Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

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Yueying Liu

2012-01-01

Full Text Available Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA, a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.

stg fimbrial operon from S. Typhi STH2370 contributes to association and cell disruption of epithelial and macrophage-like cells.

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Berrocal, Liliana; Fuentes, Juan A; Trombert, A Nicole; Jofré, Matías R; Villagra, Nicolás A; Valenzuela, Luis M; Mora, Guido C

2015-07-07

Salmonella enterica serovar Typhi (S. Typhi) stg operon, encoding a chaperone/usher fimbria (CU), contributes to an increased adherence to human epithelial cells. However, one report suggests that the presence of the Stg fimbria impairs the monocyte--bacteria association, as deduced by the lower level of invasion to macrophage-like cells observed when the stg fimbrial cluster was overexpressed. Nevertheless, since other CU fimbrial structures increase the entry of S. Typhi into macrophages, and considering that transcriptomic analyses revealed that stg operon is indeed expressed in macrophages, we reassessed the role of the stg operon in the interaction between S. Typhi strain STH2370 and human cells, including macrophage-like cells and mononuclear cells directly taken from human peripheral blood. We compared S. Typhi STH2370 WT, a Chilean clinical strain, and the S. Typhi STH2370 Δstg mutant with respect to association and invasion using epithelial and macrophage-like cells. We observed that deletion of stg operon reduced the association and invasion of S. Typhi, in both cellular types. The presence of the cloned stg operon restored the WT phenotype in all the cases. Moreover, we compared Salmonella enterica sv. Typhimurium 14028s (S. Typhimurium, a serovar lacking stg operon) and S. Typhimurium heterologously expressing S. Typhi stg. We found that the latter presents an increased cell disruption of polarized epithelial cells and an increased association in both epithelial and macrophage-like cells. S. Typhi stg operon encodes a functional adhesin that participates in the interaction bacteria-eukaryotic cells, including epithelial cells and macrophages-like cells. The phenotypes associated to stg operon include increased association and consequent invasion in bacteria-eukaryotic cells, and cell disruption.

Disrupted epithelial/macrophage crosstalk via Spinster homologue 2-mediated S1P signaling may drive defective macrophage phagocytic function in COPD.

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Hai B Tran

Full Text Available We have previously established a link between impaired phagocytic capacity and deregulated S1P signaling in alveolar macrophages from COPD subjects. We hypothesize that this defect may include a disruption of epithelial-macrophage crosstalk via Spns2-mediated intercellular S1P signaling.Primary alveolar macrophages and bronchial epithelial cells from COPD subjects and controls, cell lines, and a mouse model of chronic cigarette smoke exposure were studied. Cells were exposed to 10% cigarette smoke extract, or vehicle control. Spns2 expression and subcellular localization was studied by immunofluorescence, confocal microscopy and RT-PCR. Phagocytosis was assessed by flow-cytometry. Levels of intra- and extracellular S1P were measured by S1P [3H]-labeling.Spns2 expression was significantly increased (p<0.05 in alveolar macrophages from current-smokers/COPD patients (n = 5 compared to healthy nonsmokers (n = 8 and non-smoker lung transplant patients (n = 4. Consistent with this finding, cigarette smoke induced a significant increase in Spns2 expression in both human alveolar and THP-1 macrophages. In contrast, a remarkable Spns2 down-regulation was noted in response to cigarette smoke in 16HBE14o- cell line (p<0.001 in 3 experiments, primary nasal epithelial cells (p<0.01 in 2 experiments, and in smoke-exposed mice (p<0.001, n = 6 animals per group. Spns2 was localized to cilia in primary bronchial epithelial cells. In both macrophage and epithelial cell types, Spns2 was also found localized to cytoplasm and the nucleus, in line with a predicted bipartile Nuclear Localization Signal at the position aa282 of the human Spns2 sequence. In smoke-exposed mice, alveolar macrophage phagocytic function positively correlated with Spns2 protein expression in bronchial epithelial cells.Our data suggest that the epithelium may be the major source for extracellular S1P in the airway and that there is a possible disruption of epithelial/macrophage cross talk via

Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

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Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

2009-09-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis

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Lesko, Alyssa C.; Goss, Kathleen H.; Yang, Frank F.; Schwertner, Adam; Hulur, Imge; Onel, Kenan; Prosperi, Jenifer R.

2015-01-01

The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/β-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further support the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis. PMID:25578398

Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in mice.

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Sun-Kyoung Im

Full Text Available Sorting nexin 5 (Snx5 has been posited to regulate the degradation of epidermal growth factor receptor and the retrograde trafficking of cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor. Snx5 has also been suggested to interact with Mind bomb-1, an E3 ubiquitin ligase that regulates the activation of Notch signaling. However, the in vivo functions of Snx5 are largely unknown. Here, we report that disruption of the Snx5 gene in mice (Snx5(-/- mice resulted in partial perinatal lethality; 40% of Snx5(-/- mice died shortly after birth due to cyanosis, reduced air space in the lungs, and respiratory failure. Histological analysis revealed that Snx5(-/- mice exhibited thickened alveolar walls associated with undifferentiated alveolar epithelial type I cells. In contrast, alveolar epithelial type II cells were intact, exhibiting normal surfactant synthesis and secretion. Although the expression levels of surfactant proteins and saturated phosphatidylcholine in the lungs of Snx5(-/- mice were comparable to those of Snx5(+/+ mice, the expression levels of T1α, Aqp5, and Rage, markers for distal alveolar epithelial type I cells, were significantly decreased in Snx5 (-/- mice. These results demonstrate that Snx5 is necessary for the differentiation of alveolar epithelial type I cells, which may underlie the adaptation to air breathing at birth.

Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells

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Fournier, Marcia V.; Fata, Jimmie E.; Martin, Katherine J.; Yaswen, Paul; Bissell, Mina J.

2009-06-03

PTEN is a dual function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two non-malignant human mammary epithelial cell lines (HMECs) that form polarized, growth-arrested structures (acini) when cultured in 3-dimensional laminin-rich extracellular matrix gels (3D lrECM). As acini begin to form, PTEN accumulates in both the cytoplasm, and at cell-cell contacts where it colocalizes with E-cadherin/{beta}-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function-blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in SKBR3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in 3D lrECM indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus appears to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells.

Host Epithelial Interactions with Helicobacter Pylori: A Role for Disrupted Gastric Barrier Function in the Clinical Outcome of Infection?

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Andre G Buret

2005-01-01

Full Text Available Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.

Towards a Disruptive Digital Platform Model

DEFF Research Database (Denmark)

Kazan, Erol

that digital platforms leverage on three strategic design elements (i.e., business, architecture, and technology design) to create supportive conditions for facilitating disruption. To shed light on disruptive digital platforms, I opted for payment platforms as my empirical context and unit of analysis......Digital platforms are layered modular information technology architectures that support disruption. Digital platforms are particularly disruptive, as they facilitate the quick release of digital innovations that may replace established innovations. Yet, despite their support for disruption, we have...... not fully understood how such digital platforms can be strategically designed and configured to facilitate disruption. To that end, this thesis endeavors to unravel disruptive digital platforms from the supply perspective that are grounded on strategic digital platform design elements. I suggest...

Polarity in Mammalian Epithelial Morphogenesis

OpenAIRE

Roignot, Julie; Peng, Xiao; Mostov, Keith

2013-01-01

Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture model...

Plausibility of stromal initiation of epithelial cancers without a mutation in the epithelium: a computer simulation of morphostats

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Cappuccio Antonio

2009-03-01

Full Text Available Abstract Background There is experimental evidence from animal models favoring the notion that the disruption of interactions between stroma and epithelium plays an important role in the initiation of carcinogenesis. These disrupted interactions are hypothesized to be mediated by molecules, termed morphostats, which diffuse through the tissue to determine cell phenotype and maintain tissue architecture. Methods We developed a computer simulation based on simple properties of cell renewal and morphostats. Results Under the computer simulation, the disruption of the morphostat gradient in the stroma generated epithelial precursors of cancer without any mutation in the epithelium. Conclusion The model is consistent with the possibility that the accumulation of genetic and epigenetic changes found in tumors could arise after the formation of a founder population of aberrant cells, defined as cells that are created by low or insufficient morphostat levels and that no longer respond to morphostat concentrations. Because the model is biologically plausible, we hope that these results will stimulate further experiments.

Oral epithelial dysplasia classification systems

DEFF Research Database (Denmark)

Warnakulasuriya, S; Reibel, J; Bouquot, J

2008-01-01

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers....... In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine...... use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria...

Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

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Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

2004-07-14

Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

Characterization of a continuous feline mammary epithelial cell line susceptible to feline epitheliotropic viruses.

Science.gov (United States)

Pesavento, Patricia; Liu, Hongwei; Ossiboff, Robert J; Stucker, Karla M; Heymer, Anna; Millon, Lee; Wood, Jason; van der List, Deborah; Parker, John S L

2009-04-01

Mucosal epithelial cells are the primary targets for many common viral pathogens of cats. Viral infection of epithelia can damage or disrupt the epithelial barrier that protects underlying tissues. In vitro cell culture systems are an effective means to study how viruses infect and disrupt epithelial barriers, however no true continuous or immortalized feline epithelial cell culture lines are available. A continuous cell culture of feline mammary epithelial cells (FMEC UCD-04-2) that forms tight junctions with high transepithelial electrical resistance (>2000Omegacm(-1)) 3-4 days after reaching confluence was characterized. In addition, it was shown that FMECs are susceptible to infection with feline calicivirus (FCV), feline herpesvirus (FHV-1), feline coronavirus (FeCoV), and feline panleukopenia virus (FPV). These cells will be useful for studies of feline viral disease and for in vitro studies of feline epithelia.

Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage

NARCIS (Netherlands)

P. Aparicio-Domingo (Patricia); M. Romera Hernández (Mónica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)

2015-01-01

textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence

Five disruptive technology directions for 5G

DEFF Research Database (Denmark)

Boccardi, Federico; W. Heath Jr., Robert; Lozano, Angel

2014-01-01

New research directions will lead to fundamental changes in the design of future fifth generation (5G) cellular networks. This article describes five technologies that could lead to both architectural and component disruptive design changes: device-centric architectures, millimeter wave, massive ...

Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

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Alexandre N Ermilov

2016-11-01

Full Text Available For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings

Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

Science.gov (United States)

Ermilov, Alexandre N; Kumari, Archana; Li, Libo; Joiner, Ariell M; Grachtchouk, Marina A; Allen, Benjamin L; Dlugosz, Andrzej A; Mistretta, Charlotte M

2016-11-01

For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings suggest that taste

Engineering stromal-epithelial interactions in vitro for ...

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Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells

Science.gov (United States)

Yang, Guang; Hinson, Maurice D.; Bordner, Jessica E.; Lin, Qing S.; Fernando, Amal P.; La, Ping; Wright, Clyde J.

2011-01-01

Postnatal lung development requires proliferation and differentiation of specific cell types at precise times to promote proper alveolar formation. Hyperoxic exposure can disrupt alveolarization by inhibiting cell growth; however, it is not fully understood how this is mediated. The transcription factor CCAAT/enhancer binding protein-α (C/EBPα) is highly expressed in the lung and plays a role in cell proliferation and differentiation in many tissues. After 72 h of hyperoxia, C/EBPα expression was significantly enhanced in the lungs of newborn mice. The increased C/EBPα protein was predominantly located in alveolar type II cells. Silencing of C/EBPα with a transpulmonary injection of C/EBPα small interfering RNA (siRNA) prior to hyperoxic exposure reduced expression of markers of type I cell and differentiation typically observed after hyperoxia but did not rescue the altered lung morphology at 72 h. Nevertheless, when C/EBPα hyperoxia-exposed siRNA-injected mice were allowed to recover for 2 wk in room air, lung epithelial cell proliferation was increased and lung morphology was restored compared with hyperoxia-exposed control siRNA-injected mice. These data suggest that C/EBPα is an important regulator of postnatal alveolar epithelial cell proliferation and differentiation during injury and repair. PMID:21571903

Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Chanson, L. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Brownfield, D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering; Garbe, J. C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Kuhn, I. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Stampfer, M. R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bissell, M. J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; LaBarge, M. A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

2011-02-07

Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal human mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells.

Rap1 integrates tissue polarity, lumen formation, and tumorigenicpotential in human breast epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Itoh, Masahiko; Nelson, Celeste M.; Myers, Connie A.; Bissell,Mina J.

2006-09-29

Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Here we show that the small GTPase Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably higher than in S1 cells, their non-malignant counterparts. Expression of dominant-negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to formation of acinar structures with correct apico-basal polarity, and dramatically reduced tumor incidence despite the persistence of genomic abnormalities. The resulting acini contained prominent central lumina not observed when other reverting agents were used. Conversely, expression of dominant-active Rap1 in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness and tumorigenicity. Thus, Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing apical polarity during acinar morphogenesis, and increased activation inducing tumor formation and progression to malignancy.

Cell volume regulation in epithelial physiology and cancer

DEFF Research Database (Denmark)

Pedersen, Stine Helene Falsig; Hoffmann, Else Kay; Novak, Ivana

2013-01-01

expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion...... such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered...... transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed....

AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

Science.gov (United States)

Chen, Peili; Li, Yan Chun; Toback, F Gary

2015-01-01

Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

Directory of Open Access Journals (Sweden)

Peili Chen

Full Text Available Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD. We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

Science.gov (United States)

Tugizov, Sharof

2016-01-01

Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments

Science.gov (United States)

Lewis, Katherine Jean Reeder

The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar epithelium and local fibroblasts has been implicated in the progression of several pulmonary diseases. However, given the complexity of alveolar tissue architecture and the multitude of signaling pathways involved, designing appropriate experimental platforms for this biological system has been difficult. In order to isolate key factors regulating cellular behavior, the researcher ideally should have control over biophysical properties of the ECM, as well as the ability to organize multiple cell types within the scaffold. This thesis aimed to develop a 3D synthetic hydrogel platform to control alveolar epithelial cyst formation, which could then be used to explore how extracellular cues influence cell behavior in a tissue-relevant cellular arrangement. To accomplish this, a poly(ethylene glycol) (PEG) hydrogel network containing enzymatically-degradable crosslinks and bioadhesive pendant peptides was employed as a base material for encapsulating primary alveolar epithelial cells. First, an array of microwells of various cross-sectional shapes was photopatterned into a PEG gel containing photo-labile crosslinks, and primary ATII cells were seeded into the wells to examine the role of geometric confinement on differentiation and multicellular arrangement

Understanding Enterprise Architecture with Topic Modeling

DEFF Research Database (Denmark)

Nardello, Marco; Møller, Charles; Gøtze, John

2018-01-01

The next 3 years will be more important than the last 50 due to the digital transformation across industries. Enterprise Architecture (EA), the discipline that should lead enterprise responses to disruptive forces, is far from ready to drive the next wave of change. The state of the art in the di......The next 3 years will be more important than the last 50 due to the digital transformation across industries. Enterprise Architecture (EA), the discipline that should lead enterprise responses to disruptive forces, is far from ready to drive the next wave of change. The state of the art...

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

Science.gov (United States)

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E.

2011-01-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. PMID:21777561

Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

DEFF Research Database (Denmark)

Xia, Jingjing; Swiercz, Jakub M.; Bañón-Rodríguez, Inmaculada

2015-01-01

Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we...... show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading...... to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central...

Adherent-invasive Escherichia coli, strain LF82 disrupts apical junctional complexes in polarized epithelia

Directory of Open Access Journals (Sweden)

Ossa Juan C

2009-08-01

Full Text Available Abstract Background Although bacteria are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD, mechanisms of intestinal injury and immune activation remain unclear. Identification of adherent-invasive Escherichia coli (AIEC strains in IBD patients offers an opportunity to characterize the pathogenesis of microbial-induced intestinal inflammation in IBD. Previous studies have focused on the invasive phenotype of AIEC and the ability to replicate and survive in phagocytes. However, the precise mechanisms by which these newly identified microbes penetrate the epithelial lining remain to be clarified. Therefore, the aim of this study was to delineate the effects of AIEC, strain LF82 (serotype O83:H1 on model polarized epithelial monolayers as a contributor to intestinal injury in IBD. Results Infection of T84 and Madin-Darby Canine Kidney-I polarized epithelial cell monolayers with AIEC, strain LF82 led to a reduction in transepithelial electrical resistance and increased macromolecular (10 kilodalton dextran flux. Basolateral AIEC infection resulted in more severe disruption of the epithelial barrier. Increased permeability was accompanied by a redistribution of the tight junction adaptor protein, zonula occludens-1, demonstrated by confocal microscopy and formation of gaps between cells, as shown by transmission electron microscopy. After 4 h of infection of intestine 407 cells, bacteria replicated in the cell cytoplasm and were enclosed in membrane-bound vesicles positive for the late endosomal marker, LAMP1. Conclusion These findings indicate that AIEC, strain LF82 disrupts the integrity of the polarized epithelial cell barrier. This disruption enables bacteria to penetrate into the epithelium and replicate in the host cell cytoplasm. These findings provide important links between microbes related to IBD, the intestinal epithelial cell barrier and disease pathogenesis.

Plasma membrane disruption: repair, prevention, adaptation

Science.gov (United States)

McNeil, Paul L.; Steinhardt, Richard A.

2003-01-01

Many metazoan cells inhabit mechanically stressful environments and, consequently, their plasma membranes are frequently disrupted. Survival requires that the cell rapidly repair or reseal the disruption. Rapid resealing is an active and complex structural modification that employs endomembrane as its primary building block, and cytoskeletal and membrane fusion proteins as its catalysts. Endomembrane is delivered to the damaged plasma membrane through exocytosis, a ubiquitous Ca2+-triggered response to disruption. Tissue and cell level architecture prevent disruptions from occurring, either by shielding cells from damaging levels of force, or, when this is not possible, by promoting safe force transmission through the plasma membrane via protein-based cables and linkages. Prevention of disruption also can be a dynamic cell or tissue level adaptation triggered when a damaging level of mechanical stress is imposed. Disease results from failure of either the preventive or resealing mechanisms.

Lentiviral-Mediated Transgene Expression Can Potentiate Intestinal Mesenchymal-Epithelial Signaling

Directory of Open Access Journals (Sweden)

Kohn Aimee

2009-01-01

Full Text Available Abstract Mesenchymal-epithelial signaling is essential for the development of many organs and is often disrupted in disease. In this study, we demonstrate the use of lentiviral-mediated transgene delivery as an effective approach for ectopic transgene expression and an alternative to generation of transgenic animals. One benefit to this approach is that it can be used independently or in conjunction with established transgenic or knockout animals for studying modulation of mesenchymal-epithelial interactions. To display the power of this approach, we explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme and demonstrate its functional influence on the adjacent epithelium. Our findings highlight the efficient use of lentiviral-mediated transgene expression for modulating mesenchymal-epithelial interactions in vivo.

Lentiviral-Mediated Transgene Expression Can Potentiate Intestinal Mesenchymal-Epithelial Signaling

Directory of Open Access Journals (Sweden)

Dismuke Adria D

2009-07-01

Full Text Available Abstract Mesenchymal-epithelial signaling is essential for the development of many organs and is often disrupted in disease. In this study, we demonstrate the use of lentiviral-mediated transgene delivery as an effective approach for ectopic transgene expression and an alternative to generation of transgenic animals. One benefit to this approach is that it can be used independently or in conjunction with established transgenic or knockout animals for studying modulation of mesenchymal-epithelial interactions. To display the power of this approach, we explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme and demonstrate its functional influence on the adjacent epithelium. Our findings highlight the efficient use of lentiviral-mediated transgene expression for modulating mesenchymal-epithelial interactions in vivo.

Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

2008-06-26

Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a 'cuboidal' epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-{beta}-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.

Gastrointestinal Epithelial Organoid Cultures from Postsurgical Tissues.

Science.gov (United States)

Hahn, Soojung; Yoo, Jongman

2017-08-17

An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells. Thus far, gastrointestinal organoids have been extensively used for generating gastrointestinal disease models. This protocol describes the method of isolating a gland or crypt using stomach or colon tissue after surgery and establishing them into gastroids or colonoids.

Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells.

Science.gov (United States)

Lefevre, James G; Chiu, Han S; Combes, Alexander N; Vanslambrouck, Jessica M; Ju, Ali; Hamilton, Nicholas A; Little, Melissa H

2017-03-15

Human pluripotent stem cells, after directed differentiation in vitro , can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here, we investigate the timing and underlying mechanisms driving self-organisation after dissociation of the embryonic kidney using time-lapse imaging, high-resolution confocal analyses and mathematical modelling. Organotypic self-organisation sufficient for nephron initiation was observed within a 24 h period. This involved cell movement, with structure emerging after the clustering of ureteric epithelial cells, a process consistent with models of random cell movement with preferential cell adhesion. Ureteric epithelialisation rapidly followed the formation of ureteric cell clusters with the reformation of nephron-forming niches representing a later event. Disruption of P-cadherin interactions was seen to impair this ureteric epithelial cell clustering without affecting epithelial maturation. This understanding could facilitate improved regulation of patterning within organoids and facilitate kidney engineering approaches guided by cell-cell self-organisation. © 2017. Published by The Company of Biologists Ltd.

Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation.

Directory of Open Access Journals (Sweden)

Fiona L Cousins

Full Text Available BACKGROUND: In women dynamic changes in uterine tissue architecture occur during each menstrual cycle. Menses, characterised by the shedding of the upper functional layer of the endometrium, is the culmination of a cascade of irreversible changes in tissue function including stromal decidualisation, inflammation and production of degradative enzymes. The molecular mechanisms that contribute to the rapid restoration of tissue homeostasis at time of menses are poorly understood. METHODOLOGY: A modified mouse model of menses was developed to focus on the events occurring within the uterine lining during endometrial shedding/repair. Decidualisation, vaginal bleeding, tissue architecture and cell proliferation were evaluated at 4, 8, 12, and 24 hours after progesterone (P4 withdrawal; mice received a single injection of bromodeoxyuridine (BrdU 90 mins before culling. Expression of genes implicated in the regulation of mesenchymal to epithelial transition (MET was determined using a RT2 PCR profiler array, qRTPCR and bioinformatic analysis. PRINCIPAL FINDINGS: Mice exhibited vaginal bleeding between 4 and 12 hours after P4 withdrawal, concomitant with detachment of the decidualised cell mass from the basal portion of the endometrial lining. Immunostaining for BrdU and pan cytokeratin revealed evidence of epithelial cell proliferation and migration. Cells that appeared to be in transition from a mesenchymal to an epithelial cell identity were identified within the stromal compartment. Analysis of mRNAs encoding genes expressed exclusively in the epithelial or stromal compartments, or implicated in MET, revealed dynamic changes in expression, consistent with a role for reprogramming of mesenchymal cells so that they could contribute to re-epithelialisation. CONCLUSIONS/SIGNIFICANCE: These studies have provided novel insights into the cellular processes that contribute to re-epithelialisation post-menses implicating both epithelial cell migration and

Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation.

Science.gov (United States)

Cousins, Fiona L; Murray, Alison; Esnal, Arantza; Gibson, Douglas A; Critchley, Hilary O D; Saunders, Philippa T K

2014-01-01

In women dynamic changes in uterine tissue architecture occur during each menstrual cycle. Menses, characterised by the shedding of the upper functional layer of the endometrium, is the culmination of a cascade of irreversible changes in tissue function including stromal decidualisation, inflammation and production of degradative enzymes. The molecular mechanisms that contribute to the rapid restoration of tissue homeostasis at time of menses are poorly understood. A modified mouse model of menses was developed to focus on the events occurring within the uterine lining during endometrial shedding/repair. Decidualisation, vaginal bleeding, tissue architecture and cell proliferation were evaluated at 4, 8, 12, and 24 hours after progesterone (P4) withdrawal; mice received a single injection of bromodeoxyuridine (BrdU) 90 mins before culling. Expression of genes implicated in the regulation of mesenchymal to epithelial transition (MET) was determined using a RT2 PCR profiler array, qRTPCR and bioinformatic analysis. Mice exhibited vaginal bleeding between 4 and 12 hours after P4 withdrawal, concomitant with detachment of the decidualised cell mass from the basal portion of the endometrial lining. Immunostaining for BrdU and pan cytokeratin revealed evidence of epithelial cell proliferation and migration. Cells that appeared to be in transition from a mesenchymal to an epithelial cell identity were identified within the stromal compartment. Analysis of mRNAs encoding genes expressed exclusively in the epithelial or stromal compartments, or implicated in MET, revealed dynamic changes in expression, consistent with a role for reprogramming of mesenchymal cells so that they could contribute to re-epithelialisation. These studies have provided novel insights into the cellular processes that contribute to re-epithelialisation post-menses implicating both epithelial cell migration and mesenchymal cell differentiation in restoration of an intact epithelial cell layer. These

Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.

Science.gov (United States)

Lechuga, Susana; Ivanov, Andrei I

2017-07-01

The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

International Nuclear Information System (INIS)

Gao, Rundi; Chen, Ruilin; Cao, Yu; Wang, Yuan; Song, Kang; Zhang, Ya; Yang, Junchao

2017-01-01

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Gao, Rundi; Chen, Ruilin; Cao, Yu [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Wang, Yuan [Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Song, Kang [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China); Zhang, Ya [Zhejiang Chinese Medicine University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province 310006 (China); Yang, Junchao, E-mail: yangjunchaozj@zcmu.edu.cn [Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, NO. 56, Youdian Road, Shangcheng District, Hangzhou, Zhejiang Province 310006 (China)

2017-03-01

Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway. Emodin inhibits the proliferation of Rat alveolar type II epithelial cells RLE-6TN in a concentration-dependent manner; reduces the expression of Collagen I, α-SMA and Vimentin, promotes the expression of E-cadherin. Moreover, Emodin could regulate the expression patterns of the Notch signaling pathway-related factors and reduce the Notch-1 nucleus translocation. Knockdown of Notch-1 enhances the inhibitory effect of Emodin on TGF-β1-induced EMT in RLE-6TN cells. In conclusion, the data of the present study suggests that Emodin suppresses TGF-β1-induced EMT in alveolar epithelial cells through Notch signaling pathway and shows the potential to be effective in the treatment of pulmonary fibrosis. - Highlights: • Emodin inhibits TGF-β1-induced EMT in alveolar epithelial cells. • Emodin regulates the expression patterns of the Notch signaling pathway-related factors. • Emodin inhibits TGF-β1-induced Notch-1 nucleus translocation and activation.

A Generic Architecture for Autonomous Uninhabited Vehicles

National Research Council Canada - National Science Library

Barbier, Magali; Gabard, Jean-Francois; Ayreault, Herve

2007-01-01

...; few solutions propose architecture adaptive to several types of platform. Autonomous vehicles that move in partially known and dynamic environments have to deal with asynchronous disruptive events...

Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

Science.gov (United States)

Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

2017-08-01

Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.

Science.gov (United States)

Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda

2012-01-01

The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.

Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure.

Science.gov (United States)

Aghapour, Mahyar; Raee, Pourya; Moghaddam, Seyed Javad; Hiemstra, Pieter S; Heijink, Irene H

2018-02-01

The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.

Expression of acyl-CoA synthetase 5 reflects the state of villus architecture in human small intestine

DEFF Research Database (Denmark)

Gassler, Nikolaus; Kopitz, Jürgen; Tehrani, Arman

2004-01-01

Several disorders of the small intestine are associated with disturbances in villus architecture. Thus, an understanding of the molecular mechanisms associated with the differentiation of villi represents an important step in the improvement of the understanding of small intestinal pathology......-CoA synthetase 5 pattern correlate with conversion of intestinal epithelial cells to a gastric phenotype. These results suggest that deranged acyl-CoA synthetase 5 expression, synthesis, and activity are closely related to the state of villus architecture and epithelial homeostasis in human small intestine....

Vocal Fold Epithelial Barrier in Health and Injury A Research Review

Science.gov (United States)

Levendoski, Elizabeth Erickson; Leydon, Ciara; Thibeault, Susan L.

2015-01-01

Purpose Vocal fold epithelium is composed of layers of individual epithelial cells joined by junctional complexes constituting a unique interface with the external environment. This barrier provides structural stability to the vocal folds and protects underlying connective tissue from injury while being nearly continuously exposed to potentially hazardous insults including environmental or systemic-based irritants such as pollutants and reflux, surgical procedures, and vibratory trauma. Small disruptions in the epithelial barrier may have a large impact on susceptibility to injury and overall vocal health. The purpose of this article is to provide a broad-based review of our current knowledge of the vocal fold epithelial barrier. Methods A comprehensive review of the literature was conducted. Details of the structure of the vocal fold epithelial barrier are presented and evaluated in the context of function in injury and pathology. The importance of the epithelial-associated vocal fold mucus barrier is also introduced. Results/Conclusions Information presented in this review is valuable for clinicians and researchers as it highlights the importance of this understudied portion of the vocal folds to overall vocal health and disease. Prevention and treatment of injury to the epithelial barrier is a significant area awaiting further investigation. PMID:24686981

VERO cells harbor a poly-ADP-ribose belt partnering their epithelial adhesion belt

Directory of Open Access Journals (Sweden)

Laura Lafon-Hughes

2014-10-01

Full Text Available Poly-ADP-ribose (PAR is a polymer of up to 400 ADP-ribose units synthesized by poly-ADP-ribose-polymerases (PARPs and degraded by poly-ADP-ribose-glycohydrolase (PARG. Nuclear PAR modulates chromatin compaction, affecting nuclear functions (gene expression, DNA repair. Diverse defined PARP cytoplasmic allocation patterns contrast with the yet still imprecise PAR distribution and still unclear functions. Based on previous evidence from other models, we hypothesized that PAR could be present in epithelial cells where cadherin-based adherens junctions are linked with the actin cytoskeleton (constituting the adhesion belt. In the present work, we have examined through immunofluorescence and confocal microscopy, the subcellular localization of PAR in an epithelial monkey kidney cell line (VERO. PAR was distinguished colocalizing with actin and vinculin in the epithelial belt, a location that has not been previously reported. Actin filaments disruption with cytochalasin D was paralleled by PAR belt disruption. Conversely, PARP inhibitors 3-aminobenzamide, PJ34 or XAV 939, affected PAR belt synthesis, actin distribution, cell shape and adhesion. Extracellular calcium chelation displayed similar effects. Our results demonstrate the existence of PAR in a novel subcellular localization. An initial interpretation of all the available evidence points towards TNKS-1 as the most probable PAR belt architect, although TNKS-2 involvement cannot be discarded. Forthcoming research will test this hypothesis as well as explore the existence of the PAR belt in other epithelial cells and deepen into its functional implications.

Disruption of epithelial cell migration as a potential mechanism of cleft palate induction

Science.gov (United States)

Cleft palate occurs in about one in seven hundred births per year, making it the most prevalent craniofacial birth defect in the world. During embryonic development, tissue fusion is a critical step in the formation of the palate, cornea, urethra, and neural tube. Epithelial cell...

A multicellular view of cytokinesis in epithelial tissue.

Science.gov (United States)

Herszterg, Sophie; Pinheiro, Diana; Bellaïche, Yohanns

2014-05-01

The study of cytokinesis in single-cell systems provided a wealth of knowledge on the molecular and biophysical mechanisms controlling daughter cell separation. In this review, we outline recent advances in the understanding of cytokinesis in epithelial tissues. These findings provide evidence for how the cytokinetic machinery adapts to a multicellular context and how the cytokinetic machinery is itself exploited by the tissue for the preservation of tissue function and architecture during proliferation. We propose that cytokinesis in epithelia should be viewed as a multicellular process, whereby the biochemical and mechanical interactions between the dividing cell and its neighbors are essential for successful daughter cell separation while defining epithelial tissue organization and preserving tissue integrity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Circadian Disruption Changes Gut Microbiome Taxa and Functional Gene Composition.

Science.gov (United States)

Deaver, Jessica A; Eum, Sung Y; Toborek, Michal

2018-01-01

Disrupted circadian rhythms and alterations of the gut microbiome composition were proposed to affect host health. Therefore, the aim of this research was to identify whether these events are connected and if circadian rhythm disruption by abnormal light-dark (LD) cycles affects microbial community gene expression and host vulnerability to intestinal dysfunction. Mice were subjected to either a 4-week period of constant 24-h light or of normal 12-h LD cycles. Stool samples were collected at the beginning and after the circadian rhythm disruption. A metatranscriptomic analysis revealed an increase in Ruminococcus torques , a bacterial species known to decrease gut barrier integrity, and a decrease in Lactobacillus johnsonii , a bacterium that helps maintain the intestinal epithelial cell layer, after circadian rhythm disruption. In addition, genes involved in pathways promoting host beneficial immune responses were downregulated, while genes involved in the synthesis and transportation of the endotoxin lipopolysaccharide were upregulated in mice with disrupted circadian cycles. Importantly, these mice were also more prone to dysfunction of the intestinal barrier. These results further elucidate the impact of light-cycle disruption on the gut microbiome and its connection with increased incidence of disease in response to circadian rhythm disturbances.

Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

Science.gov (United States)

Gon, Yasuhiro; Hashimoto, Shu

2018-01-01

Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

Science.gov (United States)

Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

2016-06-01

Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease.

Science.gov (United States)

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E

2011-09-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

Directory of Open Access Journals (Sweden)

Qiurong Li

Full Text Available BACKGROUND: The intestinal chronic rejection (CR is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. METHODS/PRINCIPAL FINDINGS: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. CONCLUSIONS/SIGNIFICANCE: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

Initial Characterization of Optical Communications with Disruption-Tolerant Network Protocols

Science.gov (United States)

Schoolcraft, Joshua; Wilson, Keith

2011-01-01

Disruption-tolerant networks (DTNs) are groups of network assets connected with a suite of communication protocol technologies designed to mitigate the effects of link delay and disruption. Application of DTN protocols to diverse groups of network resources in multiple sub-networks results in an overlay network-of-networks with autonomous data routing capability. In space environments where delay or disruption is expected, performance of this type of architecture (such as an interplanetary internet) can increase with the inclusion of new communications mediums and techniques. Space-based optical communication links are therefore an excellent building block of space DTN architectures. When compared to traditional radio frequency (RF) communications, optical systems can provide extremely power-efficient and high bandwidth links bridging sub-networks. Because optical links are more susceptible to link disruption and experience the same light-speed delays as RF, optical-enabled DTN architectures can lessen potential drawbacks and maintain the benefits of autonomous optical communications over deep space distances. These environment-driven expectations - link delay and interruption, along with asymmetric data rates - are the purpose of the proof-of-concept experiment outlined herein. In recognizing the potential of these two technologies, we report an initial experiment and characterization of the performance of a DTN-enabled space optical link. The experiment design employs a point-to-point free-space optical link configured to have asymmetric bandwidth. This link connects two networked systems running a DTN protocol implementation designed and written at JPL for use on spacecraft, and further configured for higher bandwidth performance. Comparing baseline data transmission metrics with and without periodic optical link interruptions, the experiment confirmed the DTN protocols' ability to handle real-world unexpected link outages while maintaining capability of

Trends in Microfabrication Capabilities & Device Architectures.

Energy Technology Data Exchange (ETDEWEB)

Bauer, Todd [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jones, Adam [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lentine, Tony [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mudrick, John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Okandan, Murat [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rodrigues, Arun [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-06-01

The last two decades have seen an explosion in worldwide R&D, enabling fundamentally new capabilities while at the same time changing the international technology landscape. The advent of technologies for continued miniaturization and electronics feature size reduction, and for architectural innovations, will have many technical, economic, and national security implications. It is important to anticipate possible microelectronics development directions and their implications on US national interests. This report forecasts and assesses trends and directions for several potentially disruptive microfabrication capabilities and device architectures that may emerge in the next 5-10 years.

Dual Function of Novel Pollen Coat (Surface) Proteins: IgE-binding Capacity and Proteolytic Activity Disrupting the Airway Epithelial Barrier

Science.gov (United States)

Bashir, Mohamed Elfatih H.; Ward, Jason M.; Cummings, Matthew; Karrar, Eltayeb E.; Root, Michael; Mohamed, Abu Bekr A.; Naclerio, Robert M.; Preuss, Daphne

2013-01-01

Background The pollen coat is the first structure of the pollen to encounter the mucosal immune system upon inhalation. Prior characterizations of pollen allergens have focused on water-soluble, cytoplasmic proteins, but have overlooked much of the extracellular pollen coat. Due to washing with organic solvents when prepared, these pollen coat proteins are typically absent from commercial standardized allergenic extracts (i.e., “de-fatted”), and, as a result, their involvement in allergy has not been explored. Methodology/Principal Findings Using a unique approach to search for pollen allergenic proteins residing in the pollen coat, we employed transmission electron microscopy (TEM) to assess the impact of organic solvents on the structural integrity of the pollen coat. TEM results indicated that de-fatting of Cynodon dactylon (Bermuda grass) pollen (BGP) by use of organic solvents altered the structural integrity of the pollen coat. The novel IgE-binding proteins of the BGP coat include a cysteine protease (CP) and endoxylanase (EXY). The full-length cDNA that encodes the novel IgE-reactive CP was cloned from floral RNA. The EXY and CP were purified to homogeneity and tested for IgE reactivity. The CP from the BGP coat increased the permeability of human airway epithelial cells, caused a clear concentration-dependent detachment of cells, and damaged their barrier integrity. Conclusions/Significance Using an immunoproteomics approach, novel allergenic proteins of the BGP coat were identified. These proteins represent a class of novel dual-function proteins residing on the coat of the pollen grain that have IgE-binding capacity and proteolytic activity, which disrupts the integrity of the airway epithelial barrier. The identification of pollen coat allergens might explain the IgE-negative response to available skin-prick-testing proteins in patients who have positive symptoms. Further study of the role of these pollen coat proteins in allergic responses is

Dual function of novel pollen coat (surface proteins: IgE-binding capacity and proteolytic activity disrupting the airway epithelial barrier.

Directory of Open Access Journals (Sweden)

Mohamed Elfatih H Bashir

Full Text Available BACKGROUND: The pollen coat is the first structure of the pollen to encounter the mucosal immune system upon inhalation. Prior characterizations of pollen allergens have focused on water-soluble, cytoplasmic proteins, but have overlooked much of the extracellular pollen coat. Due to washing with organic solvents when prepared, these pollen coat proteins are typically absent from commercial standardized allergenic extracts (i.e., "de-fatted", and, as a result, their involvement in allergy has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Using a unique approach to search for pollen allergenic proteins residing in the pollen coat, we employed transmission electron microscopy (TEM to assess the impact of organic solvents on the structural integrity of the pollen coat. TEM results indicated that de-fatting of Cynodon dactylon (Bermuda grass pollen (BGP by use of organic solvents altered the structural integrity of the pollen coat. The novel IgE-binding proteins of the BGP coat include a cysteine protease (CP and endoxylanase (EXY. The full-length cDNA that encodes the novel IgE-reactive CP was cloned from floral RNA. The EXY and CP were purified to homogeneity and tested for IgE reactivity. The CP from the BGP coat increased the permeability of human airway epithelial cells, caused a clear concentration-dependent detachment of cells, and damaged their barrier integrity. CONCLUSIONS/SIGNIFICANCE: Using an immunoproteomics approach, novel allergenic proteins of the BGP coat were identified. These proteins represent a class of novel dual-function proteins residing on the coat of the pollen grain that have IgE-binding capacity and proteolytic activity, which disrupts the integrity of the airway epithelial barrier. The identification of pollen coat allergens might explain the IgE-negative response to available skin-prick-testing proteins in patients who have positive symptoms. Further study of the role of these pollen coat proteins in allergic

Small intestine epithelial barrier function is compromised in pigs with low feed intake at weaning.

NARCIS (Netherlands)

Spreeuwenberg, M.A.; Verdonk, J.M.; Gaskins, H.R.; Verstegen, M.W.A.

2001-01-01

Compromising alterations in gastrointestinal architecture are common during the weaning transition of pigs. The relation between villous atrophy and epithelial barrier function at weaning is not well understood. This study evaluated in vitro transepithelial transport by Ussing metabolic chambers,

Quantitative analysis of epithelial papillae in patients with oral lichen planus.

Science.gov (United States)

López-Jornet, P; Camacho-Alonso, F; Molina-Miñano, F

2009-06-01

The oral mucosa is relatively vulnerable to pathological processes, and is often affected by autoimmune and malignant diseases. The oral epithelium is normally non-homogeneous, and joins to the connective tissue through interlocking of its downward projections in the form of papillae. This study aims to conduct a histomorphometric study of the epithelial papillae in patients with oral lichen planus (OLP). This study was based on 100 cheek mucosa biopsies from patients with OLP (66 white reticular and 34 atrophic-erosive) (13 males and 87 females, with a mean age of 54.95 +/- 13.64 years). A histological and morphometric evaluation was made, based on imaging analysis with MIP software 4.5 for studying the papillary structure in the patients with OLP. The mean epithelial thickness was 227.5 +/- 78.5 microm. The different papillary measures--BLS (distance from basal layer to epithelial surface), DPS (distance from dermal papilla top to epithelial surface), DPW (dermal papilla width), and DPD (interdermal papilla distance between two papillae)--yielded no statistically significant differences with respect to age, sex, smoking and clinical form. However, a significant correlation was observed in relation to papilla width and inflammatory infiltrate (P = 0.031). The application of this imaging system is useful for measuring variations in epithelial papillary architecture.

A Pub/Sub Message Distribution Architecture for Disruption Tolerant Networks

Science.gov (United States)

Carrilho, Sergio; Esaki, Hiroshi

Access to information is taken for granted in urban areas covered by a robust communication infrastructure. Nevertheless most of the areas in the world, are not covered by such infrastructures. We propose a DTN publish and subscribe system called Hikari, which uses nodes' mobility in order to distribute messages without using a robust infrastructure. The area of Disruption/Delay Tolerant Networks (DTN) focuses on providing connectivity to locations separated by networks with disruptions and delays. The Hikari system does not use node identifiers for message forwarding thus eliminating the complexity of routing associated with many forwarding schemes in DTN. Hikari uses nodes paths' information, advertised by special nodes in the system or predicted by the system itself, for optimizing the message dissemination process. We have used the Paris subway system, due to it's complexity, to validate Hikari and to analyze it's performance. We have shown that Hikari achieves a superior deliver rate while keeping redundant messages in the system low, which is ideal when using devices with limited resources for message dissemination.

Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast epithelial cells.

Science.gov (United States)

Hilmarsdottir, Bylgja; Briem, Eirikur; Halldorsson, Skarphedinn; Kricker, Jennifer; Ingthorsson, Sævar; Gustafsdottir, Sigrun; Mælandsmo, Gunhild M; Magnusson, Magnus K; Gudjonsson, Thorarinn

2017-05-11

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell-cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype.

Inhibition of PTP1B disrupts cell–cell adhesion and induces anoikis in breast epithelial cells

Science.gov (United States)

Hilmarsdottir, Bylgja; Briem, Eirikur; Halldorsson, Skarphedinn; Kricker, Jennifer; Ingthorsson, Sævar; Gustafsdottir, Sigrun; Mælandsmo, Gunhild M; Magnusson, Magnus K; Gudjonsson, Thorarinn

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell–cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype. PMID:28492548

Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

Science.gov (United States)

Sakai, Norihiko; Tager, Andrew M.

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes

Directory of Open Access Journals (Sweden)

Shih-Han Kao

2016-02-01

Full Text Available Tumor hypoxia is a pathophysiologic outcome of disrupted microcirculation with inadequate supply of oxygen, leading to enhanced proliferation, epithelial-mesenchymal transition (EMT, metastasis, and chemo-resistance. Epigenetic changes induced by hypoxia are well documented, and they lead to tumor progression. Recent advances show that DNA demethylation mediated by the Ten-eleven translocation (TET proteins induces major epigenetic changes and controls key steps of cancer development. TET enzymes serve as 5mC (5-methylcytosine-specific dioxygenases and cause DNA demethylation. Hypoxia activates the expression of TET1, which also serves as a co-activator of HIF-1α transcriptional regulation to modulate HIF-1α downstream target genes and promote epithelial-mesenchymal transition. As HIF is a negative prognostic factor for tumor progression, hypoxia-activated prodrugs (HAPs may provide a favorable therapeutic approach to lessen hypoxia-induced malignancy.

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

DEFF Research Database (Denmark)

Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C

2016-01-01

studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian...

The architecture and fine structure of gill filaments in the brown ...

African Journals Online (AJOL)

Special attention was paid to filament architecture, ennervation of filaments, number and type of cells populating filament epithelia and variations in epithelial cell morphology and cilia ultrastructure. Filament shape was maintained by thickened chi-tln and strategically placed smooth myocytes. The epithelium was populated ...

Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation

NARCIS (Netherlands)

Loerke, D.; le Duc, Q.; Blonk, I.; Kerstens, A.; Spanjaard, E.; Machacek, M.; Danuser, G.; de Rooij, J.

2012-01-01

The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that

Architecture and fine structure of gill filaments in the brown mussel, perna perna

CSIR Research Space (South Africa)

Gregory, MA

1996-10-01

Full Text Available attention was paid to filament architecture, enervation of filaments, number and type of cells populating filament epithelia and variations in epithelial cell morphotogy and cilia ultra structure. Filament shape was maintained by thickened chitin...

Space Mobile Network: A Near Earth Communication and Navigation Architecture

Science.gov (United States)

Israel, Dave J.; Heckler, Greg; Menrad, Robert J.

2016-01-01

This paper describes a Space Mobile Network architecture, the result of a recently completed NASA study exploring architectural concepts to produce a vision for the future Near Earth communications and navigation systems. The Space Mobile Network (SMN) incorporates technologies, such as Disruption Tolerant Networking (DTN) and optical communications, and new operations concepts, such as User Initiated Services, to provide user services analogous to a terrestrial smartphone user. The paper will describe the SMN Architecture, envisioned future operations concepts, opportunities for industry and international collaboration and interoperability, and technology development areas and goals.

Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells: Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein response

International Nuclear Information System (INIS)

Mukhopadhyay, Somshuvra; Shah, Mehul; Patel, Kirit; Sehgal, Pravin B.

2006-01-01

The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension by inducing a 'megalocytosis' phenotype in target pulmonary arterial endothelial, smooth muscle and Type II alveolar epithelial cells. In cultured endothelial cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP) results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and increased vacuoles. However, these cells fail to enter mitosis. Largely based upon data from endothelial cells, we proposed earlier that a disruption of the trafficking and mitosis-sensor functions of the Golgi (the 'Golgi blockade' hypothesis) may represent the subcellular mechanism leading to MCTP-induced megalocytosis. In the present study, we investigated the applicability of the Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis in cultures of lung A549 and breast MCF-7 cells. This was associated with a change in the distribution of the cis-Golgi scaffolding protein GM130 from a discrete juxtanuclear localization to a circumnuclear distribution consistent with an anterograde block of GM130 trafficking to/through the Golgi. There was also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together with a circumnuclear accumulation of clathrin heavy chain (CHC) and α-tubulin. Flotation analyses revealed losses/alterations in the association of caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis was accompanied by an enhanced unfolded protein response (UPR) as evidenced by nuclear translocation of Ire1α and glucose regulated protein 58 (GRP58/ER-60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide isomerase (PDI). These data further support the hypothesis that an MCTP-induced Golgi blockade and enhanced UPR may represent the subcellular mechanism leading to enlargement of ER and Golgi and subsequent megalocytosis

3D view to tumor suppression: Lkb1, polarity and the arrest of oncogenic c-Myc.

Science.gov (United States)

Partanen, Johanna I; Nieminen, Anni I; Klefstrom, Juha

2009-03-01

Machiavelli wrote, in his famous political treatise Il Principe, about disrupting organization by planting seeds of dissension or by eliminating necessary support elements. Tumor cells do exactly that by disrupting the organized architecture of epithelial cell layers during progression from contained benign tumor to full-blown invasive cancer. However, it is still unclear whether tumor cells primarily break free by activating oncogenes powerful enough to cause chaos or by eliminating tumor suppressor genes guarding the order of the epithelial organization. Studies in Drosophila have exposed genes that encode key regulators of the epithelial apicobasal polarity and which, upon inactivation, cause disorganization of the epithelial layers and promote unscheduled cell proliferation. These polarity regulator/tumor suppressor proteins, which include products of neoplastic tumor suppressor genes (nTSGs), are carefully positioned in polarized epithelial cells to maintain the order of epithelial structures and to impose a restraint on cell proliferation. In this review, we have explored the presence and prevalence of somatic mutations in the human counterparts of Drosophila polarity regulator/tumor suppressor genes across the human cancers. The screen points out LKB1, which is a causal genetic lesion in Peutz-Jeghers cancer syndrome, a gene mutated in certain sporadic cancers and a human homologue of the fly polarity gene par-4. We review the evidence linking Lkb1 protein to polarity regulation in the scope of our recent results suggesting a coupled role for Lkb1 as an architect of organized acinar structures and a suppressor of oncogenic c-Myc. We finally present models to explain how Lkb1-dependent formation of epithelial architecture is coupled to suppression of normal and oncogene-induced proliferation.

Alveolocapillary model system to study alveolar re-epithelialization

Energy Technology Data Exchange (ETDEWEB)

Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands); Cohen Tervaert, Jan Willem [Division of Clinical and Experimental Immunology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht (Netherlands); Duimel, Hans J.Q.; Verheyen, Fons K.C.P. [Electron Microscopy Unit, Department of Molecular Cell Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Iwaarden, J. Freek van, E-mail: f.vaniwaarden@maastrichtuniversity.nl [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands)

2013-01-01

In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ► Model system for vital imaging and high throughput screening. ► Microvascular endothelium influences re-epithelialization. ► A549 cells form protrusions through membrane to contact HPMEC. ► A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

Science.gov (United States)

Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

2017-01-01

Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway.

Science.gov (United States)

Sibony, Michal; Abdullah, Majd; Greenfield, Laura; Raju, Deepa; Wu, Ted; Rodrigues, David M; Galindo-Mata, Esther; Mascarenhas, Heidi; Philpott, Dana J; Silverberg, Mark S; Jones, Nicola L

2015-12-01

Autophagy is implicated in Crohn's disease (CD) pathogenesis. Recent evidence suggests autophagy regulates the microRNA (miRNA)-induced silencing complex (miRISC). Therefore, autophagy may play a novel role in CD by regulating expression of miRISC, thereby altering miRNA silencing. As microbes associated with CD can alter autophagy, we hypothesized that microbial disruption of autophagy affects the critical miRISC component AGO2. AGO2 expression was assessed in epithelial and immune cells, and intestinal organoids with disrupted autophagy. Microarray technology was used to determine the expression of downstream miRNAs in cells with defective autophagy. Increased AGO2 was detected in autophagy-deficient ATG5-/- and ATG16-/- mouse embryonic fibroblast cells (MEFs) in comparison with wild-type MEFs. Chemical agents and VacA toxin, which disrupt autophagy, increased AGO2 expression in MEFs, epithelial cells lines, and human monocytes, respectively. Increased AGO2 was also detected in ATG7-/- intestinal organoids, in comparison with wild-type organoids. Five miRNAs were differentially expressed in autophagy-deficient MEFs. Pathway enrichment analysis of the differentially expressed miRNAs implicated signaling pathways previously associated with CD. Taken together, our results suggest that autophagy is involved in the regulation of the critical miRISC component AGO2 in epithelial and immune cells and primary intestinal epithelial cells. We propose a mechanism by which autophagy alters miRNA expression, which likely impacts the regulation of CD-associated pathways. Furthermore, as enteric microbial products can manipulate autophagy and AGO2, our findings suggest a novel mechanism by which enteric microbes could influence miRNA to promote disease.

Sonographic ally Detected Architectural Distortion: Clinical Significance

Energy Technology Data Exchange (ETDEWEB)

Kim, Shin Kee; Seo, Bo Kyoung; Yi, Ann; Cha, Sang Hoon; Kim, Baek Hyun; Cho, Kyu Ran; Kim, Young Sik; Son, Gil Soo; Kim, Young Soo; Kim, Hee Young [Korea University Ansan Hospital, Ansan (Korea, Republic of)

2008-12-15

Architectural distortion is a suspicious abnormality for the diagnosis of breast cancer. The aim of this study was to investigate the clinical significance of sonographic ally detected architectural distortion. From January 2006 to June 2008, 20 patients were identified who had sonographic ally detected architectural distortions without a history of trauma or surgery and abnormal mammographic findings related to an architectural distortion. All of the lesions were pathologically verified. We evaluated the clinical and pathological findings and then assessed the clinical significance of the sonographic ally detected architectural distortions. Based on the clinical findings, one (5%) of the 20 patients had a palpable lump and the remaining 19 patients had no symptoms. No patient had a family history of breast cancer. Based on the pathological findings, three (15%) patients had malignancies. The malignant lesions included invasive ductal carcinomas (n = 2) and ductal carcinoma in situ (n = 1). Four (20%) patients had high-risk lesions: atypical ductal hyperplasia (n = 3) and lobular carcinoma in situ (n = 1). The remaining 13 (65%) patients had benign lesions, however, seven (35%) out of 13 patients had mild-risk lesions (three intraductal papillomas, three moderate or florid epithelial hyperplasia and one sclerosing adenosis). Of the sonographic ally detected architectural distortions, 35% were breast cancers or high-risk lesions and 35% were mild-risk lesions. Thus, a biopsy might be needed for an architectural distortion without an associated mass as depicted on breast ultrasound, even though the mammographic findings are normal

Sonographic ally Detected Architectural Distortion: Clinical Significance

International Nuclear Information System (INIS)

Kim, Shin Kee; Seo, Bo Kyoung; Yi, Ann; Cha, Sang Hoon; Kim, Baek Hyun; Cho, Kyu Ran; Kim, Young Sik; Son, Gil Soo; Kim, Young Soo; Kim, Hee Young

2008-01-01

Architectural distortion is a suspicious abnormality for the diagnosis of breast cancer. The aim of this study was to investigate the clinical significance of sonographic ally detected architectural distortion. From January 2006 to June 2008, 20 patients were identified who had sonographic ally detected architectural distortions without a history of trauma or surgery and abnormal mammographic findings related to an architectural distortion. All of the lesions were pathologically verified. We evaluated the clinical and pathological findings and then assessed the clinical significance of the sonographic ally detected architectural distortions. Based on the clinical findings, one (5%) of the 20 patients had a palpable lump and the remaining 19 patients had no symptoms. No patient had a family history of breast cancer. Based on the pathological findings, three (15%) patients had malignancies. The malignant lesions included invasive ductal carcinomas (n = 2) and ductal carcinoma in situ (n = 1). Four (20%) patients had high-risk lesions: atypical ductal hyperplasia (n = 3) and lobular carcinoma in situ (n = 1). The remaining 13 (65%) patients had benign lesions, however, seven (35%) out of 13 patients had mild-risk lesions (three intraductal papillomas, three moderate or florid epithelial hyperplasia and one sclerosing adenosis). Of the sonographic ally detected architectural distortions, 35% were breast cancers or high-risk lesions and 35% were mild-risk lesions. Thus, a biopsy might be needed for an architectural distortion without an associated mass as depicted on breast ultrasound, even though the mammographic findings are normal

Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin.

Science.gov (United States)

Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A

2015-03-01

Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.

Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

Science.gov (United States)

Mao, Lulu; Dauchy, Robert T.; Blask, David E.; Slakey, Lauren M.; Xiang, Shulin; Yuan, Lin; Dauchy, Erin M.; Shan, Bin; Brainard, George C.; Hanifin, John P.; Duplessis, Tamika T.; Hill, Steven M.

2012-01-01

Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients. PMID:23002080

Disruption of contact inhibition in rat liver epithelial cells by various types of AhR ligands

Energy Technology Data Exchange (ETDEWEB)

Vondracek, J.; Chramostova, K.; Kozubik, A. [Institute of Biophysics, Brno (Czech Republic); Krcmar, P.; Machala, M. [Veterinary Research Institute, Brno (Czech Republic)

2004-09-15

The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell population for both tumor initiating and tumor promoting chemicals4. 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) has been found to release rat liver epithelial cells from contact inhibition by upregulating cyclin A expression and cyclin A/cdk2 activity. Our previous studies have shown that a number of AhR ligands5,6 can stimulate proliferation of confluent of rat liver epithelial ''stem-like'' WB-F344 cells. Such mechanism could play a role in liver tumor promotion. In the present study, we used flavonoid compounds that have been reported to act either as pure agonists, such as beta-naphthoflavone (BNF), or as partial/complete antagonists of AhR - alpha-naphthoflavone (ANF) and 3'-methoxy-4'-nitroflavone (3'M4'NF), in order to investigate effects of AhR agonists/antagonists on confluent rat liver epithelial cells. The present study aimed to investigate the effects of model flavonoids on the release of rat liver epithelial cells from contact inhibition, and on inducibility of

Disruptive Innovations as a Driving Force for the Change of Wireless Telecommunication Infrastructures

DEFF Research Database (Denmark)

Kyoseva, Tsvetoslava; Poulkov, Vladimir; Mihaylov, Mihail Rumenov

2014-01-01

the current trends in mobile communications, we reason that the emergence of new telecommunication architectures and infrastructures is inevitable. An important consideration in the analysis is the driving role of disruptive technologies for the future of telecommunications. Based on a model for evaluating...

Analyzing Resiliency of the Smart Grid Communication Architectures

Energy Technology Data Exchange (ETDEWEB)

None, None

2016-08-01

Smart grids are susceptible to cyber-attack as a result of new communication, control and computation techniques employed in the grid. In this paper, we characterize and analyze the resiliency of smart grid communication architecture, specifically an RF mesh based architecture, under cyber attacks. We analyze the resiliency of the communication architecture by studying the performance of high-level smart grid functions such as metering, and demand response which depend on communication. Disrupting the operation of these functions impacts the operational resiliency of the smart grid. Our analysis shows that it takes an attacker only a small fraction of meters to compromise the communication resiliency of the smart grid. We discuss the implications of our result to critical smart grid functions and to the overall security of the smart grid.

Solid and papillary epithelial neoplasm of the pancreas: radiologic and pathologic correlation

International Nuclear Information System (INIS)

Yang, Ik; Lim, Joo Won; Ko, Young Tae; Lim, Jae Hoon; Yang, Dal Mo; Kim, Eun Kyung; Kwak, Jeong Ho

1994-01-01

Computed tomographic(CT), ultrasonographic(US) findings of solid and papillary epithelial neoplasm of the pancreas were correlated with pathologic findings for the better understanding of this disease entity. A retrospective review of CT and US of 14 cases of solid and papillary epithelial neoplasm of the pancreas was carried out in terms of the margin, internal architecture, calcification and septation, and this was correlated with gross pathologic findings. CT and US findings were well defined round masses consisting of both solid and cystic components. Five cases were cystic, four cases were solid and five cases were mixed. Cystic portion of the tumor represented variable degree of hemorrhagic necrosis. Six cases contained foci of calcification, which were linear, marginal and amorphous. Marginal calcification interfered US examination of the mass in three cases. Internal septum was demonstrated in four cases on CT, one case on US and three cases on gross specimen. Our results indicate that calcification and internal septum were considered as a part of radiologic findings in solid and papillary epithelial neoplasm of the pancreas

Free-floating epithelial micro-tissue arrays: a low cost and versatile technique.

Science.gov (United States)

Flood, P; Alvarez, L; Reynaud, E G

2016-10-11

Three-dimensional (3D) tissue models are invaluable tools that can closely reflect the in vivo physiological environment. However, they are usually difficult to develop, have a low throughput and are often costly; limiting their utility to most laboratories. The recent availability of inexpensive additive manufacturing printers and open source 3D design software offers us the possibility to easily create affordable 3D cell culture platforms. To demonstrate this, we established a simple, inexpensive and robust method for producing arrays of free-floating epithelial micro-tissues. Using a combination of 3D computer aided design and 3D printing, hydrogel micro-moulding and collagen cell encapsulation we engineered microenvironments that consistently direct the growth of micro-tissue arrays. We described the adaptability of this technique by testing several immortalised epithelial cell lines (MDCK, A549, Caco-2) and by generating branching morphology and micron to millimetre scaled micro-tissues. We established by fluorescence and electron microscopy that micro-tissues are polarised, have cell type specific differentiated phenotypes and regain native in vivo tissue qualities. Finally, using Salmonella typhimurium we show micro-tissues display a more physiologically relevant infection response compared to epithelial monolayers grown on permeable filter supports. In summary, we have developed a robust and adaptable technique for producing arrays of epithelial micro-tissues. This in vitro model has the potential to be a valuable tool for studying epithelial cell and tissue function/architecture in a physiologically relevant context.

Functional evaluations of genes disrupted in patients with Tourette’s Disorder

Directory of Open Access Journals (Sweden)

Nawei eSun

2016-02-01

Full Text Available Tourette Disorder (TD is a highly heritable neurodevelopmental disorder with complex genetic architecture and unclear neuropathology. Disruptions of particular genes have been identified in subsets of TD patients. However, none of the findings has been replicated, probably due to the complex and heterogeneous genetic architecture of TD that involves both common and rare variants. To understand the etiology of TD, functional analyses are required to characterize the molecular and cellular consequences caused by mutations in candidate genes. Such molecular and cellular alterations may converge into common biological pathways underlying the heterogeneous genetic etiology of TD patients. Herein, we review specific genes implicated in TD etiology, discuss the functions of these genes in the mammalian central nervous system and the corresponding behavioral anomalies exhibited in animal models and, importantly, review functional analyses that can be performed to evaluate the role(s that the genetic disruptions might play in TD. Specifically, the functional assays include novel cell culture systems, genome editing techniques, bioinformatics approaches, transcriptomic analyses and genetically modified animal models applied or developed to study genes associated with TD or with other neurodevelopmental and neuropsychiatric disorders. By describing methods used to study diseases with genetic architecture similar to TD, we hope to develop a systematic framework for investigating the etiology of TD and related disorders.

The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis

Science.gov (United States)

Yates, Laura L.; Schnatwinkel, Carsten; Murdoch, Jennifer N.; Bogani, Debora; Formstone, Caroline J.; Townsend, Stuart; Greenfield, Andy; Niswander, Lee A.; Dean, Charlotte H.

2010-01-01

The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia. Defects in lung architecture are also associated with adult lung disease, particularly in cases of idiopathic lung fibrosis. Identifying the signalling pathways which drive epithelial tube formation will likely shed light on both congenital and adult lung disease. Here we show that mutations in the planar cell polarity (PCP) genes Celsr1 and Vangl2 lead to disrupted lung development and defects in lung architecture. Lungs from Celsr1Crsh and Vangl2Lp mouse mutants are small and misshapen with fewer branches, and by late gestation exhibit thickened interstitial mesenchyme and defective saccular formation. We observe a recapitulation of these branching defects following inhibition of Rho kinase, an important downstream effector of the PCP signalling pathway. Moreover, epithelial integrity is disrupted, cytoskeletal remodelling perturbed and mutant endoderm does not branch normally in response to the chemoattractant FGF10. We further show that Celsr1 and Vangl2 proteins are present in restricted spatial domains within lung epithelium. Our data show that the PCP genes Celsr1 and Vangl2 are required for foetal lung development thereby revealing a novel signalling pathway critical for this process that will enhance our understanding of congenital and adult lung diseases and may in future lead to novel therapeutic strategies. PMID:20223754

Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats.

Science.gov (United States)

Pocivavsek, Ana; Baratta, Annalisa M; Mong, Jessica A; Viechweg, Shaun S

2017-11-01

Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality. Adult male Wistar rats were treated with vehicle (saline) and kynurenine (25, 50, 100, and 250 mg/kg), the direct bioprecursor of KYNA, intraperitoneally at zeitgeber time (ZT) 0 to rapidly increase brain KYNA. Levels of KYNA in the brainstem, cortex, and hippocampus were determined at ZT 0, ZT 2, and ZT 4, respectively. Analyses of vigilance state-related parameters categorized as wake, rapid eye movement (REM), and non-REM (NREM) as well as spectra power analysis during NREM and REM were assessed during the light phase. Separate animals were tested in the passive avoidance paradigm, testing contextual memory. When KYNA levels were elevated in the brain, total REM duration was reduced and total wake duration was increased. REM and wake architecture, assessed as number of vigilance state bouts and average duration of each bout, and theta power during REM were significantly impacted. Kynurenine challenge impaired performance in the hippocampal-dependent contextual memory task. Our results introduce kynurenine pathway metabolism and formation of KYNA as a novel molecular target contributing to sleep disruptions and cognitive impairments. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress

Science.gov (United States)

Ohashi, Wakana; Kimura, Shunsuke; Iwanaga, Toshihiko; Furusawa, Yukihiro; Irié, Tarou; Izumi, Hironori; Watanabe, Takashi; Hara, Takafumi; Ohara, Osamu; Koseki, Haruhiko; Sato, Toshiro; Robine, Sylvie; Mori, Hisashi; Hattori, Yuichi; Mishima, Kenji; Ohno, Hiroshi; Hase, Koji; Fukada, Toshiyuki

2016-01-01

Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER) stress in proliferative progenitor cells, leading to significant cell death of progenitor cells. Zip7 deficiency led to the loss of Olfm4+ intestinal stem cells and the degeneration of post-mitotic Paneth cells, indicating a fundamental requirement for Zip7 in homeostatic intestinal regeneration. Taken together, these findings provide evidence for the importance of ZIP7 in maintenance of intestinal epithelial homeostasis through the regulation of ER function in proliferative progenitor cells and maintenance of intestinal stem cells. Therapeutic targeting of ZIP7 could lead to effective treatment of gastrointestinal disorders. PMID:27736879

Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress.

Directory of Open Access Journals (Sweden)

Wakana Ohashi

2016-10-01

Full Text Available Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER stress in proliferative progenitor cells, leading to significant cell death of progenitor cells. Zip7 deficiency led to the loss of Olfm4+ intestinal stem cells and the degeneration of post-mitotic Paneth cells, indicating a fundamental requirement for Zip7 in homeostatic intestinal regeneration. Taken together, these findings provide evidence for the importance of ZIP7 in maintenance of intestinal epithelial homeostasis through the regulation of ER function in proliferative progenitor cells and maintenance of intestinal stem cells. Therapeutic targeting of ZIP7 could lead to effective treatment of gastrointestinal disorders.

Distributed hierarchical control architecture for integrating smart grid assets during normal and disrupted operations

Science.gov (United States)

Kalsi, Karan; Fuller, Jason C.; Somani, Abhishek; Pratt, Robert G.; Chassin, David P.; Hammerstrom, Donald J.

2017-09-12

Disclosed herein are representative embodiments of methods, apparatus, and systems for facilitating operation and control of a resource distribution system (such as a power grid). Among the disclosed embodiments is a distributed hierarchical control architecture (DHCA) that enables smart grid assets to effectively contribute to grid operations in a controllable manner, while helping to ensure system stability and equitably rewarding their contribution. Embodiments of the disclosed architecture can help unify the dispatch of these resources to provide both market-based and balancing services.

Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

Science.gov (United States)

Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

2017-12-01

Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Quantification of acute vocal fold epithelial surface damage with increasing time and magnitude doses of vibration exposure.

Directory of Open Access Journals (Sweden)

Tsuyoshi Kojima

Full Text Available Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes and magnitude-doses (control, modal intensity phonation, or raised intensity phonation of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure.

Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

Directory of Open Access Journals (Sweden)

Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

2010-01-01

Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

Perlecan and Dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization

DEFF Research Database (Denmark)

Schneider, Martina; Khalil, Ashraf A; Poulton, John

2006-01-01

and the cytoskeleton. Disruption of this linkage in skeletal muscle leads to various types of muscular dystrophies. In epithelial cells, reduced expression of Dg is associated with increased invasiveness of cancer cells. We have previously shown that Dg is required for epithelial cell polarity in Drosophila......, but the mechanisms of this polarizing activity and upstream/downstream components are largely unknown. Using the Drosophila follicle-cell epithelium (FCE) as a model system, we show that the ECM molecule Perlecan (Pcan) is required for maintenance of epithelial-cell polarity. Follicle cells that lack Pcan develop...... polarity defects similar to those of Dg mutant cells. Furthermore, Dg depends on Pcan but not on Laminin A for its localization in the basal-cell membrane, and the two proteins bind in vitro. Interestingly, the Dg form that interacts with Pcan in the FCE lacks the mucin-like domain, which is thought...

Crystal structure of the epithelial calcium channel TRPV6.

Science.gov (United States)

Saotome, Kei; Singh, Appu K; Yelshanskaya, Maria V; Sobolevsky, Alexander I

2016-06-23

Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K(+) channel-like transmembrane domain, Ca(2+) selectivity is determined by direct coordination of Ca(2+) by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca(2+) permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca(2+) uptake and its role in pathophysiology.

The Role of Epithelial Stat3 in Amelogenesis during Mouse Incisor Renewal.

Science.gov (United States)

Zhang, Bin; Meng, Bo; Viloria, Edward; Naveau, Adrien; Ganss, Bernhard; Jheon, Andrew H

2018-03-16

The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14Cre/+;Stat3fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis. © 2018 S. Karger AG, Basel.

Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix

International Nuclear Information System (INIS)

Link, R.E.; Paus, R.; Stenn, K.S.; Kuklinska, E.; Moellmann, G.

1990-01-01

An in vitro assay utilizing the rat vibrissa anagen follicle as a model for studying the epithelial-mesenchymal interactions (EMI) in hair growth is described. Through selective disruption of the epithelial-mesenchymal interface, we investigate whether the specialized extracellular matrix (ECM) of the dermal papilla and basement membrane zone (BMZ) serves a crucial function in hair follicle EMI. Epithelial bulbs incubated intact within their follicular sheaths incorporate thymidine primarily into cells of the hair matrix and outer root sheath, as shown by autoradiography. However, after removal of its mesenchymal associations (dermal papilla and extrabulbar connective tissue), the epithelial bulb showed no incorporation. Neither externally added collagen (type I or IV) nor the basement membrane components in Matrigel could substitute for the growth supporting influence of native surrounding stroma. Mechanical separation of the bulb from the dermal papilla in the basement membrane zone inhibited thymidine incorporation by the epithelium even though mesenchyme was still in close proximity. Enzymatic digestion of the dermal papilla ECM and the basal lamina by Dispase, a fibronectinase and type IV collagenase, also inhibited bulb growth without evidence of cytotoxicity. These experiments suggest that direct epithelial to mesenchymal contact is required for the support of follicular epithelial growth in vitro and that specific ECM components, possibly fibronectin and/or type IV collagen, rather than diffusable factors alone, play a crucial role in the mechanism of hair follicle EMI. The in vitro system described here provides an alternative to developmental EMI models and may serve as a valuable tool for studying EMI in the adult mammalian organism

Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine.

Science.gov (United States)

Pagel, René; Bär, Florian; Schröder, Torsten; Sünderhauf, Annika; Künstner, Axel; Ibrahim, Saleh M; Autenrieth, Stella E; Kalies, Kathrin; König, Peter; Tsang, Anthony H; Bettenworth, Dominik; Divanovic, Senad; Lehnert, Hendrik; Fellermann, Klaus; Oster, Henrik; Derer, Stefanie; Sina, Christian

2017-11-01

Endogenous circadian clocks regulate 24-h rhythms of physiology and behavior. Circadian rhythm disruption (CRD) is suggested as a risk factor for inflammatory bowel disease. However, the underlying molecular mechanisms remain unknown. Intestinal biopsies from Per1/2 mutant and wild-type (WT) mice were investigated by electron microscopy, immunohistochemistry, and bromodeoxyuridine pulse-chase experiments. TNF-α was injected intraperitoneally, with or without necrostatin-1, into Per1/2 mice or rhythmic and externally desynchronized WT mice to study intestinal epithelial cell death. Experimental chronic colitis was induced by oral administration of dextran sodium sulfate. In vitro , caspase activity was assayed in Per1/2-specific small interfering RNA-transfected cells. Wee1 was overexpressed to study antiapoptosis and the cell cycle. Genetic ablation of circadian clock function or environmental CRD in mice increased susceptibility to severe intestinal inflammation and epithelial dysregulation, accompanied by excessive necroptotic cell death and a reduced number of secretory epithelial cells. Receptor-interacting serine/threonine-protein kinase (RIP)-3-mediated intestinal necroptosis was linked to increased mitotic cell cycle arrest via Per1/2-controlled Wee1, resulting in increased antiapoptosis via cellular inhibitor of apoptosis-2. Together, our data suggest that circadian rhythm stability is pivotal for the maintenance of mucosal barrier function. CRD increases intestinal necroptosis, thus rendering the gut epithelium more susceptible to inflammatory processes.-Pagel, R., Bär, F., Schröder, T., Sünderhauf, A., Künstner, A., Ibrahim, S. M., Autenrieth, S. E., Kalies, K., König, P., Tsang, A. H., Bettenworth, D., Divanovic, S., Lehnert, H., Fellermann, K., Oster, H., Derer, S., Sina, C. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. © FASEB.

Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).

Science.gov (United States)

Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y; Permuth-Wey, Jennifer; Aben, Katja Kh; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Vierkant, Robert A; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Schernhammer, Eva; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M; Kelemen, Linda E; Ramus, Susan J; Monteiro, Alvaro N A; Goode, Ellen L; Narod, Steven A; Gayther, Simon A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10 -4 ]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1 , may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.

Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation

International Nuclear Information System (INIS)

Dublineau, I.; Lebrun, F.; Grison, S.; Griffiths, N.M.

2004-01-01

Irradiation of the digestive system leads to alterations of the small intestine. We have characterized the disruption of the barrier integrity in rat ileum from 1 to 14 days following irradiation ranging from 6 to 12 Gy. The intestinal permeability to 14 C-mannitol and 3 H-dextran 70,000 was measured in vitro in Ussing chambers. In parallel to these functional studies, immunohistochemical analyses of junctional proteins (ZO-1 and β-catenin) of ileal epithelium were performed by confocal microscopy. Irradiation with 10 Gy induced a marked decrease in epithelial tissue resistance at three days and a fivefold increase in mannitol permeability, without modifications of dextran permeability. A disorganization of the localization for ZO-1 and β-catenin was also observed. At 7 days after irradiation, we observed a recovery of the organization of junctional proteins in parallel to a return of intestinal permeability to control value. In addition to these time-dependent effects, a gradual effect on epithelial integrity of the radiation doses was observed 3 days after irradiation. This study shows a disruption of the integrity of the intestinal barrier in rat ileum following abdominal X-irradiation, depending on the time postirradiation and on the delivered dose. The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions, leading to increased intestinal permeability to mannitol. (author)

Realizing improved patient care through human-centered operating room design: a human factors methodology for observing flow disruptions in the cardiothoracic operating room.

Science.gov (United States)

Palmer, Gary; Abernathy, James H; Swinton, Greg; Allison, David; Greenstein, Joel; Shappell, Scott; Juang, Kevin; Reeves, Scott T

2013-11-01

Human factors engineering has allowed a systematic approach to the evaluation of adverse events in a multitude of high-stake industries. This study sought to develop an initial methodology for identifying and classifying flow disruptions in the cardiac operating room (OR). Two industrial engineers with expertise in human factors workflow disruptions observed 10 cardiac operations from the moment the patient entered the OR to the time they left for the intensive care unit. Each disruption was fully documented on an architectural layout of the OR suite and time-stamped during each phase of surgery (preoperative [before incision], operative [incision to skin closure], and postoperative [skin closure until the patient leaves the OR]) to synchronize flow disruptions between the two observers. These disruptions were then categorized. The two observers made a total of 1,158 observations. After the elimination of duplicate observations, a total of 1,080 observations remained to be analyzed. These disruptions were distributed into six categories such as communication, usability, physical layout, environmental hazards, general interruptions, and equipment failures. They were further organized into 33 subcategories. The most common disruptions were related to OR layout and design (33%). By using the detailed architectural diagrams, the authors were able to clearly demonstrate for the first time the unique role that OR design and equipment layout has on the generation of physical layout flow disruptions. Most importantly, the authors have developed a robust taxonomy to describe the flow disruptions encountered in a cardiac OR, which can be used for future research and patient safety improvements.

Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

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Shuxian Jiang

2010-03-01

Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

When to remove the urethral catheter after endoscopic realignment of traumatic disruption of the posterior urethra?

Science.gov (United States)

El Darawany, H M

2017-09-01

To detect the optimal time for urethral stent removal after endoscopic urethral realignment and its effect on the incidence of development of urethral stricture. Eighteen patients underwent endoscopic urethral realignment after traumatic disruption of the posterior urethra. Post-operative urethroscopy was done using the flexible cystoscope to assess progress of urethral healing. The urethral Foley catheter that served as a stent and for urine drainage was removed only when complete mucosal healing was observed by flexible urethroscopy. There was a post-operative follow-up period of 12-36months. Uroflowmetry was performed at the end of the follow-up period. Endoscopy 6weeks after realignment showed 50-75% mucosal epithelialization at the site of urethral disruption in all patients. Epithelialization was complete at 9weeks in 15/18 patients (83%) and at 12weeks in the remaining 3 patients (17%). One patient (5.6%) developed a mild symptomatic stricture 5months post stent removal that was successfully treated by a single session of visual urethrotomy. All 18 patients had normal uroflowmetry readings at 12-36months after realignment. Urethral stenting should be continued till mucosal healing at the site of urethral disruption became complete. Removal of the stent at this optimal time decreases the incidence of post-operative urethral stricture. Flexible urethroscopy was a safe procedure for post-operative follow-up of endoscopic urethral realignment to assess the progress and completion of mucosal healing at the site of realignment. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Low frequency vibrations disrupt left-right patterning in the Xenopus embryo.

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Laura N Vandenberg

Full Text Available The development of consistent left-right (LR asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia. Investigating one frequency (7 Hz, we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs.

Phototherapeutic LASEK for a persistent epithelial defect and a recurrent epithelial erosion.

Science.gov (United States)

Hondur, Ahmet; Bilgihan, Kamil; Hasanreisoglu, Berati

2005-01-01

To present two patients, one with persistent epithelial defect and one with recurrent epithelial erosion, unresponsive to conventional therapy treated with phototherapeutic keratectomy (PTK) with the laser subepithelial keratomileusis (LASEK) technique (phototherapeutic LASEK). The epithelial flap was created following 18% ethanol application for 20 seconds. A 10-microm deep ablation was performed in the central 7.0-mm zone. A contact lens was placed and the patient examined daily until epithelial closure. Upon epithelial closure, the contact lens was removed. A mild topical steroid and artificial tears were applied for 2 weeks. The epithelium healed in 4 days in both patients. Patients reported only mild pain until epithelial closure. The manifest refraction and uncorrected visual acuity remained unchanged in both eyes. No haze was noted. The first patient has remained asymptomatic without any recurrence for 12 months, and the second for 9 months. Phototherapeutic LASEK provides a therapeutic option for refractory recurrent erosions and persistent epithelial defects, with the additional benefit of being less painful and less risky for haze development than conventional PTK.

SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells.

Science.gov (United States)

Wu, Di; Huang, Chun-Jie; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Liu, Xiao-Ming; Pandupuspitasari, Nuruliarizki Shinta; Brohi, Rahim Dad; Huo, Li-Jun

2017-08-29

Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation. SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis, and knockdown of SENP3 compromises tight junction in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells, which could attribute to the conspicuous dysfunction of tight junction (TJ) proteins (e.g., ZO-1, occludin) at the cell-cell interface due to the inactivation of STAT3. Moreover, SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance. Our study pinpoints SENP3 might be a novel determinant of multiple pathways governing BTB dynamics in testis to support germ cells development in mammals.

In vivo architectural analysis of 3.2 mm clear corneal incisions for phacoemulsification using optical coherence tomography.

Science.gov (United States)

Torres, Luis F; Saez-Espinola, Fidelia; Colina, Juner M; Retchkiman, Myriam; Patel, Milan R; Agurto, Ricardo; Garcia, Gerardo; Diaz, Jose L; Huang, David; Schanzlin, David J; Chayet, Arturo S

2006-11-01

To analyze in vivo the architecture of clear corneal incisions (CCIs) for phacoemulsification using optical coherence tomography (OCT). Anterior Segment Department, Asociacion Para Evitar la Ceguera en Mexico, Hospital Dr Luis Sanchez Bulnes, Mexico. A prospective masked study analyzed 20 unsutured CCIs placed superiorly and created in a uniplanar fashion with a 3.2 mm slit-angled metal keratome. All wounds were evaluated with a retinal OCT model 1, 3, and 30 days postoperatively. Intraocular pressure (IOP) and incision leakage were checked. The architecture was described according to the angle of incidence, apposition of the epithelial and endothelial margins, and wound sealing. No leakage was detected. The angle varied from 33 to 85 degrees; angles greater than 75 degrees were done by a surgeon in training. Wound apposition at the epithelial margin was achieved in all cases. In contrast, imperfect apposition of the endothelial margin was seen in 45% of incisions on day 1 and in 15% on day 30. Incomplete sealing of the wound was seen by OCT in 25% of cases at 24 hours and persisted in 10% of all cases at 1 month. This gaping occurred on the endothelial side and never translated to the epithelial margin. No statistical correlation was found between gaping and the angle of the incision, IOP variations, or surgeon experience. Although in vivo CCIs caused minor anatomic imperfections, they were clinically stable independent of incision angle, IOP variation, and surgeon experience. Incision stability may be related to careful wound construction, epithelial viability, stromal edema, and efficient endothelial pumping.

mCRAN: A radio access network architecture for 5G indoor ccommunications

NARCIS (Netherlands)

Chandra, Kishor; Cao, Zizheng; Bruintjes, Tom; Prasad, R.V.; Karagiannis, Georgios; Tangdiongga, E.; van den Boom, H.P.A.; Kokkeler, Andre B.J.

2015-01-01

Millimeter wave (mmWave) communication is being seen as a disruptive technology for 5G era. In particular, 60GHz frequency band has emerged as a promising candidate for multi-Gbps connectivity in indoor and hotspot areas. In terms of network architecture, cloud radio access network (CRAN) has

mCRAN : a radio access network architecture for 5G indoor communications

NARCIS (Netherlands)

Chandra, Kishor; Cao, Zizheng; Bruintjes, T. M.; Prasad, R. Venkatesha; Karagiannis, G.; Tangdiongga, Eduward; van den Boom, H.P.A.; Kokkeler, A. B J

2015-01-01

Millimeter wave (mmWave) communication is being seen as a disruptive technology for 5G era. In particular, 60GHz frequency band has emerged as a promising candidate for multi-Gbps connectivity in indoor and hotspot areas. In terms of network architecture, cloud radio access network (CRAN) has

Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

Science.gov (United States)

Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

2012-01-01

Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna.

Science.gov (United States)

Ku, Hui-Yu; Sun, Y Henry

2017-07-01

Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold. Disruption of Notch signaling or the actomyosin network reduces apical constriction and epithelial fold, so that Dll and Lim1 cells become intermingled. Our results demonstrate a new mechanism of boundary formation by actomyosin-dependent tissue folding, which provides a physical barrier to prevent mixing of cells from adjacent developmental fields.

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

Science.gov (United States)

Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

2011-01-01

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

Understanding Enterprise Architecture with Topic Modeling Preliminary Research Based on Journal Articles

DEFF Research Database (Denmark)

Nardello, Marco; Møller, Charles; Gøtze, John

2018-01-01

The next 3 years will be more important than the last 50 due to the digital transformation across industries. Enterprise Architecture (EA), the discipline that should lead enterprise responses to disruptive forces, is far from ready to drive the next wave of change. The state of the art in the di...

Experimental Evaluation of TCP-Based DTN for Cislunar Communications in Presence of Long Link Disruption

Directory of Open Access Journals (Sweden)

Zhang Zhensheng

2011-01-01

Full Text Available Delay/disruption tolerant networking (DTN technology is considered a new solution to highly stressed communications in space environments. To date, little work has been done in evaluating the effectiveness and performance of the available DTN protocols when they are applied to an interplanetary Internet, especially in presence of a long link disruption. In this paper, we present an experimental investigation of the DTN architecture with a Bundle Protocol (BP running over TCP-based convergence layer (TCPCL protocol in a simulated cislunar communication environment characterized by a long link disruption. The intent of this work is to investigate the effectiveness of the TCPCL-based DTN protocol in coping with long link disruptions, through realistic file transfer experiments using a PC-based test-bed. The experiment results show that the DTN protocol is effective in handling a long link disruption experienced in data transmission accompanied by a cislunar link delay and a high BER. The performance of the DTN is most adversely affected by link disruption time in comparison to the effect of link delay and BER. For the transmissions with a very long link disruption of hours, the variations in goodput are nominal with respect to the change in cislunar link delay.

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

Science.gov (United States)

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

Giardia duodenalis Surface Cysteine Proteases Induce Cleavage of the Intestinal Epithelial Cytoskeletal Protein Villin via Myosin Light Chain Kinase.

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Amol Bhargava

Full Text Available Giardia duodenalis infections are among the most common causes of waterborne diarrhoeal disease worldwide. At the height of infection, G. duodenalis trophozoites induce multiple pathophysiological processes within intestinal epithelial cells that contribute to the development of diarrhoeal disease. To date, our understanding of pathophysiological processes in giardiasis remains incompletely understood. The present study reveals a previously unappreciated role for G. duodenalis cathepsin cysteine proteases in intestinal epithelial pathophysiological processes that occur during giardiasis. Experiments first established that Giardia trophozoites indeed produce cathepsin B and L in strain-dependent fashion. Co-incubation of G. duodenalis with human enterocytes enhanced cathepsin production by Assemblage A (NF and S2 isolates trophozoites, but not when epithelial cells were exposed to Assemblage B (GSM isolate trophozoites. Direct contact between G. duodenalis parasites and human intestinal epithelial monolayers resulted in the degradation and redistribution of the intestinal epithelial cytoskeletal protein villin; these effects were abolished when parasite cathepsin cysteine proteases were inhibited. Interestingly, inhibition of parasite proteases did not prevent degradation of the intestinal tight junction-associated protein zonula occludens 1 (ZO-1, suggesting that G. duodenalis induces multiple pathophysiological processes within intestinal epithelial cells. Finally, this study demonstrates that G. duodenalis-mediated disruption of villin is, at least, in part dependent on activation of myosin light chain kinase (MLCK. Taken together, this study indicates a novel role for parasite cathepsin cysteine proteases in the pathophysiology of G. duodenalis infections.

Disrupted resting-state functional architecture of the brain after 45-day simulated microgravity

Science.gov (United States)

Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Liang, Zhu-Yuan; Chen, Xiao-Ping; Zheng, Dang; Tan, Cheng; Tian, Zhi-Qiang; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

2014-01-01

Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of −6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of −6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of −6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity. PMID:24926242

Network architecture test-beds as platforms for ubiquitous computing.

Science.gov (United States)

Roscoe, Timothy

2008-10-28

Distributed systems research, and in particular ubiquitous computing, has traditionally assumed the Internet as a basic underlying communications substrate. Recently, however, the networking research community has come to question the fundamental design or 'architecture' of the Internet. This has been led by two observations: first, that the Internet as it stands is now almost impossible to evolve to support new functionality; and second, that modern applications of all kinds now use the Internet rather differently, and frequently implement their own 'overlay' networks above it to work around its perceived deficiencies. In this paper, I discuss recent academic projects to allow disruptive change to the Internet architecture, and also outline a radically different view of networking for ubiquitous computing that such proposals might facilitate.

Development of an efficient real-time disruption predictor from scratch on JET and implications for ITER

International Nuclear Information System (INIS)

Dormido-Canto, S.; Ramírez, J.M.; Vega, J.; Moreno, R.; Pereira, A.; Murari, A.; López, J.M.

2013-01-01

Prediction of disruptions from scratch is an ITER-relevant topic. The first operations with the new ITER-like wall constitute a good opportunity to test the development of new predictors from scratch and the related methodologies. These methodologies have been based on the Advanced Predictor Of DISruptions (APODIS) architecture. APODIS is a real-time disruption predictor that is in operation in the JET real-time network. Balanced and unbalanced datasets are used to develop real-time predictors from scratch. The discharges are used in chronological order. Also, different criteria to decide when to re-train a predictor are discussed. The best results are obtained by applying a hybrid method (balanced/unbalanced datasets) for training and with the criterion of re-training after every missed alarm. The predictors are tested off-line with all the discharges (disruptive/non-disruptive) corresponding to the first three JET ITER-like wall campaigns. The results give a success rate of 93.8% and a false alarm rate of 2.8%. It should be considered that these results are obtained from models trained with no more than 42 disruptive discharges. (paper)

The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

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Masako Osada

2006-01-01

Full Text Available Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs. Kremen1 (Krm1 is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk by competing for the lipoprotein receptor-related protein (LRP-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2 stage and continuing until the CD4+CD8+(DP stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5 Keratin 8+(K8 stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+ and medullary (UEA-1+ EpCAMhi epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

AziSA: An architecture for underground measurement and control networks - 2nd CSIR Biennial Conference

CSIR Research Space (South Africa)

Stewart, R

2008-11-01

Full Text Available products from various manufacturers. SOLUTION The architecture that has been developed at the CSIR is called AziSA, an isiZulu word meaning ‘to inform’. The AziSA architecture AziSA is a specification for an open measurement and control network... for in-mine communications even if the link with the outside world is disrupted. This requirement for robustness implies that processing in the system must be distributed and not totally dependent on central coordination. Decisions should be made...

Severe Burn-Induced Intestinal Epithelial Barrier Dysfunction Is Associated With Endoplasmic Reticulum Stress and Autophagy in Mice

Science.gov (United States)

Huang, Yalan; Feng, Yanhai; Wang, Yu; Wang, Pei; Wang, Fengjun; Ren, Hui

2018-01-01

The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction. Mice received a 30% total body surface area (TBSA) full-thickness burn, and were sacrificed at 0, 1, 2, 6, 12 and 24 h postburn. The results showed that intestinal permeability was increased significantly after burn injury, accompanied by the damage of mucosa and the alteration of TJ proteins. Severe burn induced ER stress, as indicated by increased intraluminal chaperone binding protein (BIP), CCAAT/enhancer-binding protein homologous protein (CHOP) and inositol-requiring enzyme 1(IRE1)/X-box binding protein 1 splicing (XBP1). Autophagy was activated after burn injury, as evidenced by the increase of autophagy related protein 5 (ATG5), Beclin 1 and LC3II/LC3I ratio and the decrease of p62. Besides, the number of autophagosomes was also increased after burn injury. The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. PMID:29740349

Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

Science.gov (United States)

Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

2008-09-01

Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study

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S Matsubara

2010-01-01

Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of the present study was to investigate the subcellular localization of G6PD in alveolar cells in the rat lung using a newly- developed enzyme-cytochemistry (copper-ferrocyanide method. Type I cells and stromal endothelia and fibroblasts showed no activities. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of type II alveolar epithelial cells. The cytochemical controls ensured specific detection of enzyme activity. This enzyme may play a role in airway defense by delivering substances for cell proliferation and antioxidant forces, thus maintaining the airway architecture.

Modulation of epithelial sodium channel in human alveolar epithelial ...

African Journals Online (AJOL)

Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng1,2, Li-Wei Pan2, Sheng-Rong Zhang3, Bin-Yu Ying2, Ben-Ji. Wang2, Guo-Liang Lin2 and Shi-Fang Ding1*. 1Department of Critical Care Medicine, Qilu Hospital of Shandong ...

Promotion of malignant phenotype after disruption of the three-dimensional structure of cultured spheroids from colorectal cancer.

Science.gov (United States)

Piulats, Jose M; Kondo, Jumpei; Endo, Hiroko; Ono, Hiromasa; Hagihara, Takeshi; Okuyama, Hiroaki; Nishizawa, Yasuko; Tomita, Yasuhiko; Ohue, Masayuki; Okita, Kouki; Oyama, Hidejiro; Bono, Hidemasa; Masuko, Takashi; Inoue, Masahiro

2018-03-23

Individual and small clusters of cancer cells may detach from the edges of a main tumor and invade vessels, which can act as the origin of metastasis; however, the mechanism for this phenomenon is not well understood. Using cancer tissue-originated spheroids, we studied whether disturbing the 3D architecture of cancer spheroids can provoke the reformation process and progression of malignancy. We developed a mechanical disruption method to achieve homogenous disruption of the spheroids while maintaining cell-cell contact. After the disruption, 9 spheroid lines from 9 patient samples reformed within a few hours, and 3 of the 9 lines exhibited accelerated spheroid growth. Marker expression, spheroid forming capacity, and tumorigenesis indicated that stemness increased after spheroid disruption. In addition, the spheroid forming capacity increased in 6 of 11 spheroid lines. The disruption signature determined by gene expression profiling supported the incidence of remodeling and predicted the prognosis of patients with colorectal cancer. Furthermore, WNT and HER3 signaling were increased in the reformed spheroids, and suppression of these signaling pathways attenuated the increased proliferation and stemness after the disruption. Overall, the disruption and subsequent reformation of cancer spheroids promoted malignancy-related phenotypes through the activation of the WNT and ERBB pathways.

FOXN1: a master regulator gene of thymic epithelial development programme

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Rosa eRomano

2013-07-01

Full Text Available T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs drive T cell differentiation, education and selection processes, while the thymocyte-dependent signals allow TECs to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1 and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1 gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the postnatal thymus. An inborn null mutation in FOXN1 leads to Nude/SCID phenotype in mouse, rat and humans. In Foxn1-/- nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality.

From green architecture to architectural green

DEFF Research Database (Denmark)

Earon, Ofri

2011-01-01

that describes the architectural exclusivity of this particular architecture genre. The adjective green expresses architectural qualities differentiating green architecture from none-green architecture. Currently, adding trees and vegetation to the building’s facade is the main architectural characteristics...... they have overshadowed the architectural potential of green architecture. The paper questions how a green space should perform, look like and function. Two examples are chosen to demonstrate thorough integrations between green and space. The examples are public buildings categorized as pavilions. One......The paper investigates the topic of green architecture from an architectural point of view and not an energy point of view. The purpose of the paper is to establish a debate about the architectural language and spatial characteristics of green architecture. In this light, green becomes an adjective...

Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

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Araki Hiromasa

2007-04-01

Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

Investigating Disruption

DEFF Research Database (Denmark)

Lundgaard, Stine Schmieg; Rosenstand, Claus Andreas Foss

This book shares knowledge collected from 2015 and onward within the Consortium for Digital Disruption anchored at Aalborg University (www.dd.aau.dk). Evidenced by this publication, the field of disruptive innovation research has gone through several stages of operationalizing the theory. In recent...... years, researchers are increasingly looking back towards the origins of the theory in attempts to cure it from its most obvious flaws. This is especially true for the use of the theory in making predictions about future disruptions. In order to continue to develop a valuable theory of disruption, we...... find it useful to first review what the theory of disruptive innovation initially was, how it has developed, and where we are now. A cross section of disruptive innovation literature has been reviewed in order to form a general foundation from which we might better understand the changing world...

Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

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Francesca M. Filbey

2015-12-01

Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

Corneal epithelial alterations resulting from use of chlorine-disinfected contact tonometer after myopic photorefractive keratectomy.

Science.gov (United States)

Maldonado, M J

1998-08-01

This study aimed to describe a previously unreported complication associated with the use of chlorine-disinfected applanation tonometer heads for intraocular pressure measurement after excimer laser photorefractive keratectomy. Two retrospective case reports. Two patients underwent, respectively, a 7-diopter and a 4-diopter myopic excimer laser correction in their first eye 2 weeks apart. Complete epithelial closure of the ablated area was observed by biomicroscopy in the first-week examination. Four weeks after photorefractive keratectomy, a complete ophthalmic examination was performed. Goldmann applanation tonometry was performed bilaterally after thoroughly rinsing and drying the tonometer biprism, which had been immersed regularly in a chlorine 5000-parts per million solution. Slit-lamp examination and corneal topographic surface regularity were measured. A few minutes after applanation tonometry, both patients reported ocular discomfort in the excimer laser-treated eyes, whereas the untreated fellow eyes were painless. Punctate corneal lesions and superficial epithelial cell clumping were present in the first patient's treated eye, predominantly in the inferior aspect of the applanated cornea. Visual inspection showed a normal tonometer tip. In the second patient's treated cornea, a focal epithelial defect was identified biomicroscopically, which corresponded to the steeper region within the ablation zone on the videokeratograph. In this case, crystal deposits were found on the tonometer tip. The epithelial alterations resolved without sequelae in both cases. Disinfecting solutions of chlorine can cause crystal deposit formation on the tonometer head. Applanation tonometry after repeated disinfection with chlorine solutions appears to have the potential for disrupting the epithelial layer of the healing cornea. Covered contact tonometry or noncontact tonometry should be evaluated as alternative methods to chemically disinfected contact tonometry for

Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

Science.gov (United States)

Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

2016-10-01

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

Architecture on Architecture

DEFF Research Database (Denmark)

Olesen, Karen

2016-01-01

that is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that can...... correlation between the study of existing architectures and the training of competences to design for present-day realities.......This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...

The world of epithelial sheets.

Science.gov (United States)

Honda, Hisao

2017-06-01

An epithelium is a layer of closely connected cells covering the body or lining a body cavity. In this review, several fundamental questions are addressed regarding the epithelium. (i) While an epithelium functions as barrier against the external environment, how is barrier function maintained during its construction? (ii) What determines the apical and basal sides of epithelial layer? (iii) Is there any relationship between the apical side of the epithelium and the apical membrane of an epithelial cell? (iv) Why are hepatocytes (liver cells) called epithelial, even though they differ completely from column-like shape of typical epithelial cells? Keeping these questions in mind, multiple shapes of epithelia were considered, extracting a few of their elemental processes, and constructing a virtual world of epithelia by combining them. Epithelial cells were also classified into several types based on the number of apical domains of each cell. In addition, an intracellular organelle was introduced within epithelial cells, the vacuolar apical compartment (VAC), which is produced within epithelial cells surrounded by external cell matrix (ECM). The VAC interacts with areas of cell-cell contact of the cell surface membrane and is converted to apical membrane. The properties of VACs enable us to answer the initial questions posed above. Finally, the genetic and molecular mechanisms of epithelial morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

Lecithin-Bound Iodine Prevents Disruption of Tight Junctions of Retinal Pigment Epithelial Cells under Hypoxic Stress

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Masahiko Sugimoto

2016-01-01

Full Text Available Aim. We investigated whether lecithin-bound iodine (LBI can protect the integrity of tight junctions of retinal pigment epithelial cells from hypoxia. Method. Cultured human retinal pigment epithelial (ARPE-19 cells were pretreated with LBI. To mimic hypoxic conditions, cells were incubated with CoCl2. We compared the integrity of the tight junctions (TJs of control to cells with either LBI alone, CoCl2 alone, or LBI + CoCl2. The levels of cytokines in the conditioned media were also determined. Results. Significant decrease in the zonula occludens-1 (ZO-1 intensity in the CoCl2 group compared to the control (5787.7 ± 4126.4 in CoCl2 group versus 29244.6 ± 2981.2 in control; average ± standard deviation. But the decrease was not significant in the LBI + CoCl2 (27189.0 ± 11231.1. The levels of monocyte chemoattractant protein-1 (MCP-1 and Chemokine (C-C Motif Ligand 11 (CCL-11 were significantly higher in the CoCl2 than in the control (340.8 ± 43.3 versus 279.7 ± 68.3 pg/mL for MCP-1, and 15.2 ± 12.9 versus 12.5 ± 6.1 pg/mL for CCL-11. With LBI pretreatment, the levels of both cytokines were decreased to 182.6 ± 23.8 (MCP-1 and 5.46 ± 1.9 pg/mL for CCL-11. Blockade of MCP-1 or CCL-11 also shows similar result representing TJ protection from hypoxic stress. Conclusions. LBI results in a protective action from hypoxia.

Hakai reduces cell-substratum adhesion and increases epithelial cell invasion

International Nuclear Information System (INIS)

Rodríguez-Rigueiro, Teresa; Valladares-Ayerbes, Manuel; Haz-Conde, Mar; Aparicio, Luis A; Figueroa, Angélica

2011-01-01

The dynamic regulation of cell-cell adhesions is crucial for developmental processes, including tissue formation, differentiation and motility. Adherens junctions are important components of the junctional complex between cells and are necessary for maintaining cell homeostasis and normal tissue architecture. E-cadherin is the prototype and best-characterized protein member of adherens junctions in mammalian epithelial cells. Regarded as a tumour suppressor, E-cadherin loss is associated with poor prognosis in carcinoma. The E3 ubiquitin-ligase Hakai was the first reported posttranslational regulator of the E-cadherin complex. Hakai specifically targetted E-cadherin for internalization and degradation and thereby lowered epithelial cell-cell contact. Hakai was also implicated in controlling proliferation, and promoted cancer-related gene expression by increasing the binding of RNA-binding protein PSF to RNAs encoding oncogenic proteins. We sought to investigate the possible implication of Hakai in cell-substratum adhesions and invasion in epithelial cells. Parental MDCK cells and MDCK cells stably overexpressing Hakai were used to analyse cell-substratum adhesion and invasion capabilities. Western blot and immunofluoresecence analyses were performed to assess the roles of Paxillin, FAK and Vinculin in cell-substratum adhesion. The role of the proteasome in controlling cell-substratum adhesion was studied using two proteasome inhibitors, lactacystin and MG132. To study the molecular mechanisms controlling Paxillin expression, MDCK cells expressing E-cadherin shRNA in a tetracycline-inducible manner was employed. Here, we present evidence that implicate Hakai in reducing cell-substratum adhesion and increasing epithelial cell invasion, two hallmark features of cancer progression and metastasis. Paxillin, an important protein component of the cell-matrix adhesion, was completely absent from focal adhesions and focal contacts in Hakai-overexpressing MDCK cells. The

Disruption of polyubiquitin gene Ubc leads to defective proliferation of hepatocytes and bipotent fetal liver epithelial progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Park, Hyejin; Yoon, Min-Sik; Ryu, Kwon-Yul, E-mail: kyryu@uos.ac.kr

2013-06-07

Highlights: •Proliferation capacity of Ubc{sup −/−} FLCs was reduced during culture in vitro. •Ubc is required for proliferation of both hepatocytes and bipotent FLEPCs. •Bipotent FLEPCs exhibit highest Ubc transcription and proliferation capacity. •Cell types responsible for Ubc{sup −/−} fetal liver developmental defect were identified. -- Abstract: We have previously demonstrated that disruption of polyubiquitin gene Ubc leads to mid-gestation embryonic lethality most likely due to a defect in fetal liver development, which can be partially rescued by ectopic expression of Ub. In a previous study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We confirmed that Ubc{sup −/−} embryonic lethality could not be attributed to impaired function of hematopoietic stem cells, which raises the question of whether or not FLECs such as hepatocytes and bile duct cells, the most abundant cell types in the liver, are affected by disruption of Ubc and contribute to embryonic lethality. To answer this, we isolated FLCs from E13.5 embryos and cultured them in vitro. We found that proliferation capacity of Ubc{sup −/−} cells was significantly reduced compared to that of control cells, especially during the early culture period, however we did not observe the increased number of apoptotic cells. Furthermore, levels of Ub conjugate, but not free Ub, decreased upon disruption of Ubc expression in FLCs, and this could not be compensated for by upregulation of other poly- or mono-ubiquitin genes. Intriguingly, the highest Ubc expression levels throughout the entire culture period were observed in bipotent FLEPCs. Hepatocytes and bipotent FLEPCs were most affected by disruption of Ubc, resulting in defective proliferation as well as reduced cell numbers in vitro. These results suggest that defective proliferation of these cell types may contribute to severe reduction of fetal liver size and potentially mid

The 18-kDa translocator protein (TSPO disrupts mammary epithelial morphogenesis and promotes breast cancer cell migration.

Directory of Open Access Journals (Sweden)

Xiaoting Wu

Full Text Available Mitochondria play important roles in cancer progression and have emerged as viable targets for cancer therapy. Increasing levels of the outer mitochondrial membrane protein, 18-kDa translocator protein (TSPO, are associated with advancing breast cancer stage. In particular, higher TSPO levels are found in estrogen receptor (ER-negative breast tumors, compared with ER-positive tumors. In this study, we sought to define the roles of TSPO in the acquisition of breast cancer malignancy. Using a three-dimensional Matrigel culture system, we determined the impact of elevated TSPO levels on mammary epithelial morphogenesis. Our studies demonstrate that stable overexpression of TSPO in mammary epithelial MCF10A acini drives proliferation and provides partial resistance to luminal apoptosis, resulting in enlarged acinar structures with partially filled lumen that resemble early stage breast lesions leading to breast cancer. In breast cancer cell lines, TSPO silencing or TSPO overexpression significantly altered the migratory activity. In addition, we found that combination treatment with the TSPO ligands (PK 11195 or Ro5-4864 and lonidamine, a clinical phase II drug targeting mitochondria, decreased viability of ER-negative breast cancer cell lines. Taken together, these data demonstrate that increases in TSPO levels at different stages of breast cancer progression results in the acquisition of distinct properties associated with malignancy. Furthermore, targeting TSPO, particularly in combination with other mitochondria-targeting agents, may prove useful for the treatment of ER-negative breast cancer.

Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

Science.gov (United States)

Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

2017-11-01

Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

MARCKS-related protein regulates cytoskeletal organization at cell-cell and cell-substrate contacts in epithelial cells.

Science.gov (United States)

Van Itallie, Christina M; Tietgens, Amber Jean; Aponte, Angel; Gucek, Marjan; Cartagena-Rivera, Alexander X; Chadwick, Richard S; Anderson, James M

2018-02-02

Treatment of epithelial cells with interferon-γ and TNF-α (IFN/TNF) results in increased paracellular permeability. To identify relevant proteins mediating barrier disruption, we performed proximity-dependent biotinylation (BioID) of occludin and found that tagging of MARCKS-related protein (MRP; also known as MARCKSL1) increased ∼20-fold following IFN/TNF administration. GFP-MRP was focused at the lateral cell membrane and its overexpression potentiated the physiological response of the tight junction barrier to cytokines. However, deletion of MRP did not abrogate the cytokine responses, suggesting that MRP is not required in the occludin-dependent IFN/TNF response. Instead, our results reveal a key role for MRP in epithelial cells in control of multiple actin-based structures, likely by regulation of integrin signaling. Changes in focal adhesion organization and basal actin stress fibers in MRP-knockout (KO) cells were reminiscent of those seen in FAK-KO cells. In addition, we found alterations in cell-cell interactions in MRP-KO cells associated with increased junctional tension, suggesting that MRP may play a role in focal adhesion-adherens junction cross talk. Together, our results are consistent with a key role for MRP in cytoskeletal organization of cell contacts in epithelial cells. © 2018. Published by The Company of Biologists Ltd.

Digital Disruption

DEFF Research Database (Denmark)

Rosenstand, Claus Andreas Foss

det digitale domæne ud over det niveau, der kendetegner den nuværende debat, så præsenteres der ny viden om digital disruption. Som noget nyt udlægges Clayton Christens teori om disruptiv innovation med et særligt fokus på små organisationers mulighed for eksponentiel vækst. Specielt udfoldes...... forholdet mellem disruption og den stadig accelererende digitale udvikling i konturerne til ny teoridannelse om digital disruption. Bogens undertitel ”faretruende og fascinerende forandringer” peger på, at der er behov for en nuanceret debat om digital disruption i modsætning til den tone, der er slået an i...... videre kalder et ”disruption-råd”. Faktisk er rådet skrevet ind i 2016 regeringsgrundlaget for VLK-regeringen. Disruption af organisationer er ikke et nyt fænomen; men hastigheden, hvormed det sker, er stadig accelererende. Årsagen er den globale mega-trend: Digitalisering. Og derfor er specielt digital...

Engineering Plant Architecture via CRISPR/Cas9-mediated Alteration of Strigolactone Biosynthesis

KAUST Repository

Butt, Haroon

2018-01-28

Precision plant genome engineering holds much promise for targeted improvement of crop traits via unprecedented single-base level control over the genetic material. Strigolactones (SLs) are a key determinant of plant architecture, known for their role in inhibiting shoot branching (tillering). Here, we used CRISPR/Cas9 in rice (Oryza sativa) for targeted disruption of CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7), which controls a key step in SL biosynthesis. The ccd7 mutants exhibited a striking increase in tillering, combined with a dwarf phenotype, which could be rescued by application of the synthetic SL analog GR24. Striga germination assays and liquid chromatography mass spectrometry analysis showed that root exudates of ccd7 mutants were also SL deficient. Taken together, our results show the power of CRISPR/Cas9 for targeted engineering of plant architecture and for elucidating the molecular underpinnings of architecture-related traits.

Engineering Plant Architecture via CRISPR/Cas9-mediated Alteration of Strigolactone Biosynthesis

KAUST Repository

Butt, Haroon; Jamil, Muhammad; Wang, Jian You; Al-Babili, Salim; Mahfouz, Magdy M.

2018-01-01

Precision plant genome engineering holds much promise for targeted improvement of crop traits via unprecedented single-base level control over the genetic material. Strigolactones (SLs) are a key determinant of plant architecture, known for their role in inhibiting shoot branching (tillering). Here, we used CRISPR/Cas9 in rice (Oryza sativa) for targeted disruption of CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7), which controls a key step in SL biosynthesis. The ccd7 mutants exhibited a striking increase in tillering, combined with a dwarf phenotype, which could be rescued by application of the synthetic SL analog GR24. Striga germination assays and liquid chromatography mass spectrometry analysis showed that root exudates of ccd7 mutants were also SL deficient. Taken together, our results show the power of CRISPR/Cas9 for targeted engineering of plant architecture and for elucidating the molecular underpinnings of architecture-related traits.

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

Science.gov (United States)

Ewald, Andrew J.; Huebner, Robert J.; Palsdottir, Hildur; Lee, Jessie K.; Perez, Melissa J.; Jorgens, Danielle M.; Tauscher, Andrew N.; Cheung, Kevin J.; Werb, Zena; Auer, Manfred

2012-01-01

Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in three-dimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix. The basolateral marker scribble and the apical marker atypical protein kinase C zeta localized to all interior cell membranes, whereas PAR3 displayed a cytoplasmic localization, suggesting that the apico-basal polarity was incomplete. Despite membrane localization of E-cadherin and β-catenin, we did not observe a defined zonula adherens connecting interior cells. Instead, interior cells were connected through desmosomes and exhibited complex interdigitating membrane protrusions. Single-cell labeling revealed that individual cells were both protrusive and migratory within the epithelial multilayer. Inhibition of Rho kinase (ROCK) further reduced intercellular adhesion on apical and lateral surfaces but did not disrupt basal tissue organization. Following morphogenesis, segregated membrane domains were re-established and junctional complexes re-formed. We observed similar epithelial organization during mammary morphogenesis in organotypic culture and in vivo. We conclude that mammary epithelial morphogenesis involves a reversible, spatially limited, reduction in polarity and intercellular junctions and active individualistic cell migration. Our data suggest that reductions in polarity and adhesion during breast cancer progression might reflect partial recapitulation of a normal developmental program. PMID:22344263

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Directory of Open Access Journals (Sweden)

Yanan Gao

2017-12-01

Full Text Available Aflatoxin M1 (AFM1 and ochratoxin A (OTA are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 μM and OTA (0.2 and 20 μM individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC-dextrans (4 and 40 kDa and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1, and p44/42 mitogen-activated protein kinase (MAPK partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05 than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered.

The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold.

Science.gov (United States)

O'Leary, Cian; Cavanagh, Brenton; Unger, Ronald E; Kirkpatrick, C James; O'Dea, Shirley; O'Brien, Fergal J; Cryan, Sally-Ann

2016-04-01

Today, chronic respiratory disease is one of the leading causes of mortality globally. Epithelial dysfunction can play a central role in its pathophysiology. The development of physiologically-representative in vitro model systems using tissue-engineered constructs might improve our understanding of epithelial tissue and disease. This study sought to engineer a bilayered collagen-hyaluronate (CHyA-B) scaffold for the development of a physiologically-representative 3D in vitro tracheobronchial epithelial co-culture model. CHyA-B scaffolds were fabricated by integrating a thin film top-layer into a porous sub-layer with lyophilisation. The film layer firmly connected to the sub-layer with delamination occurring at stresses of 12-15 kPa. Crosslinked scaffolds had a compressive modulus of 1.9 kPa and mean pore diameters of 70 μm and 80 μm, depending on the freezing temperature. Histological analysis showed that the Calu-3 bronchial epithelial cell line attached and grew on CHyA-B with adoption of an epithelial monolayer on the film layer. Immunofluorescence and qRT-PCR studies demonstrated that the CHyA-B scaffolds facilitated Calu-3 cell differentiation, with enhanced mucin expression, increased ciliation and the formation of intercellular tight junctions. Co-culture of Calu-3 cells with Wi38 lung fibroblasts was achieved on the scaffold to create a submucosal tissue analogue of the upper respiratory tract, validating CHyA-B as a platform to support co-culture and cellular organisation reminiscent of in vivo tissue architecture. In summary, this study has demonstrated that CHyA-B is a promising tool for the development of novel 3D tracheobronchial co-culture in vitro models with the potential to unravel new pathways in drug discovery and drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disruption?

DEFF Research Database (Denmark)

2016-01-01

This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray......This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray...

Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

Science.gov (United States)

Yates, Laura L.; Schnatwinkel, Carsten; Hazelwood, Lee; Chessum, Lauren; Paudyal, Anju; Hilton, Helen; Romero, M. Rosario; Wilde, Jonathan; Bogani, Debora; Sanderson, Jeremy; Formstone, Caroline; Murdoch, Jennifer N.; Niswander, Lee A.; Greenfield, Andy; Dean, Charlotte H.

2013-01-01

During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in ScribCrc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen

Epstein–Barr virus (EBV-associated epithelial and non-epithelial lesions of the oral cavity

Directory of Open Access Journals (Sweden)

Kentaro Kikuchi

2017-08-01

Full Text Available Epstein–Barr virus (EBV is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC, salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related and DLBCLs of the oral cavity.

Pseudomonas aeruginosa Transmigrates at Epithelial Cell-Cell Junctions, Exploiting Sites of Cell Division and Senescent Cell Extrusion.

Directory of Open Access Journals (Sweden)

Guillaume Golovkine

2016-01-01

Full Text Available To achieve systemic infection, bacterial pathogens must overcome the critical and challenging step of transmigration across epithelial barriers. This is particularly true for opportunistic pathogens such as Pseudomonas aeruginosa, an agent which causes nosocomial infections. Despite extensive study, details on the mechanisms used by this bacterium to transmigrate across epithelial tissues, as well as the entry sites it uses, remain speculative. Here, using real-time microscopy and a model epithelial barrier, we show that P. aeruginosa employs a paracellular transmigration route, taking advantage of altered cell-cell junctions at sites of cell division or when senescent cells are expelled from the cell layer. Once a bacterium transmigrates, it is followed by a cohort of bacteria using the same entry point. The basal compartment is then invaded radially from the initial penetration site. Effective transmigration and propagation require type 4 pili, the type 3 secretion system (T3SS and a flagellum, although flagellum-deficient bacteria can occasionally invade the basal compartment from wounded areas. In the basal compartment, the bacteria inject the T3SS toxins into host cells, disrupting the cytoskeleton and focal contacts to allow their progression under the cells. Thus, P. aeruginosa exploits intrinsic host cell processes to breach the epithelium and invade the subcellular compartment.

Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties

International Nuclear Information System (INIS)

Miroshnikova, Y A; Sarang-Sieminski, A L; Jorgens, D M; Auer, M; Spirio, L; Weaver, V M

2011-01-01

The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide (SAP) gels that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of viscoelasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal and tumor-like phenotypes and gene expression patterns in nonmalignant mammary epithelial cells. Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context

CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

International Nuclear Information System (INIS)

Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

2009-01-01

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFβ1-mediated lytic phase. EBV lytic reactivation by TGFβ1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM 1 81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

2009-07-01

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

Legionella dumoffii Tex-KL Mutated in an Operon Homologous to traC-traD is Defective in Epithelial Cell Invasion.

Science.gov (United States)

Qin, Tian; Ken-Ichiro, Iida; Ren, Hong Yu; Zhou, Hai Jian; Yoshida, Shin-Ichi

2016-06-01

To understand the mechanism of invasion by Legionella dumoffii. The L. dumoffii strain Tex-KL was mutated using the Tn903 derivative, Tn903dIIlacZ. After screening 799 transposon insertion mutants, we isolated one defective mutant. We then constructed the gene-disrupted mutant, KL16, and studied its invasion of and intracellular growth in HeLa and A549 cells, and in A/J mice survival experiments. The structure of traC-traD operon was analyzed by RT-PCR. The transposon insertion was in a gene homologous to Salmonella typhi traC, which is required for the assembly of F pilin into the mature F pilus structure and for conjugal DNA transmission. Results from RT-PCR suggested that the traC-traD region formed an operon. We found that when the traC gene was disrupted, invasion and intracellular growth of L. dumoffii Tex-KL were impaired in human epithelial cells. When mice were infected by intranasal inoculation with a traC deficient mutant, their survival significantly increased when compared to mice infected with the wild-type strain.. Our results indicated that the traC-traD operon is required for the invasion and intracellular growth abilities of L. dumoffii Tex-KL in epithelial cells. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells.

Science.gov (United States)

Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M; Yue, Junming

2017-01-01

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells.

Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures

DEFF Research Database (Denmark)

Claesson, Mogens Helweg; Ropke, C

1990-01-01

We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is conclu......We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level...

Epithelial-mesenchymal transition in breast epithelial cells treated with cadmium and the role of Snail.

Science.gov (United States)

Wei, Zhengxi; Shan, Zhongguo; Shaikh, Zahir A

2018-04-01

Epidemiological and experimental studies have implicated cadmium (Cd) with breast cancer. In breast epithelial MCF10A and MDA-MB-231 cells, Cd has been shown to promote cell growth. The present study examined whether Cd also promotes epithelial-mesenchymal transition (EMT), a hallmark of cancer progression. Human breast epithelial cells consisting of non-cancerous MCF10A, non-metastatic HCC 1937 and HCC 38, and metastatic MDA-MB-231 were treated with 1 or 3 μM Cd for 4 weeks. The MCF10A epithelial cells switched to a more mesenchymal-like morphology, which was accompanied by a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal markers N-cadherin and vimentin. In both non-metastatic HCC 1937 and HCC 38 cells, treatment with Cd decreased the epithelial marker claudin-1. In addition, E-cadherin also decreased in the HCC 1937 cells. Even the mesenchymal-like MDA-MB-231 cells exhibited an increase in the mesenchymal marker vimentin. These changes indicated that prolonged treatment with Cd resulted in EMT in both normal and cancer-derived breast epithelial cells. Furthermore, both the MCF10A and MDA-MB-231 cells labeled with Zcad, a dual sensor for tracking EMT, demonstrated a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker ZEB-1. Treatment of cells with Cd significantly increased the level of Snail, a transcription factor involved in the regulation of EMT. However, the Cd-induced Snail expression was completely abolished by actinomycin D. Luciferase reporter assay indicated that the expression of Snail was regulated by Cd at the promotor level. Snail was essential for Cd-induced promotion of EMT in the MDA-MB-231 cells, as knockdown of Snail expression blocked Cd-induced cell migration. Together, these results indicate that Cd promotes EMT in breast epithelial cells and does so by modulating the transcription of Snail. Copyright © 2018 Elsevier Inc. All rights reserved.

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells.

Science.gov (United States)

Fang, Mingzhu; Kang, Hwan-Goo; Park, Youngil; Estrella, Brian; Zarbl, Helmut

2017-09-28

The circadian rhythm is a fundamental physiological process present in all organisms that regulates biological processes ranging from gene expression to sleep behavior. In vertebrates, circadian rhythm is controlled by a molecular oscillator that functions in both the suprachiasmatic nucleus (SCN; central pacemaker) and individual cells comprising most peripheral tissues. More importantly, disruption of circadian rhythm by exposure to light-at-night, environmental stressors and/or toxicants is associated with increased risk of chronic diseases and aging. The ability to identify agents that can disrupt central and/or peripheral biological clocks, and agents that can prevent or mitigate the effects of circadian disruption, has significant implications for prevention of chronic diseases. Although rodent models can be used to identify exposures and agents that induce or prevent/mitigate circadian disruption, these experiments require large numbers of animals. In vivo studies also require significant resources and infrastructure, and require researchers to work all night. Thus, there is an urgent need for a cell-type appropriate in vitro system to screen for environmental circadian disruptors and enhancers in cell types from different organs and disease states. We constructed a vector that drives transcription of the destabilized luciferase in eukaryotic cells under the control of the human PERIOD 2 gene promoter. This circadian reporter construct was stably transfected into human mammary epithelial cells, and circadian responsive reporter cells were selected to develop the in vitro bioluminescence assay. Here, we present a detailed protocol to establish and validate the assay. We further provide details for proof of concept experiments demonstrating the ability of our in vitro assay to recapitulate the in vivo effects of various chemicals on the cellular biological clock. The results indicate that the assay can be adapted to a variety of cell types to screen for both

Disruptions in JET

International Nuclear Information System (INIS)

Wesson, J.A.; Gill, R.D.; Hugon, M.

1989-01-01

In JET, both high density and low-q operation are limited by disruptions. The density limit disruptions are caused initially by impurity radiation. This causes a contraction of the plasma temperature profile and leads to an MHD unstable configuration. There is evidence of magnetic island formation resulting in minor disruptions. After several minor disruptions, a major disruption with a rapid energy quench occurs. This event takes place in two stages. In the first stage there is a loss of energy from the central region. In the second stage there is a more rapid drop to a very low temperature, apparently due to a dramatic increase in impurity radiation. The final current decay takes place in the resulting cold plasma. During the growth of the MHD instability the initially rotating mode is brought to rest. This mode locking is believed to be due to an electromagnetic interaction with the vacuum vessel and external magnetic field asymmetries. The low-q disruptions are remarkable for the precision with which they occur at q ψ = 2. These disruptions do not have extended precursors or minor disruptions. The instability grows and locks rapidly. The energy quench and current decay are generally similar to those of the density limit. (author). 43 refs, 35 figs, 3 tabs

Tissue architecture: the ultimate regulator of breast epithelial function

Energy Technology Data Exchange (ETDEWEB)

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

2003-10-20

discuss the following: first, how our laboratory came to develop a model of the mammary gland acinus; second, what this model has told us about mechanisms that govern tissue specificity and malignancy; and third, possible directions for future studies. We summarize the evidence for the central role of ECM signaling in the maintenance of mammary function in culture and (more briefly) its role in tumorigenesis. This is followed by a discussion of the role that tissue architecture and tissue polarity (as opposed to cell polarity) may play in these processes. In an elegantly written and reasoned essay, Kirschner et al. coined the new science of developmental biology 'molecular vitalism'. They framed new concepts for self-organization as well as schemes for information flow in biological organization. Rao et al. reviewed and elaborated on differential-equation-based models of biochemical reaction networks and intracellular noise, with emphasis on bacteria and phage. Similarly, Hartwell et al. discussed the synergy between experiment and theory in elucidating 'modules' - collections of interacting molecules - and in unraveling how these modules collaborate to perform cellular functions such as signal transduction. We believe that many of these ideas will also be applicable to the maintenance of tissue specificity. As much as we agree with Kirschner et al. regarding the limitations of the machine analogy to biological systems, we conclude with thoughts on how we may proceed to model the complex tissue networks that govern breast tissue architecture. We suggest that our understanding of the structure and function of breast tissue would benefit from examining recent techniques for modeling large complex networks such as the World Wide Web and the Internet backbone among others.

Digital disruption ?syndromes.

Science.gov (United States)

Sullivan, Clair; Staib, Andrew

2017-05-18

The digital transformation of hospitals in Australia is occurring rapidly in order to facilitate innovation and improve efficiency. Rapid transformation can cause temporary disruption of hospital workflows and staff as processes are adapted to the new digital workflows. The aim of this paper is to outline various types of digital disruption and some strategies for effective management. A large tertiary university hospital recently underwent a rapid, successful roll-out of an integrated electronic medical record (EMR). We observed this transformation and propose several digital disruption "syndromes" to assist with understanding and management during digital transformation: digital deceleration, digital transparency, digital hypervigilance, data discordance, digital churn and post-digital 'depression'. These 'syndromes' are defined and discussed in detail. Successful management of this temporary digital disruption is important to ensure a successful transition to a digital platform. What is known about this topic? Digital disruption is defined as the changes facilitated by digital technologies that occur at a pace and magnitude that disrupt established ways of value creation, social interactions, doing business and more generally our thinking. Increasing numbers of Australian hospitals are implementing digital solutions to replace traditional paper-based systems for patient care in order to create opportunities for improved care and efficiencies. Such large scale change has the potential to create transient disruption to workflows and staff. Managing this temporary disruption effectively is an important factor in the successful implementation of an EMR. What does this paper add? A large tertiary university hospital recently underwent a successful rapid roll-out of an integrated electronic medical record (EMR) to become Australia's largest digital hospital over a 3-week period. We observed and assisted with the management of several cultural, behavioural and

Patterning bacterial communities on epithelial cells.

Directory of Open Access Journals (Sweden)

Mohammed Dwidar

Full Text Available Micropatterning of bacteria using aqueous two phase system (ATPS enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibriobacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactions.

Equine tracheal epithelial membrane strips - An alternate method for examining epithelial cell arachidonic acid metabolism

International Nuclear Information System (INIS)

Gray, P.R.; Derksen, F.J.; Robinson, N.E.; Peter-Golden, M.L.

1990-01-01

Arachidonic acid metabolism by tracheal epithelium can be studied using enzymatically dispersed cell suspensions or cell cultures. Both techniques require considerable tissue disruption and manipulation and may not accurately represent in vivo activity. The authors have developed an alternate method for obtaining strips of equine tracheal epithelium without enzymatic digestion. In the horse, a prominent elastic lamina supports the tracheal epithelium. By physical splitting this lamina, they obtained strips (≤12 x 1.5 cm) of pseudostratified columnar epithelium attached to a layer of elastic tissue 30-100 μm thick. Epithelial strips (1.2 x 0.5 cm) were attached to plexiglass rods and incubated with [ 3 H]arachidonic acid in M199 medium (0.5 μCi/ml) for 24 hours at 37C. The strips incorporated 36±4% (mean ± SEM) of the total radioactivity and released 8.0±1.2% of incorporated radioactivity when stimulated by 5.0 μM calcium ionophore A23187. The extracted supernatant was processed using HPLC, resulting in peaks of radioactivity that co-eluted with authentic PGE 2 , PGF 2 α, and 12-HETE standards. The greatest activity corresponded to the PGE 2 and PGF 2 α standards, which is a similar pattern to that reported for cultured human tracheal epithelium

Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix.

Science.gov (United States)

Piotrowski-Daspit, Alexandra S; Nelson, Celeste M

2016-07-10

The architecture of branched organs such as the lungs, kidneys, and mammary glands arises through the developmental process of branching morphogenesis, which is regulated by a variety of soluble and physical signals in the microenvironment. Described here is a method created to study the process of branching morphogenesis by forming engineered three-dimensional (3D) epithelial tissues of defined shape and size that are completely embedded within an extracellular matrix (ECM). This method enables the formation of arrays of identical tissues and enables the control of a variety of environmental factors, including tissue geometry, spacing, and ECM composition. This method can also be combined with widely used techniques such as traction force microscopy (TFM) to gain more information about the interactions between cells and their surrounding ECM. The protocol can be used to investigate a variety of cell and tissue processes beyond branching morphogenesis, including cancer invasion.

Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion.

Science.gov (United States)

Scott, Kevin G-E; Meddings, Jonathon B; Kirk, David R; Lees-Miller, Susan P; Buret, André G

2002-10-01

Giardiasis causes malabsorptive diarrhea, and symptoms can be present in the absence of any significant morphologic injury to the intestinal mucosa. The effects of giardiasis on epithelial permeability in vivo remain unknown, and the role of T cells and myosin light chain kinase (MLCK) in altered intestinal barrier function is unclear. This study was conducted to determine whether Giardia spp. alters intestinal permeability in vivo, to assess whether these abnormalities are dependent on T cells, and to assess the role of MLCK in altered epithelial barrier function. Immunocompetent and isogenic athymic mice were inoculated with axenic Giardia muris trophozoites or sterile vehicle (control), then assessed for trophozoite colonization and gastrointestinal permeability. Mechanistic studies using nontransformed human duodenal epithelial monolayers (SCBN) determined the effects of Giardia on myosin light chain (MLC) phosphorylation, transepithelial fluorescein isothiocyanate-dextran fluxes, cytoskeletal F-actin, tight junctional zonula occludens-1 (ZO-1), and MLCK. Giardia infection caused a significant increase in small intestinal, but not gastric or colonic, permeability that correlated with trophozoite colonization in both immunocompetent and athymic mice. In vitro, Giardia increased permeability and phosphorylation of MLC and reorganized F-actin and ZO-1. These alterations were abolished with an MLCK inhibitor. Disruption of small intestinal barrier function is T cell independent, disappears on parasite clearance, and correlates with reorganization of cytoskeletal F-actin and tight junctional ZO-1 in an MLCK-dependent fashion.

Effects of sleep disruption and high fat intake on glucose metabolism in mice.

Science.gov (United States)

Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

2016-06-01

Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

Architectural slicing

DEFF Research Database (Denmark)

Christensen, Henrik Bærbak; Hansen, Klaus Marius

2013-01-01

Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...... of architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given...... a system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java....

Disruptions in Tokamaks

International Nuclear Information System (INIS)

Bondeson, A.

1987-01-01

This paper discusses major and minor disruptions in Tokamaks. A number of models and numerical simulations of disruptions based on resistive MHD are reviewed. A discussion is given of how disruptive current profiles are correlated with the experimentally known operational limits in density and current. It is argued that the q a =2 limit is connected with stabilization of the m=2/n=1 tearing mode for a approx.< 2.7 by resistive walls and mode rotation. Experimental and theoretical observations indicate that major disruptions usually occur in at least two phases, first a 'predisruption', or loss of confinement in the region 1 < q < 2, leaving the q approx.= 1 region almost unaffected, followed by a final disruption of the central part, interpreted here as a toroidal n = 1 external kink mode. (author)

Epithelial rotation is preceded by planar symmetry breaking of actomyosin and protects epithelial tissue from cell deformations.

Science.gov (United States)

Viktorinová, Ivana; Henry, Ian; Tomancak, Pavel

2017-11-01

Symmetry breaking is involved in many developmental processes that form bodies and organs. One of them is the epithelial rotation of developing tubular and acinar organs. However, how epithelial cells move, how they break symmetry to define their common direction, and what function rotational epithelial motions have remains elusive. Here, we identify a dynamic actomyosin network that breaks symmetry at the basal surface of the Drosophila follicle epithelium of acinar-like primitive organs, called egg chambers, and may represent a candidate force-generation mechanism that underlies the unidirectional motion of this epithelial tissue. We provide evidence that the atypical cadherin Fat2, a key planar cell polarity regulator in Drosophila oogenesis, directs and orchestrates transmission of the intracellular actomyosin asymmetry cue onto a tissue plane in order to break planar actomyosin symmetry, facilitate epithelial rotation in the opposite direction, and direct the elongation of follicle cells. In contrast, loss of this rotational motion results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and causes cell deformations in the epithelial tissue of Drosophila eggs. Our work demonstrates that atypical cadherins play an important role in the control of symmetry breaking of cellular mechanics in order to facilitate tissue motion and model epithelial tissue. We propose that their functions may be evolutionarily conserved in tubular/acinar vertebrate organs.

Architectural protein subclasses shape 3-D organization of genomes during lineage commitment

Science.gov (United States)

Phillips-Cremins, Jennifer E.; Sauria, Michael E. G.; Sanyal, Amartya; Gerasimova, Tatiana I.; Lajoie, Bryan R.; Bell, Joshua S. K.; Ong, Chin-Tong; Hookway, Tracy A.; Guo, Changying; Sun, Yuhua; Bland, Michael J.; Wagstaff, William; Dalton, Stephen; McDevitt, Todd C.; Sen, Ranjan; Dekker, Job; Taylor, James; Corces, Victor G.

2013-01-01

Summary Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in looping interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge shortrange enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales. PMID:23706625

SUSTAINABLE ARCHITECTURE : WHAT ARCHITECTURE STUDENTS THINK

OpenAIRE

SATWIKO, PRASASTO

2013-01-01

Sustainable architecture has become a hot issue lately as the impacts of climate change become more intense. Architecture educations have responded by integrating knowledge of sustainable design in their curriculum. However, in the real life, new buildings keep coming with designs that completely ignore sustainable principles. This paper discusses the results of two national competitions on sustainable architecture targeted for architecture students (conducted in 2012 and 2013). The results a...

The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells.

Science.gov (United States)

Yamada, Mitsuhiro; Kubo, Hiroshi; Ota, Chiharu; Takahashi, Toru; Tando, Yukiko; Suzuki, Takaya; Fujino, Naoya; Makiguchi, Tomonori; Takagi, Kiyoshi; Suzuki, Takashi; Ichinose, Masakazu

2013-09-24

The excess and persistent accumulation of fibroblasts due to aberrant tissue repair results in fibrotic diseases such as idiopathic pulmonary fibrosis. Recent reports have revealed significant changes in microRNAs during idiopathic pulmonary fibrosis and evidence in support of a role for microRNAs in myofibroblast differentiation and the epithelial-mesenchymal transition in the context of fibrosis. It has been reported that microRNA-21 is up-regulated in myofibroblasts during fibrosis and promotes transforming growth factor-beta signaling by inhibiting Smad7. However, expression changes in microRNA-21 and the role of microRNA-21 in epithelial-mesenchymal transition during lung fibrosis have not yet been defined. Lungs from saline- or bleomycin-treated C57BL/6 J mice and lung specimens from patients with idiopathic pulmonary fibrosis were analyzed. Enzymatic digestions were performed to isolate single lung cells. Lung epithelial cells were isolated by flow cytometric cell sorting. The expression of microRNA-21 was analyzed using both quantitative PCR and in situ hybridization. To induce epithelial-mesenchymal transition in culture, isolated mouse lung alveolar type II cells were cultured on fibronectin-coated chamber slides in the presence of transforming growth factor-β, thus generating conditions that enhance epithelial-mesenchymal transition. To investigate the role of microRNA-21 in epithelial-mesenchymal transition, we transfected cells with a microRNA-21 inhibitor. Total RNA was isolated from the freshly isolated and cultured cells. MicroRNA-21, as well as mRNAs of genes that are markers of alveolar epithelial or mesenchymal cell differentiation, were quantified using quantitative PCR. The lung epithelial cells isolated from the bleomycin-induced lung fibrosis model system had decreased expression of epithelial marker genes, whereas the expression of mesenchymal marker genes was increased. MicroRNA-21 was significantly upregulated in isolated lung epithelial

Architecture

OpenAIRE

Clear, Nic

2014-01-01

When discussing science fiction’s relationship with architecture, the usual practice is to look at the architecture “in” science fiction—in particular, the architecture in SF films (see Kuhn 75-143) since the spaces of literary SF present obvious difficulties as they have to be imagined. In this essay, that relationship will be reversed: I will instead discuss science fiction “in” architecture, mapping out a number of architectural movements and projects that can be viewed explicitly as scien...

Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation.

Science.gov (United States)

An, Gary

2008-05-27

One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM) can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure. ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems. A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents

Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum.

Science.gov (United States)

Page, Robert B; Monaghan, James R; Samuels, Amy K; Smith, Jeramiah J; Beachy, Christopher K; Voss, S Randal

2007-02-01

Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a >2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma.

Endothelial Cell Migration and Vascular Endothelial Growth Factor Expression Are the Result of Loss of Breast Tissue Polarity

Energy Technology Data Exchange (ETDEWEB)

Chen, Amy; Cuevas, Ileana; Kenny, Paraic A; Miyake, Hiroshi; Mace, Kimberley; Ghajar, Cyrus; Boudreau, Aaron; Bissell, Mina; Boudreau, Nancy

2009-05-26

Recruiting a new blood supply is a rate-limiting step in tumor progression. In a three-dimensional model of breast carcinogenesis, disorganized, proliferative transformed breast epithelial cells express significantly higher expression of angiogenic genes compared with their polarized, growth-arrested nonmalignant counterparts. Elevated vascular endothelial growth factor (VEGF) secretion by malignant cells enhanced recruitment of endothelial cells (EC) in heterotypic cocultures. Significantly, phenotypic reversion of malignant cells via reexpression of HoxD10, which is lost in malignant progression, significantly attenuated VEGF expression in a hypoxia-inducible factor 1{alpha}-independent fashion and reduced EC migration. This was due primarily to restoring polarity: forced proliferation of polarized, nonmalignant cells did not induce VEGF expression and EC recruitment, whereas disrupting the architecture of growth-arrested, reverted cells did. These data show that disrupting cytostructure activates the angiogenic switch even in the absence of proliferation and/or hypoxia and restoring organization of malignant clusters reduces VEGF expression and EC activation to levels found in quiescent nonmalignant epithelium. These data confirm the importance of tissue architecture and polarity in malignant progression.

Modeling Architectural Patterns Using Architectural Primitives

NARCIS (Netherlands)

Zdun, Uwe; Avgeriou, Paris

2005-01-01

Architectural patterns are a key point in architectural documentation. Regrettably, there is poor support for modeling architectural patterns, because the pattern elements are not directly matched by elements in modeling languages, and, at the same time, patterns support an inherent variability that

Can Riboflavin Penetrate Stroma Without Disrupting Integrity of Corneal Epithelium in Rabbits? Iontophoresis and Ultraperformance Liquid Chromatography With Electrospray Ionization Tandem Mass Spectrometry.

Science.gov (United States)

Novruzlu, Şahin; Türkcü, Ümmühani Özel; Kvrak, İbrahim; Kvrak, Şeyda; Yüksel, Erdem; Deniz, Nuriye Gökçen; Bilgihan, Ayşe; Bilgihan, Kamil

2015-08-01

To examine riboflavin concentrations in corneas and aqueous humor from rabbits with standard and transepithelial methods and iontophoresis without disrupting the integrity of the corneal epithelium before corneal collagen cross-linking. Twenty-four eyes of 12 adult New Zealand rabbits were used. They were assigned to 4 groups, each including 6 eyes. Group 1 was exposed to the standard method and given riboflavin 0.1% after epithelial debridement. Group 2 was exposed to the transepithelial method and given benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA), trometamol (TRIS), hydroxypropylmethylcellulose (HPMC), and riboflavin 0.2% 3 times at 1.5-minute intervals followed by riboflavin 0.2%. Group 3 was given riboflavin 0.1% by using 1-mA electric current for 10 minutes with the help of iontophoresis without using substances disrupting the integrity of the corneal epithelium. Group 4 received the same treatment as did group 3, except that it was given riboflavin 0.2%. Following these treatments, riboflavin concentrations in aqueous humor and corneas were measured with ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). Riboflavin concentrations in the cornea and aqueous humor were higher in group 1 (42.4 ± 5.4 μg/g) than in the other groups. They were significantly higher in group 4 (34.2 ± 6.6 μg/g) than in group 2 (24.4 ± 1.2 μg/g) (P = 0.009) and group 3 (23.6 ± 6.1 μg/g) (P = 0.026). There was not a significant difference in corneal riboflavin concentrations between group 2 and group 3 (P = 0.937). Intrastromal and aqueous riboflavin concentrations after administration of riboflavin 0.2% through iontophoresis without disrupting the integrity of the corneal epithelium were lower than those after the standard method, but higher than those after the transepithelial method. In this study, in which riboflavin concentrations were measured with a very sensitive method

Influence of adhesion and bacteriocin production by Lactobacillus salivarius on the intestinal epithelial cell transcriptional response.

Science.gov (United States)

O'Callaghan, John; Buttó, Ludovica F; MacSharry, John; Nally, Kenneth; O'Toole, Paul W

2012-08-01

Lactobacillus salivarius strain UCC118 is a human intestinal isolate that has been extensively studied for its potential probiotic effects in human and animal models. The objective of this study was to determine the effect of L. salivarius UCC118 on gene expression responses in the Caco-2 cell line to improve understanding of how the strain might modulate intestinal epithelial cell phenotypes. Exposure of Caco-2 cells to UCC118 led to the induction of several human genes (TNFAIP3, NFKBIA, and BIRC3) that are negative regulators of inflammatory signaling pathways. Induction of chemokines (CCL20, CXCL-1, and CXCL-2) with antimicrobial functions was also observed. Disruption of the UCC118 sortase gene srtA causes reduced bacterial adhesion to epithelial cells. Transcription of three mucin genes was reduced significantly when Caco-2 cells were stimulated with the ΔsrtA derivative of UCC118 compared to cells stimulated with the wild type, but there was no significant change in the transcription levels of the anti-inflammatory genes. UCC118 genes that were significantly upregulated upon exposure to Caco-2 cells were identified by bacterial genome microarray and consisted primarily of two groups of genes connected with purine metabolism and the operon for synthesis of the Abp118 bacteriocin. Following incubation with Caco-2 cells, the bacteriocin synthesis genes were transcribed at higher levels in the wild type than in the ΔsrtA derivative. These data indicate that L. salivarius UCC118 influences epithelial cells both through modulation of the inflammatory response and by modulation of intestinal cell mucin production. Sortase-anchored cell surface proteins of L. salivarius UCC118 have a central role in promoting the interaction between the bacterium and epithelial cells.

The use of disruptive information technologies for competitive advantage in the banking sector of South Africa.

OpenAIRE

Windell, Anneke C.; Kroeze, Jan H.

2009-01-01

The main focus of this paper is to determine the impact of disruptive technology in the ICT environment and how new technologies can be managed in a secured architecture framework of organisations in the banking sector. Change management has a specific role to play as any introduction of new technology in the workplace is dependent on a successful change management process. Furthermore, the purpose of the research is to provide insight and principles when companies need to make informat...

Induction of cell scattering by expression of beta1 integrins in beta1-deficient epithelial cells requires activation of members of the rho family of GTPases and downregulation of cadherin and catenin function

DEFF Research Database (Denmark)

Gimond, C; van Der Flier, A; van Delft, S

1999-01-01

different beta1-null cell lines, epithelial GE11 and fibroblast-like GD25 cells. Expression of beta1A or the cytoplasmic splice variant beta1D, induced the disruption of intercellular adherens junctions and cell scattering in both GE11 and GD25 cells. In GE11 cells, the morphological change correlated...... for a complete morphological transition towards the spindle-shaped fibroblast-like phenotype. The expression of an interleukin-2 receptor (IL2R)-beta1A chimera and its incorporation into focal adhesions also induced the disruption of cadherin-based adhesions and the reorganization of ECM-cell contacts...

Wound Disruption Following Colorectal Operations.

Science.gov (United States)

Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

2015-12-01

Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells.

Science.gov (United States)

Hulshof, Frits; Schophuizen, Carolien; Mihajlovic, Milos; van Blitterswijk, Clemens; Masereeuw, Rosalinde; de Boer, Jan; Stamatialis, Dimitrios

2018-02-01

Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell-based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone-polyvinyl pyrrolidone (PES-PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L-dopamine coating of the PES-PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES-PVP topographies with large features disrupted the monolayer. In contrast, the PES-PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES-PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

Energy Technology Data Exchange (ETDEWEB)

Hansen, R K; Bissell, M J

2000-06-01

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

Sleep architecture in school-aged children with primary snoring.

Science.gov (United States)

Zhu, Yin; Au, Chun-Ting; Lam, Hugh S; Chan, Ching-Ching K; Ho, Crover; Wing, Yun-Kwok; Li, Albert M

2014-03-01

We aimed to examine if sleep architecture was altered in school-aged children with primary snoring (PS). Children ages 6 to 13 years from 13 primary schools were randomly recruited. A validated obstructive sleep apnea (OSA) screening questionnaire was completed by their parents. Children at high risk for OSA and a randomly chosen low-risk group were invited to undergo overnight polysomnography (PSG) and clinical examination. Participants were classified into healthy controls, PS, mild OSA, and moderate to severe OSA (MS OSA) groups for comparison. A total of 619 participants underwent PSG (mean age, 10.0 ± 1.8 years; 396 (64.0%) boys; 524 (84.7%) prepubertal). For the cohort as a whole, there were no significant differences in measures of sleep architecture between PS and nonsnoring healthy controls. In the multiple regression model, percentage of nonrapid eye movement (NREM) stage 1 (N1) sleep had a significantly positive association, whereas percentage of slow-wave sleep (SWS) had a significantly negative association with sleep-disordered breathing (SDB) severity after controlling for age, gender, body mass index (BMI) z score, and pubertal status. In prepubertal children with PS, no significant disruption of sleep architecture was found. However, pubertal adolescent PS participants had significantly higher adjusted percentage of N1 sleep and wake after sleep onset (WASO) compared to healthy controls. PS did not exert significant adverse influences on normal sleep architecture in prepubertal school-aged children. Nevertheless, pubertal adolescents with PS had increased N1 sleep and WASO. Copyright © 2013 Elsevier B.V. All rights reserved.

Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

Science.gov (United States)

Roxas, Jennifer Lising; Viswanathan, V K

2018-03-25

The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

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.

Endocrine Disrupting Chemicals (EDCs)

Science.gov (United States)

... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

Disruptions in the TFTR tokamak

International Nuclear Information System (INIS)

Janos, A.; Fredrickson, E.D.; McGuire, K.; Batha, S.H.; Bell, M.G.; Bitter, M.; Budny, R.; Bush, C.E.; Efthimion, P.C.; Hawryluk, R.J.; Hill, K.W.; Hosea, J.; Jobes, F.C.; Johnson, D.W.; Levinton, F.; Mansfield, D.; Meade, D.; Medley, S.S.; Monticello, D.; Mueller, D.; Nagayama, Y.; Owens, D.K.; Park, H.; Park, W.; Post, D.E.; Schivell, J.; Strachan, J.D.; Taylor, G.; Ulrickson, M.; Goeler, S. von; Wilfrid, E.; Wong, K.L.; Yamada, M.; Young, K.M.; Zarnstorff, M.C.; Zweben, S.J.; Drake, J.F.; Kleva, R.G.; Fleischmann, H.H.

1993-03-01

For a successful reactor, it will be useful to predict the occurrence of disruptions and to understand disruption effects including how a plasma disrupts onto the wall and how reproducibly it does so. Studies of disruptions on TFTR at both high-β pol and high-density have shown that, in both types, a fast growing m/n=1/1 mode plays an important role. In highdensity disruptions, a newly observed fast m/n = 1/1 mode occurs early in the thermal decay phase. For the first time in TFTR q-profile measurements just prior to disruptions have been made. Experimental studies of heat deposition patterns on the first wall of TFTR due to disruptions have provided information on MHD phenomena prior to or during the disruption, how the energy is released to the wall, and the reproducibility of the heat loads from disruptions. This information is important in the design of future devices such as ITER. Several new processes of runaway electron generation are theoretically suggested and their application to TFTR and ITER is considered, together with a preliminary assessment of x-ray data from runaways generated during disruptions

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

Science.gov (United States)

Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

2012-01-01

Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

Gremlin Activates the Smad Pathway Linked to Epithelial Mesenchymal Transdifferentiation in Cultured Tubular Epithelial Cells

Directory of Open Access Journals (Sweden)

Raquel Rodrigues-Diez

2014-01-01

Full Text Available Gremlin is a developmental gene upregulated in human chronic kidney disease and in renal cells in response to transforming growth factor-β (TGF-β. Epithelial mesenchymal transition (EMT is one process involved in renal fibrosis. In tubular epithelial cells we have recently described that Gremlin induces EMT and acts as a downstream TGF-β mediator. Our aim was to investigate whether Gremlin participates in EMT by the regulation of the Smad pathway. Stimulation of human tubular epithelial cells (HK2 with Gremlin caused an early activation of the Smad signaling pathway (Smad 2/3 phosphorylation, nuclear translocation, and Smad-dependent gene transcription. The blockade of TGF-β, by a neutralizing antibody against active TGF-β, did not modify Gremlin-induced early Smad activation. These data show that Gremlin directly, by a TGF-β independent process, activates the Smad pathway. In tubular epithelial cells long-term incubation with Gremlin increased TGF-β production and caused a sustained Smad activation and a phenotype conversion into myofibroblasts-like cells. Smad 7 overexpression, which blocks Smad 2/3 activation, diminished EMT changes observed in Gremlin-transfected tubuloepithelial cells. TGF-β neutralization also diminished Gremlin-induced EMT changes. In conclusion, we propose that Gremlin could participate in renal fibrosis by inducing EMT in tubular epithelial cells through activation of Smad pathway and induction of TGF-β.

BINARY DISRUPTION BY MASSIVE BLACK HOLES: HYPERVELOCITY STARS, S STARS, AND TIDAL DISRUPTION EVENTS

Energy Technology Data Exchange (ETDEWEB)

Bromley, Benjamin C. [Department of Physics and Astronomy, University of Utah, 115 S 1400 E, Rm 201, Salt Lake City, UT 84112 (United States); Kenyon, Scott J.; Geller, Margaret J.; Brown, Warren R., E-mail: bromley@physics.utah.edu, E-mail: skenyon@cfa.harvard.edu, E-mail: mgeller@cfa.harvard.edu, E-mail: wbrown@cfa.harvard.edu [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States)

2012-04-20

We examine whether disrupted binary stars can fuel black hole growth. In this mechanism, tidal disruption produces a single hypervelocity star (HVS) ejected at high velocity and a former companion star bound to the black hole. After a cluster of bound stars forms, orbital diffusion allows the black hole to accrete stars by tidal disruption at a rate comparable to the capture rate. In the Milky Way, HVSs and the S star cluster imply similar rates of 10{sup -5} to 10{sup -3} yr{sup -1} for binary disruption. These rates are consistent with estimates for the tidal disruption rate in nearby galaxies and imply significant black hole growth from disrupted binaries on 10 Gyr timescales.

Inhibition of transforming growth factor-beta1-induced signaling and epithelial-to-mesenchymal transition by the Smad-binding peptide aptamer Trx-SARA.

Science.gov (United States)

Zhao, Bryan M; Hoffmann, F Michael

2006-09-01

Overexpression of the inhibitory Smad, Smad7, is used frequently to implicate the Smad pathway in cellular responses to transforming growth factor beta (TGF-beta) signaling; however, Smad7 regulates several other proteins, including Cdc42, p38MAPK, and beta-catenin. We report an alternative approach for more specifically disrupting Smad-dependent signaling using a peptide aptamer, Trx-SARA, which comprises a rigid scaffold, the Escherichia coli thioredoxin A protein (Trx), displaying a constrained 56-amino acid Smad-binding motif from the Smad anchor for receptor activation (SARA) protein. Trx-SARA bound specifically to Smad2 and Smad3 and inhibited both TGF-beta-induced reporter gene expression and epithelial-to-mesenchymal transition in NMuMG murine mammary epithelial cells. In contrast to Smad7, Trx-SARA had no effect on the Smad2 or 3 phosphorylation levels induced by TGF-beta1. Trx-SARA was primarily localized to the nucleus and perturbed the normal cytoplasmic localization of Smad2 and 3 to a nuclear localization in the absence of TGF-beta1, consistent with reduced Smad nuclear export. The key mode of action of Trx-SARA was to reduce the level of Smad2 and Smad3 in complex with Smad4 after TGF-beta1 stimulation, a mechanism of action consistent with the preferential binding of SARA to monomeric Smad protein and Trx-SARA-mediated disruption of active Smad complexes.

Statistical analysis of JET disruptions

International Nuclear Information System (INIS)

Tanga, A.; Johnson, M.F.

1991-07-01

In the operation of JET and of any tokamak many discharges are terminated by a major disruption. The disruptive termination of a discharge is usually an unwanted event which may cause damage to the structure of the vessel. In a reactor disruptions are potentially a very serious problem, hence the importance of studying them and devising methods to avoid disruptions. Statistical information has been collected about the disruptions which have occurred at JET over a long span of operations. The analysis is focused on the operational aspects of the disruptions rather than on the underlining physics. (Author)

Disruptions in DIII-D

International Nuclear Information System (INIS)

Reiman, A.; Taylor, P.; Kellman, A.; LaHaye, R.

1996-01-01

We report on the results of a statistical analysis of the DIII-D disruption data base, and on an examination of a selected subset of the shots to determine the likely causes of disruptions. The statistical analysis focuses on the dependence of the disruption rate on key dimensionless parameters. We find that the disruption frequency is high at modest values of the parameters, and that it can be relatively low at operational limits. For example, the disruption frequency in an ITER relevant regime (β N /l i ∼ 2, 3 G > 0.6, where n G is the Greenwald limit) is approximately 23%. For this range of q, the disruption frequency rises only modestly to about 35% at the β limit, consistent with previous observations of a soft β limit for this q regime. For the range 6 95 G G < .9) in all q regimes we have studied. The location of the minimum moves to higher density with increasing q

Architectural prototyping

DEFF Research Database (Denmark)

Bardram, Jakob Eyvind; Christensen, Henrik Bærbak; Hansen, Klaus Marius

2004-01-01

A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders...

Disruption model

International Nuclear Information System (INIS)

Murray, J.G.; Bronner, G.

1982-07-01

Calculations of disruption time and energy dissipation have been obtained by simulating the plasma as an electrical conducting loop that varies in resistivity, current density, major radius. The calculations provide results which are in good agreement with experimental observations. It is believed that this approach allows engineering designs for disruptions to be completed in large tokamaks such as INTOR or FED

Architectural communication: Intra and extra activity of architecture

Directory of Open Access Journals (Sweden)

Stamatović-Vučković Slavica

2013-01-01

Full Text Available Apart from a brief overview of architectural communication viewed from the standpoint of theory of information and semiotics, this paper contains two forms of dualistically viewed architectural communication. The duality denotation/connotation (”primary” and ”secondary” architectural communication is one of semiotic postulates taken from Umberto Eco who viewed architectural communication as a semiotic phenomenon. In addition, architectural communication can be viewed as an intra and an extra activity of architecture where the overall activity of the edifice performed through its spatial manifestation may be understood as an act of communication. In that respect, the activity may be perceived as the ”behavior of architecture”, which corresponds to Lefebvre’s production of space.

Internal disruption in tokamaks

International Nuclear Information System (INIS)

Kuvshinov, B.N.; Savrukhin, P.V.

1990-01-01

A review of results of experimental and theoretical investigations of internal disruption in tokamaks is given. Specific features of various types of saw-tooth oscillations are described and their classification is performed. Theoretical models of the process of development of internal disruption instability are discussed. Effect of internal disruption on parameters of plasma, confined in tokamak, is considered. Scalings of period and amplitude of saw-tooth oscillations, as well as version radius are presented. Different methods for stabilizing instability of internal disruption are described

Internal disruptions in tokamaks

International Nuclear Information System (INIS)

Kuvshinov, B.N.; Savrukhin, P.V.

1990-01-01

Experimental and theoretical studies of the phenomenon of internal disruptions in tokamaks are reviewed. A classification scheme is introduced and the features of different types of sawtooth oscillations are described. A theoretical model for the development of the internal disruption instability is discussed. The effect of internal disruptions on the parameters of plasma confined in tokamaks is discussed. Scaling laws for the period and amplitude of sawtooth oscillations, as well as for the inversion radius, are presented. Different methods of stabilizing the internal disruption instability are described

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

Science.gov (United States)

Hansen, R K; Bissell, M J

2010-01-01

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function. PMID:10903527

Solo and keratin filaments regulate epithelial tubule morphology.

Science.gov (United States)

Nishimura, Ryosuke; Kato, Kagayaki; Fujiwara, Sachiko; Ohashi, Kazumasa; Mizuno, Kensaku

2018-04-28

Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.

Rat glomerular epithelial cells in culture. Parietal or visceral epithelial origin

International Nuclear Information System (INIS)

Norgaard, J.O.

1987-01-01

Isolated glomeruli from rats were explanted under standard culture conditions and outgrowths were studied by light and electron microscopy in order to identify the cells. Rat glomerular samples contained 20 to 30% structurally well-preserved encapsulated glomeruli which had a large rate of attachment to the substrate and very constantly gave rise to cellular outgrowth. In order to label cells from which outgrowth originated the glomerular incorporation of [ 3 H]thymidine was studied in the preattachment phase. By light and electron microscope autoradiograph it was demonstrated that label was located only over visceral and parietal epithelial cells during the first 3 days of culture. Incorporation of [ 3 H]thymidine was seen in mesangial cells after 5 days, i.e., after the glomeruli had attached to the culture vessels and the initial outgrowth had appeared. Consequently the first cells to grow out were of epithelial origin. Glomeruli were then incubated with [ 3 H]thymidine for the first 2 1/2 days of culture in order to label the epithelial cells, then were allowed to attach to the substrate and induce cell outgrowth. By light microscope autoradiography performed with the outgrowths in situ two types of cells with labeled nuclei were seen: (a) a small, polyhedral ciliated cell which grew in colonies where the cells were joined by junctional complexes (type I), and (b) a second very large, often multinucleated cell (type II). Based on the structural resemblance with their counterparts in situ and on comparisons with positively identified visceral epithelial cells in outgrowths from other species it is suggested that type I cells are derived from the parietal epithelium of Bowman's capsule and type II cells from the visceral epithelium

Architectural freedom and industrialized architecture

DEFF Research Database (Denmark)

Vestergaard, Inge

2012-01-01

to explain that architecture can be thought as a complex and diverse design through customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performing expression in direct relation to the given context. Through the last couple of years we have...... proportions, to organize the process on site choosing either one room wall components or several rooms wall components – either horizontally or vertically. Combined with the seamless joint the playing with these possibilities the new industrialized architecture can deliver variations in choice of solutions...... for retrofit design. If we add the question of the installations e.g. ventilation to this systematic thinking of building technique we get a diverse and functional architecture, thereby creating a new and clearer story telling about new and smart system based thinking behind architectural expression....

Architectural freedom and industrialized architecture

DEFF Research Database (Denmark)

Vestergaard, Inge

2012-01-01

to explain that architecture can be thought as a complex and diverse design through customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performing expression in direct relation to the given context. Through the last couple of years we have...... expression in the specific housing area. It is the aim of this article to expand the different design strategies which architects can use – to give the individual project attitudes and designs with architectural quality. Through the customized component production it is possible to choose different...... for retrofit design. If we add the question of the installations e.g. ventilation to this systematic thinking of building technique we get a diverse and functional architecture, thereby creating a new and clearer story telling about new and smart system based thinking behind architectural expression....

Architectural freedom and industrialised architecture

DEFF Research Database (Denmark)

Vestergaard, Inge

2012-01-01

Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l inge.vestergaard@aarch.dk Based on the repetitive architecture from the "building boom" 1960...... customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performed expression in direct relation to the given context. Through the last couple of years we have in Denmark been focusing a more sustainable and low energy building technique, which also include...... to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...

Galectin-3 modulates the polarized surface delivery of β1-integrin in epithelial cells.

Science.gov (United States)

Hönig, Ellena; Ringer, Karina; Dewes, Jenny; von Mach, Tobias; Kamm, Natalia; Kreitzer, Geri; Jacob, Ralf

2018-05-10

Epithelial cells require a precise intracellular transport and sorting machinery in order to establish and maintain their polarized architecture. This machinery includes beta-galactoside binding galectins for glycoprotein targeting to the apical membrane. Galectin-3 sorts cargo destined for the apical plasma membrane into vesicular carriers. After delivery of cargo to the apical milieu, galectin-3 recycles back into sorting organelles. We analyzed the role of galectin-3 in the polarized distribution of β1-integrin in MDCK cells. Integrins are located primarily at the basolateral domain of epithelial cells. We demonstrate that a minor pool of β1-integrin interacts with galectin-3 at the apical plasma membrane. Knockdown of galectin-3 decreases apical delivery of β1-integrin. This loss is restored by supplementation with recombinant galectin-3 and galectin-3 overexpression. Our data suggest that galectin-3 targets newly synthesized β1-integrin to the apical membrane and promotes apical delivery of β1-integrin internalized from the basolateral membrane. In parallel, galectin-3 knockout results in a reduction in cell proliferation and an impairment in proper cyst development. Our results suggest that galectin-3 modulates the surface distribution of β1-integrin and affects the morphogenesis of polarized cells. © 2018. Published by The Company of Biologists Ltd.

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

Science.gov (United States)

Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.

Science.gov (United States)

Kayastha, Forum; Johar, Kaid; Gajjar, Devarshi; Arora, Anshul; Madhu, Hardik; Ganatra, Darshini; Vasavada, Abhay

2015-06-01

Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown. The purpose of this study is to evaluate the effect of andrographolide on EMT induced by growth factors in the fetal human lens epithelial cell line (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed that FHL 124 cells treated with growth factors had a significant decrease in protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After administering andrographolide, these levels significantly increased. It was noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly decreased after treatment with andrographolide when compared to the other group. Treatment with andrographolide significantly inhibited phosphorylation of ERK and JNK. Cell cycle analysis showed that andrographolide did not arrest cells at G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide helps sustain epithelial characteristics by modulating EMT markers and inhibiting the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it can prove to be useful in curbing EMT-mediated PCO.

Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway.

Science.gov (United States)

Pelegrino, F S A; Pflugfelder, S C; De Paiva, C S

2012-01-01

Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized MedicineSummary

Directory of Open Access Journals (Sweden)

Kelly A. Whelan

Full Text Available The stratified squamous epithelium of the esophagus shows a proliferative basal layer of keratinocytes that undergo terminal differentiation in overlying suprabasal layers. Esophageal pathologies, including eosinophilic esophagitis, gastroesophageal reflux disease, Barrett's esophagus, squamous cell carcinoma, and adenocarcinoma, cause perturbations in the esophageal epithelial proliferation-differentiation gradient. Three-dimensional (3D culture platforms mimicking in vivo esophageal epithelial tissue architecture ex vivo have emerged as powerful experimental tools for the investigation of esophageal biology in the context of homeostasis and pathology. Herein, we describe types of 3D culture that are used to model the esophagus, including organotypic, organoid, and spheroid culture systems. We discuss the development and optimization of various esophageal 3D culture models; highlight the applications, strengths, and limitations of each method; and summarize how these models have been used to evaluate the esophagus under homeostatic conditions as well as under the duress of inflammation and precancerous/cancerous conditions. Finally, we present future perspectives regarding the use of esophageal 3D models in basic science research as well as translational studies with the potential for personalized medicine. Keywords: Organotypic Culture, Organoid, Spheroid Culture, Esophageal Disease

High-grain diets altered rumen fermentation and epithelial bacterial community and resulted in rumen epithelial injuries of goats.

Science.gov (United States)

Zhang, Ruiyang; Ye, Huimin; Liu, Junhua; Mao, Shengyong

2017-09-01

This study evaluated the effects of high-grain diets on the rumen fermentation, epithelial bacterial community, morphology of rumen epithelium, and local inflammation of goats during high-grain feeding. Twelve 8-month-old goats were randomly assigned to two different diets, a hay diet or a high-grain diet (65% grain, HG). At the end of 7 weeks of treatment, samples of rumen content and rumen epithelium were collected. Rumen pH was lower (P rumen epithelial bacterial community, with an increase in the proportion of genus Prevotella and a decrease in the relative abundance of the genera Shuttleworthia and Fibrobacteres. PICRUSt analysis suggested that the HG-fed group had a higher (P rumen epithelial injury and upregulated (P rumen pH, LPS level, and rumen epithelial bacteria abundance. In conclusion, our results indicated that the alterations in the rumen environment and epithelial bacterial community which were induced by HG feeding may result in the damage and local inflammation in the rumen epithelium, warranting further study of rumen microbial-host interactions in the HG feeding model.

Enterprise architecture evaluation using architecture framework and UML stereotypes

Directory of Open Access Journals (Sweden)

Narges Shahi

2014-08-01

Full Text Available There is an increasing need for enterprise architecture in numerous organizations with complicated systems with various processes. Support for information technology, organizational units whose elements maintain complex relationships increases. Enterprise architecture is so effective that its non-use in organizations is regarded as their institutional inability in efficient information technology management. The enterprise architecture process generally consists of three phases including strategic programing of information technology, enterprise architecture programing and enterprise architecture implementation. Each phase must be implemented sequentially and one single flaw in each phase may result in a flaw in the whole architecture and, consequently, in extra costs and time. If a model is mapped for the issue and then it is evaluated before enterprise architecture implementation in the second phase, the possible flaws in implementation process are prevented. In this study, the processes of enterprise architecture are illustrated through UML diagrams, and the architecture is evaluated in programming phase through transforming the UML diagrams to Petri nets. The results indicate that the high costs of the implementation phase will be reduced.

Disruption of Pyridine Nucleotide Redox Status During Oxidative Challenge at Normal and Low-Glucose States: Implications for Cellular Adenosine Triphosphate, Mitochondrial Respiratory Activity, and Reducing Capacity in Colon Epithelial Cells

Science.gov (United States)

Circu, Magdalena L.; Maloney, Ronald E.

2011-01-01

Abstract We recently demonstrated that menadione (MQ), a redox cycling quinone, mediated the loss of mitochondrial glutathione/glutathione disulfide redox balance. In this study, we showed that MQ significantly disrupted cellular pyridine nucleotide (NAD+/NADH, NADP+/NADPH) redox balance that compromised cellular ATP, mitochondrial respiratory activity, and NADPH-dependent reducing capacity in colonic epithelial cells, a scenario that was exaggerated by low glucose. In the cytosol, MQ induced NAD+ loss concurrent with increased NADP+ and NAD kinase activity, but decreased NADPH. In the mitochondria, NADH loss occurred in conjunction with increased nicotinamide nucleotide transhydrogenase activity and NADP+, and decreased NADPH. These results are consistent with cytosolic NAD+-to-NADP+ and mitochondrial NADH-to-NADPH shifts, but compromised NADPH availability. Thus, despite the sacrifice of NAD+/NADH in favor of NADPH generation, steady-state NADPH levels were not maintained during MQ challenge. Impairments of cellular bioenergetics were evidenced by ATP losses and increased mitochondrial O2 dependence of pyridine nucleotide oxidation–reduction; half-maximal oxidation (P50) was 10-fold higher in low glucose, which was lowered by glutamate or succinate supplementation. This exaggerated O2 dependence is consistent with increased O2 diversion to nonmitochondrial O2 consumption by MQ-semiquinone redox cycling secondary to decreased NADPH-dependent MQ detoxication at low glucose, a situation that was corrected by glucose-sparing mitochondrial substrates. Antioxid. Redox Signal. 14, 2151–2162. PMID:21083422

Symposium on disruptive instabilities at Garching

International Nuclear Information System (INIS)

Lackner, K.

1979-01-01

The phenomenon of disruptive instabilities was investigated with a special care at the IPP at Garching. After lectures and panel sessions it appears suitable, to subdivide the disruptive phenomena into four classes: 1. The internal disruption (the socalled saw-tooth oscillators). 2. the socalled reconnection disruptions. 3. The large disruptions. 4. The small disruptions. The four appearance forms of the phenomena are briefly explained. (GG) [de

Adrenomedullin stimulates cyclic AMP production in the airway epithelial cells of guinea-pigs and in the human epithelial cell line

Directory of Open Access Journals (Sweden)

Takashi Kawaguchi

1999-01-01

Full Text Available This study was designed to examine the effects of adrenomedullin (AM on airway epithelial cells. Primary cultures of guinea-pig tracheal epithelial cells and the human bronchiolar epithelial cell line NCI-H441 were used. Intracellular cyclic adenosine monophosphate (cAMP, cyclic guanosine monophosphate (cGMP, prostaglandin E2 (PGE2, and stable end-products of nitric oxide were assayed. Adrenomedullin (10−6 mol/L stimulated cAMP production in guinea-pig epithelial cells. Indomethacin (10−5 mol/L significantly decreased the basal level of intracellular cAMP in guinea-pig epithelial cells, but not in NCI-H441 cells. However, AM did not stimulate production of PGE2, a major product that can increase cAMP formation. In the case of NCI-H441 cells, AM (10−8 – 10−6 mol/L did not significantly affect intracellular cGMP levels or nitrite content in conditioned medium. Adrenomedullin and calcitonin gene-related peptide (CGRP each stimulated cAMP production in NCI-H441 cells, but AM-stimulated cAMP production was antagonized by the CGRP fragment CGRP8–37. These findings suggest that AM stimulates cAMP production and functionally competes with CGRP for binding sites in airway epithelial cells, at least in human epithelial cells, but that it does not stimulate the release of PGE2 and nitric oxide. Though cyclooxygenase products contribute to some extent to cAMP formation in guinea-pigs, AM independently stimulates intracellular cAMP formation in airway epithelial cells.

Software architecture 2

CERN Document Server

Oussalah, Mourad Chabanne

2014-01-01

Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural templa

Lightweight enterprise architectures

CERN Document Server

Theuerkorn, Fenix

2004-01-01

STATE OF ARCHITECTUREArchitectural ChaosRelation of Technology and Architecture The Many Faces of Architecture The Scope of Enterprise Architecture The Need for Enterprise ArchitectureThe History of Architecture The Current Environment Standardization Barriers The Need for Lightweight Architecture in the EnterpriseThe Cost of TechnologyThe Benefits of Enterprise Architecture The Domains of Architecture The Gap between Business and ITWhere Does LEA Fit? LEA's FrameworkFrameworks, Methodologies, and Approaches The Framework of LEATypes of Methodologies Types of ApproachesActual System Environmen

Software architecture 1

CERN Document Server

Oussalah , Mourad Chabane

2014-01-01

Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural template

Survey of disruption causes at JET

International Nuclear Information System (INIS)

De Vries, P.C.; Johnson, M.F.; Alper, B.; Hender, T.C.; Riccardo, V.; Buratti, P.; Koslowski, H.R.

2011-01-01

A survey has been carried out into the causes of all 2309 disruptions over the last decade of JET operations. The aim of this survey was to obtain a complete picture of all possible disruption causes, in order to devise better strategies to prevent or mitigate their impact. The analysis allows the effort to avoid or prevent JET disruptions to be more efficient and effective. As expected, a highly complex pattern of chain of events that led to disruptions emerged. It was found that the majority of disruptions had a technical root cause, for example due to control errors, or operator mistakes. These bring a random, non-physics, factor into the occurrence of disruptions and the disruption rate or disruptivity of a scenario may depend more on technical performance than on physics stability issues. The main root cause of JET disruptions was nevertheless due to neo-classical tearing modes that locked, closely followed in second place by disruptions due to human error. The development of more robust operational scenarios has reduced the JET disruption rate over the last decade from about 15% to below 4%. A fraction of all disruptions was caused by very fast, precursorless unpredictable events. The occurrence of these disruptions may set a lower limit of 0.4% to the disruption rate of JET. If one considers on top of that human error and all unforeseen failures of heating or control systems this lower limit may rise to 1.0% or 1.6%, respectively.

Indigenous architecture as a context-oriented architecture, a look at ...

African Journals Online (AJOL)

What has become problematic as the achievement of international style and globalization of architecture during the time has been the purely technological look at architecture, and the architecture without belonging to a place. In recent decades, the topic of sustainable architecture and reconsidering indigenous architecture ...

Modulation of Kingella kingae adherence to human epithelial cells by type IV Pili, capsule, and a novel trimeric autotransporter.

Science.gov (United States)

Porsch, Eric A; Kehl-Fie, Thomas E; St Geme, Joseph W

2012-10-23

Kingella kingae is an emerging bacterial pathogen that is being recognized increasingly as an important etiology of septic arthritis, osteomyelitis, and bacteremia, especially in young children. Colonization of the posterior pharynx is a key step in the pathogenesis of K. kingae disease. Previous work established that type IV pili are necessary for K. kingae adherence to the respiratory epithelium. In this study, we set out to identify additional factors that influence K. kingae interactions with human epithelial cells. We found that genetic disruption of the gene encoding a predicted trimeric autotransporter protein called Knh (Kingella NhhA homolog) resulted in reduced adherence to human epithelial cells. In addition, we established that K. kingae elaborates a surface-associated polysaccharide capsule that requires a predicted ABC-type transporter export operon called ctrABCD for surface presentation. Furthermore, we discovered that the presence of a surface capsule interferes with Knh-mediated adherence to human epithelial cells by nonpiliated organisms and that maximal adherence in the presence of a capsule requires the predicted type IV pilus retraction machinery, PilT/PilU. On the basis of the data presented here, we propose a novel adherence mechanism that allows K. kingae to adhere efficiently to human epithelial cells while remaining encapsulated and more resistant to immune clearance. Kingella kingae is a Gram-negative bacterium that is being recognized increasingly as a cause of joint and bone infections in young children. The pathogenesis of disease due to K. kingae begins with bacterial colonization of the upper respiratory tract, and previous work established that surface hair-like fibers called type IV pili are necessary for K. kingae adherence to respiratory epithelial cells. In this study, we set out to identify additional factors that influence K. kingae interactions with respiratory epithelial cells. We discovered a novel surface protein called

Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation

Directory of Open Access Journals (Sweden)

An Gary

2008-05-01

Full Text Available Abstract Background One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure. Results and Discussion ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems Conclusion A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior

Andrographolide suppresses epithelial mesenchymal transition by ...

Indian Academy of Sciences (India)

Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown.

Statistical analysis of disruptions in JET

International Nuclear Information System (INIS)

De Vries, P.C.; Johnson, M.F.; Segui, I.

2009-01-01

The disruption rate (the percentage of discharges that disrupt) in JET was found to drop steadily over the years. Recent campaigns (2005-2007) show a yearly averaged disruption rate of only 6% while from 1991 to 1995 this was often higher than 20%. Besides the disruption rate, the so-called disruptivity, or the likelihood of a disruption depending on the plasma parameters, has been determined. The disruptivity of plasmas was found to be significantly higher close to the three main operational boundaries for tokamaks; the low-q, high density and β-limit. The frequency at which JET operated close to the density-limit increased six fold over the last decade; however, only a small reduction in disruptivity was found. Similarly the disruptivity close to the low-q and β-limit was found to be unchanged. The most significant reduction in disruptivity was found far from the operational boundaries, leading to the conclusion that the improved disruption rate is due to a better technical capability of operating JET, instead of safer operations close to the physics limits. The statistics showed that a simple protection system was able to mitigate the forces of a large fraction of disruptions, although it has proved to be at present more difficult to ameliorate the heat flux.

Architecture in the Islamic Civilization: Muslim Building or Islamic Architecture

OpenAIRE

Yassin, Ayat Ali; Utaberta, Dr. Nangkula

2012-01-01

The main problem of the theory in the arena of islamic architecture is affected by some of its Westernthoughts, and stereotyping the islamic architecture according to Western thoughts; this leads to the breakdownof the foundations in the islamic architecture. It is a myth that islamic architecture is subjected to theinfluence from foreign architectures. This paper will highlight the dialectical concept of islamic architecture ormuslim buildings and the areas of recognition in islamic architec...

Improvements in disruption prediction at ASDEX Upgrade

Energy Technology Data Exchange (ETDEWEB)

Aledda, R., E-mail: raffaele.aledda@diee.unica.it; Cannas, B., E-mail: cannas@diee.unica.it; Fanni, A., E-mail: fanni@diee.unica.it; Pau, A., E-mail: alessandro.pau@diee.unica.it; Sias, G., E-mail: giuliana.sias@diee.unica.it

2015-10-15

Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

Improvements in disruption prediction at ASDEX Upgrade

International Nuclear Information System (INIS)

Aledda, R.; Cannas, B.; Fanni, A.; Pau, A.; Sias, G.

2015-01-01

Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.

Directory of Open Access Journals (Sweden)

Chen Sun

Full Text Available A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs. Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.

Disruption prediction at JET

International Nuclear Information System (INIS)

Milani, F.

1998-12-01

The sudden loss of the plasma magnetic confinement, known as disruption, is one of the major issue in a nuclear fusion machine as JET (Joint European Torus). Disruptions pose very serious problems to the safety of the machine. The energy stored in the plasma is released to the machine structure in few milliseconds resulting in forces that at JET reach several Mega Newtons. The problem is even more severe in the nuclear fusion power station where the forces are in the order of one hundred Mega Newtons. The events that occur during a disruption are still not well understood even if some mechanisms that can lead to a disruption have been identified and can be used to predict them. Unfortunately it is always a combination of these events that generates a disruption and therefore it is not possible to use simple algorithms to predict it. This thesis analyses the possibility of using neural network algorithms to predict plasma disruptions in real time. This involves the determination of plasma parameters every few milliseconds. A plasma boundary reconstruction algorithm, XLOC, has been developed in collaboration with Dr. D. O'Brien and Dr. J. Ellis capable of determining the plasma wall/distance every 2 milliseconds. The XLOC output has been used to develop a multilayer perceptron network to determine plasma parameters as l i and q ψ with which a machine operational space has been experimentally defined. If the limits of this operational space are breached the disruption probability increases considerably. Another approach for prediction disruptions is to use neural network classification methods to define the JET operational space. Two methods have been studied. The first method uses a multilayer perceptron network with softmax activation function for the output layer. This method can be used for classifying the input patterns in various classes. In this case the plasma input patterns have been divided between disrupting and safe patterns, giving the possibility of

CXCL9 Regulates TGF-β1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

Science.gov (United States)

O'Beirne, Sarah L; Walsh, Sinead M; Fabre, Aurélie; Reviriego, Carlota; Worrell, Julie C; Counihan, Ian P; Lumsden, Robert V; Cramton-Barnes, Jennifer; Belperio, John A; Donnelly, Seamas C; Boylan, Denise; Marchal-Sommé, Joëlle; Kane, Rosemary; Keane, Michael P

2015-09-15

Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1-induced EMT. A decrease in TGF-β1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1-induced EMT. Copyright © 2015 by The American Association of Immunologists, Inc.

Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

Science.gov (United States)

Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

2016-03-01

The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

Epithelial Cells in Urine: MedlinePlus Lab Test Information

Science.gov (United States)

... page: https://medlineplus.gov/labtests/epithelialcellsinurine.html Epithelial Cells in Urine To use the sharing features on ... page, please enable JavaScript. What is an Epithelial Cells in Urine Test? Epithelial cells are a type ...

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice.

Science.gov (United States)

Gong, Ju-Hyun; Cho, In-Hee; Shin, Daekeun; Han, Seon-Young; Park, Sin-Hye; Kang, Young-Hee

2014-03-01

Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, submucosal fibrosis and epithelial shedding. Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF-β. In the in vitro study, we investigated whether 1-20 μM kaempferol inhibited lipopolysaccharide (LPS)-induced bronchial EMT in BEAS-2B cells. The in vivo study explored demoting effects of 10-20 mg/kg kaempferol on airway fibrosis in BALB/c mice sensitized with ovalbumin (OVA). LPS induced airway epithelial TGF-β1 signaling that promoted EMT with concurrent loss of E-cadherin and induction of α-smooth muscle actin (α-SMA). Nontoxic kaempferol significantly inhibited TGF-β-induced EMT process through reversing E-cadherin expression and retarding the induction of N-cadherin and α-SMA. Consistently, OVA inhalation resulted in a striking loss of epithelial morphology by displaying myofibroblast appearance, which led to bronchial fibrosis with submucosal accumulation of collagen fibers. Oral administration of kaempferol suppressed collagen deposition, epithelial excrescency and goblet hyperplasia observed in the lung of OVA-challenged mice. The specific inhibition of TGF-β entailed epithelial protease-activated receptor-1 (PAR-1) as with 20 μM kaempferol. The epithelial PAR-1 inhibition by SCH-79797 restored E-cadherin induction and deterred α-SMA induction, indicating that epithelial PAR-1 localization was responsible for resulting in airway EMT. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.

Engineering epithelial-stromal interactions in vitro for toxicology assessment

Science.gov (United States)

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo t...

Myosin light chain kinase mediates intestinal barrier disruption following burn injury.

Directory of Open Access Journals (Sweden)

Chuanli Chen

Full Text Available BACKGROUND: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC phosphorylation mediated by MLC kinase (MLCK is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. METHODOLOGY/PRINCIPAL FINDINGS: Male balb/c mice were assigned randomly to either sham burn (control or 30% total body surface area (TBSA full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg, an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. CONCLUSIONS/SIGNIFICANCE: The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury.

Software architecture analysis tool : software architecture metrics collection

NARCIS (Netherlands)

Muskens, J.; Chaudron, M.R.V.; Westgeest, R.

2002-01-01

The Software Engineering discipline lacks the ability to evaluate software architectures. Here we describe a tool for software architecture analysis that is based on metrics. Metrics can be used to detect possible problems and bottlenecks in software architectures. Even though metrics do not give a

HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

Science.gov (United States)

Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

2014-07-01

The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.

Epithelial cell polarity, stem cells and cancer

DEFF Research Database (Denmark)

Martin-Belmonte, Fernando; Perez-Moreno, Mirna

2011-01-01

, deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

Monitoring-induced disruption in skilled typewriting.

Science.gov (United States)

Snyder, Kristy M; Logan, Gordon D

2013-10-01

It is often disruptive to attend to the details of one's expert performance. The current work presents four experiments that utilized a monitor to report protocol to evaluate the sufficiency of three accounts of monitoring-induced disruption. The inhibition hypothesis states that disruption results from costs associated with preparing to withhold inappropriate responses. The dual-task hypothesis states that disruption results from maintaining monitored information in working memory. The implicit-explicit hypothesis states that disruption results from explicitly monitoring details of performance that are normally implicit. The findings suggest that all three hypotheses are sufficient to produce disruption, but inhibition and dual-task costs are not necessary. Experiment 1 showed that monitoring to report was disruptive even when there was no requirement to inhibit. Experiment 2 showed that maintaining information in working memory caused some disruption but much less than monitoring to report. Experiment 4 showed that monitoring to inhibit was more disruptive than monitoring to report, suggesting that monitoring is more disruptive when it is combined with other task requirements, such as inhibition. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Disruptive Intelligence - How to gather Information to deal with disruptive innovations

NARCIS (Netherlands)

Vriens, D.J.; Solberg Søilen, K.

2014-01-01

Disruptive innovations are innovations that have the capacity to transform a whole business into one with products that are more accessible and affordable (cf. Christensen et al. 2009). As Christensen et al. argue no business is immune to such disruptive innovations. If these authors are right, it

Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

Science.gov (United States)

Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

2010-01-01

This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

Ionizing radiation predisposes non-malignant human mammaryepithelial cells to undergo TGF beta-induced epithelial to mesenchymaltransition

Energy Technology Data Exchange (ETDEWEB)

Andarawewa, Kumari L.; Erickson, Anna C.; Chou, William S.; Costes, Sylvain; Gascard, Philippe; Mott, Joni D.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen

2007-04-06

Transforming growth factor {beta}1 (TGF{beta}) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGF{beta}, activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGF{beta}-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGF{beta} (0.4 ng/ml), or double-treated. All double-treated (IR+TGF{beta}) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, {beta}-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel{trademark}. Neither radiation nor TGF{beta} alone elicited EMT, even though IR increased chronic TGF{beta} signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGF{beta}-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGF{beta}, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.

Open architecture design and approach for the Integrated Sensor Architecture (ISA)

Science.gov (United States)

Moulton, Christine L.; Krzywicki, Alan T.; Hepp, Jared J.; Harrell, John; Kogut, Michael

2015-05-01

Integrated Sensor Architecture (ISA) is designed in response to stovepiped integration approaches. The design, based on the principles of Service Oriented Architectures (SOA) and Open Architectures, addresses the problem of integration, and is not designed for specific sensors or systems. The use of SOA and Open Architecture approaches has led to a flexible, extensible architecture. Using these approaches, and supported with common data formats, open protocol specifications, and Department of Defense Architecture Framework (DoDAF) system architecture documents, an integration-focused architecture has been developed. ISA can help move the Department of Defense (DoD) from costly stovepipe solutions to a more cost-effective plug-and-play design to support interoperability.

Politisk disruption

DEFF Research Database (Denmark)

Tække, Jesper

2018-01-01

Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på.......Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på....

Celiac Disease: Role of the Epithelial BarrierSummary

Directory of Open Access Journals (Sweden)

Michael Schumann

2017-03-01

Full Text Available In celiac disease (CD a T-cell–mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed. Keywords: Celiac Sprue, Gluten-Sensitive Enteropathy, Tight Junction, Epithelial Polarity, Partitioning-Defective Proteins, α-Gliadin 33mer

Epithelial cells as alternative human biomatrices for comet assay.

Science.gov (United States)

Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara

2014-01-01

The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases.

Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

NARCIS (Netherlands)

Harrison, Neil B.; Avgeriou, Paris

2008-01-01

Architecture patterns are an important tool in architectural design. However, while many architecture patterns have been identified, there is little in-depth understanding of their actual use in software architectures. For instance, there is no overview of how many patterns are used per system or

A structured architecture for advanced plasma control experiments

International Nuclear Information System (INIS)

Penaflor, B.G.; Ferron, J.R.; Walker, M.L.

1996-10-01

Recent new and improved plasma control regimes have evolved from enhancements to the systems responsible for managing the plasma configuration on the DIII-D tokamak. The collection of hardware and software components designed for this purpose is known at DIII-D as the Plasma Control System or PCS. Several new user requirements have contributed to the rapid growth of the PCS. Experiments involving digital control of the plasma vertical position have resulted in the addition of new high performance processors to operate in real-time. Recent studies in plasma disruptions involving the use of neural network based software have resulted in an increase in the number of input diagnostic signals sampled. Better methods for estimating the plasma shape and position have brought about numerous software changes and the addition of several new code modules. Furthermore, requests for performing multivariable control and feedback on the current profile are continuing to add to the demands being placed on the PCS. To support all of these demands has required a structured yet flexible hardware and software architecture for maintaining existing capabilities and easily adding new ones. This architecture along with a general overview of the DIII-D Plasma Control System is described. In addition, the latest improvements to the PCS are presented

Sleep architecture in insomniacs with severe benzodiazepine abuse.

Science.gov (United States)

Manconi, Mauro; Ferri, Raffaele; Miano, Silvia; Maestri, Michelangelo; Bottasini, Valentina; Zucconi, Marco; Ferini-Strambi, Luigi

2017-06-01

Benzodiazepines (BZDs) are the most commonly prescribed compounds in insomnia. A long-term of BZDs use may cause dependence and abuse. The aim of this study was to evaluate sleep architecture and microstructure (in terms of cyclic alternating pattern - CAP - analysis and of sleep EEG power spectral analysis) in a group of long-term users of high doses of BZDs for their primary chronic insomnia. Twenty patients consecutively admitted at the Sleep Centre for drug discontinuation and 13 matched healthy controls underwent a full nocturnal video-polysomnographic recording, after one adaptation night. Significant differences were found in time in bed, REM sleep latency and sleep stage 1% which were increased in patients compared to controls, while CAP rate was dramatically decreased. During NREM sleep, patients showed a clear decrease in the relative power of delta band. Our data demonstrate that in adults with chronic insomnia, long-term use of high doses of BZDs induces a severe disruption of sleep microstructure, while sleep architecture seems to be much less affected. The long term use of high doses of BZDs for chronic insomnia induces a marked depression of slow wave activity and of its physiological instability. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Chromosome aberration induction in human diploid fibroblast and epithelial cells

International Nuclear Information System (INIS)

Scott, D.

1986-01-01

The relative sensitivity of cultured human fibroblasts and epithelial cells to radiation-induced chromosomal aberrations was investigated. Lung fibroblast and kidney epithelial cells from the same fetus were compared, as were skin fibroblasts and epithelial keratinocytes from the same foreskin sample. After exposure of proliferating fetal cells to 1.5 Gy X-rays there was a very similar aberration yield in the fibroblasts and epithelial cells. Observations of either little or no difference in chromosomal sensitivity between human fibroblasts and epithelial cells give added confidence that quantitative cytogenetic data obtained from cultured fibroblasts are relevant to the question of sensitivity of epithelial cells which are the predominant cell type in human cancers. (author)

On the Architectural Engineering Competences in Architectural Design

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning

2007-01-01

In 1997 a new education in Architecture & Design at Department of Architecture and Design, Aalborg University was started with 50 students. During the recent years this number has increased to approximately 100 new students each year, i.e. approximately 500 students are following the 3 years...... bachelor (BSc) and the 2 years master (MSc) programme. The first 5 semesters are common for all students followed by 5 semesters with specialization into Architectural Design, Urban Design, Industrial Design or Digital Design. The present paper gives a short summary of the architectural engineering...

DNA repair in human bronchial epithelial cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

1982-01-01

The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

Science.gov (United States)

Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

2017-03-01

Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

Thigmotaxis Mediates Trail Odour Disruption.

Science.gov (United States)

Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

2017-05-10

Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

Connecting Architecture and Implementation

Science.gov (United States)

Buchgeher, Georg; Weinreich, Rainer

Software architectures are still typically defined and described independently from implementation. To avoid architectural erosion and drift, architectural representation needs to be continuously updated and synchronized with system implementation. Existing approaches for architecture representation like informal architecture documentation, UML diagrams, and Architecture Description Languages (ADLs) provide only limited support for connecting architecture descriptions and implementations. Architecture management tools like Lattix, SonarJ, and Sotoarc and UML-tools tackle this problem by extracting architecture information directly from code. This approach works for low-level architectural abstractions like classes and interfaces in object-oriented systems but fails to support architectural abstractions not found in programming languages. In this paper we present an approach for linking and continuously synchronizing a formalized architecture representation to an implementation. The approach is a synthesis of functionality provided by code-centric architecture management and UML tools and higher-level architecture analysis approaches like ADLs.

Supply disruption cost for power network planning

International Nuclear Information System (INIS)

Kjoelle, G.H.

1992-09-01

A description is given of the method of approach to calculate the total annual socio-economic cost of power supply disruption and non-supplied energy, included the utilities' cost for planning. The total socio-economic supply disruption cost is the sum of the customers' disruption cost and the utilities' cost for failure and disruption. The mean weighted disruption cost for Norway for one hour disruption is NOK 19 per kWh. The customers' annual disruption cost is calculated with basis in the specific disruption cost referred to heavy load (January) and dimensioning maximum loads. The loads are reduced by factors taking into account the time variations of the failure frequency, duration, the loads and the disruption cost. 6 refs

Disrupting the Industry with Play

DEFF Research Database (Denmark)

Lund, Henrik Hautop

2016-01-01

or two ago. This is significantly disrupting the industry in several market sectors. This paper describes the components of the playware and embodied artificial intelligence research that has led to disruption in the industrial robotics sector, and which points to the next disruption of the health care...

Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women.

Science.gov (United States)

Leonard, Sarah M; Pereira, Merlin; Roberts, Sally; Cuschieri, Kate; Nuovo, Gerard; Athavale, Ramanand; Young, Lawrence; Ganesan, Raji; Woodman, Ciarán B

2016-02-15

High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life.

Cell disruption for microalgae biorefineries.

Science.gov (United States)

Günerken, E; D'Hondt, E; Eppink, M H M; Garcia-Gonzalez, L; Elst, K; Wijffels, R H

2015-01-01

Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

Energy Technology Data Exchange (ETDEWEB)

Lasalvia, Maria [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Castellani, Stefano [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); D’Antonio, Palma [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Perna, Giuseppe [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Carbone, Annalucia [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); Colia, Anna Laura; Maffione, Angela Bruna [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Capozzi, Vito [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Conese, Massimo, E-mail: massimo.conese@unifg.it [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy)

2016-10-15

The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in

Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

International Nuclear Information System (INIS)

Lasalvia, Maria; Castellani, Stefano; D’Antonio, Palma; Perna, Giuseppe; Carbone, Annalucia; Colia, Anna Laura; Maffione, Angela Bruna; Capozzi, Vito; Conese, Massimo

2016-01-01

The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in the

Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat.

Science.gov (United States)

Adiningrat, A; Tanimura, A; Miyoshi, K; Hagita, H; Yanuaryska, R D; Arinawati, D Y; Horiguchi, T; Noma, T

2016-03-01

Disruption of the third zinc finger domain of specificity protein 6 (SP6) presents an enamel-specific defect in a rat model of amelogenesis imperfecta (AMI rats). To understand the molecular basis of amelogenesis imperfecta caused by the Sp6 mutation, we established and characterized AMI-derived rat dental epithelial (ARE) cells. ARE cell clones were isolated from the mandibular incisors of AMI rats, and amelogenesis-related gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Localization of wild-type SP6 (SP6WT) and mutant-type SP6 (SP6AMI) was analyzed by immunocytochemistry. SP6 transcriptional activity was monitored by rho-associated protein kinase 1 (Rock1) promoter activity with its specific binding to the promoter region in dental (G5 and ARE) and non-dental (COS-7) epithelial cells. Isolated ARE cells were varied in morphology and gene expression. Both SP6WT and SP6AMI were mainly detected in nuclei. The promoter analysis revealed that SP6WT and SP6AMI enhanced Rock1 promoter activity in G5 cells but that enhancement by SP6AMI was weaker, whereas no enhancement was observed in the ARE and COS-7 cells, even though SP6WT and SP6AMI bound to the promoter in all instances. ARE cell clones can provide a useful in vitro model to study the mechanism of SP6-mediated amelogenesis imperfecta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Novel Role for VICKZ Proteins in Maintaining Epithelial Integrity during Embryogenesis.

Directory of Open Access Journals (Sweden)

Michal Shoshkes Carmel

Full Text Available VICKZ (IGF2BP1,2,3/ZBP1/Vg1RBP/IMP1,2,3 proteins bind RNA and help regulate many RNA-mediated processes. In the midbrain region of early chick embryos, VICKZ is expressed in the neural folds and along the basal surface of the neural epithelium, but, upon neural tube closure, is down-regulated in prospective cranial neural crest (CNC cells, concomitant with their emigration and epithelial-to-mesenchymal transition (EMT. Electroporation of constructs that modulate cVICKZ expression demonstrates that this down-regulation is both necessary and sufficient for CNC EMT. These results suggest that VICKZ down-regulation in CNC cell-autonomously promotes EMT and migration. Reduction of VICKZ throughout the embryo, however, inhibits CNC migration non-cell-autonomously, as judged by transplantation experiments in Xenopus embryos.Given the positive role reported for VICKZ proteins in promoting cell migration of chick embryo fibroblasts and many types of cancer cells, we have begun to look for specific mRNAs that could mediate context-specific differences. We report here that the laminin receptor, integrin alpha 6, is down-regulated in the dorsal neural tube when CNC cells emigrate, this process is mediated by cVICKZ, and integrin alpha 6 mRNA is found in VICKZ ribonucleoprotein complexes. Significantly, prolonged inhibition of cVICKZ in either the neural tube or the nascent dermomyotome sheet, which also dynamically expresses cVICKZ, induces disruption of these epithelia. These data point to a previously unreported role for VICKZ in maintaining epithelial integrity.

Crossroads of Wnt and Hippo in epithelial tissues.

Science.gov (United States)

Bernascone, Ilenia; Martin-Belmonte, Fernando

2013-08-01

Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Silk Film Topography Directs Collective Epithelial Cell Migration

Science.gov (United States)

Rosenblatt, Mark I.

2012-01-01

The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

Subadventitial techniques for chronic total occlusion percutaneous coronary intervention: The concept of "vessel architecture".

Science.gov (United States)

Azzalini, Lorenzo; Carlino, Mauro; Brilakis, Emmanouil S; Vo, Minh; Rinfret, Stéphane; Uretsky, Barry F; Karmpaliotis, Dimitri; Colombo, Antonio

2018-03-01

Despite improvements in guidewire technologies, the traditional antegrade wire escalation approach to chronic total occlusion (CTO) recanalization is successful in only 60-80% of selected cases. In particular, long, calcified, and tortuous occlusions are less successfully approached with a true-to-true lumen approach. Frequently, the guidewire tracks into the subadventitial space, with no guarantee of distal re-entry into the true lumen. The ability to manage the subadventitial space has been a key step in the tremendous improvement in success rates of contemporary CTO percutaneous coronary intervention (PCI), whether operating antegradely or retrogradely. A modern approach to CTO PCI involves understanding the concept of "vessel architecture," which is based on the distinction between coronary structures (occlusive plaque, comprising the disrupted intima and media, and the outer adventitia) and extravascular space. The vessel architecture represents a safe work environment for guidewire and device manipulation. This review provides an anatomy-based description of the concept of vessel architecture, along with a historical perspective of subadventitial techniques for CTO PCI, and outcome data of CTO PCI utilizing the subadventitial space. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Polarized protein transport and lumen formation during epithelial tissue morphogenesis.

Science.gov (United States)

Blasky, Alex J; Mangan, Anthony; Prekeris, Rytis

2015-01-01

One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.

Major disruption process in tokamak

International Nuclear Information System (INIS)

Kurita, Gen-ichi; Azumi, Masafumi; Tuda, Takashi; Takizuka, Tomonori; Tsunematsu, Toshihide; Tokuda, Shinji; Itoh, Kimitaka; Takeda, Tatsuoki

1981-11-01

The major disruption in a cylindrical tokamak is investigated by using the multi-helicity code, and the destabilization of the 3/2 mode by the mode coupling with the 2/1 mode is confirmed. The evolution of the magnetic field topology caused by the major disruption is studied in detail. The effect of the internal disruption on the 2/1 magnetic island width is also studied. The 2/1 magnetic island is not enhanced by the flattening of the q-profile due to the internal disruption. (author)

Plasma disruption modeling and simulation

International Nuclear Information System (INIS)

Hassanein, A.

1994-01-01

Disruptions in tokamak reactors are considered a limiting factor to successful operation and reliable design. The behavior of plasma-facing components during a disruption is critical to the overall integrity of the reactor. Erosion of plasma facing-material (PFM) surfaces due to thermal energy dump during the disruption can severely limit the lifetime of these components and thus diminish the economic feasibility of the reactor. A comprehensive understanding of the interplay of various physical processes during a disruption is essential for determining component lifetime and potentially improving the performance of such components. There are three principal stages in modeling the behavior of PFM during a disruption. Initially, the incident plasma particles will deposit their energy directly on the PFM surface, heating it to a very high temperature where ablation occurs. Models for plasma-material interactions have been developed and used to predict material thermal evolution during the disruption. Within a few microseconds after the start of the disruption, enough material is vaporized to intercept most of the incoming plasma particles. Models for plasma-vapor interactions are necessary to predict vapor cloud expansion and hydrodynamics. Continuous heating of the vapor cloud above the material surface by the incident plasma particles will excite, ionize, and cause vapor atoms to emit thermal radiation. Accurate models for radiation transport in the vapor are essential for calculating the net radiated flux to the material surface which determines the final erosion thickness and consequently component lifetime. A comprehensive model that takes into account various stages of plasma-material interaction has been developed and used to predict erosion rates during reactor disruption, as well during induced disruption in laboratory experiments

How organisation of architecture documentation affects architectural knowledge retrieval

NARCIS (Netherlands)

de Graaf, K.A.; Liang, P.; Tang, A.; Vliet, J.C.

A common approach to software architecture documentation in industry projects is the use of file-based documents. This approach offers a single-dimensional arrangement of the architectural knowledge. Knowledge retrieval from file-based architecture documentation is efficient if the organisation of

Disrupt mig vel: Fire gode råd om disruption

DEFF Research Database (Denmark)

Rydén, Pernille; Ringberg, Torsten; Østergaard Jacobsen, Per

2017-01-01

Forandring. Ønsket om at være teknologisk foran, kommer ofte til at ske på bekostning af fokus på kundernes oplevelser. Lighedstegnet mellem disruption og ny teknologi er kun den halve sandhed.......Forandring. Ønsket om at være teknologisk foran, kommer ofte til at ske på bekostning af fokus på kundernes oplevelser. Lighedstegnet mellem disruption og ny teknologi er kun den halve sandhed....

Bax/Tubulin/Epithelial-Mesenchymal Pathways Determine the Efficacy of Silybin Analog HM015k in Colorectal Cancer Cell Growth and Metastasis

Directory of Open Access Journals (Sweden)

Haneen Amawi

2018-05-01

Full Text Available The inhibition of apoptosis, disruption of cellular microtubule dynamics, and over-activation of the epithelial mesenchymal transition (EMT, are involved in the progression, metastasis, and resistance of colorectal cancer (CRC to chemotherapy. Therefore, the design of a molecule that can target these pathways could be an effective strategy to reverse CRC progression and metastasis. In this study, twelve novel silybin derivatives, HM015a-HM015k (15a−15k and compound 17, were screened for cytotoxicity in CRC cell lines. Compounds HM015j and HM015k (15k and 15j significantly decreased cell proliferation, inhibited colony formation, and produced cell cycle arrest in CRC cells. Furthermore, 15k significantly induced the formation of reactive oxygen species and apoptosis. It induced the cleavage of the intrinsic apoptotic protein (Bax p21 to its more efficacious fragment, p18. Compound 15k also inhibited tubulin expression and disrupted its structure. Compound 15k significantly decreased metastatic LOVO cell migration and invasion. Furthermore, 15k reversed mesenchymal morphology in HCT116 and LOVO cells. Additionally, 15k significantly inhibited the expression of the mesenchymal marker N-cadherin and upregulated the expression of the epithelial marker, E-cadherin. Compound 15k inhibited the expression of key proteins known to induce EMT (i.e., DVL3, β-catenin, c-Myc and upregulated the anti-metastatic protein, cyclin B1. Overall, in vitro, 15k significantly inhibited CRC progression and metastasis by inhibiting apoptosis, tubulin activity and the EMT pathways. Overall, these data suggest that compound 15k should be tested in vivo in a CRC animal model for further development.

Globoside accelerates the differentiation of dental epithelial cells into ameloblasts

Institute of Scientific and Technical Information of China (English)

Takashi Nakamura; Yuta Chiba; Masahiro Naruse; Kan Saito; Hidemitsu Harada; Satoshi Fukumoto

2016-01-01

Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside (Gb4), a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins (including neurotrophin-4) and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.

Disrupting Business

DEFF Research Database (Denmark)

Cox, Geoff; Bazzichelli, Tatiana

Disruptive Business explores some of the interconnections between art, activism and the business concept of disruptive innovation. With a backdrop of the crisis of financial capitalism, austerity cuts in the cultural sphere, the idea is to focus on potential art strategies in relation to a broken...... economy. In a perverse way, we ask whether this presents new opportunities for cultural producers to achieve more autonomy over their production process. If it is indeed possible, or desirable, what alternative business models emerge? The book is concerned broadly with business as material for reinvention...

Sleep disruption in chronic rhinosinusitis.

Science.gov (United States)

Mahdavinia, Mahboobeh; Schleimer, Robert P; Keshavarzian, Ali

2017-05-01

Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.

Capital Architecture: Situating symbolism parallel to architectural methods and technology

Science.gov (United States)

Daoud, Bassam

Capital Architecture is a symbol of a nation's global presence and the cultural and social focal point of its inhabitants. Since the advent of High-Modernism in Western cities, and subsequently decolonised capitals, civic architecture no longer seems to be strictly grounded in the philosophy that national buildings shape the legacy of government and the way a nation is regarded through its built environment. Amidst an exceedingly globalized architectural practice and with the growing concern of key heritage foundations over the shortcomings of international modernism in representing its immediate socio-cultural context, the contextualization of public architecture within its sociological, cultural and economic framework in capital cities became the key denominator of this thesis. Civic architecture in capital cities is essential to confront the challenges of symbolizing a nation and demonstrating the legitimacy of the government'. In today's dominantly secular Western societies, governmental architecture, especially where the seat of political power lies, is the ultimate form of architectural expression in conveying a sense of identity and underlining a nation's status. Departing with these convictions, this thesis investigates the embodied symbolic power, the representative capacity, and the inherent permanence in contemporary architecture, and in its modes of production. Through a vast study on Modern architectural ideals and heritage -- in parallel to methodologies -- the thesis stimulates the future of large scale governmental building practices and aims to identify and index the key constituents that may respond to the lack representation in civic architecture in capital cities.

Membrane lipidome of an epithelial cell line

DEFF Research Database (Denmark)

Sampaio, Julio L; Gerl, Mathias J; Klose, Christian

2011-01-01

Tissue differentiation is an important process that involves major cellular membrane remodeling. We used Madin-Darby canine kidney cells as a model for epithelium formation and investigated the remodeling of the total cell membrane lipidome during the transition from a nonpolarized morphology...... to an epithelial morphology and vice versa. To achieve this, we developed a shotgun-based lipidomics workflow that enabled the absolute quantification of mammalian membrane lipidomes with minimal sample processing from low sample amounts. Epithelial morphogenesis was accompanied by a major shift from sphingomyelin...... to generate an apical membrane domain that serves as a protective barrier for the epithelial sheet....

Basolateral BMP signaling in polarized epithelial cells.

Directory of Open Access Journals (Sweden)

Masao Saitoh

Full Text Available Bone morphogenetic proteins (BMPs regulate various biological processes, mostly mediated by cells of mesenchymal origin. However, the roles of BMPs in epithelial cells are poorly understood. Here, we demonstrate that, in polarized epithelial cells, BMP signals are transmitted from BMP receptor complexes exclusively localized at the basolateral surface of the cell membrane. In addition, basolateral stimulation with BMP increased expression of components of tight junctions and enhanced the transepithelial resistance (TER, counteracting reduction of TER by treatment with TGF-β or an anti-tumor drug. We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors.

Software architecture evolution

DEFF Research Database (Denmark)

Barais, Olivier; Le Meur, Anne-Francoise; Duchien, Laurence

2008-01-01

Software architectures must frequently evolve to cope with changing requirements, and this evolution often implies integrating new concerns. Unfortunately, when the new concerns are crosscutting, existing architecture description languages provide little or no support for this kind of evolution....... The software architect must modify multiple elements of the architecture manually, which risks introducing inconsistencies. This chapter provides an overview, comparison and detailed treatment of the various state-of-the-art approaches to describing and evolving software architectures. Furthermore, we discuss...... one particular framework named Tran SAT, which addresses the above problems of software architecture evolution. Tran SAT provides a new element in the software architecture descriptions language, called an architectural aspect, for describing new concerns and their integration into an existing...

Conditional expression of the dominant-negative TGF-β receptor type II elicits lingual epithelial hyperplasia in transgenic mice.

Science.gov (United States)

Li, Feng; Zhou, Mingliang

2013-05-01

The transforming growth factor-β (TGF-β) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essential Tgfbr2 gene still maintain normal tissue homeostasis. Here, transgenic mice expressing rtTA from the human keratin 14 (K14) promoter were used to generate an inducible dominant-negative TGF-β receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF-β signaling disruption by Doxycycline treatment in K14+ epithelial stem cells. We showed that in mice lacking TGF-β signaling in K14+ cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF-β signaling. Our results contribute to the understanding of TGF-β signaling in regulating homeostasis and carcinogenesis in lingual epithelia. Copyright © 2013 Wiley Periodicals, Inc.

Architectural design decisions

NARCIS (Netherlands)

Jansen, Antonius Gradus Johannes

2008-01-01

A software architecture can be considered as the collection of key decisions concerning the design of the software of a system. Knowledge about this design, i.e. architectural knowledge, is key for understanding a software architecture and thus the software itself. Architectural knowledge is mostly

Architecture Governance: The Importance of Architecture Governance for Achieving Operationally Responsive Ground Systems

Science.gov (United States)

Kolar, Mike; Estefan, Jeff; Giovannoni, Brian; Barkley, Erik

2011-01-01

Topics covered (1) Why Governance and Why Now? (2) Characteristics of Architecture Governance (3) Strategic Elements (3a) Architectural Principles (3b) Architecture Board (3c) Architecture Compliance (4) Architecture Governance Infusion Process. Governance is concerned with decision making (i.e., setting directions, establishing standards and principles, and prioritizing investments). Architecture governance is the practice and orientation by which enterprise architectures and other architectures are managed and controlled at an enterprise-wide level

An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers.

Science.gov (United States)

Tang, H M; Kuay, K T; Koh, P F; Asad, M; Tan, T Z; Chung, V Y; Lee, S C; Thiery, J P; Huang, Ry-J

2016-01-01

Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality.

Minimalism in architecture: Architecture as a language of its identity

Directory of Open Access Journals (Sweden)

Vasilski Dragana

2012-01-01

Full Text Available Every architectural work is created on the principle that includes the meaning, and then this work is read like an artifact of the particular meaning. Resources by which the meaning is built primarily, susceptible to transformation, as well as routing of understanding (decoding messages carried by a work of architecture, are subject of semiotics and communication theories, which have played significant role for the architecture and the architect. Minimalism in architecture, as a paradigm of the XXI century architecture, means searching for essence located in the irreducible minimum. Inspired use of architectural units (archetypical elements, trough the fatasm of simplicity, assumes the primary responsibility for providing the object identity, because it participates in language formation and therefore in its reading. Volume is form by clean language that builds the expression of the fluid areas liberated of recharge needs. Reduced architectural language is appropriating to the age marked by electronic communications.

Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

Science.gov (United States)

Yu, Kyeong-Nam; Chang, Seung-Hee; Park, Soo Jin; Lim, Joohyun; Lee, Jinkyu; Yoon, Tae-Jong; Kim, Jun-Sung; Cho, Myung-Haing

2015-01-01

Nanomaterials are used in diverse fields including food, cosmetic, and medical industries. Titanium dioxide nanoparticles (TiO2-NP) are widely used, but their effects on biological systems and mechanism of toxicity have not been elucidated fully. Here, we report the toxicological mechanism of TiO2-NP in cell organelles. Human bronchial epithelial cells (16HBE14o-) were exposed to 50 and 100 μg/mL TiO2-NP for 24 and 48 h. Our results showed that TiO2-NP induced endoplasmic reticulum (ER) stress in the cells and disrupted the mitochondria-associated endoplasmic reticulum membranes (MAMs) and calcium ion balance, thereby increasing autophagy. In contrast, an inhibitor of ER stress, tauroursodeoxycholic acid (TUDCA), mitigated the cellular toxic response, suggesting that TiO2-NP promoted toxicity via ER stress. This novel mechanism of TiO2-NP toxicity in human bronchial epithelial cells suggests that further exhaustive research on the harmful effects of these nanoparticles in relevant organisms is needed for their safe application. PMID:26121477

Understanding disruptions in tokamaksa)

Science.gov (United States)

Zakharov, Leonid E.; Galkin, Sergei A.; Gerasimov, Sergei N.; contributors, JET-EFDA

2012-05-01

This paper describes progress achieved since 2007 in understanding disruptions in tokamaks, when the effect of plasma current sharing with the wall was introduced into theory. As a result, the toroidal asymmetry of the plasma current measurements during vertical disruption event (VDE) on the Joint European Torus was explained. A new kind of plasma equilibria and mode coupling was introduced into theory, which can explain the duration of the external kink 1/1 mode during VDE. The paper presents first results of numerical simulations using a free boundary plasma model, relevant to disruptions.

Architectural Narratives

DEFF Research Database (Denmark)

Kiib, Hans

2010-01-01

a functional framework for these concepts, but tries increasingly to endow the main idea of the cultural project with a spatially aesthetic expression - a shift towards “experience architecture.” A great number of these projects typically recycle and reinterpret narratives related to historical buildings......In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... and architectural heritage; another group tries to embed new performative technologies in expressive architectural representation. Finally, this essay provides a theoretical framework for the analysis of the political rationales of these projects and for the architectural representation bridges the gap between...

Studying cytokinesis in Drosophila epithelial tissues.

Science.gov (United States)

Pinheiro, D; Bellaïche, Y

2017-01-01

Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Disrupted resting brain graph measures in individuals at high risk for alcoholism.

Science.gov (United States)

Holla, Bharath; Panda, Rajanikant; Venkatasubramanian, Ganesan; Biswal, Bharat; Bharath, Rose Dawn; Benegal, Vivek

2017-07-30

Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Thyroid effects of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

2012-01-01

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert ...... thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties....

Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers.

Directory of Open Access Journals (Sweden)

Judit Váradi

Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines.

Architecture & Environment

Science.gov (United States)

Erickson, Mary; Delahunt, Michael

2010-01-01

Most art teachers would agree that architecture is an important form of visual art, but they do not always include it in their curriculums. In this article, the authors share core ideas from "Architecture and Environment," a teaching resource that they developed out of a long-term interest in teaching architecture and their fascination with the…

Exporting Humanist Architecture

DEFF Research Database (Denmark)

Nielsen, Tom

2016-01-01

The article is a chapter in the catalogue for the Danish exhibition at the 2016 Architecture Biennale in Venice. The catalogue is conceived at an independent book exploring the theme Art of Many - The Right to Space. The chapter is an essay in this anthology tracing and discussing the different...... values and ethical stands involved in the export of Danish Architecture. Abstract: Danish architecture has, in a sense, been driven by an unwritten contract between the architects and the democratic state and its institutions. This contract may be viewed as an ethos – an architectural tradition...... with inherent aesthetic and moral values. Today, however, Danish architecture is also an export commodity. That raises questions, which should be debated as openly as possible. What does it mean for architecture and architects to practice in cultures and under political systems that do not use architecture...

Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

DEFF Research Database (Denmark)

Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P

2015-01-01

where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine...... single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2......,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant...

Disruption Physics and Mitigation on DIII-D

International Nuclear Information System (INIS)

Whyte, D.G.; Humphreys, D.A.; Kellman, A.G.

2005-01-01

The contributions of the DIII-D tokamak toward the understanding and control of disruptions are reviewed. Disruptions are found to be deterministic, and the underlying causes of disruption can therefore be predicted and avoided. With sufficiently rapid detection, possible damage from disruptions can be mitigated using an understanding of disruption phenomenology and plasma physics. Regimes of high β are readily available in DIII-D and provide access to relatively high energy density disruptions, despite DIII-D's moderate magnetic field and size. DIII-D, with all-graphite wall armor and wall conditioning between discharges, has proven highly resilient to the deleterious effects that disruptions can have on plasma operations. Simultaneously, exploitation and adaptation of DIII-D's extensive core and edge plasma diagnostic set have allowed for unique plasma measurements during disruptions. These measurements have tied into the development of several physical models used to understand aspects of disruptions, such as magnetohydrodynamic growth at the disruption onset, radiation energy balance through the thermal quench, and halo currents during the current quench. Based on this fundamental understanding, DIII-D has developed techniques to mitigate the harmful effects of disruptions by radiative dissipation of the plasma energy and extrapolated these techniques for possible use on larger devices like ITER

Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

Science.gov (United States)

The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

Fragments of Architecture

DEFF Research Database (Denmark)

Bang, Jacob Sebastian

2016-01-01

Topic 3: “Case studies dealing with the artistic and architectural work of architects worldwide, and the ties between specific artistic and architectural projects, methodologies and products”......Topic 3: “Case studies dealing with the artistic and architectural work of architects worldwide, and the ties between specific artistic and architectural projects, methodologies and products”...

Enterprise architecture management

DEFF Research Database (Denmark)

Rahimi, Fatemeh; Gøtze, John; Møller, Charles

2017-01-01

Despite the growing interest in enterprise architecture management, researchers and practitioners lack a shared understanding of its applications in organizations. Building on findings from a literature review and eight case studies, we develop a taxonomy that categorizes applications of enterprise...... architecture management based on three classes of enterprise architecture scope. Organizations may adopt enterprise architecture management to help form, plan, and implement IT strategies; help plan and implement business strategies; or to further complement the business strategy-formation process....... The findings challenge the traditional IT-centric view of enterprise architecture management application and suggest enterprise architecture management as an approach that could support the consistent design and evolution of an organization as a whole....

Enterprise architecture management

DEFF Research Database (Denmark)

Rahimi, Fatemeh; Gøtze, John; Møller, Charles

2017-01-01

architecture management based on three classes of enterprise architecture scope. Organizations may adopt enterprise architecture management to help form, plan, and implement IT strategies; help plan and implement business strategies; or to further complement the business strategy-formation process......Despite the growing interest in enterprise architecture management, researchers and practitioners lack a shared understanding of its applications in organizations. Building on findings from a literature review and eight case studies, we develop a taxonomy that categorizes applications of enterprise....... The findings challenge the traditional IT-centric view of enterprise architecture management application and suggest enterprise architecture management as an approach that could support the consistent design and evolution of an organization as a whole....

Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type AlterationsSummary

Directory of Open Access Journals (Sweden)

Eitaro Aihara

2016-09-01

Full Text Available Background & Aims: The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. Methods: Gastric ulcers were induced in mice by serosal topical application of acetic acid. Results: Gastric ulcers induced by acetic acid visually healed within 30 days. However, regenerated epithelial architecture was poor. The gene profile of regenerated tissue was abnormal, indicating increased stem/progenitor cells, deficient differentiated gastric cell types, and deranged cell homeostasis. Despite up-regulation of PDX1 in the regenerated epithelium, no mature antral cell type was observed. Four months after healing, the regenerated epithelium lacks parietal cells, trefoil factor 2 (TFF2 and (sex-determining region Y-box 9 (SOX9 remain up-regulated deep in the gastric gland, and the Na/H exchanger 2 (a TFF2 effector in gastric healing remains down-regulated. Gastric ulcer healing was strongly delayed in TFF2 knockout mice, and re-epithelialization was accompanied with mucous metaplasia. After Helicobacter pylori inoculum 30 days after ulceration, we observed that the gastric ulcer selectively relapses at the same site where it originally was induced. Follow-up evaluation at 8 months showed that the relapsed ulcer was not healed in H pylori–infected tissues. Conclusions: These findings show that this macroscopically regenerated epithelium has prolonged abnormal cell distribution and is differentially susceptible to subsequent damage by H pylori. Keywords: Gastric Ulcer Healing, Metaplasia, H pylori, SOX9, TFF2, NHE2

No junctional communication between epithelial cells in hydra

DEFF Research Database (Denmark)

de Laat, S W; Tertoolen, L G; Grimmelikhuijzen, C J

1980-01-01

junctions between epithelial cells of hydra. However, until now, there has been no report published on whether these junctions enable the epithelial cells to exchange molecules of small molecular weight, as has been described in other organisms. Therefore we decided to investigate the communicative...... properties of the junctional membranes by electrophysiological methods and by intracellular-dye iontophoresis. We report here that no electrotonic coupling is detectable between epithelial cells of Hydra attenuata in: (1) intact animals, (2) head-regenerating animals, (3) cell re-aggregates, and (4) hydra...

Modeling Architectural Patterns’ Behavior Using Architectural Primitives

NARCIS (Netherlands)

Waqas Kamal, Ahmad; Avgeriou, Paris

2008-01-01

Architectural patterns have an impact on both the structure and the behavior of a system at the architecture design level. However, it is challenging to model patterns’ behavior in a systematic way because modeling languages do not provide the appropriate abstractions and because each pattern

Space and Architecture's Current Line of Research? A Lunar Architecture Workshop With An Architectural Agenda.

Science.gov (United States)

Solomon, D.; van Dijk, A.

The "2002 ESA Lunar Architecture Workshop" (June 3-16) ESTEC, Noordwijk, NL and V2_Lab, Rotterdam, NL) is the first-of-its-kind workshop for exploring the design of extra-terrestrial (infra) structures for human exploration of the Moon and Earth-like planets introducing 'architecture's current line of research', and adopting an architec- tural criteria. The workshop intends to inspire, engage and challenge 30-40 European masters students from the fields of aerospace engineering, civil engineering, archi- tecture, and art to design, validate and build models of (infra) structures for Lunar exploration. The workshop also aims to open up new physical and conceptual terrain for an architectural agenda within the field of space exploration. A sound introduc- tion to the issues, conditions, resources, technologies, and architectural strategies will initiate the workshop participants into the context of lunar architecture scenarios. In my paper and presentation about the development of the ideology behind this work- shop, I will comment on the following questions: * Can the contemporary architectural agenda offer solutions that affect the scope of space exploration? It certainly has had an impression on urbanization and colonization of previously sparsely populated parts of Earth. * Does the current line of research in architecture offer any useful strategies for com- bining scientific interests, commercial opportunity, and public space? What can be learned from 'state of the art' architecture that blends commercial and public pro- grammes within one location? * Should commercial 'colonisation' projects in space be required to provide public space in a location where all humans present are likely to be there in a commercial context? Is the wave in Koolhaas' new Prada flagship store just a gesture to public space, or does this new concept in architecture and shopping evolve the public space? * What can we learn about designing (infra-) structures on the Moon or any other

Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism.

Directory of Open Access Journals (Sweden)

Xiling Liu

2016-09-01

Full Text Available Cognitive defects in autism spectrum disorder (ASD include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans.

Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

Science.gov (United States)

Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

2016-01-01

Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

The role of Sox2 on lung epithelial airway epithelial differentiation

NARCIS (Netherlands)

J.K. Ochieng (Joshua)

2014-01-01

markdownabstract__Abstract__ The foregut is crucial for development of respiratory organs including the lungs. Foregut morphogenesis starts around embryonic day 8.0 in mouse when the endoderm epithelial sheet folds ventrally during gastrulation [1,2]. At embryonic day 9.0, the ventral folding

Disruptive innovation as an entrepreneurial process

NARCIS (Netherlands)

Chandra, Y.; Yang, S.-J.S.; Singh, P.; Prajogo, D.; O'Neill, P.; Rahman, S.

2008-01-01

Research on conditions and causal mechanisms that influence disruptive innovation has been relatively unexplored in the extant research in disruptive innovation. By re-conceptualizing disruptive innovation as an entrepreneurial process at product, firm and industry levels, this paper draws on

Automatic location of disruption times in JET

Science.gov (United States)

Moreno, R.; Vega, J.; Murari, A.

2014-11-01

The loss of stability and confinement in tokamak plasmas can induce critical events known as disruptions. Disruptions produce strong electromagnetic forces and thermal loads which can damage fundamental components of the devices. Determining the disruption time is extremely important for various disruption studies: theoretical models, physics-driven models, or disruption predictors. In JET, during the experimental campaigns with the JET-C (Carbon Fiber Composite) wall, a common criterion to determine the disruption time consisted of locating the time of the thermal quench. However, with the metallic ITER-like wall (JET-ILW), this criterion is usually not valid. Several thermal quenches may occur previous to the current quench but the temperature recovers. Therefore, a new criterion has to be defined. A possibility is to use the start of the current quench as disruption time. This work describes the implementation of an automatic data processing method to estimate the disruption time according to this new definition. This automatic determination allows both reducing human efforts to locate the disruption times and standardizing the estimates (with the benefit of being less vulnerable to human errors).

Automatic location of disruption times in JET.

Science.gov (United States)

Moreno, R; Vega, J; Murari, A

2014-11-01

The loss of stability and confinement in tokamak plasmas can induce critical events known as disruptions. Disruptions produce strong electromagnetic forces and thermal loads which can damage fundamental components of the devices. Determining the disruption time is extremely important for various disruption studies: theoretical models, physics-driven models, or disruption predictors. In JET, during the experimental campaigns with the JET-C (Carbon Fiber Composite) wall, a common criterion to determine the disruption time consisted of locating the time of the thermal quench. However, with the metallic ITER-like wall (JET-ILW), this criterion is usually not valid. Several thermal quenches may occur previous to the current quench but the temperature recovers. Therefore, a new criterion has to be defined. A possibility is to use the start of the current quench as disruption time. This work describes the implementation of an automatic data processing method to estimate the disruption time according to this new definition. This automatic determination allows both reducing human efforts to locate the disruption times and standardizing the estimates (with the benefit of being less vulnerable to human errors).

Search and Disrupt

DEFF Research Database (Denmark)

Ørding Olsen, Anders

. However, incumbent sources engaged in capability reconfiguration to accommodate disruption improve search efforts in disruptive technologies. The paper concludes that the value of external sources is contingent on more than their knowledge. Specifically, interdependence of sources in search gives rise...... to influence from individual strategic interests on the outcomes. More generally, this points to the need for understanding the two-way influence of sources, rather than viewing external search as one-way knowledge accessing....

Surgical management of anterior chamber epithelial cysts.

Science.gov (United States)

Haller, Julia A; Stark, Walter J; Azab, Amr; Thomsen, Robert W; Gottsch, John D

2003-03-01

To review management strategies for treatment of anterior chamber epithelial cysts. Retrospective review of consecutive interventional case series. Charts of patients treated for epithelial ingrowth over a 10-year period by a single surgeon were reviewed. Cases of anterior chamber epithelial cysts were identified and recorded, including details of ocular history, preoperative and postoperative acuity, intraocular pressure (IOP), and ocular examination, type of surgical intervention, and details of further procedures performed. Seven eyes with epithelial cysts were identified. Patient age ranged from 1.5 to 53 years at presentation. Four patients were children. In four eyes, cysts were secondary to trauma, one case was presumably congenital, one case developed after corneal perforation in an eye with Terrien's marginal degeneration, and one case developed after penetrating keratoplasty (PK). Three eyes were treated with vitrectomy, en bloc resection of the cyst and associated tissue, fluid-air exchange and cryotherapy. The last four eyes were treated with a new conservative strategy of cyst aspiration (three cases) or local excision (one keratin "pearl" cyst), and endolaser photocoagulation of the collapsed cyst wall/base. All epithelial tissue was successfully eradicated by clinical criteria; one case required repeat excision (follow-up, 9 to 78 months, mean 45). Two eyes required later surgery for elevated IOP, two for cataract extraction and one for repeat PK. Final visual acuity ranged from 20/20 to hand motions, depending on associated ocular damage. Best-corrected visual results were obtained in the more conservatively managed eyes. Anterior chamber epithelial cysts can be managed conservatively in selected cases with good results. This strategy may be particularly useful in children's eyes, where preservation of the lens, iris, and other structures may facilitate amblyopia management. Copyright 2003 by Elsevier Science Inc.

Epithelial-Mesenchymal Transition in Tissue Repair and Fibrosis

Science.gov (United States)

Stone, Rivka C.; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I.; Tomic-Canic, Marjana

2016-01-01

Epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics which confer migratory capacity. EMT and its converse, MET (mesenchymal-to-epithelial transition), are integral stages of many physiologic processes, and as such are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes - the resident skin epithelial cells - migrate across the wound bed to restore the epidermal barrier. Moreover, EMT also plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblast arises from cells of epithelial lineage in response to injury but is pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the impaired repair of fibrotic wounds may identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. PMID:27461257

Human papillomavirus: cause of epithelial lacrimal sac neoplasia?

DEFF Research Database (Denmark)

Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia

2007-01-01

PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....

Pursuing minimally disruptive medicine: disruption from illness and health care-related demands is correlated with patient capacity.

Science.gov (United States)

Boehmer, Kasey R; Shippee, Nathan D; Beebe, Timothy J; Montori, Victor M

2016-06-01

Chronic conditions burden patients with illness and treatments. We know little about the disruption of life by the work of dialysis in relation to the resources patients can mobilize, that is, their capacity, to deal with such demands. We sought to determine the disruption of life by dialysis and its relation to patient capacity to cope. We administered a survey to 137 patients on dialysis at an academic medical center. We captured disruption from illness and treatment, and physical, mental, personal, social, financial, and environmental aspects of patient capacity using validated scales. Covariates included number of prescriptions, hours spent on health care, existence of dependents, age, sex, and income level. On average, patients reported levels of capacity and disruption comparable to published levels. In multivariate regression models, limited physical, financial, and mental capacity were significantly associated with greater disruption. Patients in the top quartile of disruption had lower-than-expected physical, financial, and mental capacity. Our sample generally had capacity comparable to other populations and may be able to meet the demands imposed by treatment. Those with reduced physical, financial, and mental capacity reported higher disruption and represent a vulnerable group that may benefit from innovations in minimally disruptive medicine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Methodical Design of Software Architecture Using an Architecture Design Assistant (ArchE)

Science.gov (United States)

2005-04-01

PA 15213-3890 Methodical Design of Software Architecture Using an Architecture Design Assistant (ArchE) Felix Bachmann and Mark Klein Software...DATES COVERED 00-00-2005 to 00-00-2005 4. TITLE AND SUBTITLE Methodical Design of Software Architecture Using an Architecture Design Assistant...important for architecture design – quality requirements and constraints are most important Here’s some evidence: If the only concern is

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

Science.gov (United States)

Fung, Camille M; White, Jessica R; Brown, Ashley S; Gong, Huiyu; Weitkamp, Jörn-Hendrik; Frey, Mark R; McElroy, Steven J

2016-01-01

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

Directory of Open Access Journals (Sweden)

W. Cui

2010-04-01

Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

Sleep architecture, insulin resistance and the nasal cycle: Implications for positive airway pressure therapy

Directory of Open Access Journals (Sweden)

Catherine A.P. Crofts

2018-03-01

Full Text Available Background: The global pandemic of metabolic disease is worsening. The metabolic theory of obesity proposes that hormonal changes, especially hyperinsulinaemia, precede metabolic disease development. Although quality sleep is recognised as a key factor for good health, less is known about disrupted sleep as a risk factor for hyperinsulinaemia.   Aim: To explore the relationship between sleep, especially sleep architecture and the nasal cycle, on insulin secretion in obstructive sleep apnoea (OSA with comorbid metabolic disease. This review includes a discussion of the potential role of Rest-Activity-Cycler positive airway pressure (RACer-PAP, a novel non-pharmacological OSA treatment strategy.   Methods: A narrative review of all the relevant papers known to the authors was conducted. This review also included results from a polysomnographic sleep clinic pilot study (n = 3 comparing sleep efficiency of RACer-PAP to nasal continuous positive airways pressure (n-CPAP in OSA patients.   Results: Metabolic disease is strongly associated with disturbed sleep. Sleep architecture influences cerebral hormonal secretion, lateral shifts in the autonomic nervous system and nasal airflow dominance. Disturbed sleep shortens short-wave sleep periods, decreasing insulin sensitivity and glucose tolerance. Improvements to metabolic function during n-CPAP treatment are inconsistent. If RACer-PAP demonstrates superior effects on sleep architecture and autonomic function, it may offer advantages in OSA patients with comorbid metabolic disease.   Conclusion: Improving sleep architecture by maintaining the nasal cycle proposes a novel non-pharmacological treatment paradigm for treating OSA with comorbid metabolic disease. Research is required to demonstrate if RACer-PAP therapy influences whole night sleep architecture, sympathovagal balance and markers of metabolic disease.

Molecular Characterization of Gastric Epithelial Cells Using Flow Cytometry

Directory of Open Access Journals (Sweden)

Kevin A. Bockerstett

2018-04-01

Full Text Available The ability to analyze individual epithelial cells in the gastric mucosa would provide important insight into gastric disease, including chronic gastritis and progression to gastric cancer. However, the successful isolation of viable gastric epithelial cells (parietal cells, neck cells, chief cells, and foveolar cells from gastric glands has been limited due to difficulties in tissue processing. Furthermore, analysis and interpretation of gastric epithelial cell flow cytometry data has been difficult due to the varying sizes and light scatter properties of the different epithelial cells, high levels of autofluorescence, and poor cell viability. These studies were designed to develop a reliable method for isolating viable single cells from the corpus of stomachs and to optimize analyses examining epithelial cells from healthy and diseased stomach tissue by flow cytometry. We performed a two stage enzymatic digestion in which collagenase released individual gastric glands from the stromal tissue of the corpus, followed by a Dispase II digestion that dispersed these glands into greater than 1 × 106 viable single cells per gastric corpus. Single cell suspensions were comprised of all major cell lineages found in the normal gastric glands. A method describing light scatter, size exclusion, doublet discrimination, viability staining, and fluorescently-conjugated antibodies and lectins was used to analyze individual epithelial cells and immune cells. This technique was capable of identifying parietal cells and revealed that gastric epithelial cells in the chronically inflamed mucosa significantly upregulated major histocompatibility complexes (MHC I and II but not CD80 or CD86, which are costimulatory molecules involved in T cell activation. These studies describe a method for isolating viable single cells and a detailed description of flow cytometric analysis of cells from healthy and diseased stomachs. These studies begin to identify effects of

Proliferation and Polarity in Breast Cancer: Untying the GordianKnot

Energy Technology Data Exchange (ETDEWEB)

Liu, Hong; Radisky, Derek C.; Bissell, Mina J.

2005-05-09

Epithelial cancers are associated with genomic instability and alterations in signaling pathways that affect proliferation, apoptosis, and integrity of tissue structure. Overexpression of a number of oncogenic protein kinases has been shown to malignantly transform cells in culture and to cause tumors in vivo, but the interconnected signaling events induced by transformation still awaits detailed dissection. We propose that the network of cellular signaling pathways can be classified into functionally distinct branches, and that these pathways are rewired in transformed cells and tissues after they lose tissue-specific architecture to favor tumor expansion and invasion. Using three-dimensional (3D) culture systems, we recently demonstrated that polarity and proliferation of human mammary epithelial cancer cells were separable consequences of signaling pathways downstream of PI3 kinase.These, and results from a number of other laboratories are beginning to provide insight into how different signaling pathways may become interconnected in normal tissues to allow homeostasis, and how they are disrupted during malignant progression.

Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells.

Science.gov (United States)

Liu, Yuan; Kamesh, Aditya C; Xiao, Yuhong; Sun, Victor; Hayes, Michael; Daniell, Henry; Koo, Hyun

2016-10-01

Protein drugs (PD) are minimally utilized in dental medicine due to high cost and invasive surgical delivery. There is limited clinical advancement in disrupting virulent oral biofilms, despite their high prevalence in causing dental caries. Poor efficacy of antimicrobials following topical treatments or to penetrate and disrupt formed biofilms is a major challenge. We report an exciting low-cost approach using plant-made antimicrobial peptides (PMAMPs) retrocyclin or protegrin with complex secondary structures (cyclic/hairpin) for topical use to control biofilms. The PMAMPs rapidly killed the pathogen Streptococcus mutans and impaired biofilm formation following a single topical application of tooth-mimetic surface. Furthermore, we developed a synergistic approach using PMAMPs combined with matrix-degrading enzymes to facilitate their access into biofilms and kill the embedded bacteria. In addition, we identified a novel role for PMAMPs in delivering drugs to periodontal and gingival cells, 13-48 folds more efficiently than any other tested cell penetrating peptides. Therefore, PDs fused with protegrin expressed in plant cells could potentially play a dual role in delivering therapeutic proteins to gum tissues while killing pathogenic bacteria when delivered as topical oral formulations or in chewing gums. Recent FDA approval of plant-produced PDs augurs well for clinical advancement of this novel concept. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Architectural freedom and industrialised architecture

DEFF Research Database (Denmark)

Vestergaard, Inge

2012-01-01

to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...... to this systematic thinking of the building technique we get a diverse and functional architecture. Creating a new and clearer story telling about new and smart system based thinking behind the architectural expression....

Preemptive Architecture: Explosive Art and Future Architectures in Cursed Urban Zones

Directory of Open Access Journals (Sweden)

Stahl Stenslie

2017-04-01

Full Text Available This article describes the art and architectural research project Preemptive Architecture that uses artistic strategies and approaches to create bomb-ready architectural structures that act as instruments for the undoing of violence in war. Increasing environmental usability through destruction represents an inverse strategy that reverses common thinking patterns about warfare, art and architecture. Building structures predestined for a construc­tive destruction becomes a creative act. One of the main motivations behind this paper is to challenge and expand the material thinking as well as the socio-political conditions related to artistic, architectural and design based practices.   Article received: December 12, 2016; Article accepted: January 10, 2017; Published online: April 20, 2017 Original scholarly paper How to cite this article: Stenslie, Stahl, and Magne Wiggen. "Preemptive Architecture: Explosive Art and Future Architectures in Cursed Urban Zones." AM Journal of Art and Media Studies 12 (2017: 29-39. doi: 10.25038/am.v0i12.165

Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.

Science.gov (United States)

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Nakamura, Ryosuke; Otsuki, Koshi; Murono, Shigeyuki; Omori, Koichi

2017-07-01

Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

Enterprise architecture patterns practical solutions for recurring IT-architecture problems

CERN Document Server

Perroud, Thierry

2013-01-01

Every enterprise architect faces similar problems when designing and governing the enterprise architecture of a medium to large enterprise. Design patterns are a well-established concept in software engineering, used to define universally applicable solution schemes. By applying this approach to enterprise architectures, recurring problems in the design and implementation of enterprise architectures can be solved over all layers, from the business layer to the application and data layer down to the technology layer.Inversini and Perroud describe patterns at the level of enterprise architecture

Structured Literature Review of digital disruption literature

DEFF Research Database (Denmark)

Vesti, Helle; Rosenstand, Claus Andreas Foss; Gertsen, Frank

2018-01-01

Digital disruption is a term/phenomenon frequently appearing in innovation management literature. However, no academic consensus exists as to what it entails; conceptual nor theoretical. We use the SLR-method (Structured Literature Review) to investigate digital disruption literature. A SLR......-study conducted in 2017 revealed some useful information on how disruption and digital disruption literature has developed over a specific period. However, this study was less representative of papers addressing digital disruption; which is the in-depth subject of this paper. To accommodate this, we intend...... to conduct a similar SLR-study assembling a body literature having digital disruption as the only common denominator...

Mechanistic evaluation of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Taxvig, Camilla

BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects.......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

MUF architecture /art London

DEFF Research Database (Denmark)

Svenningsen Kajita, Heidi

2009-01-01

Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art......Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art...

Epithelial cell-cell junctions and plasma membrane domains

NARCIS (Netherlands)

Giepmans, Ben N. G.; van Ijzendoorn, Sven C. D.

Epithelial cells form a barrier against the environment, but are also required for the regulated exchange of molecules between an organism and its surroundings. Epithelial cells are characterised by a remarkable polarization of their plasma membrane, evidenced by the appearance of structurally,

Stromal Adipocyte Enhancer-binding Protein (AEBP1) Promotes Mammary Epithelial Cell Hyperplasia via Proinflammatory and Hedgehog Signaling*

Science.gov (United States)

Holloway, Ryan W.; Bogachev, Oleg; Bharadwaj, Alamelu G.; McCluskey, Greg D.; Majdalawieh, Amin F.; Zhang, Lei; Ro, Hyo-Sung

2012-01-01

Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1TG) mice, and the onset of ductal hyperplasia was accelerated in AEBP1TG mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1TG bone marrow cells into non-transgenic (AEBP1NT) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1TG mammary macrophages and epithelium. Shh expression was induced in AEBP1TG macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1TG mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1TG peritoneal macrophages. The conditioned AEBP1TG macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1TG macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis. PMID:22995915

Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.

Science.gov (United States)

Holloway, Ryan W; Bogachev, Oleg; Bharadwaj, Alamelu G; McCluskey, Greg D; Majdalawieh, Amin F; Zhang, Lei; Ro, Hyo-Sung

2012-11-09

Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT)) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1(TG) mammary macrophages and epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG) macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1(TG) macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis.

The Role of Cell Surface Architecture of Lactobacilli in Host-Microbe Interactions in the Gastrointestinal Tract

Directory of Open Access Journals (Sweden)

Ranjita Sengupta

2013-01-01

Full Text Available Lactobacillus species can exert health promoting effects in the gastrointestinal tract (GIT through many mechanisms, which include pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Different species of the genus Lactobacillus can evoke different responses in the host, and not all strains of the same species can be considered beneficial. Strain variations may be related to diversity of the cell surface architecture of lactobacilli and the bacteria's ability to express certain surface components or secrete specific compounds in response to the host environment. Lactobacilli are known to modify their surface structures in response to stress factors such as bile and low pH, and these adaptations may help their survival in the face of harsh environmental conditions encountered in the GIT. In recent years, multiple cell surface-associated molecules have been implicated in the adherence of lactobacilli to the GIT lining, immunomodulation, and protective effects on intestinal epithelial barrier function. Identification of the relevant bacterial ligands and their host receptors is imperative for a better understanding of the mechanisms through which lactobacilli exert their beneficial effects on human health.

Epidermal growth factor in alkali-burned corneal epithelial wound healing.

Science.gov (United States)

Singh, G; Foster, C S

1987-06-15

We conducted a double-masked study to evaluate the effect of epidermal growth factor on epithelial wound healing and recurrent erosions in alkali-burned rabbit corneas. Epithelial wounds 10 mm in diameter healed completely under the influence of topical epidermal growth factor, whereas the control corneas did not resurface in the center. On reversal of treatment, the previously nonhealing epithelial defects healed when treated with topical epidermal growth factor eyedrops. Conversely, the epidermal growth factor-treated and resurfaced corneas developed epithelial defects when treatment was discontinued. Histopathologic examination disclosed hyperplastic epithelium growing over the damaged stroma laden with polymorphonuclear leukocytes when treated with epidermal growth factor eyedrops, but it did not adhere to the underlying tissue. Hydropic changes were seen intracellularly as well as between the epithelial cells and the stroma.

Overview of core disruptive accidents

International Nuclear Information System (INIS)

Marchaterre, J.F.

1977-01-01

An overview of the analysis of core-disruptive accidents is given. These analyses are for the purpose of understanding and predicting fast reactor behavior in severe low probability accident conditions, to establish the consequences of such conditions and to provide a basis for evaluating consequence limiting design features. The methods are used to analyze core-disruptive accidents from initiating event to complete core disruption, the effects of the accident on reactor structures and the resulting radiological consequences are described

VERNACULAR ARCHITECTURE: AN INTRODUCTORY COURSE TO LEARN ARCHITECTURE IN INDIA

Directory of Open Access Journals (Sweden)

Miki Desai

2010-07-01

Full Text Available “The object in view of both my predecessors in office and by myself has been rather to bring out the reasoning powers of individual students, so that they may understand the inner meaning of the old forms and their original function and may develop and modernize and gradually produce an architecture, Indian in character, but at the same time as suited to present day India as the old styles were to their own times and environment.” Claude Batley-1940; Lang, Desai, Desai, 1997 (p.143. The article introduces teaching philosophy, content and method of Basic Design I and II for first year students of architecture at the Faculty of Architecture, Centre for Environmental Planning and Technology (CEPT University, Ahmedabad, India. It is framed within the Indian perspective of architectural education from the British colonial times. Commencing with important academic literature and biases of the initial colonial period, it quickly traces architectural education in CEPT, the sixteenth school of post-independent India, set up in 1962, discussing the foundation year teaching imparted. The school was Modernist and avant-garde. The author introduced these two courses against the back drop of the Universalist Modernist credo of architecture and education. In the courses, the primary philosophy behind learning design emerges from heuristic method. The aim of the first course is seen as infusing interest in visual world, development of manual skills and dexterity through the dictum of ‘Look-feel-reason out-evaluate’ and ‘observe-record-interpret-synthesize transform express’. Due to the lack of architectural orientation in Indian schooling; the second course assumes vernacular architecture as a reasonable tool for a novice to understand the triangular relationship of society, architecture and physical context and its impact on design. The students are analytically exposed to the regional variety of architectures logically stemming from the geo

Cytokine Tuning of Intestinal Epithelial Function

Directory of Open Access Journals (Sweden)

Caroline Andrews

2018-06-01

Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

Architecture Descriptions. A Contribution to Modeling of Production System Architecture

DEFF Research Database (Denmark)

Jepsen, Allan Dam; Hvam, Lars

a proper understanding of the architecture phenomenon and the ability to describe it in a manner that allow the architecture to be communicated to and handled by stakeholders throughout the company. Despite the existence of several design philosophies in production system design such as Lean, that focus...... a diverse set of stakeholder domains and tools in the production system life cycle. To support such activities, a contribution is made to the identification and referencing of production system elements within architecture descriptions as part of the reference architecture framework. The contribution...

Disruption studies in ASDEX Upgrade

International Nuclear Information System (INIS)

Pautasso, G.

2002-01-01

Disruption generate large thermal and mechanical stresses on the tokamak components. For a future reactor disruptions have a significant impact on the design since all loading conditions must be analyzed in accordance with stricter design criteria (due to safety or difficult maintenance). Therefore the uncertainties affecting the predicted stresses must be reduced as much as possible with a more comprehensive set of measurements and analyses in this generation of experimental machines, and avoidance/ predictive methods must be developed further. The study of disruptions on ASDEX Upgrade is focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon and learning to avoid it or to predict its occurrence (with neural networks, for example) and to mitigate its effects; (2) analyzing the effects of disruptions on the machine to determine the functional dependence of the thermal and mechanical loads upon the discharge parameters. This allows to dimension or reinforce the machine components to withstand these loads and to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions. (author)

Physiological regulation of epithelial sodium channel by proteolysis

DEFF Research Database (Denmark)

Svenningsen, Per; Friis, Ulla G; Bistrup, Claus

2011-01-01

PURPOSE OF REVIEW: Activation of epithelial sodium channel (ENaC) by proteolysis appears to be relevant for day-to-day physiological regulation of channel activity in kidney and other epithelial tissues. Pathophysiogical, proteolytic activation of ENaC in kidney has been demonstrated in proteinuric...

Disruptive event analysis: volcanism and igneous intrusion

International Nuclear Information System (INIS)

Crowe, B.M.

1979-01-01

Three basic topics are addressed for the disruptive event analysis: first, the range of disruptive consequences of a radioactive waste repository by volcanic activity; second, the possible reduction of the risk of disruption by volcanic activity through selective siting of a repository; and third, the quantification of the probability of repository disruption by volcanic activity

Routine Responses to Disruption of Routines

Science.gov (United States)

Guha, Mahua

2015-01-01

"Organisational routines" is a widely studied research area. However, there is a dearth of research on disruption of routines. The few studies on disruption of routines discussed problem-solving activities that are carried out in response to disruption. In contrast, this study develops a theory of "solution routines" that are a…

Quantitative analysis of epithelial cells in urine from men with and without urethritis: implications for studying epithelial: pathogen interactions in vivo

Directory of Open Access Journals (Sweden)

Whittington Kate

2009-07-01

Full Text Available Abstract Background Epithelial cells in first catch urine (FCU specimens from 87 men with and without urethritis were quantified. Epithelial cells were broadly categorised into transitional and squamous populations using morphological characteristics and immunostaining with anti-pan leukocyte and anti-cytokeratin monoclonal antibodies. Findings The majority (77/87 = 89% of samples contained both transitional (76/87 = 87%; range 1 × 104 – 6 × 105, median 6 × 104 and squamous (57/87 = 66%; range 1 × 104 – 8 × 105, median 2 × 104 epithelial cells. The number of transitional cells correlated with the number of squamous cells (Spearman's rho = 0.697 p Conclusion Further studies are required to explore the complexity of epithelial cell populations in urine. These would provide novel opportunities for studying cellular interactions of C. trachomatis in male urethral infections, about which little is currently known.

Epithelial-mesenchymal transition in tissue repair and fibrosis.

Science.gov (United States)

Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

2016-09-01

The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

Rabbit uterine epithelial cells: Co-culture with spermatozoa

International Nuclear Information System (INIS)

Boice, M.L.

1988-01-01

A primary culture of rabbit uterine epithelial cells was established and their effects on sperm function were examined in vitro. Epithelial cells were isolated from uteri of estrous rabbits and cultured on floating collagen gels in phenol red-free medium supplemented with 5% fetal bovine serum. Light microscopy and keratin staining showed that the epithelial cell population established in culture had morphological characteristics similar to that seen in the intact endometrium. Cells were cultured with 3 H-leucine and uptake of label by cells and its incorporation into cellular and secretory proteins determined. When compared to cells cultured for 24-48 h, incorporation of label into cellular protein was lower at 72-96 h, but secretion increased. Estradiol 17-β did not affect label uptake or incorporation, but did enhance proliferation of cells as judged by total DNA content of the cell population. Analysis of proteins in media by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography suggested that epithelial and stromal cells synthesis proteins that may be secretory in nature during 72-96 h culture. Twenty-nine to thirty-one h after initiation of epithelial cultures, 1-2 x 10 6 sperm were co-incubated with cells and sperm viability, motility, loss of acrosome and fertilizing ability determined

Subtotal Ablation of Parietal Epithelial Cells Induces Crescent Formation

Science.gov (United States)

Sicking, Eva-Maria; Fuss, Astrid; Uhlig, Sandra; Jirak, Peggy; Dijkman, Henry; Wetzels, Jack; Engel, Daniel R.; Urzynicok, Torsten; Heidenreich, Stefan; Kriz, Wilhelm; Kurts, Christian; Ostendorf, Tammo; Floege, Jürgen; Smeets, Bart

2012-01-01

Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established an inducible transgenic mouse to allow subtotal ablation of PECs. Proteinuria developed during doxycycline-induced cellular ablation but fully reversed 26 days after termination of doxycycline administration. The ablation of PECs was focal, with only 30% of glomeruli exhibiting histologic changes; however, the number of PECs was reduced up to 90% within affected glomeruli. Ultrastructural analysis revealed disruption of PEC plasma membranes with cytoplasm shedding into Bowman’s space. Podocytes showed focal foot process effacement, which was the most likely cause for transient proteinuria. After >9 days of cellular ablation, the remaining PECs formed cellular extensions to cover the denuded Bowman’s capsule and expressed the activation marker CD44 de novo. The induced proliferation of PECs persisted throughout the observation period, resulting in the formation of typical cellular crescents with periglomerular infiltrate, albeit without accompanying proteinuria. In summary, subtotal ablation of PECs leads the remaining PECs to react with cellular activation and proliferation, which ultimately forms cellular crescents. PMID:22282596

The disruption management model.

Science.gov (United States)

McAlister, James

2011-10-01

Within all organisations, business continuity disruptions present a set of dilemmas that managers may not have dealt with before in their normal daily duties. The disruption management model provides a simple but effective management tool to enable crisis management teams to stay focused on recovery in the midst of a business continuity incident. The model has four chronological primary headlines, which steer the team through a quick-time crisis decision-making process. The procedure facilitates timely, systematic, rationalised and justified decisions, which can withstand post-event scrutiny. The disruption management model has been thoroughly tested within an emergency services environment and is proven to significantly support clear and concise decision making in a business continuity context.

Sustainable Disruption Management

DEFF Research Database (Denmark)

Vaaben, Bo Valdemar

The world we live in is globalized. Goods are seldom made in the place where they are used or consumed, and we do increasingly travel to other countries for either business or pleasure. In our everyday lives we rely on well-functioning global transportations systems to continue the standard...... in the same way, when operation is disrupted. Never the less, we may recall that the Suez Canal was closed due to riots in Egypt, that the fuel price was impacted by threats of closing of the Strait of Hormuz, and we do from time to time hear about acts of piracy outside the coast of Somalia. All...... papers combining disruption management and flight planning through an integrated optimization approach. An additional contribution of the thesis is to show how flexible flight speeds can be used to improve recovery from disruptions, while at the same time allowing an airline to trade off fuel costs...

Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion

International Nuclear Information System (INIS)

Man, Yan-gao; Vinh, Tuyethoa N; Strauss, Brian L; Tai, Lisa; Barner, Ross; Vang, Russell; Saenger, Jeffrey S; Shekitka, Kris M; Bratthauer, Gary L; Wheeler, Darren T; Liang, Chang Y

2003-01-01

Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale. Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by ≥ 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability. Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers. Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation

Nuclear magnetic resonance studies of epithelial metabolism and function

International Nuclear Information System (INIS)

Balaban, R.S.

1982-01-01

Nuclear magnetic resonance (NMR) is a noninvasive technique for studying cellular metabolism and function. In this review the general applications and advantages of NMR will be discussed with specific reference to epithelial tissues. Phosphorus NMR investigations have been performed on epithelial tissues in vivo and in vitro; however, other detectable nuclei have not been utilized to date. Several new applications of phosphorus NMR to epithelial tissues are also discussed, including studies on isolated renal tubules and sheet epithelia

Architecture and Film

OpenAIRE

Mohammad Javaheri, Saharnaz

2016-01-01

Film does not exist without architecture. In every movie that has ever been made throughout history, the cinematic image of architecture is embedded within the picture. Throughout my studies and research, I began to see that there is no director who can consciously or unconsciously deny the use of architectural elements in his or her movies. Architecture offers a strong profile to distinguish characters and story. In the early days, films were shot in streets surrounde...

Hertwig’s Epithelial Root Sheath Fate during Initial Cellular Cementogenesis in Rat Molars

International Nuclear Information System (INIS)

Yamamoto, Tsuneyuki; Yamada, Tamaki; Yamamoto, Tomomaya; Hasegawa, Tomoka; Hongo, Hiromi; Oda, Kimimitsu; Amizuka, Norio

2015-01-01

To elucidate the fate of the epithelial root sheath during initial cellular cementogenesis, we examined developing maxillary first molars of rats by immunohistochemistry for keratin, vimentin, and tissue non-specific alkaline phosphatase (TNALP) and by TdT-mediated dUTP nick end labeling (TUNEL). The advancing root end was divided into three sections, which follow three distinct stages of initial cellular cementogenesis: section 1, where the epithelial sheath is intact; section 2, where the epithelial sheath becomes fragmented; and section 3, where initial cellular cementogenesis begins. After fragmentation of the epithelial sheath, many keratin-positive epithelial sheath cells were embedded in the rapidly growing cellular cementum. A few unembedded epithelial cells located on the cementum surface. Dental follicle cells, precementoblasts, and cementoblasts showed immunoreactivity for vimentin and TNALP. In all three sections, there were virtually no cells possessing double immunoreactivity for vimentin-keratin or TNALP-keratin and only embedded epithelial cells showed TUNEL reactivity. Taken together, these findings suggest that: (1) epithelial sheath cells divide into two groups; one group is embedded in the cementum and thereafter dies by apoptosis, and the other survives on the cementum surface as epithelial cell rests of Malassez; and (2) epithelial sheath cells do not undergo epithelial-mesenchymal transition during initial cellular cementogenesis

Disruption and Distinctiveness in Higher Education

Science.gov (United States)

Purcell, Wendy

2014-01-01

"Disruption"--while an evocative word triggering feelings of anxiety and perhaps even fear--also signals renewal and growth. The Higher Education (HE) sector in England has experienced some profound disruption over the years, and yet has emerged stronger and renewed in many ways. The impact of recent disruptive forces, from fees to the…

Immunohistochemical Expression of MCM-2 in Oral Epithelial Dysplasias.

Science.gov (United States)

Zakaria, Samar H; Farag, Heba A; Khater, Dina S

2016-03-17

Oral cancer is one of the most frequent cancers in the world. It arises from epithelial dysplasia. Hence, identifying these lesions in an early stage could prevent their malignant transformation. The aim of the present work was to assess the cell proliferative activity of minichromosome maintenance protein (MCM-2) in oral epithelial dysplastic lesions and to correlate the results with different grades of epithelial dysplasia in an attempt to use MCM-2 in the early detection of malignancy. MCM-2 expression was determined by the nuclear count in a total of 30 oral epithelial dysplastic specimens roughly classified into 10 cases of mild, moderate, and severe dysplasia. Five cases of early invasive squamous-cell carcinomas and 5 cases of epithelial hyperplasia were also included. The MCM-2 immunostaining was found to increase gradually from mild to moderate to severe dysplasia and reached its maximum value in early invasive squamous cell carcinoma. MCM-2 is of prognostic value in cases of oral dysplasia that have a tendency to undergo malignant transformation.

Architectural geometry

KAUST Repository

Pottmann, Helmut

2014-11-26

Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

Architectural geometry

KAUST Repository

Pottmann, Helmut; Eigensatz, Michael; Vaxman, Amir; Wallner, Johannes

2014-01-01

Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

Function and repair of dental enamel - Potential role of epithelial transport processes of ameloblasts.

Science.gov (United States)

Varga, Gábor; Kerémi, Beáta; Bori, Erzsébet; Földes, Anna

2015-07-01

The hardest mammalian tissue, dental enamel is produced by ameloblasts, which are electrolyte-transporting epithelial cells. Although the end product is very different, they show many similarities to transporting epithelia of the pancreas, salivary glands and kidney. Enamel is produced in a multi-step epithelial secretory process that features biomineralization which is an interplay of secreted ameloblast specific proteins and the time-specific transport of minerals, protons and bicarbonate. First, "secretory" ameloblasts form the entire thickness of the enamel layer, but with low mineral content. Then they differentiate into "maturation" ameloblasts, which remove organic matrix from the enamel and in turn further build up hydroxyapatite crystals. The protons generated by hydroxyapatite formation need to be buffered, otherwise enamel will not attain full mineralization. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. The whole process has been the focus of many immunohistochemical and gene knock-out studies, but, perhaps surprisingly, no functional data existed for mineral ion transport by ameloblasts. However, recent studies including ours provided a better insight for molecular mechanism of mineral formation. The secretory regulation is not completely known as yet, but its significance is crucial. Impairing regulation retards or prevents completion of enamel mineralization and results in the development of hypomineralized enamel that easily erodes after dental eruption. Factors that impair this function are fluoride and disruption of pH regulators. Revealing these factors may eventually lead to the treatment of enamel hypomineralization related to genetic or environmentally induced malformation. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Elements of Architecture

DEFF Research Database (Denmark)

Elements of Architecture explores new ways of engaging architecture in archaeology. It conceives of architecture both as the physical evidence of past societies and as existing beyond the physical environment, considering how people in the past have not just dwelled in buildings but have existed...

Digitally-Driven Architecture

Directory of Open Access Journals (Sweden)

Henriette Bier

2014-07-01

Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisation focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means.In this context, this sixth Footprint issue examines the influence of digital means as pragmatic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).

Science.gov (United States)

Hombach-Klonisch, Sabine; Pocar, Paola; Kauffold, Johannes; Klonisch, Thomas

2006-04-01

Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor), and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR, as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling in TERT-OPEC as determined by ERE-luciferase transient transfection assays. In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility.

A Cloud-based Infrastructure and Architecture for Environmental System Research

Science.gov (United States)

Wang, D.; Wei, Y.; Shankar, M.; Quigley, J.; Wilson, B. E.

2016-12-01

The present availability of high-capacity networks, low-cost computers and storage devices, and the widespread adoption of hardware virtualization and service-oriented architecture provide a great opportunity to enable data and computing infrastructure sharing between closely related research activities. By taking advantage of these approaches, along with the world-class high computing and data infrastructure located at Oak Ridge National Laboratory, a cloud-based infrastructure and architecture has been developed to efficiently deliver essential data and informatics service and utilities to the environmental system research community, and will provide unique capabilities that allows terrestrial ecosystem research projects to share their software utilities (tools), data and even data submission workflow in a straightforward fashion. The infrastructure will minimize large disruptions from current project-based data submission workflows for better acceptances from existing projects, since many ecosystem research projects already have their own requirements or preferences for data submission and collection. The infrastructure will eliminate scalability problems with current project silos by provide unified data services and infrastructure. The Infrastructure consists of two key components (1) a collection of configurable virtual computing environments and user management systems that expedite data submission and collection from environmental system research community, and (2) scalable data management services and system, originated and development by ORNL data centers.

Neural-net disruption predictor in JT-60U

International Nuclear Information System (INIS)

Yoshino, R.

2003-01-01

The prediction of major disruptions caused by the density limit, the plasma current ramp-down with high internal inductance l i , the low density locked mode and the β-limit has been investigated in JT-60U. The concept of 'stability level', newly proposed in this paper to predict the occurrence of a major disruption, is calculated from nine input parameters every 2 ms by the neural network and the start of a major disruption is predicted when the stability level decreases to a certain level, the 'alarm level'. The neural network is trained in two steps. It is first trained with 12 disruptive and six non-disruptive shots (total of 8011 data points). Second, the target output data for 12 disruptive shots are modified and the network is trained again with additional data points generated by the operator. The 'neural-net disruption predictor' obtained has been tested for 300 disruptive shots (128 945 data points) and 1008 non-disruptive shots (982 800 data points) selected from nine years of operation (1991-1999) of JT-60U. Major disruptions except for those caused by the -limit have been predicted with a prediction success rate of 97-98% at 10 ms prior to the disruption and higher than 90% at 30 ms prior to the disruption while the false alarm rate is 2.1% for non-disruptive shots. This prediction performance has been confirmed for 120 disruptive shots (56 163 data points), caused by the density limit, as well as 1032 non-disruptive shots (1004 611 data points) in the last four years of operation (1999-2002) of JT-60U. A careful selection of the input parameters supplied to the network and the newly developed two-step training of the network have reduced the false alarm rate resulting in a considerable improvement of the prediction success rate. (author)

PICNIC Architecture.

Science.gov (United States)

Saranummi, Niilo

2005-01-01

The PICNIC architecture aims at supporting inter-enterprise integration and the facilitation of collaboration between healthcare organisations. The concept of a Regional Health Economy (RHE) is introduced to illustrate the varying nature of inter-enterprise collaboration between healthcare organisations collaborating in providing health services to citizens and patients in a regional setting. The PICNIC architecture comprises a number of PICNIC IT Services, the interfaces between them and presents a way to assemble these into a functioning Regional Health Care Network meeting the needs and concerns of its stakeholders. The PICNIC architecture is presented through a number of views relevant to different stakeholder groups. The stakeholders of the first view are national and regional health authorities and policy makers. The view describes how the architecture enables the implementation of national and regional health policies, strategies and organisational structures. The stakeholders of the second view, the service viewpoint, are the care providers, health professionals, patients and citizens. The view describes how the architecture supports and enables regional care delivery and process management including continuity of care (shared care) and citizen-centred health services. The stakeholders of the third view, the engineering view, are those that design, build and implement the RHCN. The view comprises four sub views: software engineering, IT services engineering, security and data. The proposed architecture is founded into the main stream of how distributed computing environments are evolving. The architecture is realised using the web services approach. A number of well established technology platforms and generic standards exist that can be used to implement the software components. The software components that are specified in PICNIC are implemented in Open Source.

Probabilistic analysis of tokamak plasma disruptions

International Nuclear Information System (INIS)

Sanzo, D.L.; Apostolakis, G.E.

1985-01-01

An approximate analytical solution to the heat conduction equations used in modeling component melting and vaporization resulting from plasma disruptions is presented. This solution is then used to propagate uncertainties in the input data characterizing disruptions, namely, energy density and disruption time, to obtain a probabilistic description of the output variables of interest, material melted and vaporized. (orig.)

Nd:YAG laser for epithelial ingrowth after laser in situ keratomileusis.

Science.gov (United States)

Mohammed, Osama Ali; Mounir, Amr; Hassan, Amin Aboali; Alsmman, Alahmady Hamad; Mostafa, Engy Mohamed

2018-05-04

To evaluate the efficacy of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for treatment of epithelial ingrowth after laser in situ keratomileusis (LASIK). Fifty-eight patients with epithelial ingrowth presented to Sohag refractive center, Sohag, Egypt, between January 2015 and March 2017. Only 41 patients (18 females and 23 males, mean age: 33.4 years) involving 41 eyes were indicated for treatment by Nd:YAG laser as the rest of the eyes were only under observation. Patients with epithelial ingrowth were recognized at a mean of 6 months after primary LASIK procedure (range: 2-16 months). Four eyes had undergone previous LASIK enhancements. Four eyes had the epithelial ingrowth removed by flap lift and scrapping. The mean intensity of the spots used was 0.8 mJ with variable number of shots depending on the size and density of the epithelial ingrowth area. Twenty-eight eyes showed complete regression after one session, while the rest necessitated 2-3 sessions for complete resolution. Mean follow-up period was 8 months (range 5-12 months). Epithelial ingrowth was treated successfully in all 41 eyes. The uncorrected visual acuities were 20/20, and there was no evidence of recurrent epithelial ingrowth after 6 months with no complications reported. YAG laser is a simple, effective outpatient procedure for the management of epithelial ingrowth after LASIK.

Architectural Theatricality

DEFF Research Database (Denmark)

Tvedebrink, Tenna Doktor Olsen

environments and a knowledge gap therefore exists in present hospital designs. Consequently, the purpose of this thesis has been to investigate if any research-based knowledge exist supporting the hypothesis that the interior architectural qualities of eating environments influence patient food intake, health...... and well-being, as well as outline a set of basic design principles ‘predicting’ the future interior architectural qualities of patient eating environments. Methodologically the thesis is based on an explorative study employing an abductive approach and hermeneutic-interpretative strategy utilizing tactics...... and food intake, as well as a series of references exist linking the interior architectural qualities of healthcare environments with the health and wellbeing of patients. On the basis of these findings, the thesis presents the concept of Architectural Theatricality as well as a set of design principles...

Architecture of Institution & Home. Architecture as Cultural Medium

NARCIS (Netherlands)

Robinson, J.W.

2004-01-01

This dissertation addresses how architecture functions as a cultural medium. It does so by by investigating how the architecture of institution and home each construct and support different cultural practices. By studying the design of ordinary settings in terms of how qualitative differences in

On Detailing in Contemporary Architecture

DEFF Research Database (Denmark)

Kristensen, Claus; Kirkegaard, Poul Henning

2010-01-01

Details in architecture have a significant influence on how architecture is experienced. One can touch the materials and analyse the detailing - thus details give valuable information about the architectural scheme as a whole. The absence of perceptual stimulation like details and materiality...... / tactility can blur the meaning of the architecture and turn it into an empty statement. The present paper will outline detailing in contemporary architecture and discuss the issue with respect to architectural quality. Architectural cases considered as sublime piece of architecture will be presented...

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

A novel porous scaffold fabrication technique for epithelial and endothelial tissue engineering.

Science.gov (United States)

McHugh, Kevin J; Tao, Sarah L; Saint-Geniez, Magali

2013-07-01

Porous scaffolds have the ability to minimize transport barriers for both two- (2D) and three-dimensional tissue engineering. However, current porous scaffolds may be non-ideal for 2D tissues such as epithelium due to inherent fabrication-based characteristics. While 2D tissues require porosity to support molecular transport, pores must be small enough to prevent cell migration into the scaffold in order to avoid non-epithelial tissue architecture and compromised function. Though electrospun meshes are the most popular porous scaffolds used today, their heterogeneous pore size and intense topography may be poorly-suited for epithelium. Porous scaffolds produced using other methods have similar unavoidable limitations, frequently involving insufficient pore resolution and control, which make them incompatible with 2D tissues. In addition, many of these techniques require an entirely new round of process development in order to change material or pore size. Herein we describe "pore casting," a fabrication method that produces flat scaffolds with deterministic pore shape, size, and location that can be easily altered to accommodate new materials or pore dimensions. As proof-of-concept, pore-cast poly(ε-caprolactone) (PCL) scaffolds were fabricated and compared to electrospun PCL in vitro using canine kidney epithelium, human colon epithelium, and human umbilical vein endothelium. All cell types demonstrated improved morphology and function on pore-cast scaffolds, likely due to reduced topography and universally small pore size. These results suggest that pore casting is an attractive option for creating 2D tissue engineering scaffolds, especially when the application may benefit from well-controlled pore size or architecture.

Roles of Wnt/β-catenin signaling in epithelial differentiation of mesenchymal stem cells

International Nuclear Information System (INIS)

Wang, Yajing; Sun, Zhaorui; Qiu, Xuefeng; Li, Yan; Qin, Jizheng; Han, Xiaodong

2009-01-01

Bone marrow-derived mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate into epithelial lineage, but the precise mechanisms controlling this process are unclear. Our aim is to explore the roles of Wnt/β-catenin in the epithelial differentiation of MSCs. Using indirect co-culture of rat MSCs with rat airway epithelial cells (RTE), MSCs expressed several airway epithelial markers (cytokeratin 18, tight junction protein occudin, cystic fibrosis transmembrance regulator). The protein levels of some important members in Wnt/β-catenin signaling were determined, suggested down-regulation of Wnt/β-catenin with epithelial differentiation of MSCs. Furthermore, Wnt3α can inhibit the epithelial differentiation of MSCs. A loss of β-catenin induced by Dickkopf-1 can enhance MSCs differentiation into epithelial cells. Lithium chloride transiently activated β-catenin expression and subsequently decreased β-catenin level and at last inhibited MSCs to differentiate into airway epithelium. Taken together, our study indicated that RTE cells can trigger epithelial differentiation of MSCs. Blocking Wnt/β-catenin signaling may promote MSCs to differentiate towards airway epithelial cells.

LASIK flap breakthrough in Nd:YAG laser treatment of epithelial ingrowth

NARCIS (Netherlands)

Lapid-Gortzak, Ruth; Hughes, John M.; Nieuwendaal, Carla P.; Mourits, Maarten P.; van der Meulen, Ivanka J. E.

2015-01-01

To present two cases with complications after Nd:YAG laser treatment of epithelial ingrowth. Case reports. Dense central recurrent epithelial ingrowth was treated with a Nd:YAG laser directed at the epithelial nests in the LASIK flap interface in one case. Misalignment of the aiming beam after

From Digital Disruption to Business Model Scalability

DEFF Research Database (Denmark)

Nielsen, Christian; Lund, Morten; Thomsen, Peter Poulsen

2017-01-01

This article discusses the terms disruption, digital disruption, business models and business model scalability. It illustrates how managers should be using these terms for the benefit of their business by developing business models capable of achieving exponentially increasing returns to scale...... will seldom lead to business model scalability capable of competing with digital disruption(s)....... as a response to digital disruption. A series of case studies illustrate that besides frequent existing messages in the business literature relating to the importance of creating agile businesses, both in growing and declining economies, as well as hard to copy value propositions or value propositions that take...

Systemic Architecture

DEFF Research Database (Denmark)

Poletto, Marco; Pasquero, Claudia

-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto-gardens...... and the coding of proto-interfaces. These prototypes of machinic architecture materialize as synthetic hybrids embedded with biological life (proto-gardens), computational power, behavioural responsiveness (cyber-gardens), spatial articulation (coMachines and fibrous structures), remote sensing (FUNclouds...

Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland epithelial-mesenchymal ontogeny as a model

Directory of Open Access Journals (Sweden)

Huang Jing

2006-09-01

Full Text Available Abstract Background Human studies suggest, and mouse models clearly demonstrate, that cytomegalovirus (CMV is dysmorphic to early organ and tissue development. CMV has a particular tropism for embryonic salivary gland and other head mesenchyme. CMV has evolved to co-opt cell signaling networks so to optimize replication and survival, to the detriment of infected tissues. It has been postulated that mesenchymal infection is the critical step in disrupting organogenesis. If so, organogenesis dependent on epithelial-mesenchymal interactions would be particularly vulnerable. In this study, we chose to model the vulnerability by investigating the cell and molecular pathogenesis of CMV infected mouse embryonic submandibular salivary glands (SMGs. Results We infected E15 SMG explants with mouse CMV (mCMV. Active infection for up to 12 days in vitro results in a remarkable cell and molecular pathology characterized by atypical ductal epithelial hyperplasia, apparent epitheliomesenchymal transformation, oncocytic-like stromal metaplasia, β-catenin nuclear localization, and upregulation of Nfkb2, Relb, Il6, Stat3, and Cox2. Rescue with an antiviral nucleoside analogue indicates that mCMV replication is necessary to initiate and maintain SMG dysmorphogenesis. Conclusion mCMV infection of embryonic mouse explants results in dysplasia, metaplasia, and, possibly, anaplasia. The molecular pathogenesis appears to center around the activation of canonical and, perhaps more importantly, noncanonical NFκB. Further, COX-2 and IL-6 are important downstream effectors of embryopathology. At the cellular level, there appears to be a consequential interplay between the transformed SMG cells and the surrounding extracellular matrix, resulting in the nuclear translocation of β-catenin. From these studies, a tentative framework has emerged within which additional studies may be planned and performed.

β limit disruptions in the TFTR tokamak

International Nuclear Information System (INIS)

Fredrickson, E.D.; McGuire, K.; Janos, A.; Bell, M.; Budny, R.V.; Bush, C.E.; Manickam, J.; Mynick, H.; Nazikian, R.; Taylor, G.

1994-11-01

A disruptive β limit (β = plasma pressure/magnetic pressure) is observed in high performance plasmas in TFTR. The MHD character of these disruptions differs substantially from the disruptions in high density plasmas (density limit disruptions) on TFTR. The high β disruptions can occur with less than a milliseconds warning in the form of a fast growing precursor. The precursor appears to be an external kink or internal (m,n)=(1,1) kink strongly coupled through finite β effects and toroidal terms to higher m components. It does not have the open-quote cold bubble close-quote structure found in density limit disruptions. There is also no evidence for a change in the internal inductance, i.e., a major reconnection of the flux, at the time of the thermal quench

Digitally-Driven Architecture

Directory of Open Access Journals (Sweden)

Henriette Bier

2010-06-01

Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisa­tion focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means. In this context, this sixth Footprint issue examines the influence of digital means as prag­matic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells

International Nuclear Information System (INIS)

Miura, Yuka; Hagiwara, Natsumi; Radisky, Derek C.; Hirai, Yohei

2014-01-01

Activation of the epithelial-mesenchymal transition (EMT) program promotes cell invasion and metastasis, and is reversed through mesenchymal-epithelial transition (MET) after formation of distant metastases. Here, we show that an imbalance of gene products encoded by the transcriptional factor C/EBPβ, LAP (liver-enriched activating protein) and LIP (liver-enriched inhibitory protein), can regulate both EMT- and MET-like phenotypic changes in mouse mammary epithelial cells. By using tetracycline repressive LIP expression constructs, we found that SCp2 cells, a clonal epithelial line of COMMA1-D cells, expressed EMT markers, lost the ability to undergo alveolar-like morphogenesis in 3D Matrigel, and acquired properties of benign adenoma cells. Conversely, we found that inducible expression of LAP in SCg6 cells, a clonal fibroblastic line of COMMA1-D cells, began to express epithelial keratins with suppression of proliferation. The overexpression of the C/EBPβ gene products in these COMMA1-D derivatives was suppressed by long-term cultivation on tissue culture plastic, but gene expression was maintained in cells grown on Matrigel or exposed to proteasome inhibitors. Thus, imbalances of C/EBPβ gene products in mouse mammary epithelial cells, which are affected by contact with basement membrane, are defined as a potential regulator of metastatic potential. - Highlights: • We created a temporal imbalance of C/EBPβ gene products in the mammary model cells. • The temporal up-regulation of LIP protein induced EMT-like cell behaviors. • The temporal up-regulation of LAP protein induced MET-like cell behaviors. • Excess amount of C/EBPβ gene products were eliminated by proteasomal-degradation. • Basement membrane components attenuated proteasome-triggered protein elimination

3rd Annual Disruptive Technology Conference

Science.gov (United States)

2006-09-07

Panel -- The Warfighter’s Perspective The Impact of Disruptive Technologies on Joint Warfighting MG Michael Vane, USA, Vice Director for Force...Structure, Resources & Assessment, Joint Staff, J-8 Panel -- Perspectives of Change: Identifying the Emerging Commercial Disruptive Technologies Decision...Mark Lucas, Board Member OSGeo, RadiantBlue Technologies Panel -- The Search for Disruptive Technologies - a “Blue Force” Multiplier Advanced

Architecture and Stages

DEFF Research Database (Denmark)

Kiib, Hans

2009-01-01

as "experiencescape" - a space between tourism, culture, learning and economy. Strategies related to these challenges involve new architectural concepts and art as ‘engines' for a change. New expressive architecture and old industrial buildings are often combined into hybrid narratives, linking the past...... with the future. But this is not enough. The agenda is to develop architectural spaces, where social interaction and learning are enhanced by art and fun. How can we develop new architectural designs in our inner cities and waterfronts where eventscapes, learning labs and temporal use are merged with everyday...

Architecture in Its Own Shadow

Directory of Open Access Journals (Sweden)

Alexander Rappaport

2016-11-01

Full Text Available Those who consider themselves architects disapprove of the statements about destruction of the subject of architectural culture, profession and of the subject of architectural theory. At the same time, a deep crisis of both theory and practice is obvious. When theorists of architecture of the 20th and early 21st centuries turned to the subjects external to architecture – sociology, psychology, semiotics, ecology, post-structuralist criticism, etc., instead of enriching and renovating the architectural theory, the results were just the opposite. A brand new and independent paradigm of architecture is needed. It should contain three parts specific by their logical-subject nature: ontology of architecture, methodology of architectural thought and axiology of architectural thought.

Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and hepatocytes.

Science.gov (United States)

Li, Ying; Bentzley, Catherine M; Tarloff, Joan B

2005-04-01

Several chemicals, including para-aminophenol (PAP), produce kidney damage in the absence of hepatic damage. Selective nephrotoxicity may be related to the ability of the kidney to reabsorb filtered water, thereby raising the intraluminal concentration of toxicants and exposing tubular epithelial cells to higher concentrations than would be present in other tissues. The present experiments tested the hypothesis that hepatocytes and renal epithelial cells exposed to equivalent concentrations of PAP would be equally susceptible to toxicity. Hepatocytes and renal epithelial cells were prepared by collagenase digestion of tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using trypan blue exclusion, oxygen consumption and ATP content. We measured the rate of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found that renal epithelial cells accumulated trypan blue and showed declines in oxygen consumption and ATP content at significantly lower concentrations of PAP and at earlier time points than hepatocytes. The half-life of PAP in hepatocyte incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells formed significantly less glutathione conjugates of PAP (PAP-SG) than did hepatocytes, consistent with less efficient detoxification of reactive PAP intermediates by renal epithelial cells. Finally, hepatocytes contained significant more reduced glutathione (NPSH) than did renal epithelial cells, possibly explaining the enhanced formation of PAP-SG by this cell population. In conclusion, our data indicates that renal epithelial cells are intrinsically more susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity may be due to longer exposure to PAP and/or reduced detoxification of reactive intermediates due to lower concentrations

Probiotics promote endocytic allergen degradation in gut epithelial cells

International Nuclear Information System (INIS)

Song, Chun-Hua; Liu, Zhi-Qiang; Huang, Shelly; Zheng, Peng-Yuan; Yang, Ping-Chang

2012-01-01

Highlights: ► Knockdown of A20 compromised the epithelial barrier function. ► The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. ► Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. ► Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

Probiotics promote endocytic allergen degradation in gut epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Song, Chun-Hua [Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou (China); Liu, Zhi-Qiang [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Huang, Shelly [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Zheng, Peng-Yuan, E-mail: medp7123@126.com [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Yang, Ping-Chang, E-mail: yangp@mcmaster.ca [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada)

2012-09-14

Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

Architectural technology

DEFF Research Database (Denmark)

2005-01-01

The booklet offers an overall introduction to the Institute of Architectural Technology and its projects and activities, and an invitation to the reader to contact the institute or the individual researcher for further information. The research, which takes place at the Institute of Architectural...... Technology at the Roayl Danish Academy of Fine Arts, School of Architecture, reflects a spread between strategic, goal-oriented pilot projects, commissioned by a ministry, a fund or a private company, and on the other hand projects which originate from strong personal interests and enthusiasm of individual...

Humanizing Architecture

DEFF Research Database (Denmark)

Toft, Tanya Søndergaard

2015-01-01

The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

Robotic architectures

CSIR Research Space (South Africa)

Mtshali, M

2010-01-01

Full Text Available In the development of mobile robotic systems, a robotic architecture plays a crucial role in interconnecting all the sub-systems and controlling the system. The design of robotic architectures for mobile autonomous robots is a challenging...

Lingual Epithelial Stem Cells and Organoid Culture of Them

Directory of Open Access Journals (Sweden)

Hiroko Hisha

2016-01-01

Full Text Available As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP, were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine.

Immunohistochemical study of epithelial-myofibroblast interaction in Barrett metaplasia

Directory of Open Access Journals (Sweden)

Ochicha O

2010-04-01

Full Text Available Context: Sub-epithelial myofibroblasts are known to influence the biology (proliferation, differentiation and apoptosis of overlying epithelia. In the intestine, myofibroblasts have been demonstrated to be essential for epithelial differentiation. It is therefore hypothesized that myofibroblasts may also be involved in intestinal metaplasia that is characteristic of Barrett esophagus. Objective: This study endeavors to immunohistologically evaluate epithelial-myofibroblast interaction in Barrett′s metaplasia. Materials and Methods: Nineteen archival esophageal endoscopic biopsies of Barrett′s metaplasia were immune-phenotyped for the following epithelial and myofibroblast antigens - cytokeratins (CK 8, 13, 18, CDX2 (Caudal type homeobox 2, a-smooth muscle actin (SMA. Results: α-SMA immunostaining revealed close association between myofibroblasts and metaplastic Barrett′s epithelium but not with normal esophageal squamous epithelium. Myofibroblasts were more prominent in dysplastic than in non-dysplastic Barrett metaplasia. CDX2 and CK 8/18, indicators of intestinal differentiation were expressed in Barrett metaplasia but not normal esophageal squamous epithelium, while the reverse was the case for CK 13, which only stained normal esophageal squamous epithelium. Conclusion: Although their precise role is yet to be clearly defined, sub-epithelial myofibroblasts are very likely involved in the pathogenesis of Barrett′s metaplasia.

Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.

Science.gov (United States)

Fujiwara, Keiichi; McAlpine, Jessica N; Lheureux, Stephanie; Matsumura, Noriomi; Oza, Amit M

2016-01-01

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

The Effects of Disruption on Strategic Management

DEFF Research Database (Denmark)

Drejer, Anders

2017-01-01

There is a lot of interest in Disruption these days even though the concept itself is still under formation. Disruption can be traced back to the idea of disruptive technological change and the late 1990s but has reemerged in the public eye in current years under guises such as Big Data......, Digitalization, Globalization and much more. Furthermore, the effects of disruption are now being felt by organizations and industries all over the world. In this paper, we will try to outline and illustrate some of those effects using the case-study of an international, Danish, SME. The case company has been...... forced to face some challenges caused by disruption and in the process of doing so has changed its strategy process significantly towards a more learning based approach to strategic management. Keywords: disruption; case- study; SME; strategy process....

Heterogeneity of limbal basal epithelial progenitor cells.

Science.gov (United States)

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

2010-11-01

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

Architecture Sustainability

NARCIS (Netherlands)

Avgeriou, Paris; Stal, Michael; Hilliard, Rich

2013-01-01

Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

Epithelial-mesenchymal transition: Understanding the basic concept

Directory of Open Access Journals (Sweden)

Suresh Babu Ghanta

2012-01-01

Full Text Available The epithelial-mesenchymal transition (EMT is described as a rapid and reversible process of change of cell phenotype seen during embryonic development, organ fibrosis, and tumor progression. EMT was first described by Gary Greenberg and Elizabeth Hay in 1982. During EMT the epithelial cells alter their cell polarity, reorganize their cytoskeleton thus become isolated and motile. Depending upon the biological context in which they occur, EMT is divided into three types namely EMT type I, II, III. The article describes the process of EMT implicated in the oral cavity as in palate and root development (type I EMT, gingival fibromatosis and oral sub-mucous fibrosis (type II EMT, and oral squamous cell carcinoma (type III EMT. The reverse process of EMT is called as mesenchymal-epithelial transition seen in association with kidney formation.

Emergent material properties of developing epithelial tissues.

Science.gov (United States)

Machado, Pedro F; Duque, Julia; Étienne, Jocelyn; Martinez-Arias, Alfonso; Blanchard, Guy B; Gorfinkiel, Nicole

2015-11-23

Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. The Drosophila amnioserosa epithelium progressively contracts over 3 hours of dorsal closure, during which cell apices exhibit area fluctuations driven by medial myosin pulses with periods of 1.5-6 min. Linking these two timescales and understanding how pulsatile contractions drive morphogenetic movements is an urgent challenge. We present a novel framework to measure in a continuous manner the mechanical properties of epithelial cells in the natural context of a tissue undergoing morphogenesis. We show that the relationship between apicomedial myosin fluorescence intensity and strain during fluctuations is consistent with a linear behaviour, although with a lag. We thus used myosin fluorescence intensity as a proxy for active force generation and treated cells as natural experiments of mechanical response under cyclic loading, revealing unambiguous mechanical properties from the hysteresis loop relating stress to strain. Amnioserosa cells can be described as a contractile viscoelastic fluid. We show that their emergent mechanical behaviour can be described by a linear viscoelastic rheology at timescales relevant for tissue morphogenesis. For the first time, we establish relative changes in separate effective mechanical properties in vivo. Over the course of dorsal closure, the tissue solidifies and effective stiffness doubles as net contraction of the tissue commences. Combining our findings with those from previous laser ablation experiments, we show that both apicomedial and junctional stress also increase over time, with the relative increase in apicomedial stress approximately twice that of other obtained measures. Our results show that in an epithelial

Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

Directory of Open Access Journals (Sweden)

Anam Naz

2017-09-01

Full Text Available Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

High-level language computer architecture

CERN Document Server

Chu, Yaohan

1975-01-01

High-Level Language Computer Architecture offers a tutorial on high-level language computer architecture, including von Neumann architecture and syntax-oriented architecture as well as direct and indirect execution architecture. Design concepts of Japanese-language data processing systems are discussed, along with the architecture of stack machines and the SYMBOL computer system. The conceptual design of a direct high-level language processor is also described.Comprised of seven chapters, this book first presents a classification of high-level language computer architecture according to the pr

Grid Architecture 2

Energy Technology Data Exchange (ETDEWEB)

Taft, Jeffrey D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2016-01-01

The report describes work done on Grid Architecture under the auspices of the Department of Electricity Office of Electricity Delivery and Reliability in 2015. As described in the first Grid Architecture report, the primary purpose of this work is to provide stakeholder insight about grid issues so as to enable superior decision making on their part. Doing this requires the creation of various work products, including oft-times complex diagrams, analyses, and explanations. This report provides architectural insights into several important grid topics and also describes work done to advance the science of Grid Architecture as well.

TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

Directory of Open Access Journals (Sweden)

Zuraw Bruce L

2009-10-01

Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

Impact of the Stem Extract of on the Feeding Potential and Histological Architecture of the Midgut Epithelial Tissue of Early Fourth Instars of HÜbner

Directory of Open Access Journals (Sweden)

Monika Mishra

2015-01-01

Full Text Available Helicoverpa armigera HÜbner is one of the most important agricultural crop pests in the world causing heavy crop yield losses. The continued and indiscriminate use of synthetic insecticides in agriculture for their control has received wide public apprehension because of multifarious problems, including insecticide resistance, resurgence of pest species, environmental pollution, and toxic hazards to humans and nontarget organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and biodegradable plant products. In view of this, the efficacy of Thevetia neriifolia methanol stem extract was evaluated against the early fourth instars of H. armigera as an antifeedant and stomach poison agent. Feeding of larvae with the diet containing 0.005%–5.0% extract resulted in 2.06%–37.35% antifeedant index; the diet with 5.0% extract caused 54.3% reduced consumption. The negative impact of extract on larval feeding resulted in 37.5%–77.7% starvation, causing adverse effects on the larval weight. Choice between control and experimental diet resulted in feeding preference of larvae for the control diet, leading to 7.3%–42.9% reduced consumption of extract-containing diet. The only exception was the diet with 0.005% extract, which could not cause any deterrence. The midgut histological architecture of H. armigera larvae fed with 0.005%–0.05% extract-containing diet with negligible antifeedant potential showed significant damage, shrinkage, and distortion and vacuolization of gut tissues and peritrophic membrane, causing the disintegration of epithelial, goblet, and regenerative cells; the damage increased with the increase in concentration. These changes in the gut caused negative impact on the digestion and absorption of food and thus nutritional deficiency in the larvae, which could probably affect their growth and development. This study reveal the appreciable stomach poison potential of T

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

Directory of Open Access Journals (Sweden)

Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

Interaction of chitin/chitosan with salivary and other epithelial cells-An overview.

Science.gov (United States)

Patil, Sharvari Vijaykumar; Nanduri, Lalitha S Y

2017-11-01

Chitin and its deacetylated form, chitosan, have been widely used for tissue engineering of both epithelial and mesenchymal tissues. Epithelial cells characterised by their sheet-like tight cellular arrangement and polarised nature, constitute a major component in various organs and play a variety of roles including protection, secretion and maintenance of tissue homeostasis. Regeneration of damaged epithelial tissues has been studied using biomaterials such as chitin, chitosan, hyaluronan, gelatin and alginate. Chitin and chitosan are known to promote proliferation of various embryonic and adult epithelial cells. However it is not clearly understood how this activity is achieved or what are the mechanisms involved in the chitin/chitosan driven proliferation of epithelial cells. Mechanistic understanding of influence of chitin/chitosan on epithelial cells will guide us to develop more targeted regenerative scaffold/hydrogel systems. Therefore, current review attempts to elicit a mechanistic insight into how chitin and chitosan interact with salivary, mammary, skin, nasal, lung, intestinal and bladder epithelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards a semantic web layered architecture

CSIR Research Space (South Africa)

Gerber, AJ

2007-02-01

Full Text Available as an architectural pattern or architectural style [6, 43]. In this section we give a brief description of the con- cepts software architecture and layered architecture. In ad- dition we provide a summary of a list of criteria for layered architectures identified...- els caused some architectural recurrences to evolve. These are described as architectural patterns [6] or architectural styles [43]. Examples of the best known architectural patterns include, but are not limited to, the client/server architectural...

Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

Energy Technology Data Exchange (ETDEWEB)

Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole

1999-02-01

The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

Information Integration Architecture Development

OpenAIRE

Faulkner, Stéphane; Kolp, Manuel; Nguyen, Duy Thai; Coyette, Adrien; Do, Thanh Tung; 16th International Conference on Software Engineering and Knowledge Engineering

2004-01-01

Multi-Agent Systems (MAS) architectures are gaining popularity for building open, distributed, and evolving software required by systems such as information integration applications. Unfortunately, despite considerable work in software architecture during the last decade, few research efforts have aimed at truly defining patterns and languages for designing such multiagent architectures. We propose a modern approach based on organizational structures and architectural description lan...

Towards a Framework of Digital Platform Disruption

DEFF Research Database (Denmark)

Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

2014-01-01

Digital platforms are disruptive information technology (IT) artifacts that erode conventional business logic associated with traditional market structures. This paper presents a framework for examining the disruptive potential of digital platforms whereby we postulate that the strategic interplay...... digital platforms purposely decouple platform layers, to foster open innovation and accelerate market disruption. This paper therefore represents a first concrete step aimed at unravelling the disruptive potential of digital platforms....... of governance regimes and platform layers is deterministic of whether disruptive derivatives are permitted to flourish. This framework has been employed in a comparative case study between centralized (i.e., PayPal) and decentralized (i.e., Coinkite) digital payment platforms to illustrate its applicability...

Real-time disruption handling at ASDEX upgrade

International Nuclear Information System (INIS)

Zehetbauer, Th.; Pautasso, G.; Tichmann, C.; Egorov, S.; Lorenz, A.; Mertens, V.; Neu, G.; Raupp, G.; Treutterer, W.; Zasche, D.

2001-01-01

A neural network for prediction of disruptions has been developed at ASDEX Upgrade with the goal to mitigate or avoid these. The novel idea is to compute the remaining time-to-disruption to indicate the stability level of the discharge. The neural network has been specified, trained and then implemented within the real-time plasma control system. The current version of the system terminates the discharge with an impurity pellet when the computed time-to-disruption falls below a threshold of 80 ms. Routine operation shows that disruptions are recognized reliably. Vessel currents and forces are considerably reduced. The system will be enhanced to avoid disruptions with a soft landing initiated in time

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.

Family Disruptions

Science.gov (United States)

... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Disruptions Page Content Article Body No matter how ...

Architectural Contestation

NARCIS (Netherlands)

Merle, J.

2012-01-01

This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form,

Information architecture. Volume 3: Guidance

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-04-01

The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system.

Science.gov (United States)

Jijon, H B; Suarez-Lopez, L; Diaz, O E; Das, S; De Calisto, J; Yaffe, M B; Pittet, M J; Mora, J R; Belkaid, Y; Xavier, R J; Villablanca, E J

2018-05-01

Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4 + goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.

Disruption modeling in support of ITER

International Nuclear Information System (INIS)

Bandyopadhyay, I.

2015-01-01

Plasma current disruptions and Vertical Displacement Events (VDEs) are one of the major concerns in any tokamak as they lead to large electromagnetic forces to tokamak first wall components and vacuum vessel. Their occurrence also means disruption to steady state operations of tokamaks. Thus future fusion reactors like ITER must ensure that disruptions and VDEs are minimized. However, since there is still finite probability of their occurrence, one must be able to characterize disruptions and VDEs and able to predict, for example, the plasma current quench time and halo current amplitude, which mainly determine the magnitude of the electromagnetic forces. There is a concerted effort globally to understand and predict plasma and halo current evolution during disruption in tokamaks through MHD simulations. Even though Disruption and VDEs are often 3D MHD perturbations in nature, presently they are mostly simulated using 2D axisymmetric MHD codes like the Tokamak Simulation Code (TSC) and DINA. These codes are also extensively benchmarked against experimental data in present day tokamaks to improve these models and their ability to predict these events in ITER. More detailed 3D models like M3D are only recently being developed, but they are yet to be benchmarked against experiments, as also they are massively computationally exhaustive

Pathophysiology of Corneal Scarring in Persistent Epithelial Defects After PRK and Other Corneal Injuries.

Science.gov (United States)

Wilson, Steven E; Medeiros, Carla S; Santhiago, Marcony R

2018-01-01

To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK. These were studied with slit-lamp photographs, immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin (α-SMA), and transmission electron microscopy. Myofibroblasts developed at the stromal surface within the persistent epithelial defect and for a short distance peripheral to the leading edge of the epithelium. No normal epithelial basement membrane was detectable within the persistent epithelial defect or for up to 0.3 mm behind the leading edge of the epithelium, although epithelial basement membrane had normally regenerated in other areas of the zone ablated by an excimer laser where the epithelium healed promptly. A persistent epithelial defect in the cornea results in the development of myofibroblasts and disordered extracellular matrix produced by these cells that together cause opacity within, and a short distance beyond, the persistent epithelial defect. Clinicians should treat persistent epithelial defects within 10 days of non-closure of the epithelium to facilitate epithelial healing to prevent long-term stromal scarring (fibrosis). [J Refract Surg. 2018;34(1):59-64.]. Copyright 2018, SLACK Incorporated.

Software architecture as a set of architectural design decisions

NARCIS (Netherlands)

Jansen, Anton; Bosch, Jan; Nord, R; Medvidovic, N; Krikhaar, R; Khrhaar, R; Stafford, J; Bosch, J

2006-01-01

Software architectures have high costs for change, are complex, and erode during evolution. We believe these problems are partially due to knowledge vaporization. Currently, almost all the knowledge and information about the design decisions the architecture is based on are implicitly embedded in

Disrupted Disclosure

DEFF Research Database (Denmark)

Krause Hansen, Hans; Uldam, Julie

appearances become challenged through disruptive disclosures in mediaenvironments characterized by multiple levels of visibility, with companies both observing andbeing observed by civil society groups that criticize them; (c) why and how the mobilization aroundtransparency and ensuing practices...

MHD stability, operational limits and disruptions

International Nuclear Information System (INIS)

1999-01-01

The present physics understandings of magnetohydrodynamic (MHD) stability of tokamak plasmas, the threshold conditions for onset of MHD instability, and the resulting operational limits on attainable plasma pressure (beta limit) and density (density limit), and the consequences of plasma disruption and disruption related effects are reviewed and assessed in the context of their application to a future DT burning reactor prototype tokamak experiment such as ITER. The principal considerations covered within the MHD stability and beta limit assessments are (i) magnetostatic equilibrium, ideal MHD stability and the resulting ideal MHD beta limit; (ii) sawtooth oscillations and the coupling of sawtooth activity to other types of MHD instability; (iii) neoclassical island resistive tearing modes and the corresponding limits on beta and energy confinement; (iv) wall stabilization of ideal MHD instabilities and resistive wall instabilities; (v) mode locking effects of non-axisymmetric error fields; (vi) edge localized MHD instabilities (ELMs, etc.); and (vii) MHD instabilities and beta/pressure gradient limits in plasmas with actively modified current and magnetic shear profiles. The principal considerations covered within the density limit assessments are (i) empirical density limits; (ii) edge power balance/radiative density limits in ohmic and L-mode plasmas; and (iii) edge parameter related density limits in H-mode plasmas. The principal considerations covered in the disruption assessments are (i) disruption causes, frequency and MHD instability onset; (ii) disruption thermal and current quench characteristics; (iii) vertical instabilities (VDEs), both before and after disruption, and plasma and in-vessel halo currents; (iv) after disruption runaway electron formation, confinement and loss; (v) fast plasma shutdown (rapid externally initiated dissipation of plasma thermal and magnetic energies); (vi) means for disruption avoidance and disruption effect mitigation; and

The architectural design of networks of protein domain architectures.

Science.gov (United States)

Hsu, Chia-Hsin; Chen, Chien-Kuo; Hwang, Ming-Jing

2013-08-23

Protein domain architectures (PDAs), in which single domains are linked to form multiple-domain proteins, are a major molecular form used by evolution for the diversification of protein functions. However, the design principles of PDAs remain largely uninvestigated. In this study, we constructed networks to connect domain architectures that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. Our results shed light on nature's blueprint for protein architecture and provide a framework for understanding architectural design from a network perspective.

MicroRNA-122 triggers mesenchymal-epithelial transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting RhoA.

Directory of Open Access Journals (Sweden)

Sheng-Chun Wang

Full Text Available The loss of microRNA-122 (miR-122 expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC, however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the mesenchymal-epithelial transition (MET, as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4, and down-regulated mesenchymal proteins (vimentin and fibronectin. The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.

Epithelial calcium channels: from identification to function and regulation.

NARCIS (Netherlands)

Hoenderop, J.G.J.; Nilius, B.; Bindels, R.J.M.

2003-01-01

The epithelial calcium channels TRPV5 and TRPV6 have been studied extensively in the epithelial tissues controlling Ca(2+) homeostasis and exhibit a range of distinctive properties that distinguish them from other transient receptor potential (TRP) channels. These two novel members of the

induced acute cytotoxicity in human cervical epithelial carcinoma cells

African Journals Online (AJOL)

Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair

Science.gov (United States)

Parlato, Marianna; Yeretssian, Garabet

2014-01-01

The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease. PMID:24886810

Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway.

Science.gov (United States)

Sivagurunathan, Suganya; Palanisamy, Karthikka; Arunachalam, Jayamuruga Pandian; Chidambaram, Subbulakshmi

2017-03-01

PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

microRNA-4516 Contributes to Different Functions of Epithelial Permeability Barrier by Targeting Poliovirus Receptor Related Protein 1 in Enterovirus 71 and Coxsackievirus A16 Infections

Directory of Open Access Journals (Sweden)

Yajie Hu

2018-04-01

Full Text Available Enterovirus 71 (EV-A71 and coxsackievirus A16 (CV-A16 remain the predominant etiological agents of hand, foot, and mouth disease (HFMD. The clinical manifestations caused by the two viruses are obviously different. CV-A16 usually triggers a repeated infection, and airway epithelial integrity is often the potential causative factor of respiratory repeated infections. Our previous studies have demonstrated that there were some differentially expressed miRNAs involved in the regulation of adhesion function of epithelial barrier in EV-A71 and CV-A16 infections. In this study, we compared the differences between EV-A71 and CV-A16 infections on the airway epithelial barrier function in human bronchial epithelial (16HBE cells and further screened the key miRNA which leaded to the formation of these differences. Our results showed that more rapid proliferation, more serious destruction of 16HBE cells permeability, more apoptosis and disruption of intercellular adhesion-associated molecules were found in CV-A16 infection as compared to EV-A71 infection. Furthermore, we also identified that microRNA-4516 (miR-4516, which presented down-regulation in EV-A71 infection and up-regulation in CV-A16 infection was an important regulator of intercellular junctions by targeting Poliovirus receptor related protein 1(PVRL1. The expressions of PVRL1, claudin4, ZO-1 and E-cadherin in CV-A16-infected cells were significantly less than those in EV-A71-infected cells, while the expressions of these proteins were subverted when pre-treated with miR-4516-overexpression plasmid in EV-A71 infected and miR-4516-knockdown plasmid in CV-A16 infected 16HBE cells. Thus, these data suggested that the opposite expression of miR-4516 in EV-A71 and CV-A16 infections might be the initial steps leading to different epithelial impairments of 16HBE cells by destroying intercellular adhesion, which finally resulted in different outcomes of EV-A71 and CV-A16 infections.

Quantification of epithelial cells in coculture with fibroblasts by fluorescence image analysis.

Science.gov (United States)

Krtolica, Ana; Ortiz de Solorzano, Carlos; Lockett, Stephen; Campisi, Judith

2002-10-01

To demonstrate that senescent fibroblasts stimulate the proliferation and neoplastic transformation of premalignant epithelial cells (Krtolica et al.: Proc Natl Acad Sci USA 98:12072-12077, 2001), we developed methods to quantify the proliferation of epithelial cells cocultured with fibroblasts. We stained epithelial-fibroblast cocultures with the fluorescent DNA-intercalating dye 4,6-diamidino-2-phenylindole (DAPI), or expressed green fluorescent protein (GFP) in the epithelial cells, and then cultured them with fibroblasts. The cocultures were photographed under an inverted microscope with appropriate filters, and the fluorescent images were captured with a digital camera. We modified an image analysis program to selectively recognize the smaller, more intensely fluorescent epithelial cell nuclei in DAPI-stained cultures and used the program to quantify areas with DAPI fluorescence generated by epithelial nuclei or GFP fluorescence generated by epithelial cells in each field. Analysis of the image areas with DAPI and GFP fluorescences produced nearly identical quantification of epithelial cells in coculture with fibroblasts. We confirmed these results by manual counting. In addition, GFP labeling permitted kinetic studies of the same coculture over multiple time points. The image analysis-based quantification method we describe here is an easy and reliable way to monitor cells in coculture and should be useful for a variety of cell biological studies. Copyright 2002 Wiley-Liss, Inc.

Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

Science.gov (United States)

Wilson, Thad E

2017-05-01

Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Neutrophil Interactions with Epithelial Expressed ICAM-1 Enhances Intestinal Mucosal Wound Healing

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Sumagin, R; Brazil, JC; Nava, P; Nishio, H; Alam, A; Luissint, AC; Weber, DA; Neish, AS; Nusrat, A; Parkos, CA

2015-01-01

A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. While epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 plays an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing. PMID:26732677

Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing.

Science.gov (United States)

Sumagin, R; Brazil, J C; Nava, P; Nishio, H; Alam, A; Luissint, A C; Weber, D A; Neish, A S; Nusrat, A; Parkos, C A

2016-09-01

A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. Although epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 has an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing.

THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

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Dusik eKim

2014-06-01

Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

Disruption studies on ASDEX upgrade

International Nuclear Information System (INIS)

Pautasso, G.; Egorov, S.; Finken, K.H.

2003-01-01

Disruptions generate large thermal and mechanical stresses on the tokamak components and are occasionally responsible for damages to the machine. For a future reactor disruptions have a significant impact on the design since all loading conditions must be analyzed in accordance with stricter design criteria (due to safety or difficult maintenance). Therefore the uncertainties affecting the predicted stresses must be reduced as much as possible with a more comprehensive set of measurements and analyses in this generation of experimental machines, and avoidance/predictive methods must be developed further. Disruption studies on ASDEX Upgrade are focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon in order to learn to avoid it or to predict its occurrence and to mitigate its effects; (2) analyzing the effects of disruptions on the machine to determine the functional dependence of the thermal and mechanical loads upon the discharge parameters. This allows, firstly, to dimension or reinforce the machine components to withstand these loads and, secondly, to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions, i.e. thermal loads, mechanical forces and runaways with injection of impurity pellets or gas. This paper is focused on most recent results concerning points, i.e. on the analysis of the degree of asymmetry of the forces and on the use of impurity puff for mitigation

Current hybrid-electric powertrain architectures: Applying empirical design data to life cycle assessment and whole-life cost analysis

International Nuclear Information System (INIS)

Hutchinson, Tim; Burgess, Stuart; Herrmann, Guido

2014-01-01

Highlights: • Design data for 44 hybrid cars available in the US has been gathered and analysed. • An empirical life cycle assessment of greenhouse gas emissions is performed. • Empirical whole-life cost modelling is used to evaluate powertrain architectures. • The value to be seen in each architecture is highly dependent on its application. • Mild, HSD and Plug-in HSD powertrains are the most likely architectures to dominate. - Abstract: The recent introduction of hybrid-electric powertrain technology has disrupted the automotive industry, causing significant powertrain design divergence. As this radical powertrain innovation matures, will hybrid vehicles dominate the future automotive market and does this represent a positive shift in the environmental impact of the industry? The answer to this question is sought within this paper. It seeks to take advantage of the position that the industry has reached, replacing previous theoretical studies with the first extensive empirical models of life cycle emissions and whole-life costing. A comprehensive snapshot of today’s hybrid market is presented, with detailed descriptions of the various hybrid powertrain architectures. Design data has been gathered for 44 hybrid passenger cars currently available in the US. The empirical data is used to explore the relative life cycle greenhouse gas emissions and whole-life costing of different hybrid powertrain architectures. Potential dominant designs are identified and their emissions are shown to be reduced. However, both the emissions and economic competitiveness of different hybrid powertrains are shown to vary significantly depending on how the vehicle is used

Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

Energy Technology Data Exchange (ETDEWEB)

Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

1997-10-13

Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

Spontaneous regression of epithelial downgrowth from clear corneal phacoemulsification wound

Directory of Open Access Journals (Sweden)

Ryan M. Jaber

2018-06-01

Full Text Available Purpose: To report a case of spontaneous regression of optical coherence tomography (OCT and confocal microscopy-supported epithelial downgrowth associated with clear corneal phacoemulsification wound. Observations: A 66-year-old Caucasian male presented two years after phacoemulsification in the left eye with an enlarging cornea endothelial lesion in that eye. His early post-operative course had been complicated by corneal edema and iris transillumination defects. The patient presented to our clinic with a large geographic sheet of epithelial downgrowth and iris synechiae to the temporal clear corneal wound. His vision was correctable to 20/25 in his left eye. Anterior segment OCT showed a hyperreflective layer on the posterior cornea with an abrupt transition that corresponded to the clinical transition zone of the epithelial downgrowth. Confocal microscopy showed polygonal cells with hyperreflective nuclei suggestive of epithelial cells in the area of the lesion with a transition to a normal endothelial cell mosaic. Given the lack of glaucoma or inflammation and the relatively good vision, the plan was made to closely monitor for progression with the anticipation that he may require aggressive surgery. Over course of subsequent follow-up visits at three, seven and ten months; the endothelial lesion receded significantly. Confocal imaging in the area of the previously affected cornea showed essentially normal morphology with anan endothelial cell count of 1664 cells/mm2. Conclusions and importance: Epithelial downgrowth may spontaneously regress. Though the mechanism is yet understood, contact inhibition of movement may play a role. Despite this finding, epithelial downgrowth is typically a devastating process requiring aggressive treatment. Keywords: Epithelial downgrowth, Spontaneous regression, Confocal microscopy, Contact inhibition of movement

Memory architecture

NARCIS (Netherlands)

2012-01-01

A memory architecture is presented. The memory architecture comprises a first memory and a second memory. The first memory has at least a bank with a first width addressable by a single address. The second memory has a plurality of banks of a second width, said banks being addressable by components

Disruptive technologies and transportation : final report.

Science.gov (United States)

2016-06-01

Disruptive technologies refer to innovations that, at first, may be considered unproven, lacking refinement, relatively unknown, or even impractical, but ultimately they supplant existing technologies and/or applications. In general, disruptive techn...

Forces and dynamics in epithelial domes of controlled size and shape

Science.gov (United States)

Latorre-Ibars, Ernest; Casares, Laura; Gomez-Gonzalez, Manuel; Uroz, Marina; Arroyo, Marino; Trepat, Xavier

Mechanobiology of epithelia plays a central role in morphogenesis, wound healing, and tumor progression. Its current understanding relies on mechanical measurements on flat epithelial layers. However, most epithelia in vivo exhibit a curved 3D shape enclosing a pressurized lumen. Using soft micropatterned substrates we produce massive parallel arrays of epithelial domes with controlled size and basal shape. We measure epithelial traction, tension, and luminal pressure in epithelial domes. The local stress tensor on the freestanding epithelial membrane is then mapped by combining measured luminal pressure and local curvature. We show that tension and cell shape are highly anisotropic and vary along the meridional position of the domes. Finally, we establish constitutive relations between shape, tension, and pressure during perturbations of the contractile machinery, osmotic shocks, and spontaneous fluctuations of dome volume. Our findings contradict a description of the epithelium as a fluid capillary surface. Cells in the dome are unable to relax into a uniform and isotropic tensional state through sub- and supra-cellular rearrangements. Mapping epithelial shape, tension, and pressure will enable quantitative studies of mechanobiology in 3D epithelia of controlled size and shape.

'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

Science.gov (United States)

Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

2013-01-01

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666