Drosophila sosie functions with β(H)-Spectrin and actin organizers in cell migration, epithelial morphogenesis and cortical stability.

Science.gov (United States)

Urwyler, Olivier; Cortinas-Elizondo, Fabiola; Suter, Beat

2012-10-15

Morphogenesis in multicellular organisms requires the careful coordination of cytoskeletal elements, dynamic regulation of cell adhesion and extensive cell migration. sosie (sie) is a novel gene required in various morphogenesis processes in Drosophila oogenesis. Lack of sie interferes with normal egg chamber packaging, maintenance of epithelial integrity and control of follicle cell migration, indicating that sie is involved in controlling epithelial integrity and cell migration. For these functions sie is required both in the germ line and in the soma. Consistent with this, Sosie localizes to plasma membranes in the germ line and in the somatic follicle cells and is predicted to present an EGF-like domain on the extracellular side. Two positively charged residues, C-terminal to the predicted transmembrane domain (on the cytoplasmic side), are required for normal plasma membrane localization of Sosie. Because sie also contributes to normal cortical localization of β(H)-Spectrin, it appears that cortical β(H)-Spectrin mediates some of the functions of sosie. sie also interacts with the genes coding for the actin organizers Filamin and Profilin and, in the absence of sie function, F-actin is less well organized and nurse cells frequently fuse.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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...

Expression and functional role of sprouty-2 in breast morphogenesis.

Science.gov (United States)

Sigurdsson, Valgardur; Ingthorsson, Saevar; Hilmarsdottir, Bylgja; Gustafsdottir, Sigrun M; Franzdottir, Sigridur Rut; Arason, Ari Jon; Steingrimsson, Eirikur; Magnusson, Magnus K; Gudjonsson, Thorarinn

2013-01-01

Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR) and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2) in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D) culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD) resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an important regulator of

Expression and functional role of sprouty-2 in breast morphogenesis.

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Valgardur Sigurdsson

Full Text Available Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs, including epidermal growth factor receptor (EGFR and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2 in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an

Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

International Nuclear Information System (INIS)

Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.

2015-01-01

The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function

Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

Energy Technology Data Exchange (ETDEWEB)

Jumat, Muhammad Raihan [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Yan, Yan [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Ravi, Laxmi Iyer [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wong, Puisan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Huong, Tra Nguyen [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Li, Chunwei [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Tan, Boon Huan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Wang, De Yun [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Sugrue, Richard J., E-mail: rjsugrue@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)

2015-10-15

The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

Epithelial morphogenesis: the mouse eye as a model system.

Science.gov (United States)

Chauhan, Bharesh; Plageman, Timothy; Lou, Ming; Lang, Richard

2015-01-01

Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development. © 2015 Elsevier Inc. All rights reserved.

The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

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Nagalakshmi, Vidya K; Yu, Jing

2015-03-01

The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.

Science.gov (United States)

Wang, Lixin; Brugge, Joan S; Janes, Kevin A

2011-10-04

Gene expression networks are complicated by the assortment of regulatory factors that bind DNA and modulate transcription combinatorially. Single-cell measurements can reveal biological mechanisms hidden by population averages, but their value has not been fully explored in the context of mRNA regulation. Here, we adapted a single-cell expression profiling technique to examine the gene expression program downstream of Forkhead box O (FOXO) transcription factors during 3D breast epithelial acinar morphogenesis. By analyzing patterns of mRNA fluctuations among individual matrix-attached epithelial cells, we found that a subset of FOXO target genes was jointly regulated by the transcription factor Runt-related transcription factor 1 (RUNX1). Knockdown of RUNX1 causes hyperproliferation and abnormal morphogenesis, both of which require normal FOXO function. Down-regulating RUNX1 and FOXOs simultaneously causes widespread oxidative stress, which arrests proliferation and restores normal acinar morphology. In hormone-negative breast cancers lacking human epidermal growth factor receptor 2 (HER2) amplification, we find that RUNX1 down-regulation is strongly associated with up-regulation of FOXO1, which may be required to support growth of RUNX1-negative tumors. The coordinate function of these two tumor suppressors may provide a failsafe mechanism that inhibits cancer progression.

Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis.

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Mayssa Nassour

Full Text Available Morphogenesis results from the coordination of distinct cell signaling pathways controlling migration, differentiation, apoptosis, and proliferation, along stem/progenitor cell dynamics. To decipher this puzzle, we focused on epithelial-mesenchymal transition (EMT "master genes". EMT has emerged as a unifying concept, involving cell-cell adhesion, migration and apoptotic pathways. EMT also appears to mingle with stemness. However, very little is known on the physiological role and relevance of EMT master-genes. We addressed this question during mammary morphogenesis. Recently, a link between Slug/Snai2 and stemness has been described in mammary epithelial cells, but EMT master genes actual localization, role and targets during mammary gland morphogenesis are not known and we focused on this basic question.Using a Slug-lacZ transgenic model and immunolocalization, we located Slug in a distinct subpopulation covering about 10-20% basal cap and duct cells, mostly cycling cells, coexpressed with basal markers P-cadherin, CK5 and CD49f. During puberty, Slug-deficient mammary epithelium exhibited a delayed development after transplantation, contained less cycling cells, and overexpressed CK8/18, ER, GATA3 and BMI1 genes, linked to luminal lineage. Other EMT master genes were overexpressed, suggesting compensation mechanisms. Gain/loss-of-function in vitro experiments confirmed Slug control of mammary epithelial cell luminal differentiation and proliferation. In addition, they showed that Slug enhances specifically clonal mammosphere emergence and growth, cell motility, and represses apoptosis. Strikingly, Slug-deprived mammary epithelial cells lost their potential to generate secondary clonal mammospheres.We conclude that Slug pathway controls the growth dynamics of a subpopulation of cycling progenitor basal cells during mammary morphogenesis. Overall, our data better define a key mechanism coordinating cell lineage dynamics and morphogenesis, and

PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration.

Science.gov (United States)

Pichaud, Franck

2018-01-01

The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM) and zonula adherens (ZA) , thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1) gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

Epithelial topography for repetitive tooth formation

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Marcia Gaete

2015-12-01

Full Text Available During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells.

Ascidian notochord morphogenesis

OpenAIRE

Jiang, Di; Smith, William C.

2007-01-01

The development of the notochord involves a complex set of cellular behaviors. While these morphogenic behaviors are common to all chordates, the ascidian provides a particularly attractive experimental model because of its relative simplicity. In particular, all notochord morphogenesis in ascidians takes place with only 40 cells, as opposed to the hundreds of cells in vertebrate models systems. Initial steps in ascidian notochord development convert a monolayer of epithelial-like cells in th...

The regulation of tooth morphogenesis is associated with epithelial cell proliferation and the expression of Sonic hedgehog through epithelial-mesenchymal interactions

International Nuclear Information System (INIS)

Ishida, Kentaro; Murofushi, Mayumi; Nakao, Kazuhisa; Morita, Ritsuko; Ogawa, Miho; Tsuji, Takashi

2011-01-01

Research highlights: → Bioengineered teeth regulated the contact area of epithelium and mesenchyme. → The crown width is regulated by the contact area of the epithelium and mesenchyme. → This regulation is associated with cell proliferation and Sonic hedgehog expression. → The cusp number is correlated with the crown width of the bioengineered tooth. → Cell proliferation and Shh expression areas regulate the tooth morphogenesis. -- Abstract: Ectodermal organs, such as the tooth, salivary gland, hair, and mammary gland, develop through reciprocal epithelial-mesenchymal interactions. Tooth morphologies are defined by the crown width and tooth length (macro-morphologies), and by the number and locations of the cusp and roots (micro-morphologies). In our current study, we report that the crown width of a bioengineered molar tooth, which was reconstructed using dissociated epithelial and mesenchymal cells via an organ germ method, can be regulated by the contact area between epithelial and mesenchymal cell layers. We further show that this is associated with cell proliferation and Sonic hedgehog (Shh) expression in the inner enamel epithelium after the germ stage has formed a secondary enamel knot. We also demonstrate that the cusp number is significantly correlated with the crown width of the bioengineered tooth. These findings suggest that the tooth micro-morphology, i.e. the cusp formation, is regulated after the tooth width, or macro-morphology, is determined. These findings also suggest that the spatiotemporal patterning of cell proliferation and the Shh expression areas in the epithelium regulate the crown width and cusp formation of the developing tooth.

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.

PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration

Directory of Open Access Journals (Sweden)

Franck Pichaud

2018-03-01

Full Text Available The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM and zonula adherens (ZA, thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1 gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta

International Nuclear Information System (INIS)

Hirai, Yohei; Radisky, Derek; Boudreau, Rosanne; Simian, Marina; Stevens, Mary E.; Oka, Yumiko; Takebe, Kyoko; Niwa, Shinichiro; Bissell, Mina J.

2002-01-01

We have previously shown that epimorphin, a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which epimorphin mediates luminal morphogenesis. Treatment of cells with epimorphin to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, as constitutive expression of LIP was sufficient to produce lumen formation, while constitutive expression of LAP blocked epimorphin-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which epimorphin expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPbeta, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for epimorphin in luminal morphogenesis through control of C/EBPbeta expression

Engineering epithelial-stromal interactions in vitro for toxicology assessment

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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 t...

Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.

Science.gov (United States)

Townley, Anna K; Schmidt, Katy; Hodgson, Lorna; Stephens, David J

2012-02-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.

Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

Science.gov (United States)

Townley, Anna K.; Schmidt, Katy; Hodgson, Lorna; Stephens, David J.

2012-01-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture. PMID:22331354

Engineering stromal-epithelial interactions in vitro for ...

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 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

Cell vertices as independent actors during cell intercalation in epithelial morphogenesis

Science.gov (United States)

Loerke, Dinah

Epithelial sheets form the lining of organ surfaces and body cavities, and it is now appreciated that these sheets are dynamic structures that can undergo significant reorganizing events, e.g. during wound healing or morphogenesis. One of the key morphogenetic mechanisms that is utilized during development is tissue elongation, which is driven by oriented cell intercalation. In the Drosophila embryonic epithelium, this occurs through the contraction of vertical T1 interfaces and the subsequent resolution of horizontal T3 interfaces (analogous to so-called T1 transitions in soap foams), where the symmetry breaking behaviors are created by a system of planar polarity of actomyosin and adhesion complexes within the cell layer. The dominant physical model for this process posits that the anisotropy of line tension directs T1 contraction. However, this model is inconsistent with the in vivo observation that cell vertices of T1 interfaces lack physical coupling, and instead show independent movements. Thus, we propose that a more useful explanation of intercalary behaviors will be possible through a description of the radially-directed and adhesion-coupled force events that lead to vertex movements and produce subsequent dependent changes in interface lengths. This work is supported by NIH R15 GM117463-01 and by a Research Corporation for Science Advancement (RCSA) Cottrell Scholar Award.

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

International Nuclear Information System (INIS)

Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

2002-01-01

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

2002-03-06

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

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

Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

Science.gov (United States)

Hara, Yusuke

2017-06-01

The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

DEFF Research Database (Denmark)

Elias, Bertha C; Das, Amrita; Parekh, Diptiben V

2015-01-01

The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and main......The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development...

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

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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.

Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

Science.gov (United States)

Barriga, Elias H; Franze, Kristian; Charras, Guillaume; Mayor, Roberto

2018-02-22

Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

OpenAIRE

Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

2001-01-01

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth fa...

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.

Cell-based multi-parametric model of cleft progression during submandibular salivary gland branching morphogenesis.

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Shayoni Ray

Full Text Available Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft

Collective cell migration drives morphogenesis of the kidney nephron.

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Aleksandr Vasilyev

2009-01-01

Full Text Available Tissue organization in epithelial organs is achieved during development by the combined processes of cell differentiation and morphogenetic cell movements. In the kidney, the nephron is the functional organ unit. Each nephron is an epithelial tubule that is subdivided into discrete segments with specific transport functions. Little is known about how nephron segments are defined or how segments acquire their distinctive morphology and cell shape. Using live, in vivo cell imaging of the forming zebrafish pronephric nephron, we found that the migration of fully differentiated epithelial cells accounts for both the final position of nephron segment boundaries and the characteristic convolution of the proximal tubule. Pronephric cells maintain adherens junctions and polarized apical brush border membranes while they migrate collectively. Individual tubule cells exhibit basal membrane protrusions in the direction of movement and appear to establish transient, phosphorylated Focal Adhesion Kinase-positive adhesions to the basement membrane. Cell migration continued in the presence of camptothecin, indicating that cell division does not drive migration. Lengthening of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros. Complete blockade of pronephric fluid flow prevented cell migration and proximal nephron convolution. Selective blockade of proximal, filtration-driven fluid flow shifted the position of tubule convolution distally and revealed a role for cilia-driven fluid flow in persistent migration of distal nephron cells. We conclude that nephron morphogenesis is driven by fluid flow-dependent, collective epithelial cell migration within the confines of the tubule basement membrane. Our results establish intimate links between nephron function, fluid flow, and morphogenesis.

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....

The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway

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Zakia A. Abdelhamed

2015-06-01

Full Text Available Ciliopathies are a group of developmental disorders that manifest with multi-organ anomalies. Mutations in TMEM67 (MKS3 cause a range of human ciliopathies, including Meckel-Gruber and Joubert syndromes. In this study we describe multi-organ developmental abnormalities in the Tmem67tm1Dgen/H1 knockout mouse that closely resemble those seen in Wnt5a and Ror2 knockout mice. These include pulmonary hypoplasia, ventricular septal defects, shortening of the body longitudinal axis, limb abnormalities, and cochlear hair cell stereociliary bundle orientation and basal body/kinocilium positioning defects. The basal body/kinocilium complex was often uncoupled from the hair bundle, suggesting aberrant basal body migration, although planar cell polarity and apical planar asymmetry in the organ of Corti were normal. TMEM67 (meckelin is essential for phosphorylation of the non-canonical Wnt receptor ROR2 (receptor-tyrosine-kinase-like orphan receptor 2 upon stimulation with Wnt5a-conditioned medium. ROR2 also colocalises and interacts with TMEM67 at the ciliary transition zone. Additionally, the extracellular N-terminal domain of TMEM67 preferentially binds to Wnt5a in an in vitro binding assay. Cultured lungs of Tmem67 mutant mice failed to respond to stimulation of epithelial branching morphogenesis by Wnt5a. Wnt5a also inhibited both the Shh and canonical Wnt/β-catenin signalling pathways in wild-type embryonic lung. Pulmonary hypoplasia phenotypes, including loss of correct epithelial branching morphogenesis and cell polarity, were rescued by stimulating the non-canonical Wnt pathway downstream of the Wnt5a-TMEM67-ROR2 axis by activating RhoA. We propose that TMEM67 is a receptor that has a main role in non-canonical Wnt signalling, mediated by Wnt5a and ROR2, and normally represses Shh signalling. Downstream therapeutic targeting of the Wnt5a-TMEM67-ROR2 axis might, therefore, reduce or prevent pulmonary hypoplasia in ciliopathies and other congenital

Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension.

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Miles, Lee B; Darido, Charbel; Kaslin, Jan; Heath, Joan K; Jane, Stephen M; Dworkin, Sebastian

2017-12-14

The grainyhead-like (grhl) transcription factors play crucial roles in craniofacial development, epithelial morphogenesis, neural tube closure, and dorso-ventral patterning. By utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3, we show that both genes regulate epithelial migration, particularly convergence-extension (CE) type movements, during embryogenesis. Genetic deletion of grhl3 via CRISPR/Cas9 results in failure to complete epiboly and pre-gastrulation embryonic rupture, whereas morpholino (MO)-mediated knockdown of grhl3 signalling leads to aberrant neural tube morphogenesis at the midbrain-hindbrain boundary (MHB), a phenotype likely due to a compromised overlying enveloping layer (EVL). Further disruptions of grhl3-dependent pathways (through co-knockdown of grhl3 with target genes spec1 and arhgef19) confirm significant MHB morphogenesis and neural tube closure defects. Concomitant MO-mediated disruption of both grhl2b and grhl3 results in further extensive CE-like defects in body patterning, notochord and somite morphogenesis. Interestingly, over-expression of either grhl2b or grhl3 also leads to numerous phenotypes consistent with disrupted cellular migration during gastrulation, including embryo dorsalisation, axial duplication and impaired neural tube migration leading to cyclopia. Taken together, our study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis.

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

Interference by 2,3,7,8-tetrachlorodibenzo-p-dioxin with cultured mouse submandibular gland branching morphogenesis involves reduced epidermal growth factor receptor signaling

International Nuclear Information System (INIS)

Kiukkonen, Anu; Sahlberg, Carin; Partanen, Anna-Maija; Alaluusua, Satu; Pohjanvirta, Raimo; Tuomisto, Jouko; Lukinmaa, Pirjo-Liisa

2006-01-01

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to mouse embryonic teeth, sharing features of early development with salivary glands in common, involves enhanced apoptosis and depends on the expression of epidermal growth factor (EGF) receptor. EGF receptor signaling, on the other hand, is essential for salivary gland branching morphogenesis. To see if TCDD impairs salivary gland morphogenesis and if the impairment is associated with EGF receptor signaling, we cultured mouse (NMRI) E13 submandibular glands with TCDD or TCDD in combination with EGF or fibronectin (FN), both previously found to enhance branching morphogenesis. Explants were examined stereomicroscopically and processed to paraffin sections. TCDD exposure impaired epithelial branching and cleft formation, resulting in enlarged buds. The glands were smaller than normal. EGF and FN alone concentration-dependently stimulated or inhibited branching morphogenesis but when co-administered with TCDD, failed to compensate for its effect. TCDD induced cytochrome P4501A1 expression in the glandular epithelium, indicating activation of the aryl hydrocarbon receptor. TCDD somewhat increased epithelial apoptosis as observed by terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling method but the increase could not be correlated with morphological changes. The frequency of proliferating cells was not altered. Corresponding to the reduced cleft sites in TCDD-exposed explants, FN immunoreactivity in the epithelium was reduced. The results show that TCDD, comparably with EGF and FN at morphogenesis-inhibiting concentrations, impaired salivary gland branching morphogenesis in vitro. Together with the failure of EGF and FN at morphogenesis-stimulating concentrations to compensate for the effect of TCDD this implies that TCDD toxicity to developing salivary gland involves reduced EGF receptor signaling

Studying cytokinesis in Drosophila epithelial tissues.

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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.

Time-lapse analysis and mathematical characterization elucidate novel mechanisms underlying muscle morphogenesis.

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Chelsi J Snow

2008-10-01

Full Text Available Skeletal muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction (MTJ. In vertebrates, a great deal is known about muscle specification as well as how somitic cells, as a cohort, generate the early myotome. However, the cellular mechanisms that generate long muscle fibers from short cells and the molecular factors that limit elongation are unknown. We show that zebrafish fast muscle fiber morphogenesis consists of three discrete phases: short precursor cells, intercalation/elongation, and boundary capture/myotube formation. In the first phase, cells exhibit randomly directed protrusive activity. The second phase, intercalation/elongation, proceeds via a two-step process: protrusion extension and filling. This repetition of protrusion extension and filling continues until both the anterior and posterior ends of the muscle fiber reach the MTJ. Finally, both ends of the muscle fiber anchor to the MTJ (boundary capture and undergo further morphogenetic changes as they adopt the stereotypical, cylindrical shape of myotubes. We find that the basement membrane protein laminin is required for efficient elongation, proper fiber orientation, and boundary capture. These early muscle defects in the absence of either lamininbeta1 or laminingamma1 contrast with later dystrophic phenotypes in lamininalpha2 mutant embryos, indicating discrete roles for different laminin chains during early muscle development. Surprisingly, genetic mosaic analysis suggests that boundary capture is a cell-autonomous phenomenon. Taken together, our results define three phases of muscle fiber morphogenesis and show that the critical second phase of elongation proceeds by a repetitive process of protrusion extension and protrusion filling. Furthermore, we show that laminin is a novel and critical molecular cue mediating fiber orientation and limiting muscle cell length.

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.

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.

JNK Promotes Epithelial Cell Anoikis by Transcriptional and Post-translational Regulation of BH3-Only Proteins

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Nomeda Girnius

2017-11-01

Full Text Available Summary: Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis. While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that JNK acts through a BAK/BAX-dependent apoptotic pathway by increasing BIM expression and phosphorylating BMF, leading to death of detached epithelial cells. : Developmental morphogenesis, tissue injury, and oncogenic transformation can cause epithelial cell detachment. These cells are eliminated by a specialized form of apoptosis termed anoikis. Girnius and Davis show that anoikis is mediated by the cJUN NH2-terminal kinase (JNK, which increases BIM expression and phosphorylates BMF to engage BAK/BAX-dependent apoptosis. Keywords: apoptosis, anoikis, epithelial cell, mammary gland, JNK, BAX, BAK, BH3-only protein, BIM, BMF

Growth and morphogenesis of embryonic mouse organs on non-coated and extracellular matrix-coated Biopore membrane

Science.gov (United States)

Hardman, P.; Klement, B. J.; Spooner, B. S.

1993-01-01

Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression

Energy Technology Data Exchange (ETDEWEB)

Nelson, Celeste M.; Inman, Jamie L.; Bissell, Mina J.

2008-02-13

Here we describe a simple micromolding method to construct three-dimensional arrays of organotypic epithelial tissue structures that approximate in vivo histology. An elastomeric stamp containing an array of posts of defined geometry and spacing is used to mold microscale cavities into the surface of type I collagen gels. Epithelial cells are seeded into the cavities and covered with a second layer of collagen. The cells reorganize into hollow tissues corresponding to the geometry of the cavities. Patterned tissue arrays can be produced in 3-4 h and will undergo morphogenesis over the following one to three days. The protocol can easily be adapted to study a variety of tissues and aspects of normal and neoplastic development.

Rac1 controls epithelial tube length through the apical secretion and polarity pathways

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Kévin Sollier

2016-01-01

Full Text Available The morphometric parameters of epithelial tubes are critical to the physiology and homeostasis of most organs. In addition, many human diseases are associated with tube-size defects. Here, we show that Rac1 limits epithelial tube elongation in the developing fly trachea by promoting Rab5-dependent endocytosis of the apical determinant Crumbs. Rac1 is also involved in a positive feedback loop with the septate junction protein Coracle. Thereby, Rac1 precludes paracellular diffusion and contributes to the septate junction-dependent secretion of the chitin-modifying enzymes Vermiform and Serpentine, which restrict epithelial tube length independently of Crumbs. Thus, Rac1 is a critical component of two important pathways controlling epithelial tube morphogenesis.

Homology with vesicle fusion mediator syntaxin-1a predicts determinants ofepimorphin/syntaxin-2 function in mammary epithelial morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Chen, Connie S.; Nelson, Celeste M.; Khauv, Davitte; Bennett, Simone; Radisky, Evette S.; Hirai, Yohei; Bissell, Mina J.; Radisky, Derek C.

2009-06-03

We have shown that branching morphogenesis of mammary ductal structures requires the action of the morphogen epimorphin/syntaxin-2. Epimorphin, originally identified as an extracellular molecule, is identical to syntaxin-2, an intracellular molecule that is a member of the extensively investigated syntaxin family of proteins that mediate vesicle trafficking. We show here that although epimorphin/syntaxin-2 is highly homologous to syntaxin-1a, only epimorphin/syntaxin-2 can stimulate mammary branching morphogenesis. We construct a homology model of epimorphin/syntaxin-2 based on the published structure of syntaxin-1a, and we use this model to identify the structural motif responsible for the morphogenic activity. We identify four residues located within the cleft between helices B and C that differ between syntaxin-1a and epimorphin/syntaxin-2; through site-directed mutagenesis of these four amino acids, we confer the properties of epimorphin for cell adhesion, gene activation, and branching morphogenesis onto the inactive syntaxin-1a template. These results provide a dramatic demonstration of the use of structural information about one molecule to define a functional motif of a second molecule that is related at the sequence level but highly divergent functionally.

Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis.

Science.gov (United States)

Wang, Yifan; Zhou, Binhua P

2013-03-01

Epithelial-mesenchymal transition (EMT) is a highly conserved cellular program that converts polarized, immotile epithelial cells to migratory mesenchymal cells. In addition, EMT was initially recognized as a key step for morphogenesis during embryonic development. Emerging evidences indicate that this important developmental program promotes metastasis, drug resistance, and tumor recurrence, features that are associated with a poor clinical outcome for patients with breast cancer. Therefore, better understanding of regulation and signaling pathways in EMT is essential to develop novel targeted therapeutics. In this review, we present updated developments underlying EMT in tumor progression and metastasis, and discuss the challenges remaining in breast cancer research.

Shape self-regulation in early lung morphogenesis.

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Raphaël Clément

Full Text Available The arborescent architecture of mammalian conductive airways results from the repeated branching of lung endoderm into surrounding mesoderm. Subsequent lung's striking geometrical features have long raised the question of developmental mechanisms involved in morphogenesis. Many molecular actors have been identified, and several studies demonstrated the central role of Fgf10 and Shh in growth and branching. However, the actual branching mechanism and the way branching events are organized at the organ scale to achieve a self-avoiding tree remain to be understood through a model compatible with evidenced signaling. In this paper we show that the mere diffusion of FGF10 from distal mesenchyme involves differential epithelial proliferation that spontaneously leads to branching. Modeling FGF10 diffusion from sub-mesothelial mesenchyme where Fgf10 is known to be expressed and computing epithelial and mesenchymal growth in a coupled manner, we found that the resulting laplacian dynamics precisely accounts for the patterning of FGF10-induced genes, and that it spontaneously involves differential proliferation leading to a self-avoiding and space-filling tree, through mechanisms that we detail. The tree's fine morphological features depend on the epithelial growth response to FGF10, underlain by the lung's complex regulatory network. Notably, our results suggest that no branching information has to be encoded and that no master routine is required to organize branching events at the organ scale. Despite its simplicity, this model identifies key mechanisms of lung development, from branching to organ-scale organization, and could prove relevant to the development of other branched organs relying on similar pathways.

Pancreatic morphogenesis and extracellular matrix organization during rat development.

Science.gov (United States)

Hisaoka, M; Haratake, J; Hashimoto, H

1993-07-01

pancreas, especially in the branching epithelial morphogenesis, and the major alterations appeared prior to distinct acinar cell differentiation.

From cells to tissue: A continuum model of epithelial mechanics

Science.gov (United States)

Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

2017-08-01

A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane

Energy Technology Data Exchange (ETDEWEB)

BARCELLOS-HOFF, M. H; AGGELER, J.; RAM, T. G; BISSELL, M. J

1989-02-01

An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrixensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar

Myoepithelial Cells: Their Origin and Function in Lacrimal Gland Morphogenesis, Homeostasis, and Repair.

Science.gov (United States)

Makarenkova, Helen P; Dartt, Darlene A

2015-09-01

Lacrimal gland (LG) is an exocrine tubuloacinar gland that secretes the aqueous layer of the tear film. LG epithelium is composed of ductal, acinar, and myoepithelial cells (MECs) bordering the basal lamina and separating the epithelial layer from the extracellular matrix. Mature MECs have contractile ability and morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. Increasing evidence supports the assertion that myoepithelial cells (MECs) play key roles in the lacrimal gland development, homeostasis, and stabilizing the normal structure and polarity of LG secretory acini. MECs take part in the formation of extracellular matrix gland and participate in signal exchange between epithelium and stroma. MECs have a high level of plasticity and are able to differentiate into several cell lineages. Here, we provide a review on some of the MEC characteristics and their role in LG morphogenesis, maintenance, and repair.

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.

Glycoprotein A repetitions predominant (GARP) positively regulates transforming growth factor (TGF) β3 and is essential for mouse palatogenesis.

Science.gov (United States)

Wu, Bill X; Li, Anqi; Lei, Liming; Kaneko, Satoshi; Wallace, Caroline; Li, Xue; Li, Zihai

2017-11-03

Glycoprotein A repetitions predominant (GARP) (encoded by the Lrrc32 gene) plays important roles in cell-surface docking and activation of TGFβ. However, GARP's role in organ development in mammalian systems is unclear. To determine the function of GARP in vivo , we generated a GARP KO mouse model. Unexpectedly, the GARP KO mice died within 24 h after birth and exhibited defective palatogenesis without apparent abnormalities in other major organs. Furthermore, we observed decreased apoptosis and SMAD2 phosphorylation in the medial edge epithelial cells of the palatal shelf of GARP KO embryos at embryonic day 14.5 (E14.5), indicating a defect in the TGFβ signaling pathway in the GARP-null developing palates. Of note, the failure to develop the secondary palate and concurrent reduction of SMAD phosphorylation without other defects in GARP KO mice phenocopied TGFβ3 KO mice, although GARP has not been suggested previously to interact with TGFβ3. We found that GARP and TGFβ3 co-localize in medial edge epithelial cells at E14.5. In vitro studies confirmed that GARP and TGFβ3 directly interact and that GARP is indispensable for the surface expression of membrane-associated latent TGFβ3. Our findings indicate that GARP is essential for normal morphogenesis of the palate and demonstrate that GARP plays a crucial role in regulating TGFβ3 signaling during embryogenesis. In conclusion, we have uncovered a novel function of GARP in positively regulating TGFβ3 activation and function. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A dynamic cellular vertex model of growing epithelial tissues

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Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

2017-04-01

Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

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Zhao, Tiankai; Zhang, Yao; Wei, Qiong; Shi, Xuechen; Zhao, Peng; Chen, Long-Qing; Zhang, Sulin

2018-03-01

Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.

A novel role for integrin-linked kinase in epithelial sheet morphogenesis.

Science.gov (United States)

Vespa, Alisa; D'Souza, Sudhir J A; Dagnino, Lina

2005-09-01

Integrin-linked kinase (ILK) is a multidomain protein involved in cell motility and cell-extracellular matrix interactions. ILK is found in integrin-containing focal adhesions in undifferentiated primary epidermal keratinocytes. Induction of keratinocyte differentiation by treatment with Ca(2+) triggers formation of cell-cell junctions, loss of focal adhesions, and ILK distribution to cell borders. We now show that Ca(2+) treatment of keratinocytes induces rapid (6 h) localization of tight junction (TJ) proteins. The kinetics of ILK movement toward the cell periphery mimics that of AJ components, suggesting that ILK plays a role in the early formation of cell-cell contacts. Whereas the N terminus in ILK mediates localization to cell borders, expression of an ILK deletion mutant incapable of localizing to the cell membrane (ILK 191-452) interferes with translocation of E-cadherin/beta-catenin to cell borders, precluding Ca(2+)-induced AJ formation. Cells expressing ILK 191-452 also fail to form TJ and sealed cell-cell borders and do not form epithelial sheets. Thus, we have uncovered a novel role for ILK in epithelial cell-cell adhesion, independent of its well-established role in integrin-mediated adhesion and migration.

Rac1 modulates mammalian lung branching morphogenesis in part through canonical Wnt signaling.

Science.gov (United States)

Danopoulos, Soula; Krainock, Michael; Toubat, Omar; Thornton, Matthew; Grubbs, Brendan; Al Alam, Denise

2016-12-01

Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation. Copyright © 2016 the American Physiological Society.

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.

Epithelial progenitor cell lines as models of normal breast morphogenesis and neoplasia

DEFF Research Database (Denmark)

Petersen, Ole William; Gudjonsson, Thorarinn; Villadsen, René

2003-01-01

The majority of human breast carcinomas exhibit luminal characteristics and as such, are most probably derived from progenitor cells within the luminal epithelial compartment. This has been subdivided recently into at least three luminal subtypes based on gene expression patterns. The value of kn...

Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis.

Directory of Open Access Journals (Sweden)

Paul Riccio

2016-02-01

Full Text Available Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM, combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret-/- or Etv4-/- sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret

A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues

NARCIS (Netherlands)

Parsons, Linda M.; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

2017-01-01

In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein

Calcium as a signal integrator in developing epithelial tissues.

Science.gov (United States)

Brodskiy, Pavel A; Zartman, Jeremiah J

2018-05-16

Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

GATA4 Regulates Epithelial Cell Proliferation to Control Intestinal Growth and Development in MiceSummary

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Bridget M. Kohlnhofer

2016-03-01

Full Text Available Background & Aims: The embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium is unknown. Methods: By using Sonic Hedgehog Cre to eliminate GATA4 in the midgut endoderm of mouse embryos, we determined the impact of loss of GATA4 on intestinal development, including epithelial cell proliferation, between embryonic day (E9.5 and E18.5. Results: We found that intestinal length and width were decreased in GATA4 mutants compared with controls. GATA4-deficient intestinal epithelium contained fewer cells, and epithelial girth was decreased. We further observed a decreased proportion of proliferating epithelial cells at E10.5 and E11.5 in GATA4 mutants. We showed that GATA4 binds to chromatin containing GATA4 consensus binding sites within cyclin D2 (Ccnd2, cyclin-dependent kinase 6 (Cdk6, and frizzled 5 (Fzd5. Moreover, Ccnd2, Cdk6, and Fzd5 transcripts were reduced at E11.5 in GATA4 mutant tissue. Villus morphogenesis was delayed, and villus structure was abnormal in GATA4 mutant intestine. Conclusions: Our data identify GATA4 as an essential regulator of early intestinal epithelial cell proliferation. We propose that GATA4 controls proliferation in part by directly regulating transcription of cell-cycle mediators. Our data further suggest that GATA4 affects proliferation through transcriptional regulation of Fzd5, perhaps by influencing the response of the epithelium to WNT signaling. Keywords: Transcriptional Regulation, WNT Signaling, Villus Morphogenesis

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis.

Science.gov (United States)

Ohsawa, Shizue; Vaughen, John; Igaki, Tatsushi

2018-02-05

Epithelial tissues robustly respond to internal and external stressors via dynamic cellular rearrangements. Cell extrusion acts as a key regulator of epithelial homeostasis by removing apoptotic cells, orchestrating morphogenesis, and mediating competitive cellular battles during tumorigenesis. Here, we delineate the diverse functions of cell extrusion during development and disease. We emphasize the expanding role for apoptotic cell extrusion in exerting morphogenetic forces, as well as the strong intersection of cell extrusion with cell competition, a homeostatic mechanism that eliminates aberrant or unfit cells. While cell competition and extrusion can exert potent, tumor-suppressive effects, dysregulation of either critical homeostatic program can fuel cancer progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells.

Directory of Open Access Journals (Sweden)

Junnian Zhou

Full Text Available Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3alpha and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, beta1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role.

Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

Energy Technology Data Exchange (ETDEWEB)

Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

2008-02-13

Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

Friend or foe: Endoplasmic reticulum protein 29 (ERp29) in epithelial cancer

Science.gov (United States)

Chen, Shaohua; Zhang, Daohai

2015-01-01

The endoplasmic reticulum (ER) protein 29 (ERp29) is a molecular chaperone that plays a critical role in protein secretion from the ER in eukaryotic cells. Recent studies have also shown that ERp29 plays a role in cancer. It has been demonstrated that ERp29 is inversely associated with primary tumor development and functions as a tumor suppressor by inducing cell growth arrest in breast cancer. However, ERp29 has also been reported to promote epithelial cell morphogenesis, cell survival against genotoxic stress and distant metastasis. In this review, we summarize the current understanding on the biological and pathological functions of ERp29 in cancer and discuss the pivotal aspects of ERp29 as “friend or foe” in epithelial cancer. PMID:25709888

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

Science.gov (United States)

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 microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis.

Science.gov (United States)

Hoefert, Jaimee E; Bjerke, Glen A; Wang, Dongmei; Yi, Rui

2018-06-04

The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how the two subfamilies of the five-miRNA family, distinguished by a single nucleotide within the seed region, regulate their targets. By directly ligating miRNAs to their targeted mRNA regions, we identify numerous miR-200 targets involved in the regulation of focal adhesion, actin cytoskeleton, cell cycle, and Hippo/Yap signaling. The two subfamilies bind to largely distinct target sites, but many genes are coordinately regulated by both subfamilies. Using inducible and knockout mouse models, we show that the miR-200 family regulates cell adhesion and orientation in the hair germ, contributing to precise cell fate specification and hair morphogenesis. Our findings demonstrate that combinatorial targeting of many genes is critical for miRNA function and provide new insights into miR-200's functions. © 2018 Hoefert et al.

Perithecium morphogenesis in Sordaria macrospora.

Science.gov (United States)

Lord, Kathryn M; Read, Nick D

2011-04-01

The perithecium of the self-fertile ascomycete Sordaria macrospora provides an excellent model in which to analyse fungal multicellular development. This study provides a detailed analysis of perithecium morphogenesis in the wild type and eight developmental mutants of S. macrospora, using a range of correlative microscopical techniques. Fundamentally, perithecia and other complex multicellular structures produced by fungi arise by hyphal aggregation and adhesion, and these processes are followed by specialization and septation of hyphal compartments within the aggregates. Perithecial morphogenesis can be divided into the ascogonial, protoperithecial, and perithecial stages of development. At least 13 specialized, morphologically distinct cell-types are involved in perithecium morphogenesis, and these fall into three basic classes: hyphae, conglutinate cells and spores. Conglutinate cells arise from hyphal adhesion and certain perithecial hyphae develop from conglutinate cells. Various hypha-conglutinate cell transitions play important roles during the development of the perithecial wall and neck. Copyright © 2010. Published by Elsevier Inc.

A spatially-averaged mathematical model of kidney branching morphogenesis

KAUST Repository

Zubkov, V.S.

2015-08-01

© 2015 Published by Elsevier Ltd. Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

A spatially-averaged mathematical model of kidney branching morphogenesis

KAUST Repository

Zubkov, V.S.; Combes, A.N.; Short, K.M.; Lefevre, J.; Hamilton, N.A.; Smyth, I.M.; Little, M.H.; Byrne, H.M.

2015-01-01

© 2015 Published by Elsevier Ltd. Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.

Science.gov (United States)

Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I

2015-05-01

Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. Copyright © 2015 the American Physiological Society.

A global sensitivity analysis approach for morphogenesis models

KAUST Repository

Boas, Sonja E. M.; Navarro, Marí a; Merks, Roeland M. H.; Blom, Joke G.

2015-01-01

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand

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

Establishment of three-dimensional cultures of human pancreatic duct epithelial cells

International Nuclear Information System (INIS)

Gutierrez-Barrera, Angelica M.; Menter, David G.; Abbruzzese, James L.; Reddy, Shrikanth A.G.

2007-01-01

Three-dimensional (3D) cultures of epithelial cells offer singular advantages for studies of morphogenesis or the role of cancer genes in oncogenesis. In this study, as part of establishing a 3D culture system of pancreatic duct epithelial cells, we compared human pancreatic duct epithelial cells (HPDE-E6E7) with pancreatic cancer cell lines. Our results show, that in contrast to cancer cells, HPDE-E6E7 organized into spheroids with what appeared to be apical and basal membranes and a luminal space. Immunostaining experiments indicated that protein kinase Akt was phosphorylated (Ser473) and CTMP, a negative Akt regulator, was expressed in both HPDE-E6E7 and cancer cells. However, a nuclear pool of CTMP was detectable in HPDE-E6E7 cells that showed a dynamic concentrated expression pattern, a feature that further distinguished HPDE-E637 cells from cancer cells. Collectively, these data suggest that 3D cultures of HPDE-E6E7 cells are useful for investigating signaling and morphological abnormalities in pancreatic cancer cells

[Immunomorphologic features of epithelial-stromal relationships at hyperplasia and endometrial carcinoma].

Science.gov (United States)

Bantysh, B B; Paukov, v S; Kogan, E A

2012-01-01

The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

Emergent material properties of developing epithelial tissues.

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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

Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

Directory of Open Access Journals (Sweden)

Stephanie E Westcot

Full Text Available Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP, an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish. In vivo selection for skin-specific expression of gene-break transposon (GBT mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a revealed a novel requirement for a Neuregulin 2a (Nrg2a-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity

Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis.

Science.gov (United States)

Westcot, Stephanie E; Hatzold, Julia; Urban, Mark D; Richetti, Stefânia K; Skuster, Kimberly J; Harm, Rhianna M; Lopez Cervera, Roberto; Umemoto, Noriko; McNulty, Melissa S; Clark, Karl J; Hammerschmidt, Matthias; Ekker, Stephen C

2015-01-01

Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape

In Vitro Experimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells.

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Hagiwara, Masaya; Maruta, Naomichi; Marumoto, Moegi

2017-06-01

Lung branching morphogenesis has been studied for decades, but the underlying developmental mechanisms are still not fully understood. Cellular movements dynamically change during the branching process, but it is difficult to observe long-term cellular dynamics by in vivo or tissue culture experiments. Therefore, developing an in vitro experimental model of bronchial tree would provide an essential tool for developmental biology, pathology, and systems biology. In this study, we succeeded in reconstructing a bronchial tree in vitro by using primary human bronchial epithelial cells. A high concentration gradient of bronchial epithelial cells was required for branching initiation, whereas homogeneously distributed endothelial cells induced the formation of successive branches. Subsequently, the branches grew in size to the order of millimeter. The developed model contains only two types of cells and it facilitates the analysis of lung branching morphogenesis. By taking advantage of our experimental model, we carried out long-term time-lapse observations, which revealed self-assembly, collective migration with leader cells, rotational motion, and spiral motion of epithelial cells in each developmental event. Mathematical simulation was also carried out to analyze the self-assembly process and it revealed simple rules that govern cellular dynamics. Our experimental model has provided many new insights into lung development and it has the potential to accelerate the study of developmental mechanisms, pattern formation, left-right asymmetry, and disease pathogenesis of the human lung.

A global sensitivity analysis approach for morphogenesis models

NARCIS (Netherlands)

S.E.M. Boas (Sonja); M.I. Navarro Jimenez (Maria); R.M.H. Merks (Roeland); J.G. Blom (Joke)

2015-01-01

textabstract{\\bf Background} %if any Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the

Repetition and the Concept of Repetition

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Arne Grøn

2013-11-01

Full Text Available This paper offers a description of the meaning of the category of repetition. Firstly, it is pointed out that Constantin uses repetition as a concept that means the creation of epochs; the passing from Greece to Modernity is accomplished distinguishing between recollection, a concept that looks back to the past, and repetition, a concept that looks forward to future. Secondly, it is showed that the category of repetition, as a religious category, relates with what Climacus calls “ethic despair” and with what Vigilius calls “second ethics”; it is through repetition that it can be understood that sin finds its place in ethics and these shows the tension between it and dogmatics. And thirdly, it is showed that the descovery of the new category of repetition is a rediscovery of what Kierkegaard calls category of spirit; repetition has for its object the individuality, and coming to be oneself is what Kierkegaard undertands as liberty. At the end of the paper it is questioned if the category of repetition is inconsistent with the book Repetition.

A global sensitivity analysis approach for morphogenesis models

KAUST Repository

Boas, Sonja E. M.

2015-11-21

Background Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such ‘black-box’ models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. Results To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. Conclusions We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all ‘black-box’ models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

A global sensitivity analysis approach for morphogenesis models.

Science.gov (United States)

Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

2015-11-21

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Sea Urchin Morphogenesis.

Science.gov (United States)

McClay, David R

2016-01-01

In the sea urchin morphogenesis follows extensive molecular specification. The specification controls the many morphogenetic events and these, in turn, precede patterning steps that establish the larval body plan. To understand how the embryo is built it was necessary to understand those series of molecular steps. Here an example of the historical sequence of those discoveries is presented as it unfolded over the last 50 years, the years during which major progress in understanding development of many animals and plants was documented by CTDB. In sea urchin development a rich series of experimental studies first established many of the phenomenological components of skeletal morphogenesis and patterning without knowledge of the molecular components. The many discoveries of transcription factors, signals, and structural proteins that contribute to the shape of the endoskeleton of the sea urchin larva then followed as molecular tools became available. A number of transcription factors and signals were discovered that were necessary for specification, morphogenesis, and patterning. Perturbation of the transcription factors and signals provided the means for assembling models of the gene regulatory networks used for specification and controlled the subsequent morphogenetic events. The earlier experimental information informed perturbation experiments that asked how patterning worked. As a consequence it was learned that ectoderm provides a series of patterning signals to the skeletogenic cells and as a consequence the skeletogenic cells secrete a highly patterned skeleton based on their ability to genotypically decode the localized reception of several signals. We still do not understand the complexity of the signals received by the skeletogenic cells, nor do we understand in detail how the genotypic information shapes the secreted skeletal biomineral, but the current knowledge at least outlines the sequence of events and provides a useful template for future

Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations that leads to stable epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells

Energy Technology Data Exchange (ETDEWEB)

Lochter, A.; Galosy, S.; Muschler, J.; Freedman, N.; Werb, Z.; Bissell, M.J.

1997-08-11

Matrix metalloproteinases (MMPs) regulate ductal morphogenesis, apoptosis, and neoplastic progression in mammary epithelial cells. To elucidate the direct effects of MMPs on mammary epithelium, we generated functionally normal cells expressing an inducible autoactivating stromelysin-1 (SL-1) transgene. Induction of SL-1 expression resulted in cleavage of E-cadherin, and triggered progressive phenotypic conversion characterized by disappearance of E-cadherin and catenins from cell-cell contacts, downregulation of cytokeratins, upregulation of vimentin, induction of keratinocyte growth factor expression and activation, and upregulation of endogenous MMPs. Cells expressing SL-1 were unable to undergo lactogenic differentiation and became invasive. Once initiated, this phenotypic conversion was essentially stable, and progressed even in the absence of continued SL-1 expression. These observations demonstrate that inappropriate expression of SL-1 initiates a cascade of events that may represent a coordinated program leading to loss of the differentiated epithelial phenotype and gain of some characteristics of tumor cells. Our data provide novel insights into how MMPs function in development and neoplastic conversion.

Site-Specific Expression of Gelatinolytic Activity during Morphogenesis of the Secondary Palate in the Mouse Embryo

Science.gov (United States)

Gkantidis, Nikolaos; Blumer, Susan; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

2012-01-01

Morphogenesis of the secondary palate in mammalian embryos involves two major events: first, reorientation of the two vertically oriented palatal shelves into a horizontal position above the tongue, and second, fusion of the two shelves at the midline. Genetic evidence in humans and mice indicates the involvement of matrix metalloproteinases (MMPs). As MMP expression patterns might differ from sites of activity, we used a recently developed highly sensitive in situ zymography technique to map gelatinolytic MMP activity in the developing mouse palate. At embryonic day 14.5 (E14.5), we detected strong gelatinolytic activity around the lateral epithelial folds of the nasopharyngeal cavity, which is generated as a consequence of palatal shelf elevation. Activity was concentrated in the basement membrane of the epithelial fold but extended into the adjacent mesenchyme, and increased in intensity with lateral outgrowth of the cavity at E15.5. Gelatinolytic activity at this site was not the consequence of epithelial fold formation, as it was also observed in Bmp7-deficient embryos where shelf elevation is delayed. In this case, gelatinolytic activity appeared in vertical shelves at the exact position where the epithelial fold will form during elevation. Mmp2 and Mmp14 (MT1-MMP), but not Mmp9 and Mmp13, mRNAs were expressed in the mesenchyme around the epithelial folds of the elevated palatal shelves; this was confirmed by immunostaining for MMP-2 and MT1-MMP. Weak gelatinolytic activity was also found at the midline of E14.5 palatal shelves, which increased during fusion at E15.5. Whereas MMPs have been implicated in palatal fusion before, this is the first report showing that gelatinases might contribute to tissue remodeling during early stages of palatal shelf elevation and formation of the nasopharynx. PMID:23091646

Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

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Shan Meltzer

2017-10-01

Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

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.

Physics and the canalization of morphogenesis: a grand challenge in organismal biology

International Nuclear Information System (INIS)

Von Dassow, Michelangelo; Davidson, Lance A

2011-01-01

Morphogenesis takes place against a background of organism-to-organism and environmental variation. Therefore, fundamental questions in the study of morphogenesis include: How are the mechanical processes of tissue movement and deformation affected by that variability, and in turn, how do the mechanic of the system modulate phenotypic variation? We highlight a few key factors, including environmental temperature, embryo size and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics—including feedback from mechanical cues—might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects

Programming Morphogenesis through Systems and Synthetic Biology.

Science.gov (United States)

Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

2018-04-01

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis

Science.gov (United States)

Bryan, Chase D.; Chien, Chi-Bin; Kwan, Kristen M.

2016-01-01

The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1UW1) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1UW1 mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis.

Science.gov (United States)

Nakrieko, Kerry-Ann; Welch, Ian; Dupuis, Holly; Bryce, Dawn; Pajak, Agnieszka; St Arnaud, René; Dedhar, Shoukat; D'Souza, Sudhir J A; Dagnino, Lina

2008-04-01

Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function.

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

Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury

Directory of Open Access Journals (Sweden)

Elie El Agha

2014-01-01

Full Text Available Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context.

Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury.

Science.gov (United States)

El Agha, Elie; Bellusci, Saverio

2014-01-01

Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context.

Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

Science.gov (United States)

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

Computational models of airway branching morphogenesis.

Science.gov (United States)

Varner, Victor D; Nelson, Celeste M

2017-07-01

The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches - geometric modeling, reaction-diffusion modeling, and continuum mechanical modeling - and discuss how, taken together, these models have identified the geometric principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify airway geometry in the developing embryo. We emphasize models that are integrated with biological experiments and suggest how recent progress in computational modeling has advanced our understanding of airway branching morphogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Morphogenesis and pattern formation in biological systems experiments and models

CERN Document Server

Noji, Sumihare; Ueno, Naoto; Maini, Philip

2003-01-01

A central goal of current biology is to decode the mechanisms that underlie the processes of morphogenesis and pattern formation. Concerned with the analysis of those phenomena, this book covers a broad range of research fields, including developmental biology, molecular biology, plant morphogenesis, ecology, epidemiology, medicine, paleontology, evolutionary biology, mathematical biology, and computational biology. In Morphogenesis and Pattern Formation in Biological Systems: Experiments and Models, experimental and theoretical aspects of biology are integrated for the construction and investigation of models of complex processes. This collection of articles on the latest advances by leading researchers not only brings together work from a wide spectrum of disciplines, but also provides a stepping-stone to the creation of new areas of discovery.

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

Science.gov (United States)

Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis

Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

International Nuclear Information System (INIS)

Ji, Jiayao; Li, Qinggang; Xie, Yuansheng; Zhang, Xueguang; Cui, Shaoyuan; Shi, Suozhu; Chen, Xiangmei

2012-01-01

Highlights: ► Overexpression of Robo2 caused reduced UB branching and glomerular number. ► Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. ► No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. ► Overexpression of Robo2 affected MM cells migration and caused UB deficit. ► The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2–Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2–Robo2 signaling is also important for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that overexpression of Robo2 by microinjection in embryonic kidneys is an effective approach to study the function of Robo2.

Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Ji, Jiayao [Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), The Chinese PLA General Hospital, Beijing 100853 (China); Medical College of NanKai University, Tianjin (China); Li, Qinggang; Xie, Yuansheng; Zhang, Xueguang; Cui, Shaoyuan; Shi, Suozhu [Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), The Chinese PLA General Hospital, Beijing 100853 (China); Chen, Xiangmei, E-mail: xmchen301@126.com [Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), The Chinese PLA General Hospital, Beijing 100853 (China); Medical College of NanKai University, Tianjin (China)

2012-05-11

Highlights: Black-Right-Pointing-Pointer Overexpression of Robo2 caused reduced UB branching and glomerular number. Black-Right-Pointing-Pointer Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. Black-Right-Pointing-Pointer No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. Black-Right-Pointing-Pointer Overexpression of Robo2 affected MM cells migration and caused UB deficit. Black-Right-Pointing-Pointer The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2-Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2-Robo2 signaling is also important for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that

Imaging morphogenesis: technological advances and biological insights.

Science.gov (United States)

Keller, Philipp J

2013-06-07

Morphogenesis, the development of the shape of an organism, is a dynamic process on a multitude of scales, from fast subcellular rearrangements and cell movements to slow structural changes at the whole-organism level. Live-imaging approaches based on light microscopy reveal the intricate dynamics of this process and are thus indispensable for investigating the underlying mechanisms. This Review discusses emerging imaging techniques that can record morphogenesis at temporal scales from seconds to days and at spatial scales from hundreds of nanometers to several millimeters. To unlock their full potential, these methods need to be matched with new computational approaches and physical models that help convert highly complex image data sets into biological insights.

Repetitive Stress Injuries

Science.gov (United States)

... Safe Videos for Educators Search English Español Repetitive Stress Injuries KidsHealth / For Teens / Repetitive Stress Injuries What's ... t had any problems since. What Are Repetitive Stress Injuries? Repetitive stress injuries (RSIs) are injuries that ...

Hypoxia activated EGFR signaling induces epithelial to mesenchymal transition (EMT.

Directory of Open Access Journals (Sweden)

Ashish Misra

Full Text Available Metastasis is a multi-step process which requires the conversion of polarized epithelial cells to mesenchymal cells, Epithelial-Mesenchymal Transition (EMT. EMT is essential during embryonic morphogenesis and has been implicated in the progression of primary tumors towards metastasis. Hypoxia is known to induce EMT; however the molecular mechanism is still poorly understood. Using the A431 epithelial cancer cell line, we show that cells grown under hypoxic conditions migrated faster than cells grown under normal oxygen environment. Cells grown under hypoxia showed reduced adhesion to the extracellular matrix (ECM probably due to reduced number of Vinculin patches. Growth under hypoxic conditions also led to down regulation of E-cadherin and up regulation of vimentin expression. The increased motility of cells grown under hypoxia could be due to redistribution of Rac1 to the plasma membrane as opposed to increased expression of Rac1. EGF (Epidermal Growth Factor is a known inducer of EMT and growth of A431 cells in the absence of oxygen led to increased expression of EGFR (EGF Receptor. Treatment of A431 cells with EGF led to reduced cell adhesion to ECM, increased cell motility and other EMT characteristics. Furthermore, this transition was blocked by the monoclonal antibody Cetuximab. Cetuximab also blocked the hypoxia-induced EMT suggesting that cell growth under hypoxic conditions led to activation of EGFR signaling and induction of EMT phenotype.

Supplementary Material for: A global sensitivity analysis approach for morphogenesis models

KAUST Repository

Boas, Sonja

2015-01-01

Abstract Background Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such ‘black-box’ models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. Results To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. Conclusions We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all ‘black-box’ models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Drosophila convoluted/dALS is an essential gene required for tracheal tube morphogenesis and apical matrix organization.

Science.gov (United States)

Swanson, Lianna E; Yu, Marcus; Nelson, Kevin S; Laprise, Patrick; Tepass, Ulrich; Beitel, Greg J

2009-04-01

Insulin-like growth factors (IGFs) control cell and organism growth through evolutionarily conserved signaling pathways. The mammalian acid-labile subunit (ALS) is a secreted protein that complexes with IGFs to modulate their activity. Recent work has shown that a Drosophila homolog of ALS, dALS, can also complex with and modulate the activity of a Drosophila IGF. Here we report the first mutations in the gene encoding dALS. Unexpectedly, we find that these mutations are allelic to a previously described mutation in convoluted (conv), a gene required for epithelial morphogenesis. In conv mutants, the tubes of the Drosophila tracheal system become abnormally elongated without altering tracheal cell number. conv null mutations cause larval lethality, but do not disrupt several processes required for tracheal tube size control, including septate junction formation, deposition of a lumenal/apical extracellular matrix, and lumenal secretion of Vermiform and Serpentine, two putative matrix-modifying proteins. Clearance of lumenal matrix and subcellular localization of clathrin also appear normal in conv mutants. However, we show that Conv/dALS is required for the dynamic organization of the transient lumenal matrix and normal structure of the cuticle that lines the tracheal lumen. These and other data suggest that the Conv/dALS-dependent tube size control mechanism is distinct from other known processes involved in tracheal tube size regulation. Moreover, we present evidence indicating that Conv/dALS has a novel, IGF-signaling independent function in tracheal morphogenesis.

Targeted Expression of Stromelysin-1 in Mammary Gland Provides Evidence for a Role of Proteinases in Branching Morphogenesis and the Requirement for an Intact Basement Membrane for Tissue-specific Gene Expression

Energy Technology Data Exchange (ETDEWEB)

Sympson, Carolyn J; Talhouk, Rabih S; Alexander, Caroline M; Chin, Jennie R; Cliff, Shirley M; Bissell, Mina J; Werb, Zena

1994-05-01

The extracellular matrix (ECM) is an important regulator of the differentiated phenotype of mammary epithelial cells in culture. Despite the fact that ECM-degrading enzymes have been implicated in morphogenesis and tissue remodeling, there is little evidence for a direct role for such regulation in vivo. We generated transgenic mice that express autoactivated isoforms of the matrix metalloproteinase stromelysin-1, under the control of the whey acidic protein gene promoter, to examine the effect of inappropriate expression of this enzyme. Stromelysin-1 is implicated as the primary player in the loss of basement membrane and loss of function in the mammary gland during involution. The transgene was expressed at low levels in mammary glands of virgin female mice, leading to an unexpected phenotype: The primary ducts had supernumerary branches and showed precocious development of alveoli that expressed beta-casein at levels similar to that of an early- to mid-pregnant gland. Lactating glands showed high levels of transgene expression, with accumulation at the basement membrane, and a decrease in laminin and collagen IV, resulting in a loss of basement membrane integrity; this was accompanied by a dramatic alteration of alveolar morphology, with decreased size and shrunken lumina containing little beta-casein. During pregnancy, expression of endogenous whey acidic protein and beta-casein was reduced in transgenic glands, confirming the observed dependence of milk protein transcription of ECM in mammary epithelial cells in culture. These data provide direct evidence that stromelysin-1 activity can be morphogenic for mammary epithelial cells, inducing hyperproliferation and differentiation in virgin animals, and that its lytic activity can, indeed, disrupt membrane integrity and reduce mammary-specific function. We conclude that the balance of ECM-degrading enzymes with their inhibitors, and the associated regulation of ECM structure, is crucial for tissue-specific gene

Feedback, Lineages and Self-Organizing Morphogenesis.

Directory of Open Access Journals (Sweden)

Sameeran Kunche

2016-03-01

Full Text Available Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities.

Feedback, Lineages and Self-Organizing Morphogenesis

Science.gov (United States)

Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

2016-01-01

Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

International Nuclear Information System (INIS)

Pei, Xin-Hong; Lv, Xin-Quan; Li, Hui-Xiang

2014-01-01

Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression

Active tension network model suggests an exotic mechanical state realized in epithelial tissues

Science.gov (United States)

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streichan, Sebastian J.; Shraiman, Boris I.

2017-12-01

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behaviour remains an open problem. Here we formulate and analyse the active tension network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodelling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal--`isogonal'--deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit fly embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena.

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

Conserved RNA-Binding Proteins Required for Dendrite Morphogenesis in Caenorhabditis elegans Sensory Neurons

Science.gov (United States)

Antonacci, Simona; Forand, Daniel; Wolf, Margaret; Tyus, Courtney; Barney, Julia; Kellogg, Leah; Simon, Margo A.; Kerr, Genevieve; Wells, Kristen L.; Younes, Serena; Mortimer, Nathan T.; Olesnicky, Eugenia C.; Killian, Darrell J.

2015-01-01

The regulation of dendritic branching is critical for sensory reception, cell−cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level. Because RNA-binding proteins mediate many posttranscriptional mechanisms, we decided to investigate the extent to which conserved RNA-binding proteins contribute to dendrite morphogenesis across phyla. Here we identify a core set of RNA-binding proteins that are important for dendrite morphogenesis in the PVD multidendritic sensory neuron in Caenorhabditis elegans. Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons. Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species. Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans. PMID:25673135

Morphogenesis in bat wings: linking development, evolution and ecology.

Science.gov (United States)

Adams, Rick A

2008-01-01

The evolution of powered flight in mammals required specific developmental shifts from an ancestral limb morphology to one adapted for flight. Through studies of comparative morphogenesis, investigators have quantified points and rates of divergence providing important insights into how wings evolved in mammals. Herein I compare growth,development and skeletogenesis of forelimbs between bats and the more ancestral state provided by the rat (Rattus norvegicus)and quantify growth trajectories that illustrate morphological divergence both developmentally and evolutionarily. In addition, I discuss how wing shape is controlled during morphogenesis by applying multivariate analyses of wing bones and wing membranes and discuss how flight dynamics are stabilized during flight ontogeny. Further, I discuss the development of flight in bats in relation to the ontogenetic niche and how juveniles effect populational foraging patterns. In addition, I provide a hypothetical ontogenetic landscape model that predicts how and when selection is most intense during juvenile morphogenesis and test this model with data from a population of the little brown bat, Myotis lucifugus. (c) 2007 S. Karger AG, Basel

Differential sensitivity of epithelial cells to extracellular matrix in polarity establishment.

Directory of Open Access Journals (Sweden)

Shigenobu Yonemura

Full Text Available Establishment of apical-basal polarity is crucial for epithelial sheets that form a compartment in the body, which function to maintain the environment in the compartment. Effects of impaired polarization are easily observed in three-dimensional (3-D culture systems rather than in two-dimensional (2-D culture systems. Although the mechanisms for establishing the polarity are not completely understood, signals from the extracellular matrix (ECM are considered to be essential for determining the basal side and eventually generating polarity in the epithelial cells. To elucidate the common features and differences in polarity establishment among various epithelial cells, we analyzed the formation of epithelial apical-basal polarity using three cell lines of different origin: MDCK II cells (dog renal tubules, EpH4 cells (mouse mammary gland, and R2/7 cells (human colon expressing wild-type α-catenin (R2/7 α-Cate cells. These cells showed clear apical-basal polarity in 2-D cultures. In 3-D cultures, however, each cell line displayed different responses to the same ECM. In MDCK II cells, spheroids with a single lumen formed in both Matrigel and collagen gel. In R2/7 α-Cate cells, spheroids showed similar apical-basal polarity as that seen in MDCK II cells, but had multiple lumens. In EpH4 cells, the spheroids displayed an apical-basal polarity that was opposite to that seen in the other two cell types in both ECM gels, at least during the culture period. On the other hand, the three cell lines showed the same apical-basal polarity both in 2-D cultures and in 3-D cultures using the hanging drop method. The three lines also had similar cellular responses to ECM secreted by the cells themselves. Therefore, appropriate culture conditions should be carefully determined in advance when using various epithelial cells to analyze cell polarity or 3-D morphogenesis.

Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

International Nuclear Information System (INIS)

Perkins, Timothy N.; Dentener, Mieke A.; Stassen, Frank R.; Rohde, Gernot G.; Mossman, Brooke T.; Wouters, Emiel F.M.; Reynaert, Niki L.

2016-01-01

Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Perkins, Timothy N.; Dentener, Mieke A. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Stassen, Frank R. [Department of Medical Microbiology, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Rohde, Gernot G. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Mossman, Brooke T. [Department of Pathology, University of Vermont College of Medicine, Burlington, VT (United States); Wouters, Emiel F.M. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Reynaert, Niki L., E-mail: n.reynaert@maastrichtuniversity.nl [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands)

2016-06-15

Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

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

Energy Technology Data Exchange (ETDEWEB)

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.

Apoptosis during budding morphogenesis of dentition

Czech Academy of Sciences Publication Activity Database

Peterková, Renata; Peterka, Miroslav; Viriot, L.; Lesot, H.

2002-01-01

Roč. 70, č. 7 (2002), s. 353 ISSN 0301-4681. [International Conference of the International Society of Differentiation /12./. Lyon, France, 14.09.2002-17.09.2002] R&D Projects: GA ČR GA304/02/0448 Institutional research plan: CEZ:AV0Z5039906 Keywords : morphogenesis of dentition Subject RIV: FF - HEENT, Dentistry Impact factor: 2.078, year: 2002

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Science.gov (United States)

Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

2018-02-08

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases

Science.gov (United States)

Li, W; Chen, Y-T; Hayashida, Y; Blanco, G; Kheirkah, A; He, H; Chen, S-Y; Liu, C-Y; Tseng, SCG

2010-01-01

Pax6 is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens–Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying EGFP–Pax6 transgenes into these Pax6− clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium. PMID:18027901

Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

Science.gov (United States)

Davidson, Lance A

2011-01-01

Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

Science.gov (United States)

Schnorr, J D; Holdcraft, R; Chevalier, B; Berg, C A

2001-10-01

Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

Repetition and Translation Shifts

Directory of Open Access Journals (Sweden)

Simon Zupan

2006-06-01

Full Text Available Repetition manifests itself in different ways and at different levels of the text. The first basic type of repetition involves complete recurrences; in which a particular textual feature repeats in its entirety. The second type involves partial recurrences; in which the second repetition of the same textual feature includes certain modifications to the first occurrence. In the article; repetitive patterns in Edgar Allan Poe’s short story “The Fall of the House of Usher” and its Slovene translation; “Konec Usherjeve hiše”; are compared. The author examines different kinds of repetitive patterns. Repetitions are compared at both the micro- and macrostructural levels. As detailed analyses have shown; considerable microstructural translation shifts occur in certain types of repetitive patterns. Since these are not only occasional; sporadic phenomena; but are of a relatively high frequency; they reduce the translated text’s potential for achieving some of the gothic effects. The macrostructural textual property particularly affected by these shifts is the narrator’s experience as described by the narrative; which suffers a reduction in intensity.

Chiral cell sliding drives left-right asymmetric organ twisting

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Inaki, Mikiko; Hatori, Ryo; Nakazawa, Naotaka; Okumura, Takashi; Ishibashi, Tomoki; Kikuta, Junichi; Ishii, Masaru

2018-01-01

Polarized epithelial morphogenesis is an essential process in animal development. While this process is mostly attributed to directional cell intercalation, it can also be induced by other mechanisms. Using live-imaging analysis and a three-dimensional vertex model, we identified ‘cell sliding,’ a novel mechanism driving epithelial morphogenesis, in which cells directionally change their position relative to their subjacent (posterior) neighbors by sliding in one direction. In Drosophila embryonic hindgut, an initial left-right (LR) asymmetry of the cell shape (cell chirality in three dimensions), which occurs intrinsically before tissue deformation, is converted through LR asymmetric cell sliding into a directional axial twisting of the epithelial tube. In a Drosophila inversion mutant showing inverted cell chirality and hindgut rotation, cell sliding occurs in the opposite direction to that in wild-type. Unlike directional cell intercalation, cell sliding does not require junctional remodeling. Cell sliding may also be involved in other cases of LR-polarized epithelial morphogenesis. PMID:29891026

Complex furrows in a 2D epithelial sheet code the 3D structure of a beetle horn.

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Matsuda, Keisuke; Gotoh, Hiroki; Tajika, Yuki; Sushida, Takamichi; Aonuma, Hitoshi; Niimi, Teruyuki; Akiyama, Masakazu; Inoue, Yasuhiro; Kondo, Shigeru

2017-10-24

The external organs of holometabolous insects are generated through two consecutive processes: the development of imaginal primordia and their subsequent transformation into the adult structures. During the latter process, many different phenomena at the cellular level (e.g. cell shape changes, cell migration, folding and unfolding of epithelial sheets) contribute to the drastic changes observed in size and shape. Because of this complexity, the logic behind the formation of the 3D structure of adult external organs remains largely unknown. In this report, we investigated the metamorphosis of the horn in the Japanese rhinoceros beetle Trypoxylus dichotomus. The horn primordia is essentially a 2D epithelial cell sheet with dense furrows. We experimentally unfolded these furrows using three different methods and found that the furrow pattern solely determines the 3D horn structure, indicating that horn formation in beetles occurs by two distinct processes: formation of the furrows and subsequently unfolding them. We postulate that this developmental simplicity offers an inherent advantage to understanding the principles that guide 3D morphogenesis in insects.

Aposymbiotic culture of the sepiolid squid Euprymna scolopes: role of the symbiotic bacterium Vibrio fischeri in host animal growth, development, and light organ morphogenesis.

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Claes, M F; Dunlap, P V

2000-02-15

The sepiolid squid Euprymna scolopes forms a bioluminescent mutualism with the luminous bacterium Vibrio fischeri, harboring V. fischeri cells in a complex ventral light organ and using the bacterial light in predator avoidance. To characterize the contribution of V. fischeri to the growth and development of E. scolopes and to define the long-term effects of bacterial colonization on light organ morphogenesis, we developed a mariculture system for the culture of E. scolopes from hatching to adulthood, employing artificial seawater, lighting that mimicked that of the natural environment, and provision of prey sized to match the developmental stage of E. scolopes. Animals colonized by V. fischeri and animals cultured in the absence of V. fischeri (aposymbiotic) grew and survived equally well, developed similarly, and reached sexual maturity at a similar age. Development of the light organ accessory tissues (lens, reflectors, and ink sac) was similar in colonized and aposymbiotic animals with no obvious morphometric or histological differences. Colonization by V. fischeri influenced regression of the ciliated epithelial appendages (CEAs), the long-term growth of the light organ epithelial tubules, and the appearance of the cells composing the ciliated ducts, which exhibit characteristics of secretory tissue. In certain cases, aposymbiotic animals retained the CEAs in a partially regressed state and remained competent to initiate symbiosis with V. fischeri into adulthood. In other cases, the CEAs regressed fully in aposymbiotic animals, and these animals were not colonizable. The results demonstrate that V. fischeri is not required for normal growth and development of the animal or for development of the accessory light organ tissues and that morphogenesis of only those tissues coming in contact with the bacteria (CEAs, ciliated ducts, and light organ epithelium) is altered by bacterial colonization of the light organ. Therefore, V. fischeri apparently makes no major

Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish

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Swartz, Mary E.; McCarthy, Neil; Norrie, Jacqueline L.; Eberhart, Johann K.

2016-01-01

The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood. Using genetic and chemical inhibitor approaches, we show that pouch morphogenesis requires Bmp signaling from 10-18 h post-fertilization, immediately following gastrulation. Blocking Bmp signaling during this window results in morphological defects to the pouches and craniofacial skeleton. Using genetic chimeras we show that Bmp signals directly to the endoderm for proper morphogenesis. Time-lapse imaging and analysis of reporter transgenics show that Bmp signaling is necessary for pouch outpocketing via the Fibroblast growth factor (Fgf) pathway. Double loss-of-function analyses demonstrate that Bmp and Fgf signaling interact synergistically in craniofacial development. Collectively, our analyses shed light on the tissue and signaling interactions that regulate development of the vertebrate face. PMID:27122171

Collective cell migration in morphogenesis, regeneration and cancer.

NARCIS (Netherlands)

Friedl, P.H.A.; Gilmour, D.

2009-01-01

The collective migration of cells as a cohesive group is a hallmark of the tissue remodelling events that underlie embryonic morphogenesis, wound repair and cancer invasion. In such migration, cells move as sheets, strands, clusters or ducts rather than individually, and use similar actin- and

EphB/syndecan-2 signaling in dendritic spine morphogenesis

DEFF Research Database (Denmark)

Ethell, I M; Irie, F; Kalo, M S

2001-01-01

We previously reported that the cell surface proteoglycan syndecan-2 can induce dendritic spine formation in hippocampal neurons. We demonstrate here that the EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this phosphorylation event is crucial for syndecan-2 clustering and spine...... formation. Syndecan-2 is tyrosine phosphorylated and forms a complex with EphB2 in mouse brain. Dominant-negative inhibition of endogenous EphB receptor activities blocks clustering of endogenous syndecan-2 and normal spine formation in cultured hippocampal neurons. This is the first evidence that Eph...... receptors play a physiological role in dendritic spine morphogenesis. Our observations suggest that spine morphogenesis is triggered by the activation of Eph receptors, which causes tyrosine phosphorylation of target molecules, such as syndecan-2, in presumptive spines....

Roles of repetitive sequences

Energy Technology Data Exchange (ETDEWEB)

Bell, G.I.

1991-12-31

The DNA of higher eukaryotes contains many repetitive sequences. The study of repetitive sequences is important, not only because many have important biological function, but also because they provide information on genome organization, evolution and dynamics. In this paper, I will first discuss some generic effects that repetitive sequences will have upon genome dynamics and evolution. In particular, it will be shown that repetitive sequences foster recombination among, and turnover of, the elements of a genome. I will then consider some examples of repetitive sequences, notably minisatellite sequences and telomere sequences as examples of tandem repeats, without and with respectively known function, and Alu sequences as an example of interspersed repeats. Some other examples will also be considered in less detail.

A Nonword Repetition Task for Speakers with Misarticulations: The Syllable Repetition Task (SRT)

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Shriberg, Lawrence D.; Lohmeier, Heather L.; Campbell, Thomas F.; Dollaghan, Christine A.; Green, Jordan R.; Moore, Christopher A.

2009-01-01

Purpose: Conceptual and methodological confounds occur when non(sense) word repetition tasks are administered to speakers who do not have the target speech sounds in their phonetic inventories or who habitually misarticulate targeted speech sounds. In this article, the authors (a) describe a nonword repetition task, the Syllable Repetition Task…

Binding of Glutathione to Enterovirus Capsids Is Essential for Virion Morphogenesis

Science.gov (United States)

Thibaut, Hendrik Jan; Thys, Bert; Canela, María-Dolores; Aguado, Leire; Wimmer, Eckard; Paul, Aniko; Pérez-Pérez, María-Jesús; van Kuppeveld, Frank J. M.; Neyts, Johan

2014-01-01

Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH), thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis. PMID:24722756

Review of aragonite and calcite crystal morphogenesis in thermal spring systems

Science.gov (United States)

Jones, Brian

2017-06-01

Aragonite and calcite crystals are the fundamental building blocks of calcareous thermal spring deposits. The diverse array of crystal morphologies found in these deposits, which includes monocrystals, mesocrystals, skeletal crystals, dendrites, and spherulites, are commonly precipitated under far-from-equilibrium conditions. Such crystals form through both abiotic and biotic processes. Many crystals develop through non-classical crystal growth models that involve the arrangement of nanocrystals in a precisely controlled crystallographic register. Calcite crystal morphogenesis has commonly been linked to a ;driving force;, which is a conceptual measure of the distance of the growth conditions from equilibrium conditions. Essentially, this scheme indicates that increasing levels of supersaturation and various other parameters that produce a progressive change from monocrystals and mesocrystals to skeletal crystals to crystallographic and non-crystallographic dendrites, to dumbbells, to spherulites. Despite the vast amount of information available from laboratory experiments and natural spring systems, the precise factors that control the driving force are open to debate. The fact that calcite crystal morphogenesis is still poorly understood is largely a reflection of the complexity of the factors that influence aragonite and calcite precipitation. Available information indicates that variations in calcite crystal morphogenesis can be attributed to physical and chemical parameters of the parent water, the presence of impurities, the addition of organic or inorganic additives to the water, the rate of crystal growth, and/or the presence of microbes and their associated biofilms. The problems in trying to relate crystal morphogenesis to specific environmental parameters arise because it is generally impossible to disentangle the controlling factor(s) from the vast array of potential parameters that may act alone or in unison with each other.

Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.

Directory of Open Access Journals (Sweden)

Hendrik Jan Thibaut

2014-04-01

Full Text Available Enteroviruses (family of the Picornaviridae cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH, thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis.

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.

Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

Science.gov (United States)

Rodrigues, Pedro L.; Rodrigues, Nuno F.; Duque, Duarte; Granja, Sara; Correia-Pinto, Jorge; Vilaça, João L.

2014-01-01

Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers. PMID:25250057

Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

Directory of Open Access Journals (Sweden)

Pedro L. Rodrigues

2014-01-01

Full Text Available Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers.

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

Science.gov (United States)

Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

Using organotypic (raft) epithelial tissue cultures for the biosynthesis and isolation of infectious human papillomaviruses.

Science.gov (United States)

Ozbun, Michelle A; Patterson, Nicole A

2014-08-01

Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection. Copyright © 2014 John Wiley

MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

Science.gov (United States)

Wang, Chia-Hui; Lee, Daniel Y; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B

2008-06-18

Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

Directory of Open Access Journals (Sweden)

Chia-Hui Wang

Full Text Available Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

Haben repetitive DNA-Sequenzen biologische Funktionen?

Science.gov (United States)

John, Maliyakal E.; Knöchel, Walter

1983-05-01

By DNA reassociation kinetics it is known that the eucaryotic genome consists of non-repetitive DNA, middle-repetitive DNA and highly repetitive DNA. Whereas the majority of protein-coding genes is located on non-repetitive DNA, repetitive DNA forms a constitutive part of eucaryotic DNA and its amount in most cases equals or even substantially exceeds that of non-repetitive DNA. During the past years a large body of data on repetitive DNA has accumulated and these have prompted speculations ranging from specific roles in the regulation of gene expression to that of a selfish entity with inconsequential functions. The following article summarizes recent findings on structural, transcriptional and evolutionary aspects and, although by no means being proven, some possible biological functions are discussed.

The unfolded protein response is required for dendrite morphogenesis

Science.gov (United States)

Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

2015-01-01

Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis.

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Alon Peled

2016-10-01

Full Text Available Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs, the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1

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Courtoy Pierre J

2009-12-01

Full Text Available Abstract Background The exocrine pancreas is composed of a branched network of ducts connected to acini. They are lined by a monolayered epithelium that derives from the endoderm and is surrounded by mesoderm-derived mesenchyme. The morphogenic mechanisms by which the ductal network is established as well as the signaling pathways involved in this process are poorly understood. Results By morphological analyzis of wild-type and mutant mouse embryos and using cultured embryonic explants we investigated how epithelial morphogenesis takes place and is regulated by chemokine signaling. Pancreas ontogenesis displayed a sequence of two opposite epithelial transitions. During the first transition, the monolayered and polarized endodermal cells give rise to tissue buds composed of a mass of non polarized epithelial cells. During the second transition the buds reorganize into branched and polarized epithelial monolayers that further differentiate into tubulo-acinar glands. We found that the second epithelial transition is controlled by the chemokine Stromal cell-Derived Factor (SDF-1. The latter is expressed by the mesenchyme, whereas its receptor CXCR4 is expressed by the epithelium. Reorganization of cultured pancreatic buds into monolayered epithelia was blocked in the presence of AMD3100, a SDF-1 antagonist. Analyzis of sdf1 and cxcr4 knockout embryos at the stage of the second epithelial transition revealed transient defective morphogenesis of the ventral and dorsal pancreas. Reorganization of a globular mass of epithelial cells in polarized monolayers is also observed during submandibular glands development. We found that SDF-1 and CXCR4 are expressed in this organ and that AMD3100 treatment of submandibular gland explants blocks its branching morphogenesis. Conclusion In conclusion, our data show that the primitive pancreatic ductal network, which is lined by a monolayered and polarized epithelium, forms by remodeling of a globular mass of non

Repetition and lag effects in movement recognition.

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Hall, C R; Buckolz, E

1982-03-01

Whether repetition and lag improve the recognition of movement patterns was investigated. Recognition memory was tested for one repetition, two-repetitions massed, and two-repetitions distributed with movement patterns at lags of 3, 5, 7, and 13. Recognition performance was examined both immediately afterwards and following a 48 hour delay. Both repetition and lag effects failed to be demonstrated, providing some support for the claim that memory is unaffected by repetition at a constant level of processing (Craik & Lockhart, 1972). There was, as expected, a significant decrease in recognition memory following the retention interval, but this appeared unrelated to repetition or lag.

Prediction of the Maximum Number of Repetitions and Repetitions in Reserve From Barbell Velocity.

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García-Ramos, Amador; Torrejón, Alejandro; Feriche, Belén; Morales-Artacho, Antonio J; Pérez-Castilla, Alejandro; Padial, Paulino; Haff, Guy Gregory

2018-03-01

To provide 2 general equations to estimate the maximum possible number of repetitions (XRM) from the mean velocity (MV) of the barbell and the MV associated with a given number of repetitions in reserve, as well as to determine the between-sessions reliability of the MV associated with each XRM. After determination of the bench-press 1-repetition maximum (1RM; 1.15 ± 0.21 kg/kg body mass), 21 men (age 23.0 ± 2.7 y, body mass 72.7 ± 8.3 kg, body height 1.77 ± 0.07 m) completed 4 sets of as many repetitions as possible against relative loads of 60%1RM, 70%1RM, 80%1RM, and 90%1RM over 2 separate sessions. The different loads were tested in a randomized order with 10 min of rest between them. All repetitions were performed at the maximum intended velocity. Both the general equation to predict the XRM from the fastest MV of the set (CV = 15.8-18.5%) and the general equation to predict MV associated with a given number of repetitions in reserve (CV = 14.6-28.8%) failed to provide data with acceptable between-subjects variability. However, a strong relationship (median r 2  = .984) and acceptable reliability (CV  .85) were observed between the fastest MV of the set and the XRM when considering individual data. These results indicate that generalized group equations are not acceptable methods for estimating the XRM-MV relationship or the number of repetitions in reserve. When attempting to estimate the XRM-MV relationship, one must use individualized relationships to objectively estimate the exact number of repetitions that can be performed in a training set.

Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory.

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Nasrollahi, Samila; Walter, Christopher; Loza, Andrew J; Schimizzi, Gregory V; Longmore, Gregory D; Pathak, Amit

2017-11-01

During morphogenesis and cancer metastasis, grouped cells migrate through tissues of dissimilar stiffness. Although the influence of matrix stiffness on cellular mechanosensitivity and motility are well-recognized, it remains unknown whether these matrix-dependent cellular features persist after cells move to a new microenvironment. Here, we interrogate whether priming of epithelial cells by a given matrix stiffness influences their future collective migration on a different matrix - a property we refer to as the 'mechanical memory' of migratory cells. To prime cells on a defined matrix and track their collective migration onto an adjoining secondary matrix of dissimilar stiffness, we develop a modular polyacrylamide substrate through step-by-step polymerization of different PA compositions. We report that epithelial cells primed on a stiff matrix migrate faster, display higher actomyosin expression, form larger focal adhesions, and retain nuclear YAP even after arriving onto a soft secondary matrix, as compared to their control behavior on a homogeneously soft matrix. Priming on a soft ECM causes a reverse effect. The depletion of YAP dramatically reduces this memory-dependent migration. Our results present a previously unidentified regulation of mechanosensitive collective cell migration by past matrix stiffness, in which mechanical memory depends on YAP activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

If you negate, you may forget: negated repetitions impair memory compared with affirmative repetitions.

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Mayo, Ruth; Schul, Yaacov; Rosenthal, Meytal

2014-08-01

One of the most robust laws of memory is that repeated activation improves memory. Our study shows that the nature of repetition matters. Specifically, although both negated repetition and affirmative repetition improve memory compared with no repetition, negated repetition hinders memory compared with affirmative repetition. After showing participants different entities, we asked them about features of these entities, leading to either "yes" or "no" responses. Our findings show that correctly negating an incorrect feature of an entity elicits an active forgetting effect compared with correctly affirming its true features. For example, after seeing someone drink a glass of white wine, answering "no" to "was it red wine?" may lead one to greater memory loss of the individual drinking wine at all compared with answering "yes" to "was it white wine?" We find this negation-induced forgetting effect in 4 experiments that differ in (a) the meaning given for the negation, (b) the type of stimuli (visual or verbal), and (c) the memory measure (recognition or free recall). We discuss possible underlying mechanisms and offer theoretical and applied implications of the negation-induced forgetting effect in relation to other known inhibition effects. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Ionizing radiation induces heritable disruption of epithelial cell interactions

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Park, Catherine C.; Henshall-Powell, Rhonda L.; Erickson, Anna C.; Talhouk, Rabih; Parvin, Bahram; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Chatterjee, A. (Principal Investigator)

2003-01-01

Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

New robust algorithm for tracking cells in videos of Drosophila morphogenesis based on finding an ideal path in segmented spatio-temporal cellular structures.

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Bellaïche, Yohanns; Bosveld, Floris; Graner, François; Mikula, Karol; Remesíková, Mariana; Smísek, Michal

2011-01-01

In this paper, we present a novel algorithm for tracking cells in time lapse confocal microscopy movie of a Drosophila epithelial tissue during pupal morphogenesis. We consider a 2D + time video as a 3D static image, where frames are stacked atop each other, and using a spatio-temporal segmentation algorithm we obtain information about spatio-temporal 3D tubes representing evolutions of cells. The main idea for tracking is the usage of two distance functions--first one from the cells in the initial frame and second one from segmented boundaries. We track the cells backwards in time. The first distance function attracts the subsequently constructed cell trajectories to the cells in the initial frame and the second one forces them to be close to centerlines of the segmented tubular structures. This makes our tracking algorithm robust against noise and missing spatio-temporal boundaries. This approach can be generalized to a 3D + time video analysis, where spatio-temporal tubes are 4D objects.

HER2 induced EMT and tumorigenicity in breast epithelial progenitor cells is inhibited by coexpression of EGFR.

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Ingthorsson, S; Andersen, K; Hilmarsdottir, B; Maelandsmo, G M; Magnusson, M K; Gudjonsson, T

2016-08-11

The members of the epidermal growth factor receptor (EGFR) kinase family are important players in breast morphogenesis and cancer. EGFR2/HER2 and EGFR expression have a prognostic value in certain subtypes of breast cancer such as HER2-amplified, basal-like and luminal type B. Many clinically approved small molecular inhibitors and monoclonal antibodies have been designed to target HER2, EGFR or both. There is, however, still limited knowledge on how the two receptors are expressed in normal breast epithelium, what effects they have on cellular differentiation and how they participate in neoplastic transformation. D492 is a breast epithelial cell line with stem cell properties that can undergo epithelial to mesenchyme transition (EMT), generate luminal- and myoepithelial cells and form complex branching structures in three-dimensional (3D) culture. Here, we show that overexpression of HER2 in D492 (D492(HER2)) resulted in EMT, loss of contact growth inhibition and increased oncogenic potential in vivo. HER2 overexpression, furthermore, inhibited endogenous EGFR expression. Re-introducing EGFR in D492(HER2) (D492(HER2/EGFR)) partially reversed the mesenchymal state of the cells, as an epithelial phenotype reappeared both in 3D cultures and in vivo. The D492(HER2/EGFR) xenografts grow slower than the D492(HER2) tumors, while overexpression of EGFR alone (D492(EGFR)) was not oncogenic in vivo. Consistent with the EGFR-mediated epithelial phenotype, overexpression of EGFR drove the cells toward a myoepithelial phenotype in 3D culture. The effect of two clinically approved anti-HER2 and EGFR therapies, trastuzumab and cetuximab, was tested alone and in combination on D492(HER2) xenografts. While trastuzumab had a growth inhibitory effect compared with untreated control, the effect of cetuximab was limited. When administered in combination, the growth inhibitory effect of trastuzumab was less pronounced. Collectively, our data indicate that in HER2-overexpressing D492

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

OpenAIRE

Papusheva, Ekaterina; Heisenberg, Carl-Philipp

2010-01-01

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

Repetitive Questioning Exasperates Caregivers

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R. C. Hamdy MD

2018-01-01

Full Text Available Repetitive questioning is due to an impaired episodic memory and is a frequent, often presenting, problem in patients with Alzheimer’s disease (amnestic type. It is due to the patients’ difficulties learning new information, retaining it, and recalling it, and is often aggravated by a poor attention span and easy distractibility. A number of factors may trigger and maintain repetitive questioning. Caregivers should try to identify and address these triggers. In the case discussion presented, it is due to the patient’s concerns about her and her family’s safety triggered by watching a particularly violent movie aired on TV. What went wrong in the patient/caregiver interaction and how it could have been avoided or averted are explored. Also reviewed are the impact of repetitive questioning, the challenges it raises for caregivers, and some effective intervention strategies that may be useful to diffuse the angst that caregivers experience with repetitive questioning.

From single cells to tissues: interactions between the matrix and human breast cells in real time.

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Clifford Barnes

Full Text Available Mammary gland morphogenesis involves ductal elongation, branching, and budding. All of these processes are mediated by stroma--epithelium interactions. Biomechanical factors, such as matrix stiffness, have been established as important factors in these interactions. For example, epithelial cells fail to form normal acinar structures in vitro in 3D gels that exceed the stiffness of a normal mammary gland. Additionally, heterogeneity in the spatial distribution of acini and ducts within individual collagen gels suggests that local organization of the matrix may guide morphogenesis. Here, we quantified the effects of both bulk material stiffness and local collagen fiber arrangement on epithelial morphogenesis.The formation of ducts and acini from single cells and the reorganization of the collagen fiber network were quantified using time-lapse confocal microscopy. MCF10A cells organized the surrounding collagen fibers during the first twelve hours after seeding. Collagen fiber density and alignment relative to the epithelial surface significantly increased within the first twelve hours and were a major influence in the shaping of the mammary epithelium. The addition of Matrigel to the collagen fiber network impaired cell-mediated reorganization of the matrix and increased the probability of spheroidal acini rather than branching ducts. The mechanical anisotropy created by regions of highly aligned collagen fibers facilitated elongation and branching, which was significantly correlated with fiber organization. In contrast, changes in bulk stiffness were not a strong predictor of this epithelial morphology.Localized regions of collagen fiber alignment are required for ductal elongation and branching suggesting the importance of local mechanical anisotropy in mammary epithelial morphogenesis. Similar principles may govern the morphology of branching and budding in other tissues and organs.

Extending Graphic Statics for User-Controlled Structural Morphogenesis

OpenAIRE

Fivet, Corentin; Zastavni, Denis; Cap, Jean-François; Structural Morphology Group International Seminar 2011

2011-01-01

The first geometrical definitions of any structure are of primary importance when considering pertinence and efficiency in structural design processes. Engineering history has taught us how graphic statics can be a very powerful tool since it allows the designer to take shapes and forces into account simultaneously. However, current and past graphic statics methods are more suitable for analysis than structural morphogenesis. This contribution introduces new graphical methods that can supp...

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

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Lu, Kai; Gordon, Richard; Cao, Tong

2015-03-01

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

Computer-Related Repetitive Stress Injuries

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... Staying Safe Videos for Educators Search English Español Computer-Related Repetitive Stress Injuries KidsHealth / For Parents / Computer-Related Repetitive Stress Injuries What's in this article? ...

Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

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Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

Gravity alterations are widely recognized to influence living systems. They may cause temporary or permanent effects on physiology and development at different levels, from gene expression to morphogenesis. However, the molecular mechanisms underlying these effects are often unclear, and adequate model systems to study them are required. To address this problem we developed a new experimental model of how gravity affects morphogenesis during tail regeneration in the newt Pleurodeles waltl. The effects of increased gravity on newt tail morphogenesis were first documented in two joint Russian-US NASA spaceflight experiments in the Russian Foton-M2 (2005) and Foton-M3 (2007) missions. In these experiments the shape of newt tail regenerate was found to depend on the gravity level, being dorso-ventrally symmetrical in microgravity and in neutrally-buoyant aquarium controls, versus hook-like and bent downward in 1g controls. These 1g controls were conducted in spaceflight habitats using a water-saturated PVA sponge mat. These results were reproducible in multiple spaceflight, and ground laboratory studies, both in the US at NASA ARC and in Russia at IDB RAS, and were characterized in detail using morphometry and histology approaches. The role of hypergravity in shaping morphogenesis was confirmed at NASA ARC with an experiment in the ISS Testbed 8-foot diameter centrifuge operating at 2g. Animals that experienced two-week centrifugation (the period of time used in the Foton flights) developed the same hook-like regenerates as 1g controls, and morphometric analysis revealed no significant difference between 1g and 2g groups, however both were significantly different from aquarium controls. We hypothesize that exposure to 1g or 2g during tail morphogenesis constitutes excessive loading for newts that are adapted to microgravity-like conditions in their aquatic habitat. Because Heat Shock Proteins (HSPs) are stress-induced molecules that respond to a broad variety of

The role of short-term memory impairment in nonword repetition, real word repetition, and nonword decoding: A case study.

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Peter, Beate

2018-01-01

In a companion study, adults with dyslexia and adults with a probable history of childhood apraxia of speech showed evidence of difficulty with processing sequential information during nonword repetition, multisyllabic real word repetition and nonword decoding. Results suggested that some errors arose in visual encoding during nonword reading, all levels of processing but especially short-term memory storage/retrieval during nonword repetition, and motor planning and programming during complex real word repetition. To further investigate the role of short-term memory, a participant with short-term memory impairment (MI) was recruited. MI was confirmed with poor performance during a sentence repetition and three nonword repetition tasks, all of which have a high short-term memory load, whereas typical performance was observed during tests of reading, spelling, and static verbal knowledge, all with low short-term memory loads. Experimental results show error-free performance during multisyllabic real word repetition but high counts of sequence errors, especially migrations and assimilations, during nonword repetition, supporting short-term memory as a locus of sequential processing deficit during nonword repetition. Results are also consistent with the hypothesis that during complex real word repetition, short-term memory is bypassed as the word is recognized and retrieved from long-term memory prior to producing the word.

Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study

NARCIS (Netherlands)

de Groot, I. J.; Lamers, W. H.; Moorman, A. F.

1989-01-01

An immunohistochemical study of cardiac alpha and beta myosin heavy chain (MHC) expression during rat heart morphogenesis was performed. In tubular hearts (embryonic days, ED10-11) coexpression of both cardiac alpha and beta MHC was found throughout the heart, except for the left free wall of the

Akap350 Recruits Eb1 to The Spindle Poles, Ensuring Proper Spindle Orientation and Lumen Formation in 3d Epithelial Cell Cultures.

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Almada, Evangelina; Tonucci, Facundo M; Hidalgo, Florencia; Ferretti, Anabela; Ibarra, Solange; Pariani, Alejandro; Vena, Rodrigo; Favre, Cristián; Girardini, Javier; Kierbel, Arlinet; Larocca, M Cecilia

2017-11-02

The organization of epithelial cells to form hollow organs with a single lumen requires the accurate three-dimensional arrangement of cell divisions. Mitotic spindle orientation is defined by signaling pathways that provide molecular links between specific spots at the cell cortex and astral microtubules, which have not been fully elucidated. AKAP350 is a centrosomal/Golgi scaffold protein, implicated in the regulation of microtubule dynamics. Using 3D epithelial cell cultures, we found that cells with decreased AKAP350 expression (AKAP350KD) formed polarized cysts with abnormal lumen morphology. Analysis of mitotic cells in AKAP350KD cysts indicated defective spindle alignment. We established that AKAP350 interacts with EB1, a microtubule associated protein that regulates spindle orientation, at the spindle poles. Decrease of AKAP350 expression lead to a significant reduction of EB1 levels at spindle poles and astral microtubules. Conversely, overexpression of EB1 rescued the defective spindle orientation induced by deficient AKAP350 expression. The specific delocalization of the AKAP350/EB1complex from the centrosome decreased EB1 levels at astral microtubules and lead to the formation of 3D-organotypic structures which resembled AKAP350KD cysts. We conclude that AKAP350 recruits EB1 to the spindle poles, ensuring EB1 presence at astral microtubules and proper spindle orientation during epithelial morphogenesis.

Dynamics of Spore Coat Morphogenesis in Bacillus subtilis

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McKenney, Peter T.; Eichenberger, Patrick

2011-01-01

SUMMARY Spores of Bacillus subtilis are encased in a protective coat made up of at least 70 proteins. The structure of the spore coat has been examined using a variety of genetic, imaging and biochemical techniques, however, the majority of these studies have focused on mature spores. In this study we use a library of 41 spore coat proteins fused to the Green Fluorescent Protein (GFP) to examine spore coat morphogenesis over the time-course of sporulation. We found considerable diversity in the localization dynamics of coat proteins and were able to establish 6 classes based on localization kinetics. Localization dynamics correlate well with the known transcriptional regulators of coat gene expression. Previously, we described the existence of multiple layers in the mature spore coat. Here, we find that the spore coat initially assembles a scaffold that is organized into multiple layers on one pole of the spore. The coat then encases the spore in multiple coordinated waves. Encasement is driven, at least partially, by transcription of coat genes and deletion of sporulation transcription factors arrests encasement. We also identify the trans-compartment SpoIIIAH-SpoIIQ channel as necessary for encasement. This is the first demonstration of a forespore contribution to spore coat morphogenesis. PMID:22171814

Role of epimorphin in bile duct formation of rat liver epithelial stem-like cells: involvement of small G protein RhoA and C/EBPβ.

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Jia, Yali; Yao, Hailei; Zhou, Junnian; Chen, Lin; Zeng, Quan; Yuan, Hongfeng; Shi, Lei; Nan, Xue; Wang, Yunfang; Yue, Wen; Pei, Xuetao

2011-11-01

Epimorphin/syntaxin 2 is a high conserved and very abundant protein involved in epithelial morphogenesis in various organs. We have shown recently that epimorphin (EPM), a protein exclusively expressed on the surface of hepatic stellate cells and myofibroblasts of the liver, induces bile duct formation of hepatic stem-like cells (WB-F344 cells) in a putative biophysical way. Therefore, the aim of this study was to present some of the molecular mechanisms by which EPM mediates bile duct formation. We established a biliary differentiation model by co-culture of EPM-overexpressed mesenchymal cells (PT67(EPM)) with WB-F344 cells. Here, we showed that EPM could promote WB-F344 cells differentiation into bile duct-like structures. Biliary differentiation markers were also elevated by EPM including Yp, Cx43, aquaporin-1, CK19, and gamma glutamyl transpeptidase (GGT). Moreover, the signaling pathway of EPM was analyzed by focal adhesion kinase (FAK), extracellular regulated kinase 1/2 (ERK1/2), and RhoA Western blot. Also, a dominant negative (DN) RhoA-WB-F344 cell line (WB(RhoA-DN)) was constructed. We found that the levels of phosphorylation (p) of FAK and ERK1/2 were up-regulated by EPM. Most importantly, we also showed that RhoA is necessary for EPM-induced activation of FAK and ERK1/2 and bile duct formation. In addition, a dual luciferase-reporter assay and CHIP assay was performed to reveal that EPM regulates GGT IV and GGT V expression differentially, possibly mediated by C/EBPβ. Taken together, these data demonstrated that EPM regulates bile duct formation of WB-F344 cells through effects on RhoA and C/EBPβ, implicating a dual aspect of this morphoregulator in bile duct epithelial morphogenesis. Copyright © 2011 Wiley-Liss, Inc.

Morphogenesis of Pestiviruses: New Insights from Ultrastructural Studies of Strain Giraffe-1

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Mast, Jan; Thiel, Heinz-Jürgen; König, Matthias

2014-01-01

Knowledge on the morphogenesis of pestiviruses is limited due to low virus production in infected cells. In order to localize virion morphogenesis and replication sites of pestiviruses and to examine intracellular virion transport, a cell culture model was established to facilitate ultrastructural studies. Based on results of virus growth kinetic analysis and quantification of viral RNA, pestivirus strain Giraffe-1 turned out to be a suitable candidate for studies on virion generation and export from culture cells. Using conventional transmission electron microscopy and single-tilt electron tomography, we found virions located predominately in the lumen of the endoplasmic reticulum (ER) in infected cells and were able to depict the budding process of virions at ER membranes. Colocalization of the viral core protein and the envelope glycoprotein E2 with the ER marker protein disulfide isomerase (PDI) was demonstrated by immunogold labeling of cryosections. Moreover, pestivirions could be shown in transport vesicles and the Golgi complex and during exocytosis. Interestingly, viral capsid protein and double-stranded RNA (dsRNA) were detected in multivesicular bodies (MVBs), which implies that the endosomal compartment plays a role in pestiviral replication. Significant cellular membrane alterations such as those described for members of the Flavivirus and Hepacivirus genera were not found. Based on the gained morphological data, we present a consistent model of pestivirus morphogenesis. PMID:24352462

Synergy Repetition Training versus Task Repetition Training in Acquiring New Skill.

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Patel, Vrajeshri; Craig, Jamie; Schumacher, Michelle; Burns, Martin K; Florescu, Ionut; Vinjamuri, Ramana

2017-01-01

Traditionally, repetitive practice of a task is used to learn a new skill, exhibiting as immediately improved performance. Research suggests, however, that a more experience-based rather than exposure-based training protocol may allow for better transference of the skill to related tasks. In synergy-based motor control theory, fundamental motor skills, such as hand grasping, are represented with a synergy subspace that captures essential motor patterns. In this study, we propose that motor-skill learning through synergy-based mechanisms may provide advantages over traditional task repetition learning. A new task was designed to highlight the range of motion and dexterity of the human hand. Two separate training strategies were tested in healthy subjects: task repetition training and synergy training versus a control. All three groups showed improvements when retested on the same task. When tested on a similar, but different set of tasks, only the synergy group showed improvements in accuracy (9.27% increase) compared to the repetition (3.24% decline) and control (3.22% decline) groups. A kinematic analysis revealed that although joint angular peak velocities decreased, timing benefits stemmed from the initial feed-forward portion of the task (reaction time). Accuracy improvements may have derived from general improved coordination among the four involved fingers. These preliminary results warrant further investigation of synergy-based motor training in healthy individuals, as well as in individuals undergoing hand-based rehabilitative therapy.

Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.

NARCIS (Netherlands)

Thibaut, H.J.; Linden, L. van der; Jiang, P.; Thys, B.; Canela, M.D.; Aguado, L.; Rombaut, B.; Wimmer, E.; Paul, A.; Perez-Perez, M.J.; Kuppeveld, F.J.M. van; Neyts, J.

2014-01-01

Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We

Binding of glutathione to enterovirus capsids is essential for virion morphogenesis

NARCIS (Netherlands)

Thibaut, Hendrik Jan; van der Linden, Lonneke; Jiang, Ping; Thys, Bert; Canela, María-Dolores; Aguado, Leire; Rombaut, Bart; Wimmer, Eckard; Paul, Aniko; Pérez-Pérez, María-Jesús; van Kuppeveld, Frank J M; Neyts, Johan

Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We

Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.

Science.gov (United States)

Gansner, John M; Madsen, Erik C; Mecham, Robert P; Gitlin, Jonathan D

2008-10-01

Recent studies demonstrate that lysyl oxidase cuproenzymes are critical for zebrafish notochord formation, but the molecular mechanisms of copper-dependent notochord morphogenesis are incompletely understood. We, therefore, conducted a forward genetic screen for zebrafish mutants that exhibit notochord sensitivity to lysyl oxidase inhibition, yielding a mutant with defects in notochord and vascular morphogenesis, puff daddygw1 (pfdgw1). Meiotic mapping and cloning reveal that the pfdgw1 phenotype results from disruption of the gene encoding the extracellular matrix protein fibrillin-2, and the spatiotemporal expression of fibrillin-2 is consistent with the pfdgw1 phenotype. Furthermore, each aspect of the pfdgw1 phenotype is recapitulated by morpholino knockdown of fibrillin-2. Taken together, the data reveal a genetic interaction between fibrillin-2 and the lysyl oxidases in notochord formation and demonstrate the importance of fibrillin-2 in specific early developmental processes in zebrafish. Copyright (c) 2008 Wiley-Liss, Inc.

A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis

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Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

2017-01-01

The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways. DOI: http://dx.doi.org/10.7554/eLife.25453.001 PMID:28463112

Giga-voxel computational morphogenesis for structural design

DEFF Research Database (Denmark)

Aage, Niels; Andreassen, Erik; Lazarov, Boyan Stefanov

2017-01-01

In the design of industrial products ranging from hearing aidsto automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer...... aeroplane wing designs, which translates into are duction in fuel consumption of about 40–200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems3, antennas4,nano-optics5 and micro-systems6,7...

ILK modulates epithelial polarity and matrix formation in hair follicles.

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Rudkouskaya, Alena; Welch, Ian; Dagnino, Lina

2014-03-01

Hair follicle morphogenesis requires coordination of multiple signals and communication between its epithelial and mesenchymal constituents. Cell adhesion protein platforms, which include integrins and integrin-linked kinase (ILK), are critical for hair follicle formation. However, their precise contribution to this process is poorly understood. We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical-basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla. Addition of exogenous laminin-511 restores morphological and molecular markers associated with hair matrix formation, indicating that ILK regulates hair bud cell polarity and functions upstream from laminin-511 assembly to regulate the developmental progression of hair follicles beyond the germ stage.

Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development.

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Tsuji, Kenji; Kitamura, Shinji; Makino, Hirofumi

2014-04-25

The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. In this study, we examined whether HIF regulates kidney development. We harvested kidneys from day 13 rat embryos (E13Ks) and cultured the organs under normoxic (20% O2/5% CO2) or hypoxic (5% O2/5% CO2) conditions. We evaluated the kidneys based on morphology and gene expression. E13Ks cultured under hypoxic conditions had significantly more ureteric bud (UB) branching than the E13Ks cultured under normoxic conditions. In addition, the mRNA levels of GDNF and GDNF receptor (GFR-α1), increased under hypoxic conditions in E13Ks. When we cultured E13Ks with the HIF-1α inhibitor digoxin or with siRNA targeting HIF-1α under hypoxic conditions, we did not observe increased UB branching. In addition, the expression of GDNF and GFR-α1 was inhibited under hypoxic conditions when the kidneys were treated with siRNA targeting HIF-1α. We also elucidated that hypoxia inhibited UB cell apoptosis and promoted the expression of FGF7 mRNA levels in metanephric mesenchymal (MM) cells in vitro. These findings suggest that hypoxic condition has important roles in inducing branching morphogenesis during kidney development. Hypoxia might mediate branching morphogenesis via not only GDNF/Ret but also FGF signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila.

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Freymuth, Patrick S; Fitzsimons, Helen L

2017-08-29

Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton. Rearrangement of the actin cytoskeleton drives both neuronal morphogenesis and the structural changes in neurons that are required for long-term memory formation. Moesin has been identified as a candidate memory gene in Drosophila, however, whether it is required for memory formation has not been evaluated. Here, we investigate the role of Moesin in neuronal morphogenesis and in short- and long-term memory formation in the courtship suppression assay, a model of associative memory. We found that both knockdown and overexpression of Moesin led to defects in axon growth and guidance as well as dendritic arborization. Moreover, reduction of Moesin expression or expression of a constitutively active phosphomimetic in the adult Drosophila brain had no effect on short term memory, but prevented long-term memory formation, an effect that was independent of its role in development. These results indicate a critical role for Moesin in both neuronal morphogenesis and long-term memory formation.

Linked expression of Ah receptor, ARNT, CYP1A1, and CYP1B1 in rat mammary epithelia, in vitro, is each substantially elevated by specific extracellular matrix interactions that precede branching morphogenesis.

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Larsen, Michele Campaigne; Brake, Paul B; Pollenz, Richard S; Jefcoate, Colin R

2004-11-01

Cytochrome P4501B1 (CYP1B1), the major constitutively expressed CYP in the rat mammary gland, is induced by Ah-receptor (AhR) ligands, while CYP1A1 is predominantly expressed only after induction. These CYPs contribute to carcinogenic activation of polycyclic aromatic hydrocarbons (PAHs). AhR, ARNT, and CYP1B1 were only weakly expressed, even after 2,3,7,8-tetrachlorodibenzo-p-dioxin induction, when rat mammary epithelial cells (RMEC) were cultured on plastic. RMEC cultured on the extracellular matrix (ECM), Matrigel, or on a floating gel of collagen I demonstrated branching morphogenesis and substantially increased basal CYP1B1 and induced CYP1A1 expression, in parallel with large increases in AhR and ARNT expression. Branching was more pronounced in the Wistar Kyoto than in the Wistar Furth rat strain. Although EGF enhanced branching, neither strain nor growth factor treatment substantially impacted CYP expression. Increased AhR and ARNT expression is observed within 24 h of dispersal on Matrigel, substantially prior to branch formation. Culture on thin layers of collagen I, collagen IV, and laminin, respectively, failed to reproduce the branching morphogenesis or increases in AhR, ARNT, or CYP expression. However, adherent, gelled collagen I recapitulated the increased protein expression, without supporting branching. This increased protein expression was closely paralleled by enhanced expression of beta-catenin and E-cadherin, components of cell-cell adhesion complexes. A synthetic peptide that selectively antagonizes integrin-ECM interactions reduced branch formation, without diminishing AhR, ARNT, and CYP expression. These data demonstrate that early ECM surface adhesion interactions mediate AhR and ARNT expression, which enhances CYP expression, independent of branching morphogenesis.

FLI-1 Flightless-1 and LET-60 Ras control germ line morphogenesis in C. elegans

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Dentler William L

2008-05-01

Full Text Available Abstract Background In the C. elegans germ line, syncytial germ line nuclei are arranged at the cortex of the germ line as they exit mitosis and enter meiosis, forming a nucleus-free core of germ line cytoplasm called the rachis. Molecular mechanisms of rachis formation and germ line organization are not well understood. Results Mutations in the fli-1 gene disrupt rachis organization without affecting meiotic differentiation, a phenotype in C. elegans referred to here as the germ line morphogenesis (Glm phenotype. In fli-1 mutants, chains of meiotic germ nuclei spanned the rachis and were partially enveloped by invaginations of germ line plasma membrane, similar to nuclei at the cortex. Extensions of the somatic sheath cells that surround the germ line protruded deep inside the rachis and were associated with displaced nuclei in fli-1 mutants. fli-1 encodes a molecule with leucine-rich repeats and gelsolin repeats similar to Drosophila flightless 1 and human Fliih, which have been shown to act as cytoplasmic actin regulators as well as nuclear transcriptional regulators. Mutations in let-60 Ras, previously implicated in germ line development, were found to cause the Glm phenotype. Constitutively-active LET-60 partially rescued the fli-1 Glm phenotype, suggesting that LET-60 Ras and FLI-1 might act together to control germ line morphogenesis. Conclusion FLI-1 controls germ line morphogenesis and rachis organization, a process about which little is known at the molecular level. The LET-60 Ras GTPase might act with FLI-1 to control germ line morphogenesis.

Exocrine Gland Morphogenesis: Insights into the Role of Amphiregulin from Development to Disease.

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Sisto, Margherita; Lorusso, Loredana; Ingravallo, Giuseppe; Lisi, Sabrina

2017-12-01

Amphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key role in mammalian development and in the control of branching morphogenesis in various organs. Furthermore, AREG participates in a wide range of physiological and pathological processes activating the major intracellular signalling cascades governing cell survival, proliferation and motility. In this article, we review current advances in exocrine glands morphogenesis, focusing on the salivary gland, and discuss the essential aspects of AREG structure, function and regulation, and its differential role within the EGFR family of ligands. Finally, we identify emerging aspects in AREG research applied to mammary gland development and the salivary gland autoimmune disease, Sjögren's syndrome.

Notochord morphogenesis in mice: Current understanding & open questions.

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Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

2016-05-01

The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Repetitive Questioning II

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R. C. Hamdy MD

2018-02-01

Full Text Available Repetitive questioning is a major problem for caregivers, particularly taxing if they are unable to recognize and understand the reasons why their loved one keeps asking the same question over and over again. Caregivers may be tempted to believe that the patient does not even try to remember the answer given or is just getting obnoxious. This is incorrect. Repetitive questioning is due to the underlying disease: The patient’s short term memory is impaired and he is unable to register, encode, retain and retrieve the answer. If he is concerned about a particular topic, he will keep asking the same question over and over again. To the patient each time she asks the question, it is as if she asked it for the first time. Just answering repetitive questioning by providing repeatedly the same answer is not sufficient. Caregivers should try to identify the underlying cause for this repetitive questioning. In an earlier case study, the patient was concerned about her and her family’s safety and kept asking whether the doors are locked. In this present case study, the patient does not know how to handle the awkward situation he finds himself in. He just does not know what to do. He is not able to adjust to the new unexpected situation. So he repeatedly wants to reassure himself that he is not intruding by asking the same question over and over again. We discuss how the patient’s son-in-law could have avoided this situation and averted the catastrophic ending.

Transgenic Expression of Constitutively Active RAC1 Disrupts Mouse Rod Morphogenesis

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Song, Hongman; Bush, Ronald A.; Vijayasarathy, Camasamudram; Fariss, Robert N.; Kjellstrom, Sten; Sieving, Paul A.

2014-01-01

Purpose. Dominant-active RAC1 rescues photoreceptor structure in Drosophila rhodopsin-null mutants, indicating an important role in morphogenesis. This report assesses the morphogenetic effect of activated RAC1 during mammalian rod photoreceptor development using transgenic mice that express constitutively active (CA) RAC1. Methods. Transgenic mice were generated by expressing CA RAC1 under control of the Rhodopsin promoter, and morphological features of the photoreceptors were evaluated by histology, immunohistochemistry, and transmission electron microscopy. Function was evaluated by electroretinography. Potential protein partners of CA RAC1 were identified by co-immunoprecipitation of retinal extracts. Results. Constitutively active RAC1 expression in differentiating rods disrupted outer retinal lamination as early as postnatal day (P)6, and many photoreceptor cell nuclei were displaced apically into the presumptive subretinal space. These photoreceptors did not develop normal inner and outer segments and had abnormal placement of synaptic elements. Some photoreceptor nuclei were also mislocalized into the inner nuclear layer. Extensive photoreceptor degeneration was subsequently observed in the adult animal. Constitutively active RAC1 formed a complex with the polarity protein PAR6 and with microtubule motor dynein in mouse retina. The normal localization of the PAR6 complex was disrupted in CA RAC1-expressing rod photoreceptors. Conclusions. Constitutively active RAC1 had a profound negative effect on mouse rod cell viability and development. Rod photoreceptors in the CA RAC1 retina exhibited a defect in polarity and migration. Constitutively active RAC1 disrupted rod morphogenesis and gave a phenotype resembling that found in the Crumbs mutant. PAR6 and dynein are two potential downstream effectors that may be involved in CA RAC1-mediated defective mouse photoreceptor morphogenesis. PMID:24651551

Emotional response to musical repetition.

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Livingstone, Steven R; Palmer, Caroline; Schubert, Emery

2012-06-01

Two experiments examined the effects of repetition on listeners' emotional response to music. Listeners heard recordings of orchestral music that contained a large section repeated twice. The music had a symmetric phrase structure (same-length phrases) in Experiment 1 and an asymmetric phrase structure (different-length phrases) in Experiment 2, hypothesized to alter the predictability of sensitivity to musical repetition. Continuous measures of arousal and valence were compared across music that contained identical repetition, variation (related), or contrasting (unrelated) structure. Listeners' emotional arousal ratings differed most for contrasting music, moderately for variations, and least for repeating musical segments. A computational model for the detection of repeated musical segments was applied to the listeners' emotional responses. The model detected the locations of phrase boundaries from the emotional responses better than from performed tempo or physical intensity in both experiments. These findings indicate the importance of repetition in listeners' emotional response to music and in the perceptual segmentation of musical structure.

Isotropic actomyosin dynamics promote organization of the apical cell cortex in epithelial cells.

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Klingner, Christoph; Cherian, Anoop V; Fels, Johannes; Diesinger, Philipp M; Aufschnaiter, Roland; Maghelli, Nicola; Keil, Thomas; Beck, Gisela; Tolić-Nørrelykke, Iva M; Bathe, Mark; Wedlich-Soldner, Roland

2014-10-13

Although cortical actin plays an important role in cellular mechanics and morphogenesis, there is surprisingly little information on cortex organization at the apical surface of cells. In this paper, we characterize organization and dynamics of microvilli (MV) and a previously unappreciated actomyosin network at the apical surface of Madin-Darby canine kidney cells. In contrast to short and static MV in confluent cells, the apical surfaces of nonconfluent epithelial cells (ECs) form highly dynamic protrusions, which are often oriented along the plane of the membrane. These dynamic MV exhibit complex and spatially correlated reorganization, which is dependent on myosin II activity. Surprisingly, myosin II is organized into an extensive network of filaments spanning the entire apical membrane in nonconfluent ECs. Dynamic MV, myosin filaments, and their associated actin filaments form an interconnected, prestressed network. Interestingly, this network regulates lateral mobility of apical membrane probes such as integrins or epidermal growth factor receptors, suggesting that coordinated actomyosin dynamics contributes to apical cell membrane organization. © 2014 Klingner et al.

Regulation of cellulase expression, sporulation, and morphogenesis by velvet family proteins in Trichoderma reesei.

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Liu, Kuimei; Dong, Yanmei; Wang, Fangzhong; Jiang, Baojie; Wang, Mingyu; Fang, Xu

2016-01-01

Homologs of the velvet protein family are encoded by the ve1, vel2, and vel3 genes in Trichoderma reesei. To test their regulatory functions, the velvet protein-coding genes were disrupted, generating Δve1, Δvel2, and Δvel3 strains. The phenotypic features of these strains were examined to identify their functions in morphogenesis, sporulation, and cellulase expression. The three velvet-deficient strains produced more hyphal branches, indicating that velvet family proteins participate in the morphogenesis in T. reesei. Deletion of ve1 and vel3 did not affect biomass accumulation, while deletion of vel2 led to a significantly hampered growth when cellulose was used as the sole carbon source in the medium. The deletion of either ve1 or vel2 led to the sharp decrease of sporulation as well as a global downregulation of cellulase-coding genes. In contrast, although the expression of cellulase-coding genes of the ∆vel3 strain was downregulated in the dark, their expression in light condition was unaffected. Sporulation was hampered in the ∆vel3 strain. These results suggest that Ve1 and Vel2 play major roles, whereas Vel3 plays a minor role in sporulation, morphogenesis, and cellulase expression.

Differentiated roles for MreB-actin isologues and autolytic enzymes in Bacillus subtilis morphogenesis.

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Domínguez-Cuevas, Patricia; Porcelli, Ida; Daniel, Richard A; Errington, Jeff

2013-09-01

Cell morphogenesis in most bacteria is governed by spatiotemporal growth regulation of the peptidoglycan cell wall layer. Much is known about peptidoglycan synthesis but regulation of its turnover by hydrolytic enzymes is much less well understood. Bacillus subtilis has a multitude of such enzymes. Two of the best characterized are CwlO and LytE: cells lacking both enzymes have a lethal block in cell elongation. Here we show that activity of CwlO is regulated by an ABC transporter, FtsEX, which is required for cell elongation, unlike cell division as in Escherichia coli. Actin-like MreB proteins are thought to play a key role in orchestrating cell wall morphogenesis. B. subtilis has three MreB isologues with partially differentiated functions. We now show that the three MreB isologues have differential roles in regulation of the CwlO and LytE systems and that autolysins control different aspects of cell morphogenesis. The results add major autolytic activities to the growing list of functions controlled by MreB isologues in bacteria and provide new insights into the different specialized functions of essential cell wall autolysins. © 2013 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells.

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Sunpaweravong, S; Sunpaweravong, P; Sathitruangsak, C; Mai, S

2016-05-01

Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture

Spermine modulates fungal morphogenesis and activates plasma membrane H+-ATPase during yeast to hyphae transition

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Antônio Jesus Dorighetto Cogo

2018-02-01

Full Text Available Polyamines play a regulatory role in eukaryotic cell growth and morphogenesis. Despite many molecular advances, the underlying mechanism of action remains unclear. Here, we investigate a mechanism by which spermine affects the morphogenesis of a dimorphic fungal model of emerging relevance in plant interactions, Yarrowia lipolytica, through the recruitment of a phytohormone-like pathway involving activation of the plasma membrane P-type H+-ATPase. Morphological transition was followed microscopically, and the H+-ATPase activity was analyzed in isolated membrane vesicles. Proton flux and acidification were directly probed at living cell surfaces by a non-invasive selective ion electrode technique. Spermine and indol-3-acetic acid (IAA induced the yeast-hypha transition, influencing the colony architecture. Spermine induced H+-ATPase activity and H+ efflux in living cells correlating with yeast-hypha dynamics. Pharmacological inhibition of spermine and IAA pathways prevented the physio-morphological responses, and indicated that spermine could act upstream of the IAA pathway. This study provides the first compelling evidence on the fungal morphogenesis and colony development as modulated by a spermine-induced acid growth mechanism analogous to that previously postulated for the multicellular growth regulation of plants.

Repetitive learning control of continuous chaotic systems

International Nuclear Information System (INIS)

Chen Maoyin; Shang Yun; Zhou Donghua

2004-01-01

Combining a shift method and the repetitive learning strategy, a repetitive learning controller is proposed to stabilize unstable periodic orbits (UPOs) within chaotic attractors in the sense of least mean square. If nonlinear parts in chaotic systems satisfy Lipschitz condition, the proposed controller can be simplified into a simple proportional repetitive learning controller

Novel porcine repetitive elements

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Nonneman Dan J

2006-12-01

Full Text Available Abstract Background Repetitive elements comprise ~45% of mammalian genomes and are increasingly known to impact genomic function by contributing to the genomic architecture, by direct regulation of gene expression and by affecting genomic size, diversity and evolution. The ubiquity and increasingly understood importance of repetitive elements contribute to the need to identify and annotate them. We set out to identify previously uncharacterized repetitive DNA in the porcine genome. Once found, we characterized the prevalence of these repeats in other mammals. Results We discovered 27 repetitive elements in 220 BACs covering 1% of the porcine genome (Comparative Vertebrate Sequencing Initiative; CVSI. These repeats varied in length from 55 to 1059 nucleotides. To estimate copy numbers, we went to an independent source of data, the BAC-end sequences (Wellcome Trust Sanger Institute, covering approximately 15% of the porcine genome. Copy numbers in BAC-ends were less than one hundred for 6 repeat elements, between 100 and 1000 for 16 and between 1,000 and 10,000 for 5. Several of the repeat elements were found in the bovine genome and we have identified two with orthologous sites, indicating that these elements were present in their common ancestor. None of the repeat elements were found in primate, rodent or dog genomes. We were unable to identify any of the replication machinery common to active transposable elements in these newly identified repeats. Conclusion The presence of both orthologous and non-orthologous sites indicates that some sites existed prior to speciation and some were generated later. The identification of low to moderate copy number repetitive DNA that is specific to artiodactyls will be critical in the assembly of livestock genomes and studies of comparative genomics.

Morfogenesis dan Diferensiasi Sel dalam Perkembangan Gigi (Tinjauan Molekuler

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Yani Corvianindya

2015-11-01

Full Text Available Tooth development provides a dynamic process that has recently been studied at molecular level. There has been much progress toward the understanding of epithelial-mesenchymal cell signaling in tooth germ formation, morphogenesis and cell differentiation. The epithelial-mesenchym interaction is suggested to be the most important mechanism in organogenesis that stimulate mitosis and prevent apoptosis adjacent to the tissue surface. Moreover it affects cell formation and cell differentiation. Enamel knot is assumed to act as a signaling center in the tooth germ epithelial in organizing the tooth pattern as well as controlling the tooth growth. The genes involved in this mechanism are p21, Fgf-4, Shh, Bmp-2, bmp-4, Msx-1 and Lef-1 which are expressed in the enamel knot during the bud stage and cap stage. At the further step of differentiation, epithelial ameloblast and mesenchymal odontoblast will deposit organic matrix in enamel and dentin. This article reviews the molecular morphogenesis of tooth development.

Document retrieval on repetitive string collections.

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Gagie, Travis; Hartikainen, Aleksi; Karhu, Kalle; Kärkkäinen, Juha; Navarro, Gonzalo; Puglisi, Simon J; Sirén, Jouni

2017-01-01

Most of the fastest-growing string collections today are repetitive, that is, most of the constituent documents are similar to many others. As these collections keep growing, a key approach to handling them is to exploit their repetitiveness, which can reduce their space usage by orders of magnitude. We study the problem of indexing repetitive string collections in order to perform efficient document retrieval operations on them. Document retrieval problems are routinely solved by search engines on large natural language collections, but the techniques are less developed on generic string collections. The case of repetitive string collections is even less understood, and there are very few existing solutions. We develop two novel ideas, interleaved LCPs and precomputed document lists , that yield highly compressed indexes solving the problem of document listing (find all the documents where a string appears), top- k document retrieval (find the k documents where a string appears most often), and document counting (count the number of documents where a string appears). We also show that a classical data structure supporting the latter query becomes highly compressible on repetitive data. Finally, we show how the tools we developed can be combined to solve ranked conjunctive and disjunctive multi-term queries under the simple [Formula: see text] model of relevance. We thoroughly evaluate the resulting techniques in various real-life repetitiveness scenarios, and recommend the best choices for each case.

Plant morphogenesis, auxin, and the signal-trafficking network incompleteness theorem

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Karl J. Niklas

2012-03-01

Full Text Available Plant morphogenesis (the development of form and function requires signal-trafficking and cross-talking among all levels of organization to coordinate the operation of metabolic and genomic networked systems. Many if not all of these biological features can be rendered as logic circuits supervising the operation of one or more signal-activated metabolic or genome networks. This approach simplifies complex morphogenetic phenomena and allows for their aggregation into diagrams of larger, more "global" networked systems. This conceptualization is illustrated for morphogenesis in model plants such as maize (Zea mays and Thale cress (Arabidopsis thaliana from an evolutionary perspective. The phytohormone indole-acetic acid (IAA is used as an example for a well-known signaling chemical and discussed in terms of the logic circuits and signal-activated sub-systems for hormone-mediated wall loosening and cell expansion as well as polar/lateral intercellular IAA transport. For each of these phenomena, a circuit/sub-system diagram highlights missing components, either in the logic circuit or in the sub-system it supervises, that must be identified experimentally if each of these basic phenomena is to be fully understood within a phylogen

REPETITIVE STRENGTH AMONG STUDENTS OF AGE 14

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Besim Halilaj

2014-06-01

Full Text Available The study involved 82 male students of the primary school “Qamil Ilazi” in Kaçanik-Kosovo.Four movement tests, which test the repetitive strength, were conducted: 1. Pull-up, 2. Sit-Up, 3. Back extension, 4. Push-up.The main goal of this study was to verify the actual motor status, respectively the component of the repetitive strength among students of age 14 of masculine gender. In addition to verifying the actual motor status, another objective was to verify the relationship between the variables employed.Basic statistical parameters show a distribution which is not significantly different from the normal distribution, yielded highly correlative values among the repetitive strength tests. Space factorization resulted in extracting two latent squares defined as repetitive strength of arms factor, and repetitive strength of body factor.

Tissue Motion and Assembly During Early Cardiovascular Morphogenesis

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Rongish, Brenda

2010-03-01

Conventional dogma in the field of cardiovascular developmental biology suggests that cardiac precursor cells migrate to the embryonic midline to form a tubular heart. These progenitors are believed to move relative to their extracellular matrix (ECM); responding to stimulatory and inhibitory cues in their environment. The tubular heart that is formed by 30 hours post fertilization is comprised of two concentric layers: the muscular myocardium and the endothelial-like endocardium, which are separated by a thick layer of ECM believed to be secreted predominantly by the myocardial cells. Here we describe the origin and motility of fluorescently tagged endocardial precursors in transgenic (Tie1-YFP) quail embryos (R. Lansford, Caltech) using epifluorescence time-lapse imaging. To visualize the environment of migrating endocardial progenitors, we labeled two ECM components, fibronectin and fibrillin-2, via in vivo microinjection of fluorochrome-conjugated monoclonal antibodies. Dynamic imaging was performed at stages encompassing tubular heart assembly and early looping. We established the motion of endocardial precursor cells and presumptive cardiac ECM fibrils using both object tracking and particle image velocimetry (image cross correlation). We determined the relative importance of directed cell autonomous motility versus passive tissue movements in endocardial morphogenesis. The data show presumptive endocardial cells and cardiac ECM fibrils are swept passively into the anterior and posterior poles of the elongating tubular heart. These quantitative data indicate the contribution of cell autonomous motility displayed by endocardial precursors is limited. Thus, tissue motion drives most of the cell displacements during endocardial morphogenesis.

CRIM1 Complexes with ß-catenin and Cadherins, Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis

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Ponferrada, Virgilio G.; Fan, Jieqing; Vallance, Jefferson E.; Hu, Shengyong; Mamedova, Aygun; Rankin, Scott A.; Kofron, Matthew; Zorn, Aaron M.; Hegde, Rashmi S.; Lang, Richard A.

2012-01-01

In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using C...

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

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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.

Giga-voxel computational morphogenesis for structural design

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Aage, Niels; Andreassen, Erik; Lazarov, Boyan S.; Sigmund, Ole

2017-10-01

In the design of industrial products ranging from hearing aids to automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer-aided design approaches. The computer-aided approach known as topology optimization enables unrestricted design freedom and shows great promise with regard to weight savings, but its applicability has so far been limited to the design of single components or simple structures, owing to the resolution limits of current optimization methods. Here we report a computational morphogenesis tool, implemented on a supercomputer, that produces designs with giga-voxel resolution—more than two orders of magnitude higher than previously reported. Such resolution provides insights into the optimal distribution of material within a structure that were hitherto unachievable owing to the challenges of scaling up existing modelling and optimization frameworks. As an example, we apply the tool to the design of the internal structure of a full-scale aeroplane wing. The optimized full-wing design has unprecedented structural detail at length scales ranging from tens of metres to millimetres and, intriguingly, shows remarkable similarity to naturally occurring bone structures in, for example, bird beaks. We estimate that our optimized design corresponds to a reduction in mass of 2-5 per cent compared to currently used aeroplane wing designs, which translates into a reduction in fuel consumption of about 40-200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems, antennas, nano-optics and micro-systems.

A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis.

Directory of Open Access Journals (Sweden)

Xuejun Chen

2009-12-01

Full Text Available Paraxial protocadherin (PAPC and fibronectin leucine-rich domain transmembrane protein-3 (FLRT3 are induced by TGFbeta signaling in Xenopus embryos and both regulate morphogenesis by inhibiting C-cadherin mediated cell adhesion.We have investigated the functional and physical relationships between PAPC, FLRT3, and C-cadherin. Although neither PAPC nor FLRT3 are required for each other to regulate C-cadherin adhesion, they do interact functionally and physically, and they form a complex with cadherins. By itself PAPC reduces cell adhesion physiologically to induce cell sorting, while FLRT3 disrupts adhesion excessively to cause cell dissociation. However, when expressed together PAPC limits the cell dissociating and tissue disrupting activity of FLRT3 to make it effective in physiological cell sorting. PAPC counteracts FLRT3 function by inhibiting the recruitment of the GTPase RND1 to the FLRT3 cytoplasmic domain.PAPC and FLRT3 form a functional complex with cadherins and PAPC functions as a molecular "governor" to maintain FLRT3 activity at the optimal level for physiological regulation of C-cadherin adhesion, cell sorting, and morphogenesis.

An integrated miRNA functional screening and target validation method for organ morphogenesis.

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Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

2016-03-16

The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

Estrogenic effect of soy isoflavones on mammary gland morphogenesis and gene expression profile

DEFF Research Database (Denmark)

Thomsen, Anni R.; Almstrup, Kristian; Nielsen, John E.

2006-01-01

We examined the effect of 17 beta-estradiol (E2) and soy isoflavones' exposure on morphogenesis and global gene expression in the murine mammary gland. Three exposure regimens were applied: isoflavones added to the diet throughout either the lactational period (via the dams) or the postweaning...... period and E2 administered orally during the lactational period. Whole mounts of mammary glands were evaluated both in juvenile and adult animals with respect to branching morphogenesis and terminal end bud (TEB) formation. At postnatal day (PND) 28, we observed a significant increase in branching...... isoflavone and E2 exposure was further substantiated by changes in gene expression, since the same groups of genes were up- and downregulated, particularly in the E2 and postweaning isoflavone regimen. All changes in gene expression correlated with changes in the cellular composition of the gland, i.e., more...

SACE_0012, a TetR-family transcriptional regulator, affects the morphogenesis of Saccharopolyspora erythraea.

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Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

2013-12-01

Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR, the relative transcription of SACE_7115, the amfC homolog for an aerial mycelium formation protein, was dramatically increased in SACE_0012 mutant, whereas erythromycin biosynthetic gene eryA, a pleiotropic regulatory gene bldD, and the genes SACE_2141, SACE_6464, SACE_6040, that are the homologs to the sporulation regulators WhiA, WhiB, WhiG, were not differentially expressed. SACE_0012 disruption could not restore its defect of aerial development in bldD mutant, and also did not further accelerate the mycelium formation in the mutant of SACE_7040 gene, that was previously identified to be a morphogenesis repressor. Furthermore, the transcriptional level of SACE_0012 had not markedly changed in bldD and SACE_7040 mutant over A226. Taken together, these results suggest that SACE_0012 is a negative regulator of S. erythraea morphogenesis by mainly increasing the transcription of amfC gene, independently of the BldD regulatory system.

Cellular and Nuclear Alignment Analysis for Determining Epithelial Cell Chirality

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Raymond, Michael J.; Ray, Poulomi; Kaur, Gurleen; Singh, Ajay V.; Wan, Leo Q.

2015-01-01

Left-right (LR) asymmetry is a biologically conserved property in living organisms that can be observed in the asymmetrical arrangement of organs and tissues and in tissue morphogenesis, such as the directional looping of the gastrointestinal tract and heart. The expression of LR asymmetry in embryonic tissues can be appreciated in biased cell alignment. Previously an in vitro chirality assay was reported by patterning multiple cells on microscale defined geometries and quantified the cell phenotype–dependent LR asymmetry, or cell chirality. However, morphology and chirality of individual cells on micropatterned surfaces has not been well characterized. Here, a Python-based algorithm was developed to identify and quantify immunofluorescence stained individual epithelial cells on multicellular patterns. This approach not only produces results similar to the image intensity gradient-based method reported previously, but also can capture properties of single cells such as area and aspect ratio. We also found that cell nuclei exhibited biased alignment. Around 35% cells were misaligned and were typically smaller and less elongated. This new imaging analysis approach is an effective tool for measuring single cell chirality inside multicellular structures and can potentially help unveil biophysical mechanisms underlying cellular chiral bias both in vitro and in vivo. PMID:26294010

Effects of light quality on flowering and morphogenesis in Hyoscyamus niger L.

NARCIS (Netherlands)

Hattab, El A.H.

1968-01-01

The present paper is concerned with bolting and morphogenesis of Hyoscyamus niger L. as reactions upon radiation in the visible spectrum.

Experiments are described in which Hyoscyamus plants were exposed to light of various well defined spectral regions. The light of these

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

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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

Conjoined twins: morphogenesis of the heart and a review.

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Gilbert-Barness, Enid; Debich-Spicer, Diane; Opitz, John M

2003-08-01

Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes. Copyright 2003 Wiley-Liss, Inc.

hmmr mediates anterior neural tube closure and morphogenesis in the frog Xenopus.

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Prager, Angela; Hagenlocher, Cathrin; Ott, Tim; Schambony, Alexandra; Feistel, Kerstin

2017-10-01

Development of the central nervous system requires orchestration of morphogenetic processes which drive elevation and apposition of the neural folds and their fusion into a neural tube. The newly formed tube gives rise to the brain in anterior regions and continues to develop into the spinal cord posteriorly. Conspicuous differences between the anterior and posterior neural tube become visible already during neural tube closure (NTC). Planar cell polarity (PCP)-mediated convergent extension (CE) movements are restricted to the posterior neural plate, i.e. hindbrain and spinal cord, where they propagate neural fold apposition. The lack of CE in the anterior neural plate correlates with a much slower mode of neural fold apposition anteriorly. The morphogenetic processes driving anterior NTC have not been addressed in detail. Here, we report a novel role for the breast cancer susceptibility gene and microtubule (MT) binding protein Hmmr (Hyaluronan-mediated motility receptor, RHAMM) in anterior neurulation and forebrain development in Xenopus laevis. Loss of hmmr function resulted in a lack of telencephalic hemisphere separation, arising from defective roof plate formation, which in turn was caused by impaired neural tissue narrowing. hmmr regulated polarization of neural cells, a function which was dependent on the MT binding domains. hmmr cooperated with the core PCP component vangl2 in regulating cell polarity and neural morphogenesis. Disrupted cell polarization and elongation in hmmr and vangl2 morphants prevented radial intercalation (RI), a cell behavior essential for neural morphogenesis. Our results pinpoint a novel role of hmmr in anterior neural development and support the notion that RI is a major driving force for anterior neurulation and forebrain morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Repetition and Emotive Communication in Music Versus Speech

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Elizabeth Hellmuth eMargulis

2013-04-01

Full Text Available Music and speech are often placed alongside one another as comparative cases. Their relative overlaps and disassociations have been well explored (e.g. Patel, 2010. But one key attribute distinguishing these two domains has often been overlooked: the greater preponderance of repetition in music in comparison to speech. Recent fMRI studies have shown that familiarity – achieved through repetition – is a critical component of emotional engagement with music (Pereira et al., 2011. If repetition is fundamental to emotional responses to music, and repetition is a key distinguisher between the domains of music and speech, then close examination of the phenomenon of repetition might help clarify the ways that music elicits emotion differently than speech.

Feature-based motion control for near-repetitive structures

NARCIS (Netherlands)

Best, de J.J.T.H.

2011-01-01

In many manufacturing processes, production steps are carried out on repetitive structures which consist of identical features placed in a repetitive pattern. In the production of these repetitive structures one or more consecutive steps are carried out on the features to create the final product.

Grade Repetition and Primary School Dropout in Uganda

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Kabay, Sarah

2016-01-01

Research on education in low-income countries rarely focuses on grade repetition. When addressed, repetition is typically presented along with early school dropout as the "wasting" of educational resources. Simplifying grade repetition in this way often fails to recognize significant methodological concerns and also overlooks the unique…

Analogous selection processes in declarative and procedural working memory: N-2 list-repetition and task-repetition costs.

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Gade, Miriam; Souza, Alessandra S; Druey, Michel D; Oberauer, Klaus

2017-01-01

Working memory (WM) holds and manipulates representations for ongoing cognition. Oberauer (Psychology of Learning and Motivation, 51, 45-100, 2009) distinguishes between two analogous WM sub-systems: a declarative WM which handles the objects of thought, and a procedural WM which handles the representations of (cognitive) actions. Here, we assessed whether analogous effects are observed when participants switch between memory sets (declarative representations) and when they switch between task sets (procedural representations). One mechanism assumed to facilitate switching in procedural WM is the inhibition of previously used, but currently irrelevant task sets, as indexed by n-2 task-repetition costs (Mayr & Keele, Journal of Experimental Psychology: General, 129(1), 4-26, 2000). In this study we tested for an analogous effect in declarative WM. We assessed the evidence for n-2 list-repetition costs across eight experiments in which participants switched between memory lists to perform speeded classifications, mental arithmetic, or a local recognition test. N-2 list-repetition costs were obtained consistently in conditions assumed to increase interference between memory lists, and when lists formed chunks in long-term memory. Further analyses across experiments revealed a substantial contribution of episodic memory to n-2 list-repetition costs, thereby questioning the interpretation of n-2 repetition costs as reflecting inhibition. We reanalyzed the data of eight task-switching experiments, and observed that episodic memory also contributes to n-2 task-repetition costs. Taken together, these results show analogous processing principles in declarative and procedural WM, and question the relevance of inhibitory processes for efficient switching between mental sets.

The Golden Ratio of Gait Harmony: Repetitive Proportions of Repetitive Gait Phases

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Marco Iosa

2013-01-01

Full Text Available In nature, many physical and biological systems have structures showing harmonic properties. Some of them were found related to the irrational number known as the golden ratio that has important symmetric and harmonic properties. In this study, the spatiotemporal gait parameters of 25 healthy subjects were analyzed using a stereophotogrammetric system with 25 retroreflective markers located on their skin. The proportions of gait phases were compared with , the value of which is about 1.6180. The ratio between the entire gait cycle and stance phase resulted in 1.620 ± 0.058, that between stance and the swing phase was 1.629 ± 0.173, and that between swing and the double support phase was 1.684 ± 0.357. All these ratios did not differ significantly from each other (, , repeated measure analysis of variance or from (, resp., t-tests. The repetitive gait phases of physiological walking were found in turn in repetitive proportions with each other, revealing an intrinsic harmonic structure. Harmony could be the key for facilitating the control of repetitive walking. Harmony is a powerful unifying factor between seemingly disparate fields of nature, including human gait.

Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model.

LENUS (Irish Health Repository)

Spiering, Martin J

2010-02-01

Candida albicans and Candida dubliniensis are closely related species displaying differences in virulence and genome content, therefore providing potential opportunities to identify novel C. albicans virulence genes. C. albicans gene arrays were used for comparative analysis of global gene expression in the two species in reconstituted human oral epithelium (RHE). C. albicans (SC5314) showed upregulation of hypha-specific and virulence genes within 30 min postinoculation, coinciding with rapid induction of filamentation and increased RHE damage. C. dubliniensis (CD36) showed no detectable upregulation of hypha-specific genes, grew as yeast, and caused limited RHE damage. Several genes absent or highly divergent in C. dubliniensis were upregulated in C. albicans. One such gene, SFL2 (orf19.3969), encoding a putative heat shock factor, was deleted in C. albicans. DeltaDeltasfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the DeltaDeltasfl2 strain. Moreover, SFL2 overexpression in C. albicans triggered hyphal morphogenesis. Although SFL2 deletion had no apparent effect on host survival in the murine model of systemic infection, DeltaDeltasfl2 strain-infected kidney tissues contained only yeast cells. These results suggest a role for SFL2 in morphogenesis and an indirect role in C. albicans pathogenesis in epithelial tissues.

Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis

NARCIS (Netherlands)

Lamers, Wouter H.; Moorman, Antoon F. M.

2002-01-01

Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4

Subjective duration distortions mirror neural repetition suppression.

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Pariyadath, Vani; Eagleman, David M

2012-01-01

Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

Subjective duration distortions mirror neural repetition suppression.

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Vani Pariyadath

Full Text Available Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli followed by a line presented at a different orientation (oddball stimulus. We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

The Developmental Trajectory of Nonword Repetition

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Chiat, Shula

2006-01-01

In line with the original presentation of nonword repetition as a measure of phonological short-term memory (Gathercole & Baddeley, 1989), the theoretical account Gathercole (2006) puts forward in her Keynote Article focuses on phonological storage as the key capacity common to nonword repetition and vocabulary acquisition. However, evidence that…

Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D.

Science.gov (United States)

Kniazeva, Ekaterina; Weidling, John W; Singh, Rahul; Botvinick, Elliot L; Digman, Michelle A; Gratton, Enrico; Putnam, Andrew J

2012-04-01

Reciprocal mechanical interactions between cells and the extracellular matrix (ECM) are thought to play important instructive roles in branching morphogenesis. However, most studies to date have failed to characterize these interactions on a length scale relevant to cells, especially in three-dimensional (3D) matrices. Here we utilized two complementary methods, spatio-temporal image correlation spectroscopy (STICS) and laser optical tweezers-based active microrheology (AMR), to quantify endothelial cell (EC)-mediated deformations of individual ECM elements and the local ECM mechanical properties, respectively, during the process of capillary morphogenesis in a 3D cell culture model. In experiments in which the ECM density was systematically varied, STICS revealed that the rate at which ECs deformed individual ECM fibers on the microscale positively correlated with capillary sprouting on the macroscale. ECs expressing constitutively active V14-RhoA displaced individual matrix fibers at significantly faster rates and displayed enhanced capillary sprouting relative to wild-type cells, while those expressing dominant-negative N19-RhoA behaved in an opposite fashion. In parallel, AMR revealed a local stiffening of the ECM proximal to the tips of sprouting ECs. By quantifying the dynamic physical properties of the cell-ECM interface in both space and time, we identified a correlation linking ECM deformation rates and local ECM stiffening at the microscale with capillary morphogenesis at the macroscale. This journal is © The Royal Society of Chemistry 2012

Global Repetition Influences Contextual Cueing

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Zang, Xuelian; Zinchenko, Artyom; Jia, Lina; Li, Hong

2018-01-01

Our visual system has a striking ability to improve visual search based on the learning of repeated ambient regularities, an effect named contextual cueing. Whereas most of the previous studies investigated contextual cueing effect with the same number of repeated and non-repeated search displays per block, the current study focused on whether a global repetition frequency formed by different presentation ratios between the repeated and non-repeated configurations influence contextual cueing effect. Specifically, the number of repeated and non-repeated displays presented in each block was manipulated: 12:12, 20:4, 4:20, and 4:4 in Experiments 1–4, respectively. The results revealed a significant contextual cueing effect when the global repetition frequency is high (≥1:1 ratio) in Experiments 1, 2, and 4, given that processing of repeated displays was expedited relative to non-repeated displays. Nevertheless, the contextual cueing effect reduced to a non-significant level when the repetition frequency reduced to 4:20 in Experiment 3. These results suggested that the presentation frequency of repeated relative to the non-repeated displays could influence the strength of contextual cueing. In other words, global repetition statistics could be a crucial factor to mediate contextual cueing effect. PMID:29636716

Imbalance between abstract and concrete repetitive thinking modes in schizophrenia.

Science.gov (United States)

Maurage, Pierre; Philippot, Pierre; Grynberg, Delphine; Leleux, Dominique; Delatte, Benoît; Mangelinckx, Camille; Belge, Jan-Baptist; Constant, Eric

2017-10-01

Repetitive thoughts can be divided in two modes: abstract/analytic (decontextualized and dysfunctional) and concrete/experiential (problem-focused and adaptive). They constitute a transdiagnostic process involved in many psychopathological states but have received little attention in schizophrenia, as earlier studies only indexed increased ruminations (related to dysfunctional repetitive thoughts) without jointly exploring both modes. This study explored the two repetitive thinking modes, beyond ruminations, to determine their imbalance in schizophrenia. Thirty stabilized patients with schizophrenia and 30 matched controls completed the Repetitive Response Scale and the Mini Cambridge-Exeter Repetitive Thought Scale, both measuring repetitive thinking modes. Complementary measures related to schizophrenic symptomatology, depression and anxiety were also conducted. Compared to controls, patients with schizophrenia presented an imbalance between repetitive thinking modes, with increased abstract/analytic and reduced concrete/experiential thoughts, even after controlling for comorbidities. Schizophrenia is associated with stronger dysfunctional repetitive thoughts (i.e. abstract thinking) and impaired ability to efficiently use repetitive thinking for current problem-solving (i.e. concrete thinking). This imbalance confirms the double-faced nature of repetitive thinking modes, whose influence on schizophrenia's symptomatology should be further investigated. The present results also claim for evaluating these processes in clinical settings and for rehabilitating the balance between opposite repetitive thinking modes. Copyright © 2017 Elsevier Inc. All rights reserved.

Septins from the phytopathogenic fungus Ustilago maydis are required for proper morphogenesis but dispensable for virulence.

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Isabel Alvarez-Tabarés

Full Text Available BACKGROUND: Septins are a highly conserved family of GTP-binding proteins involved in multiple cellular functions, including cell division and morphogenesis. Studies of septins in fungal cells underpin a clear correlation between septin-based structures and fungal morphology, providing clues to understand the molecular frame behind the varied morphologies found in fungal world. METHODOLOGY/PRINCIPAL FINDINGS: Ustilago maydis genome has the ability to encode four septins. Here, using loss-of-function as well as GFP-tagged alleles of these septin genes, we investigated the roles of septins in the morphogenesis of this basidiomycete fungus. We described that septins in U. maydis could assemble into at least three different structures coexisting in the same cell: bud neck collars, band-like structures at the growing tip, and long septin fibers that run from pole to pole near the cell cortex. We also found that in the absence of septins, U. maydis cells lost their elongated shape, became wider at the central region and ended up losing their polarity, pointing to an important role of septins in the morphogenesis of this fungus. These morphological defects were alleviated in the presence of an osmotic stabilizer suggesting that absence of septins affected the proper formation of the cell wall, which was coherent with a higher sensitivity of septin defective cells to drugs that affect cell wall construction as well as exocytosis. As U. maydis is a phytopathogen, we analyzed the role of septins in virulence and found that in spite of the described morphological defects, septin mutants were virulent in corn plants. CONCLUSIONS/SIGNIFICANCE: Our results indicated a major role of septins in morphogenesis in U. maydis. However, in contrast to studies in other fungal pathogens, in which septins were reported to be necessary during the infection process, we found a minor role of septins during corn infection by U. maydis.

Micro/nano-computed tomography technology for quantitative dynamic, multi-scale imaging of morphogenesis.

Science.gov (United States)

Gregg, Chelsea L; Recknagel, Andrew K; Butcher, Jonathan T

2015-01-01

Tissue morphogenesis and embryonic development are dynamic events challenging to quantify, especially considering the intricate events that happen simultaneously in different locations and time. Micro- and more recently nano-computed tomography (micro/nanoCT) has been used for the past 15 years to characterize large 3D fields of tortuous geometries at high spatial resolution. We and others have advanced micro/nanoCT imaging strategies for quantifying tissue- and organ-level fate changes throughout morphogenesis. Exogenous soft tissue contrast media enables visualization of vascular lumens and tissues via extravasation. Furthermore, the emergence of antigen-specific tissue contrast enables direct quantitative visualization of protein and mRNA expression. Micro-CT X-ray doses appear to be non-embryotoxic, enabling longitudinal imaging studies in live embryos. In this chapter we present established soft tissue contrast protocols for obtaining high-quality micro/nanoCT images and the image processing techniques useful for quantifying anatomical and physiological information from the data sets.

Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D†‡

Science.gov (United States)

Kniazeva, Ekaterina; Weidling, John W.; Singh, Rahul; Botvinick, Elliot L.; Digman, Michelle A.; Gratton, Enrico

2013-01-01

Reciprocal mechanical interactions between cells and the extracellular matrix (ECM) are thought to play important instructive roles in branching morphogenesis. However, most studies to date have failed to characterize these interactions on a length scale relevant to cells, especially in three-dimensional (3D) matrices. Here we utilized two complementary methods, spatio-temporal image correlation spectroscopy (STICS) and laser optical tweezers-based active microrheology (AMR), to quantify endothelial cell (EC)-mediated deformations of individual ECM elements and the local ECM mechanical properties, respectively, during the process of capillary morphogenesis in a 3D cell culture model. In experiments in which the ECM density was systematically varied, STICS revealed that the rate at which ECs deformed individual ECM fibers on the microscale positively correlated with capillary sprouting on the macroscale. ECs expressing constitutively active V14-RhoA displaced individual matrix fibers at significantly faster rates and displayed enhanced capillary sprouting relative to wild-type cells, while those expressing dominant-negative N19-RhoA behaved in an opposite fashion. In parallel, AMR revealed a local stiffening of the ECM proximal to the tips of sprouting ECs. By quantifying the dynamic physical properties of the cell-ECM interface in both space and time, we identified a correlation linking ECM deformation rates and local ECM stiffening at the microscale with capillary morphogenesis at the macroscale. PMID:22281872

Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.

Science.gov (United States)

Li, C; Lan, Y; Krumlauf, R; Jiang, R

2017-10-01

Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves. We found that expression of Dkk2, encoding a secreted Wnt antagonist, is significantly increased whereas the levels of active β-catenin protein, the essential transcriptional coactivator of canonical Wnt signaling, is significantly decreased in the posterior regions of the palatal shelves in embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates. We show that small molecule-mediated inhibition of Dickkopf (DKK) activity in utero during palatal shelf morphogenesis partly rescued secondary palate development in Pax9-deficient embryos. Moreover, we found that genetic inactivation of Wise, which is expressed in the developing palatal shelves and encodes another secreted antagonist of canonical Wnt signaling, also rescued palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9 del/del embryos exhibit defects in palatal shelf elevation/reorientation and significant reduction in accumulation of hyaluronic acid-a high molecular extracellular matrix glycosaminoglycan implicated in playing an important role in palatal shelf elevation-80% of Pax9 del/del ;Wise -/- double-mutant mouse embryos exhibit rescued palatal shelf elevation/reorientation, accompanied by restored

Repetitive thinking, executive functioning, and depressive mood in the elderly.

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Philippot, Pierre; Agrigoroaei, Stefan

2017-11-01

Previous findings and the depressive-executive dysfunction hypothesis suggest that the established association between executive functioning and depression is accounted for by repetitive thinking. Investigating the association between executive functioning, repetitive thinking, and depressive mood, the present study empirically tested this mediational model in a sample of older adults, while focusing on both concrete and abstract repetitive thinking. This latter distinction is important given the potential protective role of concrete repetitive thinking, in contrast to the depletive effect of abstract repetitive thinking. A sample of 43 elderly volunteers, between 75 and 95 years of age, completed tests of executive functioning (the Stroop test, the Trail Making test, and the Fluency test), and questionnaires of repetitive thinking and depression. Positive correlations were observed between abstract repetitive thinking and depressive mood, and between concrete repetitive thinking and executive functioning; a negative correlation was observed between depressive mood and executive functioning. Further, mediational analysis evidenced that the relation between executive functioning and depressive mood was mediated by abstract repetitive thinking. The present data provide, for the first time, empirical support to the depressive-executive dysfunction hypothesis: the lack of executive resources would favor a mode of abstract repetitive thinking, which in turn would deplete mood. It suggests that clinical intervention targeting depression in the elderly should take into consideration repetitive thinking modes and the executive resources needed to disengage from rumination.

DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer.

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Steven T Lott

2009-05-01

Full Text Available Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1, a novel gene encoding a member of the TRIM (tripartite motif subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS, an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young

Exploring bacteria-induced growth and morphogenesis in the green macroalga order Ulvales (Chlorophyta

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Thomas eWichard

2015-03-01

Full Text Available Green macroalgae, such as Ulvales, lose their typical morphology completely when grown under axenic conditions or in the absence of the appropriate microbiome. As a result, slow growing aberrant phenotypes or even callus-like morphotypes are observed in Ulvales. The cross-kingdom interactions between marine algae and microorganisms are hence not only restricted by the exchange of macronutrients, including vitamins and nutrients, but also by infochemicals such as bacterial morphogenetic compounds. The latter are a fundamental trait mediating the mutualism within the chemosphere where the organisms interact with each other via compounds in their surroundings.Approximately 60 years ago, pilot studies demonstrated that certain bacteria promote growth, whereas other bacteria induce morphogenesis; this is particularly true for the order of Ulvales. However, only slow progress was made towards the underlying mechanism due to the complexity of, for example, algal cultivation techniques, and the lack of standardized experiments in the laboratory.A breakthrough in this research was the discovery of the morphogenetic compound thallusin, which was isolated from an epiphytic bacterium and induces normal germination and restores the foliaceous morphotypes of Monostroma. Owing to the low concentration, the purification and structure elucidation of highly biologically active morphogenetic compounds is still challenging. Recently, it was found that only the combination of two specific bacteria from the Rhodobacteraceae and Flavobacteriaceae can completely recover the growth and morphogenesis of axenic Ulva mutabilis cultures forming a symbiotic tripartite community by chemical communication.This review combines literature detailing evidence of bacteria-induced morphogenesis in Ulvales. A set of standardized experimental approaches is further proposed for the preparation of axenic algal tissues, bacteria isolation, co-cultivation experiments, and the analysis of

Exploring bacteria-induced growth and morphogenesis in the green macroalga order Ulvales (Chlorophyta)

Science.gov (United States)

Wichard, Thomas

2015-01-01

Green macroalgae, such as Ulvales, lose their typical morphology completely when grown under axenic conditions or in the absence of the appropriate microbiome. As a result, slow growing aberrant phenotypes or even callus-like morphotypes are observed in Ulvales. The cross-kingdom interactions between marine algae and microorganisms are hence not only restricted by the exchange of macronutrients, including vitamins and nutrients, but also by infochemicals such as bacterial morphogenetic compounds. The latter are a fundamental trait mediating the mutualism within the chemosphere where the organisms interact with each other via compounds in their surroundings. Approximately 60 years ago, pilot studies demonstrated that certain bacteria promote growth, whereas other bacteria induce morphogenesis; this is particularly true for the order of Ulvales. However, only slow progress was made towards the underlying mechanism due to the complexity of, for example, algal cultivation techniques, and the lack of standardized experiments in the laboratory. A breakthrough in this research was the discovery of the morphogenetic compound thallusin, which was isolated from an epiphytic bacterium and induces normal germination restoring the foliaceous morphotypes of Monostroma. Owing to the low concentration, the purification and structure elucidation of highly biologically active morphogenetic compounds are still challenging. Recently, it was found that only the combination of two specific bacteria from the Rhodobacteraceae and Flavobacteriaceae can completely recover the growth and morphogenesis of axenic Ulva mutabilis cultures forming a symbiotic tripartite community by chemical communication. This review combines literature detailing evidences of bacteria-induced morphogenesis in Ulvales. A set of standardized experimental approaches is further proposed for the preparation of axenic algal tissues, bacteria isolation, co-cultivation experiments, and the analysis of the chemosphere

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 ...

Compartmentalised expression of Delta-like 1 in epithelial somites is required for the formation of intervertebral joints

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Gossler Achim

2007-06-01

Full Text Available Abstract Background Expression of the mouse Delta-like 1 (Dll1 gene in the presomitic mesoderm and in the caudal halves of somites of the developing embryo is required for the formation of epithelial somites and for the maintenance of caudal somite identity, respectively. The rostro-caudal polarity of somites is initiated early on within the presomitic mesoderm in nascent somites. Here we have investigated the requirement of restricted Dll1 expression in caudal somite compartments for the maintenance of rostro-caudal somite polarity and the morphogenesis of the axial skeleton. We did this by overexpressing a functional copy of the Dll1 gene throughout the paraxial mesoderm, in particular in anterior somite compartments, during somitogenesis in transgenic mice. Results Epithelial somites were generated normally and appeared histologically normal in embryos of two independent Dll1 over-expressing transgenic lines. Gene expression analyses of rostro-caudal marker genes suggested that over-expression of Dll1 without restriction to caudal compartments was not sufficient to confer caudal identity to rostral somite halves in transgenic embryos. Nevertheless, Dll1 over-expression caused dysmorphologies of the axial skeleton, in particular, in morphological structures that derive from the articular joint forming compartment of vertebrae. Accordingly, transgenic animals exhibited missing or reduced intervertebral discs, rostral and caudal articular processes as well as costal heads of ribs. In addition, the midline of the vertebral column did not develop normally. Transgenic mice had open neural arches and split vertebral bodies with ectopic pseudo-growth plates. Endochondral bone formation and ossification in the developing vertebrae were delayed. Conclusion The mice overexpressing Dll1 exhibit skeletal dysmorphologies that are also evident in several mutant mice with defects in somite compartmentalisation. The Dll1 transgenic mice demonstrate that

Directed PCR-free engineering of highly repetitive DNA sequences

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Preissler Steffen

2011-09-01

Full Text Available Abstract Background Highly repetitive nucleotide sequences are commonly found in nature e.g. in telomeres, microsatellite DNA, polyadenine (poly(A tails of eukaryotic messenger RNA as well as in several inherited human disorders linked to trinucleotide repeat expansions in the genome. Therefore, studying repetitive sequences is of biological, biotechnological and medical relevance. However, cloning of such repetitive DNA sequences is challenging because specific PCR-based amplification is hampered by the lack of unique primer binding sites resulting in unspecific products. Results For the PCR-free generation of repetitive DNA sequences we used antiparallel oligonucleotides flanked by restriction sites of Type IIS endonucleases. The arrangement of recognition sites allowed for stepwise and seamless elongation of repetitive sequences. This facilitated the assembly of repetitive DNA segments and open reading frames encoding polypeptides with periodic amino acid sequences of any desired length. By this strategy we cloned a series of polyglutamine encoding sequences as well as highly repetitive polyadenine tracts. Such repetitive sequences can be used for diverse biotechnological applications. As an example, the polyglutamine sequences were expressed as His6-SUMO fusion proteins in Escherichia coli cells to study their aggregation behavior in vitro. The His6-SUMO moiety enabled affinity purification of the polyglutamine proteins, increased their solubility, and allowed controlled induction of the aggregation process. We successfully purified the fusions proteins and provide an example for their applicability in filter retardation assays. Conclusion Our seamless cloning strategy is PCR-free and allows the directed and efficient generation of highly repetitive DNA sequences of defined lengths by simple standard cloning procedures.

Proliferation and apoptosis in early molar morphogenesis - voles as models in odontogenesis

Czech Academy of Sciences Publication Activity Database

Šetková, Jana; Lesot, H.; Matalová, Eva; Witter, K.; Matulová, Petra; Míšek, Ivan

2006-01-01

Roč. 50, 5 (2006), s. 481-489 ISSN 0214-6282 R&D Projects: GA ČR GA304/04/0101; GA MŠk OC B23.001 Grant - others:COST STSM B23-00981 Institutional research plan: CEZ:AV0Z50450515 Keywords : tooth development * morphogenesis * Microtus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.577, year: 2006

Lingual Kinematics during Rapid Syllable Repetition in Parkinson's Disease

Science.gov (United States)

Wong, Min Ney; Murdoch, Bruce E.; Whelan, Brooke-Mai

2012-01-01

Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD). Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric…

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.

Turing mechanism underlying a branching model for lung morphogenesis.

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Xu, Hui; Sun, Mingzhu; Zhao, Xin

2017-01-01

The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

Negative effects of item repetition on source memory.

Science.gov (United States)

Kim, Kyungmi; Yi, Do-Joon; Raye, Carol L; Johnson, Marcia K

2012-08-01

In the present study, we explored how item repetition affects source memory for new item-feature associations (picture-location or picture-color). We presented line drawings varying numbers of times in Phase 1. In Phase 2, each drawing was presented once with a critical new feature. In Phase 3, we tested memory for the new source feature of each item from Phase 2. Experiments 1 and 2 demonstrated and replicated the negative effects of item repetition on incidental source memory. Prior item repetition also had a negative effect on source memory when different source dimensions were used in Phases 1 and 2 (Experiment 3) and when participants were explicitly instructed to learn source information in Phase 2 (Experiments 4 and 5). Importantly, when the order between Phases 1 and 2 was reversed, such that item repetition occurred after the encoding of critical item-source combinations, item repetition no longer affected source memory (Experiment 6). Overall, our findings did not support predictions based on item predifferentiation, within-dimension source interference, or general interference from multiple traces of an item. Rather, the findings were consistent with the idea that prior item repetition reduces attention to subsequent presentations of the item, decreasing the likelihood that critical item-source associations will be encoded.

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

The morphogenesis of feathers.

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Yu, Mingke; Wu, Ping; Widelitz, Randall B; Chuong, Cheng-Ming

2002-11-21

Feathers are highly ordered, hierarchical branched structures that confer birds with the ability of flight. Discoveries of fossilized dinosaurs in China bearing 'feather-like' structures have prompted interest in the origin and evolution of feathers. However, there is uncertainty about whether the irregularly branched integumentary fibres on dinosaurs such as Sinornithosaurus are truly feathers, and whether an integumentary appendage with a major central shaft and notched edges is a non-avian feather or a proto-feather. Here, we use a developmental approach to analyse molecular mechanisms in feather-branching morphogenesis. We have used the replication-competent avian sarcoma retrovirus to deliver exogenous genes to regenerating flight feather follicles of chickens. We show that the antagonistic balance between noggin and bone morphogenetic protein 4 (BMP4) has a critical role in feather branching, with BMP4 promoting rachis formation and barb fusion, and noggin enhancing rachis and barb branching. Furthermore, we show that sonic hedgehog (Shh) is essential for inducing apoptosis of the marginal plate epithelia, which results in spaces between barbs. Our analyses identify the molecular pathways underlying the topological transformation of feathers from cylindrical epithelia to the hierarchical branched structures, and provide insights on the possible developmental mechanisms in the evolution of feather forms.

Pre-Lexical Disorders in Repetition Conduction Aphasia

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Sidiropoulos, Kyriakos; de Bleser, Ria; Ackermann, Hermann; Preilowski, Bruno

2008-01-01

At the level of clinical speech/language evaluation, the repetition type of conduction aphasia is characterized by repetition difficulties concomitant with reduced short-term memory capacities, in the presence of fluent spontaneous speech as well as unimpaired naming and reading abilities. It is still unsettled which dysfunctions of the…

Evidence for the involvement of a nonlexical route in the repetition of familiar words: A comparison of single and dual route models of auditory repetition.

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Hanley, J Richard; Dell, Gary S; Kay, Janice; Baron, Rachel

2004-03-01

In this paper, we attempt to simulate the picture naming and auditory repetition performance of two patients reported by Hanley, Kay, and Edwards (2002), who were matched for picture naming score but who differed significantly in their ability to repeat familiar words. In Experiment 1, we demonstrate that the model of naming and repetition put forward by Foygel and Dell (2000) is better able to accommodate this pattern of performance than the model put forward by Dell, Schwartz, Martin, Saffran, and Gagnon (1997). Nevertheless, Foygel and Dell's model underpredicted the repetition performance of both patients. In Experiment 2, we attempt to simulate their performance using a new dual route model of repetition in which Foygel and Dell's model is augmented by an additional nonlexical repetition pathway. The new model provided a more accurate fit to the real-word repetition performance of both patients. It is argued that the results provide support for dual route models of auditory repetition.

Apical polarity in three-dimensional culture systems: where to now?

Energy Technology Data Exchange (ETDEWEB)

Inman, J.L.; Bissell, Mina

2010-01-21

Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account.

Relationship between the number of repetitions and selected percentages of one repetition maximum in free weight exercises in trained and untrained men.

Science.gov (United States)

Shimano, Tomoko; Kraemer, William J; Spiering, Barry A; Volek, Jeff S; Hatfield, Disa L; Silvestre, Ricardo; Vingren, Jakob L; Fragala, Maren S; Maresh, Carl M; Fleck, Steven J; Newton, Robert U; Spreuwenberg, Luuk P B; Häkkinen, Keijo

2006-11-01

Resistance exercise intensity is commonly prescribed as a percent of 1 repetition maximum (1RM). However, the relationship between percent 1RM and the number of repetitions allowed remains poorly studied, especially using free weight exercises. The purpose of this study was to determine the maximal number of repetitions that trained (T) and untrained (UT) men can perform during free weight exercises at various percentages of 1RM. Eight T and 8 UT men were tested for 1RM strength. Then, subjects performed 1 set to failure at 60, 80, and 90% of 1RM in the back squat, bench press, and arm curl in a randomized, balanced design. There was a significant (p squat than the bench press or arm curl at 60% 1RM for T and UT. At 80 and 90% 1RM, there were significant differences between the back squat and other exercises; however, differences were much less pronounced. No differences in number of repetitions performed at a given exercise intensity were noted between T and UT (except during bench press at 90% 1RM). In conclusion, the number of repetitions performed at a given percent of 1RM is influenced by the amount of muscle mass used during the exercise, as more repetitions can be performed during the back squat than either the bench press or arm curl. Training status of the individual has a minimal impact on the number of repetitions performed at relative exercise intensity.

Combination of Hypomorphic Mutations of the Drosophila Homologues of Aryl Hydrocarbon Receptor and Nucleosome Assembly Protein Family Genes Disrupts Morphogenesis, Memory and Detoxification

OpenAIRE

Kuzin, Boris A.; Nikitina, Ekaterina A.; Cherezov, Roman O.; Vorontsova, Julia E.; Slezinger, Mikhail S.; Zatsepina, Olga G.; Simonova, Olga B.; Enikolopov, Grigori N.; Savvateeva-Popova, Elena V.

2014-01-01

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response...

Understanding work related musculoskeletal pain: does repetitive work cause stress symptoms?

DEFF Research Database (Denmark)

Bonde, J. P.; Mikkelsen, S.; Andersen, JH

2005-01-01

for development of regional pain in repetitive work, stress symptoms would likely be on the causal path. AIMS: To examine whether objective measures of repetitive monotonous work are related to occurrence and development of stress symptoms. METHODS: In 1994-95, 2033 unskilled workers with continuous repetitive...... Profile Inventory. RESULTS: Repetitive work, task cycle time, and quantified measures of repetitive upper extremity movements including force requirements were not related to occurrence of stress symptoms at baseline or development of stress symptoms during three years of follow up. CONCLUSIONS......: The findings do not indicate that repetitive work is associated with stress symptoms, but small effects cannot be ruled out. Thus the results question the importance of mental stress mechanisms in the causation of regional pain related to repetitive work. However, the findings should be interpreted...

CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

Science.gov (United States)

Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

2010-09-22

Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

Inverted U-shaped model: How frequent repetition affects perceived risk

OpenAIRE

Xi Lu; Xiaofei Xie; Lu Liu

2015-01-01

We asked how repeated media reports on technological hazards influence an individual's risk perception. We looked for two contradictory effects, an increasing effect of repetition on perceived risk with the first few repetitions and a decreasing effect with later repetitions, leading to the inverted U-shaped pattern. In an experiment, we demonstrated the inverted U-shaped relationship between the repetition and perceived risk in the context of food risk. The finding broaden...

De novo assembly of a 40 Mb eukaryotic genome from short sequence reads: Sordaria macrospora, a model organism for fungal morphogenesis.

Science.gov (United States)

Nowrousian, Minou; Stajich, Jason E; Chu, Meiling; Engh, Ines; Espagne, Eric; Halliday, Karen; Kamerewerd, Jens; Kempken, Frank; Knab, Birgit; Kuo, Hsiao-Che; Osiewacz, Heinz D; Pöggeler, Stefanie; Read, Nick D; Seiler, Stephan; Smith, Kristina M; Zickler, Denise; Kück, Ulrich; Freitag, Michael

2010-04-08

Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30-90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in approximately 4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb) with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data can be used for

De novo assembly of a 40 Mb eukaryotic genome from short sequence reads: Sordaria macrospora, a model organism for fungal morphogenesis.

Directory of Open Access Journals (Sweden)

Minou Nowrousian

2010-04-01

Full Text Available Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30-90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in approximately 4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data

Hanging on for the ride: adhesion to the extracellular matrix mediates cellular responses in skeletal muscle morphogenesis and disease.

Science.gov (United States)

Goody, Michelle F; Sher, Roger B; Henry, Clarissa A

2015-05-01

Skeletal muscle specification and morphogenesis during early development are critical for normal physiology. In addition to mediating locomotion, skeletal muscle is a secretory organ that contributes to metabolic homeostasis. Muscle is a highly adaptable tissue, as evidenced by the ability to increase muscle cell size and/or number in response to weight bearing exercise. Conversely, muscle wasting can occur during aging (sarcopenia), cancer (cancer cachexia), extended hospital stays (disuse atrophy), and in many genetic diseases collectively known as the muscular dystrophies and myopathies. It is therefore of great interest to understand the cellular and molecular mechanisms that mediate skeletal muscle development and adaptation. Muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction. This process requires carefully orchestrated interactions between cells and their extracellular matrix microenvironment. These interactions are dynamic, allowing muscle cells to sense biophysical, structural, organizational, and/or signaling changes within their microenvironment and respond appropriately. In many musculoskeletal diseases, these cell adhesion interactions are disrupted to such a degree that normal cellular adaptive responses are not sufficient to compensate for accumulating damage. Thus, one major focus of current research is to identify the cell adhesion mechanisms that drive muscle morphogenesis, with the hope that understanding how muscle cell adhesion promotes the intrinsic adaptability of muscle tissue during development may provide insight into potential therapeutic approaches for muscle diseases. Our objectives in this review are to highlight recent studies suggesting conserved roles for cell-extracellular matrix adhesion in vertebrate muscle morphogenesis and cellular adaptive responses in animal models of muscle diseases. Copyright © 2015 Elsevier Inc. All rights

A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling.

Science.gov (United States)

Miret, Noelia; Rico-Leo, Eva; Pontillo, Carolina; Zotta, Elsa; Fernández-Salguero, Pedro; Randi, Andrea

2017-11-01

Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05μM HCB induced cell migration and TGF-β1 signaling, whereas 5μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR+/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR+/+ mice. Primary culture of mammary epithelial cells from AhR+/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5μM). Interestingly, AhR-/- mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds. Copyright © 2017. Published by Elsevier Inc.

Translation of Syntactic Repetitions as Formal-Aesthetic Marker in Das Brot

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Rosyidah

2017-03-01

Full Text Available Translating repetition as a formal-aesthetic marker in a literary text is a hard task and challenge for translators. The topic of this study is translation of syntactic repetition as formal-aesthetic marker in literary text. The problems examined include: (1 the syntactic repetitions in the source text and (2 the strategies to translate these repetitions carried out by the students. This is a case study with a qualitative approach which is aimed to describe the syntactic repetitions as formal aesthetic markers in the German short story Das Brot written by Wolfgang Borchert and to explain the strategies used by Indonesian students to translate the syntactic repetitions. The research data are repetitive sentences gained from the German short story and from the translated versions done by 60 students. The analysis was carried out interactively and sociosemiotically. The results show that there were repetitions at the sentence level including sentence parts, sentences and content repetition in the source text. The strategies used by the students to translate the repetitions of sentence part and sentence were exact preservation and modified preservation with reduction, implicitation and addition of extra words, avoidance with deletion, explicitation, implicitation, nominalization, and synonymy. In the meantime, content repetitions were translated using the strategy of exact preservation and preservation with modification by adding extra words and using role-based terms of address. Thus, the results lead to two new variations of modified preservation, namely preservation by adding extra words and by changing addressing terms and one new variation of avoidance that is explicitation.

Microgravity simulation activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis during vasculogenesis

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Shouli Wang

2017-12-01

Full Text Available Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB model for vasculogenesis and simulated microgravity by clinorotation. We first differentiated mouse embryonic stem cells into cystic EBs containing two germ layers and then analyzed vessel formation under clinorotation. We observed that endothelial cell differentiation was slightly reduced under clinorotation, whereas vascular branch morphogenesis was markedly enhanced. EB-derived endothelial cells migrated faster, displayed multiple cellular processes, and had higher Cdc42 and Rac1 activity when subjected to clinorotation. Genetic analysis and rescue experiments demonstrated that Cdc42 but not Rac1 is required for microgravity-induced vascular branch morphogenesis. Furthermore, affinity pull-down assay and mass spectrometry identified Rap1GDS1 to be a Cdc42 guanine nucleotide exchange factor, which was upregulated by clinorotation. shRNA-mediated knockdown of Rap1GDS1 selectively suppressed Cdc42 activation and inhibited both baseline and microgravity-induced vasculogenesis. This was rescued by ectopic expression of constitutively active Cdc42. Taken together, these results support the notion that simulated microgravity activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis.

CRIM1 complexes with ß-catenin and cadherins, stabilizes cell-cell junctions and is critical for neural morphogenesis.

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Virgilio G Ponferrada

Full Text Available In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1 is a single-pass (type 1 transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ß-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ß-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions.

Grade Repetition in Queensland State Prep Classes

Science.gov (United States)

Anderson, Robyn

2012-01-01

The current study considers grade repetition rates in the early years of schooling in Queensland state schools with specific focus on the pre-schooling year, Prep. In particular, it provides empirical evidence of grade repetition in Queensland state schools along with groups of students who are more often repeated. At the same time, much of the…

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.

RPERT: Repetitive-Projects Evaluation and Review Technique

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Remon Fayek Aziz

2014-03-01

Full Text Available Estimating expected completion probability of any repetitive construction project with a specified/certain duration including repetitive identical activities by using program evaluation and review technique is the most essential part in construction areas since the activities were had optimistic, most likely and pessimistic durations. This paper focuses on the calculation of expected completion probability of any repetitive construction project within a specified/certain duration (contract duration by using Line Of Balance technique (LOB in case of single or multiple number of crews integrated with Program Evaluation and Review Technique (PERT. Repetitive-Projects Evaluation and Review Technique (RPERT, which is a simplified software, will generate the expected project completion probability of a specified/certain duration (contract duration. RPERT software is designed by java programming code system to provide a number of new and unique capabilities, including: (1 Viewing the expected project completion probability according to a set of specified durations per each identical activity (optimistic time, most likely time, and pessimistic time in the analyzed project; (2 Providing seamless integration with available project time calculations. In order to provide the aforementioned capabilities of RPERT, the system is implemented and developed in four main modules: (1 A user interface module; (2 A database module; (3 A running module; and (4 A processing module. At the end, an illustrative example will be presented to demonstrate and verify the applications of proposed software (RPERT, by using probabilistic calculations for repetitive construction projects.

Growth and morphogenesis of shoot initials of Douglas fir, Pseudotsuga menziesii (Mirb.) Franco, in vitro

NARCIS (Netherlands)

Evers, P.W.

1984-01-01

An optimalized method of micropropagation of Douglas fir is described. Seasonal changes were found in optima for nitrate and sucrose in the medium and in the optimum for the light intensity during the culture of shoot initials. Differences in morphogenesis were obtained from shoot initials that had

TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation.

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Aurélie Hayez

Full Text Available TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.

Gibberellin influence on the morphogenesis of the moss Bryum argenteum Hedw. in in vitro conditions

Directory of Open Access Journals (Sweden)

Sabovljević Aneta

2010-01-01

Full Text Available The moss Bryum argenteum Hedw. was treated with gibberellins as well as some inhibitors of gibberellin biosynthesis in order to investigate their influence on B. argenteum morphogenesis. Generally, gibberellins have not been chemically identified in bryophytes, while other groups of classical phytohormones (auxins, cytokinins, abscisic acid and ethylene have been chemically identified in these plants. The in vitro culture of the moss Bryum argenteum was established from sterilized spores. The apical shoots of untreated gametophytes grown in vitro were used to investigate the influence of different substances on secondary protonema and on the growth and multiplication of the gametophytes. B. argenteum reacts differently to the growth regulators applied. Both gibberellins applied in vitro (GA3 and GA7 have a positive effect on B. argenteum morphogenesis. Shoot multiplication was negatively affected by three tested growth retardants (ancymidol, BX-112 and chlorocholine chloride, while these substances did not have such strong effects on the moss protonema development.

A novel cell binding site in the coiled‐coil domain of laminin involved in capillary morphogenesis

DEFF Research Database (Denmark)

Sanz, Laura; García-Bermejo, Laura; Blanco, Francisco J

2003-01-01

Recently, we reported the isolation and characterization of an anti‐laminin antibody that modulates the extracellular matrix‐dependent morphogenesis of endothelial cells. Here we use this antibody to precisely map the binding site responsible for mediating this biologically important interaction....

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.

An Epigenetic Model for Pigment Patterning Based on Mechanical and Cellular Interactions

Czech Academy of Sciences Publication Activity Database

Caballero, L.; Benitez, M.; Alvarez-Buylla, E. R.; Hernandez, S.; Arzola, Alejandro V.; Cocho, G.

2012-01-01

Roč. 318, č. 3 (2012), s. 209-223 ISSN 1552-5007 Institutional support: RVO:68081731 Keywords : epithelial-mesenchymal transitions * neural crest * traction forces * morphogenesis Subject RIV: ED - Physiology Impact factor: 2.123, year: 2012

Understanding work related musculoskeletal pain: does repetitive work cause stress symptoms?

Science.gov (United States)

Bonde, J P; Mikkelsen, S; Andersen, J H; Fallentin, N; Baelum, J; Svendsen, S W; Thomsen, J F; Frost, P; Kaergaard, A

2005-01-01

Pain in the neck and upper extremity is reported with high frequency in repetitive work. Mechanical overload of soft tissues seems a plausible mechanism, but psychological factors have received considerable attention during the past decade. If psychological factors are important for development of regional pain in repetitive work, stress symptoms would likely be on the causal path. To examine whether objective measures of repetitive monotonous work are related to occurrence and development of stress symptoms. In 1994-95, 2033 unskilled workers with continuous repetitive work and 813 workers with varied work were enrolled. Measures of repetitiveness and force requirements were quantified using video observations to obtain individual exposure estimates. Stress symptoms were recorded at baseline and after approximately one, two, and three years by the Setterlind Stress Profile Inventory. Repetitive work, task cycle time, and quantified measures of repetitive upper extremity movements including force requirements were not related to occurrence of stress symptoms at baseline or development of stress symptoms during three years of follow up. The findings do not indicate that repetitive work is associated with stress symptoms, but small effects cannot be ruled out. Thus the results question the importance of mental stress mechanisms in the causation of regional pain related to repetitive work. However, the findings should be interpreted with caution because the stress inventory has not been validated against a gold standard.

Repetitive exposure: Brain and reflex measures of emotion and attention

Science.gov (United States)

Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

2010-01-01

Effects of massed repetition on the modulation of the late positive potential elicited during affective picture viewing were investigated in two experiments. Despite a difference in the number of repetitions across studies (from 5 to 30), results were quite similar: the late positive potential continued to be enhanced when viewing emotional, compared to neutral, pictures. On the other hand, massed repetition did prompt a reduction in the late positive potential that was most pronounced for emotional pictures. Startle probe P3 amplitude generally increased with repetition, suggesting diminished attention allocation to repeated pictures. The blink reflex, however, continued to be modulated by hedonic valence, despite massive massed repetition. Taken together, the data suggest that the amplitude of the late positive potential during picture viewing reflects both motivational significance and attention allocation. PMID:20701711

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...

Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia

DEFF Research Database (Denmark)

Gudjonsson, Thorarinn; Adriance, Melissa C; Sternlicht, Mark D

2005-01-01

The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most atten...

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.

Is perfectionism associated with academic burnout through repetitive negative thinking?

Science.gov (United States)

Garratt-Reed, David; Howell, Joel; Hayes, Lana; Boyes, Mark

2018-01-01

Academic burnout is prevalent among university students, although understanding of what predicts burnout is limited. This study aimed to test the direct and indirect relationship between two dimensions of perfectionism (Perfectionistic Concerns and Perfectionistic Strivings) and the three elements of Academic Burnout (Exhaustion, Inadequacy, and Cynicism) through Repetitive Negative Thinking. In a cross-sectional survey, undergraduate students ( n  = 126, M age = 23.64, 79% female) completed well-validated measures of Perfectionism, Repetitive Negative Thinking, and Academic Burnout. Perfectionistic Concerns was directly associated with all elements of burnout, as well as indirectly associated with Exhaustion and Cynicism via Repetitive Negative Thinking. Perfectionistic Strivings was directly associated with less Inadequacy and Cynicism; however, there were no indirect associations between Perfectionistic Strivings and Academic Burnout operating through Repetitive Negative Thinking. Repetitive Negative Thinking was also directly related to more burnout Exhaustion and Inadequacy, but not Cynicism. It is concluded that future research should investigate whether interventions targeting Perfectionistic Concerns and Repetitive Negative Thinking can reduce Academic Burnout in university students.

Distinct subsets of Eve-positive pericardial cells stabilise cardiac outflow and contribute to Hox gene-triggered heart morphogenesis in Drosophila.

Science.gov (United States)

Zmojdzian, Monika; de Joussineau, Svetlana; Da Ponte, Jean Philippe; Jagla, Krzysztof

2018-01-17

The Drosophila heart, composed of discrete subsets of cardioblasts and pericardial cells, undergoes Hox-triggered anterior-posterior morphogenesis, leading to a functional subdivision into heart proper and aorta, with its most anterior part forming a funnel-shaped cardiac outflow. Cardioblasts differentiate into Tin-positive 'working myocytes' and Svp-expressing ostial cells. However, developmental fates and functions of heart-associated pericardial cells remain elusive. Here, we show that the pericardial cells that express the transcription factor Even Skipped adopt distinct fates along the anterior-posterior axis. Among them, the most anterior Antp-Ubx-AbdA - negative cells form a novel cardiac outflow component we call the outflow hanging structure, whereas the Antp-expressing cells differentiate into wing heart precursors. Interestingly, Hox gene expression in the Even Skipped-positive cells not only underlies their antero-posterior diversification, but also influences heart morphogenesis in a non-cell-autonomous way. In brief, we identify a new cardiac outflow component derived from a subset of Even Skipped-expressing cells that stabilises the anterior heart tip, and demonstrate non-cell-autonomous effects of Hox gene expression in the Even Skipped-positive cells on heart morphogenesis. © 2018. Published by The Company of Biologists Ltd.

Repetition code of 15 qubits

Science.gov (United States)

Wootton, James R.; Loss, Daniel

2018-05-01

The repetition code is an important primitive for the techniques of quantum error correction. Here we implement repetition codes of at most 15 qubits on the 16 qubit ibmqx3 device. Each experiment is run for a single round of syndrome measurements, achieved using the standard quantum technique of using ancilla qubits and controlled operations. The size of the final syndrome is small enough to allow for lookup table decoding using experimentally obtained data. The results show strong evidence that the logical error rate decays exponentially with code distance, as is expected and required for the development of fault-tolerant quantum computers. The results also give insight into the nature of noise in the device.

Nanosecond radar system based on repetitive pulsed relativistic BWO

International Nuclear Information System (INIS)

Bunkin, B.V.; Gaponov-Grekhov, A.V.; Eltchaninov, A.S.; Zagulov, F.Ya.; Korovin, S.D.; Mesyats, G.A.; Osipov, M.L.; Otlivantchik, E.A.; Petelin, M.I.; Prokhorov, A.M.

1993-01-01

The paper presents the results of studies of a nanosecond radar system based on repetitive pulsed relativistic BWO. A pulsed power repetitive accelerator producing electron beams of electron energy 500-700 keV and current 5 kA in pulses of duraction 10 ns with a repetition rate of 100 pps is described. The results of experiments with a high-voltage gas-filled spark gap and a cold-cathode vacuum diode under the conditions of high repetition rates are given. Also presented are the results of studies of a relativistic BWO operating with a wavelength of 3 cm. It is shown that for a high-current beam electron energy of 500-700 keV, the BWO efficiency can reach 35%, the microwave power being 10 9 W. A superconducting solenoid creating a magnetic field of 30 kOe was used for the formation and transportation of the high-current electron beam. In conclusion, the outcome of tests of a nanosecond radar station based on a pulsed power repetitive accelerator and a relativistic BWO is reported

Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.

Science.gov (United States)

Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira

2017-01-01

In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages. © 2017. Published by The Company of Biologists Ltd.

Mechanical growth and morphogenesis of seashells

KAUST Repository

Moulton, D.E.

2012-10-01

Seashells grow through the local deposition of mass along the aperture. Many mathematical descriptions of the shapes of shells have been provided over the years, and the basic logarithmic coiling seen in mollusks can be simulated with few parameters. However, the developmental mechanisms underlying shell coiling are largely not understood and the ubiquitous presence of ornamentation such as ribs, tubercles, or spines presents yet another level of difficulty. Here we develop a general model for shell growth based entirely on the local geometry and mechanics of the aperture and mantle. This local description enables us to efficiently describe both arbitrary growth velocities and the evolution of the shell aperture itself. We demonstrate how most shells can be simulated within this framework. We then turn to the mechanics underlying the shell morphogenesis, and develop models for the evolution of the aperture. We demonstrate that the elastic response of the mantle during shell deposition provides a natural mechanism for the formation of three-dimensional ornamentation in shells. © 2012 Elsevier Ltd.

Transgenerational effects of environmental enrichment on repetitive motor behavior development.

Science.gov (United States)

Bechard, Allison R; Lewis, Mark H

2016-07-01

The favorable consequences of environmental enrichment (EE) on brain and behavior development are well documented. Much less is known, however, about transgenerational benefits of EE on non-enriched offspring. We explored whether transgenerational effects of EE might extend to the development of repetitive motor behaviors in deer mice. Repetitive motor behaviors are invariant patterns of movement that, across species, can be reduced by EE. We found that EE not only attenuated the development of repetitive behavior in dams, but also in their non-enriched offspring. Moreover, maternal behavior did not seem to mediate the transgenerational effect we found, although repetitive behavior was affected by reproductive experience. These data support a beneficial transgenerational effect of EE on repetitive behavior development and suggest a novel benefit of reproductive experience. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrical strength of vacuum gap at repetitive breakdown

International Nuclear Information System (INIS)

Dubinin, N.P.; Chistyakov, N.P.

1983-01-01

The investigation of repetitive pulse breakdown of vacuum space, which electrodes have been subjected to various treatment in vacuum and inert gas, is carried out. In case of electrode warm-up in vacuum up to 400 deg C as well as electronic heating up to 900 deg C the voltage in case of repetitive breakdown hasncreased approximately twice and in case of a through treatment, which is accomplished by a high-current glow discharge in inert gas, the maximum high voltage in case of the first breakdown at repetitive breakdown has decreased by 30...40%, remaining 2-3 times higher than in the first case

Word and nonword repetition in patients with Schizophrenia

Directory of Open Access Journals (Sweden)

Alireza Farnam

2015-08-01

Full Text Available Introduction: The assessment of the verbal repetition is important in the study of acquired language disorders and neuropsychology. It is helpful in differential diagnosis of aphasia subtypes, auditory breakdowns, and working memory (WM performance. Though different linguistic disorders have been identified in patients with schizophrenia, very little is known about their verbal repetition ability. Methods: The present study was conducted in the inpatient ward of Razi Psychiatric Hospital, Tabriz University of Medical Sciences, Iran, during the year 2013. Participants were: 30 patients diagnosed with schizophrenia during the maintenance phase of treatment and 30 healthy people as control group. They were asked to repeat 15 words and 15 nonwords immediately. The stimuli were 1, 2, and 3 syllabic in Turkish language. Any incorrect repetition scored 1 and correct repetitions scored 0. Lexicalization errors were compared between groups too. Results: Both groups repeated words better than nonwords. Patients showed lower ability to repeat nonwords than controls, especially in 3 syllabics. There was no significant difference in the repetition of words between groups though it was better in controls. Patients with schizophrenia made more errors in both words and nonwords and lexicalization errors were twice more. Conclusion: Lower ability to repeat nonwords (than words in patients with schizophrenia may show the involvement of phonological loop of WM. More lexicalization errors may take place because of dis-inhibition.

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...

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.

Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis

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Nie, Xuguang; Wang, Qin; Jiao, Kai

2014-01-01

MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis. PMID:21256960

Characterization of epithelial domains in the nasal passages of chick embryos: spatial and temporal mapping of a range of extracellular matrix and cell surface molecules during development of the nasal placode.

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Croucher, S J; Tickle, C

1989-07-01

The formation of the nasal passages involves complex morphogenesis and their lining develops a spatially ordered pattern of differentiation, with distinct domains of olfactory and respiratory epithelium. Using antibodies to the neural cell adhesion molecule (N-CAM), keratan sulphate and heparan sulphate proteoglycan (HSPG) and a panel of lectins (agglutinins of Canavalia ensiformis (ConA), Dolichos biflorus (DBA), peanut (PNA), Ricinis communis (RCA1), soybean (SBA), Ulex europaeus (UEA1), and wheatgerm (WGA], we have documented cell surface characteristics of each epithelial domain. Binding of antibodies to N-CAM and to keratan sulphate, and the lectins ConA, PNA, RCA1, SBA and WGA marks the olfactory epithelial domain only. The restriction of N-CAM to the sensory region of the epithelium has also been reported in the developing ear. This striking similarity is consistent with the idea that N-CAM may be involved in the division of functionally and histologically distinct cell groups within an epithelium. We traced the olfactory-specific cell markers during development to gain insights into the origin of the epithelial lining of the nasal passages. All reagents bind at early stages to the thickened nasal placode and surrounding head ectoderm and then become progressively restricted to the olfactory domain. The expression of these characteristics appears to be modulated during development rather than being cell autonomous. The distribution of keratan sulphate was compared with collagen type II in relation to the specification of the chondrocranium. Keratan sulphate and collagen type II are only colocalized at the epithelial-mesenchymal interface during early nasal development. At later stages, only collagen type II is expressed at the interface throughout the nasal passages, whereas keratan sulphate is absent beneath the respiratory epithelium.

Two discharge modes of a repetitive nanosecond pulsed helium glow discharge under sub-atmospheric pressure in the repetition frequency range of 20 to 600 kHz

Science.gov (United States)

Kikuchi, Yusuke; Maegawa, Takuya; Otsubo, Akira; Nishimura, Yoshimi; Nagata, Masayoshi; Yatsuzuka, Mitsuyasu

2018-05-01

Two discharge modes, α and γ, of a repetitive nanosecond pulsed helium glow discharge at a gas pressure of 10 kPa in the repetition frequency range from 20 to 600 kHz are reported for the first time. The pulsed glow discharge is produced in a pair of parallel plate metal electrodes without insertion of dielectrics. The α mode discharge is volumetrically produced in the electrode gap at a low-repetition frequency, whereas the γ mode discharge is localized at the cathode surface at a high-repetition frequency. At high-repetition frequency, the time interval between voltage pulses is shorter than the lifetime of the afterglow produced by the preceding discharge. Then, the γ mode discharge is maintained by a large number of secondary electrons emitted from the cathode exposed to high-density ions and metastable helium atoms in the afterglow. In the α mode discharge with a low-repetition frequency operation, primary electrons due to gas ionization dominate the ionization process. Thus, a large discharge voltage is needed for the excitation of the α mode discharge. It is established that the bifurcation of α-γ discharge mode, accompanied by a decrease in the discharge voltage, occurs at the high-repetition frequency of ∼120 kHz.

Recency, repetition, and the multidimensional basis of recognition memory.

Science.gov (United States)

Buchsbaum, Bradley R; Lemire-Rodger, Sabrina; Bondad, Ashley; Chepesiuk, Alexander

2015-02-25

Recency and repetition are two factors that have large effects on human memory performance. One way of viewing the beneficial impact of these variables on recognition memory is to assume that both factors modulate a unidimensional memory trace strength. Although previous functional neuroimaging studies have indicated that recency and repetition may modulate similar brain structures, particularly in the region of the inferior parietal cortex, there is extensive behavioral evidence that human subjects can make independent and accurate recognition memory judgments about both an item's recency and its frequency. In the present study, we used fMRI to examine patterns of brain activity during recognition memory for auditory-verbal stimuli that were parametrically and orthogonally manipulated in terms of recency and number of repetitions. We found in a continuous recognition paradigm that the lateral inferior parietal cortex, a region that has previously been associated with recollective forms of memory, is highly sensitive to recency but not repetition. In a multivariate analysis of whole-brain activation patterns, we found orthogonal components that dissociated recency and repetition variables, indicating largely independent neural bases underlying these two factors. The results demonstrate that although both recency and repetition dramatically improve recognition memory performance, the neural bases for this improvement are dissociable, and thus are difficult to explain in terms of access to a unitary memory trace. Copyright © 2015 the authors 0270-6474/15/353544-11$15.00/0.

Repetition of Attempted Suicide Among Immigrants in Europe

Science.gov (United States)

Lipsicas, Cendrine Bursztein; Mäkinen, Ilkka Henrik; Wasserman, Danuta; Apter, Alan; Kerkhof, Ad; Michel, Konrad; Renberg, Ellinor Salander; van Heeringen, Kees; Värnik, Airi; Schmidtke, Armin

2014-01-01

Objectives To compare frequencies of suicide attempt repetition in immigrants and local European populations, and the timing of repetition in these groups. Method: Data from 7 European countries, comprising 10 574 local and 3032 immigrant subjects, were taken from the World Health Organization European Multicentre Study on Suicidal Behaviour and the ensuing Monitoring Suicidal Behaviour in Europe (commonly referred to as MONSUE) project. The relation between immigrant status and repetition of suicide attempt within 12-months following first registered attempt was analyzed with binary logistic regression, controlling for sex, age, and method of attempt. Timing of repetition was controlled for sex, age, and the recommended type of aftercare. Results: Lower odds of repeating a suicide attempt were found in Eastern European (OR 0.50; 95% CI 0.41 to 0.61, P Europe stands in contrast to their markedly higher tendency to attempt suicide in general, possibly pointing to situational stress factors related to their suicidal crisis that are less persistent over time. Our findings also raise the possibility that suicide attempters and repeaters constitute only partially overlapping populations. PMID:25565687

Spatiotemporal mechanical variation reveals critical role for rho kinase during primitive streak morphogenesis.

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Henkels, Julia; Oh, Jaeho; Xu, Wenwei; Owen, Drew; Sulchek, Todd; Zamir, Evan

2013-02-01

Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

Over-expression of KdSOC1 gene affected plantlet morphogenesis in Kalanchoe daigremontiana.

Science.gov (United States)

Zhu, Chen; Wang, Li; Chen, Jinhua; Liu, Chenglan; Zeng, Huiming; Wang, Huafang

2017-07-17

Kalanchoe daigremontiana reproduces asexually by producing plantlets along the leaf margin. The aim of this study was to identify the function of the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 gene in Kalanchoe daigremontiana (KdSOC1) during plantlet morphogenesis. In this study, KdSOC1 gene expression was detected at stem cell niche during in vitro somatic embryogenesis and plantlet morphogenesis. Disrupting endogenous auxin transportation suppressed the KdSOC1 gene response. Knockdown of the KdSOC1 gene caused a defect in cotyledon formation during the early heart stage of somatic embryogenesis. Over-expression (OE) of the KdSOC1 gene resulted in asymmetric plantlet distribution, a reduced number of plantlets, thicker leaves, and thicker vascular fibers. Higher KdPIN1 gene expression and auxin content were found in OE plant compared to those of wild-type plant leaves, which indicated possible KdSOC1 gene role in affecting auxin distribution and accumulation. KdSOC1 gene OE in DR5-GUS Arabidopsis reporting lines resulted in an abnormal auxin response pattern during different stages of somatic embryogenesis. In summary, the KdSOC1 gene OE might alter auxin distribution and accumulation along leaf margin to initiate plantlet formation and distribution, which is crucial for plasticity during plantlet formation under various environmental conditions.

The development of interactive multimedia based on auditory, intellectually, repetition in repetition algorithm learning to increase learning outcome

Science.gov (United States)

Munir; Sutarno, H.; Aisyah, N. S.

2018-05-01

This research aims to find out how the development of interactive multimedia based on auditory, intellectually, and repetition can improve student learning outcomes. This interactive multimedia is developed through 5 stages. Analysis stages include the study of literature, questionnaire, interviews and observations. The design phase is done by the database design, flowchart, storyboards and repetition algorithm material while the development phase is done by the creation of web-based framework. Presentation material is adapted to the model of learning such as auditory, intellectually, repetition. Auditory points are obtained by recording the narrative material that presented by a variety of intellectual points. Multimedia as a product is validated by material and media experts. Implementation phase conducted on grade XI-TKJ2 SMKN 1 Garut. Based on index’s gain, an increasing of student learning outcomes in this study is 0.46 which is fair due to interest of student in using interactive multimedia. While the multimedia assessment earned 84.36% which is categorized as very well.

Morphology, morphogenesis, and phylogeny of an Anteholosticha intermedia (Ciliophora, Urostylida) population from the United States.

Science.gov (United States)

Chen, Lingyun; Wu, Weining; El-Serehy, Hamed A; Hu, Xiaozhong; Clamp, John C

2018-04-30

A distinct population of Anteholosticha intermedia was isolated from soil in the Great Smoky Mountains of North Carolina, USA, and its morphology, morphogenesis and molecular phylogeny investigated by microscopic observations of live and protargol-prepared specimens and analyses of the sequence of small subunit (SSU) rDNA. Our population closely resembles the populations from Austria and Korea. Members of the genus Anteholosticha have been regarded as ontogenetically diverse, which is confirmed by the present work. The most noteworthy ontogenetic feature of the American population of A. intermedia is that the oral primordium in the proter appears apokinetally at the posterior end of the undulating membranes anlage at the beginning of division and then dedifferentiates midway through morphogenesis. Molecular phylogenetic analyses demonstrate, with high support, that the American population of A. intermedia is clearly distinct from congeners and branches as part of a sister lineage to the Bakuella-Urostyla clade that belongs to the major clade comprising the order Urostylida. Copyright © 2018 Elsevier GmbH. All rights reserved.

Influence of plasmogenes on the productivity of morphogenesis in strawberry (Fragaria x ananassa Duch.

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Jadwiga Żebrowska

2012-12-01

Full Text Available Plasmogenes are largely located in mitochondria or plastids and they can influence the inheritance of many plant characteristics. This phenomenon is called cytoplasmic inheritance and can be detected on the basis of the expression of a trait in progeny F1 obtained from single and reciprocal crosses. The aim of this study was to examine the cytoplasmic inheritance of in vitro productivity of morphogenesis in three genotypes of Fragaria x ananassa Duch., i.e. the cultivars 'Dukat', 'Teresa' and the breeding clone no. 590. Single and reciprocal crosses were done according to Griffi ng's method 3. The value of general combining ability (GCA indicated cv. 'Teresa' as the best maternal component for crossing and 'Dukat' as the worst. The negative reciprocal cross effects (rij revealed the cytoplasmic inheritance for cv. 'Dukat' as maternal form and positive rij for the breeding clone no. 590 indicated the nuclear inheritance of morphogenetic ability. Cv. 'Teresa', as maternal component, showed nuclear inheritance of that trait in crossing with cv. 'Dukat' and with 590 cytoplasmic inheritance. The productivity of morphogenesis in strawberry depended on the parental combination and the direction of crossing.

Repetition suppression and repetition enhancement underlie auditory memory-trace formation in the human brain: an MEG study.

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Recasens, Marc; Leung, Sumie; Grimm, Sabine; Nowak, Rafal; Escera, Carles

2015-03-01

The formation of echoic memory traces has traditionally been inferred from the enhanced responses to its deviations. The mismatch negativity (MMN), an auditory event-related potential (ERP) elicited between 100 and 250ms after sound deviation is an indirect index of regularity encoding that reflects a memory-based comparison process. Recently, repetition positivity (RP) has been described as a candidate ERP correlate of direct memory trace formation. RP consists of repetition suppression and enhancement effects occurring in different auditory components between 50 and 250ms after sound onset. However, the neuronal generators engaged in the encoding of repeated stimulus features have received little interest. This study intends to investigate the neuronal sources underlying the formation and strengthening of new memory traces by employing a roving-standard paradigm, where trains of different frequencies and different lengths are presented randomly. Source generators of repetition enhanced (RE) and suppressed (RS) activity were modeled using magnetoencephalography (MEG) in healthy subjects. Our results show that, in line with RP findings, N1m (~95-150ms) activity is suppressed with stimulus repetition. In addition, we observed the emergence of a sustained field (~230-270ms) that showed RE. Source analysis revealed neuronal generators of RS and RE located in both auditory and non-auditory areas, like the medial parietal cortex and frontal areas. The different timing and location of neural generators involved in RS and RE points to the existence of functionally separated mechanisms devoted to acoustic memory-trace formation in different auditory processing stages of the human brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Full-length fibronectin drives fibroblast accumulation at the surface of collagen microtissues during cell-induced tissue morphogenesis

NARCIS (Netherlands)

Foolen, J.; Shiu, J.-Y.; Mitsi, M.; Zhang, Y.; Chen, C.; Vogel, Viola

2016-01-01

Generating and maintaining gradients of cell density and extracellular matrix (ECM) components is a prerequisite for the development of functionality of healthy tissue. Therefore, gaining insights into the drivers of spatial organization of cells and the role of ECM during tissue morphogenesis is

Frequency Adaptive Repetitive Control of Grid-Tied Three-Phase PV Inverters

DEFF Research Database (Denmark)

Zhou, Keliang; Yang, Yongheng; Blaabjerg, Frede

2016-01-01

Repetitive control offers an accurate current control scheme for grid-tied converters to feed high quality sinusoidal current into the grid. However, with grid frequency being treated as a constant value, conventional repetitive controller fail to produce high quality feeding current in the prese......Repetitive control offers an accurate current control scheme for grid-tied converters to feed high quality sinusoidal current into the grid. However, with grid frequency being treated as a constant value, conventional repetitive controller fail to produce high quality feeding current...

Alteration in the ultrastructural morphology of mycelial hyphae and the dynamics of transcriptional activity of lytic enzyme genes during basidiomycete morphogenesis.

Science.gov (United States)

Vetchinkina, Elena; Kupryashina, Maria; Gorshkov, Vladimir; Ageeva, Marina; Gogolev, Yuri; Nikitina, Valentina

2017-04-01

The morphogenesis of macromycetes is a complex multilevel process resulting in a set of molecular-genetic, physiological-biochemical, and morphological-ultrastructural changes in the cells. When the xylotrophic basidiomycetes Lentinus edodes, Grifola frondosa, and Ganoderma lucidum were grown on wood waste as the substrate, the ultrastructural morphology of the mycelial hyphal cell walls differed considerably between mycelium and morphostructures. As the macromycetes passed from vegetative to generative development, the expression of the tyr1, tyr2, chi1, chi2, exg1, exg2, and exg3 genes was activated. These genes encode enzymes such as tyrosinase, chitinase, and glucanase, which play essential roles in cell wall growth and morphogenesis.

Some peculiarities of inflorescences morphogenesis in Brexia (Celastraceae

Directory of Open Access Journals (Sweden)

Ivan A. Savinov

2013-04-01

Full Text Available Comparative analysis of inflorescences structure for 6 species of the Brexia(according to the last revision by Schatz & Lowry II (2004 is conducted. For one species, B. madagascariensis, the shoots growth and development, inflorescence morphogenesis details are studied. It is determined inflorescences of Brexiaspecies (have described in literature as cymes, pseudo-umbellate, corymbiform, sessile in fascicles; and including for some species cauliflory presents a different variations of ancestral form transformation – dichasial system (closed thyrse. Apparently, presence of a big bracts may be consider as ancestral, plesiomorphic character for the genus; and derivate ones – reduction of bracts and presence of minute bracteoles in pedicel basis only. Inflorescences of Brexiain typically may be considered as bracteous. Process of reduction the number of clusters and separate flowers is accompanied by different variations of their transformations.

Identification of putative dental epithelial stem cells in a lizard with life-long tooth replacement.

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Handrigan, Gregory R; Leung, Kelvin J; Richman, Joy M

2010-11-01

Most dentate vertebrates, including humans, replace their teeth and yet the process is poorly understood. Here, we investigate whether dental epithelial stem cells exist in a polyphyodont species, the leopard gecko (Eublepharis macularius). Since the gecko dental epithelium lacks a histologically distinct site for stem cells analogous to the mammalian hair follicle bulge, we performed a pulse-chase experiment on juvenile geckos to identify label-retaining cells (LRCs). We detected LRCs exclusively on the lingual side of the dental lamina, which exhibits low proliferation rates and is not involved in tooth morphogenesis. Lingual LRCs were organized into pockets of high density close to the successional lamina. A subset of the LRCs expresses Lgr5 and other genes that are markers of adult stem cells in mammals. Also similar to mammalian stem cells, the LRCs appear to proliferate in response to gain of function of the canonical Wnt pathway. We suggest that the LRCs in the lingual dental lamina represent a population of stem cells, the immediate descendents of which form the successional lamina and, ultimately, the replacement teeth in the gecko. Furthermore, their location on the non-tooth-forming side of the dental lamina implies that dental stem cells are sequestered from signals that might otherwise induce them to differentiate.

SACE_0012, a TetR-Family Transcriptional Regulator, Affects the Morphogenesis of Saccharopolyspora erythraea

OpenAIRE

Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

2013-01-01

Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR,...

A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1.

Science.gov (United States)

Bar-Yosef, Hagit; Gildor, Tsvia; Ramírez-Zavala, Bernardo; Schmauch, Christian; Weissman, Ziva; Pinsky, Mariel; Naddaf, Rawi; Morschhäuser, Joachim; Arkowitz, Robert A; Kornitzer, Daniel

2018-01-01

The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.

Characterization and role of p53 family members in the symbiont-induced morphogenesis of the Euprymna scolopes light organ.

Science.gov (United States)

Goodson, Michael S; Crookes-Goodson, Wendy J; Kimbell, Jennifer R; McFall-Ngai, Margaret J

2006-08-01

Within hours of hatching, the squid Euprymna scolopes forms a specific light organ symbiosis with the marine luminous bacterium Vibrio fischeri. Interactions with the symbiont result in the loss of a complex ciliated epithelium dedicated to promoting colonization of host tissue, and some or all of this loss is due to widespread, symbiont-induced apoptosis. Members of the p53 family, including p53, p63, and p73, are conserved across broad phyletic lines and p63 is thought to be the ancestral gene. These proteins have been shown to induce apoptosis and developmental morphogenesis. In this study, we characterized p63-like transcripts from mRNA isolated from the symbiotic tissues of E. scolopes and described their role in symbiont-induced morphogenesis. Using degenerate RT-PCR and RACE PCR, we identified two p63-like transcripts encoding proteins of 431 and 567 amino acids. These transcripts shared identical nucleotides where they overlapped, suggesting that they are splice variants of the same gene. Immunocytochemistry and Western blots using an antibody specific for E. scolopes suggested that the p53 family members are activated in cells of the symbiont-harvesting structures of the symbiotic light organ. We propose that once the symbiosis is initiated, a symbiont-induced signal activates p53 family members, inducing apoptosis and developmental morphogenesis of the light organ.

Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos.

Directory of Open Access Journals (Sweden)

Karen A Roddy

2011-02-01

Full Text Available Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint.

Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

Science.gov (United States)

Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula

2011-01-01

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint. PMID:21386908

EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity

DEFF Research Database (Denmark)

Löf-Öhlin, Zarah M; Nyeng, Pia; Bechard, Matthew E

2017-01-01

Apicobasal polarity is known to affect epithelial morphogenesis and cell differentiation, but it remains unknown how these processes are mechanistically orchestrated. We find that ligand-specific EGFR signalling via PI(3)K and Rac1 autonomously modulates apicobasal polarity to enforce...

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.

Generation of µW level plateau harmonics at high repetition rate.

Science.gov (United States)

Hädrich, S; Krebs, M; Rothhardt, J; Carstens, H; Demmler, S; Limpert, J; Tünnermann, A

2011-09-26

The process of high harmonic generation allows for coherent transfer of infrared laser light to the extreme ultraviolet spectral range opening a variety of applications. The low conversion efficiency of this process calls for optimization or higher repetition rate intense ultrashort pulse lasers. Here we present state-of-the-art fiber laser systems for the generation of high harmonics up to 1 MHz repetition rate. We perform measurements of the average power with a calibrated spectrometer and achieved µW harmonics between 45 nm and 61 nm (H23-H17) at a repetition rate of 50 kHz. Additionally, we show the potential for few-cycle pulses at high average power and repetition rate that may enable water-window harmonics at unprecedented repetition rate. © 2011 Optical Society of America

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

Autism and exergaming: effects on repetitive behaviors and cognition

Directory of Open Access Journals (Sweden)

Anderson-Hanley C

2011-09-01

Full Text Available Cay Anderson-Hanley, Kimberly Tureck, Robyn L Schneiderman Department of Psychology, Union College, Schenectady, NY, USA Abstract: Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR; in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum. Keywords: autism, repetitive behaviors, exergaming, exercise, executive function

Recurrent exposure to nicotine differentiates human bronchial epithelial cells via epidermal growth factor receptor activation

International Nuclear Information System (INIS)

Martinez-Garcia, Eva; Irigoyen, Marta; Anso, Elena; Martinez-Irujo, Juan Jose; Rouzaut, Ana

2008-01-01

Cigarette smoking is the major preventable cause of lung cancer in developed countries. Nicotine (3-(1-methyl-2-pyrrolidinyl)-pyridine) is one of the major alkaloids present in tobacco. Besides its addictive properties, its effects have been described in panoply of cell types. In fact, recent studies have shown that nicotine behaves as a tumor promoter in transformed epithelial cells. This research focuses on the effects of acute repetitive nicotine exposure on normal human bronchial epithelial cells (NHBE cells). Here we show that treatment of NHBE cells with recurrent doses of nicotine up to 500 μM triggered cell differentiation towards a neuronal-like phenotype: cells emitted filopodia and expressed neuronal markers such as neuronal cell adhesion molecule, neurofilament-M and the transcription factors neuronal N and Pax-3. We also demonstrate that nicotine treatment induced NF-kB translocation to the nucleus, phosphorylation of the epidermal growth factor receptor (EGFR), and accumulation of heparin binding-EGF in the extracellular medium. Moreover, addition of AG1478, an inhibitor of EGFR tyrosine phosphorylation, or cetuximab, a monoclonal antibody that precludes ligand binding to the same receptor, prevented cell differentiation by nicotine. Lastly, we show that differentiated cells increased their adhesion to the extracellular matrix and their protease activity. Given that several lung pathologies are strongly related to tobacco consumption, these results may help to better understand the damaging consequences of nicotine exposure

Early morphogenesis of heterodont dentition in minipigs

Czech Academy of Sciences Publication Activity Database

Štembírek, Jan; Buchtová, Marcela; Král, T.; Matalová, Eva; Lozanoff, S.; Míšek, Ivan

2010-01-01

Roč. 118, č. 6 (2010), s. 547-558 ISSN 0909-8836 R&D Projects: GA ČR(CZ) GP304/08/P289 Institutional research plan: CEZ:AV0Z50450515 Keywords : dental lamina * epithelial pearls * odontogenesis Subject RIV: FF - HEENT, Dentistry Impact factor: 1.890, year: 2010

A longitudinal investigation of perfectionism and repetitive negative thinking in perinatal depression.

Science.gov (United States)

Egan, Sarah J; Kane, Robert T; Winton, Karen; Eliot, Catherine; McEvoy, Peter M

2017-10-01

Repetitive negative thinking and perfectionism have both been proposed as processes that are related to depressive symptoms. The purpose of this study was to investigate concurrent and prospective relationships between antenatal and postnatal depression, perfectionism, and repetitive negative thinking. A longitudinal design was used and 71 women were followed from their third trimester of pregnancy to six weeks post birth. A structural equation model was tested with antenatal perfectionism predicting antenatal repetitive negative thinking, perfectionism predicting postnatal depression, and antenatal repetitive negative thinking predicting antenatal and postnatal depression. The final model provided an adequate fit to the data but the pathway from antenatal repetitive negative thinking to postnatal depression was not significant. The findings provide support for the role of perfectionism and repetitive negative thinking in the onset and maintenance of perinatal symptoms of depression. It is suggested that future research investigates the efficacy of targeting repetitive negative thinking and perfectionism in pregnancy to examine if this can reduce perinatal depression. Copyright © 2017. Published by Elsevier Ltd.

Concreteness of Positive, Negative, and Neutral Repetitive Thinking About the Future

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Behar, Evelyn; McGowan, Sarah Kate; McLaughlin, Katie A.; Borkovec, T.D.; Goldwin, Michelle; Bjorkquist, Olivia

2014-01-01

Consistent with assertions that the adaptiveness of repetitive thinking is influenced by both its valence and style, Stöber (e.g., Stöber & Borkovec, 2002) has argued that worry is characterized by a reduced concreteness of thought content and that the resulting abstractness contributes to its inhibition of some aspects of anxious responding. However, extant research does not provide a direct test of Stöber’s reduced concreteness theory of worry. We sought to test Stöber’s theory and to examine the adaptiveness of repetitive worrisome thinking by randomly assigning 108 participants to engage in five consecutive periods of repetitive thinking about positively, negatively, or neutrally valenced potential future events. Results based on coding of thought data indicated that (a) repetitive thinking became increasingly less concrete as periods progressed; (b) contrary to Stöber’s theory, both negative and positive repetitive future thinking were more concrete than neutral repetitive future thinking (and did not differ from each other); and (c) abstractness of thought during negative repetitive future thinking was associated with reduced reports of imagery-based activity. Results based on self-reported affect indicated that negatively valenced repetitive future thinking was uniquely associated with initial decreases in anxious affect, followed by increased anxious affect that coincided with increased imagery-based activity. This suggests that worry is associated with a sequential mitigation of anxious meaning followed by a strengthening of anxious meaning over time. Theoretical and clinical implications of these findings are discussed. PMID:22440067

Effects of repetition and temperature on Contingent Electrical Stimulation

DEFF Research Database (Denmark)

Castrillon, Eduardo E.; Zhou, Xinwen; Svensson, Peter

) activity associated with bruxism. Repetition of the electrical stimulus and skin surface temperature (ST) may affect the perception of CES and possibly also the inhibitory EMG effects.Objectives: To determine the effects of stimulus repetition and skin ST on the perception of CES.  Methods: Healthy...

Towards an automated analysis of video-microscopy images of fungal morphogenesis

Directory of Open Access Journals (Sweden)

Diéguez-Uribeondo, Javier

2005-06-01

Full Text Available Fungal morphogenesis is an exciting field of cell biology and several mathematical models have been developed to describe it. These models require experimental evidences to be corroborated and, therefore, there is a continuous search for new microscopy and image analysis techniques. In this work, we have used a Canny-edge-detector based technique to automate the generation of hyphal profiles and calculation of morphogenetic parameters such as diameter, elongation rates and hyphoid fitness. The results show that the data obtained with this technique are similar to published data generated with manualbased tracing techniques and that have been carried out on the same species or genus. Thus, we show that application of edge detector-based technique to hyphal growth represents an efficient and accurate method to study hyphal morphogenesis. This represents the first step towards an automated analysis of videomicroscopy images of fungal morphogenesis.La morfogénesis de los hongos es un área de estudio de gran relevancia en la biología celular y en la que se han desarrollado varios modelos matemáticos. Los modelos matemáticos de procesos biológicos precisan de pruebas experimentales que apoyen y corroboren las predicciones teóricas y, por este motivo, existe una búsqueda continua de nuevas técnicas de microscopía y análisis de imágenes para su aplicación en el estudio del crecimiento celular. En este trabajo hemos utilizado una técnica basada en un detector de contornos llamado “Canny-edge-detectorâ€� con el objetivo de automatizar la generación de perfiles de hifas y el cálculo de parámetros morfogenéticos, tales como: el diámetro, la velocidad de elongación y el ajuste con el perfil hifoide, es decir, el perfil teórico de las hifas de los hongos. Los resultados obtenidos son similares a los datos publicados a partir de técnicas manuales de trazado de contornos, generados en la misma especie y género. De esta manera

Post-exercise cortical depression following repetitive passive finger movement.

Science.gov (United States)

Otsuka, Ryohei; Sasaki, Ryoki; Tsuiki, Shota; Kojima, Sho; Onishi, Hideaki

2017-08-24

This study aimed to clarify the influence of range of repetitive passive finger movement on corticospinal excitability. Thirteen healthy subjects participated in this study. Passive index finger adduction-abduction movements were performed from 15° abduction to 15° adduction, 15° abduction to 0°, 0° to 15° adduction, and 15° adduction to 30° adduction, each at 15°/s for 10min on separate days. Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation and M- and F-waves were measured before and after each repetitive passive index finger movement protocol to evaluate changes in corticospinal excitability. MEP amplitude significantly decreased after all passive movements, while F-wave amplitude, F-wave persistence, and M-wave amplitude remained stable. These results suggest that cortical excitability decreases after repetitive passive movement. However, the range of repetitive passive movement does not markedly influence the magnitude of cortical depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulse repetition rate multiplication by Talbot effect in a coaxial fiber

Science.gov (United States)

Dhingra, Nikhil; Saxena, Geetika Jain; Anand, Jyoti; Sharma, Enakshi K.

2018-03-01

We use a coaxial fiber, which is a cylindrical coupled waveguide structure consisting of two concentric cores, the inner rod and an outer ring core as a first order dispersive media to achieve temporal Talbot effect for pulse repetition rate multiplication (PRRM) in high bit rate optical fiber communication. It is observed that for an input Gaussian pulse train with pulse width, 2τ0=1ps at a repetition rate of 40 Gbps (repetition period, T=25ps), an output repetition rate of 640 Gbps can be achieved without significant distortion at a length of 40.92 m.

Molecular Biology of Feather Morphogenesis: A Testable Model for Evo-Devo Research

Science.gov (United States)

WIDELITZ, RANDALL B.; JIANG, TING XIN; YU, MINGKE; SHEN, TED; SHEN, JEN-YEE; WU, PING; YU, ZHICAO; CHUONG, CHENG-MING

2015-01-01

Darwin’s theory describes the principles that are responsible for evolutionary change of organisms and their attributes. The actual mechanisms, however, need to be studied for each species and each organ separately. Here we have investigated the mechanisms underlying these principles in the avian feather. Feathers comprise one of the most complex and diverse epidermal organs as demonstrated by their shape, size, patterned arrangement and pigmentation. Variations can occur at several steps along each level of organization, leading to highly diverse forms and functions. Feathers develop gradually during ontogeny through a series of steps that may correspond to the evolutionary steps that were taken during the phylogeny from a reptilian ancestor to birds. These developmental steps include 1) the formation of feather tract fields on the skin surfaces; 2) periodic patterning of the individual feather primordia within the feather tract fields; 3) feather bud morphogenesis establishing anterio - posterior (along the cranio - caudal axis) and proximo - distal axes; 4) branching morphogenesis to create the rachis, barbs and barbules within a feather bud; and 5) gradual modulations of these basic morphological parameters within a single feather or across a feather tract. Thus, possibilities for variation in form and function of feathers occur at every developmental step. In this paper, principles guiding feather tract formation, distributions of individual feathers within the tracts and variations in feather forms are discussed at a cellular and molecular level. PMID:12949772

p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion*

Science.gov (United States)

Greenblatt, Matthew B.; Kim, Jung-Min; Oh, Hwanhee; Park, Kwang Hwan; Choo, Min-Kyung; Sano, Yasuyo; Tye, Coralee E.; Skobe, Ziedonis; Davis, Roger J.; Park, Jin Mo; Bei, Marianna; Glimcher, Laurie H.; Shim, Jae-Hyuck

2015-01-01

An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678–27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38α MAPK in ectodermal appendages using K14-cre mice (p38αK14 mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38α, expression of amelogenin and β4-integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38α in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38α functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38α MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel. PMID:25406311

Properties of water surface discharge at different pulse repetition rates

International Nuclear Information System (INIS)

Ruma,; Yoshihara, K.; Hosseini, S. H. R.; Sakugawa, T.; Akiyama, H.; Akiyama, M.; Lukeš, P.

2014-01-01

The properties of water surface discharge plasma for variety of pulse repetition rates are investigated. A magnetic pulse compression (MPC) pulsed power modulator able to deliver pulse repetition rates up to 1000 Hz, with 0.5 J per pulse energy output at 25 kV, was used as the pulsed power source. Positive pulse with a point-to-plane electrode configuration was used for the experiments. The concentration and production yield of hydrogen peroxide (H 2 O 2 ) were quantitatively measured and orange II organic dye was treated, to evaluate the chemical properties of the discharge reactor. Experimental results show that the physical and chemical properties of water surface discharge are not influenced by pulse repetition rate, very different from those observed for under water discharge. The production yield of H 2 O 2 and degradation rate per pulse of the dye did not significantly vary at different pulse repetition rates under a constant discharge mode on water surface. In addition, the solution temperature, pH, and conductivity for both water surface and underwater discharge reactors were measured to compare their plasma properties for different pulse repetition rates. The results confirm that surface discharge can be employed at high pulse repetition rates as a reliable and advantageous method for industrial and environmental decontamination applications.

Word Recognition during Reading: The Interaction between Lexical Repetition and Frequency

Science.gov (United States)

Lowder, Matthew W.; Choi, Wonil; Gordon, Peter C.

2013-01-01

Memory studies utilizing long-term repetition priming have generally demonstrated that priming is greater for low-frequency words than for high-frequency words and that this effect persists if words intervene between the prime and the target. In contrast, word-recognition studies utilizing masked short-term repetition priming typically show that the magnitude of repetition priming does not differ as a function of word frequency and does not persist across intervening words. We conducted an eye-tracking while reading experiment to determine which of these patterns more closely resembles the relationship between frequency and repetition during the natural reading of a text. Frequency was manipulated using proper names that were high-frequency (e.g., Stephen) or low-frequency (e.g., Dominic). The critical name was later repeated in the sentence, or a new name was introduced. First-pass reading times and skipping rates on the critical name revealed robust repetition-by-frequency interactions such that the magnitude of the repetition-priming effect was greater for low-frequency names than for high-frequency names. In contrast, measures of later processing showed effects of repetition that did not depend on lexical frequency. These results are interpreted within a framework that conceptualizes eye-movement control as being influenced in different ways by lexical- and discourse-level factors. PMID:23283808

Evidence-Based Behavioral Interventions for Repetitive Behaviors in Autism

Science.gov (United States)

Boyd, Brian A.; McDonough, Stephen G.; Bodfish, James W.

2012-01-01

Restricted and repetitive behaviors (RRBs) are a core symptom of autism spectrum disorders (ASD). There has been an increased research emphasis on repetitive behaviors; however, this research primarily has focused on phenomenology and mechanisms. Thus, the knowledge base on interventions is lagging behind other areas of research. The literature…

Repetitive sequences: the hidden diversity of heterochromatin in prochilodontid fish

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Maria L. Terencio

2015-08-01

Full Text Available The structure and organization of repetitive elements in fish genomes are still relatively poorly understood, although most of these elements are believed to be located in heterochromatic regions. Repetitive elements are considered essential in evolutionary processes as hotspots for mutations and chromosomal rearrangements, among other functions – thus providing new genomic alternatives and regulatory sites for gene expression. The present study sought to characterize repetitive DNA sequences in the genomes of Semaprochilodus insignis (Jardine & Schomburgk, 1841 and Semaprochilodus taeniurus (Valenciennes, 1817 and identify regions of conserved syntenic blocks in this genome fraction of three species of Prochilodontidae (S. insignis, S. taeniurus, and Prochilodus lineatus (Valenciennes, 1836 by cross-FISH using Cot-1 DNA (renaturation kinetics probes. We found that the repetitive fractions of the genomes of S. insignis and S. taeniurus have significant amounts of conserved syntenic blocks in hybridization sites, but with low degrees of similarity between them and the genome of P. lineatus, especially in relation to B chromosomes. The cloning and sequencing of the repetitive genomic elements of S. insignis and S. taeniurus using Cot-1 DNA identified 48 fragments that displayed high similarity with repetitive sequences deposited in public DNA databases and classified as microsatellites, transposons, and retrotransposons. The repetitive fractions of the S. insignis and S. taeniurus genomes exhibited high degrees of conserved syntenic blocks in terms of both the structures and locations of hybridization sites, but a low degree of similarity with the syntenic blocks of the P. lineatus genome. Future comparative analyses of other prochilodontidae species will be needed to advance our understanding of the organization and evolution of the genomes in this group of fish.

On the Morphogenesis of Feathers

Science.gov (United States)

Yu, Mingke; Wu, Ping; Widelitz, Randall B.; Chuong, Cheng-Ming

2015-01-01

The most unique character of the feather is its highly ordered hierarchical branched structure1, 2. This evolutionary novelty confers flight function to birds3–5. Recent discoveries of fossils in China have prompted keen interest in the origin and evolution of feathers6–14. However, controversy arises whether the irregularly branched integumentary fibers on dinosaurs such as Sinornithosaurus are truly feathers6, 11, and whether an integumentary appendage with a major central shaft and notched edges is a non-avian feather or a proto-feather8–10. Here we take a developmental approach to analyze molecular mechanisms in feather branching morphogenesis. We have used the replication competent avian sarcoma (RCAS) retrovirus15 to efficiently deliver exogenous genes to regenerating chicken flight feather follicles. We show that the antagonistic balance between noggin and bone morphogenetic protein 4 (BMP4) plays a critical role in feather branching, with BMP4 promoting rachis formation and barb fusion, and noggin enhancing rachis and barb branching. Furthermore we show that sonic hedgehog (SHH) is essential for apoptosis of the marginal plate epithelia to become spaces between barbs. Our analyses show the molecular pathways underlying the topological transformation of feathers from cylindrical epithelia to the hierarchical branched structures, and provide first clues on the possible developmental mechanisms in the evolution of feather forms. PMID:12442169

Hemispheric Asymmetries in Repetition Enhancement and Suppression Effects in the Newborn Brain.

Science.gov (United States)

Bouchon, Camillia; Nazzi, Thierry; Gervain, Judit

2015-01-01

The repeated presentation of stimuli typically attenuates neural responses (repetition suppression) or, less commonly, increases them (repetition enhancement) when stimuli are highly complex, degraded or presented under noisy conditions. In adult functional neuroimaging research, these repetition effects are considered as neural correlates of habituation. The development and respective functional significance of these effects in infancy remain largely unknown. This study investigates repetition effects in newborns using functional near-infrared spectroscopy, and specifically the role of stimulus complexity in evoking a repetition enhancement vs. a repetition suppression response, following up on Gervain et al. (2008). In that study, abstract rule-learning was found at birth in cortical areas specific to speech processing, as evidenced by a left-lateralized repetition enhancement of the hemodynamic response to highly variable speech sequences conforming to a repetition-based ABB artificial grammar, but not to a random ABC grammar. Here, the same paradigm was used to investigate how simpler stimuli (12 different sequences per condition as opposed to 140), and simpler presentation conditions (blocked rather than interleaved) would influence repetition effects at birth. Results revealed that the two grammars elicited different dynamics in the two hemispheres. In left fronto-temporal areas, we reproduce the early perceptual discrimination of the two grammars, with ABB giving rise to a greater response at the beginning of the experiment than ABC. In addition, the ABC grammar evoked a repetition enhancement effect over time, whereas a stable response was found for the ABB grammar. Right fronto-temporal areas showed neither initial discrimination, nor change over time to either pattern. Taken together with Gervain et al. (2008), this is the first evidence that manipulating methodological factors influences the presence or absence of neural repetition enhancement effects in

Hemispheric Asymmetries in Repetition Enhancement and Suppression Effects in the Newborn Brain.

Directory of Open Access Journals (Sweden)

Camillia Bouchon

Full Text Available The repeated presentation of stimuli typically attenuates neural responses (repetition suppression or, less commonly, increases them (repetition enhancement when stimuli are highly complex, degraded or presented under noisy conditions. In adult functional neuroimaging research, these repetition effects are considered as neural correlates of habituation. The development and respective functional significance of these effects in infancy remain largely unknown.This study investigates repetition effects in newborns using functional near-infrared spectroscopy, and specifically the role of stimulus complexity in evoking a repetition enhancement vs. a repetition suppression response, following up on Gervain et al. (2008. In that study, abstract rule-learning was found at birth in cortical areas specific to speech processing, as evidenced by a left-lateralized repetition enhancement of the hemodynamic response to highly variable speech sequences conforming to a repetition-based ABB artificial grammar, but not to a random ABC grammar.Here, the same paradigm was used to investigate how simpler stimuli (12 different sequences per condition as opposed to 140, and simpler presentation conditions (blocked rather than interleaved would influence repetition effects at birth.Results revealed that the two grammars elicited different dynamics in the two hemispheres. In left fronto-temporal areas, we reproduce the early perceptual discrimination of the two grammars, with ABB giving rise to a greater response at the beginning of the experiment than ABC. In addition, the ABC grammar evoked a repetition enhancement effect over time, whereas a stable response was found for the ABB grammar. Right fronto-temporal areas showed neither initial discrimination, nor change over time to either pattern.Taken together with Gervain et al. (2008, this is the first evidence that manipulating methodological factors influences the presence or absence of neural repetition enhancement

A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on.

Science.gov (United States)

Galletly, Cherrie A; Clarke, Patrick; Carnell, Benjamin L; Gill, Shane

2015-11-01

There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6 years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4 weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N = 167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N = 123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6 years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore

A repetitive elements perspective in Polycomb epigenetics.

Directory of Open Access Journals (Sweden)

Valentina eCasa

2012-10-01

Full Text Available Repetitive elements comprise over two-thirds of the human genome. For a long time, these elements have received little attention since they were considered non functional. On the contrary, recent evidence indicates that they play central roles in genome integrity, gene expression and disease. Indeed, repeats display meiotic instability associated with disease and are located within common fragile sites, which are hotspots of chromosome rearrangements in tumors. Moreover, a variety of diseases have been associated with aberrant transcription of repetitive elements. Overall this indicates that appropriate regulation of repetitive elements’ activity is fundamental.Polycomb group (PcG proteins are epigenetic regulators that are essential for the normal development of multicellular organisms. Mammalian PcG proteins are involved in fundamental processes, such as cellular memory, cell proliferation, genomic imprinting, X-inactivation, and cancer development. PcG proteins can convey their activity through long-distance interactions also on different chromosomes. This indicates that the 3D organization of PcG proteins contributes significantly to their function. However, it is still unclear how these complex mechanisms are orchestrated and which role PcG proteins play in the multi-level organization of gene regulation. Intriguingly, the greatest proportion of Polycomb-mediated chromatin modifications is located in genomic repeats and it has been suggested that they could provide a binding platform for Polycomb proteins.Here, these lines of evidence are woven together to discuss how repetitive elements could contribute to chromatin organization in the 3D nuclear space.

The roles of stimulus repetition and hemispheric activation in visual half-field asymmetries.

Science.gov (United States)

Sullivan, K F; McKeever, W F

1985-10-01

Hardyck, Tzeng, and Wang (1978, Brain and Language, 5, 56-71) hypothesized that ample repetition of a small number of stimuli is required in order to obtain VHF differences in tachistoscopic tasks. Four experiments, with varied levels of repetition, were conducted to test this hypothesis. Three experiments utilized the general task of object-picture naming and one utilized a word-naming task. Naming latencies constituted the dependent measure. The results demonstrate that for the object-naming paradigm repetition is required for RVF superiority to emerge. Repetition was found to be unnecessary for RVF superiority in the word-naming paradigm, with repetition actually reducing RVF superiority. Experiment I suggested the possibility that RVF superiority developed for the second half of the trials as a function of practice or hemispheric activation, regardless of repetition level. Subsequent experiments, better designed to assess this possibility, clearly refuted it. It was concluded that the effect of repetition depends on the processing requirements of the task. We propose that, for tasks which can be processed efficiently by one hemisphere, the effect of repetition will be to reduce VHF asymmetries; but tasks requiring substantial processing by both hemispheres will show shifts to RVF superiority as a function of repetition.

A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention.

Science.gov (United States)

Zardouz, Shawn; Shi, Lei; Leung, Albert

2016-01-01

This case series was conducted to determine the clinical feasibility of a repetitive transcranial magnetic stimulation protocol for the prevention of migraine (with and without aura). Five patients with migraines underwent five repetitive transcranial magnetic stimulation sessions separated in 1- to 2-week intervals for a period of 2 months at a single tertiary medical center. Repetitive transcranial magnetic stimulation was applied to the left motor cortex with 2000 pulses (20 trains with 1s inter-train interval) delivered per session, at a frequency of 10 Hz and 80% resting motor threshold. Pre- and post-treatment numerical rating pain scales were collected, and percent reductions in intensity, frequency, and duration were generated. An average decrease in 37.8%, 32.1%, and 31.2% were noted in the intensity, frequency, and duration of migraines post-repetitive transcranial magnetic stimulation, respectively. A mean decrease in 1.9±1.0 (numerical rating pain scale ± standard deviation; range: 0.4-2.8) in headache intensity scores was noted after the repetitive transcranial magnetic stimulation sessions. The tested repetitive transcranial magnetic stimulation protocol is a well-tolerated, safe, and effective method for migraine prevention.

High-repetition-rate short-pulse gas discharge.

Science.gov (United States)

Tulip, J; Seguin, H; Mace, P N

1979-09-01

A high-average-power short-pulse gas discharge is described. This consists of a volume-preionized transverse discharge of the type used in gas lasers driven by a Blumlein energy storage circuit. The Blumlein circuit is fabricated from coaxial cable, is pulse-charged from a high-repetition-rate Marx-bank generator, and is switched by a high-repetition-rate segmented rail gap. The operation of this discharge under conditions typical of rare-gas halide lasers is described. A maximum of 900 pps was obtained, giving a power flow into the discharge of 30 kW.

Complex dynamics and morphogenesis an introduction to nonlinear science

CERN Document Server

Misbah, Chaouqi

2017-01-01

This book offers an introduction to the physics of nonlinear phenomena through two complementary approaches: bifurcation theory and catastrophe theory. Readers will be gradually introduced to the language and formalisms of nonlinear sciences, which constitute the framework to describe complex systems. The difficulty with complex systems is that their evolution cannot be fully predicted because of the interdependence and interactions between their different components. Starting with simple examples and working toward an increasing level of universalization, the work explores diverse scenarios of bifurcations and elementary catastrophes which characterize the qualitative behavior of nonlinear systems. The study of temporal evolution is undertaken using the equations that characterize stationary or oscillatory solutions, while spatial analysis introduces the fascinating problem of morphogenesis. Accessible to undergraduate university students in any discipline concerned with nonlinear phenomena (physics, mathema...

Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow

International Nuclear Information System (INIS)

Semino, Carlos E.; Kamm, Roger D.; Lauffenburger, Douglas A.

2006-01-01

We show here that autocrine ligand activation of epidermal growth factor (EGF) receptor in combination with interstitial flow is critically involved in the morphogenetic response of endothelial cells to VEGF stimulation. Human umbilical vein endothelial cell (HUVEC) monolayers cultured on a collagen gel and exposed to low interstitial flow in the absence of EGF and VEGF remained viable and mitotic but exhibited little evidence of vascular morphogenesis. Addition of VEGF produced a flow-dependent morphogenetic response within 48 to 72 h, characterized by branched capillary-like structures. The response was substantially abolished by inhibitors related to the autocrine EGF receptor pathway including Galardin, AG1478, PD98059, and an EGF receptor-blocking antibody, indicating that regulation of the morphogenetic process operates via autocrine EGF receptor activation. Moreover, we observed that in our system the EGF receptor was always activated independently of the interstitial flow, and, in addition, the EGF receptor inhibitors used above reduced the phosphorylation state of the receptor, correlating with inhibition of capillary morphogenesis. Finally, 5'bromo-2'-deoxyuridine (BrdU) labeling identified dividing cells at the monolayer but not in the extending capillary-like structures. EGF pathway inhibitors Galardin and AG1478 did not reduce BrdU incorporation in the monolayer, indicating that the EGF-receptor-mediated morphogenetic behavior is mainly due to cell migration rather than proliferation. Based on these results, we propose a two-step model for in vitro capillary morphogenesis in response to VEGF stimulation with interstitial fluid flow: monolayer maintenance by mitotic activity independent of EGF receptors and a migratory response mediated by autocrine EGF receptor activation wherein cells establish capillary-like structures

Gonad morphogenesis defects drive hybrid male sterility in asymmetric hybrid breakdown of Caenorhabditis nematodes.

Science.gov (United States)

Dey, Alivia; Jin, Qi; Chen, Yen-Chu; Cutter, Asher D

2014-01-01

Determining the causes and evolution of reproductive barriers to gene flow between populations, speciation, is the key to understanding the origin of diversity in nature. Many species manifest hybrid breakdown when they intercross, characterized by increasingly exacerbated problems in later generations of hybrids. Recently, Caenorhabditis nematodes have emerged as a genetic model for studying speciation, and here we investigate the nature and causes of hybrid breakdown between Caenorhabditis remanei and C. latens. We quantify partial F1 hybrid inviability and extensive F2 hybrid inviability; the ~75% F2 embryonic arrest occurs primarily during gastrulation or embryonic elongation. Moreover, F1 hybrid males exhibit Haldane's rule asymmetrically for both sterility and inviability, being strongest when C. remanei serves as maternal parent. We show that the mechanism by which sterile hybrid males are incapable of transferring sperm or a copulatory plug involves defective gonad morphogenesis, which we hypothesize results from linker cell defects in migration and/or cell death during development. This first documented case of partial hybrid male sterility in Caenorhabditis follows expectations of Darwin's corollary to Haldane's rule for asymmetric male fitness, providing a powerful foundation for molecular dissection of intrinsic reproductive barriers and divergence of genetic pathways controlling organ morphogenesis. © 2014 Wiley Periodicals, Inc.

A Transient Exposure to Symbiosis-Competent Bacteria Induces Light Organ Morphogenesis in the Host Squid.

Science.gov (United States)

Doino, J A; McFall-Ngai, M J

1995-12-01

Recent studies of the symbiotic association between the Hawaiian sepiolid squid Euprymna scolopes and the luminous bacterium Vibrio fischeri have shown that colonization of juvenile squid with symbiosis-competent bacteria induces morphogenetic changes of the light organ. These changes occur over a 4-day period and include cell death and tissue regression of the external ciliated epithelium. In the absence of bacterial colonization, morphogenesis does not occur. To determine whether the bacteria must be present throughout the morphogenetic process, we used the antibiotic chloramphenicol to clear the light organ of bacteria at various times during the initial colonization. We provide evidence in this study that a transient, 12-hour exposure to symbiosis-competent bacteria is necessary and sufficient to induce tissue regression in the light organ over the next several days. Further, we show that successful entrance into the light organ is necessary to induce morphogenesis, suggesting that induction results from bacterial interaction with internal crypt cells and not with the external ciliated epithelium. Finally, no difference in development was observed when the light organ was colonized by a mutant strain of V. fischeri that did not produce autoinducer, a potential light organ morphogen.

Repetitively pulsed, double discharge TEA CO/sub 2/ laser

Energy Technology Data Exchange (ETDEWEB)

Hamilton, D C; James, D J; Ramsden, S A

1975-10-01

The design and operation of a repetitively pulsed TEA CO/sub 2/ laser is described. Average powers of up to 400 W at a repetition frequency of 200 pulses/s have been obtained. The system has also been used to provide long pulses (over 20 ..mu..s) and tunable single axial mode pulses.

Modeling repetitive motions using structured light.

Science.gov (United States)

Xu, Yi; Aliaga, Daniel G

2010-01-01

Obtaining models of dynamic 3D objects is an important part of content generation for computer graphics. Numerous methods have been extended from static scenarios to model dynamic scenes. If the states or poses of the dynamic object repeat often during a sequence (but not necessarily periodically), we call such a repetitive motion. There are many objects, such as toys, machines, and humans, undergoing repetitive motions. Our key observation is that when a motion-state repeats, we can sample the scene under the same motion state again but using a different set of parameters; thus, providing more information of each motion state. This enables robustly acquiring dense 3D information difficult for objects with repetitive motions using only simple hardware. After the motion sequence, we group temporally disjoint observations of the same motion state together and produce a smooth space-time reconstruction of the scene. Effectively, the dynamic scene modeling problem is converted to a series of static scene reconstructions, which are easier to tackle. The varying sampling parameters can be, for example, structured-light patterns, illumination directions, and viewpoints resulting in different modeling techniques. Based on this observation, we present an image-based motion-state framework and demonstrate our paradigm using either a synchronized or an unsynchronized structured-light acquisition method.

A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1

Directory of Open Access Journals (Sweden)

Hagit Bar-Yosef

2018-02-01

Full Text Available The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.

Chondroitin sulfate proteoglycan synthesis and reutilization of beta-D-xyloside-initiated chondroitin/dermatan sulfate glycosaminoglycans in fetal kidney branching morphogenesis

International Nuclear Information System (INIS)

Klein, D.J.; Brown, D.M.; Moran, A.; Oegema, T.R. Jr.; Platt, J.L.

1989-01-01

Branching morphogenesis and chondroitin sulfate proteoglycan synthesis by explanted fetal mouse kidneys were previously shown to be inhibited by p-nitrophenyl beta-D-xylopyranoside (beta-D-xyloside) while glomerular development and heparan sulfate proteoglycan synthesis were unaffected. The metabolic fate of fetal kidney explant proteoglycans was investigated to determine whether or not recovery of proteoglycan synthesis and morphogenesis occur after exposure to beta-D-xyloside. Chondroitin sulfate proteoglycan synthesis resumed within 4 hr of removal of beta-D-xyloside and was enhanced once beta-D-xyloside-initiated chondroitin/dermatan- 35 SO 4 glycosaminoglycans (GAGs) were released from the tissue. Radioactivity incorporated into beta-D-xyloside-initiated chondroitin/dermatan- 35 SO 4 GAGs during labeling in the presence of beta-D-xyloside was reutilized in the synthesis of chondroitin- 35 SO 4 proteoglycan during a 24-hr chase in nonradioactive medium without beta-D-xyloside. Further, highly purified beta-D-xyloside-initiated chondroitin/dermatan- 35 SO 4 GAGs were taken up by kidneys more avidly than was free [ 35 S]sulfate. These 35 S-GAGs were degraded and reutilized in the synthesis of chondroitin- 35 SO 4 proteoglycan. Ureteric bud branching resumed 48 hr after beta-D-xyloside was removed from the incubation medium. These findings support the idea that both chondroitin sulfate proteoglycan synthesis and proteoglycan processing may be involved in branching morphogenesis

Body-focused repetitive behavior disorders in ICD-11

Directory of Open Access Journals (Sweden)

Jon E. Grant

2014-01-01

Full Text Available This article addresses the question of how body-focused repetitive behavior disorders (e.g., trichotillomania and skin-picking disorder should be characterized in ICD-11. The article reviews the historical nosology of the two disorders and the current approaches in DSM-5 and ICD-10. Although data are limited and mixed regarding the optimal relationship between body-focused repetitive behavior disorders and nosological categories, these conditions should be included within the obsessive-compulsive and related disorders category, as this is how most clinicians see these behaviors, and as this may optimize clinical utility. The descriptions of these disorders should largely mirror those in DSM-5, given the evidence from recent field surveys. The recommendations regarding ICD-11 and body-focused repetitive behavior disorders should promote the global identification and treatment of these conditions in primary care settings.

Full-Length Fibronectin Drives Fibroblast Accumulation at the Surface of Collagen Microtissues during Cell-Induced Tissue Morphogenesis.

Directory of Open Access Journals (Sweden)

Jasper Foolen

Full Text Available Generating and maintaining gradients of cell density and extracellular matrix (ECM components is a prerequisite for the development of functionality of healthy tissue. Therefore, gaining insights into the drivers of spatial organization of cells and the role of ECM during tissue morphogenesis is vital. In a 3D model system of tissue morphogenesis, a fibronectin-FRET sensor recently revealed the existence of two separate fibronectin populations with different conformations in microtissues, i.e. 'compact and adsorbed to collagen' versus 'extended and fibrillar' fibronectin that does not colocalize with the collagen scaffold. Here we asked how the presence of fibronectin might drive this cell-induced tissue morphogenesis, more specifically the formation of gradients in cell density and ECM composition. Microtissues were engineered in a high-throughput model system containing rectangular microarrays of 12 posts, which constrained fibroblast-populated collagen gels, remodeled by the contractile cells into trampoline-shaped microtissues. Fibronectin's contribution during the tissue maturation process was assessed using fibronectin-knockout mouse embryonic fibroblasts (Fn-/- MEFs and floxed equivalents (Fnf/f MEFs, in fibronectin-depleted growth medium with and without exogenously added plasma fibronectin (full-length, or various fragments. In the absence of full-length fibronectin, Fn-/- MEFs remained homogenously distributed throughout the cell-contracted collagen gels. In contrast, in the presence of full-length fibronectin, both cell types produced shell-like tissues with a predominantly cell-free compacted collagen core and a peripheral surface layer rich in cells. Single cell assays then revealed that Fn-/- MEFs applied lower total strain energy on nanopillar arrays coated with either fibronectin or vitronectin when compared to Fnf/f MEFs, but that the presence of exogenously added plasma fibronectin rescued their contractility. While collagen

Repetition suppression and multi-voxel pattern similarity differentially track implicit and explicit visual memory.

Science.gov (United States)

Ward, Emily J; Chun, Marvin M; Kuhl, Brice A

2013-09-11

Repeated exposure to a visual stimulus is associated with corresponding reductions in neural activity, particularly within visual cortical areas. It has been argued that this phenomenon of repetition suppression is related to increases in processing fluency or implicit memory. However, repetition of a visual stimulus can also be considered in terms of the similarity of the pattern of neural activity elicited at each exposure--a measure that has recently been linked to explicit memory. Despite the popularity of each of these measures, direct comparisons between the two have been limited, and the extent to which they differentially (or similarly) relate to behavioral measures of memory has not been clearly established. In the present study, we compared repetition suppression and pattern similarity as predictors of both implicit and explicit memory. Using functional magnetic resonance imaging, we scanned 20 participants while they viewed and categorized repeated presentations of scenes. Repetition priming (facilitated categorization across repetitions) was used as a measure of implicit memory, and subsequent scene recognition was used as a measure of explicit memory. We found that repetition priming was predicted by repetition suppression in prefrontal, parietal, and occipitotemporal regions; however, repetition priming was not predicted by pattern similarity. In contrast, subsequent explicit memory was predicted by pattern similarity (across repetitions) in some of the same occipitotemporal regions that exhibited a relationship between priming and repetition suppression; however, explicit memory was not related to repetition suppression. This striking double dissociation indicates that repetition suppression and pattern similarity differentially track implicit and explicit learning.

Repetition Blindness: Out of Sight or Out of Mind?

Science.gov (United States)

Morris, Alison L.; Harris, Catherine L.

2004-01-01

Does repetition blindness represent a failure of perception or of memory? In Experiment 1, participants viewed rapid serial visual presentation (RSVP) sentences. When critical words (C1 and C2) were orthographically similar, C2 was frequently omitted from serial report; however, repetition priming for C2 on a postsentence lexical decision task was…

Physiological Signaling and Structure of the HGF Receptor MET

Directory of Open Access Journals (Sweden)

Gianluca Baldanzi

2014-12-01

Full Text Available The “hepatocyte growth factor” also known as “scatter factor”, is a multifunctional cytokine with the peculiar ability of simultaneously triggering epithelial cell proliferation, movement and survival. The combination of those proprieties results in the induction of an epithelial to mesenchymal transition in target cells, fundamental for embryogenesis but also exploited by tumor cells during metastatization. The hepatocyte growth factor receptor, MET, is a proto-oncogene and a prototypical transmembrane tyrosine kinase receptor. Inhere we discuss the MET molecular structure and the hepatocyte growth factor driven physiological signaling which coordinates epithelial proliferation, motility and morphogenesis.

Progress in developing repetitive pulse systems utilizing inductive energy storage

Energy Technology Data Exchange (ETDEWEB)

Honig, E.M.

1983-01-01

High-power, fast-recovery vacuum switches were used in a new repetitive counterpulse and transfer circuit to deliver a 5-kHz pulse train with a peak power of 75 MW (at 8.6 kA) to a 1-..cap omega.. load, resulting in the first demonstration of fully controlled, high-power, high-repetition-rate operation of an inductive energy-storage and transfer system with nondestructive switches. New circuits, analytical and experimental results, and feasibility of 100-kV repetitive pulse generation are discussed. A new switching concept for railgun loads is presented.

Topological laser speckle analyzer of differentiation and proliferation activity during morphogenesis in cell cultures

OpenAIRE

Notchenko A.V.; Gradov O.V.

2011-01-01

An automated system for morpho-topological determination of cell division phases and structur al differentiation of tissues during morphogenesis was implemented on the basis of topological properties of cell cultures, considered within the framework of set and manifold theories. A simple robotic hardware and software system based on Zeiss microscope with a modified stage and a Velleman manipulator KSR-1 allow to control the laser module position, carrying out the angular irradiation of s...

ABA content in shoots and roots of pea mutants af and tl as related to their growth and morphogenesis

Czech Academy of Sciences Publication Activity Database

Kof, E.M.; Vinogradova, I.A.; Oorzhak, A.S.; Karyagin, V.V.; Kalibernaya, Z.V.; Macháčková, Ivana; Kondykov, I.V.; Chuvasheva, E.S.

2006-01-01

Roč. 53, č. 3 (2006), s. 359-365 ISSN 1021-4437 Institutional research plan: CEZ:AV0Z50380511 Keywords : Pisum sativum * af and tl leaf mutants * morphogenesis Subject RIV: EF - Botanics Impact factor: 0.321, year: 2006

Repetitive laser fusion experiment and operation using a target injection system

International Nuclear Information System (INIS)

Nishimura, Yasuhiko; Komeda, Osamu; Mori, Yoshitaka

2017-01-01

Since 2008, a collaborative research project on laser fusion development based on a high-speed ignition method using repetitive laser has been carried out with several collaborative research institutes. This paper reports the current state of operation of high repetition laser fusion experiments, such as target introduction and control based on a target injection system that allows free falling under 1 Hz, using a high repetition laser driver that has been under research and development, as well as the measurement of targets that freely fall. The HAMA laser driver that enabled high repetition fusion experiments is a titanium sapphire laser using a diode-pumped solid-state laser KURE-I of green light output as a driver pump light source. In order to carry out high repetition laser fusion experiments, the target injection device allows free falling of deuterated polystyrene solid sphere targets of 1 mm in diameter under 1 Hz. The authors integrated the developed laser and injection system, and succeeded first in the world in making the nuclear fusion reaction continuously by hitting the target to be injected with laser, which is essential technology for future laser nuclear fusion reactor. In order to realize repetition laser fusion experiments, stable laser, target synchronization control, and target position measurement technologies are indispensable. (A.O.)

A βPIX-PAK2 complex confers protection against Scrib-dependent and cadherin-mediated apoptosis

DEFF Research Database (Denmark)

Frank, Scott R; Bell, Jennifer H; Frödin, Morten

2012-01-01

During epithelial morphogenesis, a complex comprising the βPIX (PAK-interacting exchange factor β) and class I PAKs (p21-activated kinases) is recruited to adherens junctions. Scrib, the mammalian ortholog of the Drosophila polarity determinant and tumor suppressor Scribble, binds βPIX directly. ...

Emergent properties during dorsal closure in Drosophila morphogenesis

International Nuclear Information System (INIS)

Peralta, X G; Toyama, Y; Edwards, G S; Kiehart, D P

2008-01-01

Dorsal closure is an essential stage of Drosophila development that is a model system for research in morphogenesis and biological physics. Dorsal closure involves an orchestrated interplay between gene expression and cell activities that produce shape changes, exert forces and mediate tissue dynamics. We investigate the dynamics of dorsal closure based on confocal microscopic measurements of cell shortening in living embryos. During the mid-stages of dorsal closure we find that there are fluctuations in the width of the leading edge cells but the time-averaged analysis of measurements indicate that there is essentially no net shortening of cells in the bulk of the leading edge, that contraction predominantly occurs at the canthi as part of the process for zipping together the two leading edges of epidermis and that the rate constant for zipping correlates with the rate of movement of the leading edges. We characterize emergent properties that regulate dorsal closure, i.e., a velocity governor and the coordination and synchronization of tissue dynamics

Study on Seed Morphogenesis of Orobanchaceae in Taiwan

Directory of Open Access Journals (Sweden)

Jao-Shien Chen

2011-11-01

Full Text Available Seed morphogenesis of Orobanchaceae was not completely investigated previously. Here, we observed seed development of Orobanchaceous species in Taiwan using light and scanning electron microscopies. Results indicated that seeds of Aeginetia indica, Boschniakia himalaica, and Orobanche caerulescens all consisted of embryo, endosperm and testa. Ontogeny of the embryo in A. indica was Solanad type, while in both B. himalaica and O. caerulescens was Onagrad type. The mature embryos of the three species lacked embryonic organs, and their endosperm development was the cellular type and, at maturity, appeared as several cell layers of storage tissue. Ontogeny of the testa was all non-multiplicative, with the residues of the outermost cell layer and reticulately-thickened secondary walls of its cells at maturity. Mature seeds of A. indica and O. caerulescens were ovate whereas those of B. himalaica were oblate. As for Christisonia hookeri, due to lack of samples, only the cellular-typed endosperm was determined. The comparative development of Orobanchaceous seeds was discussed.

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.

Repetition and brain potentials when recognizing natural scenes: task and emotion differences

Science.gov (United States)

Bradley, Margaret M.; Codispoti, Maurizio; Karlsson, Marie; Lang, Peter J.

2013-01-01

Repetition has long been known to facilitate memory performance, but its effects on event-related potentials (ERPs), measured as an index of recognition memory, are less well characterized. In Experiment 1, effects of both massed and distributed repetition on old–new ERPs were assessed during an immediate recognition test that followed incidental encoding of natural scenes that also varied in emotionality. Distributed repetition at encoding enhanced both memory performance and the amplitude of an old–new ERP difference over centro-parietal sensors. To assess whether these repetition effects reflect encoding or retrieval differences, the recognition task was replaced with passive viewing of old and new pictures in Experiment 2. In the absence of an explicit recognition task, ERPs were completely unaffected by repetition at encoding, and only emotional pictures prompted a modestly enhanced old–new difference. Taken together, the data suggest that repetition facilitates retrieval processes and that, in the absence of an explicit recognition task, differences in old–new ERPs are only apparent for affective cues. PMID:22842817

On the genetic control of planar growth during tissue morphogenesis in plants.

Science.gov (United States)

Enugutti, Balaji; Kirchhelle, Charlotte; Schneitz, Kay

2013-06-01

Tissue morphogenesis requires extensive intercellular communication. Plant organs are composites of distinct radial cell layers. A typical layer, such as the epidermis, is propagated by stereotypic anticlinal cell divisions. It is presently unclear what mechanisms coordinate cell divisions relative to the plane of a layer, resulting in planar growth and maintenance of the layer structure. Failure in the regulation of coordinated growth across a tissue may result in spatially restricted abnormal growth and the formation of a tumor-like protrusion. Therefore, one way to approach planar growth control is to look for genetic mutants that exhibit localized tumor-like outgrowths. Interestingly, plants appear to have evolved quite robust genetic mechanisms that govern these aspects of tissue morphogenesis. Here we provide a short summary of the current knowledge about the genetics of tumor formation in plants and relate it to the known control of coordinated cell behavior within a tissue layer. We further portray the integuments of Arabidopsis thaliana as an excellent model system to study the regulation of planar growth. The value of examining this process in integuments was established by the recent identification of the Arabidopsis AGC VIII kinase UNICORN as a novel growth suppressor involved in the regulation of planar growth and the inhibition of localized ectopic growth in integuments and other floral organs. An emerging insight is that misregulation of central determinants of adaxial-abaxial tissue polarity can lead to the formation of spatially restricted multicellular outgrowths in several tissues. Thus, there may exist a link between the mechanisms regulating adaxial-abaxial tissue polarity and planar growth in plants.

Repetition or Reconfiguration

DEFF Research Database (Denmark)

Andersen, Kristina Vaarst

, the cognitive quality of knowledge held by individual professionals is the key microfoundation for project level performance. This paper empirically tests effects of project participants with and without knowledge diversity for project level performance for projects aiming for varying degrees of repetition...... and reconfiguration. The results indicate that project performance benefits form contributions from individuals holding diverse knowledge only when projects aim for high differentiation levels. This positive association is not just moderated, it may even be reversed in the case of professionals participating in low...

Visual attention to advertising : The impact of motivation and repetition

NARCIS (Netherlands)

Pieters, RGM; Rosbergen, E; Hartog, M; Corfman, KP; Lynch, JG

1996-01-01

Using eye-tracking data, we examine the impact of motivation and repetition on visual attention to advertisements differing in argument quality. Our analyses indicate that repetition leads to an overall decrease in the amount of attention. However, while at first high motivation subjects attend to

Pull-production in repetitive remanufacturing

Energy Technology Data Exchange (ETDEWEB)

McCaskey, D.W. Jr.

1992-09-01

In the past, production activity control practices in most repetitive remanufacturing facilities resembled those used in intermittent production operations. These operations were characterized by large amounts of work-in-process (WIP), frequent work stoppages due to part shortages, excessive overtime, low product velocity, informal scheduling between dependent operations, low employee and management moral, and a lot of wasted time, material, labor, and space. Improvement in production activity control (PAC) methods for repetitive remanufactures has been hampered by uncertainty in: supply of incoming assets, configuration of assets, process times to refurbish assets, and yields in reclamation processes. collectively these uncertainties make shop floor operations seem uncontrollable. However, one United States Army depot has taken on the challenge. Through management supported, cross-functional teams, the Tooele Army Depot has designed and implemented pull-production systems for two of its major products, with several others to follow. This article presents a generalized version of Tooele`s pull-production system and highlights design characteristics which are specific to remanufacturing applications.

Pull-production in repetitive remanufacturing

Energy Technology Data Exchange (ETDEWEB)

McCaskey, D.W. Jr.

1992-09-01

In the past, production activity control practices in most repetitive remanufacturing facilities resembled those used in intermittent production operations. These operations were characterized by large amounts of work-in-process (WIP), frequent work stoppages due to part shortages, excessive overtime, low product velocity, informal scheduling between dependent operations, low employee and management moral, and a lot of wasted time, material, labor, and space. Improvement in production activity control (PAC) methods for repetitive remanufactures has been hampered by uncertainty in: supply of incoming assets, configuration of assets, process times to refurbish assets, and yields in reclamation processes. collectively these uncertainties make shop floor operations seem uncontrollable. However, one United States Army depot has taken on the challenge. Through management supported, cross-functional teams, the Tooele Army Depot has designed and implemented pull-production systems for two of its major products, with several others to follow. This article presents a generalized version of Tooele's pull-production system and highlights design characteristics which are specific to remanufacturing applications.

Active power filter for harmonic compensation using a digital dual-mode-structure repetitive control approach

DEFF Research Database (Denmark)

Zou, Zhixiang; Wang, Zheng; Cheng, Ming

2012-01-01

This paper presents an digital dual-mode-structure repetitive control approach for the single-phase shunt active power filter (APF), which aims to enhance the tracking ability and eliminate arbitrary order harmonic. The proposed repetitive control scheme blends the characteristics of both odd......-harmonic repetitive control and even-harmonic repetitive control. Moreover, the convergence rate is faster than conventional repetitive controller. Additionally, the parameters have been designed and optimized for the dual-mode structure repetitive control to improve the performance of APF system. Experimental...

Gibberellin influence on the morphogenesis of the moss Bryum argenteum Hedw. in in vitro conditions

OpenAIRE

Sabovljević Aneta; Sabovljević Marko; Grubišić D.

2010-01-01

The moss Bryum argenteum Hedw. was treated with gibberellins as well as some inhibitors of gibberellin biosynthesis in order to investigate their influence on B. argenteum morphogenesis. Generally, gibberellins have not been chemically identified in bryophytes, while other groups of classical phytohormones (auxins, cytokinins, abscisic acid and ethylene) have been chemically identified in these plants. The in vitro culture of the moss Bryum argenteum was established from sterilized spores. Th...

A Julia set model of field-directed morphogenesis: developmental biology and artificial life.

Science.gov (United States)

Levin, M

1994-04-01

One paradigm used in understanding the control of morphogenetic events is the concept of positional information, where sub-organismic components (such as cells) act in response to positional cues. It is important to determine what kinds of spatiotemporal patterns may be obtained by such a method, and what the characteristics of such a morphogenetic process might be. This paper presents a computer model of morphogenesis based on gene activity driven by interpreting a positional information field. In this model, the interactions of mutually regulating developmental genes are viewed as a map from R2 to R2, and are modeled by the complex number algebra. Functions in complex variables are used to simulate genetic interactions resulting in position-dependent differentiation. This is shown to be equivalent to computing modified Julia sets, and is seen to be sufficient to produce a very rich set of morphologies which are similar in appearance and several important characteristics to those of real organisms. The properties of this model can be used to study the potential role of fields and positional information as guiding factors in morphogenesis, as the model facilitates the study of static images, time-series (movies) and experimental alterations of the developmental process. It is thus shown that gene interactions can be modeled as a multi-dimensional algebra, and that only two interacting genes are sufficient for (i) complex pattern formation, (ii) chaotic differentiation behavior, and (iii) production of sharp edges from a continuous positional information field. This model is meant to elucidate the properties of the process of positional information-guided biomorphogenesis, not to serve as a simulation of any particular organism's development. Good quantitative data are not currently available on the interplay of gene products in morphogenesis. Thus, no attempt is made to link the images produced with actual pictures of any particular real organism. A brief

Msx-2 expression and glucocorticoid-induced overexpression in embryonic mouse submandibular glands.

Science.gov (United States)

Jaskoll, T; Luo, W; Snead, M L

1998-01-01

It is well known that the process of branching morphogenesis requires epithelial-mesenchymal interactions. One outstanding model for the study of tissue interactions during branching morphogenesis is the embryonic mouse submandibular gland (SMG). Although it has been clearly demonstrated that the branching pattern is dependent on interactions between the epithelium and the surrounding mesenchyme, little is known about the molecular mechanism underlying the branching process. One group of transcription factors that likely participates in the control of epithelial-mesenchymal inductive interactions are the Msx-class of homeodomain-containing proteins. In this paper, we focus on Msx-2 because its developmental expression is correlated with inductive interactions, suggesting that Msx-2 may play a functional role during cell-cell interactions. We demonstrate the expression of Msx-2 mRNA and protein to be primarily in the branching epithelia with progressive embryonic (E13 to E15) SMG development and, to a lesser extent, in the mesenchyme. We also show that Msx-2 is expressed by embryonic SMG primordia cultured under defined conditions. In addition, to begin to delineate a functional role for Msx-2, we employed an experimental strategy by using exogenous glucocorticoid (CORT) treatment of embryonic SMGs in vitro and in vivo to significantly enhance branching morphogenesis and evaluate the effect of CORT treatment on embryonic SMG Msx-2 expression. A marked increase in Msx-2 transcripts and protein is detected with in vitro and in vivo CORT treatment. Our studies indicate that one mechanism of CORT regulation of salivary gland morphogenesis is likely through the modulation of Msx-2 gene expression.

Negative effects of item repetition on source memory

OpenAIRE

Kim, Kyungmi; Yi, Do-Joon; Raye, Carol L.; Johnson, Marcia K.

2012-01-01

In the present study, we explored how item repetition affects source memory for new item–feature associations (picture–location or picture–color). We presented line drawings varying numbers of times in Phase 1. In Phase 2, each drawing was presented once with a critical new feature. In Phase 3, we tested memory for the new source feature of each item from Phase 2. Experiments 1 and 2 demonstrated and replicated the negative effects of item repetition on incidental source memory. Prior item re...

Functional dissociations in top-down control dependent neural repetition priming.

NARCIS (Netherlands)

Klaver, P.; Schnaidt, M.; Fell, J.; Ruhlmann, J.; Elger, C.E.; Fernandez, G.S.E.

2007-01-01

Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either

Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders: A meta-analysis.

Science.gov (United States)

Zhang, Yingli; Liang, Wei; Yang, Shichang; Dai, Ping; Shen, Lijuan; Wang, Changhong

2013-10-05

This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hallucination of patients with schizophrenia spectrum disorders. Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Controlled Trials databases from January 1985 to May 2012. Key words were "transcranial magnetic stimulation", "TMS", "repetitive transcranial magnetic stimulation", and "hallucination". Selected studies were randomized controlled trials assessing therapeutic efficacy of repetitive transcranial magnetic stimulation for hallucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hallucination in schizophrenia spectrum disorders. Control groups received sham stimulation. The primary outcome was total scores of Auditory Hallucinations Rating Scale, Auditory Hallucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hallucination item, and Hallucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. All data were completely effective, involving 398 patients. Overall mean weighted effect size for repetitive transcranial magnetic stimulation versus sham stimulation was statistically significant (MD = -0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P = 0.005). No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for

An Antarctic hypotrichous ciliate, Parasterkiella thompsoni (Foissner) nov. gen., nov. comb., recorded in Argentinean peat-bogs: morphology, morphogenesis, and molecular phylogeny.

Science.gov (United States)

Küppers, Gabriela Cristina; Paiva, Thiago da Silva; Borges, Bárbara do Nascimento; Harada, Maria Lúcia; Garraza, Gabriela González; Mataloni, Gabriela

2011-05-01

The ciliate Parasterkiella thompsoni (Foissner, 1996) nov. gen., nov. comb. was originally described from Antarctica. In the present study, we report the morphology, morphogenesis during cell division, and molecular phylogeny inferred from the 18S-rDNA sequence of a population isolated from the Rancho Hambre peat bog, Tierra del Fuego Province (Argentina). The study is based on live and protargol-impregnated specimens. Molecular phylogeny was inferred from trees constructed by means of the maximum parsimony, neighbor joining, and Bayesian analyses. The interphase morphology matches the original description of the species. During the cell division, stomatogenesis begins with the de novo proliferation of two fields of basal bodies, each one left of the postoral ventral cirri and of transverse cirri, which later unify. Primordia IV-VI of the proter develop from disaggregation of cirrus IV/3, while primordium IV of the opisthe develops from cirrus IV/2 and primordia V and VI from cirrus V/4. Dorsal morphogenesis occurs in the Urosomoida pattern-that is, the fragmentation of kinety 3 is lacking. Three macronuclear nodules are generated before cytokinesis. Phylogenetic analyses consistently placed P. thompsoni within the stylonychines. New data on the morphogenesis of the dorsal ciliature justifies the transference of Sterkiella thompsoni to a new genus Parasterkiella. Copyright © 2011 Elsevier GmbH. All rights reserved.

Autism and exergaming: effects on repetitive behaviors and cognition.

Science.gov (United States)

Anderson-Hanley, Cay; Tureck, Kimberly; Schneiderman, Robyn L

2011-01-01

Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR); in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum.

Understanding the relationship between repetition priming and mere exposure.

Science.gov (United States)

Butler, Laurie T; Berry, Dianne C

2004-11-01

Over the last two decades interest in implicit memory, most notably repetition priming, has grown considerably. During the same period, research has also focused on the mere exposure effect. Although the two areas have developed relatively independently, a number of studies has described the mere exposure effect as an example of implicit memory. Tacit in their comparisons is the assumption that the effect is more specifically a demonstration of repetition priming. Having noted that this assumption has attracted relatively little attention, this paper reviews current evidence and shows that it is by no means conclusive. Although some evidence is suggestive of a common underlying mechanism, even a modified repetition priming (perceptual fluency/attribution) framework cannot accommodate all of the differences between the two phenomena. Notwithstanding this, it seems likely that a version of this theoretical framework still offers the best hope of a comprehensive explanation for the mere exposure effect and its relationship to repetition priming. As such, the paper finishes by offering some initial guidance as to ways in which the perceptual fluency/attribution framework might be extended, as well as outlining important areas for future research.

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

BOLD repetition decreases in object-responsive ventral visual areas depend on spatial attention.

Science.gov (United States)

Eger, E; Henson, R N A; Driver, J; Dolan, R J

2004-08-01

Functional imaging studies of priming-related repetition phenomena have become widely used to study neural object representation. Although blood oxygenation level-dependent (BOLD) repetition decreases can sometimes be observed without awareness of repetition, any role for spatial attention in BOLD repetition effects remains largely unknown. We used fMRI in 13 healthy subjects to test whether BOLD repetition decreases for repeated objects in ventral visual cortices depend on allocation of spatial attention to the prime. Subjects performed a size-judgment task on a probe object that had been attended or ignored in a preceding prime display of 2 lateralized objects. Reaction times showed faster responses when the probe was the same object as the attended prime, independent of the view tested (identical vs. mirror image). No behavioral effect was evident from unattended primes. BOLD repetition decreases for attended primes were found in lateral occipital and fusiform regions bilaterally, which generalized across identical and mirror-image repeats. No repetition decreases were observed for ignored primes. Our results suggest a critical role for attention in achieving visual representations of objects that lead to both BOLD signal decreases and behavioral priming on repeated presentation.

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.

The cell wall-localized atypical β-1,3 glucanase ZERZAUST controls tissue morphogenesis in Arabidopsis thaliana.

Science.gov (United States)

Vaddepalli, Prasad; Fulton, Lynette; Wieland, Jennifer; Wassmer, Katrin; Schaeffer, Milena; Ranf, Stefanie; Schneitz, Kay

2017-06-15

Orchestration of cellular behavior in plant organogenesis requires integration of intercellular communication and cell wall dynamics. The underlying signaling mechanisms are poorly understood. Tissue morphogenesis in Arabidopsis depends on the receptor-like kinase STRUBBELIG. Mutations in ZERZAUST were previously shown to result in a strubbelig -like mutant phenotype. Here, we report on the molecular identification and functional characterization of ZERZAUST We show that ZERZAUST encodes a putative GPI-anchored β-1,3 glucanase suggested to degrade the cell wall polymer callose. However, a combination of in vitro , cell biological and genetic experiments indicate that ZERZAUST is not involved in the regulation of callose accumulation. Nonetheless, Fourier-transformed infrared-spectroscopy revealed that zerzaust mutants show defects in cell wall composition. Furthermore, the results indicate that ZERZAUST represents a mobile apoplastic protein, and that its carbohydrate-binding module family 43 domain is required for proper subcellular localization and function whereas its GPI anchor is dispensable. Our collective data reveal that the atypical β-1,3 glucanase ZERZAUST acts in a non-cell-autonomous manner and is required for cell wall organization during tissue morphogenesis. © 2017. Published by The Company of Biologists Ltd.

Coupling gene expression and multicellular morphogenesis during fruiting body formation in Myxococcus xanthus

DEFF Research Database (Denmark)

Søgaard-Andersen, L.; Overgaard, M.; Lobedanz, S.

2003-01-01

xanthus illustrates this coupling in the construction of a multicellular structure. Fruiting body formation involves two stages: aggregation of cells into mounds and the position-specific sporulation of cells that have accumulated inside mounds. Developmental gene expression propels these two processes...... morphogenesis. Accumulation of the C-signal is tightly regulated and involves transcriptional activation of the csgA gene and proteolysis of the full-length CsgA protein to produce the shorter cell surface-associated 17 kDa C-signal protein. The C-signal induces aggregation, sporulation and developmental gene...

Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

DEFF Research Database (Denmark)

Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae

2015-01-01

that line the ducts during development, and in the ducts after birth, but not in differentiated endocrine or acinar cells. Genetic inactivation of Bicc1 leads to ductal cell over-proliferation and cyst formation. Transcriptome comparison between WT and Bicc1 KO pancreata, before the phenotype onset, reveals......(+) endocrine progenitor production. Its deletion leads to a late but sustained endocrine progenitor decrease, resulting in a 50% reduction of endocrine cells. We show that BICC1 functions downstream of ONECUT1 in the pathway controlling both NEUROG3(+) endocrine cell production and ductal morphogenesis...

A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis

NARCIS (Netherlands)

Siegel, Gabriele; Obernosterer, Gregor; Fiore, Roberto; Oehmen, Martin; Bicker, Silvia; Christensen, Mette; Khudayberdiev, Sharof; Leuschner, Philipp F; Busch, Clara J L; Kane, Christina; Hübel, Katja; Dekker, Frank; Hedberg, Christian; Rengarajan, Balamurugan; Drepper, Carsten; Waldmann, Herbert; Kauppinen, Sakari; Greenberg, Michael E; Draguhn, Andreas; Rehmsmeier, Marc; Martinez, Javier; Schratt, Gerhard M; Dekker, Frank

The microRNA pathway has been implicated in the regulation of synaptic protein synthesis and ultimately in dendritic spine morphogenesis, a phenomenon associated with long-lasting forms of memory. However, the particular microRNAs (miRNAs) involved are largely unknown. Here we identify specific

Risk factors for hand-wrist disorders in repetitive work

DEFF Research Database (Denmark)

Thomsen, J. F.; Mikkelsen, S.; Andersen, JH

2007-01-01

OBJECTIVES: To identify the risk of hand-wrist disorders related to repetitive movements, use of hand force and wrist position in repetitive monotonous work. METHODS: Using questionnaires and physical examinations, the prevalence and incidence of hand-wrist pain and possible extensor tendonitis...... (wrist pain and palpation tenderness) were determined in 3123 employees in 19 industrial settings. With the use of questionnaires and video recordings of homogenous work tasks number of wrist movements, hand force requirements and wrist position were analysed as risk factors for hand-wrist disorders......, controlling for potential personal and psychosocial confounders. All participants were re-examined three times during a follow-up period of three years. RESULTS: Force but not repetition and position was related to hand-wrist pain and possible tendonitis in the baseline analyses showing an exposure...

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.

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.

Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis.

Science.gov (United States)

Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

2017-11-15

Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by Acanthamoeba castellanii , causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus. IMPORTANCE Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a

Ultrastructural analysis of volutin-acidocalciumosomes formation in some species of bacteria, spirochetes, yeast and protozoa during morphogenesis and under environment different factors action

International Nuclear Information System (INIS)

Hovnanyan, K.O.; Hovnanyan, M.K.; Navasardyan, L.A.; Trchounian, A.A.

2012-01-01

Ultrastructure organization of volutin granules in some species of bacteria, spirochetes, yeast and protozoa cellular architecture was studied during morphogenesis and under environment different factors action leading to pathological changes. As the result of complex electron microscopic studies of morphogenesis in some species of prokaryotes and eukaryotic organisms the formation of new structures of volutin-acidocal-ciumosomes has been established within cell cytoplasm. In addition, under the ionizing roentgen and irradiation as well as some antibiotics action morphometric changes and changes in optical properties were also shown. Electron microscopic identification of volutin granules changes in structural organization in bacteria, spirochetes, yeast and protozoa might serve as appropriate express-method for visual evaluation of damage and reparation processes during environment

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.

Characterization and distribution of repetitive elements in association with genes in the human genome.

Science.gov (United States)

Liang, Kai-Chiang; Tseng, Joseph T; Tsai, Shaw-Jenq; Sun, H Sunny

2015-08-01

Repetitive elements constitute more than 50% of the human genome. Recent studies implied that the complexity of living organisms is not just a direct outcome of a number of coding sequences; the repetitive elements, which do not encode proteins, may also play a significant role. Though scattered studies showed that repetitive elements in the regulatory regions of a gene control gene expression, no systematic survey has been done to report the characterization and distribution of various types of these repetitive elements in the human genome. Sequences from 5' and 3' untranslated regions and upstream and downstream of a gene were downloaded from the Ensembl database. The repetitive elements in the neighboring of each gene were identified and classified using cross-matching implemented in the RepeatMasker. The annotation and distribution of distinct classes of repetitive elements associated with individual gene were collected to characterize genes in association with different types of repetitive elements using systems biology program. We identified a total of 1,068,400 repetitive elements which belong to 37-class families and 1235 subclasses that are associated with 33,761 genes and 57,365 transcripts. In addition, we found that the tandem repeats preferentially locate proximal to the transcription start site (TSS) of genes and the major function of these genes are involved in developmental processes. On the other hand, interspersed repetitive elements showed a tendency to be accumulated at distal region from the TSS and the function of interspersed repeat-containing genes took part in the catabolic/metabolic processes. Results from the distribution analysis were collected and used to construct a gene-based repetitive element database (GBRED; http://www.binfo.ncku.edu.tw/GBRED/index.html). A user-friendly web interface was designed to provide the information of repetitive elements associated with any particular gene(s). This is the first study focusing on the gene

Repetitive Bibliographical Information in Relational Databases.

Science.gov (United States)

Brooks, Terrence A.

1988-01-01

Proposes a solution to the problem of loading repetitive bibliographic information in a microcomputer-based relational database management system. The alternative design described is based on a representational redundancy design and normalization theory. (12 references) (Author/CLB)

Morphogenesis of the infectious HIV-1 virion

Directory of Open Access Journals (Sweden)

Jun-Ichi eSakuragi

2011-12-01

Full Text Available The virion of HIV-1 is spherical and viral glycoprotein spikes (gp120, gp41 protrude from its envelope. The characteristic cone-shaped core exists within the virion, caging the ribonucleoprotein (RNP complex, which is comprised of viral RNA, nucleocapsid (NC and viral enzymes. The HIV-1 virion is budded and released from the infected cell as an immature donut-shaped particle. During or immediately after release, viral protease (PR is activated and subsequently processes the viral structural protein Gag. Through this maturation process, virions acquire infectivity, but its mechanism and transition of morphology largely remain unclear. Recent technological advances in experimental devices and techniques have made it possible to closely dissect the viral production site on the cell, the exterior – or even the interior – of an individual virion, and many new aspects on virion morphology and maturation. In this manuscript, I review the morphogenesis of HIV-1 virions. I focus on several studies, including some of our recent findings, which examined virion formation and/or maturation processes. The story of novel compound, which inhibits virion maturation, and the importance of maturation research are also discussed.

A copper bromide vapour laser with a high pulse repetition rate

International Nuclear Information System (INIS)

Shiyanov, D V; Evtushenko, Gennadii S; Sukhanov, V B; Fedorov, V F

2002-01-01

The results of an experimental study of a copper bromide vapour laser with a discharge-channel diameter above 2.5 cm and a high pump-pulse repetition rate are presented. A TGU1-1000/25 high-power tacitron used as a switch made it possible to obtain for the first time a fairly high output radiation power for pump-pulse repetition rates exceeding 200 kHz. At a maximum pump-pulse repetition rate of 250 kHz achieved in a laser tube 2.6 cm in diameter and 76 cm long, the output power was 1.5 W. The output powers of 3 and 10.5 W were reached for pump-pulse repetition rates of 200 and 100 kHz, respectively. These characteristics were obtained without circulating a buffer gas and (or) low-concentration active impurities through the active volume. (active media. lasers)

The repetition effect in building and construction works

DEFF Research Database (Denmark)

Gottlieb, Stefan Christoffer; Haugbølle, Kim

are then applied on the Public Transport Authorities' main account structure of units and costs, and a method for assessing the possibilities of achieving effects of repetition for each account is described. Finally, the report summarises the core conditions necessary to take into consideration in relation......This report summarises the results from the work undertaken for the Public Transport Authority on the effect of learning and repetition in building and construction works. The results are applied by the Public Transport Authority in a new budgeting model, while the agency investigates...

Contribution of fronto-striatal regions to emotional valence and repetition under cognitive conflict.

Science.gov (United States)

Chun, Ji-Won; Park, Hae-Jeong; Kim, Dai Jin; Kim, Eosu; Kim, Jae-Jin

2017-07-01

Conflict processing mediated by fronto-striatal regions may be influenced by emotional properties of stimuli. This study aimed to examine the effects of emotion repetition on cognitive control in a conflict-provoking situation. Twenty-one healthy subjects were scanned using functional magnetic resonance imaging while performing a sequential cognitive conflict task composed of emotional stimuli. The regional effects were analyzed according to the repetition or non-repetition of cognitive congruency and emotional valence between the preceding and current trials. Post-incongruence interference in error rate and reaction time was significantly smaller than post-congruence interference, particularly under repeated positive and non-repeated positive, respectively, and post-incongruence interference, compared to post-congruence interference, increased activity in the ACC, DLPFC, and striatum. ACC and DLPFC activities were significantly correlated with error rate or reaction time in some conditions, and fronto-striatal connections were related to the conflict processing heightened by negative emotion. These findings suggest that the repetition of emotional stimuli adaptively regulates cognitive control and the fronto-striatal circuit may engage in the conflict adaptation process induced by emotion repetition. Both repetition enhancement and repetition suppression of prefrontal activity may underlie the relationship between emotion and conflict adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Michael T. Veeman

2016-06-01

Full Text Available Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa.

Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders A meta-analysis***

Institute of Scientific and Technical Information of China (English)

Yingli Zhang; Wei Liang; Shichang Yang; Ping Dai; Lijuan Shen; Changhong Wang

2013-01-01

OBJECTIVE: This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hal ucination of patients with schizophrenia spectrum disorders. DATA SOURCES: Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Control ed Trials databases from January 1985 to May 2012. Key words were “transcranial magnetic stimulation”, “TMS”, “repetitive transcranial magnetic stimulation”, and “hal ucination”. STUDY SELECTION: Selected studies were randomized control ed trials assessing therapeutic ef-ficacy of repetitive transcranial magnetic stimulation for hal ucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hal ucination in schizophrenia spectrum disorders. Control groups received sham stimulation. MAIN OUTCOME MEASURES: The primary outcome was total scores of Auditory Hal ucinations Rating Scale, Auditory Hal ucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hal ucination item, and Hal ucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. RESULTS: Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. Al data were completely effective, involving 398 patients. Overal mean weighted effect size for repeti-tive transcranial magnetic stimulation versus sham stimulation was statistical y significant (MD =-0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P =0.005). No significant differences were found

Comparison of concentric and eccentric bench press repetitions to failure.

Science.gov (United States)

Kelly, Stephen B; Brown, Lee E; Hooker, Steven P; Swan, Pamela D; Buman, Matthew P; Alvar, Brent A; Black, Laurie E

2015-04-01

Eccentric muscle actions (ECC) are characterized by muscle lengthening, despite actin-myosin crossbridge formation. Muscles acting eccentrically are capable of producing higher levels of force compared with muscles acting concentrically. The purpose of this study was to determine whether ECC bench press yields greater strength than concentric (CON) as determined by 1 repetition maximum (1RM). Additionally, a comparison was made examining differences in the number of repetitions to failure at different relative intensities of 1RM. Thirty healthy men (age = 24.63 ± 5.6 years) were tested for 1RM in CON and ECC bench press and the number of repetitions completed at 60, 70, 80, and 90% 1RM. For CON repetitions, the weight was mechanically lowered to the chest, and the participant pressed it up until the elbows were fully extended. The ECC bench press consisted of lowering a barbell from a fully extended elbow position to the chest in a continuous controlled manner for 3 seconds as determined by electronic metronome. Paired t-tests showed that ECC 1RM (115.99 ± 31.08 kg) was significantly (p ≤ 0.05) greater than CON 1RM (93.56 ± 26.56 kg), and the number of repetitions completed at 90% 1RM was significantly (p ≤ 0.05) greater in ECC (7.67 ± 3.24) as compared with CON (4.57 ± 2.21). There were no significant differences in number of completed repetitions during CON and ECC bench press at 60, 70, and 80% 1RM. These data indicate that ECC actions yield increased force capabilities (∼120%) as compared with CON in the bench press and may be less prone to fatigue, especially at higher intensities. These differences suggest a need to develop unique strategies for training eccentrically.

Pulsed electron beam generation with fast repetitive double pulse system

Energy Technology Data Exchange (ETDEWEB)

Sharma, Surender Kumar; Deb, Pankaj; Shyam, Anurag, E-mail: surender80@gmail.com [Energetics and Electromagnetics Division, Bhabha Atomic Research Centre, Visakhapatnam (India); Sharma, Archana [Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Mumbai (India)

2014-07-01

Longer duration high voltage pulse (∼ 100 kV, 260 ns) is generated and reported using helical pulse forming line in compact geometry. The transmission line characteristics of the helical pulse forming line are also used to develop fast repetition double pulse system with very short inter pulse interval. It overcomes the limitations caused due to circuit parameters, power supplies and load characteristics for fast repetitive high voltage pulse generation. The high voltage double pulse of 100 kV, 100 ns with an inter pulse repetition interval of 30 ns is applied across the vacuum field emission diode for pulsed electron beam generation. The electron beam is generated from cathode material by application of negative high voltage (> 100 kV) across the diode by explosive electron emission process. The vacuum field emission diode is made of 40 mm diameter graphite cathode and SS mesh anode. The anode cathode gap was 6 mm and the drift tube diameter was 10 cm. The initial experimental results of pulsed electron beam generation with fast repetitive double pulse system are reported and discussed. (author)

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 .

Spared behavioral repetition effects in Alzheimer's disease linked to an altered neural mechanism at posterior cortex.

Science.gov (United States)

Broster, Lucas S; Li, Juan; Wagner, Benjamin; Smith, Charles D; Jicha, Gregory A; Schmitt, Frederick A; Munro, Nancy; Haney, Ryan H; Jiang, Yang

2018-02-20

Individuals with dementia of the Alzheimer type (AD) classically show disproportionate impairment in measures of working memory, but repetition learning effects are relatively preserved. As AD affects brain regions implicated in both working memory and repetition effects, the neural basis of this discrepancy is poorly understood. We hypothesized that the posterior repetition effect could account for this discrepancy due to the milder effects of AD at visual cortex. Participants with early AD, amnestic mild cognitive impairment (MCI), and healthy controls performed a working memory task with superimposed repetition effects while electroencephalography was collected to identify possible neural mechanisms of preserved repetition effects. Participants with AD showed preserved behavioral repetition effects and a change in the posterior repetition effect. Visual cortex may play a role in maintained repetition effects in persons with early AD.

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.

Repetitive trauma and nerve compression.

Science.gov (United States)

Carragee, E J; Hentz, V R

1988-01-01

Repetitive movement of the upper extremity, whether recreational or occupational, may result in various neuropathies, the prototype of which is the median nerve neuropathic in the carpal canal. The pathophysiology of this process is incompletely understood but likely involves both mechanical and ischemic features. Experimentally increased pressures within the carpal canal produced reproducible progressive neuropathy. Changes in vibratory (threshold-type) sensibility appears to be more sensitive than two-point (innervation density-type) sensibility. The specific occupational etiologies of carpal neuropathy are obscured by methodologic and sociological difficulties, but clearly some occupations have high incidences of CTS. History and physical examination are usually sufficient for the diagnosis, but diagnostic assistance when required is available through electrophysiological testing, CT scanning, and possibly MRI. Each of these tests has limitations in both sensitivity and specificity. Treatment by usual conservative means should be combined with rest from possible provocative activities. Surgical release of the carpal canal is helpful in patients failing conservative therapy. Occupational modifications are important in both treatment and prevention of median neuropathy due to repetitive trauma.

The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGF alpha and FGF7 in morphogenesis of mouse mammary epithelium

Energy Technology Data Exchange (ETDEWEB)

Fata, Jimmie E; Mori, Hidetoshi; Ewald, Andrew J; Zhang, Hui; Yao, Evelyn; Werb, Zena; Bissell, Mina J

2006-10-03

Transforming growth factor-{alpha} (TGF{alpha}) and fibroblast growth factor-7 (FGF7) exhibit distinct expression patterns in the mammary gland. Both factors signal through mitogen-activated kinase/extracellular regulated kinase-1,2 (MAPK{sup ERK1,2}); however, their unique and/or combined contributions to mammary morphogenesis have not been examined. In ex vivo mammary explants, we show that a sustained activation of MAPK{sup ERK1,2} for 1 h, induced by TGF{alpha}, was necessary and sufficient to initiate branching morphogenesis, whereas a transient activation (15 min) of MAPK{sup ERK1,2}, induced by FGF7, led to growth without branching. Unlike TGF{alpha}, FGF7 promoted sustained proliferation as well as ectopic localization of, and increase in, keratin-6 expressing cells. The response of the explants to FGF10 was similar to that to FGF7. Simultaneous stimulation by FGF7 and TGF{alpha} indicated that the FGF7-induced MAPK{sup ERK1,2} signaling and associated phenotypes were dominant: FGF7 may prevent branching by suppression of two necessary TGF{alpha}-induced morphogenetic effectors, matrix metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK{sup ERK1,2} activation.

High plasticity in epithelial morphogenesis during insect dorsal closure

Directory of Open Access Journals (Sweden)

Kristen A. Panfilio

2013-09-01

Insect embryos complete the outer form of the body via dorsal closure (DC of the epidermal flanks, replacing the transient extraembryonic (EE tissue. Cell shape changes and morphogenetic behavior are well characterized for DC in Drosophila, but these data represent a single species with a secondarily reduced EE component (the amnioserosa that is not representative across the insects. Here, we examine DC in the red flour beetle, Tribolium castaneum, providing the first detailed, functional analysis of DC in an insect with complete EE tissues (distinct amnion and serosa. Surprisingly, we find that differences between Drosophila and Tribolium DC are not restricted to the EE tissue, but also encompass the dorsal epidermis, which differs in cellular architecture and method of final closure (zippering. We then experimentally manipulated EE tissue complement via RNAi for Tc-zen1, allowing us to eliminate the serosa and still examine viable DC in a system with a single EE tissue (the amnion. We find that the EE domain is particularly plastic in morphogenetic behavior and tissue structure. In contrast, embryonic features and overall kinetics are robust to Tc-zen1RNAi manipulation in Tribolium and conserved with a more distantly related insect, but remain substantially different from Drosophila. Although correct DC is essential, plasticity and regulative, compensatory capacity have permitted DC to evolve within the insects. Thus, DC does not represent a strong developmental constraint on the nature of EE development, a property that may have contributed to the reduction of the EE component in the fly lineage.

Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

Directory of Open Access Journals (Sweden)

Amanda Malvessi Cattani

Full Text Available Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

Science.gov (United States)

Cattani, Amanda Malvessi; Siqueira, Franciele Maboni; Guedes, Rafael Lucas Muniz; Schrank, Irene Silveira

2016-01-01

Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

Multiscale information modelling for heart morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Abdulla, T; Imms, R; Summers, R [Department of Electronic and Electrical Engineering, Loughborough University, Loughborough (United Kingdom); Schleich, J M, E-mail: T.Abdulla@lboro.ac.u [LTSI Signal and Image Processing Laboratory, University of Rennes 1, Rennes (France)

2010-07-01

Science is made feasible by the adoption of common systems of units. As research has become more data intensive, especially in the biomedical domain, it requires the adoption of a common system of information models, to make explicit the relationship between one set of data and another, regardless of format. This is being realised through the OBO Foundry to develop a suite of reference ontologies, and NCBO Bioportal to provide services to integrate biomedical resources and functionality to visualise and create mappings between ontology terms. Biomedical experts tend to be focused at one level of spatial scale, be it biochemistry, cell biology, or anatomy. Likewise, the ontologies they use tend to be focused at a particular level of scale. There is increasing interest in a multiscale systems approach, which attempts to integrate between different levels of scale to gain understanding of emergent effects. This is a return to physiological medicine with a computational emphasis, exemplified by the worldwide Physiome initiative, and the European Union funded Network of Excellence in the Virtual Physiological Human. However, little work has been done on how information modelling itself may be tailored to a multiscale systems approach. We demonstrate how this can be done for the complex process of heart morphogenesis, which requires multiscale understanding in both time and spatial domains. Such an effort enables the integration of multiscale metrology.

Multiscale information modelling for heart morphogenesis

International Nuclear Information System (INIS)

Abdulla, T; Imms, R; Summers, R; Schleich, J M

2010-01-01

Science is made feasible by the adoption of common systems of units. As research has become more data intensive, especially in the biomedical domain, it requires the adoption of a common system of information models, to make explicit the relationship between one set of data and another, regardless of format. This is being realised through the OBO Foundry to develop a suite of reference ontologies, and NCBO Bioportal to provide services to integrate biomedical resources and functionality to visualise and create mappings between ontology terms. Biomedical experts tend to be focused at one level of spatial scale, be it biochemistry, cell biology, or anatomy. Likewise, the ontologies they use tend to be focused at a particular level of scale. There is increasing interest in a multiscale systems approach, which attempts to integrate between different levels of scale to gain understanding of emergent effects. This is a return to physiological medicine with a computational emphasis, exemplified by the worldwide Physiome initiative, and the European Union funded Network of Excellence in the Virtual Physiological Human. However, little work has been done on how information modelling itself may be tailored to a multiscale systems approach. We demonstrate how this can be done for the complex process of heart morphogenesis, which requires multiscale understanding in both time and spatial domains. Such an effort enables the integration of multiscale metrology.

A long-pulse repetitive operation magnetically insulated transmission line oscillator

International Nuclear Information System (INIS)

Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang

2014-01-01

The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO

A long-pulse repetitive operation magnetically insulated transmission line oscillator

Energy Technology Data Exchange (ETDEWEB)

Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang [College of Optoelectric Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

2014-05-15

The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO.

A long-pulse repetitive operation magnetically insulated transmission line oscillator.

Science.gov (United States)

Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang

2014-05-01

The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO.

Repetitive elements in parasitic protozoa

Directory of Open Access Journals (Sweden)

Clayton Christine

2010-05-01

Full Text Available Abstract A recent paper published in BMC Genomics suggests that retrotransposition may be active in the human gut parasite Entamoeba histolytica. This adds to our knowledge of the various types of repetitive elements in parasitic protists and the potential influence of such elements on pathogenicity. See research article http://www.biomedcentral.com/1471-2164/11/321

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...

Reassessing the roles of PIN proteins and anticlinal microtubules during pavement cell morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Belteton, Samuel; Sawchuk, Megan G.; Donohoe, Bryon S.; Scarpella, Enrico; Szymanski, Daniel B.

2017-11-30

The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here we used Arabidopsis reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells, and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls.

Oxotremorine treatment reduces repetitive behaviors in BTBR T+ tf/J mice

Directory of Open Access Journals (Sweden)

Dionisio A. Amodeo

2014-08-01

Full Text Available Repetitive behaviors with restricted interests is one of the core criteria for the diagnosis of autism spectrum disorder (ASD. Current pharmacotherapies that target the dopaminergic or serotonergic systems have limited effectiveness in treating repetitive behaviors. Previous research has demonstrated that administration of muscarinic cholinergic receptor (mAChR antagonists can exacerbate motor stereotypies while mAChR agonists reduce stereotypies. The present study determined whether the mAChR agonist, oxotremorine affected repetitive behaviors in the BTBR T+ tf/J (BTBR mouse model of autism. To test the effects of oxotremorine on repetitive behaviors, marble burying and grooming behavior were measured in BTBR mice and compared to that in C57BL/6J (B6 mice. The effects of oxotremorine on locomotor activity was also measured. Thirty minutes before each test, mice received an intraperitoneal injection of saline, 0.001 mg or 0.01 mg of oxotremorine methiodide. Saline- treated BTBR mice exhibited increased marble burying and self-grooming behavior compared to that of saline-treated B6 mice. Oxotremorine significantly reduced marble burying and self-grooming behavior in BTBR mice, but had no significant effect in B6 mice. In addition, oxotremorine did not affect locomotor activity in BTBR mice, but significantly reduced locomotor activity in B6 mice at the 0.01 mg dose. These findings demonstrate that activation of mAChRs reduces repetitive behavior in the BTBR mouse and suggest that treatment with a mAChR agonist may be effective in reducing repetitive behaviors in ASD.

Optimality based repetitive controller design for track-following servo system of optical disk drives.

Science.gov (United States)

Chen, Wentao; Zhang, Weidong

2009-10-01

In an optical disk drive servo system, to attenuate the external periodic disturbances induced by inevitable disk eccentricity, repetitive control has been used successfully. The performance of a repetitive controller greatly depends on the bandwidth of the low-pass filter included in the repetitive controller. However, owing to the plant uncertainty and system stability, it is difficult to maximize the bandwidth of the low-pass filter. In this paper, we propose an optimality based repetitive controller design method for the track-following servo system with norm-bounded uncertainties. By embedding a lead compensator in the repetitive controller, both the system gain at periodic signal's harmonics and the bandwidth of the low-pass filter are greatly increased. The optimal values of the repetitive controller's parameters are obtained by solving two optimization problems. Simulation and experimental results are provided to illustrate the effectiveness of the proposed method.

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.

Combined effect of repetitive work and cold on muscle function and fatigue.

Science.gov (United States)

Oksa, Juha; Ducharme, Michel B; Rintamäki, Hannu

2002-01-01

This study compared the effect of repetitive work in thermoneutral and cold conditions on forearm muscle electromyogram (EMG) and fatigue. We hypothesize that cold and repetitive work together cause higher EMG activity and fatigue than repetitive work only, thus creating a higher risk for overuse injuries. Eight men performed six 20-min work bouts at 25 degrees C (W-25) and at 5 degrees C while exposed to systemic (C-5) and local cooling (LC-5). The work was wrist flexion-extension exercise at 10% maximal voluntary contraction. The EMG activity of the forearm flexors and extensors was higher during C-5 (31 and 30%, respectively) and LC-5 (25 and 28%, respectively) than during W-25 (P forearm flexors at the end of W-25 was 15%. The corresponding values at the end of C-5 and LC-5 were 37% (P < 0.05 in relation to W-25) and 20%, respectively. Thus repetitive work in the cold causes higher EMG activity and fatigue than repetitive work in thermoneutral conditions.

Electrophysiological Repetition Effects in Persons with Mild Cognitive Impairment depend upon Working Memory Demand.

Science.gov (United States)

Broster, Lucas S; Jenkins, Shonna L; Holmes, Sarah D; Edwards, Matthew G; Jicha, Gregory A; Jiang, Yang

2018-05-07

Forms of implicit memory, including repetition effects, are preserved relative to explicit memory in clinical Alzheimer's disease. Consequently, cognitive interventions for persons with Alzheimer's disease have been developed that leverage this fact. However, despite the clinical robustness of behavioral repetition effects, altered neural mechanisms of repetition effects are studied as biomarkers of both clinical Alzheimer's disease and pre-morbid Alzheimer's changes in the brain. We hypothesized that the clinical preservation of behavioral repetition effects results in part from concurrent operation of discrete memory systems. We developed two experiments that included probes of emotional repetition effects differing in that one included an embedded working memory task. We found that neural repetition effects manifested in patients with amnestic mild cognitive impairment, the earliest form of clinical Alzheimer's disease, during emotional working memory tasks, but they did not manifest during the task that lacked the embedded working memory manipulation. Specifically, the working memory task evoked neural repetition effects in the P600 time-window, but the same neural mechanism was only minimally implicated in the task without a working memory component. We also found that group differences in behavioral repetition effects were smaller in the experiment with a working memory task. We suggest that cross-domain cognitive challenge can expose "defunct" neural capabilities of individuals with amnestic mild cognitive impairment. Copyright © 2018. Published by Elsevier Ltd.

Transcriptome analysis of Anopheles stephensi embryo using ...

Indian Academy of Sciences (India)

Germ band retraction (GBR) stage is one of the important stages during insect development. It is associated with an extensive epithelial morphogenesis and may also be pivotal in generation of morphological diversity in insects. Despite its importance, only a handful of studies report the transcriptome repertoire of this stage ...

Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

DEFF Research Database (Denmark)

Christensen, Mark Schram; Lundbye-Jensen, Jesper; Grey, Michael James

2010-01-01

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement...... and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over...... premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement....

Physiological responses to four hours of low-level repetitive work

DEFF Research Database (Denmark)

Garde, A Helene; Hansen, Åse Marie; Jensen, Bente R

2003-01-01

OBJECTIVES: The study investigated physiological responses to 4 hours of standardized low-level repetitive work. It was hypothesized that accumulative effects not observed after 1 hour could be found after 4 hours of repetitive work. METHODS: Ten healthy women performed intermittent (5 seconds + 5...... muscle activity during a mental reference task with low exerted force indicated attention-related muscle activity. Finally, it was indicated that repetitive work including high demands for attention is performed at the expense of the precision of the exerted force....... seconds) handgrip contractions at 10% of the maximal voluntary contraction combined with mental demands for concentration and attention. Muscle activity in the working forearm muscles, cardiovascular responses, and concentrations of biomarkers in biological fluids were recorded along with exerted force...

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.

Bacteria-induced morphogenesis of Ulva intestinalis and Ulva mutabilis (Chlorophyta): a contribution to the lottery theory.

Science.gov (United States)

Ghaderiardakani, Fatemeh; Coates, Juliet C; Wichard, Thomas

2017-08-01

The green marine macroalgae of the class Ulvophyceae (Ulvophytes) are common algae distributed worldwide particularly in intertidal areas, which play a key role in aquatic ecosystems. They are potentially valuable resources for food, animal feed and fuel but can also cause massive nuisance blooms. Members of Ulvaceae, like many other seaweeds, harbour a rich diversity of epiphytic bacteria with functions related to host growth and morphological development. In the absence of appropriate bacterially derived signals, germ cells of the genus Ulva develop into 'atypical' colonies consisting of undifferentiated cells with abnormal cell walls. This paper examines the specificity of bacteria-induced morphogenesis in Ulva, by cross-testing bacteria isolated from several Ulva species on two Ulva species, the emerging model system Ulva mutabilis and the prominent biofouler species Ulva intestinalis. We show that pairs of bacterial strains isolated from species other than U. mutabilis and U. intestinalis can fully rescue axenic plantlets generated either from U. mutabilis or U. intestinalis gametes. This laboratory-based study demonstrates that different compositions of microbial communities with similar functional characteristics can enable complete algal morphogenesis and thus supports the 'competitive lottery' theory for how symbiotic bacteria drive algal development. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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)

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

GPI-repetitive control for linear systems with parameter uncertainty / variation

Directory of Open Access Journals (Sweden)

John A. Cortés-Romero

2015-01-01

Full Text Available Robust repetitive control problems for uncertain linear systems have been considered by different approaches. This article proposes the use of Repetitive Control and Generalized Proportional Integral (GPI Control in a complementary fashion. The conditioning and coupling of these techniques has been done in a time discrete context. Repetitive control is a control technique, based on the internal model principle, which yields perfect asymptotic tracking and rejection of periodic signals. On the other hand, GPI control is established as a robust linear control system design technique that is able to reject structured time polynomial additive perturbation, in particular, parameter uncertainty that can be locally approximated by time polynomial signal. GPI control provides a suitable stability and robustness conditions for the proper Repetitive Control operation. A stability analysis is presented under the frequency response framework using plant samples for different parameter uncertainty conditions. We carry out some comparative stability analysis with other complementary control approaches that has been effective for this kind of task, enhancing a better robustness and an improved performance for the GPI case. Illustrative simulation examples are presented which validate the proposed approach.

Exploration of verbal repetition in people with dementia using an online symptom-tracking tool.

Science.gov (United States)

Reeve, Emily; Molin, Pierre; Hui, Amaris; Rockwood, Kenneth

2017-06-01

Online tools can be used by people with dementia and their caregivers to self-identify and track troubling symptoms, such as verbal repetition. We aimed to explore verbal repetition behaviors in people with dementia. Participants were recruited via an online resource for people with dementia and their caregivers. Respondents were instructed to complete information about symptoms that are most important to them for tracking over time. In this cross-sectional study, we analyzed data pertaining to individuals with dementia who had at least three symptoms selected for tracking. Of the 3,573 participants who began a user profile, 1,707 fulfilled criteria for analysis. Verbal repetition was identified as a treatment target in 807 respondents (47.3%). Verbal repetition was more frequent in individuals with mild dementia compared to those with moderate and severe dementia (57.2% vs. 36.0% and 39.9%, p < 0.01) and in those with Alzheimer's disease versus other dementias (65.2% vs. 29.7%, p < 0.001). Repetitive questioning was the most frequent type of verbal repetition (90.5% of individuals with verbal repetition). Verbal repetition was most strongly associated with difficulties operating gadgets/appliances (OR 3.65, 95%CI: 2.82-4.72), lack of interest and/or initiative (3.52: 2.84-4.36), misplacing or losing objects (3.25: 2.64-4.01), and lack of attention and/or concentration (2.62: 2.12-3.26). Verbal repetition is a common symptom in people at all stages of dementia but is most commonly targeted for monitoring and treatment effects in its mild stage. Much research is required to further elucidate the underlying mechanisms and the effect of different treatment strategies.

Quantifying repetitive speech in autism spectrum disorders and language impairment.

Science.gov (United States)

van Santen, Jan P H; Sproat, Richard W; Hill, Alison Presmanes

2013-10-01

We report on an automatic technique for quantifying two types of repetitive speech: repetitions of what the child says him/herself (self-repeats) and of what is uttered by an interlocutor (echolalia). We apply this technique to a sample of 111 children between the ages of four and eight: 42 typically developing children (TD), 19 children with specific language impairment (SLI), 25 children with autism spectrum disorders (ASD) plus language impairment (ALI), and 25 children with ASD with normal, non-impaired language (ALN). The results indicate robust differences in echolalia between the TD and ASD groups as a whole (ALN + ALI), and between TD and ALN children. There were no significant differences between ALI and SLI children for echolalia or self-repetitions. The results confirm previous findings that children with ASD repeat the language of others more than other populations of children. On the other hand, self-repetition does not appear to be significantly more frequent in ASD, nor does it matter whether the child's echolalia occurred within one (immediate) or two turns (near-immediate) of the adult's original utterance. Furthermore, non-significant differences between ALN and SLI, between TD and SLI, and between ALI and TD are suggestive that echolalia may not be specific to ALN or to ASD in general. One important innovation of this work is an objective fully automatic technique for assessing the amount of repetition in a transcript of a child's utterances. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Multidisciplinary Inquiry-Based Investigation Learning Using an Ex Ovo Chicken Culture Platform: Role of Vitamin A on Embryonic Morphogenesis

Science.gov (United States)

Buskohl, Philip R.; Gould, Russell A.; Curran, Susan; Archer, Shivaun D.; Butcher, Jonathan T.

2012-01-01

Embryonic development offers a unique perspective on the function of many biological processes because of embryos' heightened sensitivity to environmental factors. This hands-on lesson investigates the effects of elevated vitamin A on the morphogenesis of chicken embryos. The active form of vitamin A (retinoic acid) is applied to shell-less (ex…

Homeobox genes Msx-1 and Msx-2 are associated with induction and growth of skin appendages.

Science.gov (United States)

Noveen, A; Jiang, T X; Ting-Berreth, S A; Chuong, C M

1995-05-01

The mechanism involved in the morphogenesis of skin appendages is a fundamental issue underlying the development and healing of skin. To identify molecules involved in the induction and growth of skin appendages, we studied the expression of two homeobox genes, Msx-1 and Msx-2, during embryonic chicken skin development. We found that i) both Msx-1 and Msx-2 are early markers of epithelial placodes for skin appendages; ii) both Msx-1 and Msx-2 are expressed in the growing feather bud epithelia but not in the interbud epithelia; iii) although mostly overlapping, there are differences between the expression of the two Msx genes, Msx-1 being expressed more toward the anterior whereas Msx-2 is expressed more toward the distal feather bud; iv) there is no body-position-specific expression pattern as was observed for members of the Hox A-D clusters; v) in the feather follicle, Msx-1 and 2 are expressed in the collar and barb ridge epithelia, both regions of continuous cell proliferation; vi) when feather-bud growth was inhibited by forskolin, an activator of adenylyl cyclase, the expression of both genes was reduced. These results showed that Msx genes are specifically expressed in epithelial domains destined to become skin appendages. Its function in skin-appendage morphogenesis may be twofold, first in making epithelial cells competent to become skin appendages and, second, in making epithelial cells maintain their potential for continuous growth.

β-Catenin signaling regulates temporally discrete phases of anterior taste bud development

Science.gov (United States)

Thirumangalathu, Shoba; Barlow, Linda A.

2015-01-01

The sense of taste is mediated by multicellular taste buds located within taste papillae on the tongue. In mice, individual taste buds reside in fungiform papillae, which develop at mid-gestation as epithelial placodes in the anterior tongue. Taste placodes comprise taste bud precursor cells, which express the secreted factor sonic hedgehog (Shh) and give rise to taste bud cells that differentiate around birth. We showed previously that epithelial activation of β-catenin is the primary inductive signal for taste placode formation, followed by taste papilla morphogenesis and taste bud differentiation, but the degree to which these later elements were direct or indirect consequences of β-catenin signaling was not explored. Here, we define discrete spatiotemporal functions of β-catenin in fungiform taste bud development. Specifically, we show that early epithelial activation of β-catenin, before taste placodes form, diverts lingual epithelial cells from a taste bud fate. By contrast, β-catenin activation a day later within Shh+ placodes, expands taste bud precursors directly, but enlarges papillae indirectly. Further, placodal activation of β-catenin drives precocious differentiation of Type I glial-like taste cells, but not other taste cell types. Later activation of β-catenin within Shh+ precursors during papilla morphogenesis also expands taste bud precursors and accelerates Type I cell differentiation, but papilla size is no longer enhanced. Finally, although Shh regulates taste placode patterning, we find that it is dispensable for the accelerated Type I cell differentiation induced by β-catenin. PMID:26525674

Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

Directory of Open Access Journals (Sweden)

Rajiv Sainath

Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

Eye and heart morphogenesis are dependent on melatonin signaling in chick embryos.

Science.gov (United States)

Nogueira, Renato C; Sampaio, Lucia de Fatima S

2017-10-15

Calmodulin is vital for chick embryos morphogenesis in the incubation time 48-66 h when the rudimentary C-shaped heart attains an S-shaped pattern and the optic vesicles develop into optic cups. Melatonin is in the extraembryonic yolk sac of the avian egg; melatonin binds calmodulin. The aim of this study was to investigate the function of melatonin in the formation of the chick embryo optic cups and S-shaped heart, by pharmacological methods and immunoassays. Mel1a melatonin receptor immunofluorescence was distributed in the optic cups and rudimentary hearts. We separated embryonated chicken eggs at 48 h of incubation into basal, control and drug-treated groups, with treatment applied in the egg air sac. At 66 h of incubation, embryos were excised from the eggs and analyzed. Embryos from the basal, control (distilled water), melatonin and 6-chloromelatonin (melatonin receptor agonist) groups had regular optic cups and an S-shaped heart, while those from the calmidazolium (calmodulin inhibitor) group did not. Embryos from the luzindole (melatonin receptor antagonist) and prazosin (Mel1c melatonin receptor antagonist) groups did not have regular optic cups. Embryos from the 4-P-PDOT (Mel1b melatonin receptor antagonist) group did not have an S-shaped heart. Previous application of the melatonin, 6-chloromelatonin or forskolin (adenylate cyclase enhancer) prevented the abnormal appearance of chick embryos from the calmidazolium, luzindole, prazosin and 4-P-PDOT groups. However, 6-chloromelatonin and forskolin only partially prevented the development of defective eye cups in embryos from the calmidazolium group. The results suggested that melatonin modulates chick embryo morphogenesis via calmodulin and membrane receptors. © 2017. Published by The Company of Biologists Ltd.

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

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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

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

Repetitive Behavior in Rubinstein-Taybi Syndrome: Parallels with Autism Spectrum Phenomenology

Science.gov (United States)

Waite, Jane; Moss, Joanna; Beck, Sarah R.; Richards, Caroline; Nelson, Lisa; Arron, Kate; Burbidge, Cheryl; Berg, Katy; Oliver, Chris

2015-01-01

Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein-Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals…

Repetitive, small-bore two-stage light gas gun

International Nuclear Information System (INIS)

Combs, S.K.; Foust, C.R.; Fehling, D.T.; Gouge, M.J.; Milora, S.L.

1991-01-01

A repetitive two-stage light gas gun for high-speed pellet injection has been developed at Oak Ridge National Laboratory. In general, applications of the two-stage light gas gun have been limited to only single shots, with a finite time (at least minutes) needed for recovery and preparation for the next shot. The new device overcomes problems associated with repetitive operation, including rapidly evacuating the propellant gases, reloading the gun breech with a new projectile, returning the piston to its initial position, and refilling the first- and second-stage gas volumes to the appropriate pressure levels. In addition, some components are subjected to and must survive severe operating conditions, which include rapid cycling to high pressures and temperatures (up to thousands of bars and thousands of kelvins) and significant mechanical shocks. Small plastic projectiles (4-mm nominal size) and helium gas have been used in the prototype device, which was equipped with a 1-m-long pump tube and a 1-m-long gun barrel, to demonstrate repetitive operation (up to 1 Hz) at relatively high pellet velocities (up to 3000 m/s). The equipment is described, and experimental results are presented. 124 refs., 6 figs., 5 tabs

Tooth Morphogenesis and FGF4 Expression During Development of Molar Tooth in Three Muroid Rodents: Calomyscus elburzensis (Calomyscidae), Mesocricetus auratus (Cricetidae) and Mus musculus (Muridae).

Science.gov (United States)

Hamidi, Kordiyeh; Darvish, Jamshid; Matin, Maryam M; Javanmard, Athar Sadat; Kilpatrick, C William

2017-12-01

To date, no studies have examined the tooth formation during developmental stages of brush-tailed mice (Calomyscidae) and true hamsters (Cricetidae). Herein, we compared the timing of tooth morphogenesis and FGF4 expression pattern during development of the first lower molar in Goodwin's brush-tailed mouse, Calomyscus elburzensis with two other muroid rodents; the house mouse, Mus musculus (Muridae), model organism for tooth morphogenesis, and the golden hamster, Mesocricetus auratus which shares great similarities in cusp pattern with brush-tailed mice. All three species were bred in captivity and developing embryos were isolated at different embryonic days (E). Histological evaluation of lower molars was performed and spatiotemporal pattern of FGF4 expression was determined by immunohistochemistry. Results indicated that morphogenesis of the tooth cusps starts at the beginning of the cap stage of the first lower molar (E14 in house mouse, about E11.5 in golden hamster and E22 in Goodwin's brush-tailed mouse). During the cap to bell stage (E15 in house mouse, E12 in golden hamster and at about E24 in Goodwin's brush-tailed mouse), a decrease in the expression of FGF4 was observed in the mesenchyme, except for the cusp tips. According to our observations, the developmental process of the first lower molar formation in Goodwin's brush-tailed mouse began much later as compared with the other two species. Despite the differences in the temporal pattern of molar development between these three members of the same superfamily (Muroidea), the correlation in the expression of FGF4 with specific stages of tooth morphogenesis supported its regulatory function. Anat Rec, 300:2138-2149, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

Effects of slow repetitive transcranial magnetic stimulation in patients with corticobasal syndrome.

Science.gov (United States)

Civardi, Carlo; Pisano, Fabrizio; Delconte, Carmen; Collini, Alessandra; Monaco, Francesco

2015-06-01

Corticobasal syndrome is characterized by asymmetric cortical sensorimotor dysfunction and parkinsonism; an altered cortical excitability has been reported. We explored with transcranial magnetic stimulation the motor cortical excitability in corticobasal syndrome, and the effects of slow repetitive transcranial magnetic stimulation. With transcranial magnetic stimulation, we studied two corticobasal syndrome patients. We determined bilaterally from the first dorsal interosseous muscle: relaxed threshold, and contralateral and ipsilateral silent period. We also evaluated the contralateral silent period after active/sham slow repetitive transcranial magnetic stimulation on the most affected side. At T0 the silent period was bilaterally short. On the most affected side, active slow repetitive transcranial magnetic stimulation induced a short lasting prolongation of the contralateral silent period. In corticobasal syndrome, transcranial magnetic stimulation showed a reduction cortical inhibitory phenomenon potentially reversed transiently by slow repetitive transcranial magnetic stimulation.

Dissociating mere exposure and repetition priming as a function of word type.

Science.gov (United States)

Butler, Laurie T; Berry, Dianne C; Helman, Shaun

2004-07-01

The mere exposure effect is defined as enhanced attitude toward a stimulus that has been repeatedly exposed. Repetition priming is defined as facilitated processing of a previously exposed stimulus. We conducted a direct comparison between the two phenomena to test the assumption that the mere exposure effect represents an example of repetition priming. In two experiments, having studied a set of words or nonwords, participants were given a repetition priming task (perceptual identification) or one of two mere exposure (affective liking or preference judgment) tasks. Repetition priming was obtained for both words and nonwords, but only nonwords produced a mere exposure effect. This demonstrates a key boundary for observing the mere exposure effect, one not readily accommodated by a perceptual representation systems (Tulving & Schacter, 1990) account, which assumes that both phenomena should show some sensitivity to nonwords and words.

Sustainment of spherical tokamak by means of repetitive injection of compact torus plasma

International Nuclear Information System (INIS)

Shimamura, Shin; Matsura, Ken; Takahashi, Tsutomu; Nogi, Yasuyuki

2000-01-01

Sustainment of spherical tokamak (S.T.) has been studied. A compact torus (C.T.) plasma was injected into confinement region by magnetized coaxial gun. For start-up and sustainment of large main spherical tokamak, single pulsed injection of small C.T. is not sufficient in many cases. C.T.plasma injection of high repetition rate is required. For this purpose magnetized coaxial gun was driven with high repetition rate current. The first injected C.T. plasma could start-up S.T. without other help. The repetitive C.T. injection grew and sustained the S.T. plasma. A CCD camera with fast gated image intensifier took a cross sectional view of S.T. during the repetitive C.T. injection. (author)

PCR amplification of repetitive sequences as a possible approach in relative species quantification

DEFF Research Database (Denmark)

Ballin, Nicolai Zederkopff; Vogensen, Finn Kvist; Karlsson, Anders H

2012-01-01

Abstract Both relative and absolute quantifications are possible in species quantification when single copy genomic DNA is used. However, amplification of single copy genomic DNA does not allow a limit of detection as low as one obtained from amplification of repetitive sequences. Amplification...... of repetitive sequences is therefore frequently used in absolute quantification but problems occur in relative quantification as the number of repetitive sequences is unknown. A promising approach was developed where data from amplification of repetitive sequences were used in relative quantification of species...... to relatively quantify the amount of chicken DNA in a binary mixture of chicken DNA and pig DNA. However, the designed PCR primers lack the specificity required for regulatory species control....

Design and implementation of fast charging circuit for repetitive compact torus injector

International Nuclear Information System (INIS)

Onchi, T.; McColl, D.; Dreval, M.; Wolfe, S.; Xiao, C.; Hirose, A.

2014-01-01

A novel circuit for compact torus (CT) injector operated at high repetition rates has been developed. The core technology adopted in the present work is to charge a large storage capacitor bank and quickly charge the CT capacitor bank through a stack of insulated-gate bipolar transistors (IGBTs). A system consisting of IGBTs and slow banks for the repetitive operation has been developed and installed for each discharge circuit of the University of Saskatchewan Compact Torus Injector (USCTI). A repetition rate up to 1.7 Hz and a burst of 8 CTs have been achieved

Universal data compression and repetition times

NARCIS (Netherlands)

Willems, Frans M J

1989-01-01

A new universal data compression algorithm is described. This algorithm encodes L source symbols at a time. For the class of binary stationary sources, its rate does not exceed [formula omitted] [formula omitted] bits per source symbol. In our analysis, a property of repetition times turns out to be

Independent and additive repetition priming of motion direction and color in visual search.

Science.gov (United States)

Kristjánsson, Arni

2009-03-01

Priming of visual search for Gabor patch stimuli, varying in color and local drift direction, was investigated. The task relevance of each feature varied between the different experimental conditions compared. When the target defining dimension was color, a large effect of color repetition was seen as well as a smaller effect of the repetition of motion direction. The opposite priming pattern was seen when motion direction defined the target--the effect of motion direction repetition was this time larger than for color repetition. Finally, when neither was task relevant, and the target defining dimension was the spatial frequency of the Gabor patch, priming was seen for repetition of both color and motion direction, but the effects were smaller than in the previous two conditions. These results show that features do not necessarily have to be task relevant for priming to occur. There is little interaction between priming following repetition of color and motion, these two features show independent and additive priming effects, most likely reflecting that the two features are processed at separate processing sites in the nervous system, consistent with previous findings from neuropsychology & neurophysiology. The implications of the findings for theoretical accounts of priming in visual search are discussed.

Gene Expression in the Third Dimension: The ECM-nucleus Connection

Energy Technology Data Exchange (ETDEWEB)

Spencer, Virginia A; Xu, Ren; Bissell, Mina

2009-10-01

Decades ago, we and others proposed that the dynamic interplay between a cell and its surrounding environment dictates cell phenotype and tissue structure. Whereas much has been discovered about the effects of extracellular matrix molecules on cell growth and tissue specific gene expression, the nuclear mechanisms through which these molecules promote these physiological events remain unknown. Using mammary epithelial cells as a model, the purpose of this review is to discuss how the extracellular matrix influences nuclear structure and function in a three-dimensional context to promote epithelial morphogenesis and function in the mammary gland.

High-repetition-rate hydrogen chamber: Preliminary studies; Chambre a hydrogene a haut taux de repetition: Etudes preliminaires

Energy Technology Data Exchange (ETDEWEB)

NONE

1967-01-01

This report is a conclusion to the tests realised with an experimental bubbles chamber in view to study the possibilities to increase the repetition rate. The more important parameters (the evolution of the bubbles, the expansion system) are considered in a theoretical way. Then the hardware is described. To end, experimental results are compared with the first evaluations. The calculations and the experimentation are against an oscillation system for the expansion. A system with a locking is to he considered. (authors) [French] Ce rapport est une conclusion aux essais realises avec une chambre a bulles experimentale en vue d'etudier les possibilites d'accroitre les taux de repetition. Les parametres les plus importants (evolution des bulles, mecanique de la detente) sont etudies par voie theorique. Puis l'appareillage est decrit. Enfin, les resultats experimentaux sont compares aux evaluations donnees au debut. Ces calculs et cette experimentation ne sont pas en faveur d'un systeme oscillant pour la detente et il faut envisager un systeme avec verrouillage. (auteurs)

Macroalgal Morphogenesis Induced by Waterborne Compounds and Bacteria in Coastal Seawater.

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Jan Grueneberg

Full Text Available Axenic gametes of the marine green macroalga Ulva mutabilis Føyn (Ria Formosa, locus typicus exhibit abnormal development into slow-growing callus-like colonies with aberrant cell walls. Under laboratory conditions, it was previously demonstrated that all defects in growth and thallus development can be completely abolished when axenic gametes are inoculated with a combination of two specific bacterial strains originally identified as Roseobacter sp. strain MS2 and Cytophaga sp. strain MS6. These bacteria release diffusible morphogenetic compounds (= morphogens, which act similar to cytokinin and auxin. To investigate the ecological relevance of the waterborne bacterial morphogens, seawater samples were collected in the Ria Formosa lagoon (Algarve, Southern Portugal at 20 sampling sites and tidal pools to assess their morphogenetic effects on the axenic gametes of U. mutabilis. Specifically the survey revealed that sterile-filtered seawater samples can completely recover growth and morphogenesis of U. mutabilis under axenic conditions. Morphogenetic activities of free-living and epiphytic bacteria isolated from the locally very abundant Ulva species (i.e., U. rigida were screened using a multiwell-based testing system. The most represented genera isolated from U. rigida were Alteromonas, Pseudoalteromonas and Sulfitobacter followed by Psychrobacter and Polaribacter. Several naturally occurring bacterial species could emulate MS2 activity (= induction of cell divisions regardless of taxonomic affiliation, whereas the MS6 activity (= induction of cell differentiation and cell wall formation was species-specific and is probably a feature of difficult-to-culture bacteria. Interestingly, isolated bacteroidetes such as Algoriphagus sp. and Polaribacter sp. could individually trigger complete Ulva morphogenesis and thus provide a novel mode of action for bacterial-induced algal development. This study also highlights that the accumulation of algal

Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement Cell Morphogenesis.

Science.gov (United States)

Belteton, Samuel A; Sawchuk, Megan G; Donohoe, Bryon S; Scarpella, Enrico; Szymanski, Daniel B

2018-01-01

The leaf epidermis is a biomechanical shell that influences the size and shape of the organ. Its morphogenesis is a multiscale process in which nanometer-scale cytoskeletal protein complexes, individual cells, and groups of cells pattern growth and define macroscopic leaf traits. Interdigitated growth of neighboring cells is an evolutionarily conserved developmental strategy. Understanding how signaling pathways and cytoskeletal proteins pattern cell walls during this form of tissue morphogenesis is an important research challenge. The cellular and molecular control of a lobed cell morphology is currently thought to involve PIN-FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin gradients. Auxin gradients were proposed to function across cell boundaries to encode stable offset patterns of cortical microtubules and actin filaments between adjacent cells. Many models suggest that long-lived microtubules along the anticlinal cell wall generate local cell wall heterogeneities that restrict local growth and specify the timing and location of lobe formation. Here, we used Arabidopsis ( Arabidopsis thaliana ) reverse genetics and multivariate long-term time-lapse imaging to test current cell shape control models. We found that neither PIN proteins nor long-lived microtubules along the anticlinal wall predict the patterns of lobe formation. In fields of lobing cells, anticlinal microtubules are not correlated with cell shape and are unstable at the time scales of cell expansion. Our analyses indicate that anticlinal microtubules have multiple functions in pavement cells and that lobe initiation is likely controlled by complex interactions among cell geometry, cell wall stress patterns, and transient microtubule networks that span the anticlinal and periclinal walls. © 2018 American Society of Plant Biologists. All Rights Reserved.

Basolateral BMP signaling in polarized epithelial cells.

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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.

Iodine laser of high efficiency and fast repetition rate

Energy Technology Data Exchange (ETDEWEB)

Hohla, K; Witte, K J

1976-07-01

The scaling laws of an iodine laser of high efficiency and fast repetition rate are reported. The laser is pumped with a new kind of low pressure Hg-UV-lamps which convert 32% of the electrical input in UV-light in the absorption band of the iodine laser and which can be fired up to 100 Hz. Details of a 10 kJ/1 nsec system as dimensions, energy density, repetition rate, flow velocity, gas composition and gas pressure and the overall efficiency are given which is expected to be about 2%.

Heavy-duty high-repetition-rate generators

NARCIS (Netherlands)

Heesch, van E.J.M.; Yan, K.; Pemen, A.J.M.

2002-01-01

We present our results on high-power repetitive pulse sources for continuous operation. Two 1-10-kW systems using advanced spark gap technology and a transmission line transformer have been tested for several hundred hours at a 60-MW pulse level. High reliability and above 90% overall efficiency are

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.

Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.

Science.gov (United States)

D'Arcangelo, G; Panuccio, G; Tancredi, V; Avoli, M

2005-01-01

Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg(2+)-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308-9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 microM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2-10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency

Mechanical basis of morphogenesis and convergent evolution of spiny seashells

KAUST Repository

Chirat, R.; Moulton, D. E.; Goriely, A.

2013-01-01

Convergent evolution is a phenomenon whereby similar traits evolved independently in not closely related species, and is often interpreted in functional terms. Spines in mollusk seashells are classically interpreted as having repeatedly evolved as a defense in response to shell-crushing predators. Here we consider the morphogenetic process that shapes these structures and underlies their repeated emergence. We develop a mathematical model for spine morphogenesis based on the mechanical interaction between the secreting mantle edge and the calcified shell edge to which the mantle adheres during shell growth. It is demonstrated that a large diversity of spine structures can be accounted for through small variations in control parameters of this natural mechanical process. This physical mechanism suggests that convergent evolution of spines can be understood through a generic morphogenetic process, and provides unique perspectives in understanding the phenotypic evolution of this second largest phylum in the animal kingdom.

Mechanical basis of morphogenesis and convergent evolution of spiny seashells

KAUST Repository

Chirat, R.

2013-03-25

Convergent evolution is a phenomenon whereby similar traits evolved independently in not closely related species, and is often interpreted in functional terms. Spines in mollusk seashells are classically interpreted as having repeatedly evolved as a defense in response to shell-crushing predators. Here we consider the morphogenetic process that shapes these structures and underlies their repeated emergence. We develop a mathematical model for spine morphogenesis based on the mechanical interaction between the secreting mantle edge and the calcified shell edge to which the mantle adheres during shell growth. It is demonstrated that a large diversity of spine structures can be accounted for through small variations in control parameters of this natural mechanical process. This physical mechanism suggests that convergent evolution of spines can be understood through a generic morphogenetic process, and provides unique perspectives in understanding the phenotypic evolution of this second largest phylum in the animal kingdom.

A computational framework for 3D mechanical modeling of plant morphogenesis with cellular resolution.

Directory of Open Access Journals (Sweden)

Frédéric Boudon

2015-01-01

Full Text Available The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth.

High repetition rate intense ion beam source

International Nuclear Information System (INIS)

Hammer, D.A.; Glidden, S.C.; Noonan, B.

1992-01-01

This final report describes a ≤ 150kV, 40kA, 100ns high repetition rate pulsed power system and intense ion beam source which is now in operation at Cornell University. Operation of the Magnetically-controlled Anode Plasma (MAP) ion diode at > 100Hz (burst mode for up to 10 pulse bursts) provides an initial look at repetition rate limitations of both the ion diode and beam diagnostics. The pulsed power systems are capable of ≥ 1kHz operation (up to 10 pulse bursts), but ion diode operation was limited to ∼100Hz because of diagnostic limitations. By varying MAP diode operating parameters, ion beams can be extracted at a few 10s of keV or at up to 150keV, the corresponding accelerating gap impedance ranging from about 1Ω to about 10Ω. The ability to make hundreds of test pulses per day at an average repetition rate of about 2 pulses per minute permits statistical analysis of diode operation as a function of various parameters. Most diode components have now survived more than 10 4 pulses, and the design and construction of the various pulsed power components of the MAP diode which have enabled us to reach this point are discussed. A high speed data acquisition system and companion analysis software capable of acquiring pulse data at 1ms intervals (in bursts of up to 10 pulses) and processing it in ≤ min is described

MIMICRY, DIFFERENCE AND REPETITION

Directory of Open Access Journals (Sweden)

Marcelo Mendes de Souza

2008-07-01

Full Text Available This article addresses Homi K. Bhabha’s concept of mimicry in a broader context, other than that of cultural studies and post-colonial studies, bringing together other concepts, such as that of Gilles Deleuze in Difference and repetition, among other texts, and other names, such as Silviano Santiago, Jorge Luís Borges, Franz Kafka and Giorgio Agamben. As a partial conclusion, the article intends to oppose Bhabha’s freudian-marxist view to Five propositions on Psychoanalysis (1973, Gilles Deleuze’s text about Psychoanalysis published right after his book The Anti-Oedipus.

Neurobehavioural Correlates of Abnormal Repetitive Behaviour

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R. A. Ford

1991-01-01

Full Text Available Conditions in which echolalia and echopraxia occur are reviewed, followed by an attempt to elicit possible mechanisms of these phenomena. A brief description of stereotypical and perseverative behaviour and obsessional phenomena is given. It is suggested that abnormal repetitive behaviour may occur partly as a result of central dopaminergic dysfunction.

Laterality of repetitive finger movement performance and clinical features of Parkinson's disease.

Science.gov (United States)

Stegemöller, Elizabeth; Zaman, Andrew; MacKinnon, Colum D; Tillman, Mark D; Hass, Chris J; Okun, Michael S

2016-10-01

Impairments in acoustically cued repetitive finger movement often emerge at rates near to and above 2Hz in persons with Parkinson's Disease (PD) in which some patients move faster (hastening) and others move slower (bradykinetic). The clinical features impacting this differential performance of repetitive finger movement remain unknown. The purpose of this study was to compare repetitive finger movement performance between the more and less affected side, and the difference in clinical ratings among performance groups. Forty-one participants diagnosed with idiopathic PD completed an acoustically cued repetitive finger movement task while "on" medication. Eighteen participants moved faster, 10 moved slower, and 13 were able to maintain the appropriate rate at rates above 2Hz. Clinical measures of laterality, disease severity, and the UPDRS were obtained. There were no significant differences between the more and less affected sides regardless of performance group. Comparison of disease severity, tremor, and rigidity among performance groups revealed no significant differences. Comparison of posture and postural instability scores revealed that the participants that demonstrated hastening had worse posture and postural instability scores. Consideration of movement rate during the clinical evaluation of repetitive finger movement may provide additional insight into varying disease features in persons with PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Longer repetition duration increases muscle activation and blood lactate response in matched resistance training protocols

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Hugo Cesar Martins-Costa

2016-03-01

Full Text Available Abstract This study analyzed the effect of different repetition durations on electromyographic and blood lactate responses of the bench press exercise. Fifteen recreationally trained male volunteers completed two training protocols, matched for intensity (% one-repetition maximum; 1RM, number of sets, number of repetitions, and rest intervals. One of the protocols was performed with a repetition duration of 4 s (2 s concentric: 2 s eccentric; 2:2 protocol, whereas the second protocol had a repetition duration of 6 s (2 s concentric: 4 s eccentric; 2:4 protocol. The results showed higher normalized integrated electromyography (pectoralis major and triceps brachii for the 2:4 protocol. Blood lactate concentration was also higher in the 2:4 protocol across all sets. These results show that adding 2 s to the eccentric action in matched training protocols increases muscle activation and blood lactate response, which reinforces the notion that increasing repetition duration is an alternative load progression in resistance training.

Structure-function analysis of STRUBBELIG, an Arabidopsis atypical receptor-like kinase involved in tissue morphogenesis.

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Prasad Vaddepalli

Full Text Available Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis.

Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.

Science.gov (United States)

Prudencio, Mercedes; Gonzales, Patrick K; Cook, Casey N; Gendron, Tania F; Daughrity, Lillian M; Song, Yuping; Ebbert, Mark T W; van Blitterswijk, Marka; Zhang, Yong-Jie; Jansen-West, Karen; Baker, Matthew C; DeTure, Michael; Rademakers, Rosa; Boylan, Kevin B; Dickson, Dennis W; Petrucelli, Leonard; Link, Christopher D

2017-09-01

Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD. © The Author 2017. Published by Oxford University Press.

SAMA: A Method for 3D Morphological Analysis.

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Tessie Paulose

Full Text Available Three-dimensional (3D culture models are critical tools for understanding tissue morphogenesis. A key requirement for their analysis is the ability to reconstruct the tissue into computational models that allow quantitative evaluation of the formed structures. Here, we present Software for Automated Morphological Analysis (SAMA, a method by which epithelial structures grown in 3D cultures can be imaged, reconstructed and analyzed with minimum human intervention. SAMA allows quantitative analysis of key features of epithelial morphogenesis such as ductal elongation, branching and lumen formation that distinguish different hormonal treatments. SAMA is a user-friendly set of customized macros operated via FIJI (http://fiji.sc/Fiji, an open-source image analysis platform in combination with a set of functions in R (http://www.r-project.org/, an open-source program for statistical analysis. SAMA enables a rapid, exhaustive and quantitative 3D analysis of the shape of a population of structures in a 3D image. SAMA is cross-platform, licensed under the GPLv3 and available at http://montevil.theobio.org/content/sama.

Nonword Repetition and Vocabulary Knowledge as Predictors of Children's Phonological and Semantic Word Learning.

Science.gov (United States)

Adlof, Suzanne M; Patten, Hannah

2017-03-01

This study examined the unique and shared variance that nonword repetition and vocabulary knowledge contribute to children's ability to learn new words. Multiple measures of word learning were used to assess recall and recognition of phonological and semantic information. Fifty children, with a mean age of 8 years (range 5-12 years), completed experimental assessments of word learning and norm-referenced assessments of receptive and expressive vocabulary knowledge and nonword repetition skills. Hierarchical multiple regression analyses examined the variance in word learning that was explained by vocabulary knowledge and nonword repetition after controlling for chronological age. Together with chronological age, nonword repetition and vocabulary knowledge explained up to 44% of the variance in children's word learning. Nonword repetition was the stronger predictor of phonological recall, phonological recognition, and semantic recognition, whereas vocabulary knowledge was the stronger predictor of verbal semantic recall. These findings extend the results of past studies indicating that both nonword repetition skill and existing vocabulary knowledge are important for new word learning, but the relative influence of each predictor depends on the way word learning is measured. Suggestions for further research involving typically developing children and children with language or reading impairments are discussed.

Developmental toxicity assessment of common excipients using a stem cell-based in vitro morphogenesis model.

Science.gov (United States)

Yuan, Chloe J; Marikawa, Yusuke

2017-11-01

Various chemical compounds can inflict developmental toxicity when sufficiently high concentrations are exposed to embryos at the critical stages of development. Excipients, such as coloring agents and preservatives, are pharmacologically inactive ingredients that are included in various medications, foods, and cosmetics. However, concentrations that may adversely affect embryo development are largely unknown for most excipients. Here, the lowest observed adverse effect level (LOAEL) to inflict developmental toxicity was assessed for three coloring agents (allura red, brilliant blue, and tartrazine) and three preservatives (butylated hydroxyanisole, metabisulfite, and methylparaben). Adverse impact of a compound exposure was determined using the stem cell-based in vitro morphogenesis model, in which three-dimensional cell aggregates, or embryoid bodies (EBs), recapitulate embryonic processes of body axis elongation and patterning. LOAEL to impair EB morphogenesis was 200 μM for methylparaben, 400 μM for butylated hydroxyanisole, 600 μM for allura red and brilliant blue, and 1000 μM for metabisulfite. Gene expression analyses of excipient-treated EBs revealed that butylated hydroxyanisole and methylparaben significantly altered profiles of developmental regulators involved in axial elongation and patterning of the body. The present study may provide a novel in vitro approach to investigate potential developmental toxicity of common excipients with mechanistic insights. Copyright © 2017 Elsevier Ltd. All rights reserved.

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...

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....

High-speed repetitive pellet injector prototype for magnetic confinement fusion devices

International Nuclear Information System (INIS)

Frattolillo, A.; Gasparotto, M.; Migliori, S.; Angelone, G.; Baldarelli, M.; Scaramuzzi, F.; Ronci, G.; Reggiori, A.; Riva, G.; Carlevaro, R.; Daminelli, G.B.

1992-01-01

The design of a test facility aimed at demonstrating the feasibility of high-speed repetitive acceleration of solid D 2 pellets for fusion applications, developed in a collaboration between Oak Ridge National Laboratory and ENEA Frascati, is presented. The results of tests performed at the CNPM/CNR on the piston wear in a repetitively operating two-stage gun are also reported

Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

Science.gov (United States)

Kuzin, Boris A; Nikitina, Ekaterina A; Cherezov, Roman O; Vorontsova, Julia E; Slezinger, Mikhail S; Zatsepina, Olga G; Simonova, Olga B; Enikolopov, Grigori N; Savvateeva-Popova, Elena V

2014-01-01

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.