WorldWideScience

Sample records for plate cilia architecture

  1. Foxj1 regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling

    Science.gov (United States)

    Cruz, Catarina; Ribes, Vanessa; Kutejova, Eva; Cayuso, Jordi; Lawson, Victoria; Norris, Dominic; Stevens, Jonathan; Davey, Megan; Blight, Ken; Bangs, Fiona; Mynett, Anita; Hirst, Elizabeth; Chung, Rachel; Balaskas, Nikolaos; Brody, Steven L.; Marti, Elisa; Briscoe, James

    2010-01-01

    Sonic hedgehog signalling is essential for the embryonic development of many tissues including the central nervous system, where it controls the pattern of cellular differentiation. A genome-wide screen of neural progenitor cells to evaluate the Shh signalling-regulated transcriptome identified the forkhead transcription factor Foxj1. In both chick and mouse Foxj1 is expressed in the ventral midline of the neural tube in cells that make up the floor plate. Consistent with the role of Foxj1 in the formation of long motile cilia, floor plate cells produce cilia that are longer than the primary cilia found elsewhere in the neural tube, and forced expression of Foxj1 in neuroepithelial cells is sufficient to increase cilia length. In addition, the expression of Foxj1 in the neural tube and in an Shh-responsive cell line attenuates intracellular signalling by decreasing the activity of Gli proteins, the transcriptional mediators of Shh signalling. We show that this function of Foxj1 depends on cilia. Nevertheless, floor plate identity and ciliogenesis are unaffected in mouse embryos lacking Foxj1 and we provide evidence that additional transcription factors expressed in the floor plate share overlapping functions with Foxj1. Together, these findings identify a novel mechanism that modifies the cellular response to Shh signalling and reveal morphological and functional features of the amniote floor plate that distinguish these cells from the rest of the neuroepithelium. PMID:21098568

  2. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans.

    Science.gov (United States)

    Mukhopadhyay, Saikat; Lu, Yun; Shaham, Shai; Sengupta, Piali

    2008-05-01

    Nonmotile primary cilia are sensory organelles composed of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis, and signaling protein targeting and localization via as yet poorly understood mechanisms. Here, we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory signaling results in alteration of axoneme length and expansion of a membraneous structure, thereby altering the topological distribution of a subset of ciliary transmembrane signaling molecules. Signaling-regulated alteration of ciliary structures can be bypassed by modulation of intracellular cGMP or calcium levels and requires kinesin-II-driven intraflagellar transport (IFT), as well as BBS- and RAB8-related proteins. Our results suggest that compensatory mechanisms in response to altered levels of sensory activity modulate AWB cilia architecture, revealing remarkable plasticity in the regulation of cilia structure.

  3. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Directory of Open Access Journals (Sweden)

    Rosemary C Challis

    Full Text Available We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII, a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found, similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  4. A prefoldin-associated WD-repeat protein (WDR92) is required for the correct architectural assembly of motile cilia

    Science.gov (United States)

    Patel-King, Ramila S.; King, Stephen M.

    2016-01-01

    WDR92 is a highly conserved WD-repeat protein that has been proposed to be involved in apoptosis and also to be part of a prefoldin-like cochaperone complex. We found that WDR92 has a phylogenetic signature that is generally compatible with it playing a role in the assembly or function of specifically motile cilia. To test this hypothesis, we performed an RNAi-based knockdown of WDR92 gene expression in the planarian Schmidtea mediterranea and were able to achieve a robust reduction in mRNA expression to levels undetectable under our standard RT-PCR conditions. We found that this treatment resulted in a dramatic reduction in the rate of organismal movement that was caused by a switch in the mode of locomotion from smooth, cilia-driven gliding to muscle-based, peristaltic contractions. Although the knockdown animals still assembled cilia of normal length and in similar numbers to controls, these structures had reduced beat frequency and did not maintain hydrodynamic coupling. By transmission electron microscopy we observed that many cilia had pleiomorphic defects in their architecture, including partial loss of dynein arms, incomplete closure of the B-tubule, and occlusion or replacement of the central pair complex by accumulated electron-dense material. These observations suggest that WDR92 is part of a previously unrecognized cytoplasmic chaperone system that is specifically required to fold key components necessary to build motile ciliary axonemes. PMID:26912790

  5. Cilia Dysfunction in Lung Disease

    Science.gov (United States)

    Tilley, Ann E.; Walters, Matthew S.; Shaykhiev, Renat; Crystal, Ronald G.

    2015-01-01

    A characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes comprised of microtubules and dynein arms, which provide ATP-driven motility. In the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. The prototypical disorder of respiratory cilia is primary ciliary dyskinesia, an inherited disorder that leads to impaired mucociliary clearance, repeated chest infections, and progressive destruction of lung architecture. Numerous acquired lung diseases are also marked by abnormalities in both cilia structure and function. In this review we summarize current knowledge regarding airway ciliated cells and cilia, how they function to maintain a healthy epithelium, and how disorders of cilia structure and function contribute to inherited and acquired lung disease. PMID:25386990

  6. Cilia in vertebrate left-right patterning.

    Science.gov (United States)

    Dasgupta, Agnik; Amack, Jeffrey D

    2016-12-19

    Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

  7. Small GTPases and cilia.

    Science.gov (United States)

    Li, Yujie; Hu, Jinghua

    2011-01-01

    Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane- and cytoskeleton-related cellular processes. Recently, mounting evidences have highlighted the role of various small GTPases, including the members in Arf/Arl, Rab, and Ran subfamilies, in cilia formation and function. Once overlooked as an evolutionary vestige, the primary cilium has attracted more and more attention in last decade because of its role in sensing various extracellular signals and the association between cilia dysfunction and a wide spectrum of human diseases, now called ciliopathies. Here we review recent advances about the function of small GTPases in the context of cilia, and the correlation between the functional impairment of small GTPases and ciliopathies. Understanding of these cellular processes is of fundamental importance for broadening our view of cilia development and function in normal and pathological states and for providing valuable insights into the role of various small GTPases in disease processes, and their potential as therapeutic targets.

  8. Assembly of primary cilia

    DEFF Research Database (Denmark)

    Pedersen, Lotte B; Veland, Iben R; Schrøder, Jacob M

    2008-01-01

    in primary cilia assembly or function have been associated with a panoply of disorders and diseases, including polycystic kidney disease, left-right asymmetry defects, hydrocephalus, and Bardet Biedl Syndrome. Here we provide an up-to-date review focused on the molecular mechanisms involved in the assembly...

  9. Magnetic Nanocomposite Cilia Sensors

    KAUST Repository

    Alfadhel, Ahmed

    2016-07-19

    Recent progress in the development of artificial skin concepts is a result of the increased demand for providing environment perception such as touch and flow sensing to robots, prosthetics and surgical tools. Tactile sensors are the essential components of artificial skins and attracted considerable attention that led to the development of different technologies for mimicking the complex sense of touch in humans. This dissertation work is devoted to the development of a bioinspired tactile sensing technology that imitates the extremely sensitive hair-like cilia receptors found in nature. The artificial cilia are fabricated from permanent magnetic, biocompatible and highly elastic nanocomposite material, and integrated on a giant magneto-impedance magnetic sensor to measure the stray field. A force that bends the cilia changes the stray field and is therefore detected with the magnetic sensor, providing high performance in terms of sensitivity, power consumption and versatility. The nanocomposite is made of Fe nanowires (NWs) incorporated into polydimethylsiloxane (PDMS). Fe NWs have a high remanent magnetization, due the shape anisotropy; thus, they are acting as permanent nano-magnets. This allows remote device operation and avoids the need for a magnetic field to magnetize the NWs, benefiting miniaturization and the possible range of applications. The magnetic properties of the nanocomposite can be easily tuned by modifying the NWs concentration or by aligning the NWs to define a magnetic anisotropy. Tactile sensors are realized on flexible and rigid substrates that can detect flow, vertical and shear forces statically and dynamically, with a high resolution and wide operating range. The advantage to operate the sensors in liquids and air has been utilized to measure flows in different fluids in a microfluidic channel. Various dynamic studies were conducted with the tactile sensor demonstrating the detection of moving objects or the texture of objects. Overall

  10. Microfluidic propulsion by the metachronal beating of magnetic artificial cilia: a numerical analysis

    CERN Document Server

    Khaderi, Syed; Onck, Patrick

    2011-01-01

    In this work we study the effect of metachronal waves on the flow created by magnetically-driven plate-like artificial cilia in microchannels using numerical simulations. The simulations are performed using a coupled magneto-mechanical solid-fluid computational model that captures the physical interactions between the fluid flow, ciliary deformation and applied magnetic field. When a rotating magnetic field is applied to super-paramagnetic artificial cilia, they mimic the asymmetric motion of natural cilia, consisting of an effective and recovery stroke. When a phase-difference is prescribed between neighbouring cilia, metachronal waves develop. Due to the discrete nature of the cilia, the metachronal waves change direction when the phase difference becomes sufficiently large, resulting in antiplectic as well as symplectic metachrony. We show that the fluid flow created by the artificial cilia is significantly enhanced in the presence of metachronal waves and that the fluid flow becomes unidirectional. Antipl...

  11. Asymmetric vs. symmetric deep lithospheric architecture of intra-plate continental orogens

    Science.gov (United States)

    Calignano, Elisa; Sokoutis, Dimitrios; Willingshofer, Ernst; Gueydan, Frédéric; Cloetingh, Sierd

    2015-08-01

    The initiation and subsequent evolution of intra-plate orogens, resulting from continental plate interior deformation due to transmission of stresses over large distances from the active plate boundaries, is controlled by lateral and vertical strength contrasts in the lithosphere. We present lithospheric-scale analogue models combining 1) lateral strength variations in the continental lithosphere, and 2) different vertical rheological stratifications. The experimental continental lithosphere has a four-layer brittle-ductile rheological stratification. Lateral heterogeneity is implemented in all models by increased crustal strength in a central narrow block. The main investigated parameters are strain rate and strength of the lithospheric mantle, both playing an important role in crust-mantle coupling. The experiments show that the presence of a strong crustal domain is effective in localizing deformation along its boundaries. After deformation is localized, the evolution of the orogenic system is governed by the mechanical properties of the lithosphere such that the final geometry of the intra-plate mountain depends on the interplay between crust-mantle coupling and folding versus fracturing of the lithospheric mantle. Underthrusting is the main deformation mode in case of high convergence velocity and/or thick brittle mantle with a final asymmetric architecture of the deep lithosphere. In contrast, lithospheric folding is dominant in case of low convergence velocity and low strength brittle mantle, leading to the development of a symmetric lithospheric root. The presented analogue modelling results provide novel insights for 1) strain localization and 2) the development of the asymmetric architecture of the Pyrenees.

  12. Biomimetic Cilia Based on MEMS Technology

    Institute of Scientific and Technical Information of China (English)

    Zhi-guo Zhou; Zhi-wen Liu

    2008-01-01

    A review on the research of Micro Electromechanical Systems (MEMS) technology based biomimetic cilia is presented. Biomimetic cilia, enabled by the advancement of MEMS technology, have been under dynamic development for the past decade. After a brief description of the background of cilia and MEMS technology, different biomimetic cilia applications are reviewed. Biomimetic cilia micro-actuators, including micromachined polyimide bimorph biomimetic cilia micro-actuator, electro-statically actuated polymer biomimetic cilia micro-actuator, and magnetically actuated nanorod array biomimetic cilia micro-actuator, are presented. Subsequently micromachined underwater flow biomimetic cilia micro-sensor is studied, followed by acoustic flow micro-sensor. The fabrication of these MEMS-based biomimetic cilia devices, characterization of their physical properties, and the results of their application experiments are discussed.

  13. Architectural Blueprint for Plate Boundary Observatories based on interoperable Data Management Platforms

    Science.gov (United States)

    Kerschke, D. I.; Häner, R.; Schurr, B.; Oncken, O.; Wächter, J.

    2014-12-01

    Interoperable data management platforms play an increasing role in the advancement of knowledge and technology in many scientific disciplines. Through high quality services they support the establishment of efficient and innovative research environments. Well-designed research environments can facilitate the sustainable utilization, exchange, and re-use of scientific data and functionality by using standardized community models. Together with innovative 3D/4D visualization, these concepts provide added value in improving scientific knowledge-gain, even across the boundaries of disciplines. A project benefiting from the added value is the Integrated Plate boundary Observatory in Chile (IPOC). IPOC is a European-South American network to study earthquakes and deformation at the Chilean continental margin and to monitor the plate boundary system for capturing an anticipated great earthquake in a seismic gap. In contrast to conventional observatories that monitor individual signals only, IPOC captures a large range of different processes through various observation methods (e.g., seismographs, GPS, magneto-telluric sensors, creep-meter, accelerometer, InSAR). For IPOC a conceptual design has been devised that comprises an architectural blueprint for a data management platform based on common and standardized data models, protocols, and encodings as well as on an exclusive use of Free and Open Source Software (FOSS) including visualization components. Following the principles of event-driven service-oriented architectures, the design enables novel processes by sharing and re-using functionality and information on the basis of innovative data mining and data fusion technologies. This platform can help to improve the understanding of the physical processes underlying plate deformations as well as the natural hazards induced by them. Through the use of standards, this blueprint can not only be facilitated for other plate observing systems (e.g., the European Plate

  14. Axoneme Structure from Motile Cilia.

    Science.gov (United States)

    Ishikawa, Takashi

    2017-01-03

    The axoneme is the main extracellular part of cilia and flagella in eukaryotes. It consists of a microtubule cytoskeleton, which normally comprises nine doublets. In motile cilia, dynein ATPase motor proteins generate sliding motions between adjacent microtubules, which are integrated into a well-orchestrated beating or rotational motion. In primary cilia, there are a number of sensory proteins functioning on membranes surrounding the axoneme. In both cases, as the study of proteomics has elucidated, hundreds of proteins exist in this compartmentalized biomolecular system. In this article, we review the recent progress of structural studies of the axoneme and its components using electron microscopy and X-ray crystallography, mainly focusing on motile cilia. Structural biology presents snapshots (but not live imaging) of dynamic structural change and gives insights into the force generation mechanism of dynein, ciliary bending mechanism, ciliogenesis, and evolution of the axoneme. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  15. Primary cilia utilize glycoprotein-dependent adhesion mechanisms to stabilize long-lasting cilia-cilia contacts

    Directory of Open Access Journals (Sweden)

    Ott Carolyn

    2012-04-01

    Full Text Available Abstract Background The central tenet of cilia function is sensing and transmitting information. The capacity to directly contact extracellular surfaces would empower primary cilia to probe the environment for information about the nature and location of nearby surfaces. It has been well established that flagella and other motile cilia perform diverse cellular functions through adhesion. We hypothesized that mammalian primary cilia also interact with the extracellular environment through direct physical contact. Methods We identified cilia in rod photoreceptors and cholangiocytes in fixed mouse tissues and examined the structures that these cilia contact in vivo. We then utilized an MDCK cell culture model to characterize the nature of the contacts we observed. Results In retina and liver tissue, we observed that cilia from nearby cells touch one another. Using MDCK cells, we found compelling evidence that these contacts are stable adhesions that form bridges between two cells, or networks between many cells. We examined the nature and duration of the cilia-cilia contacts and discovered primary cilia movements that facilitate cilia-cilia encounters. Stable adhesions form as the area of contact expands from a single point to a stretch of tightly bound, adjacent cilia membranes. The cilia-cilia contacts persisted for hours and were resistant to several harsh treatments such as proteases and DTT. Unlike many other cell adhesion mechanisms, calcium was not required for the formation or maintenance of cilia adhesion. However, swainsonine, which blocks maturation of N-linked glycoproteins, reduced contact formation. We propose that cellular control of adhesion maintenance is active because cilia adhesion did not prevent cell division; rather, contacts dissolved during mitosis as cilia were resorbed. Conclusions The demonstration that mammalian primary cilia formed prolonged, direct, physical contacts supports a novel paradigm: that mammalian primary

  16. Magnetic Nanocomposite Cilia Energy Harvester

    KAUST Repository

    Khan, Mohammed Asadullah

    2016-02-11

    An energy harvester capable of converting low frequency vibrations into electrical energy is presented. The operating principle, fabrication process and output characteristics at different frequencies are discussed. The harvester is realized by fabricating an array of polydimethylsiloxane (PDMS) - iron nanowire nanocomposite cilia on a planar coil array. Each coil element consists of 14 turns and occupies an area of 600 μm x 600μm. The cilia are arranged in a 12x5 array and each cilium is 250 μm wide and 2 mm long. The magnetic characteristics of the fabricated cilia indicate that the nanowires are well aligned inside of the nanocomposite, increasing the efficiency of energy harvesting. The energy harvester occupies an area of 66.96 mm2 and produces an output r.m.s voltage of 206.47μV, when excited by a 40 Hz vibration of 1 mm amplitude.

  17. Microfluidic manipulation with artificial/bioinspired cilia

    NARCIS (Netherlands)

    den Toonder, Jaap M. J.; Onck, Patrick R.

    2013-01-01

    A recent development, inspired by nature, is the use of 'artificial cilia' to create pumping and/or mixing in microfluidic devices. Cilia are small hairs that can be found in biology and are used for (fluid) actuation and sensing. Microscopic actuators resembling cilia, actuated to move under the in

  18. A dynamic cell adhesion surface regulates tissue architecture in growth plate cartilage.

    Science.gov (United States)

    Romereim, Sarah M; Conoan, Nicholas H; Chen, Baojiang; Dudley, Andrew T

    2014-05-01

    The architecture and morphogenetic properties of tissues are founded in the tissue-specific regulation of cell behaviors. In endochondral bones, the growth plate cartilage promotes bone elongation via regulated chondrocyte maturation within an ordered, three-dimensional cell array. A key event in the process that generates this cell array is the transformation of disordered resting chondrocytes into clonal columns of discoid proliferative cells aligned with the primary growth vector. Previous analysis showed that column-forming chondrocytes display planar cell divisions, and the resulting daughter cells rearrange by ∼90° to align with the lengthening column. However, these previous studies provided limited information about the mechanisms underlying this dynamic process. Here we present new mechanistic insights generated by application of a novel time-lapse confocal microscopy method along with immunofluorescence and electron microscopy. We show that, during cell division, daughter chondrocytes establish a cell-cell adhesion surface enriched in cadherins and β-catenin. Rearrangement into columns occurs concomitant with expansion of this adhesion surface in a process more similar to cell spreading than to migration. Column formation requires cell-cell adhesion, as reducing cadherin binding via chelation of extracellular calcium inhibits chondrocyte rearrangement. Importantly, physical indicators of cell polarity, such as cell body alignment, are not prerequisites for oriented cell behavior. Our results support a model in which regulation of adhesive surface dynamics and cortical tension by extrinsic signaling modifies the thermodynamic landscape to promote organization of daughter cells in the context of the three-dimensional growth plate tissue.

  19. Primary cilia and graded Sonic Hedgehog signaling.

    Science.gov (United States)

    Sasai, Noriaki; Briscoe, James

    2012-01-01

    Cilia are evolutionary-conserved microtubule-containing organelles protruding from the surface of cells. They are classified into two types--primary and motile cilia. Primary cilia are nearly ubiquitous, at least in vertebrate cells, and it has become apparent that they play an essential role in the intracellular transduction of a range of stimuli. Most notable among these is Sonic Hedgehog. In this article we briefly summarize the structure and biogenesis of primary cilia. We discuss the evidence implicating cilia in the transduction of extrinsic signals. We focus on the involvement and molecular mechanism of cilia in signaling by Sonic Hedgehog in embryonic tissues, specifically the neural tube, and we discuss how cilia play an active role in the interpretation of gradients of Sonic Hedgehog (Shh) signaling.

  20. [The importance of model organisms to study cilia and flagella biology].

    Science.gov (United States)

    Vincensini, Laetitia; Blisnick, Thierry; Bastin, Philippe

    2011-01-01

    Cilia and flagella are ubiquitous organelles that protrude from the surfaces of many cells, and whose architecture is highly conserved from protists to humans. These complex organelles, composed of over 500 proteins, can be either immotile or motile. They are involved in a myriad of biological processes, including sensing (non-motile cilia) and/or cell motility or movement of extracellular fluids (motile cilia). The ever-expanding list of human diseases linked to defective cilia illustrates the functional importance of cilia and flagella. These ciliopathies are characterised by an impressive diversity of symptoms and an often complex genetic etiology. A precise knowledge of cilia and flagella biology is thus critical to better understand these pathologies. However, multi-ciliated cells are terminally differentiated and difficult to manipulate, and a primary cilium is assembled only when the cell exits from the cell cycle. In this context the use of model organisms, that relies on the high degree of structural but also of molecular conservation of these organelles across evolution, is instrumental to decipher the many facets of cilia and flagella biology. In this review, we highlight the specific strengths of the main model organisms to investigate the molecular composition, mode of assembly, sensing and motility mechanisms and functions of cilia and flagella. Pioneering studies carried out in the green alga Chlamydomonas established the link between cilia and several genetic diseases. Moreover, multicellular organisms such as mouse, zebrafish, Xenopus, C. elegans or Drosophila, and protists like Paramecium, Tetrahymena and Trypanosoma or Leishmania each bring specific advantages to the study of cilium biology. For example, the function of genes involved in primary ciliary dyskinesia (due to defects in ciliary motility) can be efficiently assessed in trypanosomes.

  1. Structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren T

    2008-01-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...... of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation. This view has had unanticipated consequences for our understanding of developmental processes and human disease....

  2. Selective particle capture by asynchronously beating cilia

    Science.gov (United States)

    Ding, Yang; Kanso, Eva

    2015-12-01

    Selective particle filtration is fundamental in many engineering and biological systems. For example, many aquatic microorganisms use filter feeding to capture food particles from the surrounding fluid, using motile cilia. One of the capture strategies is to use the same cilia to generate feeding currents and to intercept particles when the particles are on the downstream side of the cilia. Here, we develop a 3D computational model of ciliary bands interacting with flow suspended particles and calculate particle trajectories for a range of particle sizes. Consistent with experimental observations, we find optimal particle sizes that maximize capture rate. The optimal size depends nonlinearly on cilia spacing and cilia coordination, synchronous vs. asynchronous. These parameters affect the cilia-generated flow field, which in turn affects particle trajectories. The low capture rate of smaller particles is due to the particles' inability to cross the flow streamlines of neighboring cilia. Meanwhile, large particles have difficulty entering the sub-ciliary region once advected downstream, also resulting in low capture rates. The optimal range of particle sizes is enhanced when cilia beat asynchronously. These findings have potentially important implications on the design and use of biomimetic cilia in processes such as particle sorting in microfluidic devices.

  3. Directed Fluid Flow Produced by Arrays of Magnetically Actuated Core-Shell Biomimetic Cilia

    Science.gov (United States)

    Fiser, B. L.; Shields, A. R.; Evans, B. A.; Superfine, R.

    2010-03-01

    We have developed a novel core-shell microstructure that we use to fabricate arrays of flexible, magnetically actuated biomimetic cilia. Our biomimetic cilia mimic the size and beat shape of biological cilia in order to replicate the transport of fluid driven by cilia in many biological systems including the determination of left-right asymmetry in the vertebrate embryonic nodal plate and mucociliary clearance in the lung. Our core-shell structures consist of a flexible poly(dimethylsiloxane) (PDMS) core surrounded by a shell of nickel approximately forty nanometers thick; by using a core-shell structure, we can tune the mechanical and magnetic properties independently. We present the fabrication process and the long-range transport that occurs above the beating biomimetic cilia tips and will report on progress toward biomimetic cilia induced flow in viscoelastic fluids similar to mucus in the human airway. These flows may have applications in photonics and microfluidics, and our structures may be further useful as sensors or actuators in microelectromechanical systems.

  4. Artificial Cilia : Mimicking Nature Through Magnetic Actuation

    NARCIS (Netherlands)

    Khaderi, S. N.; Baltussen, M. G. H. M.; Anderson, P. D.; Ioan, D.; den Toonder, J.M.J.; Onck, P. R.; Murthy, SK; Khan, SA; Ugaz, VM; Zeringue, HC

    2009-01-01

    Manipulation of bio-fluids in microchannels faces many challenges in the development of lab-on-a-chip devices. We propose magnetically actuated artificial cilia which can propel fluids in microchannels. These cilia are magnetic films which can be actuated by an external magnetic field, leading to an

  5. Intraocular cilia associated with perforating injury

    Directory of Open Access Journals (Sweden)

    Gopal Lingam

    2000-01-01

    Full Text Available Purpose: To report a case series of penetrating injury complicated by occurrence of intraocular cilia. Methods: Retrospective analysis of charts of 11 eyes of 11 patients with penetrating injury and intraocular cilia, presenting between September 1978 and November 1998. Ten eyes underwent surgery for trauma-related problems such as cataract, vitritis, retinal detachment etc., at which time intraocular cilia were removed. One eye did not have surgery and continues to harbour cilia at the posterior perforation site. Results: Metallic wire was responsible for injury in 6 of 11 eyes with intraocular cilia. Five eyes had significant intraocular inflammation. The cilia were located in the anterior segment in 4 eyes; in the posterior segment in 6 eyes and in both in one eye. At the last follow up, 72.7% had 6/18 or better vision. Poor vision in the rest was due to recurrent retinal detachment (2 eyes and macular scarring (1 eye. Conclusion: Intraocular cilia are more commonly associated with injury by a metallic wire. The presentation and management of an injured eye does not seem to be influenced by the presence of cilia in the eye.

  6. Role of Primary Cilia in Odontogenesis.

    Science.gov (United States)

    Hampl, M; Cela, P; Szabo-Rogers, H L; Bosakova, M Kunova; Dosedelova, H; Krejci, P; Buchtova, M

    2017-08-01

    Primary cilium is a solitary organelle that emanates from the surface of most postmitotic mammalian cells and serves as a sensory organelle, transmitting the mechanical and chemical cues to the cell. Primary cilia are key coordinators of various signaling pathways during development and maintenance of tissue homeostasis. The emerging evidence implicates primary cilia function in tooth development. Primary cilia are located in the dental epithelium and mesenchyme at early stages of tooth development and later during cell differentiation and production of hard tissues. The cilia are present when interactions between both the epithelium and mesenchyme are required for normal morphogenesis. As the primary cilium coordinates several signaling pathways essential for odontogenesis, ciliary defects can interrupt the latter process. Genetic or experimental alterations of cilia function lead to various developmental defects, including supernumerary or missing teeth, enamel and dentin hypoplasia, or teeth crowding. Moreover, dental phenotypes are observed in ciliopathies, including Bardet-Biedl syndrome, Ellis-van Creveld syndrome, Weyers acrofacial dysostosis, cranioectodermal dysplasia, and oral-facial-digital syndrome, altogether demonstrating that primary cilia play a critical role in regulation of both the early odontogenesis and later differentiation of hard tissue-producing cells. Here, we summarize the current evidence for the localization of primary cilia in dental tissues and the impact of disrupted cilia signaling on tooth development in ciliopathies.

  7. Microfluidic propulsion by the metachronal beating of magnetic artificial cilia : A numerical analysis

    NARCIS (Netherlands)

    Khaderi, S. N.; den Toonder, J.M.J.; Onck, P. R.

    2011-01-01

    In this work we study the effect of metachronal waves on the flow created by magnetically driven plate-like artificial cilia in microchannels using numerical simulations. The simulations are performed using a coupled magneto-mechanical solid fluid computational model that captures the physical

  8. Out of the cleanroom, self-assembled magnetic artificial cilia.

    Science.gov (United States)

    Wang, Ye; Gao, Yang; Wyss, Hans; Anderson, Patrick; den Toonder, Jaap

    2013-09-01

    Micro-sized hair-like structures, such as cilia, are abundant in nature and have various functionalities. Many efforts have been made to mimic the fluid pumping function of cilia, but most of the fabrication processes for these "artificial cilia" are tedious and expensive, hindering their practical application. In this paper a cost-effective in situ fabrication technique for artificial cilia is demonstrated. The cilia are constructed by self-assembly of micron sized magnetic beads and encapsulated with soft polymer coatings. Actuation of the cilia induces an effective fluid flow, and the cilia lengths and distribution can be adjusted by varying the magnetic bead concentration and fabrication parameters.

  9. PLATE

    DEFF Research Database (Denmark)

    Kling, Joyce; Hjulmand, Lise-Lotte

    2008-01-01

    ’s level of English is sufficient for the increasing number of courses offered in English each semester. This paper addresses these concerns and describes a pilot project initiated in 2003 at CBS to gauge the overall English language proficiency of those teaching content courses in English. Through......Copenhagen Business School (CBS) finds itself needing to address the issue of English-medium instruction for its increasing number of foreign exchange and full degree students. With internationalisation as a main pillar of the institution’s agenda, there are concerns whether the teaching faculty...... the Project in Language Assessment for Teaching in English (PLATE) language professionals from CBS’s Language Center observe teachers and provide feedback using evaluation criteria from the Common European Framework for Reference (CEFR) supplemented by some additional criteria which take the LSP nature...

  10. PLATE

    DEFF Research Database (Denmark)

    Kling, Joyce; Hjulmand, Lise-Lotte

    2008-01-01

    Copenhagen Business School (CBS) finds itself needing to address the issue of English-medium instruction for its increasing number of foreign exchange and full degree students. With internationalisation as a main pillar of the institution’s agenda, there are concerns whether the teaching faculty......’s level of English is sufficient for the increasing number of courses offered in English each semester. This paper addresses these concerns and describes a pilot project initiated in 2003 at CBS to gauge the overall English language proficiency of those teaching content courses in English. Through...... the Project in Language Assessment for Teaching in English (PLATE) language professionals from CBS’s Language Center observe teachers and provide feedback using evaluation criteria from the Common European Framework for Reference (CEFR) supplemented by some additional criteria which take the LSP nature...

  11. Switching on cilia: transcriptional networks regulating ciliogenesis.

    Science.gov (United States)

    Choksi, Semil P; Lauter, Gilbert; Swoboda, Peter; Roy, Sudipto

    2014-04-01

    Cilia play many essential roles in fluid transport and cellular locomotion, and as sensory hubs for a variety of signal transduction pathways. Despite having a conserved basic morphology, cilia vary extensively in their shapes and sizes, ultrastructural details, numbers per cell, motility patterns and sensory capabilities. Emerging evidence indicates that this diversity, which is intimately linked to the different functions that cilia perform, is in large part programmed at the transcriptional level. Here, we review our understanding of the transcriptional control of ciliary biogenesis, highlighting the activities of FOXJ1 and the RFX family of transcriptional regulators. In addition, we examine how a number of signaling pathways, and lineage and cell fate determinants can induce and modulate ciliogenic programs to bring about the differentiation of distinct cilia types.

  12. Electrical Signaling in Motile and Primary Cilia

    OpenAIRE

    Steven J Kleene; Van Houten, Judith L.

    2014-01-01

    Cilia are highly conserved for their structure and also for their sensory functions. They serve as antennae for extracellular information. Whether the cilia are motile or not, they respond to environmental mechanical and chemical stimuli and signal to the cell body. The information from extracellular stimuli is commonly converted to electrical signals through the repertoire of ion-conducting channels in the ciliary membrane resulting in changes in concentrations of ions, esp...

  13. Cilia driven flow networks in the brain

    Science.gov (United States)

    Wang, Yong; Faubel, Regina; Westendorf, Chrsitian; Eichele, Gregor; Bodenschatz, Eberhard

    Neurons exchange soluble substances via the cerebrospinal fluid (CSF) that fills the ventricular system. The walls of the ventricular cavities are covered with motile cilia that constantly beat and thereby induce a directional flow. We recently discovered that cilia in the third ventricle generate a complex flow pattern leading to partitioning of the ventricular volume and site-directed transport paths along the walls. Transient and daily recurrent alterations in the cilia beating direction lead to changes in the flow pattern. This has consequences for delivery of CSF components along the near wall flow. The contribution of this cilia-induced flow to overall CSF flow remains to be investigated. The state-of-art lattice Boltzmann method is adapted for studying the CFS flow. The 3D geometry of the third ventricle at high resolution was reconstructed. Simulation of CSF flow without cilia in this geometry confirmed that the previous idea about unidirectional flow does not explain how different components of CSF can be delivered to their various target sites. We study the contribution of the cilia-induced flow pattern to overall CSF flow and identify target areas for site-specific delivery of CSF-constituents with respect to the temporal changes.

  14. Ufa : une architecture ultra plate pour les réseaux mobiles du futur

    OpenAIRE

    Daoud Triki, Khadija

    2011-01-01

    Mobile networks have a layered model, with: (1) an IP access network providing IP connectivity to users, (2) a service control layer, IMS, (3) an interaction layer for policy control, PCC. This model, centralized and hierarchical, will cause scalability and QoS problems in case of data volume explosion. In this thesis, a new model for future mobile networks is proposed: Ultra Flat Architecture (UFA). UFA uses IMS to control all application types. UFA is flat since it reduces the number of net...

  15. Artificial cilia : a physical model for ciliary propulsion

    OpenAIRE

    Babataheri, Avin

    2009-01-01

    Most microorganisms use cilia or flagella as a means of propulsion. These low Reynolds number swimming mechanisms have been studied theoretically and experimentally on living organisms. However, so far very few physical experimental models have been realised. We describe here the fabrication of microscopic artificial cilia, actuated by a magnetic field. These artificial cilia share with real cilia a large aspect ratio, great flexibility, and the actuation by a magnetic torque distributed alon...

  16. Identification of ICIS-1, a new protein involved in cilia stability.

    Science.gov (United States)

    Ponsard, Cecile; Skowron-Zwarg, Marie; Seltzer, Virginie; Perret, Eric; Gallinger, Julia; Fisch, Cathy; Dupuis-Williams, Pascale; Caruso, Nathalie; Middendorp, Sandrine; Tournier, Frederic

    2007-01-01

    Cilia are specialized organelles that exert critical functions in numerous organisms, including that of cell motility, fluid transport and protozoan locomotion. Ciliary architecture and function strictly depend on basal body formation, migration and axoneme elongation. Numerous ultrastructural studies have been undertaken in different species to elucidate the process of ciliogenesis. Recent analyses have led to identification of genes specifically expressed in ciliated organisms, but most proteins involved in ciliogenesis remain uncharacterized. Using human nasal epithelial cells capable of ciliary differentiation in vitro, differential display was carried out to identify new proteins associated with ciliogenesis. We isolated a new gene, ICIS-1 (Involved in CIlia Stability-1), upregulated during mucociliary differentiation. This gene is localized within the TGF-beta1 promoter and is ubiquitously expressed in human tissues. Functional analyses of gene expression inhibition by RNA interference in Paramecium tetraurelia indicated that the ICIS-1 homologue interfered with cilia stability or formation. These findings demonstrate that ICIS-1 is a new protein associated with ciliated cells and potentially related to cilia stability.

  17. Cilia and coordination of signaling networks during heart development

    DEFF Research Database (Denmark)

    Koefoed, Karen; Veland, Iben Rønn; Pedersen, Lotte Bang;

    2014-01-01

    of developmental disorders and diseases called ciliopathies. Recent studies have indicated a major role of different populations of cilia, including nodal and cardiac primary cilia, in coordinating heart development, and defects in these cilia are associated with congenital heart diseases. Here, we present......Primary cilia are unique sensory organelles that coordinate a wide variety of different signaling pathways to control cellular processes during development and in tissue homeostasis. Defects in function or assembly of these antenna-like structures are therefore associated with a broad range...... an overview of the role of nodal and cardiac primary cilia in heart development....

  18. Cildb: a knowledgebase for centrosomes and cilia.

    Science.gov (United States)

    Arnaiz, Olivier; Malinowska, Agata; Klotz, Catherine; Sperling, Linda; Dadlez, Michal; Koll, France; Cohen, Jean

    2009-01-01

    Ciliopathies, pleiotropic diseases provoked by defects in the structure or function of cilia or flagella, reflect the multiple roles of cilia during development, in stem cells, in somatic organs and germ cells. High throughput studies have revealed several hundred proteins that are involved in the composition, function or biogenesis of cilia. The corresponding genes are potential candidates for orphan ciliopathies. To study ciliary genes, model organisms are used in which particular questions on motility, sensory or developmental functions can be approached by genetics. In the course of high throughput studies of cilia in Paramecium tetraurelia, we were confronted with the problem of comparing our results with those obtained in other model organisms. We therefore developed a novel knowledgebase, Cildb, that integrates ciliary data from heterogeneous sources. Cildb links orthology relationships among 18 species to high throughput ciliary studies, and to OMIM data on human hereditary diseases. The web interface of Cildb comprises three tools, BioMart for complex queries, BLAST for sequence homology searches and GBrowse for browsing the human genome in relation to OMIM information for human diseases. Cildb can be used for interspecies comparisons, building candidate ciliary proteomes in any species, or identifying candidate ciliopathy genes.Database URL:http://cildb.cgm.cnrs-gif.fr.

  19. Cilia and ciliopathies:From Chlamydomonas and beyond

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The biological function of motile cilia/flagella has long been recognized. The non-motile primary cilium, once regarded as a vestigial organelle, however, has been found recently to play unexpected roles in mammalian physiology and development. Defects in cilia have profound impact on human health. Diseases related to cilia, collectively called ciliopathies include male infertility, primary cilia dyskinesia, renal cyst formation, blindness, polydactyly, obesity, hypertension, and even mental retardation. Our current understanding of cilia and ciliopathies has been fueled by basic research employing various model organisms including Chlamydomonas, a unicellular green alga. This review article provides a general introduction to the cell biology of cilia and an overview of various cilia-related diseases.

  20. Wnt11b is involved in cilia-mediated symmetry breakage during Xenopus left-right development.

    Directory of Open Access Journals (Sweden)

    Peter Walentek

    Full Text Available Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1, a regulator of motile cilia, and Wnt/planar cell polarity (PCP dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM, from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus.

  1. Cilia containing 9 + 2 structures grown from immortalized cells

    Institute of Scientific and Technical Information of China (English)

    Ming Zhang; Jose G Assouline

    2007-01-01

    Cilia depend on their highly differentiated structure, a 9 + 2 arrangement, to remove particles from the lung and to transport reproductive cells. Immortalized cells could potentially be of great use in cilia research. Immortalization of cells with cilia structure containing the 9 + 2 arrangement might be able to generate cell lines with such cilia structure. However, whether immortalized cells can retain such a highly differentiated structure remains unclear. Here we demonstrate that (1) using E1a gene transfection, tracheal cells are immortalized; (2) interestingly, in a gel culture the immortalized cells form spherical aggregations within which a lumen is developed; and (3) surprisingly, inside the aggregation, cilia containing a 9 + 2 arrangement grow from the cell's apical pole and protrude into the lumen. These results may influence future research in many areas such as understanding the mechanisms of cilia differentiation, cilia generation in other existing cell lines, cilia disorders, generation of other highly differentiated structures besides cilia using the gel culture,immortalization of other ciliated cells with the E1a gene, development of cilia motile function, and establishment of a research model to provide uniform ciliated cells.

  2. Ciliae-based actuator with piezoelectric excitation

    Science.gov (United States)

    Pott, Peter P.; Carrasco, Alvaro; Schlaak, Helmut F.

    2012-06-01

    Small actuators based on the inverse piezoelectric effect are successfully deployed in commercial applications. Usually, ultrasonic motors are used. Based on resonance effects these motors provide a pronounced nonlinearity at low speeds and thus put high demands on the control algorithm. In contrast, piezoelectric stepping motors are mechanically complex and provide only low speeds. The contribution at hand describes a proposed design for a new piezoelectric motor based on cilia friction that can be manufactured at low costs. The cilia are made from uniaxial carbon-fibre reinforced plastics. The derived CFRP-brushes are pressed perpendicularly to the rotor surface to produce force or torque. First experiments prove the feasibility of the concept. A net pushing force of 500 mN is achieved.

  3. The Roles of Primary Cilia in Cardiovascular System

    Science.gov (United States)

    2015-10-01

    cells also play an important role in regu- lating pluripotent neural stem cells (Rietze et al., 2001). Beating of ependymal cilia is required for normal...beating and hydrody- namic forces has been proposed to regulate planar cell polarity during development or stroke (Guirao et al., 2010; Mirzadeh et al...ependymal cilia beating but also reduces the efficiency of each cilia stroke . At least 10 independent preparations were used for each ependymal cell

  4. Primary cilia are lost in preinvasive and invasive prostate cancer.

    Directory of Open Access Journals (Sweden)

    Nadia B Hassounah

    Full Text Available Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN, and invasive prostate cancer (including perineural invasion were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for β-catenin as a measure of Wnt signaling. Nuclear β-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human

  5. Cilia and coordination of signaling networks during heart development

    DEFF Research Database (Denmark)

    Koefoed, Karen; Veland, Iben Rønn; Pedersen, Lotte Bang

    2014-01-01

    Primary cilia are unique sensory organelles that coordinate a wide variety of different signaling pathways to control cellular processes during development and in tissue homeostasis. Defects in function or assembly of these antenna-like structures are therefore associated with a broad range...... of developmental disorders and diseases called ciliopathies. Recent studies have indicated a major role of different populations of cilia, including nodal and cardiac primary cilia, in coordinating heart development, and defects in these cilia are associated with congenital heart diseases. Here, we present...

  6. Adenylate Cyclase Type III Is Not a Ubiquitous Marker for All Primary Cilia during Development

    Science.gov (United States)

    Antal, Maria Cristina; Bénardais, Karelle; Samama, Brigitte; Auger, Cyril; Schini-Kerth, Valérie; Ghandour, Said; Boehm, Nelly

    2017-01-01

    Adenylate cyclase type III (AC3) is localized in plasma membrane of neuronal primary cilium and can be used as a marker of this cilium. AC3 has also been detected in some other primary cilia such as those of fibroblasts, synoviocytes or astrocytes. Despite the presence of a cilium in almost all cell types, we show that AC3 is not a common marker of all primary cilia of different human and mouse tissues during development. In peripheral organs, AC3 is present mainly in primary cilia in cells of the mesenchymal lineage (fibroblasts, chondroblasts, osteoblasts-osteocytes, odontoblasts, muscle cells and endothelial cells). In epithelia, the apical cilium of renal and pancreatic tubules and of ductal plate in liver is AC3-negative whereas the cilium of basal cells of stratified epithelia is AC3-positive. Using fibroblasts cell culture, we show that AC3 appears at the plasma membrane of the primary cilium as soon as this organelle develops. The functional significance of AC3 localization at the cilium membrane in some cells but not others has to be investigated in relationship with cell physiology and expression at the cilium plasma membrane of specific upstream receptors. PMID:28122017

  7. Analysis of primary cilia in directional cell migration in fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht;

    2013-01-01

    Early studies of migrating fibroblasts showed that primary cilia orient in front of the nucleus and point toward the leading edge. Recent work has shown that primary cilia coordinate a series of signaling pathways critical to fibroblast cell migration during development and in wound healing. In p...

  8. A case of ectopic cilia in nail-patella syndrome.

    Science.gov (United States)

    Edmunds, Matthew R; Kipioti, Athina; Colloby, Peter S; Reuser, Tristan T Q

    2012-06-01

    Both ectopic cilia and nail-patella syndrome (NPS) are rare entities. To our knowledge we report the first case of the two anomalies coexisting in one patient. We present the case of a 2-year-old girl, with no other ophthalmic complication of NPS, who had an excellent cosmetic outcome and no lesion recurrence following surgical excision of ectopic cilia.

  9. Magnetically Actuated Artificial Cilia : The Effect of Fluid Inertia

    NARCIS (Netherlands)

    Khaderi, S. N.; den Toonder, J.M.J.; Onck, P. R.

    2012-01-01

    Natural cilia are hairlike microtubule-based structures that are able to move fluid on the micrometer scale using asymmetric motion. In this article, we follow a biomimetic approach to design artificial cilia lining the inner surfaces of microfluidic channels with the goal of propelling fluid. The

  10. Cilia and polycystic kidney disease, kith and kin.

    Science.gov (United States)

    Huang, Liwei; Lipschutz, Joshua H

    2014-06-01

    In the past decade, cilia have been found to play important roles in renal cystogenesis. Many genes, such as PKD1 and PKD2 which, when mutated, cause autosomal dominant polycystic kidney disease (ADPKD), have been found to localize to primary cilia. The cilium functions as a sensor to transmit extracellular signals into the cell. Abnormal cilia structure and function are associated with the development of polyscystic kidney disease (PKD). Cilia assembly includes centriole migration to the apical surface of the cell, ciliary vesicle docking and fusion with the cell membrane at the intended site of cilium outgrowth, and microtubule growth from the basal body. This review summarizes the most recent advances in cilia and PKD research, with special emphasis on the mechanisms of cytoplasmic and intraciliary protein transport during ciliogenesis.

  11. Adenylate cyclase regulates elongation of mammalian primary cilia

    Energy Technology Data Exchange (ETDEWEB)

    Ou, Young; Ruan, Yibing; Cheng, Min; Moser, Joanna J. [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); Rattner, Jerome B. [Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada); Hoorn, Frans A. van der, E-mail: fvdhoorn@ucalgary.ca [Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 (Canada)

    2009-10-01

    The primary cilium is a non-motile microtubule-based structure that shares many similarities with the structures of flagella and motile cilia. It is well known that the length of flagella is under stringent control, but it is not known whether this is true for primary cilia. In this study, we found that the length of primary cilia in fibroblast-like synoviocytes, either in log phase culture or in quiescent state, was confined within a range. However, when lithium was added to the culture to a final concentration of 100 mM, primary cilia of synoviocytes grew beyond this range, elongating to a length that was on average approximately 3 times the length of untreated cilia. Lithium is a drug approved for treating bipolar disorder. We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation. Inhibition of GSK-3{beta} by four different inhibitors did not induce primary cilia elongation. ACIII was found in primary cilia of a variety of cell types, and lithium treatment of these cell types led to their cilium elongation. Further, we demonstrate that different cell types displayed distinct sensitivities to the lithium treatment. However, in all cases examined primary cilia elongated as a result of lithium treatment. In particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human astrocytes, developed long primary cilia when lithium was used at or close to the therapeutic relevant concentration (1-2 mM). These results suggest that the length of primary cilia is controlled, at least in part, by the ACIII-cAMP signaling pathway.

  12. An age of enlightenment for cilia: The FASEB summer research conference on the "Biology of Cilia and Flagella".

    Science.gov (United States)

    Tran, Pamela V; Lechtreck, Karl F

    2016-01-15

    From July 19-24, 2015, 169 clinicians and basic scientists gathered in the vertiginous heights of Snowmass, Colorado (2502 m) for the fourth FASEB summer research conference on the 'Biology of Cilia and Flagella'. Organizers Maureen Barr (Rutgers University), Iain Drummond (Massachusetts General Hospital/Harvard Medical School), and Jagesh Shah (Brigham and Women's Hospital/Harvard Medical School) assembled a program filled with new data and forward-thinking ideas documenting the ongoing growth of the field. Sixty oral presentations and 77 posters covered novel aspects of cilia structure, ciliogenesis, cilia motility, cilia-mediated signaling, and cilia-related disease. In this report, we summarize the meeting, highlight exciting developments and discuss open questions.

  13. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination

    OpenAIRE

    Daniel T Grimes; Keynton, Jennifer L.; Buenavista, Maria T.; Jin, Xingjian; Saloni H Patel; Kyosuke, Shinohara; Vibert, Jennifer; Williams, Debbie J.; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M.; Norris, Dominic P

    2016-01-01

    During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been i...

  14. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

    OpenAIRE

    Daniel T Grimes; Keynton, Jennifer L.; Buenavista, Maria T.; Jin, Xingjian; Saloni H Patel; Kyosuke, Shinohara; Vibert, Jennifer; Williams, Debbie J.; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M.; Norris, Dominic P

    2016-01-01

    During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been i...

  15. Biomimetic cilia arrays generate simultaneous pumping and mixing regimes.

    Science.gov (United States)

    Shields, A R; Fiser, B L; Evans, B A; Falvo, M R; Washburn, S; Superfine, R

    2010-09-07

    Living systems employ cilia to control and to sense the flow of fluids for many purposes, such as pumping, locomotion, feeding, and tissue morphogenesis. Beyond their use in biology, functional arrays of artificial cilia have been envisaged as a potential biomimetic strategy for inducing fluid flow and mixing in lab-on-a-chip devices. Here we report on fluid transport produced by magnetically actuated arrays of biomimetic cilia whose size approaches that of their biological counterparts, a scale at which advection and diffusion compete to determine mass transport. Our biomimetic cilia recreate the beat shape of embryonic nodal cilia, simultaneously generating two sharply segregated regimes of fluid flow: Above the cilia tips their motion causes directed, long-range fluid transport, whereas below the tips we show that the cilia beat generates an enhanced diffusivity capable of producing increased mixing rates. These two distinct types of flow occur simultaneously and are separated in space by less than 5 microm, approximately 20% of the biomimetic cilium length. While this suggests that our system may have applications as a versatile microfluidics device, we also focus on the biological implications of our findings. Our statistical analysis of particle transport identifying an enhanced diffusion regime provides novel evidence for the existence of mixing in ciliated systems, and we demonstrate that the directed transport regime is Poiseuille-Couette flow, the first analytical model consistent with biological measurements of fluid flow in the embryonic node.

  16. Dynamics of cilia length in left–right development

    Science.gov (United States)

    2017-01-01

    Reduction in the length of motile cilia in the zebrafish left–right organizer (LRO), also known as Kupffer's vesicle, has a large impact on left–right development. Here we demonstrate through genetic overexpression in zebrafish embryos and mathematical modelling that the impact of increased motile cilia length in embryonic LRO fluid flow is milder than that of short cilia. Through Arl13b overexpression, which increases cilia length without impacting cilia beat frequency, we show that the increase in cilium length is associated with a decrease in beat amplitude, resulting in similar flow strengths for Arl13b overexpression and wild-type (WT) embryos, which were not predicted by current theory. Longer cilia exhibit pronounced helical beat patterns and, consequently, lower beat amplitudes relative to WT, a result of an elastohydrodynamic shape transition. For long helical cilia, fluid dynamics modelling predicts a mild (approx. 12%) reduction in the torque exerted on the fluid relative to the WT, resulting in a proportional reduction in flow generation. This mild reduction is corroborated by experiments, providing a mechanism for the mild impact on organ situs.

  17. Fetus Sound Stimulation: Cilia Memristor Effect of Signal Transduction

    Directory of Open Access Journals (Sweden)

    Svetlana Jankovic-Raznatovic

    2014-01-01

    Full Text Available Background. This experimental study evaluates fetal middle cerebral artery (MCA circulation after the defined prenatal acoustical stimulation (PAS and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. Methods. PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. Results. Analysis of the Pulsatility index basic (PIB and before PAS and Pulsatility index reactive after the first PAS (PIR 1 shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2 shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the “memristor” property. Conclusion. Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction.

  18. Fetus sound stimulation: cilia memristor effect of signal transduction.

    Science.gov (United States)

    Jankovic-Raznatovic, Svetlana; Dragojevic-Dikic, Svetlana; Rakic, Snezana; Nikolic, Branka; Plesinac, Snezana; Tasic, Lidija; Perisic, Zivko; Sovilj, Mirjana; Adamovic, Tatjana; Koruga, Djuro

    2014-01-01

    This experimental study evaluates fetal middle cerebral artery (MCA) circulation after the defined prenatal acoustical stimulation (PAS) and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. Analysis of the Pulsatility index basic (PIB) and before PAS and Pulsatility index reactive after the first PAS (PIR 1) shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2) shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the "memristor" property. Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction.

  19. Emergence of multiple synchronization modes in hydrodynamically-coupled cilia

    Science.gov (United States)

    Guo, Hanliang; Kanso, Eva

    2016-11-01

    Motile cilia and flagella exhibit different phase coordinations. For example, closely swimming spermatozoa are observed to synchronize together; bi-flagellates Chlamydomonas regulate the flagella in a "breast-stroke" fashion; cilia on the surface of Paramecium beat in a fixed phase lag in an orchestrated wave like fashion. Experimental evidence suggests that phase coordinations can be achieved solely via hydrodynamical interactions. However, the exact mechanisms behind it remain illusive. Here, adapting a "geometric switch" model, we observe different synchronization modes in pairs of hydrodynamically-coupled cilia by changing physical parameters such as the strength of the cilia internal motor and the separation distance between cilia. Interestingly, we find regions in the parameter space where the coupled cilia reach stable phase coordinations and regions where the phase coordinations are sensitive to perturbations. We also find that leaning into the fluid reduces the sensitivity to perturbations, and produces stable phase coordination that is neither in-phase nor anti-phase, which could explain the origin of metachronal waves in large cilia populations.

  20. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  1. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  2. Crustal Architecture at the Collision Zone Between Rivera and North American Plates at the Jalisco Block: Tsujal Project

    Science.gov (United States)

    Dañobeitia, Juanjo; Bartolomé, Rafael; Prada, Manel; Nuñez-Cornú, Francisco; Córdoba, Diego; Bandy, William L.; Estrada, F.; Cameselle, Alejandra L.; Nuñez, Diana; Castellón, Arturo; Alonso, José Luis; Mortera, Carlos; Ortiz, Modesto

    2016-09-01

    Processing and analysis of new multichannel seismic records, coincident with wide-angle seismic profiles, acquired in the framework of the TsuJal project allow us to investigate in detail the complex structure of the oceanic domain in the collision zone between Rivera Plate and Block Jalisco at its northern termination. The subducting Rivera Plate, which is overridden by the North American Plate-Jalisco Block, is clearly identified up to 21.5°N (just south of Maria Magdalena Island) as a two clear reflections that we interpret as the interplate and Moho discontinuities. North of the Tres Marias Islands the seismic images display a different tectonic scenario with structures that are consistent with large faulting and rifted margin. A two-dimensional velocity approach for the crustal geometry is achieved using joint refraction/reflection travel time tomography, the uncertainty of the results is assessed by means of Monte Carlo analysis. Our results show an average oceanic crustal thickness of 6-7 km with a moderate increase towards the Jalisco Block, an anomalous thick layers (~3.0 km) displaying a relatively low velocity (~5.5 km/s) underneath Maria Magdalena Rise, and an estimated Moho depth deeper than 15 km in the collision zone between Rivera Plate and Jalisco Block. We have also determined an anomalous crust on the western flank of the Tres Marias Islands, which may be related to the initial phases of continental breakup of the Baja California Peninsula and Mexico mainland. High-resolution bathymetry provides remarkable images of intensive slope instabilities marked by relatively large slides scars of more than 40 km2 extent, and mass-wasting deposits probably triggered by the intense seismicity in the area.

  3. Crustal Architecture at the Collision Zone Between Rivera and North American Plates at the Jalisco Block: Tsujal Project

    Science.gov (United States)

    Dañobeitia, Juanjo; Bartolomé, Rafael; Prada, Manel; Nuñez-Cornú, Francisco; Córdoba, Diego; Bandy, William L.; Estrada, F.; Cameselle, Alejandra L.; Nuñez, Diana; Castellón, Arturo; Alonso, José Luis; Mortera, Carlos; Ortiz, Modesto

    2016-10-01

    Processing and analysis of new multichannel seismic records, coincident with wide-angle seismic profiles, acquired in the framework of the TsuJal project allow us to investigate in detail the complex structure of the oceanic domain in the collision zone between Rivera Plate and Block Jalisco at its northern termination. The subducting Rivera Plate, which is overridden by the North American Plate-Jalisco Block, is clearly identified up to 21.5°N (just south of Maria Magdalena Island) as a two clear reflections that we interpret as the interplate and Moho discontinuities. North of the Tres Marias Islands the seismic images display a different tectonic scenario with structures that are consistent with large faulting and rifted margin. A two-dimensional velocity approach for the crustal geometry is achieved using joint refraction/reflection travel time tomography, the uncertainty of the results is assessed by means of Monte Carlo analysis. Our results show an average oceanic crustal thickness of 6-7 km with a moderate increase towards the Jalisco Block, an anomalous thick layers (~3.0 km) displaying a relatively low velocity (~5.5 km/s) underneath Maria Magdalena Rise, and an estimated Moho depth deeper than 15 km in the collision zone between Rivera Plate and Jalisco Block. We have also determined an anomalous crust on the western flank of the Tres Marias Islands, which may be related to the initial phases of continental breakup of the Baja California Peninsula and Mexico mainland. High-resolution bathymetry provides remarkable images of intensive slope instabilities marked by relatively large slides scars of more than 40 km2 extent, and mass-wasting deposits probably triggered by the intense seismicity in the area.

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

    CSIR Research Space (South Africa)

    Gregory, MA

    1996-10-01

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

  5. Cilia propel the embryo in the right direction.

    Science.gov (United States)

    Brueckner, M

    2001-07-15

    Cilia have long been suspected to play a role in the determination of left-right asymmetry. Humans with the dominantly inherited condition Kartagener syndrome have defective cilia and a 50% incidence of mirror-image positioning of their organs (situs inversus). Analysis of mouse mutations affecting ciliary biogenesis and motility has demonstrated that the molecular motors kinesin and dynein are required to establish normal handed organismal asymmetry. The cilia that propel formation of the embryonic left-right axis are not conventional cilia, but monocilia. They are found on the node, or organizer, of the gastrulation-stage mouse embryo where they drive net leftward movement of the fluid surrounding the node, and initiate left-right asymmetry.

  6. Overview of structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren Tvorup

    2007-01-01

    controlling motility and/or linking mechanical or chemical stimuli, including sonic hedgehog and growth factors, to intracellular transduction cascades regulating differentiation, migration, and cell growth during development and in adulthood. Unique motile 9 + 0 cilia, found during development...

  7. The significance of ultrastructural abnormalities of human cilia.

    Science.gov (United States)

    Fox, B; Bull, T B; Makey, A R; Rawbone, R

    1981-12-01

    The electronmicroscopic structure of cilia was studied from the inferior turbinate of the nose in 22 adults, and in 84 biopsies from the bronchial tree of 40 adults. The incidence of compound cilia and abnormal microtubular structures was assessed. There were significant variations in the incidence of abnormalities in different parts of the airways and even within different areas of the same electronmicroscopic section. The focal nature of differences in structure of cilia indicate that abnormalities found in a single biopsy do not necessarily reflect a generalized change in the bronchial tree. Thus, such a finding should not be used as evidence that the abnormalities of cilia are the cause of decrease in mucociliary clearance or that they play a role in the pathogenesis of bronchiectasis and sinusitis.

  8. Branchial Cilia and Sperm Flagella Recruit Distinct Axonemal Components

    Science.gov (United States)

    Konno, Alu; Shiba, Kogiku; Cai, Chunhua; Inaba, Kazuo

    2015-01-01

    Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are functionally diverged to play cell-type-specific roles even in a multicellular organism. Although their structural components are therefore believed to be common, few studies have investigated the molecular diversity of the protein components of the cilia and flagella in a single organism. Here we carried out a proteomic analysis and compared protein components between branchial cilia and sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct feature of protein recruitment in branchial cilia and sperm flagella has been clarified; (1) Isoforms of α- and β-tubulins as well as those of actins are distinctly used in branchial cilia or sperm flagella. (2) Structural components, such as dynein docking complex, tektins and an outer dense fiber protein, are used differently by the cilia and flagella. (3) Sperm flagella are specialized for the cAMP- and Ca2+-dependent regulation of outer arm dynein and for energy metabolism by glycolytic enzymes. Our present study clearly demonstrates that flagellar or ciliary proteins are properly recruited according to their function and stability, despite their apparent structural resemblance and conservation. PMID:25962172

  9. Branchial cilia and sperm flagella recruit distinct axonemal components.

    Directory of Open Access Journals (Sweden)

    Alu Konno

    Full Text Available Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are functionally diverged to play cell-type-specific roles even in a multicellular organism. Although their structural components are therefore believed to be common, few studies have investigated the molecular diversity of the protein components of the cilia and flagella in a single organism. Here we carried out a proteomic analysis and compared protein components between branchial cilia and sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct feature of protein recruitment in branchial cilia and sperm flagella has been clarified; (1 Isoforms of α- and β-tubulins as well as those of actins are distinctly used in branchial cilia or sperm flagella. (2 Structural components, such as dynein docking complex, tektins and an outer dense fiber protein, are used differently by the cilia and flagella. (3 Sperm flagella are specialized for the cAMP- and Ca2+-dependent regulation of outer arm dynein and for energy metabolism by glycolytic enzymes. Our present study clearly demonstrates that flagellar or ciliary proteins are properly recruited according to their function and stability, despite their apparent structural resemblance and conservation.

  10. A single magnetic nanocomposite cilia force sensor

    KAUST Repository

    Alfadhel, Ahmed

    2016-04-20

    The advancements in fields like robotics and medicine continuously require improvements of sensor devices and more engagement of cooperative sensing technologies. For example, instruments such as tweezers with sensitive force sensory heads could provide the ability to sense a variety of physical quantities in real time, such as the amount and direction of the force applied or the texture of the gripped object. Force sensors with such abilities could be great solutions toward the development of smart surgical tools. In this work, a unique force sensor that can be integrated at the tips of robotic arms or surgical tools is reported. The force sensor consists of a single bioinspired, permanent magnetic and highly elastic nanocomposite cilia integrated on a magnetic field sensing element. The nanocomposite is prepared from permanent magnetic nanowires incorporated into the highly elastic polydimethylsiloxane. We demonstrate the potential of this concept by performing several experiments to show the performance of the force sensor. The developed sensor element has a 200 μm in diameter single cilium with 1:5 aspect ratio and shows a detection range up to 1 mN with a sensitivity of 1.6 Ω/mN and a resolution of 31 μN. The simple fabrication process of the sensor allows easy optimization of the sensor performance to meet the needs of different applications.

  11. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality

    DEFF Research Database (Denmark)

    Boskovski, Marko T; Yuan, Shiaulou; Pedersen, Nis Borbye

    2013-01-01

    , where motile cilia generate leftward flow that is detected by immotile sensory cilia, which transduce flow into downstream asymmetric signals. The mechanism that specifies these two cilia types remains unknown. Here we show that the N-acetylgalactosamine-type O-glycosylation enzyme GALNT11 is crucial...... of motile and immotile cilia at the left-right organizer. galnt11 or notch1 depletion increases the ratio of motile cilia at the expense of immotile cilia and produces a laterality defect reminiscent of loss of the ciliary sensor Pkd2. By contrast, Notch overexpression decreases this ratio, mimicking...

  12. Ectopia cilia with pedigree analysis: Second case report in the world

    Directory of Open Access Journals (Sweden)

    Tarang Goyal

    2014-01-01

    Full Text Available We present a case of ectopia cilia in a 28-year-old male patient. Ectopia cilia was were seen in the outer third of left upper eyelid. The patient′s maternal grandfather also had ectopia cilia of the left upper eyelid as reported by the patient′s mother. Ectopia cilia is a rare condition seen in humans. Only 12 cases of ectopic cilia in humans have been reported so far in the world. The present case of ectopia cilia is the second case report in the world with pedigree analysis.

  13. Conservation of ciliary proteins in plants with no cilia

    Directory of Open Access Journals (Sweden)

    Hodges Matthew E

    2011-12-01

    Full Text Available Abstract Background Eukaryotic cilia are complex, highly conserved microtubule-based organelles with a broad phylogenetic distribution. Cilia were present in the last eukaryotic common ancestor and many proteins involved in cilia function have been conserved through eukaryotic diversification. However, cilia have also been lost multiple times in different lineages, with at least two losses occurring within the land plants. Whereas all non-seed plants produce cilia for motility of male gametes, some gymnosperms and all angiosperms lack cilia. During these evolutionary losses, proteins with ancestral ciliary functions may be lost or co-opted into different functions. Results Here we identify a core set of proteins with an inferred ciliary function that are conserved in ciliated eukaryotic species. We interrogate this genomic dataset to identify proteins with a predicted ancestral ciliary role that have been maintained in non-ciliated land plants. In support of our prediction, we demonstrate that several of these proteins have a flagellar localisation in protozoan trypanosomes. The phylogenetic distribution of these genes within the land plants indicates evolutionary scenarios of either sub- or neo-functionalisation and expression data analysis shows that these genes are highly expressed in Arabidopsis thaliana pollen cells. Conclusions A large number of proteins possess a phylogenetic ciliary profile indicative of ciliary function. Remarkably, many genes with an ancestral ciliary role are maintained in non-ciliated land plants. These proteins have been co-opted to perform novel functions, most likely before the loss of cilia, some of which appear related to the formation of the male gametes.

  14. Magnetically-actuated artificial cilia for microfluidic propulsion

    CERN Document Server

    Khaderi, S N; Anderson, P D; Ioan, D; Toonder, J M J den; Onck, P R

    2009-01-01

    Natural cilia are hair-like microtubule-based structures that are able to move fluid at low Reynolds number through asymmetric motion. In this paper we follow a biomimetic approach to design artificial cilia lining the inner surface of microfluidic channels with the goal to propel fluid. The artificial cilia consist of polymer films filled with magnetic nanoparticles. The asymmetric, non-reciprocating motion is generated by tuning an external magnetic field. To obtain the magnetic field and associated magnetization local to the cilia we solve the Maxwell equations, from which the magnetic torques can be deduced. To obtain the ciliary motion we solve the dynamic equations of motion which are then fully coupled to the fluid dynamic equations that describe fluid flow around the cilia. By doing so we show that by properly tuning the applied magnetic field, asymmetric ciliary motion can be generated that is able to propel fluid in a microchannel. The results are presented in terms of three dimensionless parameters...

  15. Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans

    Directory of Open Access Journals (Sweden)

    Chunyue Miao

    2016-10-01

    Full Text Available Neural tube defects (NTDs are severe malformations of the central nervous system caused by complex genetic and environmental factors. Among genes involved in NTD, cilia-related genes have been well defined and found to be essential for the completion of neural tube closure (NTC. We have carried out next-generation sequencing on target genes in 373 NTDs and 222 healthy controls, and discovered eight disease-specific rare mutations in cilia-related gene DNAAF1. DNAAF1 plays a central role in cytoplasmic preassembly of distinct dynein-arm complexes, and is expressed in some key tissues involved in neural system development, such as neural tube, floor plate, embryonic node, and brain ependyma epithelial cells in zebrafish and mouse. Therefore, we evaluated the expression and functions of mutations in DNAAF1 in transfected cells to analyze the potential correlation of these mutants to NTDs in humans. One rare frameshift mutation (p.Gln341Argfs*10 resulted in significantly diminished DNAAF1 protein expression, compared to the wild type. Another mutation, p.Lys231Gln, disrupted cytoplasmic preassembly of the dynein-arm complexes in cellular assay. Furthermore, results from NanoString assay on mRNA from NTD samples indicated that DNAAF1 mutants altered the expression level of NTC-related genes. Altogether, these findings suggest that the rare mutations in DNAAF1 may contribute to the susceptibility for NTDs in humans.

  16. nlz1 is required for cilia formation in zebrafish embryogenesis.

    Science.gov (United States)

    Dutta, Sunit; Sriskanda, Shahila; Boobalan, Elangovan; Alur, Ramakrishna P; Elkahloun, Abdel; Brooks, Brian P

    2015-10-15

    The formation of cilia is a fundamental developmental process affecting diverse functions such as cellular signaling, tissue morphogenesis and body patterning. However, the mechanisms of ciliogenesis during vertebrate development are not fully understood. In this report we describe a novel role of the Nlz1 protein in ciliogenesis. We demonstrate morpholino-mediated knockdown of nlz1 in zebrafish causes abnormal specification of the cells of Kupffer's vesicle (KV); a severe reduction of the number of cilia in KV, the pronephros, and the neural floorplate; and a spectrum of later phenotypes reminiscent of human ciliopathies. In vitro and in vivo data indicate that Nlz1 acts downstream of Foxj1a and Wnt8a/presumed canonical Wnt signaling. Furthermore, Nlz1 contributes to motile cilia formation by positively regulating Wnt11/presumed non-canonical Wnt signaling. Together, our data suggest a novel role of nlz1 in ciliogenesis and the morphogenesis of multiple tissues.

  17. Symmetry breaking cilia-driven flow in the zebrafish embryo

    CERN Document Server

    Smith, Andrew A; Smith, David J; Blake, John R

    2013-01-01

    Fluid mechanics plays a vital role in early vertebrate embryo development, an example being the establishment of left-right asymmetry. Following the dorsal-ventral and anterior-posterior axes, the left-right axis is the last to be established; in several species it has been shown that an important process involved with this is the production of a left-right asymmetric flow driven by 'whirling' cilia. It has previously been established in experimental and mathematical models of the mouse ventral node that the combination of a consistent rotational direction and posterior tilt creates left-right asymmetric flow. The zebrafish organising structure, Kupffer's vesicle, has a more complex internal arrangement of cilia than the mouse ventral node; experimental studies show the flow exhibits an anticlockwise rotational motion when viewing the embryo from the dorsal roof, looking in the ventral direction. Reports of the arrangement and configuration of cilia suggest two possible mechanisms for the generation of this f...

  18. Novel Insights into the Development and Function of Cilia Using the Advantages of the Paramecium Cell and Its Many Cilia

    Directory of Open Access Journals (Sweden)

    Junji Yano

    2015-07-01

    Full Text Available Paramecium species, especially P. tetraurelia and caudatum, are model organisms for modern research into the form and function of cilia. In this review, we focus on the ciliary ion channels and other transmembrane proteins that control the beat frequency and wave form of the cilium by controlling the signaling within the cilium. We put these discussions in the context of the advantages that Paramecium brings to the understanding of ciliary motility: mutants for genetic dissections of swimming behavior, electrophysiology, structural analysis, abundant cilia for biochemistry and modern proteomics, genomics and molecular biology. We review the connection between behavior and physiology, which allows the cells to broadcast the function of their ciliary channels in real time. We build a case for the important insights and advantages that this model organism continues to bring to the study of cilia.

  19. TMJ development and growth require primary cilia function.

    Science.gov (United States)

    Kinumatsu, T; Shibukawa, Y; Yasuda, T; Nagayama, M; Yamada, S; Serra, R; Pacifici, M; Koyama, E

    2011-08-01

    Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction.

  20. A coating of passively oscillating flexible cilia to reduce drag

    Science.gov (United States)

    Revell, Alistair; Harwood, Adrian; O'Connor, Joseph; Sanchez, Jonathan; Favier, Julien

    2016-11-01

    We present results related to the reduction of wake drag by the coordinated action of a layer of passively oscillating flexible cilia. Inspired by the pop-up of bird feathers, this configuration is shown to self-adapt to the surrounding flow, leading to a stabilization of the wake, a reduction of the mean drag and of lift oscillations. The study is performed using Lattice Boltzmann method, coupled to a recent version of the immersed boundary method. We will present the physical analysis of the coupling between multiple beating cilia and an incoming fluid flow. The modal behaviour of the cilia dynamics will be discussed, as well as their effect on an archetype of unsteady separated boundary layer (first the oscillating channel flow and then the circular cylinder). In the latter case results demonstrate an optimal drag occurs for a particular stiffness, compared to the control case where the same cilia are fixed. It appears that the optimal results are due to a reconfiguration of the elastic coating according to the local vorticity of the flow, and a frequency lock-in, which leads to more stable wake and reduced drag. The structural parameters of the layer will be varied. Results from the PEL-SKIN project: funded by EU Grant #334954.

  1. Realizing the Physics of Motile Cilia Synchronization with Driven Colloids

    Science.gov (United States)

    Bruot, Nicolas; Cicuta, Pietro

    2016-03-01

    Cilia and flagella in biological systems often show large scale cooperative behaviors such as the synchronization of their beats in "metachronal waves." These are beautiful examples of emergent dynamics in biology, and are essential for life, allowing diverse processes from the motility of eukaryotic microorganisms, to nutrient transport and clearance of pathogens from mammalian airways. How these collective states arise is not fully understood, but it is clear that individual cilia interact mechanically, and that a strong and long-ranged component of the coupling is mediated by the viscous fluid. We review here the work by ourselves and others aimed at understanding the behavior of hydrodynamically coupled systems, and particularly a set of results that have been obtained both experimentally and theoretically by studying actively driven colloidal systems. In these controlled scenarios, it is possible to selectively test aspects of living motile cilia, such as the geometrical arrangement, the effects of the driving profile and the distance to no-slip boundaries. We outline and give examples of how it is possible to link model systems to observations on living systems, which can be made on microorganisms, on cell cultures or on tissue sections. This area of research has clear clinical application in the long term, as severe pathologies are associated with compromised cilia function in humans.

  2. Oscillatory fluid flow influences primary cilia and microtubule mechanics.

    Science.gov (United States)

    Espinha, Lina C; Hoey, David A; Fernandes, Paulo R; Rodrigues, Hélder C; Jacobs, Christopher R

    2014-07-01

    Many tissues are sensitive to mechanical stimuli; however, the mechanotransduction mechanism used by cells remains unknown in many cases. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell which extends from the basal body. The cilium is a mechanosensitive organelle and has been shown to transduce fluid flow-induced shear stress in tissues, such as the kidney and bone. The majority of microtubules assemble from the mother centriole (basal body), contributing significantly to the anchoring of the primary cilium. Several studies have attempted to quantify the number of microtubules emanating from the basal body and the results vary depending on the cell type. It has also been shown that cellular response to shear stress depends on microtubular integrity. This study hypothesizes that changing the microtubule attachment of primary cilia in response to a mechanical stimulus could change primary cilia mechanics and, possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different cell types and the microtubule attachment to the ciliary base was quantified. For the first time, an increase in microtubules around primary cilia both with time and shear rate in response to oscillatory fluid flow stimulation was demonstrated. Moreover, it is presented that the primary cilium is required for this loading-induced cellular response. This study has demonstrated a new role for the cilium in regulating alterations in the cytoplasmic microtubule network in response to mechanical stimulation, and therefore provides a new insight into how cilia may regulate its mechanics and thus the cells mechanosensitivity.

  3. Rheological fluid motion in tube by metachronal wave of cilia

    CERN Document Server

    Maiti, S

    2013-01-01

    The purpose of this paper is a theoretical study of a non-linear problem of rheological fluid transport in an axisymmetric tube by cilium. However, an attempt has been made to explain the role of cilia motion on the transport of fluid through the ductus efferentes of the male reproductive tract. Ostwald-de Waele power law viscous fluid has been considered to represent the rheological fluid to analyze pumping by means of a sequence of beat of cilia from row to row of cilia in a given row of cells and from one row of cells to the next (metachronal wave movement) under conditions for which the corresponding Reynolds number is small enough for inertial effects to be negligible and the wavelength to diameter ratio is large enough for the pressure to be considered uniform over the cross-section. Analyses and computations of the detailed fluid motions reveal that the time-averaged flow rates are directly dependent on epsilon, a non-dimensional measure involving the mean radius R of the tube and the cilia length. Thu...

  4. Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis.

    Directory of Open Access Journals (Sweden)

    Dragana Antic

    Full Text Available Left-right asymmetry in vertebrates is initiated in an early embryonic structure called the ventral node in human and mouse, and the gastrocoel roof plate (GRP in the frog. Within these structures, each epithelial cell bears a single motile cilium, and the concerted beating of these cilia produces a leftward fluid flow that is required to initiate left-right asymmetric gene expression. The leftward fluid flow is thought to result from the posterior tilt of the cilia, which protrude from near the posterior portion of each cell's apical surface. The cells, therefore, display a morphological planar polarization. Planar cell polarity (PCP is manifested as the coordinated, polarized orientation of cells within epithelial sheets, or as directional cell migration and intercalation during convergent extension. A set of evolutionarily conserved proteins regulates PCP. Here, we provide evidence that vertebrate PCP proteins regulate planar polarity in the mouse ventral node and in the Xenopus gastrocoel roof plate. Asymmetric anterior localization of VANGL1 and PRICKLE2 (PK2 in mouse ventral node cells indicates that these cells are planar polarized by a conserved molecular mechanism. A weakly penetrant Vangl1 mutant phenotype suggests that compromised Vangl1 function may be associated with left-right laterality defects. Stronger functional evidence comes from the Xenopus GRP, where we show that perturbation of VANGL2 protein function disrupts the posterior localization of motile cilia that is required for leftward fluid flow, and causes aberrant expression of the left side-specific gene Nodal. The observation of anterior-posterior PCP in the mouse and in Xenopus embryonic organizers reflects a strong evolutionary conservation of this mechanism that is important for body plan determination.

  5. Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome.

    Science.gov (United States)

    Cui, Cheng; Chatterjee, Bishwanath; Francis, Deanne; Yu, Qing; SanAgustin, Jovenal T; Francis, Richard; Tansey, Terry; Henry, Charisse; Wang, Baolin; Lemley, Bethan; Pazour, Gregory J; Lo, Cecilia W

    2011-01-01

    Meckel-Gruber syndrome (MKS) is a recessive disorder resulting in multiple birth defects that are associated with mutations affecting ciliogenesis. We recovered a mouse mutant with a mutation in the Mks1 gene (Mks1(del64-323)) that caused a 260-amino-acid deletion spanning nine amino acids in the B9 domain, a protein motif with unknown function conserved in two other basal body proteins. We showed that, in wild-type cells, Mks1 was localized to the mother centriole from which the cilium was generated. However, in mutant Mks1(del64-323) cells, Mks1 was not localized to the centriole, even though it maintained a punctate distribution. Resembling MKS patients, Mks1 mutants had craniofacial defects, polydactyly, congenital heart defects, polycystic kidneys and randomized left-right patterning. These defects reflected disturbance of functions subserved by motile and non-motile cilia. In the kidney, glomerular and tubule cysts were observed along with short cilia, and cilia were reduced in number to a near-complete loss. Underlying the left-right patterning defects were fewer and shorter nodal cilia, and analysis with fluorescent beads showed no directional flow at the embryonic node. In the cochlea, the stereocilia were mal-patterned, with the kinocilia being abnormally positioned. Together, these defects suggested disruption of planar cell polarity, which is known to regulate node, kidney and cochlea development. In addition, we also showed that Shh signaling was disrupted. Thus, in the neural tube, the floor plate was not specified posteriorly even as expression of the Shh mediator Gli2 increased. By contrast, the Shh signaling domain was expanded in the anterior neural tube and anterior limb bud, consistent with reduced Gli3-repressor (Gli3R) function. The latter probably accounted for the preaxial digit duplication exhibited by the Mks1(del64-323) mutants. Overall, these findings indicate that centriole localization of Mks1 is required for ciliogenesis of motile and

  6. Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome

    Directory of Open Access Journals (Sweden)

    Cheng Cui

    2011-01-01

    Meckel-Gruber syndrome (MKS is a recessive disorder resulting in multiple birth defects that are associated with mutations affecting ciliogenesis. We recovered a mouse mutant with a mutation in the Mks1 gene (Mks1del64-323 that caused a 260-amino-acid deletion spanning nine amino acids in the B9 domain, a protein motif with unknown function conserved in two other basal body proteins. We showed that, in wild-type cells, Mks1 was localized to the mother centriole from which the cilium was generated. However, in mutant Mks1del64-323 cells, Mks1 was not localized to the centriole, even though it maintained a punctate distribution. Resembling MKS patients, Mks1 mutants had craniofacial defects, polydactyly, congenital heart defects, polycystic kidneys and randomized left-right patterning. These defects reflected disturbance of functions subserved by motile and non-motile cilia. In the kidney, glomerular and tubule cysts were observed along with short cilia, and cilia were reduced in number to a near-complete loss. Underlying the left-right patterning defects were fewer and shorter nodal cilia, and analysis with fluorescent beads showed no directional flow at the embryonic node. In the cochlea, the stereocilia were mal-patterned, with the kinocilia being abnormally positioned. Together, these defects suggested disruption of planar cell polarity, which is known to regulate node, kidney and cochlea development. In addition, we also showed that Shh signaling was disrupted. Thus, in the neural tube, the floor plate was not specified posteriorly even as expression of the Shh mediator Gli2 increased. By contrast, the Shh signaling domain was expanded in the anterior neural tube and anterior limb bud, consistent with reduced Gli3-repressor (Gli3R function. The latter probably accounted for the preaxial digit duplication exhibited by the Mks1del64-323 mutants. Overall, these findings indicate that centriole localization of Mks1 is required for ciliogenesis of motile and non

  7. Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus

    Directory of Open Access Journals (Sweden)

    Ponting Chris P

    2011-02-01

    Full Text Available Abstract Background Evc is essential for Indian Hedgehog (Hh signalling in the cartilage growth plate. The gene encoding Evc2 is in close proximity in divergent orientation to Evc and mutations in both human genes lead to the chondrodysplasia Ellis-van Creveld syndrome. Results Bioinformatic analysis reveals that the Evc and Evc2 genes arose through a duplication event early in metazoan evolution and were subsequently lost in arthropods and nematodes. Here we demonstrate that Evc2 is essential for Hh pathway activation in response to the Smo agonist purmorphamine. A yeast two-hybrid screen using Evc as bait identified Evc2 as an Evc binding partner and we confirmed the interaction by immunoprecipitation. We developed anti-Evc2 antibodies and show that Evc2 and Evc co-localize at the basal body and also on primary cilia. In transfected cells, basal body and cilia localization is observed when Evc and Evc2 constructs are co-transfected but not when either construct is transfected individually. We show that Evc and Evc2 are cilia transmembrane proteins, the C-terminus for both being intracellular and Evc2, but not Evc, having an extracellular portion. Furthermore, Evc is absent at the basal body in Evc2 null cells. Using Western blots of cytoplasmic and nuclear protein, we also demonstrate that full length Evc2 but not Evc, is located in the nucleus. Conclusions We demonstrate for the first time that Evc2 is a positive regulator of the Hh signalling pathway and that it is located at the basal body of primary cilia. We show that the presence of Evc and Evc2 at the basal body and cilia membrane is co-dependent. In addition, Evc2, but not Evc, is present in the cell nucleus suggesting movement of Evc2 between the cilium and nucleus.

  8. Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

    Science.gov (United States)

    Ruiz-Perez, Victor L; Blair, Helen J; Rodriguez-Andres, M Elena; Blanco, Maria Jose; Wilson, Amy; Liu, Yu-Ning; Miles, Colin; Peters, Heiko; Goodship, Judith A

    2007-08-01

    EVC is a novel protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated Evc in the mouse and show that Evc(-/-) mice develop an EvC-like syndrome, including short ribs, short limbs and dental abnormalities. lacZ driven by the Evc promoter revealed that Evc is expressed in the developing bones and the orofacial region. Antibodies developed against Evc locate the protein at the base of the primary cilium. The growth plate of Evc(-/-) mice shows delayed bone collar formation and advanced maturation of chondrocytes. Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreased. Recent studies have shown that Smo localises to primary cilia and that Gli3 processing is defective in intraflagellar transport mutants. In vitro studies using Evc(-/-) cells demonstrate that the defect lies downstream of Smo. Chondrocyte cilia are present in Evc(-/-) mice and Gli3 processing appears normal by western blot analysis. We conclude that Evc is an intracellular component of the hedgehog signal transduction pathway that is required for normal transcriptional activation of Ihh target genes.

  9. Mathematical embryology: the fluid mechanics of nodal cilia

    CERN Document Server

    Smith, David J; Blake, John R

    2010-01-01

    Left-right symmetry breaking is critical to vertebrate embryonic development; in many species this process begins with cilia-driven flow in a structure termed the `node'. Primary `whirling' cilia, tilted towards the posterior, transport morphogen-containing vesicles towards the left, initiating left-right asymmetric development. We review recent theoretical models based on the point-force stokeslet and point-torque rotlet singularities, explaining how rotation and surface-tilt produce directional flow. Analysis of image singularity systems enforcing the no-slip condition shows how tilted rotation produces a far-field `stresslet' directional flow, and how time-dependent point-force and time-independent point-torque models are in this respect equivalent. Associated slender body theory analysis is reviewed; this approach enables efficient and accurate simulation of three-dimensional time-dependent flow, time-dependence being essential in predicting features of the flow such as chaotic advection, which have subse...

  10. EB1 is required for primary cilia assembly in fibroblasts

    DEFF Research Database (Denmark)

    Schrøder, Jacob M; Schneider, Linda; Christensen, Søren T

    2007-01-01

    EB1 is a small microtubule (MT)-binding protein that associates preferentially with MT plus ends and plays a role in regulating MT dynamics. EB1 also targets other MT-associated proteins to the plus end and thereby regulates interactions of MTs with the cell cortex, mitotic kinetochores, and diff......EB1 is a small microtubule (MT)-binding protein that associates preferentially with MT plus ends and plays a role in regulating MT dynamics. EB1 also targets other MT-associated proteins to the plus end and thereby regulates interactions of MTs with the cell cortex, mitotic kinetochores...... in the cilium/flagellum is unknown. We depleted EB1 from NIH3T3 fibroblasts by using siRNA and found that EB1 depletion causes a approximately 50% reduction in the efficiency of primary cilia assembly in serum-starved cells. Expression of dominant-negative EB1 also inhibited cilia formation, and expression...

  11. Cilia Control Vascular Mural Cell Recruitment in Vertebrates

    Directory of Open Access Journals (Sweden)

    Xiaowen Chen

    2017-01-01

    Full Text Available Vascular mural cells (vMCs are essential components of the vertebrate vascular system, controlling blood vessel maturation and homeostasis. Discrete molecular mechanisms have been associated with vMC development and differentiation. The function of hemodynamic forces in controlling vMC recruitment is unclear. Using transgenic lines marking developing vMCs in zebrafish embryos, we find that vMCs are recruited by arterial-fated vessels and that the process is flow dependent. We take advantage of tissue-specific CRISPR gene targeting to demonstrate that hemodynamic-dependent Notch activation and the ensuing arterial genetic program is driven by endothelial primary cilia. We also identify zebrafish foxc1b as a cilia-dependent Notch-specific target that is required within endothelial cells to drive vMC recruitment. In summary, we have identified a hemodynamic-dependent mechanism in the developing vasculature that controls vMC recruitment.

  12. Effect of Cilia Beat Frequency on Mucociliary Clearance

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    Sedaghat M. H.

    2016-12-01

    Full Text Available Background: The airway surface liquid (ASL, which is a fluid layer coating the interior epithelial surface of the bronchi and bronchiolesis, plays an important defensive role against foreign particles and chemicals entering lungs. Objective: Numerical investigation has been employed to solve two-layer model consisting of mucus layer as a viscoelastic fluid and periciliary liquid layer as a Newtonian fluid to study the effects of cilia beat frequency (CBF at various amounts of mucus properties on muco-ciliary transport problem. Methods: Hybrid finite difference-lattice Boltzmann-method (FB-LBM has been used to solve the momentum equations and to simulate cilia forces, and also the PCLmucus interface more accurately, immersed boundary method (IBM has been employed. The main contribution of the current study is to use an Oldroyd-B model as the constitutive equation of mucus. Results: Our results show that increasing CBF and decreasing mucus viscosity ratio have great effects on mucus flow, but the effect of viscosity ratio is more significant. The results also illustrate that the relation between cilia beat frequency and mean mucus velocity is almost linear and it has similar behavior at different values of viscosity ratio. Conclusion: Numerical investigation based on hybrid IB-FD-LBM has been used to study the effect of CBF at various mounts of mucus viscosity ratio on the muco-ciliary clearance. The results showed that the effect of viscosity ratio on the muco-ciliary transport process is more significant compared with CBF.

  13. Primary cilia in energy balance signaling and metabolic disorder.

    Science.gov (United States)

    Lee, Hankyu; Song, Jieun; Jung, Joo Hyun; Ko, Hyuk Wan

    2015-12-01

    Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alström syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell's antenna to obesity and type II diabetes.

  14. Intraflagellar transport gene expression associated with short cilia in smoking and COPD.

    Directory of Open Access Journals (Sweden)

    Justina Hessel

    Full Text Available Smoking and COPD are associated with decreased mucociliary clearance, and healthy smokers have shorter cilia in the large airway than nonsmokers. We hypothesized that changes in cilia length are consistent throughout the airway, and we further hypothesized that smokers with COPD have shorter cilia than healthy smokers. Because intraflagellar transport (IFT is the process by which cilia of normal length are produced and maintained, and alterations in IFT lead to short cilia in model organisms, we also hypothesized that smoking induces changes in the expression of IFT-related genes in the airway epithelium of smokers and smokers with COPD. To assess these hypotheses, airway epithelium was obtained via bronchoscopic brushing. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells per subject and Affymetrix microarrays were used to evaluate IFT gene expression in nonsmokers and healthy smokers in 2 independent data sets from large and small airway as well as in COPD smokers in a data set from the small airway. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. The gene expression data confirmed that a set of 8 IFT genes were down-regulated in smokers in both data sets; however, no differences were seen in COPD smokers compared to healthy smokers. These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies.

  15. Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction.

    Directory of Open Access Journals (Sweden)

    Louise V Wain

    2014-05-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1 despite many years of heavy smoking. We hypothesised that these "resistant smokers" may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re-sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the "resistant smokers" and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.34 × 10(-4 in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial

  16. Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development.

    Science.gov (United States)

    Marra, Amanda N; Li, Yue; Wingert, Rebecca A

    2016-09-01

    Cilia arose early during eukaryotic evolution, and their structural components are highly conserved from the simplest protists to complex metazoan species. In recent years, the role of cilia in the ontogeny of vertebrate organs has received increasing attention due to a staggering correlation between human disease and dysfunctional cilia. In particular, the presence of cilia in both the developing and mature kidney has become a deep area of research due to ciliopathies common to the kidney, such as polycystic kidney disease (PKD). Interestingly, mutations in genes encoding proteins that localize to the cilia cause similar cystic phenotypes in kidneys of various vertebrates, suggesting an essential role for cilia in kidney organogenesis and homeostasis as well. Importantly, the genes so far identified in kidney disease have conserved functions across species, whose kidneys include both primary and motile cilia. Here, we aim to provide a comprehensive description of cilia and their role in kidney development, as well as highlight the usefulness of the zebrafish embryonic kidney as a model to further understand the function of cilia in kidney health.

  17. A facile template-free approach to magnetodriven, multifunctional artificial cilia.

    Science.gov (United States)

    Timonen, Jaakko V I; Johans, Christoffer; Kontturi, Kyösti; Walther, Andreas; Ikkala, Olli; Ras, Robin H A

    2010-08-01

    Flexible and magnetic artificial cilia were grown on various substrates by a facile bottom-up approach based on template-free magnetic assembly. The magnetic cilia formed spontaneously from a suspension of micrometer-sized ferromagnetic particles and elastomeric polymer in a liquid solvent when dried in an external magnetic field. The cilia mimics were mechanically stable even in the absence of an external magnetic field and a solvent due to the polymer, which acted as "glue" holding the particles together and connecting the cilia to the substrate. The length of the magnetic cilia was in the millimeter range, that is, two to three orders of magnitude times the length of typical biological cilia. The aspect ratio reached values over 100 and was tunable with the magnetic field gradient and the size of the ferromagnetic particles. The cilia mimics responded to an external magnetic field by reversibly bending along the field. The bending actuation was sufficiently powerful to allow two functions: to translate macroscopic nonmagnetic objects placed over the cilia mimics and to mix liquids of even high viscosity. The mechanical properties of the magnetic cilia could be easily tuned by changing the impregnating polymer. The particularly simple template-free construction and fixation on various surfaces suggest applications as an externally controllable surface.

  18. Multiple essential roles for primary cilia in heart development

    Directory of Open Access Journals (Sweden)

    Willaredt Marc August

    2012-12-01

    Full Text Available Abstract Background The primary cilium is a microtubule-based, plasma membrane-ensheathed protrusion projecting from the basal bodies of almost all cell types in the mammalian body. In the past several years a plethora of papers has indicated a crucial role for primary cilia in the development of a wide variety of organs. We have investigated heart development in cobblestone, a hypomorphic allele of the gene encoding the intraflagellar transport protein Ift88, and uncovered a number of the most common congenital heart defects seen in newborn humans. Methods We generated serial sections of mutant cobblestone and wild type embryos in the region encompassing the heart and the cardiac outflow tract. The sections were further processed to generate three-dimensional reconstructions of these structures, and immunofluorescence confocal microscopy, transmission electron microscopy, and in situ hybridization were used to examine signal transduction pathways in the relevant areas. Whole mount in situ hybridization was also employed for certain developmental markers. Results In addition to an enlarged pericardium and failure of both ventricular and atrial septum formation, the cobblestone mutants displayed manifold defects in outflow tract formation, including persistent truncus arteriosus, an overriding aorta, and abnormal transformation of the aortic arches. To discern the basis of these anomalies we examined both the maintenance of primary cilia as well as endogenous and migratory embryonic cell populations that contribute to the outflow tract and atrioventricular septa. The colonization of the embryonic heart by cardiac neural crest occurred normally in the cobblestone mutant, as did the expression of Sonic hedgehog. However, with the loss of primary cilia in the mutant hearts, there was a loss of both downstream Sonic hedgehog signaling and of Islet 1 expression in the second heart field, a derivative of the pharyngeal mesoderm. In addition, defects

  19. Primary cilia and coordination of signaling pathways in heart development and tissue Homeostasis

    DEFF Research Database (Denmark)

    Clement, Christian Alexandro

    of primary cilia in coordinating Hh signaling in human pancreatic development and postnatal tissue homeostasis. In cultures of human pancreatic duct adenocarcinoma cell lines PANC-1 and CFPAC-1, Ptc in addition to Gli2 and Smo localize to primary cilia. These findings are consistent with the idea...

  20. Primary cilia and coordination of signaling pathways in heart development and tissue Homeostasis

    DEFF Research Database (Denmark)

    Clement, Christian Alexandro

    This thesis focuses on cilia and their sensory function in the mammalian organism. In particular, the Hedgehog (Hh) signaling pathway functions via the primary cilium and plays a unique role in development, differentiation, cancer and possibly in stem cell fate. Defects in primary cilia assembly...

  1. Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species.

    Science.gov (United States)

    Han, Sang Jun; Jang, Hee-Seong; Kim, Jee In; Lipschutz, Joshua H; Park, Kwon Moo

    2016-02-29

    The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS).

  2. Fluid-structure interaction of three-dimensional magnetic artificial cilia

    NARCIS (Netherlands)

    Khaderi, S. N.; Onck, P. R.

    2012-01-01

    A numerical model is developed to analyse the interaction of artificial cilia with the surrounding fluid in a three-dimensional setting in the limit of vanishing fluid inertia forces. The cilia are modelled using finite shell elements and the fluid is modelled using a boundary element approach. The

  3. Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.

    Directory of Open Access Journals (Sweden)

    Astrid Cornils

    2016-12-01

    Full Text Available The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT. Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.

  4. 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.

  5. 5-HT6 receptor blockade regulates primary cilia morphology in striatal neurons.

    Science.gov (United States)

    Brodsky, Matthew; Lesiak, Adam J; Croicu, Alex; Cohenca, Nathalie; Sullivan, Jane M; Neumaier, John F

    2017-04-01

    The 5-HT6 receptor has been implicated in a variety of cognitive processes including habitual behaviors, learning, and memory. It is found almost exclusively in the brain, is expressed abundantly in striatum, and localizes to neuronal primary cilia. Primary cilia are antenna-like, sensory organelles found on most neurons that receive both chemical and mechanical signals from other cells and the surrounding environment; however, the effect of 5-HT6 receptor function on cellular morphology has not been examined. We confirmed that 5-HT6 receptors were localized to primary cilia in wild-type (WT) but not 5-HT6 knockout (5-HT6KO) in both native mouse brain tissue and primary cultured striatal neurons then used primary neurons cultured from WT or 5-HT6KO mice to study the function of these receptors. Selective 5-HT6 antagonists reduced cilia length in neurons cultured from wild-type mice in a concentration and time-dependent manner without altering dendrites, but had no effect on cilia length in 5-HT6KO cultured neurons. Varying the expression levels of heterologously expressed 5-HT6 receptors affected the fidelity of ciliary localization in both WT and 5-HT6KO neurons; overexpression lead to increasing amounts of 5-HT6 localization outside of the cilia but did not alter cilia morphology. Introducing discrete mutations into the third cytoplasmic loop of the 5-HT6 receptor greatly reduced, but did not entirely eliminate, trafficking of the 5-HT6 receptor to primary cilia. These data suggest that blocking 5-HT6 receptor activity reduces the length of primary cilia and that mechanisms that regulate trafficking of 5-HT6 receptors to cilia are more complex than previously thought. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Energy modelling of PREMIO platform, an architecture dedicated to dynamic load management on electric grid; Modelisation energetique de la plate-forme PREMIO, une architecture dediee a la gestion dynamique de la charge sur le reseau electrique

    Energy Technology Data Exchange (ETDEWEB)

    Bougnol, P.; Imbert, P. [ParisTech et l' Institut EIFER, 75 (France); Chartres, S. [Institut EIFER (France); Normand, O. [EDF R and D/EIFER (France)

    2010-01-15

    The cluster of competencies CapEnergies in co-founding with the PACA region launched PREMIO project in 2008. This project aims at implementing a local, innovative and replicable energy architecture that optimizes dynamic load management in order to diminish constraints on power grid and CO{sub 2} emissions. Technical, economical, environmental and sociological impacts of this technology are a strategic issue for project partners that elaborate the business models and future energy policies.The model developed in the frame of PREMIO project provides at local scale (district to city) a method to assess the impact of PREMIO architecture on load curve, CO{sub 2} emissions and energy savings. A case study realised in Lambesc (PACA region) simulates two deployment scenarios of manageable systems: 100% and 50% of the territory consumption, storage and production usages. The exploitation of these results gives prospects to improve this model. (authors)

  7. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...... that is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that can...... the autonomy of architecture, not as an esoteric concept but as a valid source of information in a pragmatic design practice, may help us overcome the often-proclaimed dichotomy between formal autonomy and a societally committed architecture. It follows that in architectural education there can be a close...

  8. Role of cilia in normal pancreas function and in diseased states.

    Science.gov (United States)

    diIorio, Philip; Rittenhouse, Ann R; Bortell, Rita; Jurczyk, Agata

    2014-06-01

    Primary cilia play an essential role in modulating signaling cascades that shape cellular responses to environmental cues to maintain proper tissue development. Mutations in primary cilium proteins have been linked to several rare developmental disorders, collectively known as ciliopathies. Together with other disorders associated with dysfunctional cilia/centrosomes, affected individuals have increased risk of developing metabolic syndrome, neurologic disorders, and diabetes. In pancreatic tissues, cilia are found exclusively in islet and ductal cells where they play an essential role in pancreatic tissue organization. Their absence or disorganization leads to pancreatic duct abnormalities, acinar cell loss, polarity defects, and dysregulated insulin secretion. Cilia in pancreatic tissues are hubs for cellular signaling. Many signaling components, such as Hh, Notch, and Wnt, localize to pancreatic primary cilia and are necessary for proper development of pancreatic epithelium and β-cell morphogenesis. Receptors for neuroendocrine hormones, such as Somatostatin Receptor 3, also localize to the cilium and may play a more direct role in controlling insulin secretion due to somatostatin's inhibitory function. Finally, unique calcium signaling, which is at the heart of β-cell function, also occurs in primary cilia. Whereas voltage-gated calcium channels trigger insulin secretion and serve a variety of homeostatic functions in β-cells, transient receptor potential channels regulate calcium levels within the cilium that may serve as a feedback mechanism, regulating insulin secretion. This review article summarizes our current understanding of the role of primary cilia in normal pancreas function and in the diseased state.

  9. INPP5E regulates phosphoinositide-dependent cilia transition zone function.

    Science.gov (United States)

    Dyson, Jennifer M; Conduit, Sarah E; Feeney, Sandra J; Hakim, Sandra; DiTommaso, Tia; Fulcher, Alex J; Sriratana, Absorn; Ramm, Georg; Horan, Kristy A; Gurung, Rajendra; Wicking, Carol; Smyth, Ian; Mitchell, Christina A

    2017-01-02

    Human ciliopathies, including Joubert syndrome (JBTS), arise from cilia dysfunction. The inositol polyphosphate 5-phosphatase INPP5E localizes to cilia and is mutated in JBTS. Murine Inpp5e ablation is embryonically lethal and recapitulates JBTS, including neural tube defects and polydactyly; however, the underlying defects in cilia signaling and the function of INPP5E at cilia are still emerging. We report Inpp5e(-/-) embryos exhibit aberrant Hedgehog-dependent patterning with reduced Hedgehog signaling. Using mouse genetics, we show increasing Hedgehog signaling via Smoothened M2 expression rescues some Inpp5e(-/-) ciliopathy phenotypes and "normalizes" Hedgehog signaling. INPP5E's phosphoinositide substrates PI(4,5)P2 and PI(3,4,5)P3 accumulated at the transition zone (TZ) in Hedgehog-stimulated Inpp5e(-/-) cells, which was associated with reduced recruitment of TZ scaffolding proteins and reduced Smoothened levels at cilia. Expression of wild-type, but not 5-phosphatase-dead, INPP5E restored TZ molecular organization and Smoothened accumulation at cilia. Therefore, we identify INPP5E as an essential point of convergence between Hedgehog and phosphoinositide signaling at cilia that maintains TZ function and Hedgehog-dependent embryonic development.

  10. Direct recording and molecular identification of the calcium channel of primary cilia

    Science.gov (United States)

    Decaen, Paul G.; Delling, Markus; Vien, Thuy N.; Clapham, David E.

    2013-12-01

    A primary cilium is a solitary, slender, non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane. Housing components of the cell division apparatus between cell divisions, primary cilia also serve as specialized compartments for calcium signalling and hedgehog signalling pathways. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use diverse ion channels. An ion current has been measured from primary cilia of kidney cells, but the responsible genes have not been identified. The polycystin proteins (PC and PKD), identified in linkage studies of polycystic kidney disease, are candidate channels divided into two structural classes: 11-transmembrane proteins (PKD1, PKD1L1 and PKD1L2) remarkable for a large extracellular amino terminus of putative cell adhesion domains and a G-protein-coupled receptor proteolytic site, and the 6-transmembrane channel proteins (PKD2, PKD2L1 and PKD2L2; TRPPs). Evidence indicates that the PKD1 proteins associate with the PKD2 proteins via coiled-coil domains. Here we use a transgenic mouse in which only cilia express a fluorophore and use it to record directly from primary cilia, and demonstrate that PKD1L1 and PKD2L1 form ion channels at high densities in several cell types. In conjunction with an accompanying manuscript, we show that the PKD1L1-PKD2L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established hedgehog pathways.

  11. Dopamine receptor type 5 in the primary cilia has dual chemo- and mechano-sensory roles.

    Science.gov (United States)

    Abdul-Majeed, Shakila; Nauli, Surya M

    2011-08-01

    Polycystic kidney disease is characterized by cardiovascular irregularities, including hypertension. Dopamine, a circulating hormone, is implicated in essential hypertension in humans and animal models. Vascular endothelial primary cilia are known to function as mechano-sensory organelles. Although both primary cilia and dopamine receptors play important roles in vascular hypertension, their relationship has never been explored. To determine the roles of the dopaminergic system and mechano-sensory cilia, we studied the effects of dopamine on ciliary length and function in wild-type and mechano-insensitive polycystic mutant cells (Pkd1(-/)(-) and Tg737(orpk/orpk)). We show for the first time that mouse vascular endothelia exhibit dopamine receptor-type 5 (DR5), which colocalizes to primary cilia in cultured cells and mouse arteries in vivo. DR5 activation increases cilia length in arteries and endothelial cells through cofilin and actin polymerization. DR5 activation also restores cilia function in the mutant cells. In addition, silencing DR5 completely abolishes mechano-ciliary function in WT cells. We found that DR5 plays very important roles in ciliary length and function. Furthermore, the chemo-sensory function of cilia can alter the mechano-sensory function through changes in sensitivity to fluid-shear stress. We propose that ciliary DR5 has functional chemo- and mechano-sensory roles in endothelial cells.

  12. Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia

    Science.gov (United States)

    Sedykh, Irina; TeSlaa, Jessica J.; Tatarsky, Rose L.; Keller, Abigail N.; Toops, Kimberly A.; Lakkaraju, Aparna; Nyholm, Molly K.; Wolman, Marc A.; Grinblat, Yevgenya

    2016-01-01

    Cilia are cell surface organelles with key roles in a range of cellular processes, including generation of fluid flow by motile cilia. The axonemes of motile cilia and immotile kinocilia contain 9 peripheral microtubule doublets, a central microtubule pair, and 9 connecting radial spokes. Aberrant radial spoke components RSPH1, 3, 4a and 9 have been linked with primary ciliary dyskinesia (PCD), a disorder characterized by ciliary dysmotility; yet, radial spoke functions remain unclear. Here we show that zebrafish Rsph9 is expressed in cells bearing motile cilia and kinocilia, and localizes to both 9 + 2 and 9 + 0 ciliary axonemes. Using CRISPR mutagenesis, we show that rsph9 is required for motility of presumptive 9 + 2 olfactory cilia and, unexpectedly, 9 + 0 neural cilia. rsph9 is also required for the structural integrity of 9 + 2 and 9 + 0 ciliary axonemes. rsph9 mutant larvae exhibit reduced initiation of the acoustic startle response consistent with hearing impairment, suggesting a novel role for Rsph9 in the kinocilia of the inner ear and/or lateral line neuromasts. These data identify novel roles for Rsph9 in 9 + 0 motile cilia and in sensory kinocilia, and establish a useful zebrafish PCD model. PMID:27687975

  13. Be together, not the same: Spatiotemporal organization of different cilia types generates distinct transport functions

    Science.gov (United States)

    Nawroth, Janna; Guo, Hanliang; Ruby, Edward; Dabiri, John; McFall-Ngai, Margaret; Kanso, Eva

    2016-11-01

    Motile cilia are microscopic, hair-like structures on the cell surface that can sense and propel the extracellular fluid environment. Cilia are often thought to be limited to stereotypic morphologies, beat kinematics and non-discriminatory clearance functions, but we find that the spatiotemporal organization of different cilia types and beat behaviors can generate complex flow patterns and transport functions. Here, we present a case study in the Hawaiian bobtail squid where collective ciliary activity and resulting flow fields help recruit symbiont bacteria to the animal host. In particular, we demonstrate empirically and computationally how the squid's internal cilia act like a microfluidic device that actively filters the water for potential bacterial candidates and also provides a sheltered zone allowing for accumulation of mucus and bacteria into a biofilm. Moreover, in this sheltered zone, different cilia-driven flows enhance diffusion of biochemical signals, which could accelerate specific bacteria-host recognition. These results suggest that studying cilia activity on the population level might reveal a diverse range of biological transport and sensing functions. Moreover, understanding cilia as functional building blocks could inspire the design of ciliated robots and devices.

  14. Reciprocal regulation of cilia and autophagy via the MTOR and proteasome pathways.

    Science.gov (United States)

    Wang, Shixuan; Livingston, Man J; Su, Yunchao; Dong, Zheng

    2015-04-01

    Primary cilium is an organelle that plays significant roles in a number of cellular functions ranging from cell mechanosensation, proliferation, and differentiation to apoptosis. Autophagy is an evolutionarily conserved cellular function in biology and indispensable for cellular homeostasis. Both cilia and autophagy have been linked to different types of genetic and acquired human diseases. Their interaction has been suggested very recently, but the underlying mechanisms are still not fully understood. We examined autophagy in cells with suppressed cilia and measured cilium length in autophagy-activated or -suppressed cells. It was found that autophagy was repressed in cells with short cilia. Further investigation showed that MTOR activation was enhanced in cilia-suppressed cells and the MTOR inhibitor rapamycin could largely reverse autophagy suppression. In human kidney proximal tubular cells (HK2), autophagy induction was associated with cilium elongation. Conversely, autophagy inhibition by 3-methyladenine (3-MA) and chloroquine (CQ) as well as bafilomycin A1 (Baf) led to short cilia. Cilia were also shorter in cultured atg5-knockout (KO) cells and in atg7-KO kidney proximal tubular cells in mice. MG132, an inhibitor of the proteasome, could significantly restore cilium length in atg5-KO cells, being concomitant with the proteasome activity. Together, the results suggest that cilia and autophagy regulate reciprocally through the MTOR signaling pathway and ubiquitin-proteasome system.

  15. The Par-PrkC polarity complex is required for cilia growth in zebrafish photoreceptors.

    Directory of Open Access Journals (Sweden)

    Bryan L Krock

    Full Text Available Specification and development of the apical membrane in epithelial cells requires the function of polarity proteins, including Pard3 and an atypical protein kinase C (PrkC. Many epithelial cells possess microtubule-based organelles, known as cilia, that project from their apical surface and the membrane surrounding the cilium is contiguous with the apical cell membrane. Although cilia formation in cultured cells required Pard3, the in vivo requirement for Pard3 in cilia development remains unknown. The vertebrate photoreceptor outer segment represents a highly specialized cilia structure in which to identify factors necessary for apical and ciliary membrane formation. Pard3 and PrkC localized to distinct domains within vertebrate photoreceptors. Using partial morpholino knockdown, photo-morpholinos, and pharmacological approaches, the function of Pard3 and PrkC were found to be required for the formation of both the apical and ciliary membrane of vertebrate photoreceptors. Inhibition of Pard3 or PrkC activity significantly reduced the size of photoreceptor outer segments and resulted in mislocalization of rhodopsin. Suppression of Pard3 or PrkC also led to a reduction in cilia size and cilia number in Kupffer's Vesicle, which resulted in left-right asymmetry defects. Thus, the Par-PrkC complex functions in cilia formation in vivo and this likely reflects a general role in specifying non-ciliary and ciliary compartments of the apical domain.

  16. [Establishment of osteoblast primary cilia model removed by chloral hyrate].

    Science.gov (United States)

    Ma, Xiao-ni; Shi, Wen-gui; Xie, Yan-fang; Ma, Hui-ping; Ge, Bao-feng; Zhen, Ping; Chen, Ke-ming

    2015-06-01

    To establish osteoblast model, primary cilla model was removed by chloral hyrate, observe effects of osteoblast primary cilla moved on enhancing ALP staining and calcified nodules staining in electromagnetic field. Three 3-day-old male SD rats weighed between 6 and 9 g were killed, cranial osteoblast was drawed and adherencing cultured respectively. Cells were subcultured and randomly divided into 4 groups until reach to fusion states. The four groups included chloral hydrate non-involved group (control group), 2 mM, 4 mM and 8 mM chloral hydrate group, and cultured in 37 °C, 5% CO2 incubator for 72 h. Morphology of primary cilla was observed by laser confocal scanning microscope, and incidence of osteoblast primary cilia was analyzed by Image-Pro Plus 6.0 software. Cells in the correct concentration group which can removed cillia most effectively were selected and divided into 3 groups, including control group (C), Electromagnetic fields group (EMFs), and EMFs with 4 mM chloral hydrate group. DMEM nutrient solution contained 10%FBS were added into three groups and cultured for 9 days and formation of ALP were observed by histochemical staining of alkaline phosphatase. After 12 days' cultivation, formation of mineralization nodes was observed by alizarin red staining. Compared with control group and 2mM chloral hydrate group,4 mM chloral hydrate group could effectively remove osteoblast primary cilla (P<0.01). Removal of osteoblast primary cilla could weaken the formation of ALP and mineralization nodes in osteoblast in EMFS. Compared with EMFs group, the area of ALP and mineralization nodes in EMFs with 4 mM chloral hydrate group were decreased obviously (P<0.01). 4mM chloral hydrate could effectively remove osteoblast primary cilia. Primary cilla participate in EMFs promoting formation of ALP and mineralization nodes in osteoblast and provide new ideas for exploring mechanism of EMFs promoting osteoblast maturation and mineralization.

  17. 1,25(OH)2D3 alters growth plate maturation and bone architecture in young rats with normal renal function.

    Science.gov (United States)

    Idelevich, Anna; Kerschnitzki, Michael; Shahar, Ron; Monsonego-Ornan, Efrat

    2011-01-01

    Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25(OH)(2)D(3), the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25(OH)(2)D(3) is used in pediatric patients with chronic kidney disease and mineral and bone disorder (CKD-MBD) and is strongly associated with growth retardation. Here, we investigate the effect of 1,25(OH)(2)D(3) treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 µg/kg 1,25(OH)(2)D(3) for one week, or intermittent 3 µg/kg 1,25(OH)(2)D(3) for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25(OH)(2)D(3)-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by in situ hybridization. Concomitant with altered chondrocyte maturation, 1,25(OH)(2)D(3) increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells. In vitro treatment of the chondrocytic cell line ATDC5 with 1,25(OH)(2)D(3) lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25(OH)(2)D(3)-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25(OH)(2)D(3) on intracortical bone formation. This study shows negative effects of 1,25(OH)(2)D(3) on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients.

  18. 1,25(OH2D3 alters growth plate maturation and bone architecture in young rats with normal renal function.

    Directory of Open Access Journals (Sweden)

    Anna Idelevich

    Full Text Available Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25(OH(2D(3, the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25(OH(2D(3 is used in pediatric patients with chronic kidney disease and mineral and bone disorder (CKD-MBD and is strongly associated with growth retardation. Here, we investigate the effect of 1,25(OH(2D(3 treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 µg/kg 1,25(OH(2D(3 for one week, or intermittent 3 µg/kg 1,25(OH(2D(3 for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25(OH(2D(3-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by in situ hybridization. Concomitant with altered chondrocyte maturation, 1,25(OH(2D(3 increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells. In vitro treatment of the chondrocytic cell line ATDC5 with 1,25(OH(2D(3 lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25(OH(2D(3-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25(OH(2D(3 on intracortical bone formation. This study shows negative effects of 1,25(OH(2D(3 on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients.

  19. Effect of bunching of cilia and their interplay on muco-ciliary transport.

    Science.gov (United States)

    Roy, Yagnaseni; Sivathanu, Vivek; Das, Sarit K

    2013-11-01

    Cilia are hair-like organelles projecting from a eukaryotic cell, used either for locomotion or as sensors. Cilia commonly occur in patches. To take this into consideration, we represent cilia in multiple patches, instead of the conventional 'dense mat' representation. We focus on the combined action and interplay of these patches. The effects of varying the frequency, spacing and phase lag of the beating of one cilia bunch with respect to the beating of adjacent patches are studied. We model the Airway Surface Liquid (ASL) as a three-layer structure. The possibility of an optimum frequency of beating is noted and the change of mucous flow under different spacing and phase differences are observed.

  20. Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue

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    Basten Sander G

    2013-01-01

    Full Text Available Abstract Background Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from the apical membrane of epithelia, extending into the lumen where they function in flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies renal cyst formation that is in part caused by deregulation of planar cell polarity and canonical Wnt signaling. Renal cancer pathologies occur sporadically or in heritable syndromes caused by germline mutations in tumor suppressor genes including VHL. Importantly, Von Hippel-Lindau (VHL patients frequently develop complex renal cysts that can be considered a premalignant stage. One of the well-characterized molecular functions of VHL is its requirement for the maintenance of cilia. In this study, tissue from 110 renal cancer patients who underwent nephrectomy was analyzed to determine if lower ciliary frequency is a common hallmark of renal tumorigenesis by comparing cilia frequencies in both tumor and adjacent parenchymal tissue biopsies from the same kidney. Methods We stained sections of human renal material using markers for cilia. Preliminary staining was performed using an immunofluorescent approach and a combination of acetylated-α-tubulin and pericentrin antibodies and DAPI. After validation of an alternative, higher throughput approach using acetylated-α-tubulin immunohistochemistry, we continued to manually quantify cilia in all tissues. Nuclei were separately counted in an automated fashion in order to determine ciliary frequencies. Similar staining and scoring for Ki67 positive cells was performed to exclude that proliferation obscures cilia formation potential. Results Samples from renal cell carcinoma patients deposited in our hospital tissue bank were previously used to compose a tissue microarray containing three cores of both tumor and parenchymal tissue per patient

  1. Type 3 Adenylyl Cyclase and Somatostatin Receptor 3 Expression Persists in Aged Rat Neocortical and Hippocampal Neuronal Cilia

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    Sarah eGuadiana

    2016-05-01

    Full Text Available The primary cilia of forebrain neurons assemble around birth and become enriched with neuromodulatory receptors. Our understanding of the permanence of these structures and their associated signaling pathways in the aging brain is poor, but they are worthy of investigation because disruptions in neuronal cilia signaling have been implicated in changes in learning and memory, depression-like symptoms, and sleep anomalies. Here, we asked whether neurons in aged forebrain retain primary cilia and whether the staining characteristics of aged cilia for type 3 adenylyl cyclase (ACIII, somatostatin receptor 3 (SSTR3, and pericentrin resemble those of cilia in younger forebrain. To test this, we analyzed immunostained sections of forebrain tissues taken from young and aged male Fischer 344 (F344 and Fischer 344 x Brown Norway (F344 x BN rats. Analyses of ACIII and SSTR3 in young and aged cortices of both strains of rats revealed that the staining patterns in the neocortex and hippocampus were comparable. Virtually every NeuN positive cell examined possessed an ACIII positive cilium. The lengths of ACIII positive cilia in neocortex were similar between young and aged for both strains, whereas in F344 x BN hippocampus, the cilia lengths increased with age in CA1 and CA3, but not in DG. Additionally, the percentages of ACIII positive cilia that were also SSTR3 positive did not differ between young and aged tissues in either strain. We also found that pericentrin, a protein that localizes to the basal bodies of neuronal cilia and functions in primary cilia assembly, persisted in aged cortical neurons of both rat strains. Collectively, our data show that neurons in aged rat forebrain possess primary cilia and that these cilia, like those present in younger brain, continue to localize ACIII, SSTR3, and pericentrin. Further studies will be required to determine if the function and signaling pathways regulated by cilia are similar in aged compared to young

  2. Architectural Prototyping

    DEFF Research Database (Denmark)

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

    2004-01-01

    ' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural......A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders...

  3. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

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    Wesley R Lewis

    2016-07-01

    Full Text Available Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400. While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8. GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC protein 4 (DRC4 where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR to generate one of these human missense

  4. Piracy of adhesins: attachment of superinfecting pathogens to respiratory cilia by secreted adhesins of Bordetella pertussis.

    Science.gov (United States)

    Tuomanen, E

    1986-12-01

    Two proteins secreted by Bordetella pertussis are known to mediate adherence of these bacteria to mammalian respiratory cilia. When either ciliated cells or other pathogenic bacteria were pretreated with these adhesins, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus acquired the ability to adhere to cilia in vitro and in vivo. Such piracy of adhesins may contribute to superinfection in mucosal diseases such as whooping cough.

  5. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...... the obligation to prepare students to perform in a profession that is largely defined by forces outside that discipline. It will be proposed that the autonomy of architecture can be understood as a unique kind of information: as architecture’s self-reliance or knowledge-about itself. A knowledge...... that is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that can...

  6. Biophysics and biofluid dynamics of primary cilia: evidence for and against the flow-sensing function.

    Science.gov (United States)

    Nag, Subhra; Resnick, Andrew

    2017-09-01

    Primary cilia have been called "the forgotten organelle" for over 20 yr. As cilia now have their own journal and several books devoted to their study, perhaps it is time to reconsider the moniker "forgotten organelle." In fact, during the drafting of this review, 12 relevant publications have been issued; we therefore apologize in advance for any relevant work we inadvertently omitted. What purpose is yet another ciliary review? The primary goal of this review is to specifically examine the evidence for and against the hypothesized flow-sensing function of primary cilia expressed by differentiated epithelia within a kidney tubule, bringing together differing disciplines and their respective conceptual and experimental approaches. We will show that understanding the biophysics/biomechanics of primary cilia provides essential information for understanding any potential role of ciliary function in disease. We will summarize experimental and mathematical models used to characterize renal fluid flow and incident force on primary cilia and to characterize the mechanical response of cilia to an externally applied force and discuss possible ciliary-mediated cell signaling pathways triggered by flow. Throughout, we stress the importance of separating the effects of fluid shear and stretch from the action of hydrodynamic drag. Copyright © 2017 the American Physiological Society.

  7. Hippocampal and cortical primary cilia are required for aversive memory in mice.

    Directory of Open Access Journals (Sweden)

    Nicolas F Berbari

    Full Text Available It has been known for decades that neurons throughout the brain possess solitary, immotile, microtubule based appendages called primary cilia. Only recently have studies tried to address the functions of these cilia and our current understanding remains poor. To determine if neuronal cilia have a role in behavior we specifically disrupted ciliogenesis in the cortex and hippocampus of mice through conditional deletion of the Intraflagellar Transport 88 (Ift88 gene. The effects on learning and memory were analyzed using both Morris Water Maze and fear conditioning paradigms. In comparison to wild type controls, cilia mutants displayed deficits in aversive learning and memory and novel object recognition. Furthermore, hippocampal neurons from mutants displayed an altered paired-pulse response, suggesting that loss of IFT88 can alter synaptic properties. A variety of other behavioral tests showed no significant differences between conditional cilia mutants and controls. This type of conditional allele approach could be used to distinguish which behavioral features of ciliopathies arise due to defects in neural development and which result from altered cell physiology. Ultimately, this could lead to an improved understanding of the basis for the cognitive deficits associated with human cilia disorders such as Bardet-Biedl syndrome, and possibly more common ailments including depression and schizophrenia.

  8. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    that is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that can...... the obligation to prepare students to perform in a profession that is largely defined by forces outside that discipline. It will be proposed that the autonomy of architecture can be understood as a unique kind of information: as architecture’s self-reliance or knowledge-about itself. A knowledge...... be transformed and reapplied endlessly through its confrontation with shifting information from outside the realms of architecture. A selection of architects’ statements on their own work will be used to demonstrate how in quite diverse contemporary practices the re-use of existing architectures is applied...

  9. Primary Cilia Integrate Hedgehog and Wnt Signaling during Tooth Development

    Science.gov (United States)

    Liu, B.; Chen, S.; Cheng, D.; Jing, W.; Helms, J.A.

    2014-01-01

    Many ciliopathies have clinical features that include tooth malformations but how these defects come about is not clear. Here we show that genetic deletion of the motor protein Kif3a in dental mesenchyme results in an arrest in odontogenesis. Incisors are completely missing, and molars are enlarged in Wnt1Cre+Kif3afl/fl embryos. Although amelogenesis and dentinogenesis initiate in the molar tooth bud, both processes terminate prematurely. We demonstrate that loss of Kif3a in dental mesenchyme results in loss of Hedgehog signaling and gain of Wnt signaling in this same tissue. The defective dental mesenchyme then aberrantly signals to the dental epithelia, which prompts an up-regulation in the Hedgehog and Wnt responses in the epithelia and leads to multiple attempts at invagination and an expanded enamel organ. Thus, the primary cilium integrates Hedgehog and Wnt signaling between dental epithelia and mesenchyme, and this cilia-dependent integration is required for proper tooth development. PMID:24659776

  10. [The multiple links between cilia and planar cell polarity].

    Science.gov (United States)

    Ezan, Jérôme; Montcouquiol, Mireille

    2014-11-01

    Since our seminal study in 2003, much has been written about core planar cell polarity (core PCP) signaling and the inner ear. In just a few years, and using the inner ear as a model system, our understanding of the molecular basis of this signaling pathway and how it can influence the development of tissues in mammals has increased considerably. Recently, a number of studies using various animal models of development have uncovered original relationships between the cilia and PCP, and the study of the hair cells of the inner ear has helped elucidating one of these links. In this review, we highlight the differences of PCP signaling between mammals and invertebrates. In the light of recent results, we sum up our current knowledge about PCP signaling in the mammalian cochlear epithelium and we discuss the impact of recent data in the field. We focus our attention on the interrelationship between asymmetric polarity complexes and the position of the cilium, which is essential for the establishment of the overall tissue polarity.

  11. Primary cilia integrate hedgehog and Wnt signaling during tooth development.

    Science.gov (United States)

    Liu, B; Chen, S; Cheng, D; Jing, W; Helms, J A

    2014-05-01

    Many ciliopathies have clinical features that include tooth malformations but how these defects come about is not clear. Here we show that genetic deletion of the motor protein Kif3a in dental mesenchyme results in an arrest in odontogenesis. Incisors are completely missing, and molars are enlarged in Wnt1(Cre+)Kif3a(fl/fl) embryos. Although amelogenesis and dentinogenesis initiate in the molar tooth bud, both processes terminate prematurely. We demonstrate that loss of Kif3a in dental mesenchyme results in loss of Hedgehog signaling and gain of Wnt signaling in this same tissue. The defective dental mesenchyme then aberrantly signals to the dental epithelia, which prompts an up-regulation in the Hedgehog and Wnt responses in the epithelia and leads to multiple attempts at invagination and an expanded enamel organ. Thus, the primary cilium integrates Hedgehog and Wnt signaling between dental epithelia and mesenchyme, and this cilia-dependent integration is required for proper tooth development.

  12. IFT88 Plays a Cilia- and PCP-Independent Role in Controlling Oriented Cell Divisions during Vertebrate Embryonic Development

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    Antonia Borovina

    2013-10-01

    Full Text Available The role for cilia in establishing planar cell polarity (PCP is contentious. Although knockdown of genes known to function in ciliogenesis has been reported to cause PCP-related morphogenesis defects in zebrafish, genetic mutations affecting intraflagellar transport (IFT do not show PCP phenotypes despite the requirement for IFT in cilia formation. This discrepancy has been attributed to off-target effects of antisense morpholino oligonucleotide (MO injection, confounding maternal effects in zygotic mutant embryos, or an inability to distinguish between cilia-dependent versus cilia-independent protein functions. To determine the role of cilia in PCP, we generated maternal + zygotic IFT88 (MZift88 mutant zebrafish embryos, which never form cilia. We clearly demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Our results have important implications for the interpretation of cilia gene function in normal development and in disease.

  13. IFT88 plays a cilia- and PCP-independent role in controlling oriented cell divisions during vertebrate embryonic development.

    Science.gov (United States)

    Borovina, Antonia; Ciruna, Brian

    2013-10-17

    The role for cilia in establishing planar cell polarity (PCP) is contentious. Although knockdown of genes known to function in ciliogenesis has been reported to cause PCP-related morphogenesis defects in zebrafish, genetic mutations affecting intraflagellar transport (IFT) do not show PCP phenotypes despite the requirement for IFT in cilia formation. This discrepancy has been attributed to off-target effects of antisense morpholino oligonucleotide (MO) injection, confounding maternal effects in zygotic mutant embryos, or an inability to distinguish between cilia-dependent versus cilia-independent protein functions. To determine the role of cilia in PCP, we generated maternal + zygotic IFT88 (MZift88) mutant zebrafish embryos, which never form cilia. We clearly demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Our results have important implications for the interpretation of cilia gene function in normal development and in disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Ectopic cilia associated with an orbital dermoid cyst and sinus tract: case report.

    Science.gov (United States)

    Krahulík, David; Karhanová, Marta; Vaverka, Miroslav; Brychtová, Světlana; Pospíšilová, Dagmar

    2015-08-01

    Ectopic cilia are extremely rare congenital anomalies in which eyelash follicles appear in an abnormal place on the eyelid, most typically on the lateral quadrant of the anterior surface of the upper eyelid. In the majority of cases, simple surgical excision of ectopic cilia is indicated because of its cosmetic aspect. There is usually no associated medical co-morbidity with this anomaly. The authors report an unusual case of ectopic cilia associated with an orbital dermoid cyst and sinus tract. A 3-year-old boy was initially diagnosed with ectopic cilia on the left upper eyelid. There was no history of inflammation or swelling of the eyelid. An ophthalmological examination revealed only 1 mm of ptosis; no proptosis, inferior displacement, or palpable orbital mass was present. During surgical excision of the ectopic cilia, a thin sinus tract was identified, leading posteriorly to the orbit. Magnetic resonance imaging performed after the excision showed a supraorbital extraconal mass just below the roof of the left orbit. A supraorbital 2-piece craniotomy was performed with total extirpation of the dermoid cyst. The cyst was removed en bloc without damage to the extraocular muscles, but the sinus tract could no longer be identified. Follow-up MRI was performed 6 months after surgery and showed no evidence of recurrence. A follow-up ophthalmological examination showed no signs of inferior displacement or proptosis. To the best of the authors' knowledge, this case is the first reported instance of ectopic cilia associated with a dermoid cyst and sinus tract in which no typical clinical signs and symptoms of possible orbital pathology were present. This case highlights the value of radiological examination in all cases of ectopic cilia prior to surgical excision.

  15. Characterization of tetratricopeptide repeat-containing proteins critical for cilia formation and function.

    Directory of Open Access Journals (Sweden)

    Yanan Xu

    Full Text Available Cilia formation and function require a special set of trafficking machinery termed intraflagellar transport (IFT, consisting mainly of protein complexes IFT-A, IFT-B, BBSome, and microtubule-dependent molecular motors. Tetratricopeptide repeat-containing (TTC proteins are widely involved in protein complex formation. Nine of them are known to serve as components of the IFT or BBSome complexes. How many TTC proteins are cilia-related and how they function, however, remain unclear. Here we show that twenty TTC genes were upregulated by at least 2-fold during the differentiation of cultured mouse tracheal epithelial cells (MTECs into multiciliated cells. Our systematic screen in zebrafish identified four novel TTC genes, ttc4, -9c, -36, and -39c, that are critical for cilia formation and motility. Accordingly, their zebrafish morphants displayed typical ciliopathy-related phenotypes, including curved body, abnormal otolith, hydrocephalus, and defective left-right patterning. The morphants of ttc4 and ttc25, a known cilia-related gene, additionally showed pronephric cyst formation. Immunoprecipitation indicated associations of TTC4, -9c, -25, -36, and -39c with components or entire complexes of IFT-A, IFT-B, or BBSome, implying their participations in IFT or IFT-related activities. Our results provide a global view for the relationship between TTC proteins and cilia.

  16. c21orf59/kurly Controls Both Cilia Motility and Polarization

    Directory of Open Access Journals (Sweden)

    Kimberly M. Jaffe

    2016-03-01

    Full Text Available Cilia are microtubule-based projections that function in the movement of extracellular fluid. This requires cilia to be: (1 motile and driven by dynein complexes and (2 correctly polarized on the surface of cells, which requires planar cell polarity (PCP. Few factors that regulate both processes have been discovered. We reveal that C21orf59/Kurly (Kur, a cytoplasmic protein with some enrichment at the base of cilia, is needed for motility; zebrafish mutants exhibit characteristic developmental abnormalities and dynein arm defects. kur was also required for proper cilia polarization in the zebrafish kidney and the larval skin of Xenopus laevis. CRISPR/Cas9 coupled with homologous recombination to disrupt the endogenous kur locus in Xenopus resulted in the asymmetric localization of the PCP protein Prickle2 being lost in mutant multiciliated cells. Kur also makes interactions with other PCP components, including Disheveled. This supports a model wherein Kur plays a dual role in cilia motility and polarization.

  17. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking.

    Science.gov (United States)

    Liem, Karel F; Ashe, Alyson; He, Mu; Satir, Peter; Moran, Jennifer; Beier, David; Wicking, Carol; Anderson, Kathryn V

    2012-06-11

    Two intraflagellar transport (IFT) complexes, IFT-A and IFT-B, build and maintain primary cilia and are required for activity of the Sonic hedgehog (Shh) pathway. A weak allele of the IFT-A gene, Ift144, caused subtle defects in cilia structure and ectopic activation of the Shh pathway. In contrast, strong loss of IFT-A, caused by either absence of Ift144 or mutations in two IFT-A genes, blocked normal ciliogenesis and decreased Shh signaling. In strong IFT-A mutants, the Shh pathway proteins Gli2, Sufu, and Kif7 localized correctly to cilia tips, suggesting that these pathway components were trafficked by IFT-B. In contrast, the membrane proteins Arl13b, ACIII, and Smo failed to localize to primary cilia in the absence of IFT-A. We propose that the increased Shh activity seen in partial loss-of-function IFT-A mutants may be a result of decreased ciliary ACIII and that the loss of Shh activity in the absence of IFT-A is a result of severe disruptions of cilia structure and membrane protein trafficking.

  18. Dynamics of self-oscillating cilia designed from active polymer gels

    Science.gov (United States)

    Dayal, Pratyush; Bhattacharya, Amitabh; Kuksenok, Olga; Balazs, Anna C.

    2012-02-01

    Using theory and simulations, we design active synthetic surfaces which are capable of replicating functionalities of biological cilia. In order to design such exquisite biomimetic systems we harness unique properties of polymer gels that undergo photosensitive Belousov-Zhabotinsky (BZ) reaction. Powered by internalized BZ reaction these polymer gels swell and de-swell autonomously by chemo-mechanical transduction and therefore are ideal materials for designing our system. In order to simulate the dynamics of the BZ cilia in surrounding fluid we have developed a nonlinear hybrid 3D model which captures elasto-dynamics of polymer gel and diffusive exchange of BZ reagents between the gel and the fluid. Here we show that the geometrical arrangement of cilia and the distribution of BZ activator in the fluid determine the dynamic response of the cilia. We further show that using light as an external stimulus we can sequentially modulate height of individual cilium and thereby create the ``piano effect''. Finally, we demonstrate that synchronized oscillations in the cilia result from the distribution of BZ-activator in the surrounding fluid. Our findings can be used to design active surfaces which can be remotely tuned depending upon the magnitude of external stimuli.

  19. Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles.

    Science.gov (United States)

    Siyahhan, Bercan; Knobloch, Verena; de Zélicourt, Diane; Asgari, Mahdi; Schmid Daners, Marianne; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2014-05-06

    While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation.

  20. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan); Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan)

    2009-10-30

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  1. Architectural slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

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

  2. Architectural Slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

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

  3. New insights into an old organelle: meeting report on biology of cilia and flagella.

    Science.gov (United States)

    Sengupta, Piali; Barr, Maureen M

    2014-06-01

    The rising interest of the scientific community in cilia biology was evident from the fact that registration for the third FASEB conference on 'The Biology of Cilia and Flagella' closed out before the early bird deadline. Cilia and flagella are organelles of profound medical importance; defects in their structure or function result in a plethora of human diseases called ciliopathies. 240 clinicians and basic scientists from around the world gathered from 23 June 2013 to 28 June 2013 at Sheraton at the Falls, Niagara Falls, NY to present and discuss their research on this intensely studied subcellular structure. The meeting was organized by Gregory Pazour (University of Massachusetts Medical School), Bradley Yoder (University of Alabama-Birmingham), and Maureen Barr (Rutgers University) and was sponsored by the Federation of American Societies for Experimental Biology (FASEB). Here, we report highlights, points of discussion, and emerging themes from this exciting meeting.

  4. Primary Cilia as a Possible Link between Left-Right Asymmetry and Neurodevelopmental Diseases

    Science.gov (United States)

    Trulioff, Andrey; Ermakov, Alexander; Malashichev, Yegor

    2017-01-01

    Cilia have multiple functions in the development of the entire organism, and participate in the development and functioning of the central nervous system. In the last decade, studies have shown that they are implicated in the development of the visceral left-right asymmetry in different vertebrates. At the same time, some neuropsychiatric disorders, such as schizophrenia, autism, bipolar disorder, and dyslexia, are known to be associated with lateralization failure. In this review, we consider possible links in the mechanisms of determination of visceral asymmetry and brain lateralization, through cilia. We review the functions of seven genes associated with both cilia, and with neurodevelopmental diseases, keeping in mind their possible role in the establishment of the left-right brain asymmetry. PMID:28125008

  5. Primary Cilia as a Possible Link between Left-Right Asymmetry and Neurodevelopmental Diseases

    Directory of Open Access Journals (Sweden)

    Andrey Trulioff

    2017-01-01

    Full Text Available Cilia have multiple functions in the development of the entire organism, and participate in the development and functioning of the central nervous system. In the last decade, studies have shown that they are implicated in the development of the visceral left-right asymmetry in different vertebrates. At the same time, some neuropsychiatric disorders, such as schizophrenia, autism, bipolar disorder, and dyslexia, are known to be associated with lateralization failure. In this review, we consider possible links in the mechanisms of determination of visceral asymmetry and brain lateralization, through cilia. We review the functions of seven genes associated with both cilia, and with neurodevelopmental diseases, keeping in mind their possible role in the establishment of the left-right brain asymmetry.

  6. De novo formation of left-right asymmetry by posterior tilt of nodal cilia.

    Directory of Open Access Journals (Sweden)

    Shigenori Nonaka

    2005-08-01

    Full Text Available In the developing mouse embryo, leftward fluid flow on the ventral side of the node determines left-right (L-R asymmetry. However, the mechanism by which the rotational movement of node cilia can generate a unidirectional flow remains hypothetical. Here we have addressed this question by motion and morphological analyses of the node cilia and by fluid dynamic model experiments. We found that the cilia stand, not perpendicular to the node surface, but tilted posteriorly. We further confirmed that such posterior tilt can produce leftward flow in model experiments. These results strongly suggest that L-R asymmetry is not the descendant of pre-existing L-R asymmetry within each cell but is generated de novo by combining three sources of spatial information: antero-posterior and dorso-ventral axes, and the chirality of ciliary movement.

  7. Real-time remote control of artificial cilia actuation using fingertip drawing for efficient micromixing.

    Science.gov (United States)

    Chen, Chia-Yuan; Yao, Chih-Yuan; Lin, Cheng-Yi; Hung, Shih-Hsuan

    2014-10-01

    Low-efficiency diffusion mechanism poses a significant barrier to the enhancement of micromixing efficiency in microfluidics. Actuating artificial cilia to increase the contact area of two flow streams during micromixing provides a promising alternative to enhance the mixing performance. Real-time adjustment of beating behavior in artificial cilia is necessary to accommodate various biological/chemical reagents with different hydrodynamic properties that are processed in a single microfluidic platform during micromixing. Equipping the microfluidic device with a self-troubleshooting feature for the end user, such as a bubble removal function during the process of multiple chemical solution injections, is also essential for robust micromixing. To meet these requirements, we initiated a new beating control concept by controlling the beating behavior of the artificial cilia through remote and simultaneous actuation of human fingertip drawing. A series of micromixing test cases under extreme flow conditions (Re technical difficulties encountered during micromixing operations.

  8. Levonorgestrel decreases cilia beat frequency of human fallopian tubes and rat oviducts without changing morphological structure.

    Science.gov (United States)

    Zhao, Weihong; Zhu, Qian; Yan, Mingxing; Li, Cheng; Yuan, Jiangjing; Qin, Guojuan; Zhang, Jian

    2015-02-01

    Levonorgestrel, a derivative of progesterone, effectively protects women against unwanted pregnancy as an emergency contraceptive. Previous studies have not been successful in determining the mechanism by which levonorgestrel acts. In the present study we analysed cilia beat action and cilia morphology following levonorgestrel exposure in vitro and in vivo using both light and electron microscopy. There was a significant decrease in the ciliary beat frequency (CBF) of human fallopian tubes between mucosal explants bathed in 5 μmol/L levonorgestrel and those bathed in medium alone (P levonorgestrel produced a similar reduction in CBF (~ 10%) compared with the saline control group (P levonorgestrel treatment in either system. Thus, levonorgestrel reduces CBF without damaging cilia morphology. Decreases in CBF may indicate a pathological role for levonorgestrel in the transportation of the ovum and zygote in the fallopian tube.

  9. The more we know, the more we have to discover : an exciting future for understanding cilia and ciliopathies

    NARCIS (Netherlands)

    Benmerah, Alexandre; Durand, Bénédicte; Giles, Rachel H; Harris, Tess; Kohl, Linda; Laclef, Christine; Meilhac, Sigolène M; Mitchison, Hannah M; Pedersen, Lotte B; Roepman, Ronald; Swoboda, Peter; Ueffing, Marius; Bastin, Philippe; Giles, R

    2015-01-01

    The Cilia 2014 conference was organised by four European networks: the Ciliopathy Alliance, the Groupement de Recherche CIL, the Nordic Cilia and Centrosome Network and the EU FP7 programme SYSCILIA. More than 400 delegates from 27 countries gathered at the Institut Pasteur conference centre in Pari

  10. The more we know, the more we have to discover: an exciting future for understanding cilia and ciliopathies

    NARCIS (Netherlands)

    Benmerah, A.; Durand, B.; Giles, R.H.; Harris, T.; Kohl, L.; Laclef, C.; Meilhac, S.M.; Mitchison, H.M.; Pedersen, L.B.; Roepman, R.; Swoboda, P.; Ueffing, M.; Bastin, P.

    2015-01-01

    The Cilia 2014 conference was organised by four European networks: the Ciliopathy Alliance, the Groupement de Recherche CIL, the Nordic Cilia and Centrosome Network and the EU FP7 programme SYSCILIA. More than 400 delegates from 27 countries gathered at the Institut Pasteur conference centre in Pari

  11. The more we know, the more we have to discover: an exciting future for understanding cilia and ciliopathies

    NARCIS (Netherlands)

    Benmerah, A.; Durand, B.; Giles, R.H.; Harris, T.; Kohl, L.; Laclef, C.; Meilhac, S.M.; Mitchison, H.M.; Pedersen, L.B.; Roepman, R.; Swoboda, P.; Ueffing, M.; Bastin, P.

    2015-01-01

    The Cilia 2014 conference was organised by four European networks: the Ciliopathy Alliance, the Groupement de Recherche CIL, the Nordic Cilia and Centrosome Network and the EU FP7 programme SYSCILIA. More than 400 delegates from 27 countries gathered at the Institut Pasteur conference centre in Pari

  12. CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia.

    Directory of Open Access Journals (Sweden)

    Amjad Horani

    Full Text Available BACKGROUND: Primary ciliary dyskinesia (PCD is a genetic disorder characterized by impaired ciliary function, leading to chronic sinopulmonary disease. The genetic causes of PCD are still evolving, while the diagnosis is often dependent on finding a ciliary ultrastructural abnormality and immotile cilia. Here we report a novel gene associated with PCD but without ciliary ultrastructural abnormalities evident by transmission electron microscopy, but with dyskinetic cilia beating. METHODS: Genetic linkage analysis was performed in a family with a PCD subject. Gene expression was studied in Chlamydomonas reinhardtii and human airway epithelial cells, using RNA assays and immunostaining. The phenotypic effects of candidate gene mutations were determined in primary culture human tracheobronchial epithelial cells transduced with gene targeted shRNA sequences. Video-microscopy was used to evaluate cilia motion. RESULTS: A single novel mutation in CCDC65, which created a termination codon at position 293, was identified in a subject with typical clinical features of PCD. CCDC65, an orthologue of the Chlamydomonas nexin-dynein regulatory complex protein DRC2, was localized to the cilia of normal nasal epithelial cells but was absent in those from the proband. CCDC65 expression was up-regulated during ciliogenesis in cultured airway epithelial cells, as was DRC2 in C. reinhardtii following deflagellation. Nasal epithelial cells from the affected individual and CCDC65-specific shRNA transduced normal airway epithelial cells had stiff and dyskinetic cilia beating patterns compared to control cells. Moreover, Gas8, a nexin-dynein regulatory complex component previously identified to associate with CCDC65, was absent in airway cells from the PCD subject and CCDC65-silenced cells. CONCLUSION: Mutation in CCDC65, a nexin-dynein regulatory complex member, resulted in a frameshift mutation and PCD. The affected individual had altered cilia beating patterns, and

  13. Interactive computer-assisted approach for evaluation of ultrastructural cilia abnormalities

    Science.gov (United States)

    Palm, Christoph; Siegmund, Heiko; Semmelmann, Matthias; Grafe, Claudia; Evert, Matthias; Schroeder, Josef A.

    2016-03-01

    Introduction - Diagnosis of abnormal cilia function is based on ultrastructural analysis of axoneme defects, especialy the features of inner and outer dynein arms which are the motors of ciliar motility. Sub-optimal biopsy material, methodical, and intrinsic electron microscopy factors pose difficulty in ciliary defects evaluation. We present a computer-assisted approach based on state-of-the-art image analysis and object recognition methods yielding a time-saving and efficient diagnosis of cilia dysfunction. Method - The presented approach is based on a pipeline of basal image processing methods like smoothing, thresholding and ellipse fitting. However, integration of application specific knowledge results in robust segmentations even in cases of image artifacts. The method is build hierarchically starting with the detection of cilia within the image, followed by the detection of nine doublets within each analyzable cilium, and ending with the detection of dynein arms of each doublet. The process is concluded by a rough classification of the dynein arms as basis for a computer-assisted diagnosis. Additionally, the interaction possibilities are designed in a way, that the results are still reproducible given the completion report. Results - A qualitative evaluation showed reasonable detection results for cilia, doublets and dynein arms. However, since a ground truth is missing, the variation of the computer-assisted diagnosis should be within the subjective bias of human diagnosticians. The results of a first quantitative evaluation with five human experts and six images with 12 analyzable cilia showed, that with default parameterization 91.6% of the cilia and 98% of the doublets were found. The computer-assisted approach rated 66% of those inner and outer dynein arms correct, where all human experts agree. However, especially the quality of the dynein arm classification may be improved in future work.

  14. Zebrafish ift57, ift88, and ift172 intraflagellar transport mutants disrupt cilia but do not affect hedgehog signaling.

    Science.gov (United States)

    Lunt, Shannon C; Haynes, Tony; Perkins, Brian D

    2009-07-01

    Cilia formation requires intraflagellar transport (IFT) proteins. Recent studies indicate that mammalian Hedgehog (Hh) signaling requires cilia. It is unclear, however, if the requirement for cilia and IFT proteins in Hh signaling represents a general rule for all vertebrates. Here we examine zebrafish ift57, ift88, and ift172 mutants and morphants for defects in Hh signaling. Although ift57 and ift88 mutants and morphants contained residual maternal protein, the cilia were disrupted. In contrast to previous genetic studies in mouse, mutations in zebrafish IFT genes did not affect the expression of Hh target genes in the neural tube and forebrain and had no quantitative effect on Hh target gene expression. Zebrafish IFT mutants also exhibited no dramatic changes in the craniofacial skeleton, somite formation, or motor neuron patterning. Thus, our data indicate the requirement for cilia in the Hh signal transduction pathway may not represent a universal mechanism in vertebrates.

  15. An unusual presentation of immotile-cilia syndrome with azoospermia: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Dixit Ramakant

    2009-01-01

    Full Text Available Immotile-cilia syndrome is a rare disorder characterized by chronic recurrent sino-pulmonary infection, impaired tracheobronchial clearance, situs inversus in about 50% of cases, and living but immotile spermatozoa of normal morphology in semen analysis. In this report, we describe an unusual presentation of immotile-cilia syndrome with azoospermia in a 32-year-old male patient. The diagnosis was based on history of recurrent respiratory tract infection, bronchiectasis, maxillary sinusitis, hypoplasia of frontal sinuses, dextrocardia with situs inversus, impaired nasal mucociliary clearance, etc. Semen analysis revealed azoospermia without any evidence of obstruction in epididymides or vas deference. Normal spermatogenesis was seen on testicular biopsy.

  16. A bio-inspired inner-motile photocatalyst film: a magnetically actuated artificial cilia photocatalyst

    Science.gov (United States)

    Zhang, Dunpu; Wang, Wei; Peng, Fengping; Kou, Jiahui; Ni, Yaru; Lu, Chunhua; Xu, Zhongzi

    2014-04-01

    A new type of inner-motile photocatalyst film is explored to enhance photocatalytic performance using magnetically actuated artificial cilia. The inner-motile photocatalyst film is capable of generating flow and mixing on the microscale because it produces a motion similar to that of natural cilia when it is subjected to a rotational magnetic field. Compared with traditional photocatalyst films, the inner-motile photocatalyst film exhibits the unique ability of microfluidic manipulation. It uses an impactful and self-contained design to accelerate interior mass transfer and desorption of degradation species. Moreover, the special cilia-like structures increase the surface area and light absorption. Consequently, the photocatalytic activity of the inner-motile photocatalyst film is dramatically improved to approximately 3.0 times that of the traditional planar film. The inner-motile photocatalyst film also exhibits high photocatalytic durability and can be reused several times with ease. Furthermore, this feasible yet versatile platform can be extended to other photocatalyst systems, such as TiO2, P25, ZnO, and Co3O4 systems, to improve their photocatalytic performance.A new type of inner-motile photocatalyst film is explored to enhance photocatalytic performance using magnetically actuated artificial cilia. The inner-motile photocatalyst film is capable of generating flow and mixing on the microscale because it produces a motion similar to that of natural cilia when it is subjected to a rotational magnetic field. Compared with traditional photocatalyst films, the inner-motile photocatalyst film exhibits the unique ability of microfluidic manipulation. It uses an impactful and self-contained design to accelerate interior mass transfer and desorption of degradation species. Moreover, the special cilia-like structures increase the surface area and light absorption. Consequently, the photocatalytic activity of the inner-motile photocatalyst film is dramatically

  17. Architectural Prototyping

    DEFF Research Database (Denmark)

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

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights...

  18. Architectural prototyping

    DEFF Research Database (Denmark)

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

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights...

  19. EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms

    DEFF Research Database (Denmark)

    Schrøder, Jacob M; Larsen, Jesper; Komarova, Yulia

    2011-01-01

    surrounded by vesicles. Further, GST pull-down assays, mass spectrometry and immunoprecipitation indicated that EB1 and EB3 interact with proteins implicated in MT minus-end anchoring or vesicular trafficking to the cilia base, suggesting that EB1 and EB3 promote ciliogenesis by facilitating such trafficking...

  20. Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery

    DEFF Research Database (Denmark)

    Kiprilov, Enko N; Awan, Aashir; Desprat, Romain

    2008-01-01

    Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human h...

  1. Distinctive features of cilia in metazoans and their significance for systematics.

    Science.gov (United States)

    Tyler, S

    1979-01-01

    A comparative study of epidermal cilia in the Turbellaria and Nemertea has revealed features in these organelles that are specific to certain taxonomic groups. Turbellarians of the order Acoela, in particular, have a characteristic pattern of axonemal filament termination in the distal tips of their cilia and a characteristic ciliary rootlet system that is not seen in other turbellarian orders nor in other metazoans. Each epidermal cilium in acoels has a typical 9 + 2 axonemal pattern through the main part of its length, but near its distal tip there is an abrupt shelf-life narrowing at which filaments 4-7 terminate; filaments 1, 2, 8 and 9 continue into the thinner distal-most part of the shaft along with singlet microtubules from the axonemal center. The rootlet system in acoel cilia involves an interconnecting pattern with lateral connectives. The unique structure of these cilia has systematic and phylogenetic significance for the Acoela, and it is argued that ultrastructural characters in general, including characters of organelles, can be validly applied to the phylogeny and systematics of the Metazoa.

  2. Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6.

    Science.gov (United States)

    Inaba, Yasuko; Shinohara, Kyosuke; Botilde, Yanick; Nabeshima, Ryo; Takaoka, Katsuyoshi; Ajima, Rieko; Lamri, Lynda; Takeda, Hiroyuki; Saga, Yumiko; Nakamura, Tetsuya; Hamada, Hiroshi

    2016-07-01

    Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9 + 2 arrangement of microtubules remained normal in Lrrc6(-/-) mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2-IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6(-/-) mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6-dependent mechanism.

  3. Qilin is essential for cilia assembly and normal kidney development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Jade Li

    Full Text Available Defects in the cilium, a once thought vestigial organelle, have recently been implicated in many human diseases, including a number of cystic kidney diseases such as polycystic kidney disease (PKD, Bardet Bieldl Syndrome, and Meckel-Gruber Syndrome. In a forward genetic screen, qilin was identified as a novel gene important in the pathogenesis of kidney cysts in zebrafish. In this paper we characterized qilin(hi3959A mutant's phenotypes in detail, investigated cilia formation in this mutant and performed structural and functional analysis of the Qilin protein. Results reveal Qilin's essential role in cilia assembly and maintenance in multiple organs, including the kidney, the lateral line organ, and the outer segment of the photoreceptor cell. In addition, rescue experiments suggest that defective pronephric cilia correlate with the formation of kidney cysts in qilin(hi3959A mutants. Further, genetic analysis suggests that qilin interacts with multiple intraflagellar transport (IFT complex B genes, which is supported by the striking phenotypic similarities between qilin(hi3959A and IFT complex B mutants. Finally, through deletion analysis we provide evidence that the well-conserved N-terminus and the coiled-coil domain of Qilin are both essential and sufficient for its function. Taken all the observations together, we propose that Qilin acts in a similar role as IFT complex B proteins in cilia assembly, maintenance and kidney development in zebrafish.

  4. An Outer Arm Dynein Conformational Switch Is Required for Metachronal Synchrony of Motile Cilia in Planaria

    Science.gov (United States)

    Rompolas, Panteleimon; Patel-King, Ramila S.

    2010-01-01

    Motile cilia mediate the flow of mucus and other fluids across the surface of specialized epithelia in metazoans. Efficient clearance of peri-ciliary fluids depends on the precise coordination of ciliary beating to produce metachronal waves. The role of individual dynein motors and the mechanical feedback mechanisms required for this process are not well understood. Here we used the ciliated epithelium of the planarian Schmidtea mediterranea to dissect the role of outer arm dynein motors in the metachronal synchrony of motile cilia. We demonstrate that animals that completely lack outer dynein arms display a significant decline in beat frequency and an inability of cilia to coordinate their oscillations and form metachronal waves. Furthermore, lack of a key mechanosensitive regulatory component (LC1) yields a similar phenotype even though outer arms still assemble in the axoneme. The lack of metachrony was not due simply to a decrease in ciliary beat frequency, as reducing this parameter by altering medium viscosity did not affect ciliary coordination. In addition, we did not observe a significant temporal variability in the beat cycle of impaired cilia. We propose that this conformational switch provides a mechanical feedback system within outer arm dynein that is necessary to entrain metachronal synchrony. PMID:20844081

  5. A continuum model for flow induced by metachronal coordination between beating cilia

    NARCIS (Netherlands)

    Hussong, J.; Breugem, W.-P.; Westerweel, J.

    2011-01-01

    In this numerical study we investigate the flow induced by metachronal coordination between beating cilia arranged in a densely packed layer by means of a continuum model. The continuum approach allows us to treat the problem as two-dimensional as well as stationary, in a reference frame moving with

  6. Sperm-associated antigen 6 (SPAG6 deficiency and defects in ciliogenesis and cilia function: polarity, density, and beat.

    Directory of Open Access Journals (Sweden)

    Maria E Teves

    Full Text Available SPAG6, an axoneme central apparatus protein, is essential for function of ependymal cell cilia and sperm flagella. A significant number of Spag6-deficient mice die with hydrocephalus, and surviving males are sterile because of sperm motility defects. In further exploring the ciliary dysfunction in Spag6-null mice, we discovered that cilia beat frequency was significantly reduced in tracheal epithelial cells, and that the beat was not synchronized. There was also a significant reduction in cilia density in both brain ependymal and trachea epithelial cells, and cilia arrays were disorganized. The orientation of basal feet, which determines the direction of axoneme orientation, was apparently random in Spag6-deficient mice, and there were reduced numbers of basal feet, consistent with reduced cilia density. The polarized epithelial cell morphology and distribution of intracellular mucin, α-tubulin, and the planar cell polarity protein, Vangl2, were lost in Spag6-deficient tracheal epithelial cells. Polarized epithelial cell morphology and polarized distribution of α-tubulin in tracheal epithelial cells was observed in one-week old wild-type mice, but not in the Spag6-deficient mice of the same age. Thus, the cilia and polarity defects appear prior to 7 days post-partum. These findings suggest that SPAG6 not only regulates cilia/flagellar motility, but that in its absence, ciliogenesis, axoneme orientation, and tracheal epithelial cell polarity are altered.

  7. Identification of G Protein-Coupled Receptors (GPCRs in Primary Cilia and Their Possible Involvement in Body Weight Control.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Omori

    Full Text Available Primary cilia are sensory organelles that harbor various receptors such as G protein-coupled receptors (GPCRs. We analyzed subcellular localization of 138 non-odorant GPCRs. We transfected GPCR expression vectors into NIH3T3 cells, induced ciliogenesis by serum starvation, and observed subcellular localization of GPCRs by immunofluorescent staining. We found that several GPCRs whose ligands are involved in feeding behavior, including prolactin-releasing hormone receptor (PRLHR, neuropeptide FF receptor 1 (NPFFR1, and neuromedin U receptor 1 (NMUR1, localized to the primary cilia. In addition, we found that a short form of dopamine receptor D2 (DRD2S is efficiently transported to the primary cilia, while a long form of dopamine receptor D2 (DRD2L is rarely transported to the primary cilia. Using an anti-Prlhr antibody, we found that Prlhr localized to the cilia on the surface of the third ventricle in the vicinity of the hypothalamic periventricular nucleus. We generated the Npy2r-Cre transgenic mouse line in which Cre-recombinase is expressed under the control of the promoter of Npy2r encoding a ciliary GPCR. By mating Npy2r-Cre mice with Ift80 flox mice, we generated Ift80 conditional knockout (CKO mice in which Npy2r-positive cilia were diminished in number. We found that Ift80 CKO mice exhibited a body weight increase. Our results suggest that Npy2r-positive cilia are important for body weight control.

  8. Robotic architectures

    CSIR Research Space (South Africa)

    Mtshali, M

    2010-01-01

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

  9. Robotic Architectures

    Directory of Open Access Journals (Sweden)

    Mbali Mtshali

    2010-01-01

    Full Text Available In the development of mobile robotic systems, a robotic architecture plays a crucial role in interconnecting all the sub-systems and controlling the system. The design of robotic architectures for mobile autonomous robots is a challenging and complex task. With a number of existing architectures and tools to choose from, a review of the existing robotic architecture is essential. This paper surveys the different paradigms in robotic architectures. A classification of the existing robotic architectures and comparison of different proposals attributes and properties have been carried out. The paper also provides a view on the current state of designing robot architectures. It also proposes a conceptual model of a generalised robotic architecture for mobile autonomous robots.Defence Science Journal, 2010, 60(1, pp.15-22, DOI:http://dx.doi.org/10.14429/dsj.60.96

  10. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

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

  11. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

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

  12. Paramecium BBS genes are key to presence of channels in Cilia

    Directory of Open Access Journals (Sweden)

    Valentine Megan

    2012-09-01

    Full Text Available Abstract Background Changes in genes coding for ciliary proteins contribute to complex human syndromes called ciliopathies, such as Bardet-Biedl Syndrome (BBS. We used the model organism Paramecium to focus on ciliary ion channels that affect the beat form and sensory function of motile cilia and evaluate the effects of perturbing BBS proteins on these channels. Methods We used immunoprecipitations and mass spectrometry to explore whether Paramecium proteins interact as in mammalian cells. We used RNA interference (RNAi and swimming behavior assays to examine the effects of BBS depletion on ciliary ion channels that control ciliary beating. Combining RNA interference and epitope tagging, we examined the effects of BBS depletion of BBS 7, 8 and 9 on the location of three channels and a chemoreceptor in cilia. Results We found 10 orthologs of 8 BBS genes in P. tetraurelia. BBS1, 2, 4, 5, 7, 8 and 9 co-immunoprecipitate. While RNAi reduction of BBS 7 and 9 gene products caused loss and shortening of cilia, RNAi for all BBS genes except BBS2 affected patterns of ciliary motility that are governed by ciliary ion channels. Swimming behavior assays pointed to loss of ciliary K+ channel function. Combining RNAi and epitope tagged ciliary proteins we demonstrated that a calcium activated K+ channel was no longer located in the cilia upon depletion of BBS 7, 8 or 9, consistent with the cells’ swimming behavior. The TRPP channel PKD2 was also lost from the cilia. In contrast, the ciliary voltage gated calcium channel was unaffected by BBS depletion, consistent with behavioral assays. The ciliary location of a chemoreceptor for folate was similarly unperturbed by the depletion of BBS 7, 8 or 9. Conclusions The co-immunoprecipitation of BBS 1,2,4,5,7,8, and 9 suggests a complex of BBS proteins. RNAi for BBS 7, 8 or 9 gene products causes the selective loss of K+ and PKD2 channels from the cilia while the critical voltage gated calcium channel and a

  13. Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis.

    Directory of Open Access Journals (Sweden)

    Josephine C Bodle

    Full Text Available Adipose-derived stem cells (ASC are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1, polycystin-2 (PC2 and intraflagellar transport protein-88 (IFT88, in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the cilium structure and phenotypic determination. Abrogation of PC1, PC2 and IFT88 effected changes in both hASC proliferation and differentiation activity, as measured through proliferative activity, expression of osteogenic gene markers, calcium accretion and endogenous alkaline phosphatase activity. Results indicated that IFT88 may be an early mediator of the hASC differentiation process with its knockdown increasing hASC proliferation and decreasing Runx2, alkaline phosphatase and BMP-2 mRNA expression. PC1 and PC2 knockdown affected later osteogenic gene and end-product expression. PC1 knockdown resulted in downregulation of alkaline phosphatase and osteocalcin gene expression, diminished calcium accretion and reduced alkaline phosphatase enzymatic activity. Taken together our results indicate that the structure of the primary cilium is intimately associated with the process of hASC osteogenic differentiation and that its associated proteins are critical

  14. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    compares "best practice" in Denmark and "best practice" in Austria. The modern architects accepted the fact that industrialized architecture told the storey of repetition and monotonous as basic condition. This article aims to explain that architecture can be thought as a complex and diverse design through......Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l inge.vestergaard@aarch.dk Based on the repetitive architecture from the "building boom" 1960...... to 1973 it is discussed how architects can handle these Danish element and montage buildings through the transformation to upgraded aesthetical, functional and energy efficient architecture. The method used is analysis of cases, parallels to literature studies and producer interviews. This analysis...

  15. A continuous roll-pulling approach for the fabrication of magnetic artificial cilia with microfluidic pumping capability.

    Science.gov (United States)

    Wang, Ye; den Toonder, Jaap; Cardinaels, Ruth; Anderson, Patrick

    2016-06-21

    Magnetic artificial cilia are micro-hairs covering a surface that can be actuated using a time-dependent magnetic field to pump or mix fluids in microfluidic devices. This paper presents a novel fabrication method to realize magnetic artificial cilia using a roll-pulling process, in which a cylinder decorated with micro-pillars rolls over a liquid precursor film that contains magnetic particles at a speed up to 1 m s(-1), while a magnetic field is applied. Due to the interaction between the pillars and the liquid film, micro-hairs are pulled out of the film. In this way, surfaces with slender cone-shaped magnetic artificial cilia were produced. When integrated in a closed-loop channel, the artificial cilia were shown to be capable of generating substantial microfluidic pumping using external magnetic actuation. The spatial arrangement of the cilia can be varied by altering the layout of the micro-pillars on the roll surface. In addition, the final geometry of the individual cilia depends on the rheological properties of the precursor material in combination with the processing parameters of the roll-pulling process. A rheological study and fabrication tests were carried out for a range of precursor material compositions to obtain insight into the relation between precursor rheology and processing conditions on the one hand, and cilia geometry on the other hand. The development of this cleanroom-free, high speed and potentially large area method of production of artificial cilia is another step towards their implementation in real-life applications.

  16. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

    Directory of Open Access Journals (Sweden)

    Daniel T Grimes

    2016-06-01

    Full Text Available During mammalian development, left-right (L-R asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM. Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo.

  17. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

    Science.gov (United States)

    Grimes, Daniel T; Keynton, Jennifer L; Buenavista, Maria T; Jin, Xingjian; Patel, Saloni H; Kyosuke, Shinohara; Vibert, Jennifer; Williams, Debbie J; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M; Norris, Dominic P

    2016-06-01

    During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo.

  18. A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia.

    Science.gov (United States)

    Dorn, Karolin V; Hughes, Casey E; Rohatgi, Rajat

    2012-10-16

    Vertebrate Hedgehog (Hh) signaling is initiated at primary cilia by the ligand-triggered accumulation of Smoothened (Smo) in the ciliary membrane. The underlying biochemical mechanisms remain unknown. We find that Hh agonists promote the association between Smo and Evc2, a ciliary protein that is defective in two human ciliopathies. The formation of the Smo-Evc2 complex is under strict spatial control, being restricted to a distinct ciliary compartment, the EvC zone. Mutant Evc2 proteins that localize in cilia but are displaced from the EvC zone are dominant inhibitors of Hh signaling. Disabling Evc2 function blocks Hh signaling at a specific step between Smo and the downstream regulators protein kinase A and Suppressor of Fused, preventing activation of the Gli transcription factors. Our data suggest that the Smo-Evc2 signaling complex at the EvC zone is required for Hh signal transmission and elucidate the molecular basis of two human ciliopathies.

  19. Expression of polycystins and fibrocystin on primary cilia of lung cells.

    Science.gov (United States)

    Hu, Qiaolin; Wu, Yuliang; Tang, Jingfeng; Zheng, Wang; Wang, Qian; Nahirney, Drew; Duszyk, Marek; Wang, Shaohua; Tu, Jian-Cheng; Chen, Xing-Zhen

    2014-12-01

    Mutations in polycystin-1, polycystin-2, or fibrocystin account for autosomal dominant or recessive polycystic kidney disease. Renal cystogenesis is linked to abnormal localization and function of these cystoproteins in renal primary cilia. They are also expressed in extrarenal tissues in which their functions are unclear. Here we found that human type-II alveolar epithelial A549, airway submucosal Calu-3 cells, and rat bronchioles contain primary or multiple cilia in which we detected these cystoproteins. At sub-confluency, polycystin-1 was expressed on plasma membrane, while polycystin-2 was localized to the ER of resting cells. Both polycystins were detected on the spindle and mid-body of mitotic cells, while fibrocystin was on centrosome throughout cell cycle. Polycystins and fibrocystin may participate in regulating mucociliary sensing and transport within pulmonary airways.

  20. Identification of Elongated Primary Cilia with Impaired Mechanotransduction in Idiopathic Scoliosis Patients

    Science.gov (United States)

    Oliazadeh, Niaz; Gorman, Kristen F.; Eveleigh, Robert; Bourque, Guillaume; Moreau, Alain

    2017-01-01

    The primary cilium is an outward projecting antenna-like organelle with an important role in bone mechanotransduction. The capacity to sense mechanical stimuli can affect important cellular and molecular aspects of bone tissue. Idiopathic scoliosis (IS) is a complex pediatric disease of unknown cause, defined by abnormal spinal curvatures. We demonstrate significant elongation of primary cilia in IS patient bone cells. In response to mechanical stimulation, these IS cells differentially express osteogenic factors, mechanosensitive genes, and signaling genes. Considering that numerous ciliary genes are associated with a scoliosis phenotype, among ciliopathies and knockout animal models, we expected IS patients to have an accumulation of rare variants in ciliary genes. Instead, our SKAT-O analysis of whole exomes showed an enrichment among IS patients for rare variants in genes with a role in cellular mechanotransduction. Our data indicates defective cilia in IS bone cells, which may be linked to heterogeneous gene variants pertaining to cellular mechanotransduction. PMID:28290481

  1. A simple cell-based assay reveals that diverse neuropsychiatric risk genes converge on primary cilia.

    Directory of Open Access Journals (Sweden)

    Aaron Marley

    Full Text Available Human genetic studies are beginning to identify a large number of genes linked to neuropsychiatric disorders. It is increasingly evident that different genes contribute to risk for similar syndromes and, conversely, the same genes or even the same alleles cross over traditional diagnostic categories. A current challenge is to understand the cellular biology of identified risk genes. However, most genes associated with complex neuropsychiatric phenotypes are not related through a known biochemical pathway, and many have an entirely unknown cellular function. One possibility is that diverse disease-linked genes converge at a higher-level cellular structure. The synapse is already known to be one such convergence, and emerging evidence suggests the primary cilium as another. Because many genes associated with neuropsychiatric illness are expressed also outside the nervous system, as are cilia, we tested the hypothesis that such genes affect conserved features of the primary cilium. Using RNA interference to test 41 broadly expressed candidate genes associated with schizophrenia, bipolar affective disorder, autism spectrum disorder and intellectual disability, we found 20 candidates that reduce ciliation in NIH3T3 cells when knocked down, and three whose manipulation increases cilia length. Three of the candidate genes were previously implicated in cilia formation and, altogether, approximately half of the candidates tested produced a ciliary phenotype. Our results support the hypothesis that primary cilia indeed represent a conserved cellular structure at which the effects of diverse neuropsychiatric risk genes converge. More broadly, they suggest a relatively simple cell-based approach that may be useful for exploring the complex biological underpinnings of neuropsychiatric disease.

  2. Heat transfer analysis of Rabinowitsch fluid flow due to metachronal wave of cilia

    Directory of Open Access Journals (Sweden)

    Noreen Sher Akbar

    2015-01-01

    Full Text Available The present investigation concerns with the mechanical properties of a Rabinowitsch fluid model and the effects of thermal conductivity over it. Flow is considered to be occurring due to metachronal wave produced as a result of constant beating of cilia at the walls of a horizontal circular tube. The expressions for flow characteristics have been derived results are analyzed graphically and discussed briefly.

  3. Occurrence of autoantibodies to cilia in lambs with a 'coughing syndrome'.

    Science.gov (United States)

    Niang, M; Rosenbusch, R F; Andrews, J J; Lopez-Virella, J; Kaeberle, M L

    1998-07-31

    A respiratory disease of lambs that has been termed the 'coughing syndrome' has been observed in the mid-western region of the United States of America. Mycoplasma ovipneumoniae (M. ovipneumoniae) and Mycoplasma arginini (M. arginini) were routinely isolated from the respiratory tract of lambs with this disease. A high level of antibodies reactive with ovine cilia of the upper respiratory tract was detected in the sera from many of the lambs in affected flocks but not in sera of lambs from unaffected flocks. The reactivity of these antibodies with cilia was demonstrated by ELISA and confirmed by indirect immunofluorescent staining and western immunoblotting. These antibodies were predominantly of the IgG isotype. They were distinct from cold or warm agglutinins and could be absorbed from the sera with cilia but not with antigens of common bacterial pathogens of the sheep respiratory tract including M. ovipneumoniae, M. arginini, Pasteurella haemolytica, Pasteurella multocida or Neisseria ovis. In addition, their occurrence appeared to be independent of the specific antibodies to M. ovipneumoniae and M. arginini. Western immunoblotting indicated that the antibodies were directed primarily against an antigen with apparent molecular weight of 50 kDa. In one flock from which serial serum samples were collected from the same lambs over a 10-month period, antibodies to ovine cilia developed before the onset of the clinical disease and persisted for a period of several months until most of the lambs had apparently recovered. However, colonization of the respiratory tract of the lambs by M. ovipneumoniae preceded the production of these antibodies. Sequential serum samples taken from another flock, with no known history of this coughing, showed no such antibodies throughout the sampling period. It is suggested that an immunopathologic mechanism involving production of autoantibodies directed against a ciliary antigen of the lambs could be a contributing factor to the

  4. A Smoothened-Evc2 Complex Transduces the Hedgehog Signal at Primary Cilia

    OpenAIRE

    Dorn, Karolin V.; Hughes, Casey E.; Rohatgi, Rajat

    2012-01-01

    Vertebrate Hedgehog (Hh) signaling is initiated at primary cilia by the ligand-triggered accumulation of Smoothened (Smo) in the ciliary membrane. The underlying biochemical mechanisms remain unknown. We find that Hh agonists promote the association between Smo and Evc2, a ciliary protein that is defective in two human ciliopathies. The formation of the Smo-Evc2 complex is under strict spatial control, being restricted to a distinct ciliary compartment, the EvC zone. Mutant Evc2 proteins that...

  5. Microtubule-membrane interactions in cilia. I. Isolation and characterization of ciliary membranes from Tetrahymena pyriformis

    OpenAIRE

    1980-01-01

    Tetrahymena ciliary membranes were prepared by four different techniques, and their protein composition was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), electron microscopy, and two-dimensional thin-layer peptide mapping. Extraction of the isolated cilia by nonionic detergent solubilized the ciliary membranes but left the axonemal microtubules and dyneine arms intact, as determined by quantitative electron microscopy. The proteins solubilized by detergent ...

  6. Green Architecture

    Science.gov (United States)

    Lee, Seung-Ho

    Today, the environment has become a main subject in lots of science disciplines and the industrial development due to the global warming. This paper presents the analysis of the tendency of Green Architecture in France on the threes axes: Regulations and Approach for the Sustainable Architecture (Certificate and Standard), Renewable Materials (Green Materials) and Strategies (Equipments) of Sustainable Technology. The definition of 'Green Architecture' will be cited in the introduction and the question of the interdisciplinary for the technological development in 'Green Architecture' will be raised up in the conclusion.

  7. Catalyst Architecture

    DEFF Research Database (Denmark)

    Kiib, Hans; Marling, Gitte; Hansen, Peter Mandal

    2014-01-01

    How can architecture promote the enriching experiences of the tolerant, the democratic, and the learning city - a city worth living in, worth supporting and worth investing in? Catalyst Architecture comprises architectural projects, which, by virtue of their location, context and their combination...... of programs, have a role in mediating positive social and/or cultural development. In this sense, we talk about architecture as a catalyst for: sustainable adaptation of the city’s infrastructure appropriate renovation of dilapidated urban districts strengthening of social cohesiveness in the city development...

  8. Software architecture

    CERN Document Server

    Vogel, Oliver; Chughtai, Arif

    2011-01-01

    As a software architect you work in a wide-ranging and dynamic environment. You have to understand the needs of your customer, design architectures that satisfy both functional and non-functional requirements, and lead development teams in implementing the architecture. And it is an environment that is constantly changing: trends such as cloud computing, service orientation, and model-driven procedures open up new architectural possibilities. This book will help you to develop a holistic architectural awareness and knowledge base that extends beyond concrete methods, techniques, and technologi

  9. WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia.

    Science.gov (United States)

    Patel-King, Ramila S; Gilberti, Renée M; Hom, Erik F Y; King, Stephen M

    2013-09-01

    Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle-like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly.

  10. WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia

    Science.gov (United States)

    Patel-King, Ramila S.; Gilberti, Renée M.; Hom, Erik F. Y.; King, Stephen M.

    2013-01-01

    Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle–like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

  11. Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development.

    Science.gov (United States)

    Bhattacharyya, Sohinee; Rainey, Mark A; Arya, Priyanka; Dutta, Samikshan; George, Manju; Storck, Matthew D; McComb, Rodney D; Muirhead, David; Todd, Gordon L; Gould, Karen; Datta, Kaustubh; Gelineau-van Waes, Janee; Band, Vimla; Band, Hamid

    2016-02-17

    Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling of cell surface receptors from endosomes to the plasma membrane. In this study, we show that Ehd1 gene knockout in mice on a predominantly B6 background is embryonic lethal. Ehd1-null embryos die at mid-gestation with a failure to complete key developmental processes including neural tube closure, axial turning and patterning of the neural tube. We found that Ehd1-null embryos display short and stubby cilia on the developing neuroepithelium at embryonic day 9.5 (E9.5). Loss of EHD1 also deregulates the ciliary SHH signaling with Ehd1-null embryos displaying features indicative of increased SHH signaling, including a significant downregulation in the formation of the GLI3 repressor and increase in the ventral neuronal markers specified by SHH. Using Ehd1-null MEFS we found that EHD1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation. Under the same conditions, EHD1 was shown to co-traffic with Smoothened into the developing primary cilia and we identify EHD1 as a direct binding partner of Smoothened. Overall, our studies identify the endocytic recycling regulator EHD1 as a novel regulator of the primary cilium-associated trafficking of Smoothened and Hedgehog signaling.

  12. Evolutionary implications of localization of the signaling scaffold protein parafusin to both cilia and the nucleus.

    Science.gov (United States)

    Satir, Birgit Hegner; Wyroba, Elzbieta; Liu, Li; Lethan, Mette; Satir, Peter; Christensen, Søren Tvorup

    2015-02-01

    Parafusin (PFUS), a 63 kDa protein first discovered in the eukaryote Paramecium and known for its role in apicomplexan exocytosis, provides a model for the common origin of cellular systems employing scaffold proteins for targeting and signaling. PFUS is closely related to eubacterial rather than archeal phosphoglucomutases (PGM) - as we proved by comparison of their 88 sequences - but has no PGM activity. Immunofluorescence microscopy analysis with a PFUS-specific peptide antibody showed presence of this protein around the base region of primary cilia in a variety of mammalian cell types, including mouse embryonic (MEFs) and human foreskin fibroblasts (hFFs), human carcinoma stem cells (NT-2 cells), and human retinal pigment epithelial (RPE) cells. Further, PFUS localized to the nucleus of fibroblasts, and prominently to nucleoli of MEFs. Localization studies were confirmed by Western blot analysis, showing that the PFUS antibody specifically recognizes a single protein of ca. 63 kDa in both cytoplasmic and nuclear fractions. Finally, immunofluorescence microscopy analysis showed that PFUS localized to nuclei and cilia in Paramecium. These results support the suggestion that PFUS plays a role in signaling between nucleus and cilia, and that the cilium and the nucleus both evolved around the time of eukaryotic emergence. We hypothesize that near the beginnings of eukaryotic cell evolution, scaffold proteins such as PFUS arose as peripheral membrane protein identifiers for cytoplasmic membrane trafficking and were employed similarly during the subsequent evolution of exocytic, nuclear transport, and ciliogenic mechanisms.

  13. Primary cilia regulate Shh activity in the control of molar tooth number.

    Science.gov (United States)

    Ohazama, Atsushi; Haycraft, Courtney J; Seppala, Maisa; Blackburn, James; Ghafoor, Sarah; Cobourne, Martyn; Martinelli, David C; Fan, Chen-Ming; Peterkova, Renata; Lesot, Herve; Yoder, Bradley K; Sharpe, Paul T

    2009-03-01

    Primary cilia mediate Hh signalling and mutations in their protein components affect Hh activity. We show that in mice mutant for a cilia intraflagellar transport (IFT) protein, IFT88/polaris, Shh activity is increased in the toothless diastema mesenchyme of the embryonic jaw primordia. This results in the formation of ectopic teeth in the diastema, mesial to the first molars. This phenotype is specific to loss of polaris activity in the mesenchyme since loss of Polaris in the epithelium has no detrimental affect on tooth development. To further confirm that upregulation of Shh activity is responsible for the ectopic tooth formation, we analysed mice mutant for Gas1, a Shh protein antagonist in diastema mesenchyme. Gas1 mutants also had ectopic diastema teeth and accompanying increased Shh activity. In this context, therefore, primary cilia exert a specific negative regulatory effect on Shh activity that functions to repress tooth formation and thus determine tooth number. Strikingly, the ectopic teeth adopt a size and shape characteristic of premolars, a tooth type that was lost in mice around 50-100 million years ago.

  14. Primary cilia in the basal cells of equine epididymis: a serendipitous finding.

    Science.gov (United States)

    Arrighi, Silvana

    2013-04-01

    Occurrence of a solitary cilium was an unexpected discovery while studying the ultrastructure of epididymal epithelium in equidae. Primary cilia were detected in epididymal basal cells of all individuals of the equines studied - horses, donkey and mules - independently from age and tract of the duct, emerging from the basal cell surface and insinuating into the intercellular spaces. More rarely solitary cilia occurred also at the luminal surface of the principal cells. The ciliary apparatus was constituted by a structurally typical basal body continuous with the finger-like ciliary shaft extending from the cell surface, and an adjacent centriole oriented at right angles to the basal body. The cilium was structured as the typical primary, non-motile cilia found in many mammalian cells, having a 9+0 microtubular pattern. The basal diplosome was randomly associated with other cellular organelles including the Golgi complex, the endoplasmic reticulum, the microfilament network, the plasma membrane, vesicles and pits. Primary ciliogenesis is a new and unexpected finding in the epididymal epithelium. A monitoring role of luminal factors and extracellular liquids might be attributed to this organelle, likely acting as chemical receptor of the luminal environment, thus modulating the epithelial function by a cell-to-cell crosstalk involving the entire epithelium.

  15. A complex of BBS1 and NPHP7 is required for cilia motility in zebrafish.

    Directory of Open Access Journals (Sweden)

    Yun Hee Kim

    Full Text Available Bardet-Biedl syndrome (BBS and nephronophthisis (NPH are hereditary autosomal recessive disorders, encoded by two families of diverse genes. BBS and NPH display several overlapping phenotypes including cystic kidney disease, retinitis pigmentosa, liver fibrosis, situs inversus and cerebellar defects. Since most of the BBS and NPH proteins localize to cilia and/or their appendages, BBS and NPH are considered ciliopathies. In this study, we characterized the function of the transcription factor Nphp7 in zebrafish, and addressed the molecular connection between BBS and NPH. The knockdown of zebrafish bbs1 and nphp7.2 caused similar phenotypic changes including convergent extension defects, curvature of the body axis, hydrocephalus, abnormal heart looping and cystic pronephros, all consistent with an altered ciliary function. Immunoprecipitation assays revealed a physical interaction between BBS1 and NPHP7, and the simultaneous knockdown of zbbs1 and znphp7.2 enhanced the cystic pronephros phenotype synergistically, suggesting a genetic interaction between zbbs1 and znphp7.2 in vivo. Deletion of zBbs1 or zNphp7.2 did not compromise cilia formation, but disrupted cilia motility. Although NPHP7 has been shown to act as transcriptional repressor, our studies suggest a crosstalk between BBS1 and NPHP7 in regulating normal function of the cilium.

  16. Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development

    Science.gov (United States)

    Klein, Maike K.; Haberberger, Rainer V.; Hartmann, Petra; Faulhammer, Petra; Lips, Katrin S.; Krain, Benjamin; Wess, Jürgen; Kummer, Wolfgang; König, Peter

    2014-01-01

    Ciliary beating of airway epithelial cells drives the removal of mucus and particles from the airways. Mucociliary transport and possibly airway epithelial development are governed by muscarinic acetylcholine receptors but the precise roles of the subtypes involved are unknown. This issue was addressed by determining cilia-driven particle transport, ciliary beat frequency, and the composition and ultrastructural morphology of the tracheal epithelium in M1–M5 muscarinic receptor gene-deficient mice. Knockout of M3 muscarinic receptors prevented an increase in particle transport speed and ciliary beat frequency in response to muscarine. Furthermore, the ATP response after application of muscarine was blunted. Pretreatment with atropine before application of muscarine restored the response to ATP. Additional knockout of the M2 receptor in these mice partially restored the muscarine effect most likely through the M1 receptor and normalized the ATP response. M1, M4, and M5 receptor deficient mice exhibited normal responses to muscarine. None of the investigated mutant mouse strains had any impairment of epithelial cellular structure or composition. In conclusion, M3 receptors stimulate whereas M2 receptors inhibit cilia-driven particle transport. The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptor are missing. None of the receptors is necessary for epithelial development. PMID:19213795

  17. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l inge.vestergaard@aarch.dk Based on the repetitive architecture from the "building boom" 1960...... compares "best practice" in Denmark and "best practice" in Austria. The modern architects accepted the fact that industrialized architecture told the storey of repetition and monotonous as basic condition. This article aims to explain that architecture can be thought as a complex and diverse design through...... to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...

  18. Architectural Contestation

    NARCIS (Netherlands)

    Merle, J.

    2012-01-01

    This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form, consequ

  19. Local architecture

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Local architecture refers to structures built in the countryside,such as temples,memorial halls,residences, stores,pavilions, bridges,decorated archways, and wells. Because these structures were all built by focal craftsmen and villagers in the traditional local style, they are generally called local architecture.

  20. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

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

  1. Architectural geometry

    NARCIS (Netherlands)

    Pottmann, Helmut; Eigensatz, Michael; Vaxman, A.; Wallner, Johannes

    2015-01-01

    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural

  2. Architectural Contestation

    NARCIS (Netherlands)

    Merle, J.

    2012-01-01

    This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form,

  3. Architectural geometry

    NARCIS (Netherlands)

    Pottmann, Helmut; Eigensatz, Michael; Vaxman, A.; Wallner, Johannes

    2015-01-01

    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural

  4. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    This PhD thesis is motived by a personal interest in the theoretical, practical and creative qualities of architecture. But also a wonder and curiosity about the cultural and social relations architecture represents through its occupation with both the sciences and the arts. Inspired by present...... initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture...... environments and a knowledge gap therefore exists in present hospital designs. Consequently, the purpose of this thesis has been to investigate if any research-based knowledge exist supporting the hypothesis that the interior architectural qualities of eating environments influence patient food intake, health...

  5. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    2012-01-01

    design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  6. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    and well-being, as well as outline a set of basic design principles ‘predicting’ the future interior architectural qualities of patient eating environments. Methodologically the thesis is based on an explorative study employing an abductive approach and hermeneutic-interpretative strategy utilizing tactics......This PhD thesis is motived by a personal interest in the theoretical, practical and creative qualities of architecture. But also a wonder and curiosity about the cultural and social relations architecture represents through its occupation with both the sciences and the arts. Inspired by present...... initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture...

  7. Architectural Narratives

    DEFF Research Database (Denmark)

    2010-01-01

    and architectural heritage; another group tries to embed new performative technologies in expressive architectural representation. Finally, this essay provides a theoretical framework for the analysis of the political rationales of these projects and for the architectural representation bridges the gap between......In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... identifies new rationales related to this development, and it argues that “cultural planning” has increasingly shifted its focus from a cultural institutional approach to a more market-oriented strategy that integrates art and business. The role of architecture has changed, too. It not only provides...

  8. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    , is the current building of a series of Danish ‘super hospitals’ and an increased focus among architectural practices on research-based knowledge produced with the architectural sub-disciplines Healing Architecture and Evidence-Based Design. The problem is that this research does not focus on patient eating...... environments and a knowledge gap therefore exists in present hospital designs. Consequently, the purpose of this thesis has been to investigate if any research-based knowledge exist supporting the hypothesis that the interior architectural qualities of eating environments influence patient food intake, health...... and well-being, as well as outline a set of basic design principles ‘predicting’ the future interior architectural qualities of patient eating environments. Methodologically the thesis is based on an explorative study employing an abductive approach and hermeneutic-interpretative strategy utilizing tactics...

  9. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    -anthropology. Within the field of architecture, however, there has not yet been quite the same eagerness to include anthropological approaches in design processes. This paper discusses why this is so and how and whether architectural anthropology has different conditions and objectives than other types of design...... and other spaces that architects are preoccupied with. On the other hand, the distinction between architecture and design is not merely one of scale. Design and architecture represent – at least in Denmark – also quite different disciplinary traditions and methods. Where designers develop prototypes......, and that this will restrict the creative design process. Also, the end user of architecture is not easily identified, as a new building should not just accommodate the needs of specific residents but also those of neighbours, future residents, other citizens and maybe society as such. The paper explores the challenges...

  10. The gastrocoel roof plate in embryos of different frogs.

    Science.gov (United States)

    Sáenz-Ponce, Natalia; Santillana-Ortiz, Juan-Diego; del Pino, Eugenia M

    2012-02-01

    The morphology of the gastrocoel roof plate and the presence of cilia in this structure were examined in embryos of four species of frogs. Embryos of Ceratophrys stolzmanni (Ceratophryidae) and Engystomops randi (Leiuperidae) develop rapidly, provide comparison for the analysis of gastrocoel roof plate development in the slow-developing embryos of Epipedobates machalilla (Dendrobatidae) and Gastrotheca riobambae (Hemiphractidae). Embryos of the analyzed frogs develop from eggs of different sizes, and display different reproductive and developmental strategies. In particular, dorsal convergence and extension and archenteron elongation begin during gastrulation in embryos of rapidly developing frogs, as in Xenopus laevis. In contrast, cells that involute during gastrulation are stored in the large circumblastoporal collar that develops around the closed blastopore in embryos of slow-developing frogs. Dorsal convergence and extension only start after blastopore closure in slow-developing frog embryos. However, in the neurulae, a gastrocoel roof plate develops, despite the accumulation of superficial mesodermal cells in the circumblastoporal collar. Embryos of all four species develop a ciliated gastrocoel roof plate at the beginning of neurulation. Accordingly, fluid-flow across the gastrocoel roof plate is likely the mechanism of left-right asymmetry patterning in these frogs, as in X. laevis and other vertebrates. A ciliated gastrocoel roof plate, with a likely origin as superficial mesoderm, is conserved in frogs belonging to four different families and with different modes of gastrulation.

  11. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

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

  12. Healing Architecture

    DEFF Research Database (Denmark)

    Folmer, Mette Blicher; Mullins, Michael; Frandsen, Anne Kathrine

    2012-01-01

    The project examines how architecture and design of space in the intensive unit promotes or hinders interaction between relatives and patients. The primary starting point is the relatives. Relatives’ support and interaction with their loved ones is important in order to promote the patients healing...... process. Therefore knowledge on how space can support interaction is fundamental for the architect, in order to make the best design solutions. Several scientific studies document that the hospital's architecture and design are important for human healing processes, including how the physical environment...... architectural and design solutions in order to improve quality of interaction between relative and patient in the hospital's intensive unit....

  13. Architectural technology

    DEFF Research Database (Denmark)

    2005-01-01

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

  14. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

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

  15. The zebrafish orthologue of the dyslexia candidate gene DYX1C1 is essential for cilia growth and function.

    Directory of Open Access Journals (Sweden)

    Gayathri Chandrasekar

    Full Text Available DYX1C1, a susceptibility gene for dyslexia, encodes a tetratricopeptide repeat domain containing protein that has been implicated in neuronal migration in rodent models. The developmental role of this gene remains unexplored. To understand the biological function(s of zebrafish dyx1c1 during embryonic development, we cloned the zebrafish dyx1c1 and used morpholino-based knockdown strategy. Quantitative real-time PCR analysis revealed the presence of dyx1c1 transcripts in embryos, early larval stages and in a wide range of adult tissues. Using mRNA in situ hybridization, we show here that dyx1c1 is expressed in many ciliated tissues in zebrafish. Inhibition of dyx1c1 produced pleiotropic phenotypes characteristically associated with cilia defects such as body curvature, hydrocephalus, situs inversus and kidney cysts. We also demonstrate that in dyx1c1 morphants, cilia length is reduced in several organs including Kupffer's vesicle, pronephros, spinal canal and olfactory placode. Furthermore, electron microscopic analysis of cilia in dyx1c1 morphants revealed loss of both outer (ODA and inner dynein arms (IDA that have been shown to be required for cilia motility. Considering all these results, we propose an essential role for dyx1c1 in cilia growth and function.

  16. Alcohol drives S-nitrosylation and redox activation of protein phosphatase 1, causing bovine airway cilia dysfunction.

    Science.gov (United States)

    Price, Michael E; Pavlik, Jacqueline A; Liu, Miao; Ding, Shi-Jian; Wyatt, Todd A; Sisson, Joseph H

    2017-03-01

    Individuals with alcohol (ethanol)-use disorders are at increased risk for lung infections, in part, due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated, demembranated bovine cilia (axonemes) are capable of producing nitric oxide ((∙)NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of (∙)NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosonium cations or (∙)NO to thiolate or thiyl radicals, respectively, of proteins forming S-nitrosothiols (SNOs). We quantified and compared SNO content between isolated, demembranated axonemes extracted from bovine tracheae, with or without in situ alcohol exposure (100 mM × 24 h). We demonstrate that relevant concentrations of alcohol exposure shift the S-nitrosylation status of key cilia regulatory proteins, including 20-fold increases in S-nitrosylation of proteins that include protein phosphatase 1 (PP1). With the use of an ATP-reactivated axoneme motility system, we demonstrate that alcohol-driven S-nitrosylation of PP1 is associated with PP1 activation and dysfunction of axoneme motility. These new data demonstrate that alcohol can shift the S-nitrothiol balance at the level of the cilia organelle and highlight S-nitrosylation as a novel signaling mechanism to regulate PP1 and cilia motility.

  17. Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe.

    Directory of Open Access Journals (Sweden)

    Na Luo

    Full Text Available Inositol phosphatases are important regulators of cell signaling, polarity, and vesicular trafficking. Mutations in OCRL, an inositol polyphosphate 5-phosphatase, result in Oculocerebrorenal syndrome of Lowe, an X-linked recessive disorder that presents with congenital cataracts, glaucoma, renal dysfunction and mental retardation. INPP5B is a paralog of OCRL and shares similar structural domains. The roles of OCRL and INPP5B in the development of cataracts and glaucoma are not understood. Using ocular tissues, this study finds low levels of INPP5B present in human trabecular meshwork but high levels in murine trabecular meshwork. In contrast, OCRL is localized in the trabecular meshwork and Schlemm's canal endothelial cells in both human and murine eyes. In cultured human retinal pigmented epithelial cells, INPP5B was observed in the primary cilia. A functional role for INPP5B is revealed by defects in cilia formation in cells with silenced expression of INPP5B. This is further supported by the defective cilia formation in zebrafish Kupffer's vesicles and in cilia-dependent melanosome transport assays in inpp5b morphants. Taken together, this study indicates that OCRL and INPP5B are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development.

  18. Architectural Mealscapes

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning

    2012-01-01

    the German architect Gottfried Semper developed a theory on the “four elements of Architecture” tracing the origin of architecture back to the rise of the early human settlement and the creation of fire. With the notion ‘hearth’ as the first motive in architecture and the definition of three enclosing...... motives; mounding, enclosure and roof, Semper linked the cultural and social values of the primordial fireplace with the order and shape of architecture. He claimed that any building ever made was nothing but a variation of the first primitive shelters erected around the fireplace, and that the three...... enclosing motives existed only as defenders of the “sacred flame”. In that way Semper developed the idea that any architectural scenery can be described, analyzed and explained by understanding the contextual, symbolic and social values of how the four basic motives of hearth, mounding, enclosure, and roof...

  19. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning

    2013-01-01

    and recovery through the architecture framing eating experiences, this article examines, from a theoretical perspective, two less debated concepts relating to hospitality called food design and architectural theatricality. In architectural theory the nineteenth century German architect Gottfried Semper...... is known for his writings on theatricality, understood as a holistic design approach emphasizing the contextual, cultural, ritual and social meanings rooted in architecture. Relative hereto, the International Food Design Society recently argued, in a similar holistic manner, that the methodology used...... to provide an aesthetic eating experience includes knowledge on both food and design. Based on a hermeneutic reading of Semper’s theory, our thesis is that this holistic design approach is important when debating concepts of hospitality in hospitals. We use this approach to argue for how ‘food design...

  20. Architectural Engineers

    DEFF Research Database (Denmark)

    Petersen, Rikke Premer

    The design professions have always been an amorphous phenomena difficult to merge under one label. New constellations continually emerge, questioning, stretching, and reconfiguring the understanding of design and the professional practices linked to it. In this paper the idea of architectural...... engineering is addresses from two perspectives – as an educational response and an occupational constellation. Architecture and engineering are two of the traditional design professions and they frequently meet in the occupational setting, but at educational institutions they remain largely estranged....... The paper builds on a multi-sited study of an architectural engineering program at the Technical University of Denmark and an architectural engineering team within an international engineering consultancy based on Denmark. They are both responding to new tendencies within the building industry where...

  1. A new refined theory of plates with transverse shear deformation for moderately thick and thick plates

    CERN Document Server

    Valle, Jose Miguel Martinez

    2015-01-01

    In this paper we propose a new refined shear deformation plate theory which possesses a series of desirable features, the most salient of which are as follows: (i) The loads, which are generally considered to be applied on the middle surface of the plate, act on the upper surface of the plate; (ii) The equations are applicable to the calculation of the stresses in isotropic plates and provide the same order of accuracy as several theories with second order shear deformation effects; (iii) It constitutes a theory, in the sense defined by Love, since it gives easy expressions for application to problems in different fields in architecture and civil engineering

  2. Create Your Plate

    Medline Plus

    Full Text Available ... A A A Listen En Español Create Your Plate Create Your Plate is a simple and effective ... and that your options are endless. Create Your Plate! Click on the plate sections below to add ...

  3. Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Polloneal Jymmiel R Ocbina

    Full Text Available Sonic hedgehog (Shh signaling in the mouse requires the microtubule-based organelle, the primary cilium. The primary cilium is assembled and maintained through the process of intraflagellar transport (IFT and the response to Shh is blocked in mouse mutants that lack proteins required for IFT. Although the phenotypes of mouse IFT mutants do not overlap with phenotypes of known Wnt pathway mutants, recent studies report data suggesting that the primary cilium modulates responses to Wnt signals.We therefore carried out a systematic analysis of canonical Wnt signaling in mutant embryos and cells that lack primary cilia because of loss of the anterograde IFT kinesin-II motor (Kif3a or IFT complex B proteins (Ift172 or Ift88. We also analyzed mutant embryos with abnormal primary cilia due to defects in retrograde IFT (Dync2h1. The mouse IFT mutants express the canonical Wnt target Axin2 and activate a transgenic canonical Wnt reporter, BAT-gal, in the normal spatial pattern and to the same quantitative level as wild type littermates. Similarly, mouse embryonic fibroblasts (MEFs derived from IFT mutants respond normally to added Wnt3a. The switch from canonical to non-canonical Wnt also appears normal in IFT mutant MEFs, as both wild-type and mutant cells do not activate the canonical Wnt reporter in the presence of both Wnt3a and Wnt5a.We conclude that loss of primary cilia or defects in retrograde IFT do not affect the response of the midgestation embryo or embryo-derived fibroblasts to Wnt ligands.

  4. A processed multidomain mycoplasma hyopneumoniae adhesin binds fibronectin, plasminogen, and swine respiratory cilia.

    Science.gov (United States)

    Seymour, Lisa M; Deutscher, Ania T; Jenkins, Cheryl; Kuit, Tracey A; Falconer, Linda; Minion, F Chris; Crossett, Ben; Padula, Matthew; Dixon, Nicholas E; Djordjevic, Steven P; Walker, Mark J

    2010-10-29

    Porcine enzootic pneumonia is a chronic respiratory disease that affects swine. The etiological agent of the disease, Mycoplasma hyopneumoniae, is a bacterium that adheres to cilia of the swine respiratory tract, resulting in loss of cilia and epithelial cell damage. A M. hyopneumoniae protein P116, encoded by mhp108, was investigated as a potential adhesin. Examination of P116 expression using proteomic analyses observed P116 as a full-length protein and also as fragments, ranging from 17 to 70 kDa in size. A variety of pathogenic bacterial species have been shown to bind the extracellular matrix component fibronectin as an adherence mechanism. M. hyopneumoniae cells were found to bind fibronectin in a dose-dependent and saturable manner. Surface plasmon resonance was used to show that a recombinant C-terminal domain of P116 bound fibronectin at physiologically relevant concentrations (K(D) 24 ± 6 nm). Plasmin(ogen)-binding proteins are also expressed by many bacterial pathogens, facilitating extracellular matrix degradation. M. hyopneumoniae cells were found to also bind plasminogen in a dose-dependent and saturable manner; the C-terminal domain of P116 binds to plasminogen (K(D) 44 ± 5 nm). Plasminogen binding was abolished when the C-terminal lysine of P116 was deleted, implicating this residue as part of the plasminogen binding site. P116 fragments adhere to the PK15 porcine kidney epithelial-like cell line and swine respiratory cilia. Collectively these data suggest that P116 is an important adhesin and virulence factor of M. hyopneumoniae.

  5. Primary cilia function regulates the length of the embryonic trunk axis and urogenital field in mice

    DEFF Research Database (Denmark)

    Wainwright, Elanor N.; Svingen, Terje; Ting Ng, Ee

    2014-01-01

    The issues of whether and how some organs coordinate their size and shape with the blueprint of the embryo axis, while others appear to regulate their morphogenesis autonomously, remain poorly understood. Mutations in Ift144, encoding a component of the trafficking machinery of primary cilia......–posterior domain of the gonad/mesonephros was extended at 10.5 dpc, with no change in the length of the metanephros. In XY embryos, this extension resulted in an increase in testis cord number. Moreover, we observed a concomitant extension of the trunk axis in both sexes, with no change in the length of the tail...

  6. Model of Calcium Oscillations Due to Negative Feedback in Olfactory Cilia

    DEFF Research Database (Denmark)

    Reidl, Juergen; Borowski, Peter; Sensse, Anke;

    2006-01-01

    We present a mathematical model for Ca oscillations in the cilia of olfactory sensory neurons. The underlying mechanism is based on direct negative regulation of cyclic nucleotide-gated channels by calcium/calmodulin and does not require any autocatalysis such as calcium-induced calcium release....... The model is in quantitative agreement with available experimental data, both with respect to oscillations and to fast adaptation. We give predictions for the ranges of parameters in which oscillations should be observable. Relevance of the model to calcium oscillations in other systems is discussed....

  7. Robust and stretchable indium gallium zinc oxide-based electronic textiles formed by cilia-assisted transfer printing

    Science.gov (United States)

    Yoon, Jongwon; Jeong, Yunkyung; Kim, Heeje; Yoo, Seonggwang; Jung, Hoon Sun; Kim, Yonghun; Hwang, Youngkyu; Hyun, Yujun; Hong, Woong-Ki; Lee, Byoung Hun; Choa, Sung-Hoon; Ko, Heung Cho

    2016-06-01

    Electronic textile (e-textile) allows for high-end wearable electronic devices that provide easy access for carrying, handling and using. However, the related technology does not seem to be mature because the woven fabric hampers not only the device fabrication process directly on the complex surface but also the transfer printing of ultrathin planar electronic devices. Here we report an indirect method that enables conformal wrapping of surface with arbitrary yet complex shapes. Artificial cilia are introduced in the periphery of electronic devices as adhesive elements. The cilia also play an important role in confining a small amount of glue and damping mechanical stress to maintain robust electronic performance under mechanical deformation. The example of electronic applications depicts the feasibility of cilia for `stick-&-play' systems, which provide electronic functions by transfer printing on unconventional complex surfaces.

  8. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells

    DEFF Research Database (Denmark)

    Berg Nygaard, Marie; Almstrup, Kristian; Lindbæk, Louise;

    2015-01-01

    cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components...

  9. Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans.

    NARCIS (Netherlands)

    J.A. Burghoorn (Jan); M.P.J. Dekkers (Martijn); S. Rademakers (Suzanne); A.A.W. de Jong (Ton); R. Willemsen (Rob); G. Jansen (Gert)

    2007-01-01

    textabstractIn the cilia of the nematode Caenorhabditis elegans, anterograde intraflagellar transport (IFT) is mediated by two kinesin-2 complexes, kinesin II and OSM-3 kinesin. These complexes function together in the cilia middle segments, whereas OSM-3 alone mediates transport in the distal segme

  10. Structural defects in cilia of the choroid plexus, subfornical organ and ventricular ependyma are associated with ventriculomegaly

    Directory of Open Access Journals (Sweden)

    Swiderski Ruth E

    2012-10-01

    Full Text Available Abstract Background Hydrocephalus is a heterogeneous disorder with multiple etiologies that are not yet fully understood. Animal models have implicated dysfunctional cilia of the ependyma and choroid plexus in the development of the disorder. In this report, we sought to determine the origin of the ventriculomegaly in four Bardet Biedl syndrome (BBS mutant mouse strains as models of a ciliopathy. Methods Evans Blue dye was injected into the lateral ventricle of wild- type and BBS mutant mice to determine whether obstruction of intra- or extra-ventricular CSF flow contributed to ventriculomegaly. Transmission electron microscopy (TEM was used to examine the ultrastructure of the choroid plexus, subfornical organ (SFO, subcommisural organ (SCO, and ventricular ependyma to evaluate their ultrastructure and the morphology of their primary and motile cilia. Results and discussion No obstruction of intra- or extra-ventricular CSF flow was observed, implying a communicating form of hydrocephalus in BBS mutant mice. TEM analyses of the mutants showed no evidence of choroidal papillomas or breakdown of the blood:CSF barrier. In contrast, structural defects were observed in a subpopulation of cilia lining the choroid plexus, SFO, and ventricular ependyma. These included disruptions of the microtubular structure of the axoneme and the presence of electron-dense vesicular-like material along the ciliary shaft and at the tips of cilia. Conclusions Abnormalities in cilia structure and function have the potential to influence ciliary intraflagellar transport (IFT, cilia maintenance, protein trafficking, and regulation of CSF production. Ciliary structural defects are the only consistent pathological features associated with CSF-related structures in BBS mutant mice. These defects are observed from an early age, and may contribute to the underlying pathophysiology of ventriculomegaly.

  11. Architectural geometry

    KAUST Repository

    Pottmann, Helmut

    2014-11-26

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

  12. Primary cilia and coordination of receptor tyrosine kinase (RTK) and transforming growth factor β (TGF-β) signaling

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Morthorst, Stine Kjær; Mogensen, Johanne Bay

    2017-01-01

    in their extracellular environment and integrate and transmit signaling information to the cell to regulate various cellular, developmental, and physiological processes. Many different signaling pathways have now been shown to rely on primary cilia to function properly, and mutations that lead to ciliary dysfunction...... are at the root of a pleiotropic group of diseases and syndromic disorders called ciliopathies. In this review, we present an overview of primary cilia-mediated regulation of receptor tyrosine kinase (RTK) and transforming growth factor β (TGF-β) signaling. Further, we discuss how defects in the coordination...

  13. Meckel-Gruber syndrome and the role of primary cilia in kidney, skeleton, and central nervous system development.

    Science.gov (United States)

    Barker, Amy R; Thomas, Rhys; Dawe, Helen R

    2014-01-01

    The ciliopathies are a group of related inherited diseases characterized by malformations in organ development. The diseases affect multiple organ systems, with kidney, skeleton, and brain malformations frequently observed. Research over the last decade has revealed that these diseases are due to defects in primary cilia, essential sensory organelles found on most cells in the human body. Here we discuss the genetic and cell biological basis of one of the most severe ciliopathies, Meckel-Gruber syndrome, and explain how primary cilia contribute to the development of the affected organ systems.

  14. Comparative Study of Bio-implantable Acoustic Generator Architectures

    Science.gov (United States)

    Christensen, D.; Roundy, S.

    2013-12-01

    This paper is a comparative study of the design spaces of two bio-implantable acoustically excited generator architectures: the thickness-stretch-mode circular piezoelectric plate and the bending-mode unimorph piezoelectric diaphragm. The generators are part of an acoustic power transfer system for implanted sensors and medical devices such as glucose monitors, metabolic monitors, drug delivery systems, etc. Our studies indicate that at small sizes the diaphragm architecture outperforms the plate architecture. This paper will present the results of simulation studies and initial experiments that explore the characteristics of the two architectures and compare their performance.

  15. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    , while recent material and spatial turns in anthropology have also brought an increasing interest in design, architecture and the built environment. Understanding the relationship between the social and the physical is at the heart of both disciplines, and they can obviously benefit from further......Architecture and anthropology have always had a common focus on dwelling, housing, urban life and spatial organisation. Current developments in both disciplines make it even more relevant to explore their boundaries and overlaps. Architects are inspired by anthropological insights and methods...... collaboration: How can qualitative anthropological approaches contribute to contemporary architecture? And just as importantly: What can anthropologists learn from architects’ understanding of spatial and material surroundings? Recent theoretical developments in anthropology stress the role of materials...

  16. Architectural Narratives

    DEFF Research Database (Denmark)

    2010-01-01

    In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... identifies new rationales related to this development, and it argues that “cultural planning” has increasingly shifted its focus from a cultural institutional approach to a more market-oriented strategy that integrates art and business. The role of architecture has changed, too. It not only provides...... a functional framework for these concepts, but tries increasingly to endow the main idea of the cultural project with a spatially aesthetic expression - a shift towards “experience architecture.” A great number of these projects typically recycle and reinterpret narratives related to historical buildings...

  17. Multithreading architecture

    CERN Document Server

    Nemirovsky, Mario

    2013-01-01

    Multithreaded architectures now appear across the entire range of computing devices, from the highest-performing general purpose devices to low-end embedded processors. Multithreading enables a processor core to more effectively utilize its computational resources, as a stall in one thread need not cause execution resources to be idle. This enables the computer architect to maximize performance within area constraints, power constraints, or energy constraints. However, the architectural options for the processor designer or architect looking to implement multithreading are quite extensive and

  18. Regeneration of ciliary comb plates in the ctenophore Mnemiopsis leidyi. i. morphology.

    Science.gov (United States)

    Tamm, Sidney L

    2012-01-01

    Regeneration of missing body parts in model organisms provides information on the mechanisms underlying the regeneration process. The aim here is to use ctenophores to investigate regeneration of their giant ciliary swimming plates. When part of a row of comb plates on Mnemiopsis is excised, the wound closes and heals, greatly increasing the distance between comb plates near the former cut edges. Video differential interference contrast (DIC) microscopy of the regeneration of new comb plates between widely separated plates shows localized widenings of the interplate ciliated groove (ICG) first, followed by growth of two opposing groups of comb plate cilia on either side. The split parts of a new plate elongate as their bases extend laterally away from the ICG widening and continue ciliogenesis at both ends. The split parts of a new plate grow longer and move closer together into the ICG widening until they merge into a single plate that interrupts the ICG in a normal manner. Video DIC snapshots of dissected gap preparations 1.5-3-day postoperation show that ICG widenings and/or new plates do not all appear at the same time or with uniform spacing within a gap: the lengths and distances between young plates in a gap are quite variable. Video stereo microscopy of intact animals 3-4 days after the operation show that all the new plates that will form in a gap are present, fairly evenly spaced and similar in length, but smaller and closer together than normal. Normal development of comb plates in embryos and growing animals is compared to the pattern of comb plate regeneration in adults. Comb plate regeneration differs in the cydippid Pleurobrachia that lacks ICGs and has a firmer mesoglea than Mnemiopsis. This study provides a morphological foundation for histological, cellular, and molecular analysis of ciliary regeneration in ctenophores. Copyright © 2011 Wiley Periodicals, Inc.

  19. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model

    Science.gov (United States)

    Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

    2016-01-01

    The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling. PMID:27941997

  20. The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L

    Science.gov (United States)

    Assis, L. H. P.; Silva-Junior, R. M. P.; Dolce, L. G.; Alborghetti, M. R.; Honorato, R. V.; Nascimento, A. F. Z.; Melo-Hanchuk, T. D.; Trindade, D. M.; Tonoli, C. C. C.; Santos, C. T.; Oliveira, P. S. L.; Larson, R. E.; Kobarg, J.; Espreafico, E. M.; Giuseppe, P. O.; Murakami, M. T.

    2017-01-01

    Myosin Va (MyoVa) is an actin-based molecular motor abundantly found at the centrosome. However, the role of MyoVa at this organelle has been elusive due to the lack of evidence on interacting partners or functional data. Herein, we combined yeast two-hybrid screen, biochemical studies and cellular assays to demonstrate that MyoVa interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning. MyoVa binds to the C2 domains of RPGRIP1L via residues located near or in the Rab11a-binding site, a conserved site in the globular tail domain (GTD) from class V myosins. According to proximity ligation assays, MyoVa and RPGRIP1L can interact near the cilium base in ciliated RPE cells. Furthermore, we showed that RPE cells expressing dominant-negative constructs of MyoVa are mostly unciliated, providing the first experimental evidence about a possible link between this molecular motor and cilia-related processes. PMID:28266547

  1. RFX7 is required for the formation of cilia in the neural tube.

    Science.gov (United States)

    Manojlovic, Zarko; Earwood, Ryan; Kato, Akiko; Stefanovic, Branko; Kato, Yoichi

    2014-05-01

    Regulatory Factor X (RFX) transcription factors are important for development and are likely involved in the pathogenesis of serious human diseases including ciliopathies. While seven RFX genes have been identified in vertebrates and several RFX transcription factors have been reported to be regulators of ciliogenesis, the role of RFX7 in development including ciliogenesis is not known. Here we show that RFX7 in Xenopus laevis is expressed in the neural tube, eye, otic vesicles, and somites. Knockdown of RFX7 in Xenopus embryos resulted in a defect of ciliogenesis in the neural tube and failure of neural tube closure. RFX7 controlled the formation of cilia by regulating the expression of RFX4 gene, which has been reported to be required for ciliogenesis in the neural tube. Moreover, ectopic expression of Foxj1, which is a master regulator of motile cilia formation, suppressed the expression of RFX4 but not RFX7. Taken together, RFX7 plays an important role in the process of neural tube closure at the top of the molecular cascade which controls ciliogenesis in the neural tube.

  2. Serotonin has early, cilia-independent roles in Xenopus left-right patterning

    Directory of Open Access Journals (Sweden)

    Laura N. Vandenberg

    2013-01-01

    Consistent left-right (LR patterning of the heart and viscera is a crucial part of normal embryogenesis. Because errors of laterality form a common class of birth defects, it is important to understand the molecular mechanisms and stage at which LR asymmetry is initiated. Frog embryos are a system uniquely suited to analysis of the mechanisms involved in orientation of the LR axis because of the many genetic and pharmacological tools available for use and the fate-map and accessibility of early blastomeres. Two major models exist for the origin of LR asymmetry and both implicate pre-nervous serotonergic signaling. In the first, the charged serotonin molecule is instructive for LR patterning; it is redistributed asymmetrically along the LR axis and signals intracellularly on the right side at cleavage stages. A second model suggests that serotonin is a permissive factor required to specify the dorsal region of the embryo containing chiral cilia that generate asymmetric fluid flow during neurulation, a much later process. We performed theory-neutral experiments designed to distinguish between these models. The results uniformly support a role for serotonin in the cleavage-stage embryo, long before the appearance of cilia, in ventral right blastomeres that do not contribute to the ciliated organ.

  3. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen

    2010-01-01

    Textiles can be used as building skins, adding new aesthetic and functional qualities to architecture. Just like we as humans can put on a coat, buildings can also get dressed. Depending on our mood, or on the weather, we can change coat, and so can the building. But the idea of using textiles...

  4. Architectural Tops

    Science.gov (United States)

    Mahoney, Ellen

    2010-01-01

    The development of the skyscraper is an American story that combines architectural history, economic power, and technological achievement. Each city in the United States can be identified by the profile of its buildings. The design of the tops of skyscrapers was the inspiration for the students in the author's high-school ceramic class to develop…

  5. Architectural Mealscapes

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning

    2012-01-01

    are jointed together. The purpose of this paper has therefore been to test the idea of a new paradigm for ‘Interior Design for Food’ taking into account the reflective perspective and critical thinking of architectural theory like for instance developed with Semper, when studying the eating environment...

  6. Architectural Illusion.

    Science.gov (United States)

    Doornek, Richard R.

    1990-01-01

    Presents a lesson plan developed around the work of architectural muralist Richard Haas. Discusses the significance of mural painting and gives key concepts for the lesson. Lists class activities for the elementary and secondary grades. Provides a photograph of the Haas mural on the Fountainbleau Hilton Hotel, 1986. (GG)

  7. Religious Architecture

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The main religions of ancient China were Buddhism,Taoism and Islam, of which Buddhism was the most widespread. As a result, Buddhist temples and towers are found all over China, and have become important components of the country's ancient architecture.

  8. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen

    2010-01-01

    Textiles can be used as building skins, adding new aesthetic and functional qualities to architecture. Just like we as humans can put on a coat, buildings can also get dressed. Depending on our mood, or on the weather, we can change coat, and so can the building. But the idea of using textiles...

  9. The PDZ Protein Na+/H+ Exchanger Regulatory Factor-1 (NHERF1) Regulates Planar Cell Polarity and Motile Cilia Organization.

    Science.gov (United States)

    Treat, Anny Caceres; Wheeler, David S; Stolz, Donna B; Tsang, Michael; Friedman, Peter A; Romero, Guillermo

    2016-01-01

    Directional flow of the cerebrospinal fluid requires coordinated movement of the motile cilia of the ependymal epithelium that lines the cerebral ventricles. Here we report that mice lacking the Na+/H+ Exchanger Regulatory Factor 1 (NHERF1/Slc9a3r1, also known as EBP50) develop profound communicating hydrocephalus associated with fewer and disorganized ependymal cilia. Knockdown of NHERF1/slc9a3r1 in zebrafish embryos also causes severe hydrocephalus of the hindbrain and impaired ciliogenesis in the otic vesicle. Ultrastructural analysis did not reveal defects in the shape or organization of individual cilia. Similar phenotypes have been described in animals with deficiencies in Wnt signaling and the Planar Cell Polarity (PCP) pathway. We show that NHERF1 binds the PCP core genes Frizzled (Fzd) and Vangl. We further show that NHERF1 assembles a ternary complex with Fzd4 and Vangl2 and promotes translocation of Vangl2 to the plasma membrane, in particular to the apical surface of ependymal cells. Taken together, these results strongly support an important role for NHERF1 in the regulation of PCP signaling and the development of functional motile cilia.

  10. Gli2 and gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available Intraflagellar transport (IFT proteins are essential for cilia assembly and have recently been associated with a number of developmental processes, such as left-right axis specification and limb and neural tube patterning. Genetic studies indicate that IFT proteins are required for Sonic hedgehog (Shh signaling downstream of the Smoothened and Patched membrane proteins but upstream of the Glioma (Gli transcription factors. However, the role that IFT proteins play in transduction of Shh signaling and the importance of cilia in this process remain unknown. Here we provide insights into the mechanism by which defects in an IFT protein, Tg737/Polaris, affect Shh signaling in the murine limb bud. Our data show that loss of Tg737 results in altered Gli3 processing that abrogates Gli3-mediated repression of Gli1 transcriptional activity. In contrast to the conclusions drawn from genetic analysis, the activity of Gli1 and truncated forms of Gli3 (Gli3R are unaffected in Tg737 mutants at the molecular level, indicating that Tg737/Polaris is differentially involved in specific activities of the Gli proteins. Most important, a negative regulator of Shh signaling, Suppressor of fused, and the three full-length Gli transcription factors localize to the distal tip of cilia in addition to the nucleus. Thus, our data support a model where cilia have a direct role in Gli processing and Shh signal transduction.

  11. Gli2 and Gli3 Localize to Cilia and Require the Intraflagellar Transport Protein Polaris for Processing and Function

    Energy Technology Data Exchange (ETDEWEB)

    Michaud III, Edward J [ORNL; Haycraft, Courtney J [University of Alabama, Birmingham; Aydin Son, Yesim [University of Tennessee, Knoxville (UTK); Zhang, Qihong [University of Alabama, Birmingham; Yoder, Bradley [University of Alabama, Birmingham

    2005-01-01

    Intraflagellar transport (IFT) proteins are essential for cilia assembly and have recently been associated with a number of developmental processes, such as left-right axis specification and limb and neural tube patterning. Genetic studies indicate that IFT proteins are required for Sonic hedgehog (Shh)signaling downstream of the Smoothened and Patched membrane proteins but upstream of the Glioma (Gli) transcription factors. However, the role that IFT proteins play in transduction of Shh signaling and the importance of cilia in this process remain unknown. Here we provide insights into the mechanism by which defects in an IFT protein, Tg737/Polaris, affect Shh signaling in the murine limb bud. Our data show that loss of Tg737 results in altered Gli3 processing that abrogates Gli3-mediated repression of Gli1 transcriptional activity. In contrast to the conclusions drawn from genetic analysis, the activity of Gli1 and truncated forms of Gli3 (Gli3R) are unaffected in Tg737 mutants at the molecular level, indicating that Tg737/Polaris is differentially involved in specific activities of the Gli proteins. Most important, a negative regulator of Shh signaling, Suppressor of fused, and the three full-length Gli transcription factors localize to the distal tip of cilia in addition to the nucleus. Thus, our data support a model where cilia have a direct role in Gli processing and Shh signal transduction.

  12. cAMP and cGMP signaling: sensory systems with prokaryotic roots adopted by eukaryotic cilia.

    Science.gov (United States)

    Johnson, Jacque-Lynne F; Leroux, Michel R

    2010-08-01

    An exciting discovery of the new millennium is that primary cilia, organelles found on most eukaryotic cells, play crucial roles in vertebrate development by modulating Hedgehog, Wnt and PDGF signaling. Analysis of the literature and sequence databases reveals that the ancient signal transduction pathway, which uses cGMP in eukaryotes or related cyclic di-GMP in bacteria, exists in virtually all eukaryotes. However, many eukaryotes that secondarily lost cilia during evolution, including flowering plants, slime molds and most fungi, lack otherwise evolutionarily conserved cGMP signaling components. Based on this intriguing phylogenetic distribution, the presence of cGMP signaling proteins within cilia, and the indispensable roles that cGMP plays in transducing environmental signals in divergent ciliated cells (e.g. vertebrate photoreceptors and Caenorhabditis elegans sensory neurons), we propose that cGMP signaling has a strong ciliary basis. cAMP signaling, also inherent to bacteria and crucial for cilium-dependent olfaction, similarly appears to have widespread usage in diverse cilia. Thus, we argue here that both cyclic nucleotides play essential and potentially ubiquitous roles in modulating ciliary functions.

  13. Drosophila sensory cilia lacking MKS proteins exhibit striking defects in development but only subtle defects in adults

    Science.gov (United States)

    Titlow, Joshua S.; Davis, Ilan; Barker, Amy R.; Dawe, Helen R.

    2016-01-01

    ABSTRACT Cilia are conserved organelles that have important motility, sensory and signalling roles. The transition zone (TZ) at the base of the cilium is crucial for cilia function, and defects in several TZ proteins are associated with human congenital ciliopathies such as nephronophthisis (NPHP) and Meckel–Gruber syndrome (MKS). In several species, MKS and NPHP proteins form separate complexes that cooperate with Cep290 to assemble the TZ, but flies seem to lack core components of the NPHP module. We show that MKS proteins in flies are spatially separated from Cep290 at the TZ, and that flies mutant for individual MKS genes fail to recruit other MKS proteins to the TZ, whereas Cep290 seems to be recruited normally. Although there are abnormalities in microtubule and membrane organisation in developing MKS mutant cilia, these defects are less apparent in adults, where sensory cilia and sperm flagella seem to function quite normally. Thus, localising MKS proteins to the cilium or flagellum is not essential for viability or fertility in flies. PMID:27577095

  14. The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: role of cAMP signaling in primary cilia.

    Science.gov (United States)

    Wang, Zhenshan; Phan, Trongha; Storm, Daniel R

    2011-04-13

    Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3(-/-) mice for several forms of learning and memory. Here, we report that AC3(-/-) mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.

  15. MUF architecture /art London

    DEFF Research Database (Denmark)

    Svenningsen Kajita, Heidi

    2009-01-01

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

  16. Catalyst Architecture

    DEFF Research Database (Denmark)

    the projects as case studies, which contribute with strategic knowledge rather than generalizing from average considerations. These are ‘strategic projects’ where we have looked for the specific and the particular (Flyvbjerg 1991). According to the case studies, we use the case study method developed by Bent......’ interpretations and architectural strategies are included in the analyses. This implies that there is a large variation of empirical knowledge about the selected problems. That is the reason why we give a short introduction to the exact use of approaches and methods in the beginning of each case study. Based...... in experience? Which design qualities do the best examples of architecture as urban catalysts have, and how can we as citizens, politicians and professionals use knowledge about this in the development of our cities as good places to live? We wish to throw light on these key questions through case studies...

  17. Kosmos = architecture

    Directory of Open Access Journals (Sweden)

    Tine Kurent

    1985-12-01

    Full Text Available The old Greek word "kosmos" means not only "cosmos", but also "the beautiful order", "the way of building", "building", "scenography", "mankind", and, in the time of the New Testament, also "pagans". The word "arhitekton", meaning first the "master of theatrical scenography", acquired the meaning of "builder", when the words "kosmos" and ~kosmetes" became pejorative. The fear that architecture was not considered one of the arts before Renaissance, since none of the Muses supervised the art of building, results from the misunderstanding of the word "kosmos". Urania was the Goddes of the activity implied in the verb "kosmein", meaning "to put in the beautiful order" - everything, from the universe to the man-made space, i. e. the architecture.

  18. Architectural Engineers

    DEFF Research Database (Denmark)

    Petersen, Rikke Premer

    The design professions have always been an amorphous phenomena difficult to merge under one label. New constellations continually emerge, questioning, stretching, and reconfiguring the understanding of design and the professional practices linked to it. In this paper the idea of architectural eng...... with new types of competences and be able to manoeuvre in new types of constellations, but concurrently core competences must be preserved and the time of study kept at a minimum....

  19. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    putting an emphasis on architecture as unified scenery guided by the four motives hearth, enclosure, dressing and context. This theoretical framework draws on the Gastronomic Analogy put forth by James Fergusson in 1862 and an interpretation of the writings of the 19th century architect Gottfried Semper...... with the material appearance of objects, but also the imaginary world of dreams and memories which are concealed with the communicative significance of intentions when designing the future super hospitals....

  20. Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction.

    Science.gov (United States)

    Ko, Hyuk Wan; Norman, Ryan X; Tran, John; Fuller, Kimberly P; Fukuda, Mitsunori; Eggenschwiler, Jonathan T

    2010-02-16

    Recent findings indicate that mammalian Sonic hedgehog (Shh) signal transduction occurs within primary cilia, although the cell biological mechanisms underlying both Shh signaling and ciliogenesis have not been fully elucidated. We show that an uncharacterized TBC domain-containing protein, Broad-minded (Bromi), is required for high-level Shh responses in the mouse neural tube. We find that Bromi controls ciliary morphology and proper Gli2 localization within the cilium. By use of a zebrafish model, we further show that Bromi is required for proper association between the ciliary membrane and axoneme. Bromi physically interacts with cell cycle-related kinase (CCRK), whose Chlamydomonas homolog regulates flagellar length. Biochemical and genetic interaction data indicate that Bromi promotes CCRK stability and function. We propose that Bromi and CCRK control the structure of the primary cilium by coordinating assembly of the axoneme and ciliary membrane, allowing Gli proteins to be properly activated in response to Shh signaling.

  1. Long-range interactions, wobbles, and phase defects in chains of model cilia

    Science.gov (United States)

    Brumley, Douglas R.; Bruot, Nicolas; Kotar, Jurij; Goldstein, Raymond E.; Cicuta, Pietro; Polin, Marco

    2016-12-01

    Eukaryotic cilia and flagella are chemo-mechanical oscillators capable of generating long-range coordinated motions known as metachronal waves. Pair synchronization is a fundamental requirement for these collective dynamics, but it is generally not sufficient for collective phase-locking, chiefly due to the effect of long-range interactions. Here we explore experimentally and numerically a minimal model for a ciliated surface: hydrodynamically coupled oscillators rotating above a no-slip plane. Increasing their distance from the wall profoundly affects the global dynamics, due to variations in hydrodynamic interaction range. The array undergoes a transition from a traveling wave to either a steady chevron pattern or one punctuated by periodic phase defects. Within the transition between these regimes the system displays behavior reminiscent of chimera states.

  2. Modelling the Fluid Mechanics of Cilia and Flagella in Reproduction and Development

    CERN Document Server

    Montenegro-Johnson, Thomas D; Smith, David J; Loghin, Daniel; Blake, John R

    2013-01-01

    Cilia and flagella are actively bending slender organelles, performing functions such as motility, feeding and embryonic symmetry breaking. We review the mechanics of viscous-dominated microscale flow, including time-reversal symmetry, drag anisotropy of slender bodies, and wall effects. We focus on the fundamental force singularity, higher order multipoles, and the method of images, providing physical insight and forming a basis for computational approaches. Two biological problems are then considered in more detail: (1) left-right symmetry breaking flow in the node, a microscopic structure in developing vertebrate embryos, and (2) motility of microswimmers through non-Newtonian fluids. Our model of the embryonic node reveals how particle transport associated with morphogenesis is modulated by the gradual emergence of cilium posterior tilt. Our model of swimming makes use of force distributions within a body-conforming finite element framework, allowing the solution of nonlinear inertialess Carreau flow. We ...

  3. Sensory cilia and integration of signal transduction in human health and disease

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Lotte B; Schneider, Linda

    2007-01-01

    the extracellular environment in order to control basic cellular processes during embryonic and postnatal development, as well as in tissue homeostasis in adulthood. Consequently, defects in building of the cilium or in transport or function of ciliary signal proteins are associated with a series of pathologies......, including developmental disorders and cancer. In this review, we highlight recent examples of the mechanisms by which signal components are selectively targeted and transported to the ciliary membrane and we present an overview of the signal transduction pathways associated with primary and motile cilia......The primary cilium is a hallmark of mammalian tissue cells. Recent research has shown that these organelles display unique sets of selected signal transduction modules including receptors, ion channels, effector proteins and transcription factors that relay chemical and physical stimuli from...

  4. Equilibrium shape of liquid lenses and correlations of beating cilia on the surface of frog embryos

    Science.gov (United States)

    Huisman, Fawn Mitsu

    This thesis reports the results of two unrelated projects: liquid lenses and cilia motion. A liquid lens is the equilibrium configuration of a non-wetting 3-fluid system, and the profile of the 3 interfaces can, in principle, be determined by solving the Young-Laplace differential equation for each interface if the surface tensions of all three interfaces are accurately known. Fluid interfacial tensions are not tabulated and are spectacularly sensitive to impurities, so in practice these quantities must be measured. We have developed a method of measuring these parameters by comparing the observed shape of liquid lenses to calculated equilibrium shapes. We have experimentally studied lenses of alkanes floating on water. These results were compared with various liquid lens systems. The profile of these lens systems was measured using ray tracing and Morie imaging, and found to be in excellent agreement with the calculated lens shapes for pure fluids. Upon the introduction of a surfactant, dodecyltrimethylammonium bromide(DTAB), we find that there is a minimum in the dihedral angle of the lens as a function of surfactant concentration, corresponding to the transition from partial-wetting to pseudo-partial wetting. The development and orientation of ciliated cells on Xenopus laevis larval skin was examined using high speed video microscopy. The intercellular orientation of wild-type, dominant negative mutants, and Vangl2MO morpholinos was studied by scoring the beating direction of ciliated cells and measuring the correlation with nearest neighbors. No significant difference between the mutant and wild type was found. Time lapse videos of developing cilia indicate that intracellular ordering is non-existent in early development, with ordering occurring by maturity. Further work needs to be done to determine what role fluid flow plays in that ordering.

  5. Architectural dreaming

    Institute of Scientific and Technical Information of China (English)

    Mark Godfrey

    2004-01-01

    <正> For the first 800 years of its existence, Beijing retained essentially the same character: a walled palace city at its centre, organised on a strict north-south axis and contained within a sea of courtyard houses along lanes too narrow forcars. Today Beijing’s basic unit of architectural scale has become the skyscraper, erected a dozen at a time and facing massive highways. Ancient buildings are so small and unloved by comparison that they threaten to disappear from view. Fuelled by an economic boom, and propelled by banks flushed with mortgage cash, Beijing has embarked on the largest building campaign the world has ever seen.

  6. Catalyst Architecture

    DEFF Research Database (Denmark)

    Kiib, Hans; Marling, Gitte; Hansen, Peter Mandal

    2014-01-01

    of programs, have a role in mediating positive social and/or cultural development. In this sense, we talk about architecture as a catalyst for: sustainable adaptation of the city’s infrastructure appropriate renovation of dilapidated urban districts strengthening of social cohesiveness in the city development...... meaningful for everyone. The exhibited works are designed by SANAA, Diller Scofidio + Renfro, James Corner Field Operation, JBMC Arquitetura e Urbanismo, Atelier Bow-Wow, Ateliers Jean Nouvel, COBE, Transform, BIG, Topotek1, Superflex, and by visual artist Jane Maria Petersen....

  7. Processless offset printing plates

    Directory of Open Access Journals (Sweden)

    Sanja Mahović Poljaček

    2015-06-01

    Full Text Available With the implementation of platesetters in the offset printing plate making process, imaging of the printing plate became more stable and ensured increase of the printing plate quality. But as the chemical processing of the printing plates still highly influences the plate making process and the graphic reproduction workflow, development of printing plates that do not require chemical processing for offset printing technique has been one of the top interests in graphic technology in the last few years. The main reason for that came from the user experience, where majority of the problems with plate making process could be connected with the chemical processing of the printing plate. Furthermore, increased environmental standards lead to reducing of the chemicals used in the industrial processes. Considering these facts, different types of offset printing plates have been introduced to the market today. This paper presents some of the processless printing plates.

  8. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells

    DEFF Research Database (Denmark)

    Berg Nygaard, Marie; Almstrup, Kristian; Lindbæk, Louise;

    2015-01-01

    Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about...

  9. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells

    DEFF Research Database (Denmark)

    Berg Nygaard, Marie; Almstrup, Kristian; Lindbæk, Louise

    2015-01-01

    of Hedgehog signalling, including Smoothened, Patched-1, and GLI2, which are involved in regulating Leydig cell differentiation. Stimulation of Hedgehog signalling increases the localization of Smoothened to the cilium, which is followed by transactivation of the Hedgehog target genes, Gli1 and Ptch1. Our...... findings provide new information on the spatiotemporal formation of primary cilia in the testis and show that primary cilia in immature Leydig cells mediate Hedgehog signalling....

  10. From green architecture to architectural green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    . Architectural green could signify green architecture with inclusive interrelations between green and space, built and unbuilt, inside and outside. The aim of the term is to reflect a new focus in green architecture – its architectural performance. Ecological issues are not underestimated or ignored, but so far...... they have overshadowed the architectural potential of green architecture. The paper questions how a green space should perform, look like and function. Two examples are chosen to demonstrate thorough integrations between green and space. The examples are public buildings categorized as pavilions. One...... is not limited to the architecture of pavilions and can be applied in other architectural forms and functions. The paper ends by questioning the potential of architectural green in urbanity....

  11. The elongation of primary cilia via the acetylation of α-tubulin by the treatment with lithium chloride in human fibroblast KD cells.

    Science.gov (United States)

    Nakakura, Takashi; Asano-Hoshino, Anshin; Suzuki, Takeshi; Arisawa, Kenjiro; Tanaka, Hideyuki; Sekino, Yoshihisa; Kiuchi, Yoshiko; Kawai, Kazuhiro; Hagiwara, Haruo

    2015-03-01

    Primary cilium, an organelle found on nearly every cell in the human body, typically serves as the mechanical sensor of the cell. Lithium ion is known to promote the elongation of primary cilia in a variety of cell types, but it is unknown whether lithium is involved in the acetylation of α-tubulin which is essential for the assembly of primary cilia. In order to reveal the relationship between the elongation of primary cilia with lithium and the acetylation of α-tubulin, we first observed the formation and structure of primary cilia in KD cells, a cell line deriving fibroblasts in human labium. Subsequently, by immunohistochemical and western blot analysis we elucidated that the length of primary cilia and acetylation of α-tubulin are regulated by lithium chloride (LiCl) in the medium in a time- and concentration-dependent manner. We next performed the RT-PCR, RNAi-based experiments and biochemical study using an inhibitor of glycogen synthase kinase-3βGSK-3β). We found that LiCl mobilizes the α-tubulin N-acetyltransferase 1 (αTAT1) in the signaling pathway mediating GSK-3β and adenylate cyclase III. In conclusion, our results suggested that LiCl treatments activate αTAT1 by the inhibition of GSK-3β and promote the α-tubulin acetylation, and then elongate the primary cilia.

  12. Localization of the angiopoietin receptors Tie-1 and Tie-2 on the primary cilia in the female reproductive organs

    DEFF Research Database (Denmark)

    Teilmann, Stefan C; Christensen, Søren T

    2005-01-01

    Blood vessel homeostasis and endothelial cell survival depend on proper signalling through angiopoietin receptors such as the receptor tyrosine kinases Tie-1 and Tie-2. We have studied the presence and subcellular localization of these receptors in murine female reproductive organs using confocal...... of immunohistochemical analysis on human ovarian tissues we also observed a unique localization of Tie-2 to the primary cilia of ovarian surface epithelium. These observations are the first to show ciliary localization of angiopoietin receptors. Our results support the hypothesis that cilia of the female reproductive...... organs play a novel and important sensory role in relaying physiochemical changes from the extracellular environment to epithelial cells of the oviduct, the ovary and extra-ovarian tissues....

  13. Breakup and then makeup: a predictive model of how cilia self-regulate hardness for posture control

    Science.gov (United States)

    Bandyopadhyay, Promode R.; Hansen, Joshua C.

    2013-06-01

    Functioning as sensors and propulsors, cilia are evolutionarily conserved organelles having a highly organized internal structure. How a paramecium's cilium produces off-propulsion-plane curvature during its return stroke for symmetry breaking and drag reduction is not known. We explain these cilium deformations by developing a torsional pendulum model of beat frequency dependence on viscosity and an olivo-cerebellar model of self-regulation of posture control. The phase dependence of cilia torsion is determined, and a bio-physical model of hardness control with predictive features is offered. Crossbridge links between the central microtubule pair harden the cilium during the power stroke; this stroke's end is a critical phase during which ATP molecules soften the crossbridge-microtubule attachment at the cilium inflection point where torsion is at its maximum. A precipitous reduction in hardness ensues, signaling the start of ATP hydrolysis that re-hardens the cilium. The cilium attractor basin could be used as reference for perturbation sensing.

  14. Lab architecture

    Science.gov (United States)

    Crease, Robert P.

    2008-04-01

    There are few more dramatic illustrations of the vicissitudes of laboratory architecturethan the contrast between Building 20 at the Massachusetts Institute of Technology (MIT) and its replacement, the Ray and Maria Stata Center. Building 20 was built hurriedly in 1943 as temporary housing for MIT's famous Rad Lab, the site of wartime radar research, and it remained a productive laboratory space for over half a century. A decade ago it was demolished to make way for the Stata Center, an architecturally striking building designed by Frank Gehry to house MIT's computer science and artificial intelligence labs (above). But in 2004 - just two years after the Stata Center officially opened - the building was criticized for being unsuitable for research and became the subject of still ongoing lawsuits alleging design and construction failures.

  15. Serotonin increases cilia-driven particle transport via an acetylcholine-independent pathway in the mouse trachea.

    Directory of Open Access Journals (Sweden)

    Peter König

    Full Text Available BACKGROUND: Mucociliary clearance in the airways is driven by the coordinated beating of ciliated cells. Classical neuromediators such as noradrenalin and acetylcholine increase ciliary beat frequency and thus cilia-driven transport. Despite the fact that the neuromediator serotonin is ciliostimulatory in invertebrates and has been implied in releasing acetylcholine from the airway epithelium, its role in regulating cilia function in vertebrate airways is not established. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of serotonin on ciliary beat frequency and cilia-driven particle transport in the acutely excised submerged mouse trachea and determined the sources of serotonin in this tissue by immunohistochemistry. Serotonin (100 microM increased cilary beat frequency (8.9+/-1.2 Hz to 17.0+/-2.7 Hz and particle transport speed (38.9+/-4.6 microm/s to 83.4+/-8.3 microm/s to an extent that was comparable to a supramaximal dose of ATP. The increase in particle transport speed was totally prevented by methysergide (100 microM. Blockade of muscarinic receptors by atropine (1 microM did not reduce the effect of serotonin, although it was effective in preventing the increase in particle transport speed mediated by muscarine (100 microM. Immunohistochemistry demonstrated serotonin in mast cells pointing towards mast cells and platelets as possible endogenous sources of serotonin. CONCLUSIONS/SIGNIFICANCE: These results indicate that serotonin is a likely endogenous mediator that can increase cilia-driven transport independent from acetylcholine during activation of mast cells and platelets.

  16. Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling.

    Directory of Open Access Journals (Sweden)

    Anna-Katerina Hadjantonakis

    Full Text Available BACKGROUND: The determination of left/right body axis during early embryogenesis sets up a developmental cascade that coordinates the development of the viscera and is essential to the correct placement and alignment of organ systems and vasculature. Defective left-right patterning can lead to congenital cardiac malformations, vascular anomalies and other serious health problems. Here we describe a novel role for the T-box transcription factor gene Tbx6 in left/right body axis determination in the mouse. RESULTS: Embryos lacking Tbx6 show randomized embryo turning and heart looping. Our results point to multiple mechanisms for this effect. First, Dll1, a direct target of Tbx6, is down regulated around the node in Tbx6 mutants and there is a subsequent decrease in nodal signaling, which is required for laterality determination. Secondly, in spite of a lack of expression of Tbx6 in the node, we document a profound effect of the Tbx6 mutation on the morphology and motility of nodal cilia. This results in the loss of asymmetric calcium signaling at the periphery of the node, suggesting that unidirectional nodal flow is disrupted. To carry out these studies, we devised a novel method for direct labeling and live imaging cilia in vivo using a genetically-encoded fluorescent protein fusion that labels tubulin, combined with laser point scanning confocal microscopy for direct visualization of cilia movement. CONCLUSIONS: We conclude that the transcription factor gene Tbx6 is essential for correct left/right axis determination in the mouse and acts through effects on notch signaling around the node as well as through an effect on the morphology and motility of the nodal cilia.

  17. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome.

    Directory of Open Access Journals (Sweden)

    Tom Stiff

    Full Text Available Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS, a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency.

  18. The role of Ca2+ in deflection-induced excitation of motile, mechanoresponsive balancer cilia in the ctenophore statocyst.

    Science.gov (United States)

    Lowe, B

    1997-06-01

    Motile, mechanoresponsive cilia (balancers) in ctenophore statocysts, like vertebrate hair cells, are excited or inhibited depending upon the direction in which they are deflected. Balancers, however, may become either excited (beat rapidly) or inhibited (beat slowly) by deflection in the same direction, depending on the sign of ctenophore geotaxis (positive or negative). The beat frequency of many cilia is controlled by concentrations of Ca2+, membrane potential and neural input. How these factors affect deflection-induced ciliary beating in balancers was investigated. Deflection-induced excitation of balancers in whole Mnemiopsis leidyi larvae and dissected adult (Mnemiopsis leidyi, Pleurobrachia pileus) statocysts was reversibly inhibited by the Ca2+ channel inhibitors Co2+, Mg2+, Ni2+, and Mn2+. Deflection-induced excitation in balancers of isolated adult M. leidyi balancer groups was also inhibited by Co2+ or by Ca(2+)-free medium. Isolated balancer group cilia, like balancer cilia of intact ctenophores, exhibited responses to either sign of geotaxis and graded responses to deflection. Isolated balancers that were chemically depolarized in high-[K+], Ca(2+)-free medium were excited by local application of Ca2+ onto the ciliary bases, but not onto the cell bases or the ciliary tips. It is proposed that deflection-induced excitation of balancers is due to influx of Ca2+ through stretch- and voltage-activated channel activity. The sign of geotaxis of whole larvae and dissected adult statocysts was switched by electrical stimulation. Thus, neural input may participate in reversing the directional sensitivity of balancer cells.

  19. Serotonin Increases Cilia-Driven Particle Transport via an Acetylcholine-Independent Pathway in the Mouse Trachea

    Science.gov (United States)

    Krasteva, Gabriela; Kummer, Wolfgang

    2009-01-01

    Background Mucociliary clearance in the airways is driven by the coordinated beating of ciliated cells. Classical neuromediators such as noradrenalin and acetylcholine increase ciliary beat frequency and thus cilia-driven transport. Despite the fact that the neuromediator serotonin is ciliostimulatory in invertebrates and has been implied in releasing acetylcholine from the airway epithelium, its role in regulating cilia function in vertebrate airways is not established. Methodology/Principal Findings We examined the effects of serotonin on ciliary beat frequency and cilia-driven particle transport in the acutely excised submerged mouse trachea and determined the sources of serotonin in this tissue by immunohistochemistry. Serotonin (100 µM) increased cilary beat frequency (8.9±1.2 Hz to 17.0±2.7 Hz) and particle transport speed (38.9±4.6 µm/s to 83.4±8.3 µm/s) to an extent that was comparable to a supramaximal dose of ATP. The increase in particle transport speed was totally prevented by methysergide (100 µM). Blockade of muscarinic receptors by atropine (1 µM) did not reduce the effect of serotonin, although it was effective in preventing the increase in particle transport speed mediated by muscarine (100 µM). Immunohistochemistry demonstrated serotonin in mast cells pointing towards mast cells and platelets as possible endogenous sources of serotonin. Conclusions/Significance These results indicate that serotonin is a likely endogenous mediator that can increase cilia-driven transport independent from acetylcholine during activation of mast cells and platelets. PMID:19290057

  20. dTULP, the Drosophila melanogaster homolog of tubby, regulates transient receptor potential channel localization in cilia.

    Directory of Open Access Journals (Sweden)

    Jina Park

    Full Text Available Mechanically gated ion channels convert sound into an electrical signal for the sense of hearing. In Drosophila melanogaster, several transient receptor potential (TRP channels have been implicated to be involved in this process. TRPN (NompC and TRPV (Inactive channels are localized in the distal and proximal ciliary zones of auditory receptor neurons, respectively. This segregated ciliary localization suggests distinct roles in auditory transduction. However, the regulation of this localization is not fully understood. Here we show that the Drosophila Tubby homolog, King tubby (hereafter called dTULP regulates ciliary localization of TRPs. dTULP-deficient flies show uncoordinated movement and complete loss of sound-evoked action potentials. Inactive and NompC are mislocalized in the cilia of auditory receptor neurons in the dTulp mutants, indicating that dTULP is required for proper cilia membrane protein localization. This is the first demonstration that dTULP regulates TRP channel localization in cilia, and suggests that dTULP is a protein that regulates ciliary neurosensory functions.

  1. Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13b hnn stems from abnormal Shh signaling.

    Science.gov (United States)

    Horner, Vanessa L; Caspary, Tamara

    2011-07-01

    In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals cooperate to specify neurons involved in sensation. Several signaling pathways, including Shh, rely on primary cilia in vertebrates. In this study, we used a mouse mutant with abnormal cilia, Arl13b(hnn), to study the relationship between cilia, cell signaling, and neural tube patterning. Arl13b(hnn) mutants have abnormal ventral neural tube patterning due to disrupted Shh signaling; in addition, dorsal patterning defects occur, but the cause of these is unknown. Here we show that the Arl13b(hnn) dorsal patterning defects result from abnormal BMP signaling. In addition, we find that Wnt ligands are abnormally expressed in Arl13b(hnn) mutants; surprisingly, however, downstream Wnt signaling is normal. We demonstrate that Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression, indicating that the abnormal Shh signaling environment in Arl13b(hnn) embryos indirectly causes dorsal defects.

  2. Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression

    Directory of Open Access Journals (Sweden)

    Wei Xiang

    2014-10-01

    Full Text Available Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84, and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma.

  3. Decoding the architectural theory

    Institute of Scientific and Technical Information of China (English)

    Gu Mengchao

    2008-01-01

    Starting from the illustration of the definition and concept of the architectural theory, the author established his unique understanding about the framework of the architectural theory and the innovation of the architectural theory underlined by Chinese characteristics.

  4. Angular resolution of stacked resistive plate chambers

    CERN Document Server

    Samuel, Deepak; Murgod, Lakshmi P

    2016-01-01

    We present here detailed derivations of mathematical expressions for the angular resolution of a set of stacked resistive plate chambers (RPCs). The expressions are validated against experimental results using data collected from the prototype detectors (without magnet) of the upcoming India-based Neutrino Observatory (INO). In principle, these expressions can be used for any other detector with an architecture similar to that of RPCs.

  5. SUSTAINABLE ARCHITECTURE : WHAT ARCHITECTURE STUDENTS THINK

    OpenAIRE

    SATWIKO, PRASASTO

    2013-01-01

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

  6. Software architecture 1

    CERN Document Server

    Oussalah , Mourad Chabane

    2014-01-01

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

  7. Lightweight enterprise architectures

    CERN Document Server

    Theuerkorn, Fenix

    2004-01-01

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

  8. Software architecture 2

    CERN Document Server

    Oussalah, Mourad Chabanne

    2014-01-01

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

  9. Modeling Architectural Patterns Using Architectural Primitives

    NARCIS (Netherlands)

    Zdun, Uwe; Avgeriou, Paris

    2005-01-01

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

  10. Modeling Architectural Patterns Using Architectural Primitives

    NARCIS (Netherlands)

    Zdun, Uwe; Avgeriou, Paris

    2005-01-01

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

  11. Create Your Plate

    Medline Plus

    Full Text Available ... steps to get started: Using your dinner plate, put a line down the middle of the plate. ... vegetables . Now in one of the small sections, put grains and starchy foods. See this list of ...

  12. Create Your Plate

    Medline Plus

    Full Text Available ... Your Plate It's simple and effective for both managing diabetes and losing weight. Creating your plate lets ... 2016 Articles from Diabetes Forecast® magazine: wcie-meal-planning, In this section Food Planning Meals Diabetes Meal ...

  13. Create Your Plate

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    Full Text Available ... Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal ... Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook ...

  14. Food guide plate

    Science.gov (United States)

    ... chips or cookies. VEGETABLES: MAKE HALF OF YOUR PLATE FRUITS AND VEGETABLES Vegetables can be raw, fresh, ... as a snack. FRUITS: MAKE HALF OF YOUR PLATE FRUITS AND VEGETABLES Fruits can be fresh, canned, ...

  15. Growth Plate Fractures

    Science.gov (United States)

    ... the most widely used by doctors is the Salter-Harris system, described below. Type I Fractures These ... incidence of growth plate fractures peaks in adolescence. Salter-Harris classification of growth plate fractures. AAOS does ...

  16. Create Your Plate

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    Full Text Available ... Planning Meals Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook ... Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook with Heart- ...

  17. Create Your Plate

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    Full Text Available ... Planning Meals Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook ... Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook with Heart- ...

  18. Create Your Plate

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    Full Text Available ... Your Plate It's simple and effective for both managing diabetes and losing weight. Creating your plate lets you still choose the foods you want, but changes the portion sizes so you are getting larger ...

  19. Create Your Plate

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    Full Text Available ... Your Plate It's simple and effective for both managing diabetes and losing weight. Creating your plate lets ... Sleeve Custom jerseys for your Tour de Cure team benefits the cause. Ask the Experts: Learn to ...

  20. Manipulation of zebrafish's orientation using artificial cilia in a microchannel with actively adaptive wall design.

    Science.gov (United States)

    Mani, Karthick; Chang Chien, Tsung-Chun; Panigrahi, Bivas; Chen, Chia-Yuan

    2016-11-08

    The zebrafish is a powerful genetic model organism especially in the biomedical chapter for new drug discovery and development. The genetic toolbox which this vertebrate possesses opens a new window to investigate the etiology of human diseases with a high degree genetic similarity. Still, the requirements of laborious and time-consuming of contemporary zebrafish processing assays limit the procedure in carrying out such genetic screen at high throughput. Here, a zebrafish control scheme was initiated which includes the design and validation of a microfluidic platform to significantly increase the throughput and performance of zebrafish larvae manipulation using the concept of artificial cilia actuation. A moving wall design was integrated into this microfluidic platform first time in literature to accommodate zebrafish inside the microchannel from 1 day post-fertilization (dpf) to 6 dpf and can be further extended to 9 dpf for axial orientation control in a rotational range between 0 to 25 degrees at the minimum step of 2-degree increment in a stepwise manner. This moving wall feature was performed through the deflection of shape memory alloy wire embedded inside the microchannel controlled by the electrical waveforms with high accuracy.

  1. [Correction of the position of the cilia in facial paralysis: Technical note].

    Science.gov (United States)

    Caillot, A; Labbé, D

    2015-06-01

    Facial paralysis is a incapacitating pathology that we treat with lengthening temporalis myoplasty for reanimation of the smile. To treat lagophthalmia, we use the extension of the levator of the upper eyelid according Tessier and the asymmetric external blepharorraphy. These techniques can optionally be combined with other techniques, as needed. However, many patients are embarrassed by the appearance of the lashes of the upper eyelid homolateral side facial paralysis. The cilia are lowered and horizontalised, creating a functional disorder by partial "amputation" of the visual field and aesthetic inconvenience. We describe a surgical technique to correct the malposition of the lashes. This technique can be carried out independently or in the lengthening of the temporal myoplasty or another surgical procedure on the eye. In case of extension of the levator of the upper eyelid, the technique we propose requires no additional incision. This is a simple technique and increases very little surgical time. It is fast, little or no morbid, reproducible and provides a significant improvement in the aesthetic and functional patient. This simple technique allows to provide both aesthetic and functional refinement for patients with facial paralysis sequelae.

  2. Drosophila TRPN(=NOMPC channel localizes to the distal end of mechanosensory cilia.

    Directory of Open Access Journals (Sweden)

    Jeongmi Lee

    Full Text Available BACKGROUND: A TRPN channel protein is essential for sensory transduction in insect mechanosensory neurons and in vertebrate hair cells. The Drosophila TRPN homolog, NOMPC, is required to generate mechanoreceptor potentials and currents in tactile bristles. NOMPC is also required, together with a TRPV channel, for transduction by chordotonal neurons of the fly's antennal ear, but the TRPN or TRPV channels have distinct roles in transduction and in regulating active antennal mechanics. The evidence suggests that NOMPC is a primary mechanotransducer channel, but its subcellular location-key for understanding its exact role in transduction-has not yet been established. METHODOLOGY/PRINCIPAL FINDINGS: Here, by immunostaining, we locate NOMPC at the tips of mechanosensory cilia in both external and chordotonal sensory neurons, as predicted for a mechanotransducer channel. In chordotonal neurons, the TRPN and TRPV channels are respectively segregated into distal and proximal ciliary zones. This zonal separation is demarcated by and requires the ciliary dilation, an intraciliary assembly of intraflagellar transport (IFT proteins. CONCLUSIONS: Our results provide a strong evidence for NOMPC as a primary transduction channel in Drosophila mechansensory organs. The data also reveals a structural basis for the model of auditory chordotonal transduction in which the TRPN and TRPV channels play sequential roles in generating and amplifying the receptor potential, but have opposing roles in regulating active ciliary motility.

  3. Modelling the fluid mechanics of cilia and flagella in reproduction and development.

    Science.gov (United States)

    Montenegro-Johnson, Thomas D; Smith, Andrew A; Smith, David J; Loghin, Daniel; Blake, John R

    2012-10-01

    Cilia and flagella are actively bending slender organelles, performing functions such as motility, feeding and embryonic symmetry breaking. We review the mechanics of viscous-dominated microscale flow, including time-reversal symmetry, drag anisotropy of slender bodies, and wall effects. We focus on the fundamental force singularity, higher-order multipoles, and the method of images, providing physical insight and forming a basis for computational approaches. Two biological problems are then considered in more detail: 1) left-right symmetry breaking flow in the node, a microscopic structure in developing vertebrate embryos, and 2) motility of microswimmers through non-Newtonian fluids. Our model of the embryonic node reveals how particle transport associated with morphogenesis is modulated by the gradual emergence of cilium posterior tilt. Our model of swimming makes use of force distributions within a body-conforming finite-element framework, allowing the solution of nonlinear inertialess Carreau flow. We find that a three-sphere model swimmer and a model sperm are similarly affected by shear-thinning; in both cases swimming due to a prescribed beat is enhanced by shear-thinning, with optimal Deborah number around 0.8. The sperm exhibits an almost perfect linear relationship between velocity and the logarithm of the ratio of zero to infinite shear viscosity, with shear-thickening hindering cell progress.

  4. Accelerated plate tectonics.

    Science.gov (United States)

    Anderson, D L

    1975-03-21

    The concept of a stressed elastic lithospheric plate riding on a viscous asthenosphere is used to calculate the recurrence interval of great earthquakes at convergent plate boundaries, the separation of decoupling and lithospheric earthquakes, and the migration pattern of large earthquakes along an arc. It is proposed that plate motions accelerate after great decoupling earthquakes and that most of the observed plate motions occur during short periods of time, separated by periods of relative quiescence.

  5. Mutations in zebrafish leucine-rich repeat-containing six-like affect cilia motility and result in pronephric cysts, but have variable effects on left-right patterning.

    Science.gov (United States)

    Serluca, Fabrizio C; Xu, Bo; Okabe, Noriko; Baker, Kari; Lin, Shin-Yi; Sullivan-Brown, Jessica; Konieczkowski, David J; Jaffe, Kimberly M; Bradner, Joshua M; Fishman, Mark C; Burdine, Rebecca D

    2009-05-01

    Cilia defects have been implicated in a variety of human diseases and genetic disorders, but how cilia motility contributes to these phenotypes is still unknown. To further our understanding of how cilia function in development, we have cloned and characterized two alleles of seahorse, a zebrafish mutation that results in pronephric cysts. seahorse encodes Lrrc6l, a leucine-rich repeat-containing protein that is highly conserved in organisms that have motile cilia. seahorse is expressed in zebrafish tissues known to contain motile cilia. Although mutants do not affect cilia structure and retain the ability to interact with Disheveled, both alleles of seahorse strongly affect cilia motility in the zebrafish pronephros and neural tube. Intriguingly, although seahorse mutations variably affect fluid flow in Kupffer's vesicle, they can have very weak effects on left-right patterning. Combined with recently published results, our alleles suggest that the function of seahorse in cilia motility is separable from its function in other cilia-related phenotypes.

  6. Create Your Plate

    Medline Plus

    Full Text Available ... Reset Plate Share Create Your Plate ! Share: Seven Simple Steps to Create Your Plate It's simple and effective for both managing diabetes and losing ... en.html Have Type 2 Diabetes? Our free program will help you live well. More from diabetes. ...

  7. Obliquity along plate boundaries

    Science.gov (United States)

    Philippon, Mélody; Corti, Giacomo

    2016-12-01

    Most of the plate boundaries are activated obliquely with respect to the direction of far field stresses, as roughly only 8% of the plate boundaries total length shows a very low obliquity (ranging from 0 to 10°, sub-orthogonal to the plate displacement). The obliquity along plate boundaries is controlled by (i) lateral rheological variations within the lithosphere and (ii) consistency with the global plate circuit. Indeed, plate tectonics and magmatism drive rheological changes within the lithosphere and consequently influence strain localization. Geodynamical evolution controls large-scale mantle convection and plate formation, consumption, and re-organization, thus triggering plate kinematics variations, and the adjustment and re-orientation of far field stresses. These geological processes may thus result in plate boundaries that are not perpendicular but oblique to the direction of far field stresses. This paper reviews the global patterns of obliquity along plate boundaries. Using GPlate, we provide a statistical analysis of present-day obliquity along plate boundaries. Within this framework, by comparing natural examples and geological models, we discuss deformation patterns and kinematics recorded along oblique plate boundaries.

  8. The coiled-coil domain containing protein CCDC151 is required for the function of IFT-dependent motile cilia in animals.

    Science.gov (United States)

    Jerber, Julie; Baas, Dominique; Soulavie, Fabien; Chhin, Brigitte; Cortier, Elisabeth; Vesque, Christine; Thomas, Joëlle; Durand, Bénédicte

    2014-02-01

    Cilia are evolutionarily conserved organelles endowed with essential physiological and developmental functions. In humans, disruption of cilia motility or signaling leads to complex pleiotropic genetic disorders called ciliopathies. Cilia motility requires the assembly of multi-subunit motile components such as dynein arms, but mechanisms underlying their assembly pathway and transport into the axoneme are still largely unknown. We identified a previously uncharacterized coiled-coil domain containing protein CCDC151, which is evolutionarily conserved in motile ciliated species and shares ancient features with the outer dynein arm-docking complex 2 of Chlamydomonas. In Drosophila, we show that CG14127/CCDC151 is associated with motile intraflagellar transport (IFT)-dependent cilia and required for geotaxis behavior of adult flies. In zebrafish, Ccdc151 is expressed in tissues with motile cilia, and morpholino-induced depletion of Ccdc151 leads to left-right asymmetry defects and kidney cysts. We demonstrate that Ccdc151 is required for proper motile function of cilia in the Kupffer's vesicle and in the pronephros by controlling dynein arm assembly, showing that Ccdc151 is a novel player in the control of IFT-dependent dynein arm assembly in animals. However, we observed that CCDC151 is also implicated in other cellular functions in vertebrates. In zebrafish, ccdc151 is involved in proper orientation of cell divisions in the pronephros and genetically interacts with prickle1 in this process. Furthermore, knockdown experiments in mammalian cells demonstrate that CCDC151 is implicated in the regulation of primary cilium length. Hence, CCDC151 is required for motile cilia function in animals but has acquired additional non-motile functions in vertebrates.

  9. Angular shear plate

    Science.gov (United States)

    Ruda, Mitchell C [Tucson, AZ; Greynolds, Alan W [Tucson, AZ; Stuhlinger, Tilman W [Tucson, AZ

    2009-07-14

    One or more disc-shaped angular shear plates each include a region thereon having a thickness that varies with a nonlinear function. For the case of two such shear plates, they are positioned in a facing relationship and rotated relative to each other. Light passing through the variable thickness regions in the angular plates is refracted. By properly timing the relative rotation of the plates and by the use of an appropriate polynomial function for the thickness of the shear plate, light passing therethrough can be focused at variable positions.

  10. Architecture as Design Study.

    Science.gov (United States)

    Kauppinen, Heta

    1989-01-01

    Explores the use of analogies in architectural design, the importance of Gestalt theory and aesthetic cannons in understanding and being sensitive to architecture. Emphasizes the variation between public and professional appreciation of architecture. Notes that an understanding of architectural process enables students to improve the aesthetic…

  11. Architectural design decisions

    NARCIS (Netherlands)

    Jansen, Antonius Gradus Johannes

    2008-01-01

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

  12. Can You Hear Architecture

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2016-01-01

    Taking an off set in the understanding of architectural quality being based on multisensory architecture, the paper aims to discuss the current acoustic discourse in inclusive design and its implications to the integration of inclusive design in architectural discourse and practice as well...... design and architectural quality for people with a hearing disability and a newly conducted qualitative evaluation research in Denmark as well as architectural theories on multisensory aspects of architectural experiences, the paper uses examples of existing Nordic building cases to discuss the role...... of acoustics in both inclusive design and multisensory architecture....

  13. Mucociliary and long-term particle clearance in airways of patients with immotile cilia

    Science.gov (United States)

    Möller, Winfried; Häußinger, Karl; Ziegler-Heitbrock, Löms; Heyder, Joachim

    2006-01-01

    Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients. PMID:16423294

  14. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Claas Wodarczyk

    Full Text Available Polycystin-1 (PC-1, the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD, is a very large (approximately 520 kDa plasma membrane receptor localized in several subcellular compartments including cell-cell/matrix junctions as well as cilia. While heterologous over-expression systems have allowed identification of several of the potential biological roles of this receptor, its precise function remains largely elusive. Studying PC-1 in vivo has been a challenging task due to its complexity and low expression levels. To overcome these limitations and facilitate the study of endogenous PC-1, we have inserted HA- or Myc-tag sequences into the Pkd1 locus by homologous recombination. Here, we show that our approach was successful in generating a fully functional and easily detectable endogenous PC-1. Characterization of PC-1 distribution in vivo showed that it is expressed ubiquitously and is developmentally-regulated in most tissues. Furthermore, our novel tool allowed us to investigate the role of PC-1 in brain, where the protein is abundantly expressed. Subcellular localization of PC-1 revealed strong and specific staining in ciliated ependymal and choroid plexus cells. Consistent with this distribution, we observed hydrocephalus formation both in the ubiquitous knock-out embryos and in newborn mice with conditional inactivation of the Pkd1 gene in the brain. Both choroid plexus and ependymal cilia were morphologically normal in these mice, suggesting a role for PC-1 in ciliary function or signalling in this compartment, rather than in ciliogenesis. We propose that the role of PC-1 in the brain cilia might be to prevent hydrocephalus, a previously unrecognized role for this receptor and one that might have important implications for other genetic or sporadic diseases.

  15. Architecture and dynamic of lower Cretaceous carbonate platform in sultanate of Oman: correlations between seismic data and outcrop; Architecture et dynamique des systemes carbonates de la plate-forme Cretace inferieur du Sultanat d'Oman: correlations entre donnees de sismique et d'affleurement

    Energy Technology Data Exchange (ETDEWEB)

    Le Bec, A.

    2004-12-15

    The Rayda Basin, located in northern Oman at the south-eastern passive margin of the Arabian plate, has been filled in by a pro-grading carbonate system during the Lower Cretaceous. The filling up basin realized to carbonate platform pro-gradation on 300 km. Pelagic facies represented with radiolarian chert and shallowing facies with erosive surface, mud-cracks and lagoonal mud, and displaying on seismic lines an alternation of high angle and low angle clinoforms at the 10's of kilometers scale. Detailed study of these two types of clinoforms in the nearby outcrops shows that the high angle system is dominated by high-energy, grainy facies (ooliths, rudists, stromatoporoids), while the low angle system is dominated by a low-energy, carbonate mud facies. Based on the subsurface (geometries) and outcrop (facies) data a regional depositional model is proposed for this system. The outcrop study is based on 14 measured sections (6764 meters), completed with photo panoramas, thin section analysis and geochemical analyses (carbonate and organic matter content). The subsurface dataset consists of several regional seismic lines, two high resolution 3D blocs, and is supported by core material The regional seismic lines allow to map out the position of the high and low angle clinoform belts. One high angle belt and two low angle belts are identified in the profiles. In outcrop at least one more high angle belt and one more low angle belt are present. These overall geometries probably define the large scale sequence organisation. At a smaller scale, the 3D blocs allow to show the detailed geometrical organisation of the clinoform belts. The outcrop sections provide critical sub-seismic scale data on the facies composition and depositional geometries. The high energy system of the steep clinoforms (angle estimated at several degrees), is probably a wave controlled barrier coastline system, while the muddy low angle clinoforms (angle < 0.5 degree) shows large convex and

  16. Biologically-Inspired Micro-Robots: Volume 2: Investigation of a Micro-Joint Angle Sensor Using MEMS Cilia

    Science.gov (United States)

    2005-09-01

    the wheatstone bridge are labeled “ Opamp ” and are the inputs to an operational amplifier as shown in Figure 23. pseudo-cilium cilium Note: total...select a cilium Addresses of cilia Figure 21. Decoder for 1st Generation JAS 23 R1 = 26kΩ Decoder Opamp Opamp -2.5V 2.5V R1 R1 R1 R1 Figure 22...1st Generation JAS – Individually Addressed Cilium Output to neural networkOutputs from selected wheatstone brige Output Opamp Opamp R2 R2

  17. Localization of transient receptor potential ion channels in primary and motile cilia of the female murine reproductive organs

    DEFF Research Database (Denmark)

    Teilmann, Stefan C.; Byskov, Anne Grete; Pedersen, Per Amstrup;

    2005-01-01

    We have examined the subcellular localization of transient receptor potential (TRP) ion channels and the potential sensory role of cilia in murine female reproductive organs using confocal laser scanning microscopy analysis on ovary and oviduct tissue sections as well as on primary cultures...... intensity in proximal invaginations of the epithelial folds. These observations are the first to demonstrate ciliary localization of TRP ion channels and their possible receptor function in the female reproductive organs. We suggest that polycystins 1 and 2 play an important role in granulosa cell...

  18. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation

    DEFF Research Database (Denmark)

    Becker-Heck, Anita; Zohn, Irene E; Okabe, Noriko

    2011-01-01

    -right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40...... is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms...... and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD....

  19. Generalized Fibonacci zone plates

    CERN Document Server

    Ke, Jie; Zhu, Jianqiang

    2015-01-01

    We propose a family of zone plates which are produced by the generalized Fibonacci sequences and their axial focusing properties are analyzed in detail. Compared with traditional Fresnel zone plates, the generalized Fibonacci zone plates present two axial foci with equal intensity. Besides, we propose an approach to adjust the axial locations of the two foci by means of different optical path difference, and further give the deterministic ratio of the two focal distances which attributes to their own generalized Fibonacci sequences. The generalized Fibonacci zone plates may allow for new applications in micro and nanophotonics.

  20. A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4.

    Directory of Open Access Journals (Sweden)

    Svetlana V Masyukova

    2016-02-01

    Full Text Available Nephronophthisis (NPHP is a ciliopathy in which genetic modifiers may underlie the variable penetrance of clinical features. To identify modifiers, a screen was conducted on C. elegans nphp-4(tm925 mutants. Mutations in ten loci exacerbating nphp-4(tm925 ciliary defects were obtained. Four loci have been identified, three of which are established ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66 is a missense mutation (S316F in OSM-3, a kinesin required for cilia distal segment assembly. While osm-3(yhw66 mutants alone have no overt cilia phenotype, nphp-4(tm925;osm-3(yhw66 double mutants lack distal segments and are dye-filling (Dyf and osmotic avoidance (Osm defective, similar to osm-3(mn357 null mutants. In osm-3(yhw66 mutants anterograde intraflagellar transport (IFT velocity is reduced. Furthermore, expression of OSM-3(S316F::GFP reduced IFT velocities in nphp-4(tm925 mutants, but not in wild type animals. In silico analysis indicates the S316F mutation may affect a phosphorylation site. Putative phospho-null OSM-3(S316F and phospho-mimetic OSM-3(S316D proteins accumulate at the cilia base and tip respectively. FRAP analysis indicates that the cilia entry rate of OSM-3(S316F is slower than OSM-3 and that in the presence of OSM-3(S316F, OSM-3 and OSM-3(S316D rates decrease. In the presence OSM-3::GFP or OSM-3(S316D::GFP, OSM-3(S316F::tdTomato redistributes along the cilium and accumulates in the cilia tip. OSM-3(S316F and OSM-3(S316D are functional as they restore cilia distal segment formation in osm-3(mn357 null mutants; however, only OSM-3(S316F rescues the osm-3(mn357 null Dyf phenotype. Despite rescue of cilia length in osm-3(mn357 null mutants, neither OSM-3(S316F nor OSM-3(S316D restores ciliary defects in nphp-4(tm925;osm-3(yhw66 double mutants. Thus, these OSM-3 mutations cause NPHP-4 dependent and independent phenotypes. These data indicate that in addition to regulating cilia protein entry or exit, NPHP-4

  1. Modeling Architectural Patterns' Behavior Using Architectural Primitives

    NARCIS (Netherlands)

    Kamal, Ahmad Waqas; Avgeriou, Paris; Morrison, R; Balasubramaniam, D; Falkner, K

    2008-01-01

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

  2. Modeling Architectural Patterns’ Behavior Using Architectural Primitives

    NARCIS (Netherlands)

    Waqas Kamal, Ahmad; Avgeriou, Paris

    2008-01-01

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

  3. Exporting Humanist Architecture

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2016-01-01

    values and ethical stands involved in the export of Danish Architecture. Abstract: Danish architecture has, in a sense, been driven by an unwritten contract between the architects and the democratic state and its institutions. This contract may be viewed as an ethos – an architectural tradition...... with inherent aesthetic and moral values. Today, however, Danish architecture is also an export commodity. That raises questions, which should be debated as openly as possible. What does it mean for architecture and architects to practice in cultures and under political systems that do not use architecture...... as a way of generating humanism, freedom or equality? The essay outlines the background story, identifies a number of positions in relation to architecture exports and discusses some of the dilemmas that arise when Danish architecture is seen in an export perspective....

  4. Religious architecture: anthropological perspectives

    NARCIS (Netherlands)

    O. Verkaaik

    2013-01-01

    Religious Architecture: Anthropological Perspectives develops an anthropological perspective on modern religious architecture, including mosques, churches and synagogues. Borrowing from a range of theoretical perspectives on space-making and material religion, this volume looks at how religious buil

  5. Rhein-Ruhr architecture

    DEFF Research Database (Denmark)

    2002-01-01

    katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider......katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider...

  6. Detection of copy number variants reveals association of cilia genes with neural tube defects.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    Full Text Available BACKGROUND: Neural tube defects (NTDs are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. METHODS: The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. RESULTS: Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV. Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05. Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24-5.87. Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05, corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27-8.01. Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. CONCLUSIONS: Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.

  7. Blue Willow Story Plates

    Science.gov (United States)

    Fontes, Kris

    2009-01-01

    In the December 1997 issue of "SchoolArts" is a lesson titled "Blue Willow Story Plates" by Susan Striker. In this article, the author shares how she used this lesson with her middle-school students many times over the years. Here, she describes a Blue Willow plate painting project that her students made.

  8. Create Your Plate

    Medline Plus

    Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Create Your Plate Create Your Plate is a ...

  9. Create Your Plate

    Medline Plus

    Full Text Available ... Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal Planning ... Planning Meals Diabetes Meal Plans and a Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets ...

  10. Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia.

    Science.gov (United States)

    Dai, D; Li, L; Huebner, A; Zeng, H; Guevara, E; Claypool, D J; Liu, A; Chen, J

    2013-01-01

    Genes involved in the planar cell polarity (PCP) signaling pathway are essential for a number of developmental processes in mammals, such as convergent extension and ciliogenesis. Tissue-specific PCP effector genes of the PCP signaling pathway are believed to mediate PCP signals in a tissue- and cell type-specific manner. However, how PCP signaling controls the morphogenesis of mammalian tissues remains unclear. In this study, we investigated the role of inturned (Intu), a tissue-specific PCP effector gene, during hair follicle formation in mice. Tissue-specific disruption of Intu in embryonic epidermis resulted in hair follicle morphogenesis arrest because of the failure of follicular keratinocyte to differentiate. Targeting Intu in the epidermis resulted in almost complete loss of primary cilia in epidermal and follicular keratinocytes, and a suppressed hedgehog signaling pathway. Surprisingly, the epidermal stratification and differentiation programs and barrier function were not affected. These results demonstrate that tissue-specific PCP effector genes of the PCP signaling pathway control the differentiation of keratinocytes through the primary cilia in a cell fate- and context-dependent manner, which may be critical in orchestrating the propagation and interpretation of polarity signals established by the core PCP components.

  11. Concise Review: Primary Cilia: Control Centers for Stem Cell Lineage Specification and Potential Targets for Cell-Based Therapies.

    Science.gov (United States)

    Bodle, Josephine C; Loboa, Elizabeth G

    2016-06-01

    Directing stem cell lineage commitment prevails as the holy grail of translational stem cell research, particularly to those interested in the application of mesenchymal stem cells and adipose-derived stem cells in tissue engineering. However, elucidating the mechanisms underlying their phenotypic specification persists as an active area of research. In recent studies, the primary cilium structure has been intimately associated with defining cell phenotype, maintaining stemness, as well as functioning in a chemo, electro, and mechanosensory capacity in progenitor and committed cell types. Many hypothesize that the primary cilium may indeed be another important player in defining and controlling cell phenotype, concomitant with lineage-dictated cytoskeletal dynamics. Many of the studies on the primary cilium have emerged from disparate areas of biological research, and crosstalk amongst these areas of research is just beginning. To date, there has not been a thorough review of how primary cilia fit into the current paradigm of stem cell differentiation and this review aims to summarize the current cilia work in this context. The goal of this review is to highlight the cilium's function and integrate this knowledge into the working knowledge of stem cell biologists and tissue engineers developing regenerative medicine technologies. Stem Cells 2016;34:1445-1454.

  12. Role of Ocrl1 and Inpp5E in primary cilia assembly and maintenance: a phosphatidylinositol phosphatase relay system?

    Directory of Open Access Journals (Sweden)

    Madhivanan K

    2016-02-01

    Full Text Available Kayalvizhi Madhivanan,* Swetha Ramadesikan,* R Claudio Aguilar Department of Biological Sciences, Purdue University, West Lafayette, IN, USA *These authors contributed equally to this work Abstract: The primary cilium (PC is a plasma membrane-derived structure of great importance for cell and organismal physiology. Indeed, abnormalities in assembly or function of the PC trigger the onset of a group of genetic diseases collectively known as ciliopathies. In recent years, it has become evident that the integrity and function of the PC depends substantially on signaling elements such as phosphoinositides (PI and their regulators. Because phospholipids such as PI(4,5P2 constitute recruitment platforms for cytoskeleton, signaling, and trafficking machinery, control over their levels is critical for PC function. Although information about phosphoinositol phosphate (PIP kinases in the PC is scarce, a growing body of evidence supports a role for PIP phosphatases in cilia assembly/maintenance. Indeed, deficiencies in two 5′ PIP phosphatases, Inpp5E and Ocrl1, are clearly linked to ciliopathies like Joubert/MORM syndromes, or ciliopathy-associated diseases like Lowe syndrome. Here, we review the unique roles of these proteins and their specific site of action for ensuring ciliary integrity. Further, we discuss the possibility that a phosphatase relay system able to pass PI control from a preciliary to an intraciliary compartment is in place to ensure PC integrity/function. Keywords: primary cilia, Ocrl1, Inpp5E, Pip2, Pip3

  13. Architectural Knitted Surfaces

    DEFF Research Database (Denmark)

    Mossé, Aurélie

    2010-01-01

    WGSN reports from the Architectural Knitted Surfaces workshop recently held at ShenkarCollege of Engineering and Design, Tel Aviv, which offered a cutting-edge insight into interactive knitted surfaces. With the increasing role of smart textiles in architecture, the Architectural Knitted Surfaces...

  14. A concept of PWR using plate and shell heat exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Freire, Luciano Ondir; Andrade, Delvonei Alves de, E-mail: luciano.ondir@gmail.com, E-mail: delvonei@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    In previous work it was verified the physical possibility of using plate and shell heat exchangers for steam generation in a PWR for merchant ships. This work studies the possibility of using GESMEX commercial of the shelf plate and shell heat exchanger of series XPS. It was found it is feasible for this type of heat exchanger to meet operational and accidental requirements for steam generation in PWR. Additionally, it is proposed an arrangement of such heat exchangers inside the reactor pressure vessel. Such arrangement may avoid ANSI/ANS51.1 nuclear class I requirements on those heat exchangers because they are contained in the reactor coolant pressure barrier and play no role in accidental scenarios. Additionally, those plates work under compression, preventing the risk of rupture. Being considered non-nuclear safety, having a modular architecture and working under compression may turn such architectural choice a must to meet safety objectives with improved economics. (author)

  15. Pixelated neutron image plates

    Science.gov (United States)

    Schlapp, M.; Conrad, H.; von Seggern, H.

    2004-09-01

    Neutron image plates (NIPs) have found widespread application as neutron detectors for single-crystal and powder diffraction, small-angle scattering and tomography. After neutron exposure, the image plate can be read out by scanning with a laser. Commercially available NIPs consist of a powder mixture of BaFBr : Eu2+ and Gd2O3 dispersed in a polymer matrix and supported by a flexible polymer sheet. Since BaFBr : Eu2+ is an excellent x-ray storage phosphor, these NIPs are particularly sensitive to ggr-radiation, which is always present as a background radiation in neutron experiments. In this work we present results on NIPs consisting of KCl : Eu2+ and LiF that were fabricated into ceramic image plates in which the alkali halides act as a self-supporting matrix without the necessity for using a polymeric binder. An advantage of this type of NIP is the significantly reduced ggr-sensitivity. However, the much lower neutron absorption cross section of LiF compared with Gd2O3 demands a thicker image plate for obtaining comparable neutron absorption. The greater thickness of the NIP inevitably leads to a loss in spatial resolution of the image plate. However, this reduction in resolution can be restricted by a novel image plate concept in which a ceramic structure with square cells (referred to as a 'honeycomb') is embedded in the NIP, resulting in a pixelated image plate. In such a NIP the read-out light is confined to the particular illuminated pixel, decoupling the spatial resolution from the optical properties of the image plate material and morphology. In this work, a comparison of experimentally determined and simulated spatial resolutions of pixelated and unstructured image plates for a fixed read-out laser intensity is presented, as well as simulations of the properties of these NIPs at higher laser powers.

  16. Plate removal following orthognathic surgery.

    Science.gov (United States)

    Little, Mhairi; Langford, Richard Julian; Bhanji, Adam; Farr, David

    2015-11-01

    The objectives of this study are to determine the removal rates of orthognathic plates used during orthognathic surgery at James Cook University Hospital and describe the reasons for plate removal. 202 consecutive orthognathic cases were identified between July 2004 and July 2012. Demographics and procedure details were collected for these patients. Patients from this group who returned to theatre for plate removal between July 2004 and November 2012 were identified and their notes were analysed for data including reason for plate removal, age, smoking status, sex and time to plate removal. 3.2% of plates were removed with proportionally more plates removed from the mandible than the maxilla. 10.4% of patients required removal of one or more plate. Most plates were removed within the first post-operative year. The commonest reasons for plate removal were plate exposure and infection. The plate removal rates in our study are comparable to those seen in the literature.

  17. Software architecture evolution

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  18. Anisotropic elastic plates

    CERN Document Server

    Hwu, Chyanbin

    2010-01-01

    As structural elements, anisotropic elastic plates find wide applications in modern technology. The plates here are considered to be subjected to not only in plane load but also transverse load. In other words, both plane and plate bending problems as well as the stretching-bending coupling problems are all explained in this book. In addition to the introduction of the theory of anisotropic elasticity, several important subjects have are discussed in this book such as interfaces, cracks, holes, inclusions, contact problems, piezoelectric materials, thermoelastic problems and boundary element a

  19. Plating in Top Agar

    OpenAIRE

    sprotocols

    2014-01-01

    1. Warm plates to room temperature before use. Cold plates causes the top agar to solidify irregularly. DO not warm plates to 37° as the top agar will take forever to solidify. - Prepare top agar as the appropriate liquid medium with 0.7% agar. Keeping 100 mL bottles is convenient. For phages, use λ top agar, which is less rich and yields bigger plaques. - Melt top agar in the microwave completely. Allow the agar to boil after liquification; incompletely melted agar looks liquid, but is...

  20. Ultralight shape-recovering plate mechanical metamaterials.

    Science.gov (United States)

    Davami, Keivan; Zhao, Lin; Lu, Eric; Cortes, John; Lin, Chen; Lilley, Drew E; Purohit, Prashant K; Bargatin, Igor

    2015-12-03

    Unusual mechanical properties of mechanical metamaterials are determined by their carefully designed and tightly controlled geometry at the macro- or nanoscale. We introduce a class of nanoscale mechanical metamaterials created by forming continuous corrugated plates out of ultrathin films. Using a periodic three-dimensional architecture characteristic of mechanical metamaterials, we fabricate free-standing plates up to 2 cm in size out of aluminium oxide films as thin as 25 nm. The plates are formed by atomic layer deposition of ultrathin alumina films on a lithographically patterned silicon wafer, followed by complete removal of the silicon substrate. Unlike unpatterned ultrathin films, which tend to warp or even roll up because of residual stress gradients, our plate metamaterials can be engineered to be extremely flat. They weigh as little as 0.1 g cm(-2) and have the ability to 'pop-back' to their original shape without damage even after undergoing multiple sharp bends of more than 90°.

  1. Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

    DEFF Research Database (Denmark)

    Nielsen, Sonja K; Møllgård, Kjeld; Clement, Christian A

    2008-01-01

    Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct...

  2. Immunofluorescence Microscopy and mRNA Analysis of Human Embryonic Stem Cells (hESCs) Including Primary Cilia Associated Signaling Pathways

    DEFF Research Database (Denmark)

    Vestergaard, Maj Linea; Awan, Aashir; Warzecha, Caroline Becker

    2016-01-01

    onto 16-well glass chambers, and continuing with the general IFM and qPCR anlysis. The techniques are illustrated with results on cellular localization of transcriptional factors and components of the Hedgehog, Wnt, PDGF, and TGFβ signaling pathways to primary cilia in stem cell maintenance...

  3. Create Your Plate

    Medline Plus

    Full Text Available ... blood glucose levels and lose weight. With this method, you fill your plate with more non-starchy ... but changes the portion sizes so you are getting larger portions of non-starchy vegetables and a ...

  4. Create Your Plate

    Medline Plus

    Full Text Available ... blood glucose levels and lose weight. With this method, you fill your plate with more non-starchy ... 4/Box) Taking the guesswork out of portion control has never been easier. It can be a ...

  5. Tectonic Plate Movement.

    Science.gov (United States)

    Landalf, Helen

    1998-01-01

    Presents an activity that employs movement to enable students to understand concepts related to plate tectonics. Argues that movement brings topics to life in a concrete way and helps children retain knowledge. (DDR)

  6. MyPlate

    Science.gov (United States)

    ... our stage of life, situations, preferences, access to food, culture, traditions, and the personal decisions we make over time. All your food and beverage choices count. MyPlate offers ideas and ...

  7. Create Your Plate

    Medline Plus

    Full Text Available ... blood glucose levels and lose weight. With this method, you fill your plate with more non-starchy ... you have an easy portion control solution that works. Last Reviewed: October 8, 2015 Last Edited: September ...

  8. Designing Assemblies Of Plates

    Science.gov (United States)

    Williams, F. W.; Kennedy, D.; Butler, R.; Aston, G.; Anderson, M. S.

    1992-01-01

    VICONOPT calculates vibrations and instabilities of assemblies of prismatic plates. Designed for efficient, accurate analysis of buckling and vibration, and for optimum design of panels of composite materials. Written in FORTRAN 77.

  9. Create Your Plate

    Medline Plus

    Full Text Available ... Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal Planning What Can I Eat? Making Healthy Food Choices Diabetes Superfoods Non-starchy Vegetables Grains and Starchy Vegetables ...

  10. Create Your Plate

    Medline Plus

    Full Text Available ... Recipes Association Cookbook Recipes Planning Meals Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning ... serving of dairy or both as your meal plan allows. Choose healthy fats in small amounts. For ...

  11. Create Your Plate

    Medline Plus

    Full Text Available ... 1 Diabetes Get Started Safely Get And Stay Fit Types of Activity Weight Loss Assess Your Lifestyle ... manage portion control wherever you are. Now, our best-selling, sectioned to-go plate with easy-sealing ...

  12. Create Your Plate

    Medline Plus

    Full Text Available ... Plate is a simple and effective way to manage your blood glucose levels and lose weight. With ... been easier. It can be a challenge to manage portion control wherever you are. Now, our best- ...

  13. Tectonic Plate Movement.

    Science.gov (United States)

    Landalf, Helen

    1998-01-01

    Presents an activity that employs movement to enable students to understand concepts related to plate tectonics. Argues that movement brings topics to life in a concrete way and helps children retain knowledge. (DDR)

  14. Create Your Plate

    Medline Plus

    Full Text Available ... Carbohydrates Carbohydrate Counting Make Your Carbs Count Glycemic ... to manage portion control wherever you are. Now, our best-selling, sectioned to-go plate with easy-sealing ...

  15. Origami - Folded Plate Structures

    OpenAIRE

    Buri, Hans Ulrich

    2010-01-01

    This research investigates new methods of designing folded plate structures that can be built with cross-laminated timber panels. Folded plate structures are attractive to both architects and engineers for their structural, spatial, and plastic qualities. Thin surfaces can be stiffened by a series of folds, and thus not only cover space, but also act as load bearing elements. The variation of light and shadow along the folded faces emphasizes the plas...

  16. Fractal multifiber microchannel plates

    Science.gov (United States)

    Cook, Lee M.; Feller, W. B.; Kenter, Almus T.; Chappell, Jon H.

    1992-01-01

    The construction and performance of microchannel plates (MCPs) made using fractal tiling mehtods are reviewed. MCPs with 40 mm active areas having near-perfect channel ordering were produced. These plates demonstrated electrical performance characteristics equivalent to conventionally constructed MCPs. These apparently are the first MCPs which have a sufficiently high degree of order to permit single channel addressability. Potential applications for these devices and the prospects for further development are discussed.

  17. Cardboard Houses with Wings: The Architecture of Alabama's Rural Studio

    Science.gov (United States)

    Botz-Bornstein, Thorsten

    2010-01-01

    The Rural Studio, an outreach program of Auburn University, designs innovative houses for poor people living in Alabama's Hale County by using "junk" such as car windshields, carpet tiles, baled cardboard, and old license plates. The article theorizes this particular architecture in terms of Critical Regionalism, developed by…

  18. Vibration and Buckling of Web Plate of the Plate Girder

    OpenAIRE

    高橋, 和雄; 呉, 明強; 中澤, 聡志; 筑紫, 宏之

    1998-01-01

    The vibration and buckling of the web of the plate girder are studied in this paper. The small deflection theory of the thin plate is used. The finite strip method is employed to solve vibration and buckling of the plate girder. Natural frequenies of buckling properties are shown for various plate girder bridges.

  19. Tangentially migrating neurons assemble a primary cilium that promotes their reorientation to the cortical plate.

    Science.gov (United States)

    Baudoin, Jean-Pierre; Viou, Lucie; Launay, Pierre-Serge; Luccardini, Camilla; Espeso Gil, Sergio; Kiyasova, Vera; Irinopoulou, Théano; Alvarez, Chantal; Rio, Jean-Paul; Boudier, Thomas; Lechaire, Jean-Pierre; Kessaris, Nicoletta; Spassky, Nathalie; Métin, Christine

    2012-12-20

    In migrating neurons, the centrosome nucleates and anchors a polarized network of microtubules that directs organelle movements. We report here that the mother centriole of neurons migrating tangentially from the medial ganglionic eminence (MGE) assembles a short primary cilium and exposes this cilium to the cell surface by docking to the plasma membrane in the leading process. Primary cilia are built by intraflagellar transport (IFT), which is also required for Sonic hedgehog (Shh) signal transduction in vertebrates. We show that Shh pathway perturbations influenced the leading process morphology and dynamics of MGE cells. Whereas Shh favored the exit of MGE cells away from their tangential migratory paths in the developing cortex, cyclopamine or invalidation of IFT genes maintained MGE cells in the tangential paths. Our findings show that signals transmitted through the primary cilium promote the escape of future GABAergic interneurons from their tangential routes to colonize the cortical plate.

  20. Enterprise architecture management

    DEFF Research Database (Denmark)

    Rahimi, Fatemeh; Gøtze, John; Møller, Charles

    2017-01-01

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

  1. Architecture and Stages

    DEFF Research Database (Denmark)

    Kiib, Hans

    2009-01-01

    Architecture and Art as Fuel New development zones for shopping and entertainment and space for festivals inside the city CAN be coupled with art and architecture and become ‘open minded' public domains based on cultural exchange and mutual learning. This type of space could be labelled...... as "experiencescape" - a space between tourism, culture, learning and economy. Strategies related to these challenges involve new architectural concepts and art as ‘engines' for a change. New expressive architecture and old industrial buildings are often combined into hybrid narratives, linking the past...... with the future. But this is not enough. The agenda is to develop architectural spaces, where social interaction and learning are enhanced by art and fun. How can we develop new architectural designs in our inner cities and waterfronts where eventscapes, learning labs and temporal use are merged with everyday...

  2. Knowledge and Architectural Practice

    DEFF Research Database (Denmark)

    Verbeke, Johan

    2017-01-01

    This paper focuses on the specific knowledge residing in architectural practice. It is based on the research of 35 PhD fellows in the ADAPT-r (Architecture, Design and Art Practice Training-research) project. The ADAPT-r project innovates architectural research in combining expertise from academia...... and from practice in order to highlight and extract the specific kind of knowledge which resides and is developed in architectural practice (creative practice research). The paper will discuss three ongoing and completed PhD projects and focusses on the outcomes and their contribution to the field....... Specific to these research projects is that the researcher is within academia but stays emerged in architectural practice. The projects contribute to a better understanding of architectural practice, how it develops and what kind of knowledge is crucial. Furthermore, the paper will develop a reflection...

  3. Larval spicules, cilia, and symmetry as remnants of indirect development in the direct developing sea urchin Heliocidaris erythrogramma.

    Science.gov (United States)

    Emlet, R B

    1995-02-01

    Nonfeeding larvae of the echinoid Heliocidaris erythrogramma were raised in culture and examined for expression of a larval skeleton and for the arrangement of the ciliated band. Opaque larvae were fixed, cleared, and examined under polarized light for evidence of calcification. By 35 hr after fertilization (at 22 degrees C), a pair of triradiate spicules was present at the posterior end of the larvae. Each member of this pair formed a fenestrated spicule as it grew laterally. This pair and another pair which formed subsequently, were arranged across a plane of bilateral symmetry orthagonal to the juvenile oral aboral axis. These paired larval spicules can be identified as reduced expressions of postoral and posterodorsal rods found in plutei, and their expression indicates that the juvenile rudiment of H. erythrogramma forms on the left side and that larval body axes are conserved in this modified larva. By 44 hr the ciliated band formed as an incomplete transverse loop of three segments at the posterior end and on the dorsal surface of the ovoid larva. Cilia in these segments grew to lengths of 45-50 microns, longer than other swimming and feeding cilia reported for echinoderm larvae. Band segments are interpreted as expressions of epaulettes (specialized swimming bands) rather than the feeding ciliated band of the pluteus. The ciliated band segments and the larval spicules are both bilaterally symmetrical with respect to the same plane and indicate conserved larval bilateral symmetry despite the major asymmetry of the fates of cells on either side of this plane in their contribution to juvenile development.

  4. Software Architecture Technology Initiative

    Science.gov (United States)

    2008-04-01

    2008 Carnegie Mellon University 2008 PLS March 2008 © 2008 Carnegie Mellon University Software Architecture Technology Initiative SATURN 2008...SUBTITLE Software Architecture Technology Initiative 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...SUPPLEMENTARY NOTES presented at the SEI Software Architecture Technology User Network (SATURN) Workshop, 30 Apr ? 1 May 2008, Pittsburgh, PA. 14

  5. Architecture humanitarian emergencies

    DEFF Research Database (Denmark)

    Gomez-Guillamon, Maria; Eskemose Andersen, Jørgen; Contreras, Jorge Lobos

    2013-01-01

    Introduced by scientific articles conserning architecture and human rights in light of cultures, emergencies, social equality and sustainability, democracy, economy, artistic development and science into architecture. Concluding in definition of needs for new roles, processes and education......, Architettura di Alghero in Italy, Architecture and Design of Kocaeli University in Turkey, University of Aguascalientes in Mexico, Architectura y Urbanismo of University of Chile and Escuela de Architectura of Universidad Austral in Chile....

  6. Towards a Media Architecture

    DEFF Research Database (Denmark)

    Ebsen, Tobias

    2010-01-01

    This text explores the concept of media architecture as a phenomenon of visual culture that describes the use of screen-technology in new spatial configurations in practices of architecture and art. I shall argue that this phenomenon is not necessarily a revolutionary new approach, but rather...... a result of conceptual changes in both modes visual representation and in expressions of architecture. These are changes the may be described as an evolution of ideas and consequent experiments that can be traced back to changes in the history of art and the various styles and ideologies of architecture....

  7. Grid Architecture 2

    Energy Technology Data Exchange (ETDEWEB)

    Taft, Jeffrey D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-01

    The report describes work done on Grid Architecture under the auspices of the Department of Electricity Office of Electricity Delivery and Reliability in 2015. As described in the first Grid Architecture report, the primary purpose of this work is to provide stakeholder insight about grid issues so as to enable superior decision making on their part. Doing this requires the creation of various work products, including oft-times complex diagrams, analyses, and explanations. This report provides architectural insights into several important grid topics and also describes work done to advance the science of Grid Architecture as well.

  8. Towards a Media Architecture

    DEFF Research Database (Denmark)

    Ebsen, Tobias

    2010-01-01

    This text explores the concept of media architecture as a phenomenon of visual culture that describes the use of screen-technology in new spatial configurations in practices of architecture and art. I shall argue that this phenomenon is not necessarily a revolutionary new approach, but rather...... a result of conceptual changes in both modes visual representation and in expressions of architecture. These are changes the may be described as an evolution of ideas and consequent experiments that can be traced back to changes in the history of art and the various styles and ideologies of architecture....

  9. IT Architecture For Dummies

    CERN Document Server

    Hausman, Kalani Kirk

    2010-01-01

    A solid introduction to the practices, plans, and skills required for developing a smart system architecture. Information architecture combines IT skills with business skills in order to align the IT structure of an organization with the mission, goals, and objectives of its business. This friendly introduction to IT architecture walks you through the myriad issues and complex decisions that many organizations face when setting up IT systems to work in sync with business procedures. Veteran IT professional and author Kirk Hausman explains the business value behind IT architecture and provides

  10. Elements of Architecture

    DEFF Research Database (Denmark)

    Elements of Architecture explores new ways of engaging architecture in archaeology. It conceives of architecture both as the physical evidence of past societies and as existing beyond the physical environment, considering how people in the past have not just dwelled in buildings but have existed...... and affective impacts, of these material remains. The contributions in this volume investigate the way time, performance and movement, both physically and emotionally, are central aspects of understanding architectural assemblages. It is a book about the constellations of people, places and things that emerge...

  11. Bending and stretching of plates

    CERN Document Server

    Mansfield, E H; Hemp, W S

    1964-01-01

    The Bending and Stretching of Plates deals with elastic plate theory, particularly on small- and large-deflexion theory. Small-deflexion theory concerns derivation of basic equations, rectangular plates, plates of various shapes, plates whose boundaries are amenable to conformal transformation, plates with variable rigidity, and approximate methods. Large-deflexion theory includes general equations and some exact solutions, approximate methods in large-deflexion theory, asymptotic large-deflexion theories for very thin plates. Asymptotic theories covers membrane theory, tension field theory, a

  12. Anterior cervical plating

    Directory of Open Access Journals (Sweden)

    Gonugunta V

    2005-01-01

    Full Text Available Although anterior cervical instrumentation was initially used in cervical trauma, because of obvious benefits, indications for its use have been expanded over time to degenerative cases as well as tumor and infection of the cervical spine. Along with a threefold increase in incidence of cervical fusion surgery, implant designs have evolved over the last three decades. Observation of graft subsidence and phenomenon of stress shielding led to the development of the new generation dynamic anterior cervical plating systems. Anterior cervical plating does not conclusively improve clinical outcome of the patients, but certainly enhances the efficacy of autograft and allograft fusion and lessens the rate of pseudoarthrosis and kyphosis after multilevel discectomy and fusions. A review of biomechanics, surgical technique, indications, complications and results of various anterior cervical plating systems is presented here to enable clinicians to select the appropriate construct design.

  13. On Detailing in Contemporary Architecture

    DEFF Research Database (Denmark)

    Kristensen, Claus; Kirkegaard, Poul Henning

    2010-01-01

    / tactility can blur the meaning of the architecture and turn it into an empty statement. The present paper will outline detailing in contemporary architecture and discuss the issue with respect to architectural quality. Architectural cases considered as sublime piece of architecture will be presented...

  14. A catalog of architectural primitives for modeling architectural patterns

    NARCIS (Netherlands)

    Zdun, Uwe; Avgeriou, Paris

    Architectural patterns are a fundamental aspect of the architecting process and subsequently the architectural documentation. Unfortunately, there is only poor support for modeling architectural patterns for two reasons. First, patterns describe recurring design solutions and hence do not directly

  15. License plate detection algorithm

    Science.gov (United States)

    Broitman, Michael; Klopovsky, Yuri; Silinskis, Normunds

    2013-12-01

    A novel algorithm for vehicle license plates localization is proposed. The algorithm is based on pixel intensity transition gradient analysis. Near to 2500 natural-scene gray-level vehicle images of different backgrounds and ambient illumination was tested. The best set of algorithm's parameters produces detection rate up to 0.94. Taking into account abnormal camera location during our tests and therefore geometrical distortion and troubles from trees this result could be considered as passable. Correlation between source data, such as license Plate dimensions and texture, cameras location and others, and parameters of algorithm were also defined.

  16. Digitally-Driven Architecture

    Directory of Open Access Journals (Sweden)

    Henriette Bier

    2014-07-01

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

  17. Software Architecture Evolution

    Science.gov (United States)

    Barnes, Jeffrey M.

    2013-01-01

    Many software systems eventually undergo changes to their basic architectural structure. Such changes may be prompted by new feature requests, new quality attribute requirements, changing technology, or other reasons. Whatever the causes, architecture evolution is commonplace in real-world software projects. Today's software architects, however,…

  18. Enterprise architecture intelligence

    NARCIS (Netherlands)

    Veneberg, R.K.M.; Iacob, Maria Eugenia; van Sinderen, Marten J.; Bodenstaff, L.; Reichert, M.U.; Rinderle-Ma, S.; Grossmann, G.

    2014-01-01

    Combining enterprise architecture and operational data is complex (especially when considering the actual ‘matching’ of data with enterprise architecture objects), and little has been written on how to do this. Therefore, in this paper we aim to fill this gap and propose a method to combine

  19. Aesthetics of sustainable architecture

    NARCIS (Netherlands)

    Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The chapt

  20. SMRF architecture concepts

    NARCIS (Netherlands)

    Rossum, W.L. van; Wit, J.J.M. de; Otten, M.P.G.; Huizing, A.G.

    2011-01-01

    This presents three valuable applications of scalable multifunction RF (SMRF) systems. These systems allow radar, ESM, and communication functionality using a single front-end architecture. With the use of a novel system design tool, concepts for SMRF architectures for airborne, ground-based and nav

  1. Architecture and energy

    DEFF Research Database (Denmark)

    Marsh, Rob; Lauring, Michael

    2011-01-01

    Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies.......Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies....

  2. Aesthetics of sustainable architecture

    NARCIS (Netherlands)

    Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The chapt

  3. Teaching American Indian Architecture.

    Science.gov (United States)

    Winchell, Dick

    1991-01-01

    Reviews "Native American Architecture," by Nabokov and Easton, an encyclopedic work that examines technology, climate, social structure, economics, religion, and history in relation to house design and the "meaning" of space among tribes of nine regions. Describes this book's use in a college course on Native American architecture. (SV)

  4. Architecture and Stages

    DEFF Research Database (Denmark)

    Kiib, Hans

    2009-01-01

    as "experiencescape" - a space between tourism, culture, learning and economy. Strategies related to these challenges involve new architectural concepts and art as ‘engines' for a change. New expressive architecture and old industrial buildings are often combined into hybrid narratives, linking the past...

  5. Teaching American Indian Architecture.

    Science.gov (United States)

    Winchell, Dick

    1991-01-01

    Reviews "Native American Architecture," by Nabokov and Easton, an encyclopedic work that examines technology, climate, social structure, economics, religion, and history in relation to house design and the "meaning" of space among tribes of nine regions. Describes this book's use in a college course on Native American architecture. (SV)

  6. Workflow automation architecture standard

    Energy Technology Data Exchange (ETDEWEB)

    Moshofsky, R.P.; Rohen, W.T. [Boeing Computer Services Co., Richland, WA (United States)

    1994-11-14

    This document presents an architectural standard for application of workflow automation technology. The standard includes a functional architecture, process for developing an automated workflow system for a work group, functional and collateral specifications for workflow automation, and results of a proof of concept prototype.

  7. Emerging supercomputer architectures

    Energy Technology Data Exchange (ETDEWEB)

    Messina, P.C.

    1987-01-01

    This paper will examine the current and near future trends for commercially available high-performance computers with architectures that differ from the mainstream ''supercomputer'' systems in use for the last few years. These emerging supercomputer architectures are just beginning to have an impact on the field of high performance computing. 7 refs., 1 tab.

  8. Software Architecture Evolution

    Science.gov (United States)

    Barnes, Jeffrey M.

    2013-01-01

    Many software systems eventually undergo changes to their basic architectural structure. Such changes may be prompted by new feature requests, new quality attribute requirements, changing technology, or other reasons. Whatever the causes, architecture evolution is commonplace in real-world software projects. Today's software architects, however,…

  9. Applying neuroscience to architecture.

    Science.gov (United States)

    Eberhard, John P

    2009-06-25

    Architectural practice and neuroscience research use our brains and minds in much the same way. However, the link between neuroscience knowledge and architectural design--with rare exceptions--has yet to be made. The concept of linking these two fields is a challenge worth considering.

  10. Distal radius plate of CFR-PEEK has minimal effect compared to titanium plates on bone parameters in high-resolution peripheral quantitative computed tomography: a pilot study.

    Science.gov (United States)

    de Jong, Joost J A; Lataster, Arno; van Rietbergen, Bert; Arts, Jacobus J; Geusens, Piet P; van den Bergh, Joop P W; Willems, Paul C

    2017-02-27

    Carbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK) has superior radiolucency compared to other orthopedic implant materials, e.g. titanium or stainless steel, thus allowing metal-artifact-free postoperative monitoring by computed tomography (CT). Recently, high-resolution peripheral quantitative CT (HRpQCT) proved to be a promising technique to monitor the recovery of volumetric bone mineral density (vBMD), micro-architecture and biomechanical parameters in stable conservatively treated distal radius fractures. When using HRpQCT to monitor unstable distal radius fractures that require volar distal radius plating for fixation, radiolucent CFR-PEEK plates may be a better alternative to currently used titanium plates to allow for reliable assessment. In this pilot study, we assessed the effect of a volar distal radius plate made from CFR-PEEK on bone parameters obtained from HRpQCT in comparison to two titanium plates. Plates were instrumented in separate cadaveric human fore-arms (n = 3). After instrumentation and after removal of the plates duplicate HRpQCT scans were made of the region covered by the plate. HRpQCT images were visually checked for artifacts. vBMD, micro-architectural and biomechanical parameters were calculated, and compared between the uninstrumented and instrumented radii. No visible image artifacts were observed in the CFR-PEEK plate instrumented radius, and errors in bone parameters ranged from -3.2 to 2.6%. In the radii instrumented with the titanium plates, severe image artifacts were observed and errors in bone parameters ranged between -30.2 and 67.0%. We recommend using CFR-PEEK plates in longitudinal in vivo studies that monitor the healing process of unstable distal radius fractures treated operatively by plating or bone graft ingrowth.

  11. Product Architecture Modularity Strategies

    DEFF Research Database (Denmark)

    Mikkola, Juliana Hsuan

    2003-01-01

    The focus of this paper is to integrate various perspectives on product architecture modularity into a general framework, and also to propose a way to measure the degree of modularization embedded in product architectures. Various trade-offs between modular and integral product architectures...... and how components and interfaces influence the degree of modularization are considered. In order to gain a better understanding of product architecture modularity as a strategy, a theoretical framework and propositions are drawn from various academic literature sources. Based on the literature review......, the following key elements of product architecture are identified: components (standard and new-to-the-firm), interfaces (standardization and specification), degree of coupling, and substitutability. A mathematical function, termed modularization function, is introduced to measure the degree of modularization...

  12. Architecture as Ars Combinatoria

    Directory of Open Access Journals (Sweden)

    Francesco Cacciatore

    2015-11-01

    Full Text Available Architecture today, no longer reflects the limits of experimentation and innovation. An extremely low-tech art whose field of possibilities consists of choosing and using that which has already been done in the past. It is because of this that the key skill a designer should have is the ability to recognize the complexity in forms around them: cities have the widest programming opportunities for architecture, in the two-way relationship that is established from the city that takes form in architecture and an architecture that finds its place in the contemporary city. Thus, architecture has its foundation in hospitality, an element that differentiates it significantly from the design.

  13. Architecture as liminal Space

    Directory of Open Access Journals (Sweden)

    Nilly Harag

    2015-11-01

    Full Text Available The point of departure of the architectural project has to stem from the combination of inner and outer journeys in between the real or imagined limits. The pressing challenge is to destabilize the neat division of architecture into separate bodies of knowledge and pose the architect’s mode of action on the threshold between the concrete and the universal. Architecture is a lens, an instrument one looks through to bring new perspectives into focus, enabling the transformation of experience from a magnified self-concentrated space to a wide horizon. Architecture narrates relations between spaces and examines its validity through signifying practices of design. Design for itself becomes the language of the current, of the immediate fashion. Architecture can fulfill peoples’ dreams and miraculously can provide them tools to invent new ones: Curiosity is the first motive to act.

  14. Can architecture be barbaric?

    Science.gov (United States)

    Hürol, Yonca

    2009-06-01

    The title of this article is adapted from Theodor W. Adorno's famous dictum: 'To write poetry after Auschwitz is barbaric.' After the catastrophic earthquake in Kocaeli, Turkey on the 17th of August 1999, in which more than 40,000 people died or were lost, Necdet Teymur, who was then the dean of the Faculty of Architecture of the Middle East Technical University, referred to Adorno in one of his 'earthquake poems' and asked: 'Is architecture possible after 17th of August?' The main objective of this article is to interpret Teymur's question in respect of its connection to Adorno's philosophy with a view to make a contribution to the politics and ethics of architecture in Turkey. Teymur's question helps in providing a new interpretation of a critical approach to architecture and architectural technology through Adorno's philosophy. The paper also presents a discussion of Adorno's dictum, which serves for a better understanding of its universality/particularity.

  15. Casimir force between metal plate and dielectric plate

    Institute of Scientific and Technical Information of China (English)

    刘中柱; 邵成刚; 罗俊

    1999-01-01

    The Casimir effect between metal plate and dielectric plate is discussed with 1+1-dimensional potential model without using cut-off method. Calculation shows that the Casimir force between metal plate and dielectric plate is determined not only by the potential V0, the dielectric thickness and the distance α between the metal plate and dielectric plate, but also by the dimension of the vessel. When α is far less than the dimension of the vessel, the Casimir force Fc∝α(-1); conversely Fc∝α-2. This result is significant for Casimir force experiment.

  16. Minimalism in architecture: Abstract conceptualization of architecture

    Directory of Open Access Journals (Sweden)

    Vasilski Dragana

    2015-01-01

    Full Text Available Minimalism in architecture contains the idea of the minimum as a leading creative tend to be considered and interpreted in working through phenomena of empathy and abstraction. In the Western culture, the root of this idea is found in empathy of Wilhelm Worringer and abstraction of Kasimir Malevich. In his dissertation, 'Abstraction and Empathy' Worringer presented his thesis on the psychology of style through which he explained the two opposing basic forms: abstraction and empathy. His conclusion on empathy as a psychological basis of observation expression is significant due to the verbal congruence with contemporary minimalist expression. His intuition was enhenced furthermore by figure of Malevich. Abstraction, as an expression of inner unfettered inspiration, has played a crucial role in the development of modern art and architecture of the twentieth century. Abstraction, which is one of the basic methods of learning in psychology (separating relevant from irrelevant features, Carl Jung is used to discover ideas. Minimalism in architecture emphasizes the level of abstraction to which the individual functions are reduced. Different types of abstraction are present: in the form as well as function of the basic elements: walls and windows. The case study is an example of Sou Fujimoto who is unequivocal in its commitment to the autonomy of abstract conceptualization of architecture.

  17. Nuclear reactor alignment plate configuration

    Energy Technology Data Exchange (ETDEWEB)

    Altman, David A; Forsyth, David R; Smith, Richard E; Singleton, Norman R

    2014-01-28

    An alignment plate that is attached to a core barrel of a pressurized water reactor and fits within slots within a top plate of a lower core shroud and upper core plate to maintain lateral alignment of the reactor internals. The alignment plate is connected to the core barrel through two vertically-spaced dowel pins that extend from the outside surface of the core barrel through a reinforcement pad and into corresponding holes in the alignment plate. Additionally, threaded fasteners are inserted around the perimeter of the reinforcement pad and into the alignment plate to further secure the alignment plate to the core barrel. A fillet weld also is deposited around the perimeter of the reinforcement pad. To accomodate thermal growth between the alignment plate and the core barrel, a gap is left above, below and at both sides of one of the dowel pins in the alignment plate holes through with the dowel pins pass.

  18. Create Your Plate

    Medline Plus

    Full Text Available ... 1 Type 2 About Us Online Community Meal Planning Sign In Search: Search More Sites Search ≡ Are ... Fitness Home Food MyFoodAdvisor Recipes Association Cookbook Recipes Planning Meals Diabetes Meal Plans Create Your Plate Gluten ...

  19. Create Your Plate

    Medline Plus

    Full Text Available ... Create Your Plate is a simple and effective way to manage your blood glucose levels and lose weight. With ... year of delicious meals to help prevent and manage diabetes. Healthy Recipes: ... to your day with this guide. Ways to Give: Wear Your Cause on Your Sleeve - ...

  20. The Plate Tectonics Project

    Science.gov (United States)

    Hein, Annamae J.

    2011-01-01

    The Plate Tectonics Project is a multiday, inquiry-based unit that facilitates students as self-motivated learners. Reliable Web sites are offered to assist with lessons, and a summative rubric is used to facilitate the holistic nature of the project. After each topic (parts of the Earth, continental drift, etc.) is covered, the students will…

  1. Create Your Plate

    Medline Plus

    Full Text Available ... tax-deductible gift today can fund critical diabetes research and support vital diabetes education services that improve the ... way to manage your blood glucose levels and lose weight. With this method, you fill your plate with more non-starchy ...

  2. Create Your Plate

    Medline Plus

    Full Text Available ... 1 Type 2 About Us Online Community Meal Planning Sign In Search: Search More Sites Search ≡ Are ... Fitness Home Food MyFoodAdvisor Recipes Association Cookbook Recipes Planning Meals Diabetes Meal Plans Create Your Plate Gluten ...

  3. Create Your Plate

    Medline Plus

    Full Text Available ... tax-deductible gift today can fund critical diabetes research and support vital diabetes education services that improve the ... way to manage your blood glucose levels and lose weight. With this method, you fill your plate with more non-starchy ...

  4. Create Your Plate

    Medline Plus

    Full Text Available ... unsweetened tea or coffee. Featured Product Precise Portions® Go Healthy Travel Pack (4/Box) Taking the guesswork ... you are. Now, our best-selling, sectioned to-go plate with easy-sealing lid is offered in ...

  5. Create Your Plate

    Medline Plus

    Full Text Available ... manage portion control wherever you are. Now, our best-selling, sectioned to-go plate with easy-sealing lid is offered in a 4-pack. Whether ... Research & Practice We Are Research Leaders We Support Your Doctor ...

  6. INL HIP Plate Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    B. H. Park; C. R. Clark; J. F. Jue

    2010-02-01

    This document outlines the process used to bond monolithic fuel plates by Hot Isostatic Pressing (HIP). This method was developed at Idaho National Laboratory (INL) for the Reduced Enrichment for Research and Test Reactors (RERTR) program. These foils have been used in a number of irradiation experiments in support of the United States Global Threat Reduction Initiative (GTRI) program.

  7. The Plate Tectonics Project

    Science.gov (United States)

    Hein, Annamae J.

    2011-01-01

    The Plate Tectonics Project is a multiday, inquiry-based unit that facilitates students as self-motivated learners. Reliable Web sites are offered to assist with lessons, and a summative rubric is used to facilitate the holistic nature of the project. After each topic (parts of the Earth, continental drift, etc.) is covered, the students will…

  8. Create Your Plate

    Medline Plus

    Full Text Available ... Planning Meals > Create Your Plate Share: Print Page Text Size: A A A Listen En Español Create ... somewhere in between, you have an easy portion control solution that works. Last Reviewed: October 8, 2015 Last Edited: ... Cost of Diabetes Advocate Toolkit Call to Congress Research & ...

  9. Data-Centric Enterprise Architecture

    OpenAIRE

    Zeinab Rajabi; Maryam Nooraei Abade

    2012-01-01

    Enterprises choose Enterprise Architecture (EA) solution, in order to overcome dynamic business challenges and in coordinate various enterprise elements. In this article, a solution is suggested for the Enterprise Architecture development. The solution focuses on architecture data in the Enterprise Architecture development process. Data-centric architecture approach is preferred product-centric architecture approach. We suggest using Enterprise Ontology (EO) as context for collecting architec...

  10. Using Nucleofection of siRNA Constructs for Knockdown of Primary Cilia in P19.CL6 Cancer Stem Cell Differentiation into Cardiomyocytes

    DEFF Research Database (Denmark)

    Clement, Christian Alexandro; Larsen, Lars Allan; Christensen, Søren Tvorup

    2009-01-01

    Primary cilia assemble as solitary organelles in most mammalian cells during growth arrest and are thought to coordinate a series of signal transduction pathways required for cell cycle control, cell migration, and cell differentiation during development and in tissue homeostasis. Recently, primary...... cilia were suggested to control pluripotency, proliferation, and/or differentiation of stem cells, which may comprise an important source in regenerative biology. We here provide a method using a P19.CL6 embryonic carcinoma (EC) stem cell line to study the function of the primary cilium in early...... cardiogenesis. By knocking down the formation of the primary cilium by nucleofection of plasmid DNA with siRNA sequences against genes essential in ciliogenesis (IFT88 and IFT20) we block hedgehog (Hh) signaling in P19.CL6 cells as well as the differentiation of the cells into beating cardiomyocytes (Clement et...

  11. Travels in Architectural History

    Directory of Open Access Journals (Sweden)

    Davide Deriu

    2016-11-01

    Full Text Available Travel is a powerful force in shaping the perception of the modern world and plays an ever-growing role within architectural and urban cultures. Inextricably linked to political and ideological issues, travel redefines places and landscapes through new transport infrastructures and buildings. Architecture, in turn, is reconstructed through visual and textual narratives produced by scores of modern travellers — including writers and artists along with architects themselves. In the age of the camera, travel is bound up with new kinds of imaginaries; private records and recollections often mingle with official, stereotyped views, as the value of architectural heritage increasingly rests on the mechanical reproduction of its images. Whilst students often learn about architectural history through image collections, the place of the journey in the formation of the architect itself shifts. No longer a lone and passionate antiquarian or an itinerant designer, the modern architect eagerly hops on buses, trains, and planes in pursuit of personal as well as professional interests. Increasingly built on a presumption of mobility, architectural culture integrates travel into cultural debates and design experiments. By addressing such issues from a variety of perspectives, this collection, a special 'Architectural Histories' issue on travel, prompts us to rethink the mobile conditions in which architecture has historically been produced and received.

  12. Fractal Geometry of Architecture

    Science.gov (United States)

    Lorenz, Wolfgang E.

    In Fractals smaller parts and the whole are linked together. Fractals are self-similar, as those parts are, at least approximately, scaled-down copies of the rough whole. In architecture, such a concept has also been known for a long time. Not only architects of the twentieth century called for an overall idea that is mirrored in every single detail, but also Gothic cathedrals and Indian temples offer self-similarity. This study mainly focuses upon the question whether this concept of self-similarity makes architecture with fractal properties more diverse and interesting than Euclidean Modern architecture. The first part gives an introduction and explains Fractal properties in various natural and architectural objects, presenting the underlying structure by computer programmed renderings. In this connection, differences between the fractal, architectural concept and true, mathematical Fractals are worked out to become aware of limits. This is the basis for dealing with the problem whether fractal-like architecture, particularly facades, can be measured so that different designs can be compared with each other under the aspect of fractal properties. Finally the usability of the Box-Counting Method, an easy-to-use measurement method of Fractal Dimension is analyzed with regard to architecture.

  13. Avionics Architecture for Exploration Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Avionics Architectures for Exploration Project team will develop a system level environment and architecture that will accommodate equipment from multiple...

  14. Integrated Data Assimilation Architecture Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Integrated Data Assimilation Architecture (IDAA) is a middleware architecture that facilitates the incorporation of heterogeneous sensing and control devices...

  15. Reduction of oxidative stress during recovery accelerates normalization of primary cilia length that is altered after ischemic injury in murine kidneys.

    Science.gov (United States)

    Kim, Jee In; Kim, Jinu; Jang, Hee-Seong; Noh, Mi Ra; Lipschutz, Joshua H; Park, Kwon Moo

    2013-05-15

    The primary cilium is a microtubule-based nonmotile organelle that extends from the surface of cells, including renal tubular cells. Here, we investigated the alteration of primary cilium length during epithelial cell injury and repair, following ischemia/reperfusion (I/R) insult, and the role of reactive oxygen species in this alteration. Thirty minutes of bilateral renal ischemia induced severe renal tubular cell damage and an increase of plasma creatinine (PCr) concentration. Between 8 and 16 days following the ischemia, the increased PCr returned to normal range, although without complete histological restoration. Compared with the primary cilium length in normal kidney tubule cells, the length was shortened 4 h and 1 day following ischemia, increased over normal 8 days after ischemia, and then returned to near normal 16 days following ischemia. In the urine of I/R-subjected mice, acetylated tubulin was detected. The cilium length of proliferating cells was shorter than that in nonproliferating cells. Mature cells had shorter cilia than differentiating cells. Treatment with Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, during the recovery of damaged kidneys accelerated normalization of cilia length concomitant with a decrease of oxidative stress and morphological recovery in the kidney. In the Madin-Darby canine kidney (MDCK) cells, H(2)O(2) treatment caused released ciliary fragment into medium, and MnTMPyP inhibited the deciliation. The ERK inhibitor U0126 inhibited elongation of cilia in normal and MDCK cells recovering from H(2)O(2) stress. Taken together, our results suggest that primary cilia length reflects cell proliferation and the length of primary cilium is regulated, at least, in part, by reactive oxygen species through ERK.

  16. Towards Adaptive Evolutionary Architecture

    DEFF Research Database (Denmark)

    Bak, Sebastian HOlt; Rask, Nina; Risi, Sebastian

    2016-01-01

    This paper presents first results from an interdisciplinary project, in which the fields of architecture, philosophy and artificial life are combined to explore possible futures of architecture. Through an interactive evolutionary installation, called EvoCurtain, we investigate aspects of how...... to the development of designs tailored to the individual preferences of inhabitants, changing the roles of architects and designers entirely. Architecture-as-it-could-be is a philosophical approach conducted through artistic methods to anticipate the technological futures of human-centered development within...

  17. ARCHITECTURE INFORMS HISTORY

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Clusters of ancient architecture in central China have recently been entered on the world heritage list A group of ancient architecture in Dengfeng,central China’s Henan Province,was added to the world heritage list at the 34th session of the World Heritage Committee in Brazil on August 1 this year.The architectural collection is China’s 39th property inscribed on the list,and the third world heritage site in the province after the Longmen Grottoes and Yinxu in Anyang,site of the capital of the late Shang Dynasty(1600-1046 B.C.).

  18. RECONSTRUCTING DECONSTRUCTION IN ARCHITECTURE

    Directory of Open Access Journals (Sweden)

    IDHAM Noor Cholis

    2013-12-01

    Full Text Available This paper examines deconstruction in architecture and forms used, which triggered by dispute of form and its scientification claimed by deconstructivists. Deconstruction terminologyis studied in the first part related to architecture field as a base knowledge. Some sample works of known deconstructionist architects are assessed in order to understand how their building is deconstructed and what forms they used. Discussion about form and its relation to other fields is then pursued by discussing the involvement of terminology of science, aesthetic pattern, and human life. The results of this discussion give clear understanding how form related to deconstruction in architecture are used.

  19. Computer architecture technology trends

    CERN Document Server

    1991-01-01

    Please note this is a Short Discount publication. This year's edition of Computer Architecture Technology Trends analyses the trends which are taking place in the architecture of computing systems today. Due to the sheer number of different applications to which computers are being applied, there seems no end to the different adoptions which proliferate. There are, however, some underlying trends which appear. Decision makers should be aware of these trends when specifying architectures, particularly for future applications. This report is fully revised and updated and provides insight in

  20. Architectural Knitted Surfaces

    DEFF Research Database (Denmark)

    Mossé, Aurélie

    2010-01-01

    WGSN reports from the Architectural Knitted Surfaces workshop recently held at ShenkarCollege of Engineering and Design, Tel Aviv, which offered a cutting-edge insight into interactive knitted surfaces. With the increasing role of smart textiles in architecture, the Architectural Knitted Surfaces...... workshop brought together architects and interior and textile designers to highlight recent developments in intelligent knitting. The five-day workshop was led by architects Ayelet Karmon and Mette Ramsgaard Thomsen, together with Amir Cang and Eyal Sheffer from the Knitting Laboratory, in collaboration...... with Amir Marcowitz and Yair Reshef for their expertise in interaction design....

  1. One-way calcium spill-over during signal transduction in Paramecium cells: from the cell cortex into cilia, but not in the reverse direction.

    Science.gov (United States)

    Husser, Marc R; Hardt, Martin; Blanchard, Marie-Pierre; Hentschel, Joachim; Klauke, Norbert; Plattner, Helmut

    2004-11-01

    We asked to what extent Ca(2+) signals in two different domains of Paramecium cells remain separated during different stimulations. Wild-type (7S) and pawn cells (strain d4-500r, without ciliary voltage-dependent Ca(2+)-channels) were stimulated for trichocyst exocytosis within 80 ms by quenched-flow preparation and analysed by energy-dispersive X-ray microanalysis (EDX), paralleled by fast confocal fluorochrome analysis. We also analysed depolarisation-dependent calcium signalling during ciliary beat rerversal, also by EDX, after 80-ms stimulation in the quenched-flow mode. EDX and fluorochrome analysis enable to register total and free intracellular calcium concentrations, [Ca] and [Ca(2+)], respectively. After exocytosis stimulation we find by both methods that the calcium signal sweeps into the basis of cilia, not only in 7S but also in pawn cells which then also perform ciliary reversal. After depolarisation we see an increase of [Ca] along cilia selectively in 7S, but not in pawn cells. Opposite to exocytosis stimulation, during depolarisation no calcium spill-over into the nearby cytosol and no exocytosis occurs. In sum, we conclude that cilia must contain a very potent Ca(2+) buffering system and that ciliary reversal induction, much more than exocytosis stimulation, involves strict microdomain regulation of Ca(2+) signals.

  2. Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers - Manes Kartagener and Bjorn Afzelius

    Energy Technology Data Exchange (ETDEWEB)

    Berdon, Walter E. [Department of Radiology, Children' s Hospital of New York, 3959 Broadway, CHN 3-325, NY 10032, New York (United States); Willi, Ulrich [Department of Radiology, University of Zurich Children' s Hospital, Zurich (Switzerland)

    2004-01-01

    The relationship of Kartagener's syndrome to immobile cilia syndrome is a fascinating merging of clinical observations and basic science in Zurich, Stockholm, and Toronto. In 1933, Manes Kartagener, a Zurich pulmonary physician, reported four patients with the triad of sinusitis, bronchiectasis, and situs inversus. In the following decades, he reviewed reports of hundreds of cases, but the fact that the male patients with the condition never had offspring eluded his notice. In the 1970s, Bjorn Afzelius, a Ph.D. ultrastructuralist from Stockholm, reported cilia immotility in infertile males, some of the cases occurring in families. Half of the cases had Kartagener's triad. The observation of Afzelius was soon applied to children by Jennifer Sturgess, a Ph.D. ultrastructuralist, and her medical colleagues in Toronto. With over 500 MEDLINE references since 1966 on Kartagener's and over 1,000 references on immotile cilia, the causes of the pulmonary infections have become clearer as the patients demonstrate impaired clearance of mucus with resultant sinus and bronchial disease. The cause of the situs inversus remains elusive to this day. It is appropriate to call the condition Kartagener-Afzelius syndrome. (orig.)

  3. Situs inversus, bronchiectasis, and sinusitis and its relation to immotile cilia: history of the diseases and their discoverers-Manes Kartagener and Bjorn Afzelius.

    Science.gov (United States)

    Berdon, Walter E; Willi, Ulrich

    2004-01-01

    The relationship of Kartagener's syndrome to immobile cilia syndrome is a fascinating merging of clinical observations and basic science in Zurich, Stockholm, and Toronto. In 1933, Manes Kartagener, a Zurich pulmonary physician, reported four patients with the triad of sinusitis, bronchiectasis, and situs inversus. In the following decades, he reviewed reports of hundreds of cases, but the fact that the male patients with the condition never had offspring eluded his notice. In the 1970s, Bjorn Afzelius, a Ph.D. ultrastructuralist from Stockholm, reported cilia immotility in infertile males, some of the cases occurring in families. Half of the cases had Kartagener's triad. The observation of Afzelius was soon applied to children by Jennifer Sturgess, a Ph.D. ultrastructuralist, and her medical colleagues in Toronto. With over 500 MEDLINE references since 1966 on Kartagener's and over 1,000 references on immotile cilia, the causes of the pulmonary infections have become clearer as the patients demonstrate impaired clearance of mucus with resultant sinus and bronchial disease. The cause of the situs inversus remains elusive to this day. It is appropriate to call the condition Kartagener-Afzelius syndrome.

  4. Architectures of prototypes and architectural prototyping

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Michael; Sandvad, Elmer;

    1998-01-01

    together as a team, but developed a prototype that more than fulfilled the expectations of the shipping company. The prototype should: - complete the first major phase within 10 weeks, - be highly vertical illustrating future work practice, - continuously live up to new requirements from prototyping...... sessions with users, - evolve over a long period of time to contain more functionality - allow for 6-7 developers working intensively in parallel. Explicit focus on the software architecture and letting the architecture evolve with the prototype played a major role in resolving these conflicting......This paper reports from experience obtained through development of a prototype of a global customer service system in a project involving a large shipping company and a university research group. The research group had no previous knowledge of the complex business of shipping and had never worked...

  5. Architectures of prototypes and architectural prototyping

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Michael; Sandvad, Elmer

    1998-01-01

    This paper reports from experience obtained through development of a prototype of a global customer service system in a project involving a large shipping company and a university research group. The research group had no previous knowledge of the complex business of shipping and had never worked...... together as a team, but developed a prototype that more than fulfilled the expectations of the shipping company. The prototype should: - complete the first major phase within 10 weeks, - be highly vertical illustrating future work practice, - continuously live up to new requirements from prototyping...... sessions with users, - evolve over a long period of time to contain more functionality - allow for 6-7 developers working intensively in parallel. Explicit focus on the software architecture and letting the architecture evolve with the prototype played a major role in resolving these conflicting...

  6. MyPlate Food Guide

    Science.gov (United States)

    ... Choosing the Right Sport for You Shyness MyPlate Food Guide KidsHealth > For Teens > MyPlate Food Guide Print ... other sugary drinks. Avoid oversized portions. continue Five Food Groups Different food groups meet different nutrition needs. ...

  7. What Are Growth Plate Injuries?

    Science.gov (United States)

    ... plate injuries are:  Falling down  Competitive sports (like football)  Recreational activities. Other reasons for growth plate injuries are:  Child abuse  Injury from extreme cold (for ...

  8. Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

    NARCIS (Netherlands)

    Harrison, Neil B.; Avgeriou, Paris

    2008-01-01

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

  9. Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

    NARCIS (Netherlands)

    Harrison, Neil B.; Avgeriou, Paris

    2008-01-01

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

  10. Thermal Space in Architecture

    DEFF Research Database (Denmark)

    Petersen, Mads Dines

    Present research is revolving around the design process and the use of digital applications to support the design process among architects. This work is made in relation to the current discussions about sustainable architecture and the increased focus on energy consumption and the comfort in our...... and understanding of spaces in buildings can change significantly and instead of the creation of frozen geometrical spaces, thermal spaces can be created as it is suggested in meteorological architecture where functions are distributed in relation to temperature gradients. This creates an interesting contrast......-introducing an increased adaptability in the architecture can be a part of re-defining the environmental agenda and re-establish a link between the environment of the site and the environment of the architecture and through that an increased appreciation of the sensuous space here framed in discussions about thermal...

  11. Performative Urban Architecture

    DEFF Research Database (Denmark)

    Thomsen, Bo Stjerne; Jensen, Ole B.

    The paper explores how performative urban architecture can enhance community-making and public domain using socio-technical systems and digital technologies to constitute an urban reality. Digital medias developed for the web are now increasingly occupying the urban realm as a tool for navigating...... using sensor technologies opening up for new access considerations in architecture as well as the ability for a local environment to act as real-time sources of information and facilities. Starting from the NoRA pavilion for the 10th International Architecture Biennale in Venice the paper discusses...... couple relationships between architecture, humans and society. These performative relationships between digital and physical environments are seen as illustrative of the social production of space by performance and the creative production of identity. The paper reflects on the perspectives...

  12. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  13. Architecture for the senses

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2009-01-01

    findings from the PhD thesis 'A House for the Senses' by the author, a study of architectural requirements in housing design implied by a sensory impairment. The empirical research project is based on qualitative interviews and 1:1 testing in existing housing with participants who were either blind, deaf......Accommodating sensory disabilities in architectural design requires specific design considerations. These are different from the ones included by the existing design concept 'accessibility', which primarily accommodates physical disabilites. Hence a new design concept 'sensory accessbility......' is presented as a parallel and complementary concept to the existing one. Sensory accessiblity accommodates sensory disabilities and describes architectural design requirements needed to ensure access to to the sensory experiences and architectural quality of a given space. The article is based on research...

  14. Analyzing architecture articles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In the present study, we express the quality, function, and characteristics of architecture to help people comprehensively understand what architecture is. We also reveal the problems and conflict found in population, land, water resources, pollution, energy, and the organization systems in construction. China’s economy is transforming. We should focus on the cities, architectural environment, energy conservation, emission-reduction, and low-carbon output that will result in successful green development. We should macroscopically and microscopically analyze the development, from the natural environment to the artificial environment; from the relationship between human beings and nature to the combination of social ecology in cities, and farmlands. We must learn to develop and control them harmoniously and scientifically to provide a foundation for the methods used in architecture research.

  15. The toolbus coordination architecture

    NARCIS (Netherlands)

    Bergstra, J.A.; Klint, P.

    1996-01-01

    Building large, heterogeneous, distributed software systems poses serious problems for the software engineer; achieving interoperability of software systems is still a major challenge. We describe an experiment in designing a generic software architecture for solving these problems. To get

  16. Art and Architectural Space

    DEFF Research Database (Denmark)

    Unterrainer, Walter

    2014-01-01

    art and architectural space museums and other exhibition spaces or how artists learn to love architects Over the last two decades, innumerable new museums, art galleries and other exhibition spaces have been built and opened all over the globe. The most extreme growth happened in China, where...... the promotion of tourism. What surprises: in many cities, the buildings for art are better known and more published and discussed than the art they accommodate. A lot of them are considered as art objects. This raises two questions: How much is architecture itself a form of arts? (in Western architecture...... historically considered even the mother of all arts) - but more relevant: what are appropriate architectural spaces for presenting, exhibiting, contemplating, reflecting, meditating, discussing, enjoying, dissenting, debating creations of art. Simplified, this is a question about the relation between package...

  17. Ancient Chinese Architecture

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    CHINESE people have accu-mulated a great deal ofexperience in architecture,constantly improving building ma-terials and thus creating uniquebuilding styles.The history of ancient Chinesearchitechtural development can be

  18. Robot Electronics Architecture

    Science.gov (United States)

    Garrett, Michael; Magnone, Lee; Aghazarian, Hrand; Baumgartner, Eric; Kennedy, Brett

    2008-01-01

    An electronics architecture has been developed to enable the rapid construction and testing of prototypes of robotic systems. This architecture is designed to be a research vehicle of great stability, reliability, and versatility. A system according to this architecture can easily be reconfigured (including expanded or contracted) to satisfy a variety of needs with respect to input, output, processing of data, sensing, actuation, and power. The architecture affords a variety of expandable input/output options that enable ready integration of instruments, actuators, sensors, and other devices as independent modular units. The separation of different electrical functions onto independent circuit boards facilitates the development of corresponding simple and modular software interfaces. As a result, both hardware and software can be made to expand or contract in modular fashion while expending a minimum of time and effort.

  19. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up concept......Recent years have seen an increasing variety of applications of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability....... The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or two...

  20. Bionics in architecture

    Directory of Open Access Journals (Sweden)

    Sugár Viktória

    2017-04-01

    Full Text Available The adaptation of the forms and phenomena of nature is not a recent concept. Observation of natural mechanisms has been a primary source of innovation since prehistoric ages, which can be perceived through the history of architecture. Currently, this idea is coming to the front again through sustainable architecture and adaptive design. Investigating natural innovations and the clear-outness of evolution during the 20th century led to the creation of a separate scientific discipline, Bionics. Architecture and Bionics are strongly related to each other, since the act of building is as old as the human civilization - moreover its first formal and structural source was obviously the surrounding environment. Present paper discusses the definition of Bionics and its connection with the architecture.

  1. Japan's radiant architecture

    National Research Council Canada - National Science Library

    Ruairí O'Brien

    2014-01-01

    .... If Japanese architecture in the last century could be seen as an expression of fast growth, destruction, rebirth and expansion, today's Japan promises to deliver a new hybrid of high and low tech...

  2. Cartography of architectural controversies

    DEFF Research Database (Denmark)

    Lotz, Katrine

    2009-01-01

    How can buildings be perceived not only for their properties as stable objects and spatial organisation, but also and at the same time as series of transformations, as socio-material orderings, as movements? Coming from a background in architecture and architectural theory I propose that spatial...... on the visual materials and documents produced during the process, and interviews with architects, clients and engineers, I describe the continuous efforts to establish and strengthen architectural motives, and how they eventually gain the ability to align other motives and other actors. I suggest...... that employing the visualising methods of the recent development of Actor-Network-Theory called ‘Cartography of Controversies' might contribute to trans-disciplinary efforts to develop analytic understanding of the conflicting human purposes and power-struggles at stake in the be-coming of architecture....

  3. Controlling Laminate Plate Elastic Behavior

    OpenAIRE

    Mareš, T.

    2004-01-01

    This paper aims to express the relation of a measure of laminate plate stiffness with respect to the fiber orientation of its plies. The inverse of the scalar product of the lateral displacement of the central plane and lateral loading of the plate is the measure of laminate plate stiffness. In the case of a simply supported rectangular laminate plate this measure of stiffness is maximized, and the optimum orientation of its plies is searched.

  4. Microchannel plate streak camera

    Science.gov (United States)

    Wang, Ching L.

    1989-01-01

    An improved streak camera in which a microchannel plate electron multiplier is used in place of or in combination with the photocathode used in prior streak cameras. The improved streak camera is far more sensitive to photons (UV to gamma-rays) than the conventional x-ray streak camera which uses a photocathode. The improved streak camera offers gamma-ray detection with high temporal resolution. It also offers low-energy x-ray detection without attenuation inside the cathode. Using the microchannel plate in the improved camera has resulted in a time resolution of about 150 ps, and has provided a sensitivity sufficient for 1000 KeV x-rays.

  5. BioArchitecture

    OpenAIRE

    Gunning, Peter

    2012-01-01

    Volume 1 has defined the scope of BioArchitecture. From the outset we have strived to ensure that BioArchitecture is not limited to the three major polymer systems of the cytoplasm. I am happy to say that a cursory glance at the contents of volume 1 makes it clear that we are interested in all aspects of bioarchitecture from molecules to polymers to cells to tissue to the organism.

  6. Essential software architecture

    CERN Document Server

    Gorton, Ian

    2011-01-01

    Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i

  7. Artificial cognition architectures

    CERN Document Server

    Crowder, James A; Friess, Shelli A

    2013-01-01

    The goal of this book is to establish the foundation, principles, theory, and concepts that are the backbone of real, autonomous Artificial Intelligence. Presented here are some basic human intelligence concepts framed for Artificial Intelligence systems. These include concepts like Metacognition and Metamemory, along with architectural constructs for Artificial Intelligence versions of human brain functions like the prefrontal cortex. Also presented are possible hardware and software architectures that lend themselves to learning, reasoning, and self-evolution

  8. A Multitouch Software Architecture

    OpenAIRE

    Florian Echtler; Gudrun Klinker

    2017-01-01

    In recent years, a large amount of software for multitouch in- terfaces with various degrees of similarity has been written. In order to improve interoperability, we aim to identify the common traits of these systems and present a layered soft- ware architecture which abstracts these similarities by defin- ing common interfaces between these layers. This provides developers with a unified view of the various types of mul- titouch hardware. Moreover, the layered architecture allows easy integr...

  9. ARCHITECTURE INFORMS HISTORY

    Institute of Scientific and Technical Information of China (English)

    ZAN JIFANG

    2010-01-01

    @@ Agroup of ancient architecture in Dengfeng, central China's Henan Province, was added to the world heritage list at the 34th session of the World Heritage Committee in Brazil on August 1 this year. The architectural col-lection is China's 39th property inscribed on the list, and the third world heritage site in the province after the Longmen Grottoes and Yinxu in Anyang, site of the capital of the late Shang Dynasty (1600-1046 B.C.).

  10. Greek architecture now

    DEFF Research Database (Denmark)

    Skousbøll, Karin Merete

    2006-01-01

    With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas.......With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas....

  11. Climate and architecture

    DEFF Research Database (Denmark)

    Tind Kristensen, Eva; Friis Møller, Winnie; Rotne, Georg

    2010-01-01

    Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder.......Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder....

  12. Electronic Equipment Cold Plates

    Science.gov (United States)

    1976-04-01

    equations for such a flow regiae. For laainar flow and Moderate teaperature differwwe« between the well «nd coolant, a aodifled Sieder -Tate...con- figuration. The heat-transfer coefficients, therefore, were determined by using both the Sieder -Tate and McAdams equations and the coaputed...values used In the analytical predictions. As with th* previous cold Plates, the Sieder -Tate equation gave too low of values for the heat- transfer

  13. Elastic plate spallation

    Science.gov (United States)

    Oline, L.; Medaglia, J.

    1972-01-01

    The dynamic finite element method was used to investigate elastic stress waves in a plate. Strain displacement and stress strain relations are discussed along with the stiffness and mass matrix. The results of studying point load, and distributed load over small, intermediate, and large radii are reported. The derivation of finite element matrices, and the derivation of lumped and consistent matrices for one dimensional problems with Laplace transfer solutions are included. The computer program JMMSPALL is also included.

  14. Plate Tearing by a Cone

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1997-01-01

    The present paper is concerned with steady-state plate tearing by a cone. This is a scenario where a cone is forced through a ductile metal plate with a constant lateral tip penetration in a motion in the plane of the plate. The considered process could be an idealisaton of the damage, which...

  15. Plate Tearing by a Cone

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1998-01-01

    The present paper is concerned with steady-state plate tearing by a cone. This is a scenario where a cone is forced through a ductile metal plate with a constant lateral tip penetration in a motion in the plane of the plate. The considered process could be an idealisation of the damage, which...

  16. Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands.

    Science.gov (United States)

    Ruiz-Perez, Victor L; Goodship, Judith A

    2009-11-15

    Ellis-van Creveld syndrome (EvC; OMIM 225500) is a recessive disorder comprising chondrodysplasia, polydactyly, nail dysplasia, orofacial abnormalities and, in a proportion of patients, cardiovascular malformations. Weyers acrodental dysostosis (Weyers; OMIM 193530) is an allelic dominant disorder comprising polydactyly, nail dysplasia, and orofacial abnormalities. EvC results from loss-of-function mutations in EVC or EVC2, the phenotype associated with the mutations in these two genes being indistinguishable. Three convincing causative mutations have been identified in patients with Weyers acrodental dysostosis, which are clustered in the last coding exon of EVC2 and lead to production of a truncated protein lacking the final 43 amino acids. Localization and function of EVC and EVC2 are inferred from studying the murine orthologs. Both Evc and Evc2 proteins localize to the basal bodies of primary cilia and analysis of an Ellis-van Creveld mouse model, which includes the limb shortening and tooth abnormalities of EvC patients, has demonstrated Hedgehog signaling defects in the absence of Evc. The loss of Evc2 has not been studied directly, but Hedgehog signaling is impaired when a mutant murine Evc2 Weyer variant is expressed in vitro. We conclude that the phenotypic abnormalities in EvC and Weyers syndrome result from tissue specific disruption of the response to Hh ligands.

  17. Construction of (001) facets exposed ZnO nanosheets on magnetically driven cilia film for highly active photocatalysis

    Science.gov (United States)

    Peng, Fengping; Zhou, Qiang; Lu, Chunhua; Ni, Yaru; Kou, Jiahui; Xu, Zhongzi

    2017-02-01

    ZnO nanosheet arrays with exposed (001) facets have been constructed onto a biomimetic inner-motile film, using a seed-mediated hydrothermal growth technology without adding capping agents. The growth of ZnO nanoparticles along the [001] direction is impeded because of a physical steric hindrance, and therefore (001) planes are left behind as the dominant crystal facets. In comparison to ZnO nanorod arrays film, the photocatalytic activity of the actuated (001) facets exposed ZnO nanosheet arrays film is dramatically improved to approximately 2.48 times. Moreover, when it is subjected to a rotational magnetic field, the ZnO nanosheet arrays film is driven to mimic ciliary motion like nature beating cilia, which can boost the interior mass transfer and help to promote release of active sites for improving the photocatalytic activity. As a consequence of the exposed (001) high active facets, the singular ability of microfluidic manipulation has greater effect on ZnO nanosheet arrays films. The enhancement of photocatalytic activity of the actuated ZnO nanosheet arrays film is much more than that of ZnO nanorod arrays film.

  18. Manipulation of zebrafish’s orientation using artificial cilia in a microchannel with actively adaptive wall design

    Science.gov (United States)

    Mani, Karthick; Chang Chien, Tsung-Chun; Panigrahi, Bivas; Chen, Chia-Yuan

    2016-11-01

    The zebrafish is a powerful genetic model organism especially in the biomedical chapter for new drug discovery and development. The genetic toolbox which this vertebrate possesses opens a new window to investigate the etiology of human diseases with a high degree genetic similarity. Still, the requirements of laborious and time-consuming of contemporary zebrafish processing assays limit the procedure in carrying out such genetic screen at high throughput. Here, a zebrafish control scheme was initiated which includes the design and validation of a microfluidic platform to significantly increase the throughput and performance of zebrafish larvae manipulation using the concept of artificial cilia actuation. A moving wall design was integrated into this microfluidic platform first time in literature to accommodate zebrafish inside the microchannel from 1 day post-fertilization (dpf) to 6 dpf and can be further extended to 9 dpf for axial orientation control in a rotational range between 0 to 25 degrees at the minimum step of 2-degree increment in a stepwise manner. This moving wall feature was performed through the deflection of shape memory alloy wire embedded inside the microchannel controlled by the electrical waveforms with high accuracy.

  19. Time · Space · Architecture

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In the 20th century a Swiss writer wrote a book titled Time, Space and Architecture, in which he discussed the relationship between architecture and the times. Fifty years after that, this paper adopts the same title, hoping to deepen the understanding of the space-time structure in architecture and contribute to the new exploration of architectural forms.

  20. New Energy Architecture. Myanmar

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    A global transition towards a new energy architecture is under way, driven by countries' need to respond to the changing dynamics of economic growth, environmental sustainability and energy security. The World Economic Forum, in collaboration with Accenture, has created the New Energy Architecture Initiative to address and accelerate this transition. The Initiative supports the development of national strategies and policy frameworks as countries seek to achieve the combined goals of energy security and access, sustainability, and economic growth and development. The World Economic Forum has formed a partnership with the Ministry of Energy of Myanmar to help apply the Initiative's approach to this developing and resource-rich nation. The Asian Development Bank and the World Economic Forum's Project Adviser, Accenture, have collaborated with the Forum on this consultation process, and have been supported by relevant government, industry and civil society stakeholders. The consultation process aims to understand the nation's current energy architecture challenges and provide an overview of a path to a New Energy Architecture through a series of insights. These insights could form the basis for a long-term multistakeholder roadmap to build Myanmar's energy sector in a way that is secure and sustainable, and promotes economic growth as the country makes its democratic transition. While not all recommendations can be implemented in the near term, they do provide options for creating a prioritized roadmap for Myanmar's energy transition. This report is the culmination of a nine-month multistakeholder process investigating Myanmar's energy architecture. Over the course of many visits to the country, the team has conducted numerous interviews, multistakeholder workshops, and learning and data-gathering exercises to ensure a comprehensive range of information and views. The team has also engaged with a variety of stakeholders to better

  1. Plate tectonics conserves angular momentum

    Directory of Open Access Journals (Sweden)

    C. Bowin

    2009-03-01

    Full Text Available A new combined understanding of plate tectonics, Earth internal structure, and the role of impulse in deformation of the Earth's crust is presented. Plate accelerations and decelerations have been revealed by iterative filtering of the quaternion history for the Euler poles that define absolute plate motion history for the past 68 million years, and provide an unprecedented precision for plate angular rotation variations with time at 2-million year intervals. Stage poles represent the angular rotation of a plate's motion between adjacent Euler poles, and from which the maximum velocity vector for a plate can be determined. The consistent maximum velocity variations, in turn, yield consistent estimates of plate accelerations and decelerations. The fact that the Pacific plate was shown to accelerate and decelerate, implied that conservation of plate tectonic angular momentum must be globally conserved, and that is confirmed by the results shown here (total angular momentum ~1.4 E+27 kgm2s−1. Accordingly, if a plate decelerates, other plates must increase their angular momentums to compensate. In addition, the azimuth of the maximum velocity vectors yields clues as to why the "bend" in the Emperor-Hawaiian seamount trend occurred near 46 Myr. This report summarizes processing results for 12 of the 14 major tectonic plates of the Earth (except for the Juan de Fuca and Philippine plates. Plate accelerations support the contention that plate tectonics is a product of torques that most likely are sustained by the sinking of positive density anomalies due to phase changes in subducted gabbroic lithosphere at depth in the upper lower mantle (above 1200 km depth. The tectonic plates are pulled along by the sinking of these positive mass anomalies, rather than moving at near constant velocity on the crests of convection cells driven by rising heat. These results imply that spreading centers are primarily passive reactive

  2. Vehicle License Plate Recognition Syst

    Directory of Open Access Journals (Sweden)

    Meenakshi,R. B. Dubey

    2012-12-01

    Full Text Available The vehicle license plate recognition system has greater efficiency for vehicle monitoring in automatic zone access control. This Plate recognition system will avoid special tags, since all vehicles possess a unique registration number plate. A number of techniques have been used for car plate characters recognition. This system uses neural network character recognition and pattern matching of characters as two character recognition techniques. In this approach multilayer feed-forward back-propagation algorithm is used. The performance of the proposed algorithm has been tested on several car plates and provides very satisfactory results.

  3. Using plate mapping to examine portion size and plate composition for large and small divided plates.

    Science.gov (United States)

    Sharp, David E; Sobal, Jeffery; Wansink, Brian

    2014-12-01

    Does the size of a plate influence the serving of all items equally, or does it influence the serving of some foods - such as meat versus vegetables - differently? To examine this question, we used the new method of plate mapping, where people drew a meal on a paper plate to examine sensitivity to small versus large three-compartment divided plates in portion size and meal composition in a sample of 109 university students. The total drawn meal area was 37% bigger on large plates than small plates, which showed that the portion of plate coverage did not differ by plate size. Men and women drew bigger vegetable portions and men drew bigger meat portions on large plates when compared to small plates. These results suggest that men and women are differentially sensitive to plate size for overall meal size and for meal composition. Implications for decreasing portion size and improving meal balance are that plate size may influence portion size and change the proportions of foods served.

  4. Comparing root architectural models

    Science.gov (United States)

    Schnepf, Andrea; Javaux, Mathieu; Vanderborght, Jan

    2017-04-01

    Plant roots play an important role in several soil processes (Gregory 2006). Root architecture development determines the sites in soil where roots provide input of carbon and energy and take up water and solutes. However, root architecture is difficult to determine experimentally when grown in opaque soil. Thus, root architectural models have been widely used and been further developed into functional-structural models that are able to simulate the fate of water and solutes in the soil-root system (Dunbabin et al. 2013). Still, a systematic comparison of the different root architectural models is missing. In this work, we focus on discrete root architecture models where roots are described by connected line segments. These models differ (a) in their model concepts, such as the description of distance between branches based on a prescribed distance (inter-nodal distance) or based on a prescribed time interval. Furthermore, these models differ (b) in the implementation of the same concept, such as the time step size, the spatial discretization along the root axes or the way stochasticity of parameters such as root growth direction, growth rate, branch spacing, branching angles are treated. Based on the example of two such different root models, the root growth module of R-SWMS and RootBox, we show the impact of these differences on simulated root architecture and aggregated information computed from this detailed simulation results, taking into account the stochastic nature of those models. References Dunbabin, V.M., Postma, J.A., Schnepf, A., Pagès, L., Javaux, M., Wu, L., Leitner, D., Chen, Y.L., Rengel, Z., Diggle, A.J. Modelling root-soil interactions using three-dimensional models of root growth, architecture and function (2013) Plant and Soil, 372 (1-2), pp. 93 - 124. Gregory (2006) Roots, rhizosphere and soil: the route to a better understanding of soil science? European Journal of Soil Science 57: 2-12.

  5. Temperature field of steel plate cooling process after plate rolling

    Directory of Open Access Journals (Sweden)

    Huijun Feng, Lingen Chen, Fengrui Sun

    2015-01-01

    Full Text Available Based on numerical calculation with Matlab, the study on cooling process after plate rolling is carried out, and the temperature field distribution of the plate varying with the time is obtained. The effects of the plate thickness, final rolling temperature, cooling water temperature, average flow rate of the cooling water, carbon content of the plate and cooling method on the plate surface and central temperatures as well as final cooling temperature are discussed. For the same cooling time, the plate surface and central temperatures as well as their temperature difference increase; with the decrease in rolling temperature and the increase in average flow rate of the cooling water, the plate surface and central temperatures decrease. Compared with the single water cooling process, the temperature difference between the plate centre and surface based on intermittent cooling is lower. In this case, the temperature uniformity of the plate is better, and the corresponding thermal stress is lower. The fitting equation of the final cooling temperature with respect to plate thickness, final rolling temperature, cooling water temperature and average flow rate of the cooling water is obtained.

  6. Real Plates and Dubious Microplates

    Science.gov (United States)

    Kogan, M. G.; Steblov, G. M.

    2008-12-01

    From the onset of plate tectonics, the existence of most of the plates was never put in doubt, although the boundaries of some plates, like Africa, were later revised. There are however, two microplates in northeast Asia, the Amurian and Okhotsk, whose existence and the sense of rotation was revised several times. The rms value of plate-residual GPS velocities is 0.5-0.9 mm/a for sets of stations representing the motion of the following plates: Antarctic, Australian, Eurasian, North American, Nubian, Pacific, and South American. This value can be regarded as an upper bound on deviation of real plates from infinite stiffness. The rms value of plate-residual GPS velocities is 1.2-1.8 mm/a for the Indian, Nazca, and Somalian plates. Higher rms values for India and Nazca are attributed to the noisier data. The higher rms value for Somalia appears to arise from the distributed deformation to the east of the East African Rift; whether this statement is true can only be decided from observations of denser network in the future. From the analysis of plate-residual GPS velocities, the Canadian Arctic and northeastern Siberia belong to the North American plate. The detailed GPS survey on Sakhalin Island shows that the Sea of Okhotsk region also belongs to the North American plate while the region to the west of it belongs to the Eurasian plate. These results provide a constraint on the geometry of the North American plate and put in doubt the existence of smaller plates in northeast Asia.

  7. The Simulation Intranet Architecture

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, V.P.; Linebarger, J.M.; Miller, D.J.; Vandewart, R.L.

    1998-12-02

    The Simdarion Infranet (S1) is a term which is being used to dcscribc one element of a multidisciplinary distributed and distance computing initiative known as DisCom2 at Sandia National Laboratory (http ct al. 1998). The Simulation Intranet is an architecture for satisfying Sandia's long term goal of providing an end- to-end set of scrviccs for high fidelity full physics simu- lations in a high performance, distributed, and distance computing environment. The Intranet Architecture group was formed to apply current distributed object technologies to this problcm. For the hardware architec- tures and software models involved with the current simulation process, a CORBA-based architecture is best suited to meet Sandia's needs. This paper presents the initial desi-a and implementation of this Intranct based on a three-tier Network Computing Architecture(NCA). The major parts of the architecture include: the Web Cli- ent, the Business Objects, and Data Persistence.

  8. Globalization and Landscape Architecture

    Directory of Open Access Journals (Sweden)

    Robert R. Hewitt

    2014-02-01

    Full Text Available The literature review examines globalization and landscape architecture as discourse, samples its various meanings, and proposes methods to identify and contextualize its specific literature. Methodologically, the review surveys published articles and books by leading authors and within the WorldCat.org Database associated with landscape architecture and globalization, analyzing survey results for comprehensive conceptual and co-relational frameworks. Three “higher order” dimensions frame the review’s conceptual organization, facilitating the organization of subordinate/subtopical areas of interest useful for comparative analysis. Comparative analysis of the literature suggests an uneven clustering of discipline-related subject matter across the literature’s “higher order” dimensions, with a much smaller body of literature related to landscape architecture confined primarily to topics associated with the dispersion of global phenomena. A subcomponent of this smaller body of literature is associated with other fields of study, but inferentially related to landscape architecture. The review offers separate references and bibliographies for globalization literature in general and globalization and landscape architecture literature, specifically.

  9. Service Modularity and Architecture

    DEFF Research Database (Denmark)

    Brax, Saara A.; Bask, Anu; Hsuan, Juliana

    2017-01-01

    Purpose: Services are highly important in a world economy which has increasingly become service driven. There is a growing need to better understand the possibilities for, and requirements of, designing modular service architectures. The purpose of this paper is to elaborate on the roots of the e......Purpose: Services are highly important in a world economy which has increasingly become service driven. There is a growing need to better understand the possibilities for, and requirements of, designing modular service architectures. The purpose of this paper is to elaborate on the roots...... of the emerging research stream on service modularity, provide a concise overview of existing work on the subject, and outline an agenda for future research on service modularity and architecture. The articles in the special issue offer four diverse sets of research on service modularity and architecture. Design....../methodology/approach: The paper is built on a literature review mapping the current body of literature on the topic and developing future research directions in service modularity and architecture. Findings: The growing focus on services has triggered needs to investigate the suitability and implementation of physical...

  10. Base Camp Architecture

    Directory of Open Access Journals (Sweden)

    Warebi Gabriel Brisibe

    2016-03-01

    Full Text Available Longitudinal or time line studies of change in the architecture of a particular culture are common, but an area still open to further research is change across space or place. In particular, there is need for studies on architectural change of cultures stemming from the same ethnic source split between their homeland and other Diasporas. This change may range from minor deviations to drastic shifts away from an architectural norm and the accumulation of these shifts within a time frame constitutes variations. This article focuses on identifying variations in the architecture of the Ijo fishing group that migrates along the coastline of West Africa. It examines the causes of cross-cultural variation between base camp dwellings of Ijo migrant fishermen in the Bakassi Peninsula in Cameroon and Bayelsa State in Nigeria. The study draws on the idea of the inevitability of cultural and social change over time as proposed in the theories of cultural dynamism and evolution. It tests aspects of cultural transmission theory using the principal coordinates analysis to ascertain the possible causes of variation. From the findings, this research argues that migration has enhanced the forces of cultural dynamism, which have resulted in significant variations in the architecture of this fishing group.

  11. Plate Full of Color

    Centers for Disease Control (CDC) Podcasts

    2008-08-04

    The Eagle Books are a series of four books that are brought to life by wise animal characters - Mr. Eagle, Miss Rabbit, and Coyote - who engage Rain That Dances and his young friends in the joy of physical activity, eating healthy foods, and learning from their elders about health and diabetes prevention. Plate Full of Color teaches the value of eating a variety of colorful and healthy foods.  Created: 8/4/2008 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 8/5/2008.

  12. Dynamics of Tectonic Plates

    CERN Document Server

    Pechersky, E; Sadowski, G; Yambartsev, A

    2014-01-01

    We suggest a model that describes a mutual dynamic of tectonic plates. The dynamic is a sort of stick-slip one which is modeled by a Markov random process. The process defines a microlevel of the dynamic. A macrolevel is obtained by a scaling limit which leads to a system of integro-differential equations which determines a kind of mean field systems. Conditions when Gutenberg-Richter empirical law are presented on the mean field level. These conditions are rather universal and do not depend on features of resistant forces.

  13. Dynamics of Tectonic Plates

    OpenAIRE

    2014-01-01

    We suggest a model that describes a mutual dynamic of tectonic plates. The dynamic is a sort of stick-slip one which is modeled by a Markov random process. The process defines a microlevel of the dynamic. A macrolevel is obtained by a scaling limit which leads to a system of integro-differential equations which determines a kind of mean field systems. Conditions when Gutenberg-Richter empirical law are presented on the mean field level. These conditions are rather universal and do not depend ...

  14. Architecture of Environmental Engineering

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Alting, Leo

    2004-01-01

    An architecture of Environmental Engineering has been developed comprising the various disciplines and tools involved. It identifies industry as the major actor and target group, and it builds on the concept of Eco-efficiency. To improve Eco-efficiency, there is a limited number of intervention...... of Eco-efficiency is the aim of Environmental Engineering, the discipline of synthesis – design and creation of solutions – will form a core pillar of the architecture. Other disciplines of Environmental Engineering exist forming the necessary background and frame for the synthesis. Environmental...... Engineering, thus, in essence comprise the disciplines of: management, system description & inventory, analysis & assessment, prioritisation, synthesis, and communication, each existing at all levels of intervention. The developed architecture of Environmental Engineering, thus, consists of thirty individual...

  15. Architecture of Environmental Engineering

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Alting, Leo

    2006-01-01

    An architecture of Environmental Engineering has been developed comprising the various disciplines and tools involved. It identifies industry as the major actor and target group, and it builds on the concept of Eco-efficiency. To improve Eco-efficiency, there is a limited number of intervention......-efficiency is the aim of Environmental Engineering, the discipline of synthesis – design and creation of solutions – will form a core pillar of the architecture. Other disciplines of Environmental Engineering exist forming the necessary background and frame for the synthesis. Environmental Engineering, thus, in essence...... comprise the disciplines of: management, system description & inventory, analysis & assessment, prioritisation, synthesis, and communication, each existing at all levels of intervention. The developed architecture of Environmental Engineering, thus, consists of thirty individual disciplines, within each...

  16. Architecture of Environmental Engineering

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Alting, Leo

    2004-01-01

    An architecture of Environmental Engineering has been developed comprising the various disciplines and tools involved. It identifies industry as the major actor and target group, and it builds on the concept of Eco-efficiency. To improve Eco-efficiency, there is a limited number of intervention...... of Eco-efficiency is the aim of Environmental Engineering, the discipline of synthesis – design and creation of solutions – will form a core pillar of the architecture. Other disciplines of Environmental Engineering exist forming the necessary background and frame for the synthesis. Environmental...... Engineering, thus, in essence comprise the disciplines of: management, system description & inventory, analysis & assessment, prioritisation, synthesis, and communication, each existing at all levels of intervention. The developed architecture of Environmental Engineering, thus, consists of thirty individual...

  17. Ancient Chinese Landscape Architecture

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    IN the past decade,the worldhas suddenly discovered thewonders of Chinese landscapegardening and garden architecture,and places like New York,Singaporeand London have all built Chinese-style gardens.The architectural stylespecial to Chinese gardens has,infact,developed·a“school”of itsown.In China,the landscaped gardenhas long been a part of culture,andliterature,painting,philosophy,cal-ligraphy and folk customs have alldealt with it at one time or another.Two categories of garden architec-ture exist:the imperial garden andthe private garden.The former is,ofcourse,grand and palatial and occu-pies large tracts of land,while the

  18. Agent Architectures for Compliance

    Science.gov (United States)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  19. Towards an Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    2016-01-01

    their overlaps and collaboration. However, there are also challenging differences to take into account regarding disciplinary traditions of, for example, communication, temporality, and normativity. This article explores the potentials and challenges of architectural anthropology as a distinct sub......Architecture and anthropology have always had overlapping interests regarding issues such as spatial organisation, forms of human dwellings, and the interplay between social life and physical surroundings. Recent developments in both disciplines make it even more relevant to explore and evolve......-discipline and outlines its possible theoretical, methodological, and applied contributions. It is proposed that the ambition to understand people in a different way than they understand themselves is key in both disciplines, and that architectural anthropology is consequently not only relevant in studies of vernacular...

  20. Towards an Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    2017-01-01

    Architecture and anthropology have always had overlapping interests regarding issues such as spatial organisation, forms of human dwellings, and the interplay between social life and physical surroundings. Recent developments in both disciplines make it even more relevant to explore and evolve...... their overlaps and collaboration. However, there are also challenging differences to take into account regarding disciplinary traditions of, for example, communication, temporality, and normativity. This article explores the potentials and challenges of architectural anthropology as a distinct sub......-discipline and outlines its possible theoretical, methodological, and applied contributions. It is proposed that the ambition to understand people in a different way than they understand themselves is key in both disciplines, and that architectural anthropology is consequently not only relevant in studies of vernacular...

  1. Persian architecture and mathematics

    CERN Document Server

    2012-01-01

    This volulme features eight original papers dedicated to the theme “Persian Architecture and Mathematics,” guest edited by Reza Sarhangi. All papers were approved through a rigorous process of blind peer review and edited by an interdisciplinary scientific editorial committee. Topics range from symmetry in ancient Persian architecture to the elaborate geometric patterns and complex three-dimensional structures of standing monuments of historical periods, from the expression of mathematical ideas to architectonic structures, and from decorative ornament to the representation of modern group theory and quasi-crystalline patterns. The articles discuss unique monuments Persia, including domed structures and two-dimensional patterns, which have received significant scholarly attention in recent years. This book is a unique contribution to studies of Persian architecture in relation to mathematics.

  2. Information architecture. Volume 3: Guidance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

  3. CMS Resistive plate Champers

    CERN Document Server

    Zainab, Karam

    2013-01-01

    There are many types of gas detectors which are used in CERN in LHC project, There is a main parts for the gas detectors which must be in all gas detectors types like Multiwire proportional chambers, such as the micromesh gaseous structure chamber (the MicroMegas), Gas-electron multiplier (GEM) detector, Resistive Plate Champers... Compact Muon Solenoid (CMS) experiment detecting muons which are powerful tool for recognizing signatures of interesting physics processes. The CMS detector uses: drift tube (DT), cathode strip chamber (CSC) and resistive plate chamber (RPC). Building RPC’s was my project in summer student program (hardware). RPC’s have advantages which are triggering detector and Excellent time resolution which reinforce the measurement of the correct beam crossing time. RPC’s Organized in stations :  RPC barrel (RB) there are 4 stations, namely RB1, RB2, RB3, and RB4  While in the RPC endcap (RE) the 3 stations are RE1, RE2, and RE3. In the endcaps a new starion will be added and this...

  4. Lunar architecture and urbanism

    Science.gov (United States)

    Sherwood, Brent

    1992-01-01

    Human civilization and architecture have defined each other for over 5000 years on Earth. Even in the novel environment of space, persistent issues of human urbanism will eclipse, within a historically short time, the technical challenges of space settlement that dominate our current view. By adding modern topics in space engineering, planetology, life support, human factors, material invention, and conservation to their already renaissance array of expertise, urban designers can responsibly apply ancient, proven standards to the exciting new opportunities afforded by space. Inescapable facts about the Moon set real boundaries within which tenable lunar urbanism and its component architecture must eventually develop.

  5. IT Service Management Architectures

    DEFF Research Database (Denmark)

    Tambo, Torben; Filtenborg, Jacob

    2017-01-01

    IT service providers tend to view their services as quasi-embedded in the client organisations infrastructure. Therefore, IT service providers lack a full picture of being an organisation with its own enterprise archicture. By systematically developing an enterprise architecture using the unifica......IT service providers tend to view their services as quasi-embedded in the client organisations infrastructure. Therefore, IT service providers lack a full picture of being an organisation with its own enterprise archicture. By systematically developing an enterprise architecture using...

  6. Synergetics and architecture

    Science.gov (United States)

    Maslov, V. P.; Maslova, T. V.

    2008-03-01

    A series of phenomena pertaining to economics, quantum physics, language, literary criticism, and especially architecture is studied from the standpoint of synergetics (the study of self-organizing complex systems). It turns out that a whole series of concrete formulas describing these phenomena is identical in these different situations. This is the case of formulas relating to the Bose-Einstein distribution of particles and the distribution of words from a frequency dictionary. This also allows to apply a "quantized" from of the Zipf law to the problem of the authorship of Quiet Flows the Don and to the "blending in" of new architectural structures in an existing environment.

  7. Reframing information architecture

    CERN Document Server

    Resmini, Andrea

    2014-01-01

    Information architecture has changed dramatically since the mid-1990s and earlier conceptions of the world and the internet being different and separate have given way to a much more complex scenario in the present day. In the post-digital world that we now inhabit the digital and the physical blend easily and our activities and usage of information takes place through multiple contexts and via multiple devices and unstable, emergent choreographies. Information architecture now is steadily growing into a channel- or medium-specific multi-disciplinary framework, with contributions coming from a

  8. Architecture as Ars Combinatoria

    OpenAIRE

    Francesco Cacciatore

    2015-01-01

    Architecture today, no longer reflects the limits of experimentation and innovation. An extremely low-tech art whose field of possibilities consists of choosing and using that which has already been done in the past. It is because of this that the key skill a designer should have is the ability to recognize the complexity in forms around them: cities have the widest programming opportunities for architecture, in the two-way relationship that is established from the city that takes form in arc...

  9. The Importance of cGMP Signaling in Sensory Cilia for Body Size Regulation in Caenorhabditis elegans.

    Science.gov (United States)

    Fujiwara, Manabi; Hino, Takahiro; Miyamoto, Ryuta; Inada, Hitoshi; Mori, Ikue; Koga, Makoto; Miyahara, Koji; Ohshima, Yasumi; Ishihara, Takeshi

    2015-12-01

    The body size of Caenorhabditis elegans is thought to be controlled by sensory inputs because many mutants with sensory cilium structure defects exhibit small body size. The EGL-4 cGMP-dependent protein kinase acts in sensory neurons to reduce body size when animals fail to perceive sensory signals. In addition to body size control, EGL-4 regulates various other behavioral and developmental pathways, including those involved in the regulation of egg laying and chemotaxis behavior. Here we have identified gcy-12, which encodes a receptor-type guanylyl cyclase, as a gene involved in the sensory regulation of body size. Analyses with GFP fusion constructs showed that gcy-12 is expressed in several sensory neurons and localizes to sensory cilia. Genetic analyses indicated that GCY-12 acts upstream of EGL-4 in body size control but does not affect other EGL-4 functions. Our studies indicate that the function of the GCY-12 guanylyl cyclase is to provide cGMP to the EGL-4 cGMP-dependent kinase only for limited tasks including body size regulation. We also found that the PDE-2 cyclic nucleotide phosphodiesterase negatively regulates EGL-4 in controlling body size. Thus, the cGMP level is precisely controlled by GCY-12 and PDE-2 to determine body size through EGL-4, and the defects in the sensory cilium structure may disturb the balanced control of the cGMP level. The large number of guanylyl cyclases encoded in the C. elegans genome suggests that EGL-4 exerts pleiotropic effects by partnering with different guanylyl cyclases for different downstream functions.

  10. Localised Plate Motion on Venus

    Science.gov (United States)

    Ghail, R. C.

    1996-03-01

    The volcanic and tectonic features observed in Dali Vinculum, Parga Vinculum and Imdr Regio are concentrated at long, narrow, curvilinear zones, with relatively minor volcanism and tectonism between these zones. These zones, whilst more diffuse than terrestrial plate boundaries, nevertheless define the margins of tectonic plates. In contrast to Earth, however, it appears that venusian plates are neither created nor destroyed by lateral motion. Rather, plates are thinned and intruded at vincula plate boundaries, vertically accreted by small-scale intra-plate (planitia) volcanism and perhaps destroyed by delamination of thickened crust in tesserae and montane regions such as Thetis Regio and Ishtar Terra. The diversity in age both between and within these three areas together with the evidence for infrequent, small scale resurfacing in the planitiae are difficult to reconcile with a non-uniformitarian geological process.

  11. Tectonics of the Easter plate

    Science.gov (United States)

    Engeln, J. F.; Stein, S.

    1984-01-01

    A new model for the Easter plate is presented in which rift propagation has resulted in the formation of a rigid plate between the propagating and dying ridges. The distribution of earthquakes, eleven new focal mechanisms, and existing bathymetric and magnetic data are used to describe the tectonics of this area. Both the Easter-Nazca and Easter-Pacific Euler poles are sufficiently close to the Easter plate to cause rapid changes in rates and directions of motion along the boundaries. The east and west boundaries are propagating and dying ridges; the southwest boundary is a slow-spreading ridge and the northern boundary is a complex zone of convergent and transform motion. The Easter plate may reflect the tectonics of rift propagation on a large scale, where rigid plate tectonics requires boundary reorientation. Simple schematic models to illustrate the general features and processes which occur at plates resulting from large-scale rift propagation are used.

  12. Tectonics of the Easter plate

    Science.gov (United States)

    Engeln, J. F.; Stein, S.

    1984-01-01

    A new model for the Easter plate is presented in which rift propagation has resulted in the formation of a rigid plate between the propagating and dying ridges. The distribution of earthquakes, eleven new focal mechanisms, and existing bathymetric and magnetic data are used to describe the tectonics of this area. Both the Easter-Nazca and Easter-Pacific Euler poles are sufficiently close to the Easter plate to cause rapid changes in rates and directions of motion along the boundaries. The east and west boundaries are propagating and dying ridges; the southwest boundary is a slow-spreading ridge and the northern boundary is a complex zone of convergent and transform motion. The Easter plate may reflect the tectonics of rift propagation on a large scale, where rigid plate tectonics requires boundary reorientation. Simple schematic models to illustrate the general features and processes which occur at plates resulting from large-scale rift propagation are used.

  13. The Architectural Information Map: Semantic modeling in conceptual architectural design

    NARCIS (Netherlands)

    Tunçer, E.B.

    2009-01-01

    This research focuses on the acquisition, representation, sharing and reuse of design information and knowledge in the conceptual phase of architectural design, and targets the creation of situated digital environments where communities of architectural practice communicate and collaborate using thi

  14. The Architectural Information Map: Semantic modeling in conceptual architectural design

    NARCIS (Netherlands)

    Tunçer, E.B.

    2009-01-01

    This research focuses on the acquisition, representation, sharing and reuse of design information and knowledge in the conceptual phase of architectural design, and targets the creation of situated digital environments where communities of architectural practice communicate and collaborate using

  15. Aluminum Manganese Molten Salt Plating

    Science.gov (United States)

    2006-06-01

    Dry fixture thoroughly with the air gun. Be especially careful to dry water out of crevices. Note: water is a contaminant to the plating process...easily destroyed if blown with the air. Be especially careful to dry water out of crevices. Note: water is a contaminant to the plating process and...especially careful to dry water out of crevices. 13. Carefully remove part from fixture. If residual plating solution is present at attachments points

  16. Discrete optimization in architecture architectural & urban layout

    CERN Document Server

    Zawidzki, Machi

    2016-01-01

    This book presents three projects that demonstrate the fundamental problems of architectural design and urban composition – the layout design, evaluation and optimization. Part I describes the functional layout design of a residential building, and an evaluation of the quality of a town square (plaza). The algorithm for the functional layout design is based on backtracking using a constraint satisfaction approach combined with coarse grid discretization. The algorithm for the town square evaluation is based on geometrical properties derived directly from its plan. Part II introduces a crowd-simulation application for the analysis of escape routes on floor plans, and optimization of a floor plan for smooth crowd flow. The algorithms presented employ agent-based modeling and cellular automata.

  17. Glass-bead peen plating

    Science.gov (United States)

    Graves, J. R.

    1974-01-01

    Peen plating of aluminum, copper, and nickel powders was investigated. Only aluminum was plated successfully within the range of peen plating conditions studied. Optimum plating conditions for aluminum were found to be: (1) bead/powder mixture containing 25 to 35% powder by weight, (2) peening intensity of 0.007A as measured by Almen strip, and (3) glass impact bead diameter of at least 297 microns (0.0117 inches) for depositing-100 mesh aluminum powder. No extensive cleaning or substrate preparation is required beyond removing loose dirt or heavy oil.

  18. Cartography of Architectural Controversies

    DEFF Research Database (Denmark)

    Lotz, Katrine

    2010-01-01

    or the office. The paper consists of investigations into such a stance. It is based on empiric studies, readings in architectural theory and applied actor-network theory. Furthermore the paper draws on recent examples of teaching practices pursuing this theme at the Royal Academy of Fine Arts, School...

  19. Architectural Creation of Light

    DEFF Research Database (Denmark)

    Bülow, Katja

    2015-01-01

    Bidraget "Architectural Creation of Light" indgår sammen med 108 andre bidrag i bogen "You Say Light, I Think Shadow". Bogens indhold undersøger: "Hvad er lys". I dette bidrag besvares spørgsmålet gennem iagttagelser af arkitektstuderendes undersøgelser af lyset i deres arbejdsmodeller i...

  20. Enterprise Architecture Evaluation

    DEFF Research Database (Denmark)

    Andersen, Peter; Carugati, Andrea

    2014-01-01

    By being holistically preoccupied with coherency among organizational elements such as organizational strategy, business needs and the IT functions role in supporting the business, enterprise architecture (EA) has grown to become a core competitive advantage. Though EA is a maturing research area...