, successful cartilage regeneration requires clinical-grade chondrocytes with innate characteristics. However, cartilage regeneration via chondrocyte transplantation is challenging, because chondrocytes lose their innate characteristics during in vitro expansion. Here, we investigated the mechanistic underpinning of the gene Ras homologue enriched in brain (RHEB) in the control of senescence and dedifferentiation through the modulation of oxidative stress in chondrocytes, a hallmark of osteoarthritis. Serial expansion of human chondrocytes led to senescence, dedifferentiation and oxidative stress. RHEB maintained the innate characteristics of chondrocytes by regulating senescence, dedifferentiation and oxidative stress, leading to the upregulation of COL2 expression via SOX9 and the downregulation of p27 expression via MCL1. RHEB also decreased the expression of COL10. RHEB knockdown mimics decreased the expression of SOX9, COL2 and MCL1, while abrogating the suppressive function of RHEB on p27 and COL10 in chondrocytes. RHEB-overexpressing chondrocytes successfully formed cartilage tissue in vitro as well as in vivo, with increased expression of GAG matrix and chondrogenic markers. RHEB induces a distinct gene expression signature that maintained the innate chondrogenic properties over a long period. Therefore, RHEB expression represents a potentially useful mechanism in terms of cartilage tissue regeneration from chondrocytes, by which chondrocyte phenotypic and molecular characteristics can be retained through the modulation of senescence, dedifferentiation and oxidative stress. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

    Science.gov (United States)

    Achard, V; Tassistro, V; Boullu-Ciocca, S; Grino, M

    2011-12-01

    Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

  16. Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

    Directory of Open Access Journals (Sweden)

    Sarah Phillips

    2014-05-01

    Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

  17. Carvedilol induces endogenous hydrogen sulfide tissue concentration changes in various mouse organs.

    Science.gov (United States)

    Wiliński, Bogdan; Wiliński, Jerzy; Somogyi, Eugeniusz; Piotrowska, Joanna; Góralska, Marta; Macura, Barbara

    2011-01-01

    Carvedilol, a third generation non-selective adrenoreceptor blocker, is widely used in cardiology. Its action has been proven to reach beyond adrenergic antagonism and involves multiple biological mechanisms. The interaction between carvedilol and endogenous 'gasotransmitter' hydrogen sulfide (H2S) is unknown. The aim of the study is to assess the influence of carvedilol on the H2S tissue level in mouse brain, liver, heart and kidney. Twenty eight SJL strain female mice were administered intraperitoneal injections of 2.5 mg/kg b.w./d (group D1, n=7), 5 mg/kg b.w./d (group D2, n=7) or 10 mg/kg b.w./d of carvedilol (group D3, n=7). The control group (n=7) received physiological saline in portions of the same volume (0.2 ml). Measurements of the free tissue H2S concentrations were performed according to the modified method of Siegel. A progressive decline in H2S tissue concentration along with an increase in carvedilol dose was observed in the brain (12.5%, 13.7% and 19.6%, respectively). Only the highest carvedilol dose induced a change in H2S tissue level in the heart - an increase by 75.5%. In the liver medium and high doses of carvedilol increased the H2S level by 48.1% and 11.8%, respectively. In the kidney, group D2 showed a significant decrease of H2S tissue level (22.5%), while in the D3 group the H2S concentration increased by 12.9%. Our study has proven that carvedilol affects H2S tissue concentration in different mouse organs.

  18. Fatty acid composition of muscle and adipose tissues of organic and conventional Blanca Andaluza suckling kids

    Directory of Open Access Journals (Sweden)

    F. De la Vega

    2013-01-01

    Full Text Available Interest in the preservation of autochthonous breeds such as the Blanca Andaluza goat (meat breed, raised under grazing-based management, has recently increased among Spanish farmers. A study of the possibilities of transformation to organic production needs to analyze the quality of their products. The aim of this study was to evaluate the fatty acid (FA composition of muscle and adipose tissues of Blanca Andaluza goat kids under organic and conventional grazing–based management system. Twenty-four twin kids (12 males, 12 females were selected from each system. The FA profile was determined in the longissimus thoracis muscle, kidney and pelvic fat. The percentages of C17:0, C17:1, C20:1, C20:4 n-6, C22:2 and several n-3 FAs were higher in organic meat; C12:0, C18:1 trans-11, CLA and C20:5 n-3 were lower in organic meat. The fat depots from the conventional kids showed lower percentages of C12:0, C14:0, C15:0, C17:0, C17:1, C18:3 n-3 and atherogenicity index, and higher percentage of C18:0. In the pelvic fat, the conventional kids displayed lower percentages of C16:0, C18:2 n-6 cis, PUFA, n-3 and n-6 FAs, and greater percentages of C18:1 n-9 cis and MUFA. The conventional kids displayed a major n6:n3 ratio in the kidney fat. No gender differences were observed. Significant differences were found only in some FA percentages of muscle and adipose tissues of suckling kids raised in organic and conventional livestock production systems, and due to this reason conventional grazing–based management farms could easily be transformed into organic production.

  19. 75 FR 77576 - General Regulations and Derivatives Clearing Organizations

    Science.gov (United States)

    2010-12-13

    ... Derivatives Clearing Organizations AGENCY: Commodity Futures Trading Commission. ACTION: Notice of proposed... derivatives clearing organization (DCO) Core Principles A (Compliance), H (Rule Enforcement), N (Antitrust... commission merchant (FCM) that is also registered as a securities broker-dealer (FCM/BD), and make certain...

  20. Microbial bioavailability regulates organic matter preservation in marine sediments

    NARCIS (Netherlands)

    Koho, K. A.; Nierop, K. G. J.; Moodley, L.; Middelburg, J. J.; Pozzato, L.; Soetaert, K.; van der Plicht, J.; Reichart, G-J.; Herndl, G.

    2013-01-01

    Burial of organic matter (OM) plays an important role in marine sediments, linking the short-term, biological carbon cycle with the long-term, geological subsurface cycle. It is well established that low-oxygen conditions promote organic carbon burial in marine sediments. However, the mechanism

  1. A method for the determination of potassium concentration in organic tissue samples

    International Nuclear Information System (INIS)

    Maciel, A.C.A.

    1976-12-01

    An original method has been developed to detect small variations of potassium in several samples of organic tissue. These variations are relative to elements that are biologically representative, such as carbon, oxygen, and nitrogen. The samples are irradiated with a beam of protons from a Van de Graaff accelerator (4MV). Vacancies are created in the K-shell of potassium, and x-rays are emitted when these vacancies are filled with outer electrons. These X-rays and the protons elastically scattered by the nuclei of carbon, nitrogen and oxygen are detected and their energy spectra are analysed by computer programs especially elaborated for this purpose. A technique for routine preparation of samples in the laboratory was developed including the production of aluminum support layers, and the preparation of organic tissue samples with a low temperature microtome. The unique features of this method are that it does not destroy the tissue, permitting further analysis with the microscope, and the normalization of the amount of potassium using other elements (C,O,N) instead of the total mass of the sample. (Author) [pt

  2. Tissue transglutaminase (TG2 activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

    Directory of Open Access Journals (Sweden)

    Xiaoxue Yin

    2012-08-01

    Full Text Available Tissue transglutaminase (type II, TG2 has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14 to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC mRNA, bone morphogenetic protein-2 (BMP-2 and collagen I, significantly high alkaline phosphatase (ALP activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2.

  3. Djhsp90s are crucial regulators during planarian regeneration and tissue homeostasis.

    Science.gov (United States)

    Dong, Zimei; Chu, Gengbo; Sima, Yingxu; Chen, Guangwen

    2018-04-15

    Heat shock protein 90 family members (HSP90s), as molecular chaperones, have conserved roles in the physiological processes of eukaryotes regulating cytoprotection, increasing host resistance and so on. However, whether HSP90s affect regeneration in animals is unclear. Planarians are emerging models for studying regeneration in vivo. Here, the roles of three hsp90 genes from planarian Dugesia japonica are investigated by WISH and RNAi. The results show that: (1) Djhsp90s expressions are induced by heat and cold shock, tissue damage and ionic liquid; (2) Djhsp90s mRNA are mainly distributed each side of the body in intact worms as well as blastemas in regenerative worms; (3) the worms show head regression, lysis, the body curling and the regeneration arrest or even failure after Djhsp90s RNAi; (4) Djhsp90s are involved in autophagy and locomotion of the body. The research results suggest that Djhsp90s are not only conserved in cytoprotection, but also involved in homeostasis maintenance and regeneration process by regulating different pathways in planarians. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

    Energy Technology Data Exchange (ETDEWEB)

    Valous, N. A.; Delgado, A.; Sun, D.-W., E-mail: dawen.sun@ucd.ie [School of Biosystems Engineering, University College Dublin, National University of Ireland, Belfield, Dublin 4, Dublin (Ireland); Drakakis, K. [Complex and Adaptive Systems Laboratory, University College Dublin, National University of Ireland, Belfield, Dublin 4, Dublin (Ireland)

    2014-02-14

    The study of plant tissue parenchyma's intercellular air spaces contributes to the understanding of anatomy and physiology. This is challenging due to difficulty in making direct measurements of the pore space and the complex mosaic of parenchymatous tissue. The architectural complexity of pore space has shown that single geometrical measurements are not sufficient for characterization. The inhomogeneity of distribution depends not only on the percentage content of phase, but also on how the phase fills the space. The lacunarity morphometric, as multiscale measure, provides information about the distribution of gaps that correspond to degree of spatial organization in parenchyma. Additionally, modern theories have suggested strategies, where the focus has shifted from the study of averages and histograms to the study of patterns in data fluctuations. Detrended fluctuation analysis provides information on the correlation properties of the parenchyma at different spatial scales. The aim is to quantify (with the aid of the aforementioned metrics), the mesostructural changes—that occur from one cycle of freezing and thawing—in the void phase of pome fruit parenchymatous tissue, acquired with X-ray microcomputed tomography. Complex systems methods provide numerical indices and detailed insights regarding the freezing-induced modifications upon the arrangement of cells and voids. These structural changes have the potential to lead to physiological disorders. The work can further stimulate interest for the analysis of internal plant tissue structures coupled with other physico-chemical processes or phenomena.

  5. Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

    International Nuclear Information System (INIS)

    Valous, N. A.; Delgado, A.; Sun, D.-W.; Drakakis, K.

    2014-01-01

    The study of plant tissue parenchyma's intercellular air spaces contributes to the understanding of anatomy and physiology. This is challenging due to difficulty in making direct measurements of the pore space and the complex mosaic of parenchymatous tissue. The architectural complexity of pore space has shown that single geometrical measurements are not sufficient for characterization. The inhomogeneity of distribution depends not only on the percentage content of phase, but also on how the phase fills the space. The lacunarity morphometric, as multiscale measure, provides information about the distribution of gaps that correspond to degree of spatial organization in parenchyma. Additionally, modern theories have suggested strategies, where the focus has shifted from the study of averages and histograms to the study of patterns in data fluctuations. Detrended fluctuation analysis provides information on the correlation properties of the parenchyma at different spatial scales. The aim is to quantify (with the aid of the aforementioned metrics), the mesostructural changes—that occur from one cycle of freezing and thawing—in the void phase of pome fruit parenchymatous tissue, acquired with X-ray microcomputed tomography. Complex systems methods provide numerical indices and detailed insights regarding the freezing-induced modifications upon the arrangement of cells and voids. These structural changes have the potential to lead to physiological disorders. The work can further stimulate interest for the analysis of internal plant tissue structures coupled with other physico-chemical processes or phenomena

  6. Goldfish neurokinin B: Cloning, tissue distribution, and potential role in regulating reproduction.

    Science.gov (United States)

    Qi, Xin; Zhou, Wenyi; Li, Shuisheng; Liu, Yun; Ye, Gang; Liu, Xiaochun; Peng, Chun; Zhang, Yong; Lin, Haoran

    2015-09-15

    Neurokinin B (NKB) is a member of the tackykinin (TAC) family known to play a critical role in the neuroendocrine regulation of reproduction in mammals. However, its biological functions in teleosts are less clear. The aim of this study was to determine the role of NKB in fish reproduction using goldfish as a model. Two transcripts, TAC3a and TAC3b, which encode several NKBs, including NKBa-13, NKBa-10, NKBb-13, and NKBb-11, were cloned. Phylogenetic analysis revealed that NKBa-10 and NKBb-11 are closely related to mammalian NKB, while NKB-13s are more conserved in teleosts. Quantitative real-time PCR analyses in various tissues showed that TAC3a and TAC3b mRNAs were mainly expressed in the brain. In situ hybridization further detected TAC3a and TAC3b mRNAs in several regions of the brain known to be involved in the regulation of reproduction and metabolism, as well as in the neurohypophysis of the pituitary. To investigate the potential role of NKBs in reproduction, goldfish were injected intraperitoneally with synthetic NKBa-13, -10, NKBb-13, or -11 peptides and the mRNA levels of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin subunits were measured. NKBa-13, -10, or NKBb-13, but not -11, significantly increased hypothalamic salmon GnRH and pituitary FSHβ and LHβ mRNA levels in both female and male goldfish. Finally, ovariectomy increased, while estradiol replacement reduced, TAC3a mRNA levels without affecting TAC3b expression in the hypothalamus. These data suggest that NKBa-13, -10, and NKBb-13 play a role in mediating the estrogen negative feedback regulation of gonadotropins. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Regulation and spatial organization of PCNA in Trypanosoma brucei

    International Nuclear Information System (INIS)

    Kaufmann, Doris; Gassen, Alwine; Maiser, Andreas; Leonhardt, Heinrich; Janzen, Christian J.

    2012-01-01

    Highlights: ► Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). ► TbPCNA is a suitable marker to detect replication in T. brucei. ► TbPCNA distribution and regulation is different compared to closely related parasites T. cruzi and Leishmania donovani. -- Abstract: As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes.

  8. Regulation and spatial organization of PCNA in Trypanosoma brucei

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, Doris; Gassen, Alwine [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Maiser, Andreas; Leonhardt, Heinrich [University of Munich (LMU), Department Biology II, Grosshaderner Str. 2-4, 82152 Martinsried (Germany); Janzen, Christian J., E-mail: christian.janzen@uni-wuerzburg.de [University of Munich (LMU), Department Biology I, Genetics, Grosshaderner Str. 2-4, 82152 Martinsried (Germany)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Characterization of the proliferating cell nuclear antigen in Trypanosoma brucei (TbPCNA). Black-Right-Pointing-Pointer TbPCNA is a suitable marker to detect replication in T. brucei. Black-Right-Pointing-Pointer TbPCNA distribution and regulation is different compared to closely related parasites T. cruzi and Leishmania donovani. -- Abstract: As in most eukaryotic cells, replication is regulated by a conserved group of proteins in the early-diverged parasite Trypanosoma brucei. Only a few components of the replication machinery have been described in this parasite and regulation, sub-nuclear localization and timing of replication are not well understood. We characterized the proliferating cell nuclear antigen in T. brucei (TbPCNA) to establish a spatial and temporal marker for replication. Interestingly, PCNA distribution and regulation is different compared to the closely related parasites Trypanosoma cruzi and Leishmania donovani. TbPCNA foci are clearly detectable during S phase of the cell cycle but in contrast to T. cruzi they are not preferentially located at the nuclear periphery. Furthermore, PCNA seems to be degraded when cells enter G2 phase in T. brucei suggesting different modes of replication regulation or functions of PCNA in these closely related eukaryotes.

  9. Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization.

    Science.gov (United States)

    Zheng, Chen-Xi; Sui, Bing-Dong; Hu, Cheng-Hu; Qiu, Xin-Yu; Zhao, Pan; Jin, Yan

    2018-04-27

    Failure of solid organs, such as the heart, liver, and kidney, remains a major cause of the world's mortality due to critical shortage of donor organs. Tissue engineering, which uses elements including cells, scaffolds, and growth factors to fabricate functional organs in vitro, is a promising strategy to mitigate the scarcity of transplantable organs. Within recent years, different construction strategies that guide the combination of tissue engineering elements have been applied in solid organ tissue engineering and have achieved much progress. Most attractively, construction strategy based on whole-organ decellularization has become a popular and promising approach, because the overall structure of extracellular matrix can be well preserved. However, despite the preservation of whole structure, the current constructs derived from decellularization-based strategy still perform partial functions of solid organs, due to several challenges, including preservation of functional extracellular matrix structure, implementation of functional recellularization, formation of functional vascular network, and realization of long-term functional integration. This review overviews the status quo of solid organ tissue engineering, including both advances and challenges. We have also put forward a few techniques with potential to solve the challenges, mainly focusing on decellularization-based construction strategy. We propose that the primary concept for constructing tissue-engineered solid organs is fabricating functional organs based on intact structure via simulating the natural development and regeneration processes. Copyright © 2018 John Wiley & Sons, Ltd.

  10. Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair.

    Science.gov (United States)

    Zimmermann, Wolfram-Hubertus

    2013-01-01

    The heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome (for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application.

  11. Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Grunnet, Louise G; Nilsson, Emma; Ling, Charlotte

    2009-01-01

    Objective. Common variants in FTO (the fat-mass and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and non-genetic regulation of FTO mRNA in skeletal muscle...... and adipose tissue, and their influence on in vivo glucose and fat metabolism. Research Design and Methods. The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years......) and elderly (58-66 years) non-diabetic twins examined by a hyperinsulinemic euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n=226) and skeletal muscle biopsies (n=158). Results. Heritability of FTO expression in both tissues was low, and FTO...

  12. Accumulation of polonium 210Po in tissues and organs of deer carvidae from Northern Poland.

    Science.gov (United States)

    Skwarzec, Bogdan; Prucnal, Malgorzata

    2007-01-01

    This study was undertaken to provide information on accumulation of polonium in tissues and organs of deer carvidae in order to assess the potential transport of this element via food-chain to game meat consumers. Livers, kidneys and muscles of large herbivorous animals belonging to three species: roe deer (Capreolus capreolus), red deer (Cervus elaphus) and fallow deer (Dama dama), collected in Northern Poland, were the subject of the present investigation. Activities of (210)Po were determined by means of alpha spectrometry along with relevant radiochemical procedures. The concentration of (210)Po in analyzed animals decreased in the order kidney > liver > muscle tissue. The average activity concentrations of (210)Po ranged between 0.02 +/- 0.01 Bq. kg(- 1) w.w. in muscles and 7.15 +/- 0.12 Bq. kg(- 1) w.w. in kidneys. Levels of polonium were not influenced by sampling location, sex, age and species of animals.

  13. PCBs and PCDD/Fs distribution in tissues and organs of marine animals in Russian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Amirova, Z.; Kruglov, E.; Loshkina, E.; Khalilov, R. [Environmental Research and Protection Centre, Ufa (Russian Federation); Melnikov, S.; Vlasov, S. [Regional Centre Monitoring of the Arctic, St. Petersburg (Russian Federation)

    2004-09-15

    Studies of persistent organic pollutants (POPs) in the Russian Arctic were conducted recently by a Arctic Monitoring and Assessment Program (AMAP) project. This project developed new data on the POPs pollution levels in the environment and biosphere, including PCBs and PCDD/Fs, in arctic regions of Russia. Transboundary transport and biomagnification within food chains in arctic regions result in POPs accumulation in tissues of fish and marine animals. The aim of this study was to determine the concentration of indicator PCBs, co-planar PCBs and PCDD/Fs in different tissues and organs of seals, walruses and whales caught near the seashore of Chukotski Peninsula (settlement of Lavrenty), Russia, to determine the background level of arctic biota pollution and to study distribution of toxicants in organisms of marine animals. Sampling was made in the course of the 1{sup st} and the 2{sup nd} stages of the 4{sup th} phase of Raipon/AMAP/GEF project ''Persistent Toxic Substances (PTS), Food Security and Indigenous Peoples of the Russian North'' in 2002 by researchers of the Regional Center for Monitoring of the Arctic (RCMA), St. Petersburg, Russia.

  14. Enamel tissue engineering using subcultured enamel organ epithelial cells in combination with dental pulp cells.

    Science.gov (United States)

    Honda, Masaki J; Shinmura, Yuka; Shinohara, Yoshinori

    2009-01-01

    We describe a strategy for the in vitro engineering of enamel tissue using a novel technique for culturing enamel organ epithelial (EOE) cells isolated from the enamel organ using 3T3-J2 cells as a feeder layer. These subcultured EOE cells retain the capacity to produce enamel structures over a period of extended culture. In brief, enamel organs from 6-month-old porcine third molars were dissociated into single cells and subcultured on 3T3-J2 feeder cell layers. These subcultured EOE cells were then seeded onto a collagen sponge in combination with primary dental pulp cells isolated at an early stage of crown formation, and these constructs were transplanted into athymic rats. After 4 weeks, complex enamel-dentin structures were detected in the implants. These results show that our culture technique maintained ameloblast lineage cells that were able to produce enamel in vivo. This novel subculture technique provides an important tool for tooth tissue engineering. Copyright 2008 S. Karger AG, Basel.

  15. Organ and tissue level properties are more sensitive to age than osteocyte lacunar characteristics in rat cortical bone

    DEFF Research Database (Denmark)

    Wittig, Nina; Bach-Gansmo, Fiona Linnea; Birkbak, Mie Elholm

    2016-01-01

    orientation with animal age. Hence, the evolution of organ and tissue level properties with age in rat cortical bone is not accompanied by related changes in osteocyte lacunar properties. This suggests that bone microstructure and bone matrix material properties and not the geometric properties...... of bone on the organ and tissue level, whereas features on the nano- and micrometer scale are much less explored. We investigated the age-related development of organ and tissue level bone properties such as bone volume, bone mineral density, and load to fracture and correlated these with osteocyte...

  16. World health organization perspective on implementation of International Health Regulations.

    Science.gov (United States)

    Hardiman, Maxwell Charles

    2012-07-01

    In 2005, the International Health Regulations were adopted at the 58th World Health Assembly; in June 2007, they were entered into force for most countries. In 2012, the world is approaching a major 5-year milestone in the global commitment to ensure national capacities to identify, investigate, assess, and respond to public health events. In the past 5 years, existing programs have been boosted and some new activities relating to International Health Regulations provisions have been successfully established. The lessons and experience of the past 5 years need to be drawn upon to provide improved direction for the future.

  17. Method to determine transcriptional regulation pathways in organisms

    Science.gov (United States)

    Gardner, Timothy S.; Collins, James J.; Hayete, Boris; Faith, Jeremiah

    2012-11-06

    The invention relates to computer-implemented methods and systems for identifying regulatory relationships between expressed regulating polypeptides and targets of the regulatory activities of such regulating polypeptides. More specifically, the invention provides a new method for identifying regulatory dependencies between biochemical species in a cell. In particular embodiments, provided are computer-implemented methods for identifying a regulatory interaction between a transcription factor and a gene target of the transcription factor, or between a transcription factor and a set of gene targets of the transcription factor. Further provided are genome-scale methods for predicting regulatory interactions between a set of transcription factors and a corresponding set of transcriptional target substrates thereof.

  18. Ornithine decarboxylase activity in rat organs and tissues under artificial hypobiosis.

    Science.gov (United States)

    Aksyonova, G E; Logvinovich, O S; Fialkovskaya, L A; Afanasyev, V N; Ignat'ev, D A; Kolomiytseva, I K

    2010-09-01

    The influence of hypothermia-hypoxia-hypercapnia on ornithine decarboxylase (ODC, EC 4.1.1.17) activities in rat organs and tissues and also on the thymocyte distribution throughout the cell cycle stages was studied. The state of artificial hypobiosis in rats on decrease in the body temperature to 14.4-18.0°C during 3.0-3.5 h was accompanied by drops in the ODC activities in the neocortex and liver by 50-60% and in rapidly proliferating tissues (thymus, spleen, and small intestine mucosa) by 80% of the control value. In kidneys the ODC activity raised to 200% of the control level. Twenty-four hours after termination of the cooling and replacing the rats under the standard conditions, the ODC activities in the neocortex, liver, kidneys, spleen, and intestinal mucosa returned to the control values, but remained decreased in the thymus. Forty-eight hours later the ODC activities in the thymus and spleen exceeded the normal level. The distribution of thymocytes throughout the cell cycle stages did not change in rats in the state of hypothermia (hypobiosis); 24 and 48 h after termination of the cooling the fraction of thymocytes in the S stage was decreased and the fraction of the cells in the G(0)+G(1) stage was increased. The normal distribution of thymocytes throughout the cell cycle stages recovered in 72 h. Thus, in the thymus the diminution of the ODC activity preceded the suppression of the cell proliferation rate. The tissue-specific changes in the ODC activity are suggested to reflect adaptive changes in the functional and proliferative activities of organs and tissues during the development of hypobiosis under conditions of hypothermia-hypoxia-hypercapnia.

  19. Certification of the methylmercury content in SRM 2977 mussel tissue (organic contaminants and trace elements) and SRM 1566b oyster tissue.

    Science.gov (United States)

    Tutschku, S; Schantz, M M; Horvat, M; Logar, M; Akagi, H; Emons, H; Levenson, M; Wise, S A

    2001-02-01

    The methylmercury content in two new marine bivalve mollusk tissue Standard Reference Materials (SRMs) has been certified using results of analyses from the National Institute of Standards and Technology (NIST) and two other laboratories. The certified concentrations of methylmercury were established based on the results from four and six different (independent) analytical methods, respectively, for SRM 1566b Oyster Tissue (13.2 +/- 0.7 microg/kg) and SRM 2977 Mussel Tissue (organic contaminants and trace elements) (36.2 +/- 1.7 microg/kg). The certified concentration of methylmercury in SRM 1566b is among the lowest in any certified reference material (CRM).

  20. Integrin β4 Regulates Migratory Behavior of Keratinocytes by Determining Laminin-332 Organization*s

    Science.gov (United States)

    Sehgal, Bernd U.; DeBiase, Phillip J.; Matzno, Sumio; Chew, Teng-Leong; Claiborne, Jessica N.; Hopkinson, Susan B.; Russell, Alan; Marinkovich, M. Peter; Jones, Jonathan C. R.

    2010-01-01

    Whether α6β4 integrin regulates migration remains controversial. β4 integrin-deficient (JEB) keratinocytes display aberrant migration in that they move in circles, a behavior that mirrors the circular arrays of laminin (LM)-332 in their matrix. In contrast, wild-type keratinocytes and JEB keratinocytes, induced to express β4 integrin, assemble laminin-332 in linear tracks over which they migrate. Moreover, laminin-332-dependent migration of JEB keratinocytes along linear tracks is restored when cells are plated on wild-type keratinocyte matrix, whereas wild-type keratinocytes show rotation over circular arrays of laminn-332 in JEB keratinocyte matrix. The activities of Rac1 and the actin cytoskeleton-severing protein cofilin are low in JEB keratinocytes compared with wild-type cells but are rescued following expression of wild-type β4 integrin in JEB cells. Additionally, in wild-type keratinocytes Rac1 is complexed with α6β4 integrin. Moreover, Rac1 or cofilin inactivation induces wild-type keratinocytes to move in circles over rings of laminin-332 in their matrix. Together these data indicate that laminin-332 matrix organization is determined by the α6β4 integrin/actin cytoskeleton via Rac1/cofilin signaling. Furthermore, our results imply that the organizational state of laminin-332 is a key determinant of the motility behavior of keratinocytes, an essential element of skin wound healing and the successful invasion of epidermal-derived tumor cells. PMID:16973601

  1. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

    Science.gov (United States)

    Babur, Betul Kul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B; Doran, Michael Robert

    2015-01-01

    We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

  2. Children as donors: a national study to assess procurement of organs and tissues in pediatric intensive care units.

    Science.gov (United States)

    Siebelink, Marion J; Albers, Marcel J I J; Roodbol, Petrie F; Van de Wiel, Harry B M

    2012-12-01

    A shortage of size-matched organs and tissues is the key factor limiting transplantation in children. Empirical data on procurement from pediatric donors is sparse. This study investigated donor identification, parental consent, and effectuation rates, as well as adherence to the national protocol. A national retrospective cohort study was conducted in all eight Dutch pediatric intensive care units. Records of deceased children were analyzed by an independent donation officer. Seventy-four (11%) of 683 deceased children were found to be suitable for organ donation and 132 (19%) for tissue donation. Sixty-two (84%) potential organ donors had been correctly identified; the parental consent and effectuation rate was 42%. Sixty-three (48%) potential tissue donors had been correctly identified; the parental consent and effectuation rate was 27%. Correct identification increased with age (logistic regression, organs: P = .024; tissues: P = .011). Although an overall identification rate of 84% of potential organ donors may seem acceptable, the variation observed suggests room for improvement, as does the overall low rate of identification of pediatric tissue donors. Efforts to address the shortage of organs and tissues for transplantation in children should focus on identifying potential donors and on the reasons why parents do not consent. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  3. Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Montag, Judith; Syring, Mandy; Rose, Julia; Weber, Anna-Lena; Ernstberger, Pia; Mayer, Anne-Kathrin; Becker, Edgar; Keyser, Britta; Dos Remedios, Cristobal; Perrot, Andreas; van der Velden, Jolanda; Francino, Antonio; Navarro-Lopez, Francesco; Ho, Carolyn Yung; Brenner, Bernhard; Kraft, Theresia

    2017-08-01

    HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

  4. Interactions of cadmium with copper, zinc, and iron in different organs and tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Julshamn, K.; Utne, F.; Brackkan, O.R.

    1977-01-01

    The effect of cadmium on tissue concentrations of iron, zinc and copper was studied in male rats. Two littermate groups were fed a stock diet with or without a supplement of 100 ..mu..g cadmium per g. Every three weeks ten animals from each group were sampled and the liver, kidneys, heart, lungs, spleen, testes, muscle, fur, feces and urine were individually analyzed. Except for the fur, all the other organs showed highly significantly increased levels of cadmium when compared with the control group. The iron levels were significantly depressed in all organs. As the content in the feces remained unchanged and the urinary excretion showed an increase, it could be concluded that the cadmium supplementation resulted in a depletion of the body stores of iron. The zinc levels showed a significant increase in the liver and testes and a correspondingly significant decrease in the spleen. The levels of copper generally showed no significant changes.

  5. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

  6. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis.

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J; Morrison, Shaun F

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis.

  7. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

    Science.gov (United States)

    Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

    2013-02-01

    Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

  8. Organ or tissue doses, effective dose and collective effective dose from X-ray diagnosis, in Japan

    International Nuclear Information System (INIS)

    Murayama, Takashi; Nishizawa, Kanae; Noda, Yutaka; Kumamoto, Yoshikazu; Iwai, Kazuo.

    1996-01-01

    Effective doses and collective effective doses from X-ray diagnostic examinations were calculated on the basis of the frequency of examinations estimated by a nationwide survey and the organ or tissue doses experimentally determined. The average organ or tissue doses were determined with thermoluminescence dosimeters put at various sites of organs or tissues in an adult and a child phantom. Effective doses (effective dose equivalents) were calculated as the sum of the weighted equivalent doses in all the organs or tissues of the body. As the examples of results, the effective doses per radiographic examination were approximately 7 mGy for male, and 9 mGy for female angiocardiography, and about 3 mGy for barium meal. Annual collective effective dose from X-ray diagnostic examinations in 1986 were about 104 x 10 3 person Sv from radiography and 118 x 10 3 person Sv from fluoroscopy, with the total of 222 x 10 3 person Sv. (author)

  9. Redox regulation in photosynthetic organisms: signaling, acclimation, and practical implications.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham

    2009-04-01

    Reactive oxygen species (ROS) have multifaceted roles in the orchestration of plant gene expression and gene-product regulation. Cellular redox homeostasis is considered to be an "integrator" of information from metabolism and the environment controlling plant growth and acclimation responses, as well as cell suicide events. The different ROS forms influence gene expression in specific and sometimes antagonistic ways. Low molecular antioxidants (e.g., ascorbate, glutathione) serve not only to limit the lifetime of the ROS signals but also to participate in an extensive range of other redox signaling and regulatory functions. In contrast to the low molecular weight antioxidants, the "redox" states of components involved in photosynthesis such as plastoquinone show rapid and often transient shifts in response to changes in light and other environmental signals. Whereas both types of "redox regulation" are intimately linked through the thioredoxin, peroxiredoxin, and pyridine nucleotide pools, they also act independently of each other to achieve overall energy balance between energy-producing and energy-utilizing pathways. This review focuses on current knowledge of the pathways of redox regulation, with discussion of the somewhat juxtaposed hypotheses of "oxidative damage" versus "oxidative signaling," within the wider context of physiological function, from plant cell biology to potential applications.

  10. Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

    Science.gov (United States)

    Okada, Naoyuki; Sato, Masamitsu

    2015-01-01

    Spindle microtubules capture and segregate chromosomes and, therefore, their assembly is an essential event in mitosis. To carry out their mission, many key players for microtubule formation need to be strictly orchestrated. Particularly, proteins that assemble the spindle need to be translocated at appropriate sites during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran, controls this translocation. Ran plays many roles in many cellular events: nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic spindle, and reorganization of the nuclear envelope at the mitotic exit. Although these events are seemingly distinct, recent studies demonstrate that the mechanisms underlying these phenomena are substantially the same as explained by molecular interplay of the master regulator Ran, the transport factor importin, and its cargo proteins. Our review focuses on how the transport machinery regulates mitotic progression of cells. We summarize translocation mechanisms governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP targets in fission yeast that promote spindle formation. We also discuss the coordination of the spatial and temporal regulation of proteins from the viewpoint of transport machinery. We propose that the transport machinery is an essential key that couples the spatial and temporal events in cells. PMID:26308057

  11. Ontogenetically-regulated male sterility in tissue culture - induced and spontaneous sorghum mutants

    Directory of Open Access Journals (Sweden)

    Elkonin L.A.

    2003-01-01

    Full Text Available Variability of male fertility expression in the AS-1 line, a somaclonal variant obtained from tissue culture of CMS-plant, and in the progeny of revenant '124-1' obtained from fertile tiller, which developed on CMS-plant transferred from the field to the greenhouse, was investigated. Both revertants were characterized by similar expression of male fertility during plant ontogenesis: the panicle on the main tiller was almost completely sterile whereas formation of fertile pollen grains and seed set were observed on the panicles of the shoot tillers. A clear basipetal gradient of male fertility was manifested on all panicles: the base had significantly higher per cent of fertile pollen grains in comparison with the middle part, while in the top the anthers were either absent or had few sterile pollen grains. Such an ontogenetically-regulated restoration of male fertility was controlled by nuclear genes and could be transferred through the pollen in crosses with progenitor CMS-line. Growing of AS-1 plants in the growth chambers simultaneously under a long (16/8 and a short (12/12 daylength conditions demonstrated that differences of fertility level in different tillers was not caused by change of photoperiod during plant ontogenesis and functioning of photoperiod-sensitive fertility restoring gene. Whereas, the ontogenetically-regulated expression of male fertility in both revenants was temperature-dependent and was clearly manifested under relatively cool conditions during 2-week period before the beginning of anthesis of the first panicle (average daily temperature 21°C. The increase of the average daily temperature by 2-3 С resulted in sharp increase of male fertility level. Possibility of using AS-1 line in a new "two-line system" of hybrid seed production, which require only two lines (sterile mutant and fertility restorer, is discussed.

  12. Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells

    Science.gov (United States)

    Cook, T. F.; Burke, J. S.; Bergman, K. D.; Quinn, C. O.; Jeffrey, J. J.; Partridge, N. C.

    1994-01-01

    Rat tissue inhibitor of metalloproteinases-2 (TIMP-2) was cloned from a UMR 106-01 rat osteoblastic osteosarcoma cDNA library. The 969-bp full-length clone demonstrates 98 and 86% sequence identity to human TIMP-2 at the amino acid and nucleic acid levels, respectively. Parathyroid hormone (PTH), at 10(-8) M, stimulates an approximately twofold increase in both the 4.2- and 1.0-kb transcripts over basal levels in UMR cells after 24 h of exposure. The PTH stimulation of TIMP-2 transcripts was not affected by the inhibitor of protein synthesis, cycloheximide (10(-5) M), suggesting a primary effect of the hormone. This is in contradistinction to regulation of interstitial collagenase (matrix metalloproteinase-1) by PTH in these same cells. Nuclear run-on assays demonstrate that PTH causes an increase in TIMP-2 transcription that parallels the increase in message levels. Parathyroid hormone, in its stimulation of TIMP-2 mRNA, appears to act through a signal transduction pathway involving protein kinase A (PKA) since the increase in TIMP-2 mRNA is reproduced by treatment with the cAMP analogue, 8-bromo-cAMP (5 x 10(-3) M). The protein kinase C and calcium pathways do not appear to be involved due to the lack of effect of phorbol 12-myristate 13-acetate (2.6 x 10(-6) M) and the calcium ionophore, ionomycin (10(-7) M), on TIMP-2 transcript abundance. In this respect, regulation of TIMP-2 and collagenase in osteoblastic cells by PTH are similar. However, we conclude that since stimulation of TIMP-2 transcription is a primary event, the PKA pathway must be responsible for a direct increase in transcription of this gene.

  13. Nitrogen assimilation system in maize is regulated by developmental and tissue-specific mechanisms

    KAUST Repository

    Plett, Darren

    2016-08-10

    Key message: We found metabolites, enzyme activities and enzyme transcript abundances vary significantly across the maize lifecycle, but weak correlation exists between the three groups. We identified putative genes regulating nitrate assimilation. Abstract: Progress in improving nitrogen (N) use efficiency (NUE) of crop plants has been hampered by the complexity of the N uptake and utilisation systems. To understand this complexity we measured the activities of seven enzymes and ten metabolites related to N metabolism in the leaf and root tissues of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 − throughout the lifecycle. The amino acids had remarkably similar profiles across the lifecycle except for transient responses, which only appeared in the leaves for aspartate or in the roots for asparagine, serine and glycine. The activities of the enzymes for N assimilation were also coordinated to a certain degree, most noticeably with a peak in root activity late in the lifecycle, but with wide variation in the activity levels over the course of development. We analysed the transcriptional data for gene sets encoding the measured enzymes and found that, unlike the enzyme activities, transcript levels of the corresponding genes did not exhibit the same coordination across the lifecycle and were only weakly correlated with the levels of various amino acids or individual enzyme activities. We identified gene sets which were correlated with the enzyme activity profiles, including seven genes located within previously known quantitative trait loci for enzyme activities and hypothesise that these genes are important for the regulation of enzyme activities. This work provides insights into the complexity of the N assimilation system throughout development and identifies candidate regulatory genes, which warrant further investigation in efforts to improve NUE in crop plants. © 2016, Springer Science+Business Media Dordrecht.

  14. Nitrogen assimilation system in maize is regulated by developmental and tissue-specific mechanisms

    KAUST Repository

    Plett, Darren; Holtham, Luke; Baumann, Ute; Kalashyan, Elena; Francis, Karen; Enju, Akiko; Toubia, John; Roessner, Ute; Bacic, Antony; Rafalski, Antoni; Dhugga, Kanwarpal S.; Tester, Mark A.; Garnett, Trevor; Kaiser, Brent N.

    2016-01-01

    Key message: We found metabolites, enzyme activities and enzyme transcript abundances vary significantly across the maize lifecycle, but weak correlation exists between the three groups. We identified putative genes regulating nitrate assimilation. Abstract: Progress in improving nitrogen (N) use efficiency (NUE) of crop plants has been hampered by the complexity of the N uptake and utilisation systems. To understand this complexity we measured the activities of seven enzymes and ten metabolites related to N metabolism in the leaf and root tissues of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 − throughout the lifecycle. The amino acids had remarkably similar profiles across the lifecycle except for transient responses, which only appeared in the leaves for aspartate or in the roots for asparagine, serine and glycine. The activities of the enzymes for N assimilation were also coordinated to a certain degree, most noticeably with a peak in root activity late in the lifecycle, but with wide variation in the activity levels over the course of development. We analysed the transcriptional data for gene sets encoding the measured enzymes and found that, unlike the enzyme activities, transcript levels of the corresponding genes did not exhibit the same coordination across the lifecycle and were only weakly correlated with the levels of various amino acids or individual enzyme activities. We identified gene sets which were correlated with the enzyme activity profiles, including seven genes located within previously known quantitative trait loci for enzyme activities and hypothesise that these genes are important for the regulation of enzyme activities. This work provides insights into the complexity of the N assimilation system throughout development and identifies candidate regulatory genes, which warrant further investigation in efforts to improve NUE in crop plants. © 2016, Springer Science+Business Media Dordrecht.

  15. Patterns of hybrid loss of imprinting reveal tissue- and cluster-specific regulation.

    Directory of Open Access Journals (Sweden)

    Christopher D Wiley

    Full Text Available Crosses between natural populations of two species of deer mice, Peromyscus maniculatus (BW, and P. polionotus (PO, produce parent-of-origin effects on growth and development. BW females mated to PO males (bwxpo produce growth-retarded but otherwise healthy offspring. In contrast, PO females mated to BW males (POxBW produce overgrown and severely defective offspring. The hybrid phenotypes are pronounced in the placenta and include POxBW conceptuses which lack embryonic structures. Evidence to date links variation in control of genomic imprinting with the hybrid defects, particularly in the POxBW offspring. Establishment of genomic imprinting is typically mediated by gametic DNA methylation at sites known as gDMRs. However, imprinted gene clusters vary in their regulation by gDMR sequences.Here we further assess imprinted gene expression and DNA methylation at different cluster types in order to discern patterns. These data reveal POxBW misexpression at the Kcnq1ot1 and Peg3 clusters, both of which lose ICR methylation in placental tissues. In contrast, some embryonic transcripts (Peg10, Kcnq1ot1 reactivated the silenced allele with little or no loss of DNA methylation. Hybrid brains also display different patterns of imprinting perturbations. Several cluster pairs thought to use analogous regulatory mechanisms are differentially affected in the hybrids.These data reinforce the hypothesis that placental and somatic gene regulation differs significantly, as does that between imprinted gene clusters and between species. That such epigenetic regulatory variation exists in recently diverged species suggests a role in reproductive isolation, and that this variation is likely to be adaptive.

  16. Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

    Science.gov (United States)

    Goh, Saik-Kia; Bertera, Suzanne; Olsen, Phillip; Candiello, Joe; Halfter, Willi; Uechi, Guy; Balasubramani, Manimalha; Johnson, Scott; Sicari, Brian; Kollar, Elizabeth; Badylak, Stephen F.; Banerjee, Ipsita

    2013-01-01

    Approximately 285 million people worldwide suffer from diabetes, with insulin supplementation as the most common treatment measure. Regenerative medicine approaches such as a bioengineered pancreas has been proposed as potential therapeutic alternatives. A bioengineered pancreas will benefit from the development of a bioscaffold that supports and enhances cellular function and tissue development. Perfusion-decellularized organs are a likely candidate for use in such scaffolds since they mimic compositional, architectural and biomechanical nature of a native organ. In this study, we investigate perfusion-decellularization of whole pancreas and the feasibility to recellularize the whole pancreas scaffold with pancreatic cell types. Our result demonstrates that perfusion-decellularization of whole pancreas effectively removes cellular and nuclear material while retaining intricate three-dimensional microarchitecture with perfusable vasculature and ductal network and crucial extracellular matrix (ECM) components. To mimic pancreatic cell composition, we recellularized the whole pancreas scaffold with acinar and beta cell lines and cultured up to 5 days. Our result shows successful cellular engraftment within the decellularized pancreas, and the resulting graft gave rise to strong up-regulation of insulin gene expression. These findings support biological utility of whole pancreas ECM as a biomaterials scaffold for supporting and enhancing pancreatic cell functionality and represent a step toward bioengineered pancreas using regenerative medicine approaches. PMID:23787110

  17. Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

    Directory of Open Access Journals (Sweden)

    Alicia Lundby

    2012-08-01

    Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

  18. Quantitative tissue-specific dynamics of in vivo GILZ mRNA expression and regulation by endogenous and exogenous glucocorticoids.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; Jusko, William J; DuBois, Debra C

    2015-06-01

    Glucocorticoids (GC) are steroid hormones, which regulate metabolism and immune function. Synthetic GCs, or corticosteroids (CS), have appreciable clinical utility via their ability to suppress inflammation in immune-mediated diseases like asthma and rheumatoid arthritis. Recent work has provided insight to novel GC-induced genes that mediate their anti-inflammatory effects, including glucocorticoid-induced leucine zipper (GILZ). Since GILZ comprises an important part of GC action, its regulation by both drug and hormone will influence CS therapy. In addition, GILZ expression is often employed as a biomarker of GC action, which requires judicious selection of sampling time. Understanding the in vivo regulation of GILZ mRNA expression over time will provide insight into both the physiological regulation of GILZ by endogenous GC and the dynamics of its enhancement by CS. A highly quantitative qRT-PCR assay was developed for measuring GILZ mRNA expression in tissues obtained from normal and CS-treated rats. This assay was applied to measure GILZ mRNA expression in eight tissues; to determine its endogenous regulation over time; and to characterize its dynamics in adipose tissue, muscle, and liver following treatment with CS. We demonstrate that GILZ mRNA is expressed in several tissues. GILZ mRNA expression in adipose tissue displayed a robust circadian rhythm that was entrained with the circadian oscillation of endogenous corticosterone; and is strongly enhanced by acute and chronic dosing. Single dosing also enhanced GILZ mRNA in muscle and liver, but the dynamics varied. In conclusion, GILZ is widely expressed in the rat and highly regulated by endogenous and exogenous GCs. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  19. Bioinformatical Analysis of Organ-Related (Heart, Brain, Liver, and Kidney and Serum Proteomic Data to Identify Protein Regulation Patterns and Potential Sepsis Biomarkers

    Directory of Open Access Journals (Sweden)

    Andreas Hohn

    2018-01-01

    Full Text Available During the last years, proteomic studies have revealed several interesting findings in experimental sepsis models and septic patients. However, most studies investigated protein alterations only in single organs or in whole blood. To identify possible sepsis biomarkers and to evaluate the relationship between protein alteration in sepsis affected organs and blood, proteomics data from the heart, brain, liver, kidney, and serum were analysed. Using functional network analyses in combination with hierarchical cluster analysis, we found that protein regulation patterns in organ tissues as well as in serum are highly dynamic. In the tissue proteome, the main functions and pathways affected were the oxidoreductive activity, cell energy generation, or metabolism, whereas in the serum proteome, functions were associated with lipoproteins metabolism and, to a minor extent, with coagulation, inflammatory response, and organ regeneration. Proteins from network analyses of organ tissue did not correlate with statistically significantly regulated serum proteins or with predicted proteins of serum functions. In this study, the combination of proteomic network analyses with cluster analyses is introduced as an approach to deal with high-throughput proteomics data to evaluate the dynamics of protein regulation during sepsis.

  20. Regulation of cell behavior and tissue patterning by bioelectrical signals: challenges and opportunities for biomedical engineering.

    Science.gov (United States)

    Levin, Michael; Stevenson, Claire G

    2012-01-01

    Achieving control over cell behavior and pattern formation requires molecular-level understanding of regulatory mechanisms. Alongside transcriptional networks and biochemical gradients, there functions an important system of cellular communication and control: transmembrane voltage gradients (V(mem)). Bioelectrical signals encoded in spatiotemporal changes of V(mem) control cell proliferation, migration, and differentiation. Moreover, endogenous bioelectrical gradients serve as instructive cues mediating anatomical polarity and other organ-level aspects of morphogenesis. In the past decade, significant advances in molecular physiology have enabled the development of new genetic and biophysical tools for the investigation and functional manipulation of bioelectric cues. Recent data implicate V(mem) as a crucial epigenetic regulator of patterning events in embryogenesis, regeneration, and cancer. We review new conceptual and methodological developments in this fascinating field. Bioelectricity offers a novel way of quantitatively understanding regulation of growth and form in vivo, and it reveals tractable, powerful control points that will enable truly transformative applications in bioengineering, regenerative medicine, and synthetic biology.

  1. From Prevention To Advance In Biomedicine: The Transfer Of Organs And Tissues

    Directory of Open Access Journals (Sweden)

    Gemma Flores-Pons

    2013-07-01

    Full Text Available Currently, within Western societies, we can see new practices that are at once reality and fiction as they unfold in the terrain of the possible, the imaginable and the optimum. In the present paper, we focus on the case of organ and tissues transfer to describe how those biomedical actants and practices involved are articulated, configuring it as an anticipatory process, namely as a constant movement attempting to bring mobile futures to the present. Drawing on an ethnographic study exploring the everyday activity of a Spanish transplant coordination team,, we begin by suggesting that donation gets inserted as an imperative in the increasingly individualized management of the citizens’ biological becomings. Secondly, we turn to how the articulation of the brain death diagnosis functions as an entity capable of creating coherence between the different temporalities produced in the organs and tissues transfer. Then, we show the optimization mechanisms that operate within the waiting lists materializing imagined futures. Finally, by way of describing the permanent latency in which the transplant coordination teams work, we give an account of how biomedicine is turning away from generating practices inserted in a logic of prevention to practices that obey a logic of preparation.

  2. In-house coordination project for organ and tissue procurement: social responsibility and promising results.

    Science.gov (United States)

    Silva, Vanessa Silva E; Moura, Luciana Carvalho; Martins, Luciana Ribeiro; Santos, Roberta Cristina Cardoso Dos; Schirmer, Janine; Roza, Bartira de Aguiar

    2016-01-01

    to report the results of evaluation regarding changes in the number of potential donor referrals, actual donors, and conversion rates after the implementation of an in-house organ and tissue donation for transplantation coordination project. epidemiological study, both retrospective and transversal, was performed with organ donation data from the Secretariat of Health for the State and the in-house organ donation coordination project of a beneficent hospital. The data was compared using nonparametric statistical Mann-Whitney test, and the Student's t-test, considering a significance level of 5% (p <0.05). there were statistically significant differences (p < 0.05), before and after the implementation of the project on the number of potential donor notification/month (3.05 - 4.7 ), number of actual donor/month (0.78 to 1.60) and rate of conversion ( 24.7 to 34.8 %). The hospitals 1, 2, 7 and 8 had significant results in potential donor, actual donor or conversion rate. the presence of an in-house coordinator is promising and beneficial, the specialist is important to change the indicators of efficiency, which consequently reduces the waiting lists for organ transplants.

  3. Bereaved donor families' experiences of organ and tissue donation, and perceived influences on their decision making.

    Science.gov (United States)

    Sque, Magi; Walker, Wendy; Long-Sutehall, Tracy; Morgan, Myfanwy; Randhawa, Gurch; Rodney, Amanda

    2018-06-01

    To elicit bereaved families' experiences of organ and tissue donation. A specific objective was to determine families' perceptions of how their experiences influenced donation decision-making. Retrospective, qualitative interviews were undertaken with 43 participants of 31 donor families to generate rich, informative data. Participant recruitment was via 10 National Health Service Trusts, representative of five regional organ donation services in the UK. Twelve families agreed to DBD, 18 agreed to DCD, 1 unknown. Participants' responses were contextualised using a temporal framework of 'The Past', which represented families' prior knowledge, experience, attitudes, beliefs, and intentions toward organ donation; 'The Present', which incorporated the moment in time when families experienced the potential for donation; and 'The Future', which corresponded to expectations and outcomes arising from the donation decision. Temporally interwoven experiences appeared to influence families' decisions to donate the organs of their deceased relative for transplantation. The influence of temporality on donation-decision making is worthy of consideration in the planning of future education, policy, practice, and research for improved rates of family consent to donation. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Classification of trace elements in tissues from organic and conventional French pig production.

    Science.gov (United States)

    Parinet, Julien; Royer, Eric; Saint-Hilaire, Mailie; Chafey, Claude; Noël, Laurent; Minvielle, Brice; Dervilly-Pinel, Gaud; Engel, Erwan; Guérin, Thierry

    2018-07-01

    This study assesses the impact of the farming system on the levels of copper, zinc, arsenic, cadmium, lead and mercury in pig tissues from three types of production (Organic (n = 28), Label Rouge (n = 12) and Conventional (n = 30)) randomly sampled in different slaughterhouses. All the concentrations were below regulatory limits. In muscles, Cu, Zn and As were measured at slightly higher levels in organic samples but no differences between organic and Label Rouge was observed. Livers from conventional and Label Rouge pig farms exhibited higher Zn and Cd contents than the organic ones, probably due to different practice in zinc or phytase supplementation of fattening diets. Principal component analysis indicated a correlation between Cu and As concentrations in liver and carcass weight, and between Zn and Cd liver levels and lean meat percentage. The linear discriminant analysis succeeded in predicting the farming process on the basis of the lean meat percentage and the liver Cd level. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

    International Nuclear Information System (INIS)

    Davis, W.C.; Christopher, S.J.; Pugh, Rebecca S.; Donard, O.F.X.; Krupp, Eva A.; Point, David; Horvat, Milena; Gibicar, D.; Kljakovic-Gaspic, Z.; Porter, Barbara J.; Schantz, Michele M.

    2007-01-01

    This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST. (orig.)

  6. Certification of methylmercury content in two fresh-frozen reference materials: SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis)

    Energy Technology Data Exchange (ETDEWEB)

    Davis, W.C.; Christopher, S.J.; Pugh, Rebecca S. [National Institute of Standards and Technology (NIST), Hollings Marine Laboratory, Analytical Chemistry Division, Charleston, SC (United States); Donard, O.F.X.; Krupp, Eva A. [LCABIE/CNRS Helioparc Pau-Pyrenees, Pau (France); Point, David [National Institute of Standards and Technology (NIST), Hollings Marine Laboratory, Analytical Chemistry Division, Charleston, SC (United States); LCABIE/CNRS Helioparc Pau-Pyrenees, Pau (France); Horvat, Milena; Gibicar, D. [Jozef Stefan Institute, Ljubljana (Slovenia); Kljakovic-Gaspic, Z. [Jozef Stefan Institute, Ljubljana (Slovenia); Institute for Medical Research and Occupational Health, Zagreb (Croatia); Porter, Barbara J.; Schantz, Michele M. [National Institute of Standards and Technology (NIST), Analytical Chemistry Division, Gaithersburg, MD (United States)

    2007-04-15

    This paper describes the development of two independent analytical methods for the extraction and quantification of methylmercury from marine biota. The procedures involve microwave extraction, followed by derivatization and either headspace solid-phase microextraction (SPME) with a polydimethylsiloxane (PDMS)-coated silica fiber or back-extraction into iso-octane. The identification and quantification of the extracted compounds is carried out by capillary gas chromatography/mass spectrometric (GC/MS) and inductively coupled plasma mass spectrometric (GC/ICP-MS) detection. Both methods were validated for the determination of methylmercury (MeHg) concentrations in a variety of biological standard reference materials (SRMs) including fresh-frozen tissue homogenates of SRM 1946 Lake Superior fish tissue and SRM 1974a organics in mussel tissue (Mytilus edulis) and then applied to the certification effort of SRM 1947 Lake Michigan fish tissue and SRM 1974b organics in mussel tissue (Mytilus edulis). While past certifications of methylmercury in tissue SRMs have been based on two independent methods from the National Institute of Standards and Technology (NIST) and participating laboratories, the methods described within provide improved protocols and will allow future certification efforts to be based on at least two independent analytical methods within NIST. (orig.)

  7. Specific expression of bioluminescence reporter gene in cardiomyocyte regulated by tissue specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong; Tae, Seong Ho; Le, Nguyen Uyen Chi; Min, Jung Joon [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-07-01

    As the human heart is not capable of regenerating the great numbers of cardiac cells that are lost after myocardial infarction, impaired cardiac function is the inevitable result of ischemic disease. Recently, human embryonic stem cells (hESCs) have gained popularity as a potentially ideal cell candidate for tissue regeneration. In particular, hESCs are capable of cardiac lineage-specific differentiation and confer improvement of cardiac function following transplantation into animal models. Although such data are encouraging, the specific strategy for in vivo and non-invasive detection of differentiated cardiac lineage is still limited. Therefore, in the present study, we established the gene construction in which the optical reporter gene Firefly luciferase was controlled by Myosin Heavy Chain promoter for specific expressing in heart cells. The vector consisting of - MHC promoter and a firefly luciferase coding sequence flanked by full-length bovine growth hormone (BGH) 3'-polyadenylation sequence based on pcDNA3.1- vector backbone. To test the specific transcription of this promoter in g of MHC-Fluc or CMV-Flue (for control) plasmid DNA in myocardial tissue, 20 phosphate-buffered saline was directly injected into mouse myocardium through a midline sternotomy and liver. After 1 week of injection, MHC-Fluc expression was detected from heart region which was observed under cooled CCD camera of in vivo imaging system but not from liver. In control group injected with CMV-Flue, the bioluminescence was detected from all these organs. The expression of Flue under control of Myosin Heavy Chain promoter may become a suitable optical reporter gene for stem cell-derived cardiac lineage differentiation study.

  8. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue

    Science.gov (United States)

    Salameh, Ahmad; Daquinag, Alexes C.; Staquicini, Daniela I.; An, Zhiqiang; Pasqualini, Renata; Kolonin, Mikhail G.

    2016-01-01

    We have previously identified prohibitin (PHB) and annexin A2 (ANX2) as proteins interacting on the surface of vascular endothelial cells in white adipose tissue (WAT) of humans and mice. Here, we demonstrate that ANX2 and PHB also interact in adipocytes. Mice lacking ANX2 have normal WAT vascularization, adipogenesis, and glucose metabolism but display WAT hypotrophy due to reduced fatty acid uptake by WAT endothelium and adipocytes. By using cell culture systems in which ANX2/PHB binding is disrupted either genetically or through treatment with a blocking peptide, we show that fatty acid transport efficiency relies on this protein complex. We also provide evidence that the interaction between ANX2 and PHB mediates fatty acid transport from the endothelium into adipocytes. Moreover, we demonstrate that ANX2 and PHB form a complex with the fatty acid transporter CD36. Finally, we show that the colocalization of PHB and CD36 on adipocyte surface is induced by extracellular fatty acids. Together, our results suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases. PMID:27468426

  9. Progestin and thrombin regulate tissue factor expression in human term decidual cells.

    Science.gov (United States)

    Lockwood, C J; Murk, W; Kayisli, U A; Buchwalder, L F; Huang, S-T; Funai, E F; Krikun, G; Schatz, F

    2009-06-01

    Perivascular cell membrane-bound tissue factor (TF) initiates hemostasis via thrombin generation. The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear. The objective of the study were to identify TF-expressing cells at the maternal-fetal interface in term and preterm decidual sections by immunohistochemistry and evaluate progestin, thrombin, TNF-alpha, and IL-1beta effects on TF expression by cultured human term decidual cells (DCs). Serial placental sections were immunostained for TF. Leukocyte-free term DC monolayers were incubated with 10(-8) M estradiol (E2) or E2 plus 10(-7) M medroxyprogestrone acetate (MPA) +/- thrombin or TNF-alpha or IL-1beta. ELISA and Western blotting assessed TF in cell lysates. Quantitative real-time RT-PCR measured TF mRNA levels. Immunolocalized TF in DC membranes in preterm and term placental sections displayed higher Histologic Scores than villous mesenchymal cells (P term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.

  10. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

    Science.gov (United States)

    Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

    2015-07-01

    A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model.

    Directory of Open Access Journals (Sweden)

    Darren Paul Burke

    Full Text Available Extrinsic mechanical signals have been implicated as key regulators of mesenchymal stem cell (MSC differentiation. It has been possible to test different hypotheses for mechano-regulated MSC differentiation by attempting to simulate regenerative events such as bone fracture repair, where repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues such as substrate stiffness and oxygen tension as key regulators of MSC differentiation; however it remains unclear if and how such cues determine stem cell fate in vivo. As part of this study, a computational model was developed to test the hypothesis that substrate stiffness and oxygen tension regulate stem cell differentiation during fracture healing. Rather than assuming mechanical signals act directly on stem cells to determine their differentiation pathway, it is postulated that they act indirectly to regulate angiogenesis and hence partially determine the local oxygen environment within a regenerating tissue. Chondrogenesis of MSCs was hypothesized to occur in low oxygen regions, while in well vascularised regions of the regenerating tissue a soft local substrate was hypothesised to facilitate adipogenesis while a stiff substrate facilitated osteogenesis. Predictions from the model were compared to both experimental data and to predictions of a well established computational mechanobiological model where tissue differentiation is assumed to be regulated directly by the local mechanical environment. The model predicted all the major events of fracture repair, including cartilaginous bridging, endosteal and periosteal bony bridging and bone remodelling. It therefore provides support for the hypothesis that substrate stiffness and oxygen play a key role in regulating MSC fate during regenerative events such as fracture healing.

  12. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    DEFF Research Database (Denmark)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal

    2013-01-01

    , isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several...

  13. SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

    Science.gov (United States)

    Barker, Thomas H; Baneyx, Gretchen; Cardó-Vila, Marina; Workman, Gail A; Weaver, Matt; Menon, Priya M; Dedhar, Shoukat; Rempel, Sandra A; Arap, Wadih; Pasqualini, Renata; Vogel, Viola; Sage, E Helene

    2005-10-28

    SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

  14. Selecting "saviour siblings": reconsidering the regulation in Australia of pre-implantation genetic diagnosis in conjunction with tissue typing.

    Science.gov (United States)

    Taylor-Sands, Michelle

    2007-05-01

    In recent years, pre-implantation genetic diagnosis (PGD) has been developed to enable the selection of a tissue type matched "saviour sibling" for a sick child. This article examines the current regulatory framework governing PGD in Australia. The availability of PGD in Australia to create a saviour sibling depends on the regulation of ART services by each State and Territory. The limitations on the use of PGD vary throughout Australia, according to the level of regulation of ART in each jurisdiction. This article considers the limitations on the use of PGD for tissue typing in Australia and argues that some of these should be removed for a more consistent national approach. In particular, the focus in ART legislation on the "paramount interests" of the child to be born is inappropriate for the application of tissue typing, which necessarily involves the interests of other family members.

  15. DMPD: Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andCTRPs. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17681884 Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs an...ng) (.svg) (.html) (.csml) Show Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs andC...TRPs. PubmedID 17681884 Title Adipose tissue as an immunological organ: Toll-like

  16. Environmental processes leading to the presence of organically bound plutonium in plant tissues consumed by animals

    International Nuclear Information System (INIS)

    Wildung, R.E.; Garland, T.R.; Cataldo, D.A.

    1979-01-01

    Using a proposed model for Pu behaviour to integrate current knowledge, information is presented on the chemical/biochemical processes governing the form of Pu in soils and plants and the relationship of these phenomena to gut absorption in animals. Regardless of the source term, Pu behaviour in the soil will be governed by the chemistry of Pu(IV), which predominates over Pu(VI) due to reductive reactions in the soil and at the plant root surface. The soil behaviour of Pu(IV) is governed by (1) hydrolysis, which results in insolubilization and sorption on solid phases, and (2) complexation with inorganic and organic ligands, which stabilize Pu(IV) against hydrolysis and increase solubility. These competing processes likely represent the rate-limiting step in the ingestion pathway because plants do not effectively discriminate against the soluble Pu(IV) ion. Following dissociation of soil Pu(IV) complexes at the outer root surface, Pu is transported across the plant root membrane as the Pu(IV) ion and translocated as Pu(IV) complexes with plant organic ligands. Redistribution of Pu occurs as the plant grows, with initial increases in stem tissues followed by accumulation in roots as the plant matures. The Pu concentration decreases up the plant and seeds contain the lowest Pu concentrations. The gastro-intestinal absorption of Pu requires the presence of soluble Pu forms and hydrolysis/complexation reactions in the gut likely govern solubility. The acidity of the gut is not sufficient to retard hydrolysis of Pu(IV). Therefore, the gastro-intestinal absorption of Pu organically bound in plant tissues is increased relative to Pu administered in hydrolysable solutions. (author)

  17. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

  18. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  19. Physiologically Distributed Loading Patterns Drive the Formation of Zonally Organized Collagen Structures in Tissue-Engineered Meniscus.

    Science.gov (United States)

    Puetzer, Jennifer L; Bonassar, Lawrence J

    2016-07-01

    The meniscus is a dense fibrocartilage tissue that withstands the complex loads of the knee via a unique organization of collagen fibers. Attempts to condition engineered menisci with compression or tensile loading alone have failed to reproduce complex structure on the microscale or anatomic scale. Here we show that axial loading of anatomically shaped tissue-engineered meniscus constructs produced spatial distributions of local strain similar to those seen in the meniscus when the knee is loaded at full extension. Such loading drove formation of tissue with large organized collagen fibers, levels of mechanical anisotropy, and compressive moduli that match native tissue. Loading accelerated the development of native-sized and aligned circumferential and radial collagen fibers. These loading patterns contained both tensile and compressive components that enhanced the major biochemical and functional properties of the meniscus, with loading significantly improved glycosaminoglycan (GAG) accumulation 200-250%, collagen accumulation 40-55%, equilibrium modulus 1000-1800%, and tensile moduli 500-1200% (radial and circumferential). Furthermore, this study demonstrates local changes in mechanical environment drive heterogeneous tissue development and organization within individual constructs, highlighting the importance of recapitulating native loading environments. Loaded menisci developed cartilage-like tissue with rounded cells, a dense collagen matrix, and increased GAG accumulation in the more compressively loaded horns, and fibrous collagen-rich tissue in the more tensile loaded outer 2/3, similar to native menisci. Loaded constructs reached a level of organization not seen in any previous engineered menisci and demonstrate great promise as meniscal replacements.

  20. Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice

    Directory of Open Access Journals (Sweden)

    Gue-Tae Chae

    1992-01-01

    Full Text Available RIPK 2 is adapter molecule in the signal pathway involved in Toll-like receptors. However, there has been no reported association between receptor-interacting serine/threonine kinase 2 (RIPK 2 expression and the infectious diseases involving mycobacterial infection. This study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of Mycobacterium leprae-infected nu/nu mice compared with those of the M. leprae non-infected nu/nu mice. It was observed that the interlukin-12p40 and interferon-γ genes involved in the susceptibility of M. leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection.

  1. The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix

    Science.gov (United States)

    Landis, W. J.

    1995-01-01

    High-voltage electron-microscopic tomographic (3D) studies of the ultrastructural interaction between mineral and organic matrix in a variety of calcified tissues reveal different crystal structural and organizational features in association with their respective organic matrices. In brittle or weak pathologic or ectopic calcifications, including examples of osteogenesis imperfecta, calciphylaxis, calcergy, and dermatomyositis, hydroxyapatite crystals occur in various sizes and shapes and are oriented and aligned with respect to collagen in a manner which is distinct from that found in normal calcified tissues. A model of collagen-mineral interaction is proposed which may account for the observed crystal structures and organization. The results indicate that the ultimate strength, support, and other mechanical properties provided by a calcified tissue are dependent in part upon the molecular structure and arrangement of its constituent mineral crystals within their organic matrix.

  2. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    Science.gov (United States)

    Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A.; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J.P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arking, Dan E.; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Inês; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S.F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F.; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H. Franco; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H.; Goodarzi, Mark O.; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N William N.W.R.; Renström, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H.-H.; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P.A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njølstad, Inger; Schwarz, Peter EH.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H.-Erich; Palmer, Colin N.A.; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J.F.; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation. PMID:27618452

  3. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

    Science.gov (United States)

    Ehret, Georg B; Ferreira, Teresa; Chasman, Daniel I; Jackson, Anne U; Schmidt, Ellen M; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J; Shungin, Dmitry; Hughes, Maria F; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M; Magnusson, Patrik K; Salfati, Elias L; Rallidis, Loukianos S; Theusch, Elizabeth; Smith, Andrew J P; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H; Joehanes, Roby; Kim, Stuart K; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O; Bochud, Murielle; Absher, Devin; Adair, Linda S; Amin, Najaf; Arking, Dan E; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R; Barroso, Inês; Bevan, Stephen; Bis, Joshua C; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Bornstein, Stefan R; Brown, Morris J; Burnier, Michel; Cabrera, Claudia P; Chambers, John C; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S; Chung, Ren-Hua; Collins, Francis S; Connell, John M; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F; Doney, Alex S F; Drenos, Fotios; Edkins, Sarah; Eicher, John D; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H Franco; Franco-Cereceda, Anders; Fraser, Ross M; Ganesh, Santhi K; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H; Goodarzi, Mark O; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A; Hingorani, Aroon D; Hirschhorn, Joel N; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A; Hunt, Steven C; Ikram, M Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S; Kosova, Gulum; Krauss, Ronald M; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S; Marouli, Eirini; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E; Morris, Andrew D; Morrison, Alanna C; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J; O'Reilly, Paul F; Ong, Ken K; Paccaud, Fred; Palmer, Cameron D; Parsa, Afshin; Pedersen, Nancy L; Penninx, Brenda W; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P; Psaty, Bruce M; Quertermous, Thomas; Rao, Dabeeru C; Rasheed, Asif; Rayner, N William N W R; Renström, Frida; Rettig, Rainer; Rice, Kenneth M; Roberts, Robert; Rose, Lynda M; Rossouw, Jacques; Samani, Nilesh J; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H-H; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H; Smith, Albert V; Sosa, Maria X; Spector, Tim D; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E; Stringham, Heather M; Sundstrom, Johan; Swift, Amy J; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D; Tremoli, Elena; Uitterlinden, Andre G; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M; van Iperen, Erik P A; Vasan, Ramachandran S; Verwoert, Germaine C; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F; Vollenweider, Peter; Wagner, Aline; Wain, Louise V; Wareham, Nicholas J; Watkins, Hugh; Weder, Alan B; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F; Wong, Tien Y; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S; Mohlke, Karen L; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J; Willer, Cristen J; Franke, Lude; Hovingh, G Kees; Taylor, Kent D; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L; Njølstad, Inger; Schwarz, Peter Eh; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I; Rotter, Jerome I; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G; Kuulasmaa, Kari; Franks, Paul W; Hamsten, Anders; Wichmann, H-Erich; Palmer, Colin N A; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J F; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P; Newton-Cheh, Christopher; Munroe, Patricia B

    2016-10-01

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

  4. Diversity and regulation of ATP sulfurylase in photosynthetic organisms

    Directory of Open Access Journals (Sweden)

    Laura ePrioretti

    2014-11-01

    Full Text Available ATP sulfurylase (ATPS catalyzes the first committed step in the sulfate assimilation pathway, the activation of sulfate prior to its reduction. ATPS has been studied in only a few model organisms and even in these cases to a much smaller extent than the sulfate reduction and cysteine synthesis enzymes. This is possibly because the latter were considered of greater regulatory importance for sulfate assimilation. Recent evidences (reported in this paper challenge this view and suggest that ATPSes may have a crucial regulatory role in sulfate assimilation, at least in algae.In the ensuing text, we summarize the current knowledge on ATPS, with special attention to the processes that control its activity and gene(s expression. Special attention is given to algae ATPSes. The focus on algae is the consequence of the fact that a comprehensive investigation of ATPSes revealed that the algal enzymes, especially those that are most likely involved in the pathway of sulfate reduction to cysteine, possess features that are not present in other organisms. For instance, algae ATPSes show a great diversity of isoforms and a high content of cysteine residues, whose positions are often conserved. It is interesting that, at least with respect to the number of cysteines, the ATPSes of eukaryotic algae are closer to the marine cyanobacteria of the genera Synechococcus and Prochlorococcus and are more distant from freshwater cyanobacteria. These characteristics might have evolved in parallel with the radiation of algae in the oceans and the increase of sulfate concentration in seawater.

  5. Xenopus msx-1 regulates dorso-ventral axis formation by suppressing the expression of organizer genes.

    Science.gov (United States)

    Takeda, M; Saito, Y; Sekine, R; Onitsuka, I; Maeda, R; Maéno, M

    2000-06-01

    We demonstrated previously that Xmsx-1 is involved in mesoderm patterning along the dorso-ventral axis, under the regulation of BMP-4 signaling. When Xmsx-1 RNA was injected into the dorsal blastomeres, a mass of muscle tissue formed instead of notochord. This activity was similar to that of Xwnt-8 reported previously. In this study, we investigated whether the activity of Xmsx-1 is related to the ventralizing signal and myogenesis promoting factor, Xwnt-8. Whole-mount in situ hybridization showed that Xmsx-1, Xwnt-8, and XmyoD were expressed in overlapping areas, including the ventro-lateral marginal zone at mid-gastrula stage. The expression of XmyoD was induced by the ectopic expression of either Xmsx-1 or Xwnt-8 in dorsal blastomeres, and Xwnt-8 was induced by the ectopic expression of Xmsx-1. On the other hand, the expression of Xmsx-1 was not affected by the loading of pCSKA-Xwnt-8 or dominant-negative Xwnt-8 (DN-Xwnt-8) RNA. In addition, Xmsx-1 RNA did not abrogate the formation of notochord if coinjected with DN-Xwnt-8 RNA. These results suggest that Xmsx-1 functions upstream of the Xwnt-8 signal. Furthermore, the antagonistic function of Xmsx-1 to the expression of organizer genes, such as Xlim-1 and goosecoid, was shown by in situ hybridization analysis and luciferase reporter assay using the goosecoid promoter construct. Finally if Xmsx-1/VP-16 fusion RNA, which was expected to function as a dominant-negative Xmsx-1, was injected into ventral blastomeres, a partial secondary axis formed in a significant number of embryos. In such embryos, the activity of luciferase, under the control of goosecoid promoter sequence, was significantly elevated at gastrula stage. These results led us to conclude that Xmsx-1 plays a central role in establishing dorso-ventral axis in gastrulating embryo, by suppressing the expression of organizer genes.

  6. Soft tissue organ masses of Beagles as a function of age

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Gillett, N.A.; Gerlach, R.F.

    1988-01-01

    Beagle dogs have been used for the past 30 yr for radio toxicological studies in several Department of Energy laboratories. Since the animals are maintained for their life span, it is important to recognize the potential importance of age-related changes in organ masses, particularly as they relate to dosimetry. To determine the extent and magnitude of soft-tissue organ mass changes relative to age and gender of Beagle dogs, groups of three male and three female dogs at ages 2.7, 6.0, 8.8, 11.7, and 14.0 yr were sacrificed. The resulting organ mass data were analyzed by linear regression both in terms of gross mass and mass normalized to whole-body mass. The results indicated that very little change in masses could be detected in this population over the age range studied, which includes the median life span of dogs In this colony. The rate of change of masses was shown to have an insignificant effect on the calculation of radiation dose, even over long time periods. (author)

  7. Dosimetry of {sup 223}Ra-chloride: dose to normal organs and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nosske, Dietmar [Federal Office for Radiation Protection (BfS), Department of Radiation and Health, Oberschleissheim (Germany)

    2013-02-15

    {sup 223}Ra-Chloride (also called Alpharadin {sup registered}) targets bone metastases with short range alpha particles. In recent years several clinical trials have been carried out showing, in particular, the safety and efficacy of palliation of painful bone metastases in patients with castration-resistant prostate cancer using {sup 223}Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of {sup 223}Ra-chloride according to the present International Commission on Radiological Protection (ICRP) model for radium. Absorbed doses were calculated for 25 organs or tissues. Bone endosteum and red bone marrow show the highest dose coefficients followed by liver, colon and intestines. After a treatment schedule of six intravenous injections with 0.05 MBq/kg of {sup 223}Ra-chloride each, corresponding to 21 MBq for a 70 kg patient, the absorbed alpha dose to the bone endosteal cells is about 16 Gy and the corresponding absorbed dose to the red bone marrow is approximately 1.5 Gy. The comprehensive list of dose coefficients presented in this work will assist in comparing and evaluating organ doses from various therapy modalities used in nuclear medicine and will provide a base for further development of patient-specific dosimetry. (orig.)

  8. Soft tissue organ masses of Beagles as a function of age

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, R A; Gillett, N A; Gerlach, R F

    1988-12-01

    Beagle dogs have been used for the past 30 yr for radio toxicological studies in several Department of Energy laboratories. Since the animals are maintained for their life span, it is important to recognize the potential importance of age-related changes in organ masses, particularly as they relate to dosimetry. To determine the extent and magnitude of soft-tissue organ mass changes relative to age and gender of Beagle dogs, groups of three male and three female dogs at ages 2.7, 6.0, 8.8, 11.7, and 14.0 yr were sacrificed. The resulting organ mass data were analyzed by linear regression both in terms of gross mass and mass normalized to whole-body mass. The results indicated that very little change in masses could be detected in this population over the age range studied, which includes the median life span of dogs In this colony. The rate of change of masses was shown to have an insignificant effect on the calculation of radiation dose, even over long time periods. (author)

  9. Stratum Corneum Hydration and Skin Surface pH Variation Indicate that Organ Blood Flow Is Regulated by Meridian Activity at Certain Hours

    Directory of Open Access Journals (Sweden)

    Li-Fan Chuang

    2014-11-01

    Full Text Available Day and night are regular occurrences in nature, and the organs and tissues in living bodies follow this cycle. The sympathetic nervous system (SNS at various time points regulates organ excitation to maintain healthy functions in the living body. The energy required from basal metabolism can be used to explain living organisms according to the traditional Chinese medicine (TCM concept of relationships between meridian directions and organs at various times (organs “at rest” and organs “in operation”. By monitoring skin reactions after applying a cream, we speculated regular blood flow changes, and established an animated hourglass-shaped trajectory diagram to visualize these changes. A combination of TCM and physiological perspectives were considered to explain how the cardiovascular system produces energy. These two perspectives were applied to interpret the correlation between the SNS and organ metabolism.

  10. A Radially Organized Multipatterned Device as a Diagnostic Tool for the Screening of Topographies in Tissue Engineering Biomaterials

    NARCIS (Netherlands)

    Babo, P.S.; Klymov, A.; Riet, J. te; Reis, R.L.; Jansen, J.A.; Gomes, M.E.; Walboomers, X.F.

    2016-01-01

    Micro- and nanotextured biomaterial surfaces have been widely studied for their capacity to drive the regeneration of organized tissues. Nanotopographical features in the shape of groove-ridge patterns aim at mimicking the extracellular matrix organization. However, to date, a wide array of groove

  11. Effects of organic and inorganic dietary selenium supplementation on gene expression profiles in oviduct tissue from broiler-breeder hens.

    Science.gov (United States)

    Brennan, K M; Crowdus, C A; Cantor, A H; Pescatore, A J; Barger, J L; Horgan, K; Xiao, R; Power, R F; Dawson, K A

    2011-05-01

    Selenium (Se) is an essential component of at least 25 selenoproteins involved in a multitude of physiological functions, including reproduction. However, relatively little is known about the mechanisms by which Se exerts its physiological effects in reproductive tissue. The objective of this study was to compare the effect of long-term inorganic Se (sodium selenite, SS) and organic yeast-derived Se (Sel-Plex(®), SP) supplementations on tissue Se content and gene expression patterns in the oviduct of broiler-breeder hens. Hens were randomly assigned at 6 weeks of age to one of the three treatments: basal semi-purified diet (control), basal diet+0.3 ppm Se as SP or basal diet+0.3 ppm Se as SS. At 49 weeks, oviduct tissue from hens randomly selected from each treatment (n=7) was analyzed for Se content and gene expression profiles using the Affymetrix Chicken genome array. Gene expression data were evaluated using GeneSpring GX 10.0 (Silicon Genetics, Redwood, CA) and Ingenuity Pathways Analysis software (Ingenuity Systems, Redwood City, CA). Oviduct Se concentration was greater with Se supplementation compared with the control (P≤0.05) but did not differ between SS- and SP-supplemented groups. Gene expression analysis revealed that the quantity of gene transcripts associated with energy production and protein translation were greater in the oviduct with SP but not SS supplementation. Targets up-regulated by SP, but not SS, included genes encoding several subunits of the mitochondrial respiratory complexes, ubiquinone production and ribosomal subunits. SS hens showed a decrease in transcripts of genes involved in respiratory complexes, ATP synthesis and protein translation and metabolism in oviduct relative to control hens. In this study, although tissue Se concentrations did not differ between hens fed SS- and SP-supplemented diets, expression patterns of genes involved in energy production and protein synthesis pathways differed between treatments. These

  12. Connective tissue growth factor (CTGF/CCN2 is negatively regulated during neuron-glioblastoma interaction.

    Directory of Open Access Journals (Sweden)

    Luciana F Romão

    Full Text Available Connective-tissue growth factor (CTGF/CCN2 is a matricellular-secreted protein involved in complex processes such as wound healing, angiogenesis, fibrosis and metastasis, in the regulation of cell proliferation, migration and extracellular matrix remodeling. Glioblastoma (GBM is the major malignant primary brain tumor and its adaptation to the central nervous system microenvironment requires the production and remodeling of the extracellular matrix. Previously, we published an in vitro approach to test if neurons can influence the expression of the GBM extracellular matrix. We demonstrated that neurons remodeled glioma cell laminin. The present study shows that neurons are also able to modulate CTGF expression in GBM. CTGF immnoreactivity and mRNA levels in GBM cells are dramatically decreased when these cells are co-cultured with neonatal neurons. As proof of particular neuron effects, neonatal neurons co-cultured onto GBM cells also inhibit the reporter luciferase activity under control of the CTGF promoter, suggesting inhibition at the transcription level. This inhibition seems to be contact-mediated, since conditioned media from embryonic or neonatal neurons do not affect CTGF expression in GBM cells. Furthermore, the inhibition of CTGF expression in GBM/neuronal co-cultures seems to affect the two main signaling pathways related to CTGF. We observed inhibition of TGFβ luciferase reporter assay; however phopho-SMAD2 levels did not change in these co-cultures. In addition levels of phospho-p44/42 MAPK were decreased in co-cultured GBM cells. Finally, in transwell migration assay, CTGF siRNA transfected GBM cells or GBM cells co-cultured with neurons showed a decrease in the migration rate compared to controls. Previous data regarding laminin and these results demonstrating that CTGF is down-regulated in GBM cells co-cultured with neonatal neurons points out an interesting view in the understanding of the tumor and cerebral microenvironment

  13. The land disposal of organic materials in radioactive wastes: international practice and regulation

    International Nuclear Information System (INIS)

    Hooper, A.J.

    1988-01-01

    World-wide practice and regulation with regard to organic materials in radioactive wastes for land disposal have been examined with a view to establishing, where possible, their scientific justification and their relevance to disposal of organic-bearing wastes in the UK. (author)

  14. 26 CFR 1.892-6T - Income of international organizations (temporary regulations).

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Miscellaneous Provisions § 1.892-6T Income of international organizations (temporary regulations). (a) Exempt from tax. Subject to the provisions of section 1 of the... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Income of international organizations (temporary...

  15. Organization of Concepts Relevant to Emotions and Their Regulation during Test Taking.

    Science.gov (United States)

    Schutz, Paul A.; Davis, Heather A.; Schwanenflugel, Paula J.

    2002-01-01

    Studied college students' organization of concepts related to emotions and their regulation during test taking and whether students with test anxiety have a different conceptual organization about test taking. Results with 78 and 76 students show that for students with low and moderate test anxiety, the organizational scheme for the selected…

  16. Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

    International Nuclear Information System (INIS)

    Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn

    2013-01-01

    Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i

  17. Organization and regulation of nuclear medicine and radiotherapy in Argentina

    International Nuclear Information System (INIS)

    Degrossi, O.J.; Altschuler, Noe; Mugliaroli, H.A.

    1982-01-01

    After describing the efforts carried out in Argentina during the decade of 1970 to consolidate nuclear medicine as a new clinical specialty, reference is made to the constitution, in 1979, of a Joint Advisory Committee on Nuclear Medicine and Radiotherapy integrated by members of the National Atomic Energy Commission and by members of the Public Health Ministry of the Nation, with the purpose to coordinate and plan said activities within the country. Two recommendations of said Advisory Committee are transcribed. The first one defines the different specialties of the professionals and technicians working in the new discipline. The second recommendation is referred to the regulations on ''Operation of Nuclear Medicine Units'', which set up different categories of medical establishments of the specialty (''unit'', ''service'' and ''center''), define their respective functions as well as the equipment and specialized personnel that they should be fitted with in each case, and institute the requirement to demonstrate having the corresponding academic and professional up-dating in the specialty to obtain the periodic revalidation of operation licences. (C.A.K.) [es

  18. Genetically modified organisms in light of domestic and world regulations

    Directory of Open Access Journals (Sweden)

    Nikolić Zorica

    2007-01-01

    Full Text Available At the same time as development and registration of new genetic modification of plant species have intensified, the number of countries in which they are grown has also increased considerably. Genetically modified crops were grown in 22 countries in 2006, six of which were in European Union. Protocol on Biosafety, known as Cartagena protocol was adopted at the international level in February, 2000. Presence, but not growing of GMO in food is allowed in many countries, while in some others labeling of food origination from GMO is obligatory. Labeling is obligatory in European Union, Australia, New Zealand, Japan, Norway, Switzerland and some others. In our country the Law on GMO and sub-law acts were conceived according to EU regulative. The terms for limited use, production, trade of GMO and GMO products have been prescribed. Validation and standardization of GMO testing methods are now being implemented. It is expected that the analytical GMO methods will soon be harmonized at the international level. .

  19. Differential regulation of tissue thiol-disulfide redox status in a murine model of peritonitis

    Directory of Open Access Journals (Sweden)

    Benton Shana M

    2012-10-01

    Full Text Available Abstract Background Glutathione (GSH/glutathione disulfide (GSSG and cysteine (Cys/cystine (CySS are major redox pools with important roles in cytoprotection. We determined the impact of septic peritonitis on thiol-disulfide redox status in mice. Methods FVB/N mice (6–12 week old; 8/group underwent laparotomy with cecal ligation and puncture (CLP or laparotomy alone (control. Sections of ileum, colon, lung and liver were obtained and GSH, GSSG, Cys and CySS concentrations determined by HPLC 24 h after laparotomy. Redox potential [Eh in millivolts (mV] of the GSH/GSSG and Cys/CySS pools was calculated using the Nernst equation. Data were analyzed by ANOVA (mean ± SE. Results GSH/GSSG Eh in ileum, colon, and liver was significantly oxidized in septic mice versus control mice (ileum: septic −202±4 versus control −228±2 mV; colon: -195±8 versus −214±1 mV; and liver: -194±3 vs. -210±1 mV, all Ph was unchanged with CLP, while liver and lung Cys/CySS Eh became significantly more reducing (liver: septic = −103±3 versus control −90±2 mV; lung: -101±5 versus −81±1 mV, each P Conclusions Septic peritonitis induced by CLP oxidizes ileal and colonic GSH/GSSG redox but Cys/CySS Eh remains unchanged in these intestinal tissues. In liver, CLP oxidizes the GSH/GSSG redox pool and CyS/CySS Eh becomes more reducing; in lung, CLP does not alter GSH/GSSG Eh, and Cys/CySS Eh is less oxidized. CLP-induced infection/inflammation differentially regulates major thiol-disulfide redox pools in this murine model.

  20. Intrinsic circannual regulation of brown adipose tissue form and function in tune with hibernation.

    Science.gov (United States)

    Hindle, Allyson G; Martin, Sandra L

    2014-02-01

    Winter hibernators repeatedly cycle between cold torpor and rewarming supported by nonshivering thermogenesis in brown adipose tissue (BAT). In contrast, summer animals are homeotherms, undergoing reproduction, growth, and fattening. This life history confers variability to BAT recruitment and activity. To address the components underlying prewinter enhancement and winter activation, we interrogated the BAT proteome in 13-lined ground squirrels among three summer and five winter states. We also examined mixed physiology in fall and spring individuals to test for ambient temperature and seasonal effects, as well as the timing of seasonal transitions. BAT form and function differ circannually in these animals, as evidenced by morphology and proteome dynamics. This intrinsic pattern distinguished homeothermic groups and early vs. late winter hibernators. Homeothermic variation derived from postemergence delay in growth and substrate biosynthesis. The heterothermic proteome varied less despite extreme winter physiological shifts and was optimized to exploit lipids by enhanced fatty acid binding, β-oxidation, and mitochondrial protein translocation. Surprisingly, ambient temperature did not affect the BAT proteome during transition seasons; rather, the pronounced summer-winter shift preceded environmental changes and phenotypic progression. During fall transition, differential regulation of two fatty acid binding proteins provides further evidence of recruitment and separates proteomic preparation from successful hibernation. Abundance of FABP4 correlates with torpor bout length throughout the year, clarifying its potential function in hibernation. Metabolically active BAT is a target for treating human obesity and metabolic disorders. Understanding the hibernator's extreme and seasonally distinct recruitment and activation control strategies offers untapped potential to identify novel, therapeutically relevant regulatory pathways.

  1. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

    Directory of Open Access Journals (Sweden)

    Betul Kul Babur

    Full Text Available We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage

  2. Geometric triangular chiral hexagon crystal-like complexes organization in pathological tissues biological collision order.

    Directory of Open Access Journals (Sweden)

    Jairo A Díaz

    Full Text Available The present study describes and documents self-assembly of geometric triangular chiral hexagon crystal like complex organizations (GTCHC in human pathological tissues. The authors have found this architectural geometric expression at macroscopic and microscopic levels mainly in cancer processes. This study is based essentially on macroscopic and histopathologic analyses of 3000 surgical specimens: 2600 inflammatory lesions and 400 malignant tumours. Geometric complexes identified photographically at macroscopic level were located in the gross surgical specimen, and these areas were carefully dissected. Samples were taken to carry out histologic analysis. Based on the hypothesis of a collision genesis mechanism and because it is difficult to carry out an appropriate methodological observation in biological systems, the authors designed a model base on other dynamic systems to obtain indirect information in which a strong white flash wave light discharge, generated by an electronic device, hits over the lines of electrical conductance structured in helicoidal pattern. In their experimental model, the authors were able to reproduce and to predict polarity, chirality, helicoid geometry, triangular and hexagonal clusters through electromagnetic sequential collisions. They determined that similar events among constituents of extracelular matrix which drive and produce piezoelectric activity are responsible for the genesis of GTCHC complexes in pathological tissues. This research suggests that molecular crystals represented by triangular chiral hexagons derived from a collision-attraction event against collagen type I fibrils emerge at microscopic and macroscopic scales presenting a lateral assembly of each side of hypertrophy helicoid fibers, that represent energy flow in cooperative hierarchically chiral electromagnetic interaction in pathological tissues and arises as a geometry of the equilibrium in perturbed biological systems. Further

  3. Geometric triangular chiral hexagon crystal-like complexes organization in pathological tissues biological collision order.

    Science.gov (United States)

    Díaz, Jairo A; Jaramillo, Natalia A; Murillo, Mauricio F

    2007-12-12

    The present study describes and documents self-assembly of geometric triangular chiral hexagon crystal like complex organizations (GTCHC) in human pathological tissues. The authors have found this architectural geometric expression at macroscopic and microscopic levels mainly in cancer processes. This study is based essentially on macroscopic and histopathologic analyses of 3000 surgical specimens: 2600 inflammatory lesions and 400 malignant tumours. Geometric complexes identified photographically at macroscopic level were located in the gross surgical specimen, and these areas were carefully dissected. Samples were taken to carry out histologic analysis. Based on the hypothesis of a collision genesis mechanism and because it is difficult to carry out an appropriate methodological observation in biological systems, the authors designed a model base on other dynamic systems to obtain indirect information in which a strong white flash wave light discharge, generated by an electronic device, hits over the lines of electrical conductance structured in helicoidal pattern. In their experimental model, the authors were able to reproduce and to predict polarity, chirality, helicoid geometry, triangular and hexagonal clusters through electromagnetic sequential collisions. They determined that similar events among constituents of extracelular matrix which drive and produce piezoelectric activity are responsible for the genesis of GTCHC complexes in pathological tissues. This research suggests that molecular crystals represented by triangular chiral hexagons derived from a collision-attraction event against collagen type I fibrils emerge at microscopic and macroscopic scales presenting a lateral assembly of each side of hypertrophy helicoid fibers, that represent energy flow in cooperative hierarchically chiral electromagnetic interaction in pathological tissues and arises as a geometry of the equilibrium in perturbed biological systems. Further interdisciplinary studies must

  4. Integrity of the oral tissues in patients with solid-organ transplants.

    Science.gov (United States)

    Rojas, Gonzalo; Bravo, Loreto; Cordero, Karina; Sepúlveda, Luis; Elgueta, Leticia; Díaz, Juan Carlos; Urzúa, Blanca; Morales, Irene

    2012-01-01

    The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE), decayed, missing, filled teeth (DMFT) index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%). Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

  5. Integrity of the Oral Tissues in Patients with Solid-Organ Transplants

    Directory of Open Access Journals (Sweden)

    Gonzalo Rojas

    2012-01-01

    Full Text Available The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE, decayed, missing, filled teeth (DMFT index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%. Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

  6. Laser-induced Breakdown Spectroscopy: A New Approach for Nanoparticle's Mapping and Quantification in Organ Tissue

    Science.gov (United States)

    Sancey, Lucie; Motto-Ros, Vincent; Kotb, Shady; Wang, Xiaochun; Lux, François; Panczer, Gérard; Yu, Jin; Tillement, Olivier

    2014-01-01

    Emission spectroscopy of laser-induced plasma was applied to elemental analysis of biological samples. Laser-induced breakdown spectroscopy (LIBS) performed on thin sections of rodent tissues: kidneys and tumor, allows the detection of inorganic elements such as (i) Na, Ca, Cu, Mg, P, and Fe, naturally present in the body and (ii) Si and Gd, detected after the injection of gadolinium-based nanoparticles. The animals were euthanized 1 to 24 hr after intravenous injection of particles. A two-dimensional scan of the sample, performed using a motorized micrometric 3D-stage, allowed the infrared laser beam exploring the surface with a lateral resolution less than 100 μm. Quantitative chemical images of Gd element inside the organ were obtained with sub-mM sensitivity. LIBS offers a simple and robust method to study the distribution of inorganic materials without any specific labeling. Moreover, the compatibility of the setup with standard optical microscopy emphasizes its potential to provide multiple images of the same biological tissue with different types of response: elemental, molecular, or cellular. PMID:24962015

  7. Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs.

    Science.gov (United States)

    Ji, Shen; Guvendiren, Murat

    2017-01-01

    There is a growing demand for alternative fabrication approaches to develop tissues and organs as conventional techniques are not capable of fabricating constructs with required structural, mechanical, and biological complexity. 3D bioprinting offers great potential to fabricate highly complex constructs with precise control of structure, mechanics, and biological matter [i.e., cells and extracellular matrix (ECM) components]. 3D bioprinting is an additive manufacturing approach that utilizes a "bioink" to fabricate devices and scaffolds in a layer-by-layer manner. 3D bioprinting allows printing of a cell suspension into a tissue construct with or without a scaffold support. The most common bioinks are cell-laden hydrogels, decellulerized ECM-based solutions, and cell suspensions. In this mini review, a brief description and comparison of the bioprinting methods, including extrusion-based, droplet-based, and laser-based bioprinting, with particular focus on bioink design requirements are presented. We also present the current state of the art in bioink design including the challenges and future directions.

  8. Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs

    Science.gov (United States)

    Ji, Shen; Guvendiren, Murat

    2017-01-01

    There is a growing demand for alternative fabrication approaches to develop tissues and organs as conventional techniques are not capable of fabricating constructs with required structural, mechanical, and biological complexity. 3D bioprinting offers great potential to fabricate highly complex constructs with precise control of structure, mechanics, and biological matter [i.e., cells and extracellular matrix (ECM) components]. 3D bioprinting is an additive manufacturing approach that utilizes a “bioink” to fabricate devices and scaffolds in a layer-by-layer manner. 3D bioprinting allows printing of a cell suspension into a tissue construct with or without a scaffold support. The most common bioinks are cell-laden hydrogels, decellulerized ECM-based solutions, and cell suspensions. In this mini review, a brief description and comparison of the bioprinting methods, including extrusion-based, droplet-based, and laser-based bioprinting, with particular focus on bioink design requirements are presented. We also present the current state of the art in bioink design including the challenges and future directions. PMID:28424770

  9. Uptake, retention and organ/tissue distribution of 137Cs by Japanese catfish (Silurus asotus Linnaeus)

    International Nuclear Information System (INIS)

    Malek, M.A.; Nakahara, M.; Nakamura, R.

    2004-01-01

    The work describes the uptake, retention/biological elimination and organ/tissue distribution of 137 Cs by freshwater Japanese catfish (Silurus asotus Linnaeus) under laboratory conditions. The fish were divided into three groups based on their size and age and reared in 137 Cs-spiked water. The concentration of 137 Cs in the whole body of the live fish was measured at regular intervals up to 60 days. A significant accumulation of 137 Cs was found, but a steady state condition was not achieved by the end of the experiment. The bioaccumulation factors at steady state and the required time to reach steady state were estimated to be 1.55 and 255 days, 1.76 and 180 days and 1.99 and 160 days for large, medium and small size fish, respectively. To determine the effective half-life of 137 Cs, the fish were transferred and reared in the non-contaminated host water. The concentration of the remaining 137 Cs in the whole body of the live fish was measured up to 66 days. The average effective half-life of 137 Cs in the fish species was found to be ∼142 days for fish of all sizes. The distribution of 137 Cs in different organs/tissues of the fish was determined. Accumulation of 137 Cs in muscle/flesh of the fish was found to be ∼75% of whole body accumulation. The uptake rate and the retention capability of juvenile fish were found to be higher and therefore, these were more susceptible to 137 Cs than adult and old fish, and could be an important source of 137 Cs in the human food chain

  10. Selected organic compounds and trace elements in streambed sediments and fish tissues, Cook Inlet Basin, Alaska

    Science.gov (United States)

    Frenzel, Steven A.

    2000-01-01

    Organochlorines, semivolatile organic compounds (SVOCs), and trace elements were investigated in streambed sediments and fish tissues at selected sites in the Cook Inlet Basin, Alaska, during 1998. At most sites, SVOCs and organochlorine compounds were either not detected or detected at very low concentrations. Chester Creek at Arctic Boulevard at Anchorage, which was the only site sampled with a significant degree of development in the watershed, had elevated levels of many SVOCs in streambed sediment. Coring of sediments from two ponds on Chester Creek confirmed the presence of elevated concentrations of a variety of organic compounds. Moose Creek, a stream with extensive coal deposits in its watershed, had low concentrations of numerous SVOCs in streambed sediment. Three sites located in national parks or in a national wildlife refuge had no detectable concentrations of SVOCs. Trace elements were analyzed in both streambed sediments and tissues of slimy sculpin. The two media provided similar evidence for elevated concentrations of cadmium, lead, and zinc at Chester Creek. In this study, 'probable effect levels '(PELs) were determined from sediments finer than 0.063 millimeters, where concentrations tend to be greatest. Arsenic and chromium concentrations exceeded the PEL at eight and six sites respectively. Zinc exceeded the PEL at one site. Cadmium and copper concentrations were smaller than the PEL at all sites. Mercury concentrations in streambed sediments from the Deshka River were near the PEL, and selenium concentrations at that site also appear to be elevated above background levels. At half the sites where slimy sculpin were sampled, selenium concentrations were at levels that may cause adverse effects in some species.

  11. Nutrient supply to organic agriculture as governed by EU regulations and standards in six European countries

    DEFF Research Database (Denmark)

    Løes, Anne Kristin; Bünemann, E.K.; Cooper, J.

    2017-01-01

    -farm P sources include conventional animal manure, composted or anaerobically digested organic residues, rock phosphate, and some animal residues such as meat and bone meal. The recent proposed revision of EU regulations for organic production (2014) puts less emphasis on closing nutrient cycles...... as means are taken to ensure the quality and safety of these inputs. Awareness of the need to close nutrient cycles may contribute to adapting regulations and private standards to support recycling of nutrients from society to organic agriculture. A better definition of the term “natural substance...

  12. Beneficial Autoimmunity at Body Surfaces – Immune Surveillance and Rapid Type 2 Immunity Regulate Tissue Homeostasis and Cancer

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis. PMID:25101088

  13. Beneficial autoimmunity at body surfaces - immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer.

    Science.gov (United States)

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress - a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis.

  14. Adiponectin receptor 2 is regulated by nutritional status, leptin and pregnancy in a tissue-specific manner.

    Science.gov (United States)

    González, Carmen Ruth; Caminos, Jorge Eduardo; Gallego, Rosalía; Tovar, Sulay; Vázquez, María Jesús; Garcés, María Fernanda; Lopez, Miguel; García-Caballero, Tomás; Tena-Sempere, Manuel; Nogueiras, Rubén; Diéguez, Carlos

    2010-01-12

    The aim of the present work was to study the regulation of circulating adiponectin levels and the expression of adiponectin receptor 2 (Adipo-R2) in several rat tissues in relation to fasting, leptin challenge, pregnancy, and chronic undernutrition. Using real-time PCR, we found Adipo-R2 mRNA expression in the liver, stomach, white and brown adipose tissues (WAT and BAT) of adult rats. Immunohistochemical studies confirmed protein expression in the same tissues. Adipo-R2 mRNA levels were decreased in liver after fasting, with no changes in the other tissues. Leptin decreased Adipo-R2 expression in liver and stomach, but increased its expression in WAT and BAT. Chronic caloric restriction in normal rats increased Adipo-R2 gene expression in stomach, while it decreased hepatic Adipo-R2 levels in pregnant rats. Using radioimmunoassay, we found that plasma adiponectin levels were diminished by fasting and leptin. Conversely, circulating adiponectin was increased in food-restricted rats, whereas its levels decreased in food-restricted pregnant rats by the end of gestation. In conclusion our findings provide the first evidence that (a) Adipo-R2 mRNA is regulated in a tissue-specific manner by fasting, but leptin is not responsible for those changes; (b) chronic caloric restriction in normal and pregnant rats also regulate Adipo-R2 mRNA in a tissue-specific manner; and (c) Adipo-R2 mRNA does not show a clear correlation with plasma adiponectin levels.

  15. Potential and Actual Neonatal Organ and Tissue Donation After Circulatory Determination of Death.

    Science.gov (United States)

    Stiers, Justin; Aguayo, Cecile; Siatta, Angela; Presson, Angela P; Perez, Richard; DiGeronimo, Robert

    2015-07-01

    The need for transplants continues to exceed organ and tissue donor availability. Although recent surgical advances have resulted in successful transplants using very small pediatric donors, including neonates, the actual practice of neonatal organ donation after circulatory determination of death (DCDD) remains uncommon. To describe the percentage of neonates potentially eligible for DCDD, including those who underwent successful donation, and reasons for ineligibility in those who did not in a single neonatal intensive care unit (NICU). We obtained data from the Children's Hospital Neonatal Database and Intermountain Donor Services (IDS) organ procurement records. The 136 deaths that occurred in the NICU of the Primary Children's Hospital, Salt Lake City, Utah, from January 1, 2010, through May 7, 2013, were reviewed retrospectively from January 12 through July 1, 2014, to determine potential eligibility for DCDD as determined by IDS minimum eligibility criteria (requirement of life-sustaining interventions and weight >2 kg). For patients who did not undergo DCDD, we reviewed records to determine the reasons for ineligibility. Potential eligibility for DCDD among neonates who died in the study NICU. Of 136 deaths in the NICU, 60 (44.1%) met criteria for DCDD; however, fewer than 10% were referred appropriately to the regional organ procurement organization for evaluation. Forty-five neonates (33.1%) ultimately died within 90 minutes of withdrawal of life-sustaining interventions and thus would have been eligible for organ donation based on warm ischemic time. The most common causes of death among the 60 potentially eligible neonatal donors were neonatal encephalopathy (n = 17) and multiple congenital anomalies (n = 14). Nonreferral or late referral by the medical team was the most frequent reason for donor ineligibility, including 49 neonates (36.0%). Overall, only 4 neonates (2.9%) underwent successful DCDD. Although almost half of all neonatal deaths

  16. Assessment of Abdominal Adipose Tissue and Organ Fat Content by Magnetic Resonance Imaging

    Science.gov (United States)

    Hu, Houchun H.; Nayak, Krishna S.; Goran, Michael I.

    2010-01-01

    As the prevalence of obesity continues to rise, rapid and accurate tools for assessing abdominal body and organ fat quantity and distribution are critically needed to assist researchers investigating therapeutic and preventive measures against obesity and its comorbidities. Magnetic resonance imaging (MRI) is the most promising modality to address such need. It is non-invasive, utilizes no ionizing radiation, provides unmatched 3D visualization, is repeatable, and is applicable to subject cohorts of all ages. This article is aimed to provide the reader with an overview of current and state-of-the-art techniques in MRI and associated image analysis methods for fat quantification. The principles underlying traditional approaches such as T1-weighted imaging and magnetic resonance spectroscopy as well as more modern chemical-shift imaging techniques are discussed and compared. The benefits of contiguous 3D acquisitions over 2D multi-slice approaches are highlighted. Typical post-processing procedures for extracting adipose tissue depot volumes and percent organ fat content from abdominal MRI data sets are explained. Furthermore, the advantages and disadvantages of each MRI approach with respect to imaging parameters, spatial resolution, subject motion, scan time, and appropriate fat quantitative endpoints are also provided. Practical considerations in implementing these methods are also presented. PMID:21348916

  17. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    International Nuclear Information System (INIS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Cho, Dong-Woo; Kim, Jong Young

    2012-01-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed. (paper)

  18. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    Science.gov (United States)

    Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

    2012-08-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

  19. Is There a Relationship Between Pelvic Organ Prolapse and Tissue Fibrillin-1 Levels?

    Directory of Open Access Journals (Sweden)

    Ayla Eser

    2015-09-01

    Full Text Available Purpose: Pelvic organ prolapse is a multifactorial disorder in which extracellular matrix defects are implicated. Fibrillin-1 level is reduced in stress urinary incontinence. In Marfan syndrome, which is associated with mutations in Fibrillin-1, pelvic floor disorders are commonly observed. We hypothesize that Fibrillin-1 gene expression is altered in pelvic organ prolapse. Methods: Thirty women undergoing colporrhaphy or hysterectomy because of cystocele, rectocele, cystorectocele, or uterine prolapse were assigned to a pelvic prolapse study group, and thirty women undergone hysterectomy for nonpelvic prolapse conditions were assigned to a control group. Real-time polymerase chain reaction was conducted on vaginal tissue samples to measure the expression of Fibrillin-1. Expression levels were compared between study and control groups by Mann-Whitney U test with Bonferroni revision. Results: Fibrillin-1 gene expression was not significantly lower in the study group than in the control group. Similarly, no significant correlation between Fibrillin-1 levels and grade of pelvic prolapse was found. Age over 40 years (P=0.018 and menopause (P=0.027 were both associated with reduced Fibrillin-1 levels in the pelvic prolapse group, whereas the delivery of babies weighing over 3,500 g at birth was associated with increased Fibrillin-1 expression (P=0.006. Conclusions: The results did not indicate a significant reduction in Fibrillin-1 gene expression in pelvic prolapse disorders; however, reduced Fibrillin-1 may contribute to increased pelvic organ prolapse risk with age and menopause. Increased Fibrillin-1 gene expression may be a compensatory mechanism in cases of delivery of babies with high birth weight. Further studies are needed for a better understanding of these observations.

  20. Recent Advances in Understanding Pelvic-Floor Tissue of Women With and Without Pelvic Organ Prolapse: Considerations for Physical Therapists.

    Science.gov (United States)

    Saunders, Kimberly

    2017-04-01

    Pelvic organ prolapse is a fairly common condition that imposes significant symptoms, diminished quality of life, social burden, financial expense, and surgical risk on women. As evidence supporting the benefit of pelvic-floor muscle training in nonsurgical management of pelvic organ prolapse grows, physical therapists are becoming a provider of choice interacting with women affected by pelvic organ prolapse. This perspective article will review recent research on tissue characteristics of 3 key components of pelvic organ support: skeletal muscle, ligament, and vaginal wall. This information will be summarized as implications for physical therapists. An improved understanding of pelvic-floor tissue in women with and without pelvic organ prolapse will provide a more comprehensive appreciation of the interaction of multiple systems in the disorder. © 2017 American Physical Therapy Association.

  1. Concise review: can the intrinsic power of branching morphogenesis be used for engineering epithelial tissues and organs?

    Science.gov (United States)

    Nigam, Sanjay K

    2013-12-01

    Branching morphogenesis is critical to the development of organs such as kidney, lung, mammary gland, prostate, pancreas, and salivary gland. Essentially, an epithelial bud becomes an iterative tip-stalk generator (ITSG) able to form a tree of branching ducts and/or tubules. In different organs, branching morphogenesis is governed by similar sets of genes. Epithelial branching has been recapitulated in vitro (or ex vivo) using three-dimensional cell culture and partial organ culture systems, and several such systems relevant to kidney tissue engineering are discussed here. By adapting systems like these it may be possible to harness the power inherent in the ITSG program to propagate and engineer epithelial tissues and organs. It is also possible to conceive of a universal ITSG capable of propagation that may, by recombination with organ-specific mesenchymal cells, be used for engineering many organ-like tissues similar to the organ from which the mesenchyme cells were derived, or toward which they are differentiated (from stem cells). The three-dimensional (3D) branched epithelial structure could act as a dynamic branching cellular scaffold to establish the architecture for the rest of the tissue. Another strategy-that of recombining propagated organ-specific ITSGs in 3D culture with undifferentiated mesenchymal stem cells-is also worth exploring. If feasible, such engineered tissues may be useful for the ex vivo study of drug toxicity, developmental biology, and physiology in the laboratory. Over the long term, they have potential clinical applications in the general fields of transplantation, regenerative medicine, and bioartificial medical devices to aid in the treatment of chronic kidney disease, diabetes, and other diseases.

  2. Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment

    OpenAIRE

    Kong, Wei; Wanda, Soo-Young; Zhang, Xin; Bollen, Wendy; Tinge, Steven A.; Roland, Kenneth L.; Curtiss, Roy

    2008-01-01

    We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is Salmonella typhimurium strain χ8937, with deletions of asdA and arabinose-regulated expression of murA, two genes required for peptidoglycan synthesis a...

  3. Natural regulation of Delia radicum in organic cabbage production

    DEFF Research Database (Denmark)

    Meyling, Nicolai Vitt; Navntoft, Søren; Philipsen, Holger Frederik

    2013-01-01

    In a field experiment, we evaluated effects of three different organic white cabbage-cropping systems (O1, O2, O3) on the cabbage root fly, Delia radicum, and its egg predators and pupal parasitoids over 3 years. The three systems all complied with regulations for organic production, but varied...... in external nutrient input and N-recycling, and were compared to a conventionally farmed control. One organic system (O3) included an intercropped strip of green manure between crop rows. Oviposition by D. radicum was generally not reduced in organic cropping systems. However, higher pupae/egg ratios were...... observed in the conventional compared to all organic systems, indicating that immature survival from oviposition to pupation was reduced under all the three organic farming practices. In organic system O2 most small coleopteran predators were recorded, but predation on fly eggs was not significantly higher...

  4. Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues.

    Science.gov (United States)

    Qu, Feini; Li, Qing; Wang, Xiao; Cao, Xuan; Zgonis, Miltiadis H; Esterhai, John L; Shenoy, Vivek B; Han, Lin; Mauck, Robert L

    2018-02-19

    Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.

  5. FAMILY CONSENT FOR ORGAN OR TISSUE REMOVAL FROM A DECEASED PERSON FOR TRANSPLANTATION PURPOSES IN THE REPUBLIC OF CROATIA

    Directory of Open Access Journals (Sweden)

    Tomislav Nedić

    2017-04-01

    Full Text Available The Republic of Croatia is a country with the system of presumed consent donation of organs and tissues after death, where the consent of the family, according to law, is not one of the conditions for organ or tissue removal for transplantation purposes. However, the consent is a condition required by the Codex of Medical Ethics and Deontology. The author primary proposes harmonization of the Codex with current legislation. Accordingly, this paper primarily analyses the typology of the Codex, ethical issues and ethical and positivist reasons to harmonize the Codex with current legislation. Furthermore, although the author in the first place considers that the Codex should be in line with legislation, he also considers the provision of family consent for organ and tissue removal itself flawed and poorly developed. In this regard, the author considers the comparative legislation and judgments of the European Court of Human Rights, analyses current provisions of the Codex in the part of the removal and transplantation of organs and tissues from deceased persons, states the facts that the Codex should contain so as to make the mechanism of family consent for organ and tissue removal and donation after death more effective. In fact, if the author’s original proposal for harmonization of the Codex with the current legislation is not accepted, a more detailed and precise elaboration of the mentioned current provisions of the Codex will be suggested. This will include exact definition of the family and relatives, exact deadlines and ways of informing the family, but also refining the concept of “ethical“ according to the Codex in part of the organ and tissue donation and removal from the deceased person.

  6. Genomic organization, tissue distribution and functional characterization of the rat Pate gene cluster.

    Directory of Open Access Journals (Sweden)

    Angireddy Rajesh

    Full Text Available The cysteine rich prostate and testis expressed (Pate proteins identified till date are thought to resemble the three fingered protein/urokinase-type plasminogen activator receptor proteins. In this study, for the first time, we report the identification, cloning and characterization of rat Pate gene cluster and also determine the expression pattern. The rat Pate genes are clustered on chromosome 8 and their predicted proteins retained the ten cysteine signature characteristic to TFP/Ly-6 protein family. PATE and PATE-F three dimensional protein structure was found to be similar to that of the toxin bucandin. Though Pate gene expression is thought to be prostate and testis specific, we observed that rat Pate genes are also expressed in seminal vesicle and epididymis and in tissues beyond the male reproductive tract. In the developing rats (20-60 day old, expression of Pate genes seem to be androgen dependent in the epididymis and testis. In the adult rat, androgen ablation resulted in down regulation of the majority of Pate genes in the epididymides. PATE and PATE-F proteins were found to be expressed abundantly in the male reproductive tract of rats and on the sperm. Recombinant PATE protein exhibited potent antibacterial activity, whereas PATE-F did not exhibit any antibacterial activity. Pate expression was induced in the epididymides when challenged with LPS. Based on our results, we conclude that rat PATE proteins may contribute to the reproductive and defense functions.

  7. Development of maternal seed tissue in barley is mediated by regulated cell expansion and cell disintegration and coordinated with endosperm growth.

    Science.gov (United States)

    Radchuk, Volodymyr; Weier, Diana; Radchuk, Ruslana; Weschke, Winfriede; Weber, Hans

    2011-01-01

    After fertilization, filial grain organs are surrounded by the maternal nucellus embedded within the integuments and pericarp. Rapid early endosperm growth must be coordinated with maternal tissue development. Parameters of maternal tissue growth and development were analysed during early endosperm formation. In the pericarp, cell proliferation is accomplished around the time of fertilization, followed by cell elongation predominantly in longitudinal directions. The rapid cell expansion coincides with endosperm cellularization. Distribution of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling)-positive nuclei reveals distinct patterns starting in the nucellus at anthesis and followed later by the inner cell rows of the pericarp, then spreading to the whole pericarp. The pattern suggests timely and spatially regulated programmed cell death (PCD) processes in maternal seed tissues. When the endosperm is coenocytic, PCD events are only observed within the nucellus. Thereby, remobilization of nucellar storage compounds by PCD could nourish the early developing endosperm when functional interconnections are absent between maternal and filial seed organs. Specific proteases promote PCD events. Characterization of the barley vacuolar processing enzyme (VPE) gene family identified seven gene members specifically expressed in the developing grain. HvVPE2a (known as nucellain) together with closely similar HvVPE2b and HvVPE2d might be involved in nucellar PCD. HvVPE4 is strongly cell specific for pericarp parenchyma. Correlative evidence suggests that HvVPE4 plays a role in PCD events in the pericarp. Possible functions of PCD in the maternal tissues imply a potential nutritive role or the relief of a physical restraint for endosperm growth. PCD could also activate post-phloem transport functions.

  8. Embryonic common snapping turtles (Chelydra serpentina) preferentially regulate intracellular tissue pH during acid-base challenges.

    Science.gov (United States)

    Shartau, Ryan B; Crossley, Dane A; Kohl, Zachary F; Brauner, Colin J

    2016-07-01

    The nests of embryonic turtles naturally experience elevated CO2 (hypercarbia), which leads to increased blood PCO2  and a respiratory acidosis, resulting in reduced blood pH [extracellular pH (pHe)]. Some fishes preferentially regulate tissue pH [intracellular pH (pHi)] against changes in pHe; this has been proposed to be associated with exceptional CO2 tolerance and has never been identified in amniotes. As embryonic turtles may be CO2 tolerant based on nesting strategy, we hypothesized that they preferentially regulate pHi, conferring tolerance to severe acute acid-base challenges. This hypothesis was tested by investigating pH regulation in common snapping turtles (Chelydra serpentina) reared in normoxia then exposed to hypercarbia (13 kPa PCO2 ) for 1 h at three developmental ages: 70% and 90% of incubation, and yearlings. Hypercarbia reduced pHe but not pHi, at all developmental ages. At 70% of incubation, pHe was depressed by 0.324 pH units while pHi of brain, white muscle and lung increased; heart, liver and kidney pHi remained unchanged. At 90% of incubation, pHe was depressed by 0.352 pH units but heart pHi increased with no change in pHi of other tissues. Yearlings exhibited a pHe reduction of 0.235 pH units but had no changes in pHi of any tissues. The results indicate common snapping turtles preferentially regulate pHi during development, but the degree of response is reduced throughout development. This is the first time preferential pHi regulation has been identified in an amniote. These findings may provide insight into the evolution of acid-base homeostasis during development of amniotes, and vertebrates in general. © 2016. Published by The Company of Biologists Ltd.

  9. Basic Substances under EU Pesticide Regulation: An Opportunity for Organic Production?

    Directory of Open Access Journals (Sweden)

    Patrice A. Marchand

    2017-02-01

    Full Text Available Some of the active substances allowed in organic production are now approved as basic sub- stances under the EU plant protection products regulation. Previously, all organic farming permitted active substances were approved as conventional plant protection products. In accordance with the criteria of Article 23 of the EU regulation (EC No 1107/2009, basic substances are granted without maximum residue limits and have a good prospect for being included in Annex II of organic farming Regulation (EC 889/2008. In fact, most of them are already permitted in organic farming. At this stage, it seems desirable to organize applications in order to avoid duplications and to clarify strategy across Europe. This organization should be planned in order to identify corresponding knowledge and data from field experiments, and to further constitute the most crucial issues related to organic production. A work of this nature was initially supported by IFOAM-EU for lecithin, calcium hydroxide and Quassia extract. The Institut Technique de l’Agriculture Biologique (ITAB was previously engaged in a large-scale approval plan motivated by the continuous demand for the regularization of compounds/substances already in use and has a mandate for testing and approving new compatible substances. Thus, the horsetail extract (Equisetum arvense was the first approved basic substance and ITAB has obtained 11 of the 15 basic substances approved at the EU level.

  10. The effect of plant growth regulators on optimization of tissue culture ...

    African Journals Online (AJOL)

    USER

    2010-04-05

    Apr 5, 2010 ... ISSN 1684–5315 © 2010 Academic Journals ... tissue culture system in Malaysian upland rice ... Scientists believe that using new cultivars which have potential ..... providing the financial support and to Firouzeh Ashjazadeh ...

  11. Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation

    DEFF Research Database (Denmark)

    Agudelo, Leandro Z; Ferreira, Duarte M S; Cervenka, Igor

    2018-01-01

    The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accum...

  12. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

    DEFF Research Database (Denmark)

    Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren

    2006-01-01

    in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4......Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression.......5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied...

  13. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    OpenAIRE

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

  14. Hyaluronan supplementation as a mechanical regulator of cartilage tissue development under joint-kinematic-mimicking loading.

    Science.gov (United States)

    Wu, Yabin; Stoddart, Martin J; Wuertz-Kozak, Karin; Grad, Sibylle; Alini, Mauro; Ferguson, Stephen J

    2017-08-01

    Articular cartilage plays an essential role in joint lubrication and impact absorption. Through this, the mechanical signals are coupled to the tissue's physiological response. Healthy synovial fluid has been shown to reduce and homogenize the shear stress acting on the cartilage surfaces due to its unique shear-thinning viscosity. As cartilage tissues are sensitive to mechanical changes in articulation, it was hypothesized that replacing the traditional culture medium with a healthy non-Newtonian lubricant could enhance tissue development in a cartilage engineering model, where joint-kinematic-mimicking mechanical loading is applied. Different amounts of hyaluronic acid were added to the culture medium to replicate the viscosities of synovial fluid at different health states. Hyaluronic acid supplementation, especially at a physiologically healthy concentration (2.0 mg ml -1 ), promoted a better preservation of chondrocyte phenotype. The ratio of collagen II to collagen I mRNA was 4.5 times that of the control group, implying better tissue development (however, with no significant difference of measured collagen II content), with a good retention of collagen II and proteoglycan in the mechanically active region. Simulating synovial fluid properties by hyaluronic acid supplementation created a favourable mechanical environment for mechanically loaded constructs. These findings may help in understanding the influence of joint articulation on tissue homeostasis, and moreover, improve methods for functional cartilage tissue engineering. © 2017 The Author(s).

  15. Potential donor families' experiences of organ and tissue donation-related communication, processes and outcome.

    Science.gov (United States)

    Marck, C H; Neate, S L; Skinner, M; Dwyer, B; Hickey, B B; Radford, S T; Weiland, T J; Jelinek, G A

    2016-01-01

    We aimed to describe the experiences of families of potential organ and tissue donors eligible for donation after circulatory death or brain death. Forty-nine family members of potential donors from four Melbourne hospitals were interviewed to assess their experiences of communication, processes and the outcomes of donation. Interviews were recorded, transcribed verbatim and analysed thematically. Families expressed a range of perspectives on themes of communication, hospital processes and care, the processes of consent and donation and reflected on decisions and outcomes. They expressed satisfaction overall with communication when receiving bad news, discussing death and donation. Honest and frank communication and being kept up-to-date and prepared for potential outcomes were important aspects for families, especially those of post circulatory death donors. Participants reported high levels of trust in healthcare professionals and satisfaction with the level of care received. Many donor families indicated the process was lengthy and stressful, but not significantly enough to adversely affect their satisfaction with the outcome. Both the decision itself and knowing others' lives had been saved provided them with consolation. No consenting families, and only some non-consenting families, regretted their decisions. Many expressed they would benefit from a follow-up opportunity to ask questions and clarify possible misunderstandings. Overall, while experiences varied, Australian families valued frank communication, trusted health professionals, were satisfied with the care their family member received and with donation processes, despite some apparent difficulties. Family satisfaction, infrequently assessed, is an important outcome and these findings may assist education for Australian organ donation professionals.

  16. Tracking targeted bimodal nanovaccines: immune responses and routing in cells, tissue, and whole organism.

    Science.gov (United States)

    Cruz, Luis J; Tacken, Paul J; Zeelenberg, Ingrid S; Srinivas, Mangala; Bonetto, Fernando; Weigelin, Bettina; Eich, Christina; de Vries, I Jolanda; Figdor, Carl G

    2014-12-01

    Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), involved in the induction of immunity and currently exploited for antitumor immunotherapies. An optimized noninvasive imaging modality capable of determining and quantifying DC-targeted nanoparticle (NP) trajectories could provide valuable information regarding therapeutic vaccine outcome. Here, targeted poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) recognizing DC receptors were equipped with superparamagnetic iron oxide particles (SPIO) or gold nanoparticles with fluorescently labeled antigen. The fluorescent label allowed for rapid analysis and quantification of DC-specific uptake of targeted PLGA NPs in comparison to uptake by other cells. Transmission electron microscopy (TEM) showed that a fraction of the encapsulated antigen reached the lysosomal compartment of DCs, where SPIO and gold were already partially released. However, part of the PLGA NPs localized within the cytoplasm, as confirmed by confocal microscopy. DCs targeted with NPs carrying SPIO or fluorescent antigen were detected within lymph nodes as early as 1 h after injection by magnetic resonance imaging (MRI). Despite the fact that targeting did not markedly affect PLGA NP biodistribution on organism and tissue level, it increased delivery of NPs to DCs residing in peripheral lymph nodes and resulted in enhanced T cell proliferation. In conclusion, two imaging agents within a single carrier allows tracking of targeted PLGA NPs at the subcellular, cellular, and organismal levels, thereby facilitating the rational design of in vivo targeted vaccination strategies.

  17. Doses to organs and tissues from concomitant imaging in radiotherapy: a suggested framework for clinical justification.

    Science.gov (United States)

    Harrison, R M

    2008-12-01

    The increasing use of imaging for localization and verification in radiotherapy has raised issues concerning the justifiable doses to critical organs and tissues from concomitant exposures, particularly when extensive image-guided radiotherapy is indicated. Doses at positions remote from the target volume include components from high-energy leakage and scatter, as well as from concomitant imaging. In this paper, simulated prostate, breast and larynx treatments are used to compare doses from both high-energy and concomitant exposures as a function of distance from the target volume. It is suggested that the fraction, R, of the total dose at any point within the patient that is attributable to concomitant exposures may be a useful aid in their justification. R is small within the target volume and at large distances from it. However, there is a critical region immediately adjacent to the planning target volume where the dose from concomitant imaging combines with leakage and scatter to give values of R that approach 0.5 in the examples given here. This is noteworthy because the regions just outside the target volume will receive total doses in the order of 1 Gy, where commensurately high risk factors may not be substantially reduced because of cell kill. Other studies have identified these regions as sites of second cancers. The justification of an imaging regimen might therefore usefully take into account the maximum value of R encountered from the combination of imaging and radiotherapy for particular treatment sites.

  18. The role of micro-NRA and micro-PIXE in carbon mapping of organic tissues

    International Nuclear Information System (INIS)

    Niekraszewicz, L.A.B.; Souza, C.T. de; Stori, E.M.; Jobim, P.F.C.; Amaral, L.; Dias, J.F.

    2015-01-01

    This study reports the work developed in the Ion Implantation Laboratory (Porto Alegre, RS, Brazil) in order to implement the micro-NRA technique for the study of light elements in organic tissues. In particular, the work was focused on nuclear reactions employing protons and alphas with carbon. The (p,p) resonances at 0.475 and 1.734 were investigated. The (α,α) resonance at 4.265 MeV was studied as well. The results indicate that the yields for the 0.475 and 1.734 MeV resonances are similar. Elemental maps of different structures obtained with the micro-NRA technique using the 1.734 MeV resonance were compared with those obtained with micro-PIXE employing a SDD detector equipped with an ultra-thin window. The results show that the use of micro-NRA for carbon at 1.734 MeV resonance provides good results in some cases at the expense of longer beam times. On the other hand, micro-PIXE provides enhanced yields but is limited to surface analysis since soft X-rays are greatly attenuated by matter

  19. Development and Characterization of Organic Electronic Scaffolds for Bone Tissue Engineering.

    Science.gov (United States)

    Iandolo, Donata; Ravichandran, Akhilandeshwari; Liu, Xianjie; Wen, Feng; Chan, Jerry K Y; Berggren, Magnus; Teoh, Swee-Hin; Simon, Daniel T

    2016-06-01

    Bones have been shown to exhibit piezoelectric properties, generating electrical potential upon mechanical deformation and responding to electrical stimulation with the generation of mechanical stress. Thus, the effects of electrical stimulation on bone tissue engineering have been extensively studied. However, in bone regeneration applications, only few studies have focused on the use of electroactive 3D biodegradable scaffolds at the interphase with stem cells. Here a method is described to combine the bone regeneration capabilities of 3D-printed macroporous medical grade polycaprolactone (PCL) scaffolds with the electrical and electrochemical capabilities of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). PCL scaffolds have been highly effective in vivo as bone regeneration grafts, and PEDOT is a leading material in the field of organic bioelectronics, due to its stability, conformability, and biocompatibility. A protocol is reported for scaffolds functionalization with PEDOT, using vapor-phase polymerization, resulting in a conformal conducting layer. Scaffolds' porosity and mechanical stability, important for in vivo bone regeneration applications, are retained. Human fetal mesenchymal stem cells proliferation is assessed on the functionalized scaffolds, showing the cytocompatibility of the polymeric coating. Altogether, these results show the feasibility of the proposed approach to obtain electroactive scaffolds for electrical stimulation of stem cells for regenerative medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Registration for deceased organ and tissue donation among Ontario immigrants: a population-based cross-sectional study.

    Science.gov (United States)

    Li, Alvin Ho-Ting; Lam, Ngan N; Dhanani, Sonny; Weir, Matthew; Prakash, Versha; Kim, Joseph; Knoll, Greg; Garg, Amit X

    2016-01-01

    Canada has low rates of deceased organ and tissue donation. Immigrants to Canada may differ in their registered support for deceased organ donation based on their country of origin. We used linked administrative databases in Ontario (about 11 million residents aged ≥ 16 yr) to study the proportion of immigrants and long-term residents registered for deceased organ and tissue donation as of October 2013. We used modified Poisson regression to identify and quantify predictors of donor registration. Compared with long-term residents ( n = 9 244 570), immigrants ( n = 1 947 646) were much less likely to register for deceased organ and tissue donation (11.9% v. 26.5%). Immigrants from the United States, Australia and New Zealand had the highest registration rate (40.0%), whereas immigrants with the lowest registration rates were from Eastern Europe and Central Asia (9.4%), East Asia and Pacific (8.4%) and sub-Saharan Africa (7.9%). The largest numbers of unregistered immigrants were from India ( n = 202 548), China ( n = 186 678) and the Philippines ( n = 125 686). Characteristics among the immigrant population associated with a higher likelihood of registration included economic immigrant status, living in a rural area (population speak English and French, and more years residing in Canada. Immigrants in Ontario were less likely to register for deceased organ and tissue donation than long-term residents. There is a need to better understand reasons for lower registration rates among Canadian immigrants and to create culture-sensitive materials to build support for deceased organ and tissue donation.

  1. High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats.

    Science.gov (United States)

    Tang, Haiying; Vasselli, Joseph R; Wu, Ed X; Boozer, Carol N; Gallagher, Dympna

    2002-03-01

    Magnetic resonance imaging (MRI) has the ability to discriminate between various soft tissues in vivo. Whole body, specific organ, total adipose tissue (TAT), intra-abdominal adipose tissue (IAAT), and skeletal muscle (SM) weights determined by MRI were compared with weights determined by dissection and chemical analysis in two studies with male Sprague-Dawley rats. A 4.2-T MRI machine acquired high-resolution, in vivo, longitudinal whole body images of rats as they developed obesity or aged. Weights of the whole body and specific tissues were determined using computer image analysis software, including semiautomatic segmentation algorithms for volume calculations. High correlations were found for body weight (r = 0.98), TAT (r = 0.99), and IAAT (r = 0.98) between MRI and dissection and chemical analyses. MRI estimated the weight of the brain, kidneys, and spleen with high accuracy (r > 0.9), but overestimated IAAT, SM, and liver volumes. No differences were detected in organ weights using MRI and dissection measurements. Longitudinal MRI measurements made during the development of obesity and aging accurately represented changes in organ and tissue mass.

  2. Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue.

    Science.gov (United States)

    Cederquist, Carly T; Lentucci, Claudia; Martinez-Calejman, Camila; Hayashi, Vanessa; Orofino, Joseph; Guertin, David; Fried, Susan K; Lee, Mi-Jeong; Cardamone, M Dafne; Perissi, Valentina

    2017-01-01

    Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT. The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice). Our results indicate that K63 ubiquitination is a critical component of AKT activation in the insulin signaling pathway and that counter-regulation of this step is provided by GPS2 preventing AKT ubiquitination through inhibition of Ubc13 enzymatic activity. Removal of this negative checkpoint, through GPS2 downregulation or genetic deletion, results in sustained activation of insulin signaling both in vitro and in vivo . As a result, the balance between lipid accumulation and utilization is shifted toward storage in the adipose tissue and GPS2-AKO mice become obese under normal laboratory chow diet. However, the adipose tissue of GPS2-AKO mice is not inflamed, the levels of circulating adiponectin are elevated, and systemic insulin sensitivity is overall improved. Our findings characterize a novel layer of regulation of the insulin signaling pathway based on non-proteolytic ubiquitination of AKT and define GPS2 as a previously unrecognized component of the insulin signaling cascade. In accordance with this role, we have shown that GPS2 presence in adipocytes modulates systemic metabolism by restricting the activation of insulin signaling during the fasted state, whereas in absence of GPS2, the adipose tissue is more efficient at lipid storage, and obesity becomes uncoupled from inflammation and insulin

  3. Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment.

    Science.gov (United States)

    Kong, Wei; Wanda, Soo-Young; Zhang, Xin; Bollen, Wendy; Tinge, Steven A; Roland, Kenneth L; Curtiss, Roy

    2008-07-08

    We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is Salmonella typhimurium strain chi8937, with deletions of asdA and arabinose-regulated expression of murA, two genes required for peptidoglycan synthesis and additional mutations to enhance complete lysis and antigen delivery. The second component is plasmid pYA3681, which encodes arabinose-regulated murA and asdA expression and C2-regulated synthesis of antisense asdA and murA mRNA transcribed from the P22 P(R) promoter. An arabinose-regulated c2 gene is present in the chromosome. chi8937(pYA3681) exhibits arabinose-dependent growth. Upon invasion of host tissues, an arabinose-free environment, transcription of asdA, murA, and c2 ceases, and concentrations of their gene products decrease because of cell division. The drop in C2 concentration results in activation of P(R), driving synthesis of antisense mRNA to block translation of any residual asdA and murA mRNA. A highly antigenic alpha-helical domain of Streptococcus pneumoniae Rx1 PspA was cloned into pYA3681, resulting in pYA3685 to test antigen delivery. Mice orally immunized with chi8937(pYA3685) developed antibody responses to PspA and Salmonella outer membrane proteins. No viable vaccine strain cells were detected in host tissues after 21 days. This system has potential applications with other Gram-negative bacteria in which biological containment would be desirable.

  4. Selection of reference genes for tissue/organ samples on day 3 fifth-instar larvae in silkworm, Bombyx mori.

    Science.gov (United States)

    Wang, Genhong; Chen, Yanfei; Zhang, Xiaoying; Bai, Bingchuan; Yan, Hao; Qin, Daoyuan; Xia, Qingyou

    2018-06-01

    The silkworm, Bombyx mori, is one of the world's most economically important insect. Surveying variations in gene expression among multiple tissue/organ samples will provide clues for gene function assignments and will be helpful for identifying genes related to economic traits or specific cellular processes. To ensure their accuracy, commonly used gene expression quantification methods require a set of stable reference genes for data normalization. In this study, 24 candidate reference genes were assessed in 10 tissue/organ samples of day 3 fifth-instar B. mori larvae using geNorm and NormFinder. The results revealed that, using the combination of the expression of BGIBMGA003186 and BGIBMGA008209 was the optimum choice for normalizing the expression data of the B. mori tissue/organ samples. The most stable gene, BGIBMGA003186, is recommended if just one reference gene is used. Moreover, the commonly used reference gene encoding cytoplasmic actin was the least appropriate reference gene of the samples investigated. The reliability of the selected reference genes was further confirmed by evaluating the expression profiles of two cathepsin genes. Our results may be useful for future studies involving the quantification of relative gene expression levels of different tissue/organ samples in B. mori. © 2018 Wiley Periodicals, Inc.

  5. Monte Carlo Method in the calculate of conversion coefficients for dose in children's organs and tissues subjected to dentistric radiography

    International Nuclear Information System (INIS)

    Loureiro, E.C.M.; Khoury, H.; Lima, F.R.A.

    1998-01-01

    The increasing utilization of oral X-rays, specially in youngsters and children, prompts the assessment of equivalent doses in their organs and tissues. With this purpose, Monte Carlo code was adopted to simulate an X-ray source irradiating phantoms of the MIRD-5 type with different ages (10, 15 and 40 years old) to calculate the conversion coefficients which transform the exposure at skin to equivalent doses at several organs and tissues of interest. In order to check the computer program, simulations were performed for adult patients using the original code (ADAM,FOR developed by GSF Germany) and the adapted program (MCDRO,PAS). Good agreement between results obtained by both programs was observed. Applications to incisive, canine and molar teeth were simulated. The conversion factors were calculated for the following organs and tissues: thyroid, active bone marrow (head and whole body), bone (facial skeleton, cranium and whole body), skin (head and whole body) and crystalline. Based on the obtained results, it follows that the younger the patient and the langer the field area, the higher the doses in assessed organs and tissues

  6. Life and Death Decisions: Using School-Based Health Education to Facilitate Family Discussion about Organ and Tissue Donation

    Science.gov (United States)

    Waldrop, Deborah P.; Tamburlin, Judith A.; Thompson, Sanna J.; Simon, Mark

    2004-01-01

    Public education that encourages family discussions about organ and tissue donation can enhance understanding, facilitate a donor's wishes and increase the numbers of donations. Action research methods were used to explore the impact of a student-initiated family discussion about donation. Most discussions were positive; only 7% middle school and…

  7. Children as donors : a national study to assess procurement of organs and tissues in pediatric intensive care units

    NARCIS (Netherlands)

    Siebelink, Marion J.; Albers, Marcel J. I. J.; Roodbol, Petrie F.; Van de Wiel, Harry B. M.

    2012-01-01

    A shortage of size-matched organs and tissues is the key factor limiting transplantation in children. Empirical data on procurement from pediatric donors is sparse. This study investigated donor identification, parental consent, and effectuation rates, as well as adherence to the national protocol.

  8. 3D bioprint me: a socioethical view of bioprinting human organs and tissues.

    Science.gov (United States)

    Vermeulen, Niki; Haddow, Gill; Seymour, Tirion; Faulkner-Jones, Alan; Shu, Wenmiao

    2017-09-01

    In this article, we review the extant social science and ethical literature on three-dimensional (3D) bioprinting. 3D bioprinting has the potential to be a 'game-changer', printing human organs on demand, no longer necessitating the need for living or deceased human donation or animal transplantation. Although the technology is not yet at the level required to bioprint an entire organ, 3D bioprinting may have a variety of other mid-term and short-term benefits that also have positive ethical consequences, for example, creating alternatives to animal testing, filling a therapeutic need for minors and avoiding species boundary crossing. Despite a lack of current socioethical engagement with the consequences of the technology, we outline what we see as some preliminary practical, ethical and regulatory issues that need tackling. These relate to managing public expectations and the continuing reliance on technoscientific solutions to diseases that affect high-income countries. Avoiding prescribing a course of action for the way forward in terms of research agendas, we do briefly outline one possible ethical framework 'Responsible Research Innovation' as an oversight model should 3D bioprinting promises are ever realised. 3D bioprinting has a lot to offer in the course of time should it move beyond a conceptual therapy, but is an area that requires ethical oversight and regulation and debate, in the here and now. The purpose of this article is to begin that discussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Tissue-specifically regulated site-specific excision of selectable marker genes in bivalent insecticidal, genetically-modified rice.

    Science.gov (United States)

    Hu, Zhan; Ding, Xuezhi; Hu, Shengbiao; Sun, Yunjun; Xia, Liqiu

    2013-12-01

    Marker-free, genetically-modified rice was created by the tissue-specifically regulated Cre/loxP system, in which the Cre recombinase gene and hygromycin phosphotransferase gene (hpt) were flanked by two directly oriented loxP sites. Cre expression was activated by the tissue-specific promoter OsMADS45 in flower or napin in seed, resulting in simultaneous excision of the recombinase and marker genes. Segregation of T1 progeny was performed to select recombined plants. The excision was confirmed by PCR, Southern blot and sequence analyses indicating that efficiency varied from 10 to 53 % for OsMADS45 and from 12 to 36 % for napin. The expression of cry1Ac and vip3A was detected by RT-PCR analysis in marker-free transgenic rice. These results suggested that our tissue-specifically regulated Cre/loxP system could auto-excise marker genes from transgenic rice and alleviate public concerns about the security of GM crops.

  10. Autoradiographic demonstration of unscheduled DNA synthesis in oral tissues treated with chemical carcinogens in short-term organ culture

    International Nuclear Information System (INIS)

    Ide, F.; Umemura, S.; Ishikawa, T.; Takayama, S.

    1981-01-01

    A system in which oral tissues of inbred F344 adult rats and Syrian golden hamster embryos were used in combination with autoradiography was developed for measurement of unscheduled DNA synthesis (UDS). For this, oral mucosa, submandibular gland, tooth germ and mandible in short-term organ cultures were treated with 4-nitroquinoline l-oxide or N-methyl-N-nitrosourea plus (methyl- 3 H)thymidine. Significant numbers of silver grains, indicating UDS, were detected over the nuclei of cells of all these tissues except rat salivary gland after treatment with carcinogens. This autoradiographic method is suitable for detection of UDS in oral tissues in conditions mimicking those in vivo. Results obtained in this study indicated a potential use of this system for studies on the mechanism of carcinogenesis at a cellular level comparable to in vivo carcinogenesis studies on oral tissues. (author)

  11. The meta-governance of organic seed regulation in the USA, European Union and Mexico

    NARCIS (Netherlands)

    Renaud, Erica; Lammerts van Bueren, Edith; Jiggins, Janice

    2016-01-01

    Seed governance in agriculture is a challenging global issue. This paper analyses the evolution of organic seed regulation in the USA, the European Union and Mexico as model cases of how these challenges are being addressed, based on a study conducted between 2007 and 2014. It highlights how

  12. Murine adipose tissue-derived stromal cell apoptosis and susceptibility to oxidative stress in vitro are regulated by genetic background.

    Directory of Open Access Journals (Sweden)

    Robert Pazdro

    Full Text Available Adipose tissue-derived stromal cells (ADSCs are of interest for regenerative medicine as they are isolated easily and can differentiate into multiple cell lineages. Studies of their in vitro proliferation, survival, and differentiation are common; however, genetic effects on these phenotypes remain unknown. To test if these phenotypes are genetically regulated, ADSCs were isolated from three genetically diverse inbred mouse strains--C57BL/6J (B6, BALB/cByJ (BALB, and DBA/2J (D2--in which genetic regulation of hematopoietic stem function is well known. ADSCs from all three strains differentiated into osteogenic and chondrogenic lineages in vitro. ADSCs from BALB grew least well in vitro, probably due to apoptotic cell death after several days in culture. BALB ADSCs were also the most susceptible to the free radical inducers menadione and H2O2. ADSCs from the three possible F1 hybrids were employed to further define genetic regulation of ADSC phenotypes. D2, but not B6, alleles stimulated ADSC expansion in BALB cells. In contrast, B6, but not D2, alleles rescued BALB H2O2 resistance. We conclude that low oxidative stress resistance does not limit BALB ADSC growth in vitro, as these phenotypes are genetically regulated independently. In addition, ADSCs from these strains are an appropriate model system to investigate genetic regulation of ADSC apoptosis and stress resistance in future studies. Such investigations are essential to optimize cell expansion and differentiation and thus, potential for regenerative medicine.

  13. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling

    NARCIS (Netherlands)

    Spits, Hergen; Di Santo, James P.

    2011-01-01

    Research has identified what can be considered a family of innate lymphoid cells (ILCs) that includes not only natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells but also cells that produce interleukin 5 (IL-5), IL-13, IL-17 and/or IL-22. These ILC subsets are developmentally related,

  14. Tissue specific and androgen-regulated expression of human prostate-specific transglutaminase

    NARCIS (Netherlands)

    H.J. Dubbink (Erik Jan); N.S. Verkaik (Nicole); P.W. Faber; J. Trapman (Jan); F.H. Schröder (Fritz); J.C. Romijn (Johannes)

    1996-01-01

    textabstractTransglutaminases (TGases) are calcium-dependent enzymes catalysing the post-translational cross-linking of proteins. In the prostate at least two TGases are present, the ubiquitously expressed tissue-type TGase (TGC), and a prostate-restricted TGase (TGP).

  15. Creating and validating cis-regulatory maps of tissue-specific gene expression regulation

    Science.gov (United States)

    O'Connor, Timothy R.; Bailey, Timothy L.

    2014-01-01

    Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules–CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for ‘other’ tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a ‘nearest neighbor’ heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps. PMID:25200088

  16. Tissue- and subunit-specific regulation of G-protein expression by hypo- and hyperthyroidism

    NARCIS (Netherlands)

    Michel-Reher, M. B.; Gross, G.; Jasper, J. R.; Bernstein, D.; Olbricht, T.; Brodde, O. E.; Michel, M. C.

    1993-01-01

    Thyroid hormone status has profound effects on signal transduction in various tissues throughout the body. Therefore, we quantified the signal transducing G-proteins in the rat heart, cerebral cortex, vas deferens and liver by immunoblotting and pertussis toxin labeling in response to chemically

  17. Ecdysone Receptor-based Singular Gene Switches for Regulated Transgene Expression in Cells and Adult Rodent Tissues

    Directory of Open Access Journals (Sweden)

    Seoghyun Lee

    2016-01-01

    Full Text Available Controlled gene expression is an indispensable technique in biomedical research. Here, we report a convenient, straightforward, and reliable way to induce expression of a gene of interest with negligible background expression compared to the most widely used tetracycline (Tet-regulated system. Exploiting a Drosophila ecdysone receptor (EcR-based gene regulatory system, we generated nonviral and adenoviral singular vectors designated as pEUI(+ and pENTR-EUI, respectively, which contain all the required elements to guarantee regulated transgene expression (GAL4-miniVP16-EcR, termed GvEcR hereafter, and 10 tandem repeats of an upstream activation sequence promoter followed by a multiple cloning site. Through the transient and stable transfection of mammalian cell lines with reporter genes, we validated that tebufenozide, an ecdysone agonist, reversibly induced gene expression, in a dose- and time-dependent manner, with negligible background expression. In addition, we created an adenovirus derived from the pENTR-EUI vector that readily infected not only cultured cells but also rodent tissues and was sensitive to tebufenozide treatment for regulated transgene expression. These results suggest that EcR-based singular gene regulatory switches would be convenient tools for the induction of gene expression in cells and tissues in a tightly controlled fashion.

  18. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation.

    Directory of Open Access Journals (Sweden)

    Maria Tsoli

    Full Text Available Involuntary weight loss in patients with cancer is the hallmark of cancer cachexia. The etiology of cachexia is multifactorial involving loss of skeletal muscle and adipose tissue associated with high systemic levels of acute phase proteins and inflammatory cytokines. While muscle wasting overtly impacts on cancer patient quality of life, loss of lipid depots represents a sustained energy imbalance. In this study fat depletion was examined in Colon-26 model of cancer cachexia, which is a widely used rodent model of this syndrome. We investigated diurnal expression of circadian rhythm regulators as well as key mediators of energy metabolism and cytokine signaling. Mice bearing the C26 tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5-fold increase in plasma levels of free fatty acids. These changes were associated with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated STAT3 and high SOCS3 gene expression levels. In addition perturbations in circadian regulation of lipid metabolism were also observed. Lipid catabolism did not appear to be influenced by the classical PKA pathway activating the lipase HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR pathways. This study provides evidence for activation of cytokine signaling and concomitant alterations in circadian rhythm and regulators of lipid metabolism in WAT of cachectic animals.

  19. Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

    Science.gov (United States)

    Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David

    2018-06-26

    The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. The functional role for condensin in the regulation of chromosomal organization during the cell cycle.

    Science.gov (United States)

    Kagami, Yuya; Yoshida, Kiyotsugu

    2016-12-01

    In all organisms, the control of cell cycle progression is a fundamental process that is essential for cell growth, development, and survival. Through each cell cycle phase, the regulation of chromatin organization is essential for natural cell proliferation and maintaining cellular homeostasis. During mitosis, the chromatin morphology is dramatically changed to have a "thread-like" shape and the condensed chromosomes are segregated equally into two daughter cells. Disruption of the mitotic chromosome architecture physically impedes chromosomal behaviors, such as chromosome alignment and chromosome segregation; therefore, the proper mitotic chromosome structure is required to maintain chromosomal stability. Accumulating evidence has demonstrated that mitotic chromosome condensation is induced by condensin complexes. Moreover, recent studies have shown that condensin also modulates interphase chromatin and regulates gene expression. This review mainly focuses on the molecular mechanisms that condensin uses to exert its functions during the cell cycle progression. Moreover, we discuss the condensin-mediated chromosomal organization in cancer cells.

  1. The effect of high-frequency electrical pulses on organic tissue in root canals.

    Science.gov (United States)

    Lendini, M; Alemanno, E; Migliaretti, G; Berutti, E

    2005-08-01

    To evaluate debris and smear layer scores after application of high-frequency electrical pulses produced by the Endox Endodontic System (Lysis Srl, Nova Milanese, Italy) on intact pulp tissue and organic and inorganic residues after endodontic instrumentation. The study comprised 75 teeth planned for extraction. The teeth were randomly divided into two groups (60 teeth) and a control group (15 teeth): group 1 (30 teeth) was not subjected to instrumentation; group 2 (30 teeth) was instrumented by Hero Shaper instruments and apical stops were prepared to size 40. Each group was subdivided into subgroups A and B (15 teeth); two electrical pulses were applied to subgroups 1A and 2A (one in the apical third and one in the middle third, respectively, at 3 and 6 mm from the root apices); four electrical pulses were applied to subgroups 1B and 2B (two in the apical third, two in the middle third). The control group (15 teeth) was prepared with Hero Shapers and irrigated with 5 mL of EDTA (10%) and 5 mL of 5% NaOCl at 50 degrees C but not subjected to the electrical pulse treatment. Roots were split longitudinally and canal walls were examined at 80x, 200x, 750x, 1500x and 15,000x magnifications, using a scanning electron microscope. Smear layer and debris scores were recorded at the 3 and 6 mm levels using a five-step scoring scale and a 200-microm grid. Means were tested for significance using the one-way anova model and the Bonferroni post-hoc test. The differences between groups were considered to be statistically significant when P < 0.05. The mean value for debris scores for the three groups varied from 1.80 (+/-0.77) to 4.50 (+/-0.68). The smear layer scores for group 2 and the control specimens varied from 2.00 (+/-0.91) to 2.33 (+/-0.99). A significant difference was found in mean debris scores at the 3 and 6 mm levels between the three groups (P < 0.001). The Bonferroni post-hoc test confirmed that the difference was due to group 1. In the two subgroups treated

  2. The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules

    DEFF Research Database (Denmark)

    Halberg, Kenneth Agerlin; Rainey, Stephanie M.; Veland, Iben Rønn

    2016-01-01

    Multicellular organisms rely on cell adhesion molecules to coordinate cell-cell interactions, and to provide navigational cues during tissue formation. In Drosophila, Fasciclin 2 (Fas2) has been intensively studied due to its role in nervous system development and maintenance; yet, Fas2 is most...... role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border....

  3. Heavy metal distribution in organic and siliceous marine sponge tissues measured by square wave anodic stripping voltammetry.

    Science.gov (United States)

    Illuminati, S; Annibaldi, A; Truzzi, C; Scarponi, G

    2016-10-15

    May sponge spicules represent a "tank" to accumulate heavy metals? In this study we test this hypothesis determining the distribution of Cd, Pb and Cu concentrations between organic and siliceous tissues in Antarctic Demospongia (Sphaerotylus antarcticus, Kirkpatrikia coulmani and Haliclona sp.) and in the Mediterranean species Petrosia ficiformis. Results show that although, in these sponges, spicules represent about 80% of the mass content, the accumulation of pollutant is lower in the spicules than in the corresponding organic fraction. The contribution of tissues to the total sponge content of Cd, Pb and Cu is respectively 99%, 82% and 97% for Antarctic sponges and 96%, 95% and 96% for P. ficiformis, similar in polar and temperate organisms. These results pave the way to a better understanding of the role of marine sponges in uptaking heavy metals and to their possible use as monitor of marine ecosystems, recommend by the Water Framework Directive. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Alpha-particle doses to human organs and tissues from internally-deposited 226Ra and 228Ra

    International Nuclear Information System (INIS)

    Keane, A.T.; Schlenker, R.A.

    1981-01-01

    Estimation of radiation doses to the soft tissues from internally-deposited 226 Ra and 228 Ra is relevant to an investigation of soft-tissue malignancies in radium-exposed persons being conducted at the Center for Human Radiobiology. Alpha-particle doses in a 50-year period following a single injection of 226 Ra or 228 Ra are presented for 31 soft tissues and organs of the adult human. The dose estimates were derived from the ICRP alkaline earth model fitted to data on retention of 226 Ra in soft tissues and bone, combined with reported ratios of 226 Ra to Ca in soft tissue and bone at natural levels and the distribution of Ca in the tissues of Reference Man (ICRP23). The median of the 31 organ and tissue doses from the α-particles of 226 Ra itself is 0.08 rad per injected μCi. An additional average dose of 0.01 rad per μCi 226 Ra daughter products produced in soft tissue or transferred from bone to soft tissue. Soft-tissue doses from α-particles of the 228 Ra decay series are about six times those from 226 Ra α-particles for equal injected activities of 228 Ra and 226 Ra, with the assumption that 228 Ra daughter products do not transfer from the organ in which they are produced. The 50-year dose to the red marrow of bone from α-particles originating in bone is 0.55 rad per μCi 226 Ra injected and 1.0 rad per μCi 228 Ra injected. For ingestion by dial painters of luminous compound containg 226 Ra or 228 Ra with a daughter-to-parent activity ratio of 0.5, the dose to the mucosal alyer of the lower large intestine from α-particles originating in the gut contents is about 0.1 rad per μCi systemic intake of 226 Ra or 228 Ra

  5. Occurrence of Legacy and New Persistent Organic Pollutants in Avian Tissues from King George Island, Antarctica.

    Science.gov (United States)

    Kim, Jun-Tae; Son, Min-Hui; Kang, Jung-Ho; Kim, Jeong-Hoon; Jung, Jin-Woo; Chang, Yoon-Seok

    2015-11-17

    Legacy and new persistent organic pollutants (POPs), including polychlorinated naphthalenes (PCNs), Dechlorane Plus (DPs) and related compounds (Dechloranes), hexabromocyclododecanes (HBCDs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs), were analyzed in avian tissue samples from King George Island, Antarctica. The avian species consisted of the Gentoo penguin (Pygoscelis papua), the Adelie penguin (Pygoscelis adeliae), the South polar skua (Stercorarius maccormicki), and the Brown skua (Stercorarius antarcticus). HBCDs were detected in all samples and ranged from 1.67-713 pg/g-lipid. In the penguin samples, the concentrations of PCNs ranged from 0.69-2.07 ng/g-lipid, whereas those in the skua samples ranged from 7.41-175 ng/g-lipid. The levels of Dechloranes ranged from 0.60-1.30 ng/g-lipid in the penguin samples and from 6.57-47.4 ng/g-lipid in the skua samples. The concentrations and congener distributions of OCPs and PCBs were similar to the results of previous reports. The three new POPs were detected in all samples, and this study was one of the first reports on the occurrence of these pollutants in the Antarctic biota. Because Antarctica is one of the most pristine places on Earth, the detection of new POPs in the Antarctic birds, especially penguins, is direct evidence of the long-range transport of pollutants. Furthermore, the concentration ratios of the penguin to the skua samples (BMFs-p) were greater than 1 in most legacy and new POPs, and the BMFs-p values of the new POPs were comparable to those of some OCPs, suggesting a possibility of biomagnification. Despite the small sample size, the results of this study identified POP contamination of the Antarctic avian species and long-range transport and biomagnification of HBCDs, Dechloranes, and PCNs.

  6. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  7. Multi-target determination of organic ultraviolet absorbents in organism tissues by ultrasonic assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Peng, Xianzhi; Jin, Jiabin; Wang, Chunwei; Ou, Weihui; Tang, Caiming

    2015-03-06

    A sensitive and reliable method was developed for multi-target determination of 13 most widely used organic ultraviolet (UV) absorbents (including UV filters and UV stabilizers) in aquatic organism tissues. The organic UV absorbents were extracted using ultrasonic-assisted extraction, purified via gel permeation chromatography coupled with silica gel column chromatography, and determined by ultra-high performance liquid chromatography-tandem mass spectrometry. Recoveries of the UV absorbents from organism tissues mostly ranged from 70% to 120% from fish filet with satisfactory reproducibility. Method quantification limits were 0.003-1.0ngg(-1) dry weight (dw) except for 2-ethylhexyl 4-methoxycinnamate. This method has been applied to analysis of the UV absorbents in wild and farmed aquatic organisms collected from the Pearl River Estuary, South China. 2-Hydroxy-4-methoxybenzophenone and UV-P were frequently detected in both wild and farmed marine organisms at low ngg(-1)dw. 3-(4-Methylbenzylidene)camphor and most of the benzotriazole UV stabilizers were also frequently detected in maricultured fish. Octocrylene and 2-ethylhexyl 4-methoxycinnamate were not detected in any sample. This work lays basis for in-depth study about bioaccumulation and biomagnification of the UV absorbents in marine environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

    Directory of Open Access Journals (Sweden)

    Ori Nov

    Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin

  9. Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue

    Directory of Open Access Journals (Sweden)

    Carly T. Cederquist

    2017-01-01

    Conclusions: Our findings characterize a novel layer of regulation of the insulin signaling pathway based on non-proteolytic ubiquitination of AKT and define GPS2 as a previously unrecognized component of the insulin signaling cascade. In accordance with this role, we have shown that GPS2 presence in adipocytes modulates systemic metabolism by restricting the activation of insulin signaling during the fasted state, whereas in absence of GPS2, the adipose tissue is more efficient at lipid storage, and obesity becomes uncoupled from inflammation and insulin resistance.

  10. The hemodynamically-regulated vascular microenvironment promotes migration of the steroidogenic tissue during its interaction with chromaffin cells in the zebrafish embryo.

    Directory of Open Access Journals (Sweden)

    Chih-Wei Chou

    Full Text Available BACKGROUND: While the endothelium-organ interaction is critical for regulating cellular behaviors during development and disease, the role of blood flow in these processes is only partially understood. The dorsal aorta performs paracrine functions for the timely migration and differentiation of the sympatho-adrenal system. However, it is unclear how the adrenal cortex and medulla achieve and maintain specific integration and whether hemodynamic forces play a role. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, the possible modulation of steroidogenic and chromaffin cell integration by blood flow was investigated in the teleostean counterpart of the adrenal gland, the interrenal gland, in the zebrafish (Danio rerio. Steroidogenic tissue migration and angiogenesis were suppressed by genetic or pharmacologic inhibition of blood flow, and enhanced by acceleration of blood flow upon norepinephrine treatment. Repressed steroidogenic tissue migration and angiogenesis due to flow deficiency were recoverable following restoration of flow. The regulation of interrenal morphogenesis by blood flow was found to be mediated through the vascular microenvironment and the Fibronectin-phosphorylated Focal Adhesion Kinase (Fn-pFak signaling. Moreover, the knockdown of krüppel-like factor 2a (klf2a or matrix metalloproteinase 2 (mmp2, two genes regulated by the hemodynamic force, phenocopied the defects in migration, angiogenesis, the vascular microenvironment, and pFak signaling of the steroidogenic tissue observed in flow-deficient embryos, indicating a direct requirement of mechanotransduction in these processes. Interestingly, epithelial-type steroidogenic cells assumed a mesenchymal-like character and downregulated β-Catenin at cell-cell junctions during interaction with chromaffin cells, which was reversed by inhibiting blood flow or Fn-pFak signaling. Blood flow obstruction also affected the migration of chromaffin cells, but not through

  11. Pathogenesis of cerebral palsy through the prism of immune regulation of nervous tissue homeostasis: literature review.

    Science.gov (United States)

    Lisovska, Natalya; Daribayev, Zholtay; Lisovskyy, Yevgeny; Kussainova, Kenzhe; Austin, Lana; Bulekbayeva, Sholpan

    2016-11-01

    The cerebral palsy is highly actual issue of pediatrics, causing significant neurological disability. Though the great progress in the neuroscience has been recently achieved, the pathogenesis of cerebral palsy is still poorly understood. In this work, we reviewed available experimental and clinical data concerning the role of immune cells in pathogenesis of cerebral palsy. Maintaining of homeostasis in nervous tissue and its transformation in case of periventricular leukomalacia were analyzed. The reviewed data demonstrate involvement of immune regulatory cells in the formation of nervous tissue imbalance and chronicity of inborn brain damage. The supported opinion, that periventricular leukomalacia is not a static phenomenon, but developing process, encourages our optimism about the possibility of its correction. The further studies of changes of the nervous and immune systems in cerebral palsy are needed to create fundamentally new directions of the specific therapy and individual schemes of rehabilitation.

  12. The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival

    Directory of Open Access Journals (Sweden)

    Bonkowski Drew

    2011-01-01

    Full Text Available Abstract The French scientist Charles Benjamin Rouget identified the pericyte nearly 140 years ago. Since that time the role of the pericyte in vascular function has been difficult to elucidate. It was not until the development of techniques to isolate and culture pericytes that scientists have begun to understand the true impact of this unique cell in the maintenance of tissue homeostasis. In the brain the pericyte is an integral cellular component of the blood-brain barrier and, together with other cells of the neurovascular unit (endothelial cells, astrocytes and neurons the pericyte makes fine-tuned regulatory adjustments and adaptations to promote tissue survival. These regulatory changes involve trans-cellular communication networks between cells. In this review we consider evidence for cell-to-cell crosstalk between pericytes and astrocytes during development and in adult brain.

  13. 38 CFR 1.485a - Eye, organ and tissue donation.

    Science.gov (United States)

    2010-07-01

    ... centers must verify annually in January of each calendar year with the Food and Drug Administration (FDA) that an eye bank or tissue bank has complied with the FDA registration requirements of 21 CFR part 1271 and that the registration status is active before permitting an eye bank or tissue bank to receive...

  14. Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues

    DEFF Research Database (Denmark)

    Lundby, Alicia; Secher, Anna; Lage, Kasper

    2012-01-01

    Deregulated cellular signalling is a common hallmark of disease, and delineating tissue phosphoproteomes is key to unravelling the underlying mechanisms. Here we present the broadest tissue catalogue of phosphoproteins to date, covering 31,480 phosphorylation sites on 7,280 proteins quantified ac...

  15. Catalase activity prevents exercise-induced up-regulation of vasoprotective proteins in venous tissue

    OpenAIRE

    Dao, Vu Thao-Vi; Floeren, Melanie; Kumpf, Stephanie; Both, Charlotte; Peter, B?rbel; Balz, Vera; Suvorava, Tatsiana; Kojda, Georg

    2011-01-01

    Abstract Physical activity induces favourable changes of arterial gene expression and protein activity, although little is known about its effect in venous tissue. Although our understanding of the initiating molecular signals is still incomplete, increased expression of endothelial nitric oxide synthase (eNOS) is considered a key event. This study sought to investigate the effects of two different training protocols on the expression of eNOS and extracellular superoxide dismutase (ecSOD) in ...

  16. Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

    DEFF Research Database (Denmark)

    Venø, Morten Trillingsgaard; Bramsen, Jesper Bertram; Bendixen, Christian

    2012-01-01

    Editing by ADAR enzymes is essential for mammalian life. Still, knowledge of the spatio-temporal editing patterns in mammals is limited. By use of 454 amplicon sequencing we examined the editing status of 12 regionally extracted mRNAs from porcine developing brain encompassing a total of 64...... putative ADAR editing sites. In total 24 brain tissues, dissected from up to five regions from embryonic gestation day 23, 42, 60, 80, 100 and 115, were examined for editing....

  17. Photoperiodic regulation of PER1 and PER2 protein expression in rat peripheral tissues

    Czech Academy of Sciences Publication Activity Database

    Bendová, Zdeňka; Sumová, Alena

    2006-01-01

    Roč. 55, č. 6 (2006), s. 623-632 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP309/02/D093; GA MŠk(CZ) LC554 Grant - others:EUCLOCK(XE) 018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian rhythms * peripheral tissue * PER proteins Subject RIV: FH - Neurology Impact factor: 2.093, year: 2006

  18. Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

    Directory of Open Access Journals (Sweden)

    Shiro Koizume

    2015-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

  19. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  20. Adipose tissue (PRR regulates insulin sensitivity, fat mass and body weight

    Directory of Open Access Journals (Sweden)

    Zulaykho Shamansurova

    2016-10-01

    Full Text Available Objective: We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(PRR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (PRR gene would prevent weight gain and insulin resistance. Methods: An adipose tissue-specific (PRR knockout (KO mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (PRR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. Results: KO mice had lower body weights compared to wild-types (WT. Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (PRR. Conclusions: (PRR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes. Keywords: (Prorenin receptor, Renin-angiotensin system, Adipose

  1. The effect of plant growth regulators on optimization of tissue culture ...

    African Journals Online (AJOL)

    Mature seeds of four upland rice cultivars namely Kusan, Lamsan, Selasi and Siam were assessed for callus induction and plant regeneration on different concentrations and combinations of plant growth regulators, incorporated into MS (Murashige and Skoog) basal medium. Callus induction frequency was significantly ...

  2. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Directory of Open Access Journals (Sweden)

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  3. A fish-feeding laboratory bioassay to assess the antipredatory activity of secondary metabolites from the tissues of marine organisms.

    Science.gov (United States)

    Marty, Micah J; Pawlik, Joseph R

    2015-01-11

    Marine chemical ecology is a young discipline, having emerged from the collaboration of natural products chemists and marine ecologists in the 1980s with the goal of examining the ecological functions of secondary metabolites from the tissues of marine organisms. The result has been a progression of protocols that have increasingly refined the ecological relevance of the experimental approach. Here we present the most up-to-date version of a fish-feeding laboratory bioassay that enables investigators to assess the antipredatory activity of secondary metabolites from the tissues of marine organisms. Organic metabolites of all polarities are exhaustively extracted from the tissue of the target organism and reconstituted at natural concentrations in a nutritionally appropriate food matrix. Experimental food pellets are presented to a generalist predator in laboratory feeding assays to assess the antipredatory activity of the extract. The procedure described herein uses the bluehead, Thalassoma bifasciatum, to test the palatability of Caribbean marine invertebrates; however, the design may be readily adapted to other systems. Results obtained using this laboratory assay are an important prelude to field experiments that rely on the feeding responses of a full complement of potential predators. Additionally, this bioassay can be used to direct the isolation of feeding-deterrent metabolites through bioassay-guided fractionation. This feeding bioassay has advanced our understanding of the factors that control the distribution and abundance of marine invertebrates on Caribbean coral reefs and may inform investigations in diverse fields of inquiry, including pharmacology, biotechnology, and evolutionary ecology.

  4. Development of tissue bank

    Directory of Open Access Journals (Sweden)

    R P Narayan

    2012-01-01

    Full Text Available The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

  5. Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

    Science.gov (United States)

    Shamansurova, Zulaykho; Tan, Paul; Ahmed, Basma; Pepin, Emilie; Seda, Ondrej; Lavoie, Julie L

    2016-10-01

    We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

  6. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

    DEFF Research Database (Denmark)

    Hao, Qin; Yadav, Rachita; Basse, Astrid L.

    2015-01-01

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen...... exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...

  7. Characterization of cDNA encoding molt-inhibiting hormone of the crab, Cancer pagurus; expression of MIH in non-X-organ tissues.

    Science.gov (United States)

    Lu, W; Wainwright, G; Olohan, L A; Webster, S G; Rees, H H; Turner, P C

    2001-10-31

    Synthesis of ecdysteroids (molting hormones) by crustacean Y-organs is regulated by a neuropeptide, molt-inhibiting hormone (MIH), produced in eyestalk neural ganglia. We report here the molecular cloning of a cDNA encoding MIH of the edible crab, Cancer pagurus. Full-length MIH cDNA was obtained by using reverse transcription-polymerase chain reaction (RT-PCR) with degenerate oligonucleotides based upon the amino acid sequence of MIH, in conjunction with 5'- and 3'-RACE. Full-length clones of MIH cDNA were obtained that encoded a 35 amino acid putative signal peptide and the mature 78 amino acid peptide. Of various tissues examined by Northern blot analysis, the X-organ was the sole major site of expression of the MIH gene. However, a nested-PCR approach using non-degenerate MIH-specific primers indicated the presence of MIH transcripts in other tissues. Southern blot analysis indicated a simple gene arrangement with at least two copies of the MIH gene in the genome of C. pagurus. Additional Southern blotting experiments detected MIH-hybridizing bands in another Cancer species, Cancer antennarius and another crab species, Carcinus maenas.

  8. Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.

    Science.gov (United States)

    Withers, Catherine N; Brown, Drew M; Byiringiro, Innocent; Allen, Matthew R; Condon, Keith W; Satin, Jonathan; Andres, Douglas A

    2017-10-01

    The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca 2+ channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression (Runx2, osterix, etc.) is not altered in Rad -/- calvarial osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of extracellular matrix mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher marrow adipose tissue levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of wildtype calvarial osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad and establish a role for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures

    OpenAIRE

    Blekhman, Ran; Oshlack, Alicia; Chabot, Adrien E.; Smyth, Gordon K.; Gilad, Yoav

    2008-01-01

    Author Summary It has long been hypothesized that in addition to structural changes to proteins, changes in gene regulation might underlie many of the anatomic and behavioral differences between humans and other primates. However, to date, there are only a handful of examples of regulatory adaptations in humans. In this work, we present a genome-wide study of gene expression levels in livers, kidneys, and hearts from three species: humans, chimpanzees, and rhesus macaques. These data allowed ...

  10. Species and tissue type regulate long-term decomposition of brackish marsh plants grown under elevated CO2 conditions

    Science.gov (United States)

    Jones, Joshua A; Cherry, Julia A; Mckee, Karen L.

    2016-01-01

    Organic matter accumulation, the net effect of plant production and decomposition, contributes to vertical soil accretion in coastal wetlands, thereby playing a key role in whether they keep pace with sea-level rise. Any factor that affects decomposition may affect wetland accretion, including atmospheric CO2 concentrations. Higher CO2 can influence decomposition rates by altering plant tissue chemistry or by causing shifts in plant species composition or biomass partitioning. A combined greenhouse-field experiment examined how elevated CO2 affected plant tissue chemistry and subsequent decomposition of above- and belowground tissues of two common brackish marsh species, Schoenoplectus americanus (C3) and Spartina patens (C4). Both species were grown in monoculture and in mixture under ambient (350-385 μL L-1) or elevated (ambient + 300 μL L-1) atmospheric CO2 conditions, with all other growth conditions held constant, for one growing season. Above- and belowground tissues produced under these treatments were decomposed under ambient field conditions in a brackish marsh in the Mississippi River Delta, USA. Elevated CO2 significantly reduced nitrogen content of S. americanus, but not sufficiently to affect subsequent decomposition. Instead, long-term decomposition (percent mass remaining after 280 d) was controlled by species composition and tissue type. Shoots of S. patens had more mass remaining (41 ± 2%) than those of S. americanus (12 ± 2 %). Belowground material decomposed more slowly than that placed aboveground (62 ± 1% vs. 23 ± 3% mass remaining), but rates belowground did not differ between species. Increases in atmospheric CO2concentration will likely have a greater effect on overall decomposition in this brackish marsh community through shifts in species dominance or biomass allocation than through effects on tissue chemistry. Consequent changes in organic matter accumulation may alter marsh capacity to accommodate sea-level rise

  11. Effect of supramolecular organization of a cartilaginous tissue on thermal stability of collagen II

    Science.gov (United States)

    Ignat'eva, N. Yu.; Averkiev, S. V.; Lunin, V. V.; Grokhovskaya, T. E.; Obrezkova, M. V.

    2006-08-01

    The thermal stability of collagen II in various cartilaginous tissues was studied. It was found that heating a tissue of nucleus pulposus results in collagen II melting within a temperature range of 60-70°C; an intact tissue of hyaline cartilage (of nasal septum and cartilage endplates) is a thermally stable system, where collagen II is not denatured completely up to 100°C. It was found that partial destruction of glycosaminoglycans in hyaline cartilage leads to an increase in the degree of denaturation of collagen II upon heating, although a significant fraction remains unchanged. It was shown that electrostatic interactions of proteoglycans and collagen only slightly affect the thermal stability of collagen II in the tissues. Evidently, proteoglycan aggregates play a key role: they create topological hindrances for moving polypeptide chains, thereby reducing the configurational entropy of collagen macromolecules in the state of a random coil.

  12. Side effects of ionizing radiation on healthy tissues and organs at risk

    International Nuclear Information System (INIS)

    Cosset, J.M.

    2010-01-01

    Ionizing radiations induce cell death, causing deterministic or stochastic side-effects. This paper briefly summarizes the biological mechanisms of early and late side-effects of ionizing radiations on healthy tissue. (author)

  13. Decree 831/976 Industry and Energy Ministry approve an organic regulation

    International Nuclear Information System (INIS)

    1976-01-01

    The ordinance 831 of 1976 approve the organic regulation of the Ministry of Industry and Energy and organization manuals and functions according to the principle and elaborated technical approaches and systematized by the National Office of the Civil Service. Among some of their made they are projecting the industrial politics and energetics of the country exercising supervision and control, as well as the development of the industry and diverse energy sources, to propitiate the use of the atomic energy in the Uruguay coordinating the activities that are carried out

  14. Regulating biobanking with children's tissue: a legal analysis and the experts' view.

    Science.gov (United States)

    Kranendonk, Elcke J; Ploem, M Corrette; Hennekam, Raoul C M

    2016-01-01

    Many current paediatric studies concern relationships between genes and environment and discuss aetiology, treatment and prevention of Mendelian and multifactorial diseases. Many of these studies depend on collection and long-term storage of data and biological material from affected children in biobanks. Stored material is a source of personal information of the donor and his family and could be used in an undesirable context, potentially leading to discrimination and interfering with a child's right to an open future. Here, we address the normative framework regarding biobanking with residual tissue of children, protecting the privacy interests of young biobank donors (0-12 years). We analyse relevant legal documents concerning storage and use of children's material for research purposes. We explore the views of 17 Dutch experts involved in paediatric biobank research and focus on informed consent for donation of leftover tissue as well as disclosure of individual research findings resulting from biobank research. The results of this analysis show that experts have no clear consensus about the appropriate rules for storage of and research with children's material in biobanks. Development of a framework that provides a fair balance between fundamental paediatric research and privacy protection is necessary.

  15. The regulation of subcutaneous adipose tissue blood flow in the ischaemic forefoot during 24 hours

    International Nuclear Information System (INIS)

    Jelnes, R.

    1988-01-01

    A method for continuous measurement of subcutaneous adipose tissue blood flow in the forefoot during 24 hours (SBF) is described. The method is based on the radioisotope wash-out principle using 133-Xenon. A portable semiconductor detector is placed just above a local depot of 1-2 μCi 133-Xenon in 0.1 ml isotonic saline injected into the subcutaneous adipose tissue in the forefoot. The detector is connected to a memory unit allowing for storage of data. Due to the short distance, the recorded elimination rate constant must be corrected for combined convection and diffusion of the radioactive indicator. After reconstructive vascular surgery, the 24-hour blood flow pattern normalized although the ankle/arm systolic blood pressure index did not come within normal range. SBF during day-time activities decreased by up to 50% postoperatively. This is caused by the reappearance of the local, sympathetic, veno-arteriolar vasoconstrictor response. During sleep SBF increased by 71%. The term postreconstructuve hyperamia seems improper, at least in a long-term context, normalization of preoperative ischaemia is a more correct notation. The coefficient of variation of nocturnal SBF was calculated to 10%. The method thus seems apt as a monitor in medical therapy for occlusive arterial disease. Changes of λ has, however, to be considered in each study. 94 refs. (EG)

  16. Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

    Science.gov (United States)

    Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

    2015-11-10

    The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

  17. [Rat tissues antioxidant status correction by peptide delta sleep during physiological aging of the organism].

    Science.gov (United States)

    Bondarenko, T I; Kutilin, D S; Mikhaleva, I I

    2014-01-01

    It is shown that exogenous delta-sleep inducing peptide increases glutathione antioxidant system level in rat tissues at different stages of ontogenesis, by subcutaneous injection to rats 2-24 months postnatal development in a dose of 100 mg/kg animal body weight by courses of 5 consecutive days per month, and this effect is especially marked in non-renewable postmitotic tissues.

  18. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  19. Distribution of /sup 125/I-thyroxine in different organs and tissues of dietically obese rats

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, K.; Voss, C.; Huebner, G. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic)); Weber, A. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

    1985-04-01

    The distribution of /sup 125/I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished /sup 125/I-T/sub 4/ distribution in the 'slow pool' (fat tissue, muscle) and unchanged values in the 'fast pool' (liver, kidneys) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the /sup 125/I-T/sub 4/ distribution were found in the /sup 125/I-T/sub 4/ between HFD and LFD rats with relatively equal body weight and body composition. The reduced T/sub 4/ distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity.

  20. Regulating specific organic substances and heavy metals in industrial wastewater discharged to municipal wastewater treatment plants

    DEFF Research Database (Denmark)

    Grüttner, Henrik; Munk, L.; Pedersen, F.

    1994-01-01

    Due to the extension of wastewater treatment plants to nutrient removal and the development towards reuse of sludge m agriculture, new guidelines for regulating industrial discharges m Denmark were needed. The paper describes how a concept for regulating the discharge of specific organic substances...... substances, present knowledge of fate and effects in biological treatment plants is too scarce to underpin the setting of general standards. Therefore, it has been decided to base the developed priority system on the data used in the EEC-system for classification of hazardous chemicals. This includes ready...... degradability, defined by the OECD-test, bio-sorption and bio-accumulation, defined by the octanol/water distribution coefficient and toxic effects on water organisms. Several potential effects of seven heavy metals have been evaluated, and the most critical effects were found to be the quality criteria...

  1. Perceptions of the gift relationship in organ and tissue donation: Views of intensivists and donor and recipient coordinators.

    Science.gov (United States)

    Shaw, Rhonda

    2010-02-01

    The international literature on organ donation and transplantation has drawn attention to the popularity of "gift of life" discourse among pro-donation advocates, transplantation specialists, and within organisations lobbying for improved donation rates to promote the benefits of organ donation among members of the general public. In Aotearoa/New Zealand, gift of life discourse is robust. Aside from attempts to elicit altruism by promoting tissue donation in the public domain, gift terminology separates the act of donation from that of commerce and the commodification of body tissues. In distancing donation from commodification and the potential to degrade and exploit human beings, it is assumed that gift discourse transmits the positive message that donation is a noble and morally worthy act. Recent sociological research has shown that assumptions of the gift as one-way and altruistic do not necessarily align with people's perceptions and experience of donating body tissues, and that the vocabulary used to describe these acts is often at variance with reality. This article draws on interview data with 15 critical care specialists (intensivists) and donor and recipient coordinators, examining their perceptions of the relevance of gift discourse and its applicability in the context of deceased donation in Aotearoa/New Zealand. The data indicate several problems with gift rhetoric to describe the situations health professionals encounter. In sum, gift terminology tends to downplay the sacrifice involved in tissue donation generally, as well as depoliticising the exchange relations of tissue transfer in contemporary consumer culture and in the global context. This raises questions about the underlying ethics of language choice and what, if anything, empirical accounts of tissue transfer can contribute to ethical debates. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. Knowledge About Legal Regulations Regarding Organ Transplantation Among High School and University Students in Poland.

    Science.gov (United States)

    Pawłowicz, E; Nowicki, M

    2016-06-01

    It has been reported in many studies that although young people have positive attitudes towards organ donation, their knowledge about transplantation is insufficient. This study focused on knowledge about legal regulations regarding organ transplantation in Poland. A 59-item, self-designed questionnaire was administered to 1011 young persons from Central Poland. Among the interviewees were 462 high school students, 184 students of the faculty of medicine, and 365 students from other faculties. The survey was divided into 4 parts: knowledge (basic information, maximum of 17 points; statistics, maximum of 5 points and legal regulations - maximum of 6 points), attitude, personal experience and general characteristics of the interviewees. High school and university students received 1.45 ± 1.24 and 1.54 ± 1.1 (P = .26) out of a maximal score of 6 with respect to knowledge of legal regulations. Medical students scored much higher (4.13 ± 1.23). Only 20 respondents (including 19 medical students) answered correctly all 6 questions. Those who were willing to donate their organs after death achieved better result than those who did not want to donate (1.6 ± 1.22 vs 1.34 ± 1.1; P = .002). Personal experiences did not influence knowledge about transplantation. Knowledge about legal regulations regarding organ transplantation is insufficient among young people. Structured, well-considered education programs at various levels of school and academic education are needed to improve public awareness and attitude. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.

    Science.gov (United States)

    Rothrauff, Benjamin B; Pauyo, Thierry; Debski, Richard E; Rodosky, Mark W; Tuan, Rocky S; Musahl, Volker

    2017-08-01

    The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

  4. Tissue damage in organic rainbow trout muscle investigated by proteomics and bioinformatics

    DEFF Research Database (Denmark)

    Wulff, Tune; Silva, T.; Nielsen, Michael Engelbrecht

    2013-01-01

    and magnitude of the cellular response, in the context of a regenerative process. Using a bioinformatics approach, the main biological function of these proteins were assigned, showing the regulation of proteins involved in processes like apoptosis, iron homeostasis and regulation of muscular structure...

  5. The nuclear retinoid-related orphan receptor-α regulates adipose tissue glyceroneogenesis in addition to hepatic gluconeogenesis.

    Science.gov (United States)

    Kadiri, Sarah; Monnier, Chloé; Ganbold, Munkhzul; Ledent, Tatiana; Capeau, Jacqueline; Antoine, Bénédicte

    2015-07-15

    Circadian rhythms have an essential role in feeding behavior and metabolism. RORα is a nuclear receptor involved in the interface of the circadian system and metabolism. The adipocyte glyceroneogenesis pathway derives free fatty acids (FFA) liberated by lipolysis to reesterification into triglycerides, thus regulating FFA homeostasis and fat mass. Glyceroneogenesis shares with hepatic gluconeogenesis the key enzyme phosphoenolpyruvate carboxykinase c (PEPCKc), whose gene is a RORα target in the liver. RORα-deficient mice (staggerer, ROR(sg/sg)) have been shown to exhibit a lean phenotype and fasting hypoglycemia for unsolved reasons. In the present study, we investigated whether adipocyte glyceroneogenesis might also be a target pathway of RORα, and we further evaluated the role of RORα in hepatocyte gluconeogenesis. In vivo investigations comparing ROR(sg/sg) mice with their wild-type (WT) littermates under fasting conditions demonstrated that, in the absence of RORα, the release of FFA into the bloodstream was altered and the rise in glycemia in response to pyruvate reduced. The functional analysis of each pathway, performed in adipose tissue or liver explants, confirmed the impairment of adipocyte glyceroneogenesis and liver gluconeogenesis in the ROR(sg/sg) mice; these reductions of FFA reesterification or glucose production were associated with decreases in PEPCKc mRNA and protein levels. Treatment of explants with RORα agonist or antagonist enhanced or inhibited these pathways, respectively, in tissues isolated from WT but not ROR(sg/sg) mice. Our results indicated that both adipocyte glyceroneogenesis and hepatocyte gluconeogenesis were regulated by RORα. This study demonstrates the physiological function of RORα in regulating both glucose and FFA homeostasis. Copyright © 2015 the American Physiological Society.

  6. Growth of Accountable Care Organizations in California: Number, Characteristics, and State Regulation.

    Science.gov (United States)

    Fulton, Brent D; Pegany, Vishaal; Keolanui, Beth; Scheffler, Richard M

    2015-08-01

    Accountable care organizations (ACOs) result in physician organizations' and hospitals' receiving risk-based payments tied to costs, health care quality, and patient outcomes. This article (1) describes California ACOs within Medicare, the commercial market, and Medi-Cal and the safety net; (2) discusses how ACOs are regulated by the California Department of Managed Health Care and the California Department of Insurance; and (3) analyzes the increase of ACOs in California using data from Cattaneo and Stroud. While ACOs in California are well established within Medicare and the commercial market, they are still emerging within Medi-Cal and the safety net. Notwithstanding, the state has not enacted a law or issued a regulation specific to ACOs; they are regulated under existing statutes and regulations. From August 2012 to February 2014, the number of lives covered by ACOs increased from 514,100 to 915,285, representing 2.4 percent of California's population, including 10.6 percent of California's Medicare fee-for-service beneficiaries and 2.3 percent of California's commercially insured lives. By emphasizing health care quality and patient outcomes, ACOs have the potential to build and improve on California's delegated model. If recent trends continue, ACOs will have a greater influence on health care delivery and financial risk sharing in California. Copyright © 2015 by Duke University Press.

  7. Browning and graying: novel transcriptional regulators of brown and beige fat tissues and aging

    Directory of Open Access Journals (Sweden)

    Elisabetta eMueller

    2016-03-01

    Full Text Available Obesity represents a major risk factor for the development of a number of metabolic disorders, including cardiovascular disease and type 2 diabetes. Since the discovery that brown and beige fat cells exist in adult humans and contribute to energy expenditure, increasing interest has been devoted to the understanding of the molecular switches turning on calorie utilization. It has been reported that the ability of thermogenic tissues to burn energy declines during aging, possibly contributing to the development of metabolic dysfunction late in life. This review will focus on the recently identified transcriptional modulators of brown and beige cells and will discuss the potential impact of some of these thermogenic factors on age-associated metabolic disorders.

  8. Results from a horizon scan on risks associated with transplantation of human organs, tissues and cells: from donor to patient.

    Science.gov (United States)

    Herberts, C A; Park, M V D Z; Pot, J W G A; de Vries, C G J C A

    2015-03-01

    The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient's own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.

  9. A Review on the 3D Printing of Functional Structures for Medical Phantoms and Regenerated Tissue and Organ Applications

    Directory of Open Access Journals (Sweden)

    Kan Wang

    2017-10-01

    Full Text Available Medical models, or “phantoms,” have been widely used for medical training and for doctor-patient interactions. They are increasingly used for surgical planning, medical computational models, algorithm verification and validation, and medical devices development. Such new applications demand high-fidelity, patient-specific, tissue-mimicking medical phantoms that can not only closely emulate the geometric structures of human organs, but also possess the properties and functions of the organ structure. With the rapid advancement of three-dimensional (3D printing and 3D bioprinting technologies, many researchers have explored the use of these additive manufacturing techniques to fabricate functional medical phantoms for various applications. This paper reviews the applications of these 3D printing and 3D bioprinting technologies for the fabrication of functional medical phantoms and bio-structures. This review specifically discusses the state of the art along with new developments and trends in 3D printed functional medical phantoms (i.e., tissue-mimicking medical phantoms, radiologically relevant medical phantoms, and physiological medical phantoms and 3D bio-printed structures (i.e., hybrid scaffolding materials, convertible scaffolds, and integrated sensors for regenerated tissues and organs.

  10. Impact of tissue surface properties on the desorption electrospray ionization imaging of organic acids in grapevine stem.

    Science.gov (United States)

    Dong, Yonghui; Guella, Graziano; Franceschi, Pietro

    2016-03-30

    Desorption electrospray ionization (DESI) imaging is a fast analytical technique used to assess spatially resolved biological processes over unmodified sample surfaces. Although DESI profiling experiments have demonstrated that the properties of the sample surface significantly affect the outcomes of DESI analyses, the potential implications of these phenomena in imaging applications have not yet been explored extensively. The distribution of endogenous and exogenous organic acids in pith and out pith region of grapevine stems was investigated by using DESI imaging, ion chromatography and direct infusion methods. Several common normalization strategies to account for the surface effect, including TIC normalization, addition of the internal standard in the spray solvent and deposition of the standard over the sample surface, were critically evaluated. DESI imaging results show that, in our case, the measured distributions of these small organic acids are not consistent with their 'true' localizations within the tissues. Furthermore, our results indicate that the common normalization strategies are not able to completely compensate for the observed surface effect. Variations in the tissue surface properties across the tissue sample can greatly affect the semi-quantitative detection of organic acids. Attention should be paid when interpreting DESI imaging results and an independent analytical validation step is important in untargeted DESI imaging investigations. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Succession after fire: variation in \\delta13C of organic tissues and respired CO2 in boreal forests

    Science.gov (United States)

    Fessenden, J. E.; Li, H.; Mack, M.; Schuur, T.; Warren, S.; Randerson, J. T.

    2001-12-01

    Isotope ratios of carbon dioxide and leaf organic matter were measured in 5 neighboring forests of varying ages: 7, 14, 45, 140, and 160 years. These forests are composed primarily of black spruce (Picea Mariana) and quaking aspen (Populus tremuloides) with a shift in species dominance from aspen to spruce 50 years after fire disturbance. Research on the carbon isotope ratios of leaf material and CO2 was conducted to look for influences from species composition, forest age, and time after most recent burn. Samples of organic \\delta13C in whole leaf tissue were collected from the dominant species of each forest. Concurrent aboveground NPP measurements allowed us to estimate total ecosystem \\delta13C by providing a method for weighting \\delta13C of individual species and plant tissues. \\delta13CO2 and [CO2] were measured on canopy CO2 to determine the isotopic ratio of ecosystem respiration. The atmospheric results indicated that the \\delta13C of ecosystem respiration changes with successional stage. Specifically, the aspen dominating forests showed 13C depleted values relative to the spruce dominated forests. Organic results showed more 13C-enriched values with increased forest age and vegetation functional type. Specifically, oldest trees within the coniferous species had the most 13C-enriched values in leaf tissues. These results suggest that increases in the disturbance regime of northern boreal forests will lead to a decrease in the \\delta13C of ecosystem carbon with consequences for the atmospheric \\delta13C budget.

  12. Quantitative 3D Analysis of Nuclear Morphology and Heterochromatin Organization from Whole-Mount Plant Tissue Using NucleusJ.

    Science.gov (United States)

    Desset, Sophie; Poulet, Axel; Tatout, Christophe

    2018-01-01

    Image analysis is a classical way to study nuclear organization. While nuclear organization used to be investigated by colorimetric or fluorescent labeling of DNA or specific nuclear compartments, new methods in microscopy imaging now enable qualitative and quantitative analyses of chromatin pattern, and nuclear size and shape. Several procedures have been developed to prepare samples in order to collect 3D images for the analysis of spatial chromatin organization, but only few preserve the positional information of the cell within its tissue context. Here, we describe a whole mount tissue preparation procedure coupled to DNA staining using the PicoGreen ® intercalating agent suitable for image analysis of the nucleus in living and fixed tissues. 3D Image analysis is then performed using NucleusJ, an open source ImageJ plugin, which allows for quantifying variations in nuclear morphology such as nuclear volume, sphericity, elongation, and flatness as well as in heterochromatin content and position in respect to the nuclear periphery.

  13. Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

    Science.gov (United States)

    de Landsheere, Laurent; Brieu, Mathias; Blacher, Silvia; Munaut, Carine; Nusgens, Betty; Rubod, Chrystèle; Noel, Agnès; Foidart, Jean-Michel; Nisolle, Michelle; Cosson, Michel

    2016-04-01

    The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP). Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C0) and high (C1) deformation rates. Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C0), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C0 and the elastin/collagen ratio (p = 0.048) in the lamina propria. However, at large strain levels (C1), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples. Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

  14. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.

    Directory of Open Access Journals (Sweden)

    Deborah G Nguyen

    Full Text Available Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI. This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM. Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.

  15. Down-regulation of tissue N:P ratios in terrestrial plants by elevated CO2.

    Science.gov (United States)

    Deng, Qi; Hui, Dafeng; Luo, Yiqi; Elser, James; Wang, Ying-ping; Loladze, Irakli; Zhang, Quanfa; Dennis, Sam

    2015-12-01

    Increasing atmospheric CO2 concentrations generally alter element stoichiometry in plants. However, a comprehensive evaluation of the elevated CO2 impact on plant nitrogen: phosphorus (N:P) ratios and the underlying mechanism has not been conducted. We synthesized the results from 112 previously published studies using meta-analysis to evaluate the effects of elevated CO2 on the N:P ratio of terrestrial plants and to explore the underlying mechanism based on plant growth and soil P dynamics. Our results show that terrestrial plants grown under elevated CO2 had lower N:P ratios in both above- and belowground biomass across different ecosystem types. The response ratio for plant N:P was negatively correlated with the response ratio for plant growth in croplands and grasslands, and showed a stronger relationship for P than for N. In addition, the CO2-induced down-regulation of plant N:P was accompanied by 19.3% and 4.2% increases in soil phosphatase activity and labile P, respectively, and a 10.1% decrease in total soil P. Our results show that down-regulation of plant N:P under elevated CO2 corresponds with accelerated soil P cycling. These findings should be useful for better understanding of terrestrial plant stoichiometry in response to elevated CO2 and of the underlying mechanisms affecting nutrient dynamics under climate change.

  16. Planar cell polarity proteins differentially regulate extracellular matrix organization and assembly during zebrafish gastrulation.

    Science.gov (United States)

    Dohn, Michael R; Mundell, Nathan A; Sawyer, Leah M; Dunlap, Julie A; Jessen, Jason R

    2013-11-01

    Zebrafish gastrulation cell movements occur in the context of dynamic changes in extracellular matrix (ECM) organization and require the concerted action of planar cell polarity (PCP) proteins that regulate cell elongation and mediolateral alignment. Data obtained using Xenopus laevis gastrulae have shown that integrin-fibronectin interactions underlie the formation of polarized cell protrusions necessary for PCP and have implicated PCP proteins themselves as regulators of ECM. By contrast, the relationship between establishment of PCP and ECM assembly/remodeling during zebrafish gastrulation is unclear. We previously showed that zebrafish embryos carrying a null mutation in the four-pass transmembrane PCP protein vang-like 2 (vangl2) exhibit increased matrix metalloproteinase activity and decreased immunolabeling of fibronectin. These data implicated for the first time a core PCP protein in the regulation of pericellular proteolysis of ECM substrates and raised the question of whether other zebrafish PCP proteins also impact ECM organization. In Drosophila melanogaster, the cytoplasmic PCP protein Prickle binds Van Gogh and regulates its function. Here we report that similar to vangl2, loss of zebrafish prickle1a decreases fibronectin protein levels in gastrula embryos. We further show that Prickle1a physically binds Vangl2 and regulates both the subcellular distribution and total protein level of Vangl2. These data suggest that the ability of Prickle1a to impact fibronectin organization is at least partly due to effects on Vangl2. In contrast to loss of either Vangl2 or Prickle1a function, we find that glypican4 (a Wnt co-receptor) and frizzled7 mutant gastrula embryos with disrupted non-canonical Wnt signaling exhibit the opposite phenotype, namely increased fibronectin assembly. Our data show that glypican4 mutants do not have decreased proteolysis of ECM substrates, but instead have increased cell surface cadherin protein expression and increased intercellular

  17. The histone H3K9 methylation and RNAi pathways regulate normalnucleolar and repeated DNA organization by inhibiting formation ofextrachromosomal DNAs

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jamy C.; Karpen, Gary H.

    2006-06-15

    In order to identify regulators of nuclear organization, Drosophila mutants in the Su(var)3-9 histone H3K9 methyltransferase, RNAi pathway components, and other regulators of heterochromatin-mediated gene silencing were examined for altered nucleoli and positioning of repeated DNAs. Animals lacking components of the H3K9 methylation and RNAi pathways contained disorganized nucleoli, ribosomal DNA (rDNA) and satellite DNAs. The levels of H3K9 dimethylation (H3K9me2) in chromatin associated with repeated DNAs decreased dramatically in Su(var)3-9 and dcr-2 (dicer-2) mutant tissues compared to wild type. We also observed a substantial increase in extrachromosomal repeated DNAs in mutant tissues. The disorganized nucleolus phenotype depends on the presence of Ligase 4 (Lig4), and ecc DNA formation is not induced by removal of cohesin. We conclude that H3K9 methylation of rDNA and satellites, maintained by Su(var)3-9, HP1, and the RNAi pathway, is necessary for the structural stability of repeated DNAs, which is mediated through suppression of non-homologous end joining (NHEJ). These results suggest a mechanism for how local chromatin structure can regulate genome stability, and the organization of chromosomal elements and nuclear organelles.

  18. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    OpenAIRE

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occur...

  19. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation

    DEFF Research Database (Denmark)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm

    2016-01-01

    BACKGROUND: Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways...... to measure palmitate rate of appearance (Rapalmitate) and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications. RESULTS: LPS caused...... a mean increase in serum free fatty acids (FFA) concentrations of 90% (CI-95%: 37-142, p = 0.005), a median increase in Rapalmitate of 117% (CI-95%: 77-166, penergy expenditure of 28% (CI-95%: 16-42, p...

  20. Interspecies chimeric complementation for the generation of functional human tissues and organs in large animal hosts.

    Science.gov (United States)

    Wu, Jun; Izpisua Belmonte, Juan Carlos

    2016-06-01

    The past decade's rapid progress in human pluripotent stem cell (hPSC) research has generated hope for meeting the rising demand of organ donation, which remains the only effective cure for end-stage organ failure, a major cause of death worldwide. Despite the potential, generation of transplantable organs from hPSCs using in vitro differentiation is far-fetched. An in vivo interspecies chimeric complementation strategy relying on chimeric-competent hPSCs and zygote genome editing provides an auspicious alternative for providing unlimited organ source for transplantation.

  1. Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and β1 integrin expression in vitro

    International Nuclear Information System (INIS)

    Lluri, Gentian; Langlois, Garret D.; Soloway, Paul D.; Jaworski, Diane M.

    2008-01-01

    Myogenesis in vitro involves myoblast cell cycle arrest, migration, and fusion to form multinucleated myotubes. Extracellular matrix (ECM) integrity during these processes is maintained by the opposing actions of matrix metalloproteinase (MMP) proteases and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Here, we report that TIMP-2, MMP-2, and MT1-MMP are differentially expressed during mouse myoblast differentiation in vitro. A specific role for TIMP-2 in myogenesis is demonstrated by altered TIMP-2 -/- myotube formation. When differentiated in horse serum-containing medium, TIMP-2 -/- myotubes are larger than wild-type myotubes. In contrast, when serum-free medium is used, TIMP-2 -/- myotubes are smaller than wild-type myotubes. Regardless of culture condition, myotube size is directly correlated with MMP activity and inversely correlated with β1 integrin expression. Treatment with recombinant TIMP-2 rescues reduced TIMP-2 -/- myotube size and induces increased MMP-9 activation and decreased β1 integrin expression. Treatment with either MMP-2 or MMP-9 similarly rescues reduced myotube size, but has no effect on β1 integrin expression. These data suggest a specific regulatory relationship between TIMP-2 and β1 integrin during myogenesis. Elucidating the role of TIMP-2 in myogenesis in vitro may lead to new therapeutic options for the use of TIMP-2 in myopathies and muscular dystrophies in vivo

  2. Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model.

    Science.gov (United States)

    Pawlinski, Rafal; Pedersen, Brian; Kehrle, Bettina; Aird, William C; Frank, Rolf D; Guha, Mausumee; Mackman, Nigel

    2003-05-15

    In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1(+/+) mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1(-/-) mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1(+/+) mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1(-/-) mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor alpha in endotoxemic mice. Moreover, Egr-1(+/+) and Egr-1(-/-) mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs.

  3. Distribution of heavy metals in internal organs and tissues of Korean molluscan shellfish and potential risk to human health.

    Science.gov (United States)

    Mok, Jong Soo; Kwon, Ji Young; Son, Kwang Tae; Choi, Woo Seok; Kim, Poong Ho; Lee, Tae Seek; Kim, Ji Hoe

    2015-09-01

    Molluscan shellfish (gastropods and bivalves) were collected from major fish markets on the Korean coast and analyzed for mercury by direct Hg analyzer and for other metals, such as cadmium, lead, chromium, silver, nickel, copper and zinc, using inductively coupled plasma mass spectrometry. Distribution of heavy metals in muscles, internal organs and whole tissues were determined and a potential risk assessment was conducted to evaluate their hazard for human consumption. Heavy metals were accumulated significantly higher (P hazardous metals (Cd, Pb, and Hg) in all internal-organ samples were above the regulatory limit of Korea and the mean level in whole tissue samples of the selected gastropod species, bay scallop and comb pen shell, exceeded the limit (except in a few cases). The sum of the estimated dietary intake of Cd, Pb and Hg for each part of all tested species accounted for 1.59-16.94, 0.02-0.36, and 0.07-0.16% respectively, of the provisional tolerable daily intake adopted by the Joint FAO/WHO Expert Committee on Food Additives. The hazard index for each part of gastropods and bivalves was below 1.0, however, the maximum HI for internal organs of all analysed species was quite high (0.71). These results suggest that consumption of flesh after removing the internal organs of some molluscan shellfish (all gastropod species, bay scallop and comb pen shell) is a suitable way for reducing Cd exposure.

  4. Study of the equivalent dose distribution in organs and tissues using periapical odontological radiography

    International Nuclear Information System (INIS)

    Santos, H.F.S.; Cipeli, J.F.; Fortes, M.A.B.; Federico, C.A.

    2017-01-01

    In this article presents a study of the doses obtained in periapical odontological radiography in main tissues of the head, using thermoluminescent dosemeters of type TLD-700H applied to a anthropomorphic simulator. The results indicate that the skin and salivary glands received the highest doses and the risk of calculated injury was 1.44 x 10 -6 Sv -1 per radiograph

  5. Supercritical fluid extraction of uranium from tissue paper matrix using organic extractants

    International Nuclear Information System (INIS)

    Kanekar, A.S.; Bhattacharyya, A.; Pathak, P.N.; Mohapatra, P.K.; Manchanda, V.K.

    2009-01-01

    Direct extraction of dried uranyl nitrate from tissue paper matrix was carried out using supercritical carbon dioxide modified with methanol solutions of extractants such as tri-n-butyl phosphate (TBP) and di-n-hexyl octanamide (DHOA)). The effects of temperature, pressure, extractant and nitric acid concentration on the extraction of uranyl ion were investigated. (author)

  6. RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT).

    Science.gov (United States)

    Mutoh, Mami; Kimura, Shunsuke; Takahashi-Iwanaga, Hiromi; Hisamoto, Meri; Iwanaga, Toshihiko; Iida, Junichiro

    2016-04-01

    Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer's patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2(+)Tnfaip2(+) cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2(+)Tnfaip2(+) cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation.

  7. Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

    Science.gov (United States)

    Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

    2018-06-01

    Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

  8. Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs

    Directory of Open Access Journals (Sweden)

    Kieran eAlden

    2012-07-01

    Full Text Available The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signalling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex 3-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically the role of different tissue inducer cell populations in the dynamic formation of Peyer's Patches has been examined. Utilising approaches from critical systems engineering an unbiased model of lymphoid tissue inducer cell function has been developed, that permits the development of emerging behaviours that are statistically not different from that observed in vivo. These results provide the confidence to utilise statistical methods to explore how the simulator predicts cellular behaviour and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine begins to have an influence on observed behaviour, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilising experimental approaches.

  9. Macro-and micro-autoradiographic study in comparison with the incorporation of 35S-methionine by various tissue protein in organism

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Mei Shengping; Le Shangcheng

    1990-12-01

    The purpose of the study was to observe the incorporation level of 35 S-methionine by various tissue protein in organism. By the use of the macro-and micro-autoradiographic technique, the incorporation of 35 S-methionine by the tissues has been utilized as an index of various tissue protein synthesis. On this basis, the further experiments showed that tracer agent 35 S-methionine was dominantly incorporated in the immature cells of bone marrow and the tissue of liver, kidney and spleen. Its incorporation increased gradually with time. From the experimental results it can be concluded that a strong protein biosynthesis metabolism was produced in these tissues. While the tissues have important physiological function in organism, such as heart, lung and skeletal muscle, but the protein biosynthesis in those tissues was at a low level

  10. Chitinase 3-like 1 Regulates Cellular and Tissue Responses via IL-13 Receptor α2

    Directory of Open Access Journals (Sweden)

    Chuan Hua He

    2013-08-01

    Full Text Available Members of the 18 glycosyl hydrolase (GH 18 gene family have been conserved over species and time and are dysregulated in inflammatory, infectious, remodeling, and neoplastic disorders. This is particularly striking for the prototypic chitinase-like protein chitinase 3-like 1 (Chi3l1, which plays a critical role in antipathogen responses where it augments bacterial killing while stimulating disease tolerance by controlling cell death, inflammation, and remodeling. However, receptors that mediate the effects of GH 18 moieties have not been defined. Here, we demonstrate that Chi3l1 binds to interleukin-13 receptor α2 (IL-13Rα2 and that Chi3l1, IL-13Rα2, and IL-13 are in a multimeric complex. We also demonstrate that Chi3l1 activates macrophage mitogen-activated protein kinase, protein kinase B/AKT, and Wnt/β-catenin signaling and regulates oxidant injury, apoptosis, pyroptosis, inflammasome activation, antibacterial responses, melanoma metastasis, and TGF-β1 production via IL-13Rα2-dependent mechanisms. Thus, IL-13Rα2 is a GH 18 receptor that plays a critical role in Chi3l1 effector responses.

  11. Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-01-01

    Full Text Available Wound healing is a complex process that inv